1. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27993090
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Koido S
AU - Okamoto M
AU - Shimodaira S
AU - Sugiyama H
FA - Koido, Shigeo
FA - Okamoto, Masato
FA - Shimodaira, Shigetaka
FA - Sugiyama, Haruo
IN - Koido, Shigeo. Division of Gastroenterology & Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Kashiwa Hospital, Kashiwa City, Chiba 277-8567, Japan.
IN - Koido, Shigeo. Institute of Clinical Medicine & Research, The Jikei University School of Medicine, Kashiwa City, Chiba 277-8567, Japan.
IN - Okamoto, Masato. Department of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, Tokyo 108-8641, Japan.
IN - Shimodaira, Shigetaka. Cell Processing Center, Shinshu University Hospital, Nagano 390-8621, Japan.
IN - Sugiyama, Haruo. Department of Functional Diagnostic Science, Graduate School of Medicine, Osaka University, Suita City, Osaka 565-0871, Japan.
TI - Wilms' tumor 1 (WT1)-targeted cancer vaccines to extend survival for patients with pancreatic cancer. [Review]
SO - Immunotherapy. 8(11):1309-1320, 2016 Nov
AS - Immunotherapy. 8(11):1309-1320, 2016 Nov
NJ - Immunotherapy
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101485158
IO - Immunotherapy
SB - Index Medicus
CP - England
MH - Animals
MH - *Antigens, Neoplasm/im [Immunology]
MH - *Cancer Vaccines/im [Immunology]
MH - Carcinoma, Pancreatic Ductal/im [Immunology]
MH - *Carcinoma, Pancreatic Ductal/th [Therapy]
MH - Clinical Trials as Topic
MH - Dendritic Cells/im [Immunology]
MH - *Dendritic Cells/tr [Transplantation]
MH - Humans
MH - Molecular Targeted Therapy
MH - Vaccines, Subunit
MH - *WT1 Proteins/im [Immunology]
KW - WT1; cancer vaccine; dendritic cell; pancreatic cancer; peptide
AB - Despite novel chemotherapy treatments, pancreatic ductal adenocarcinoma (PDA) remains a lethal disease. New targeted cancer vaccines may represent a viable option for patients with PDA. The Wilms' tumor 1 (WT1) antigen is one of the most widely expressed tumor-associated antigens in various types of tumors, including PDA. Recent reports have indicated that WT1-targeted cancer vaccines for patients with PDA mediated a potent antitumor effect when combined with chemotherapy in preclinical and clinical studies. This review summarizes the early-phase clinical trials of WT1-targeted cancer vaccines (peptide vaccines and dendritic cell-based vaccines) for PDA. Moreover, we will discuss future strategies for PDA treatments using WT1-specific cancer vaccines combined with immune checkpoint therapies to maximize the clinical effectiveness of PDA treatments.
RN - 0 (Antigens, Neoplasm)
RN - 0 (Cancer Vaccines)
RN - 0 (Vaccines, Subunit)
RN - 0 (WT1 Proteins)
RN - 0 (WT1 protein, human)
ES - 1750-7448
IL - 1750-743X
DO - https://dx.doi.org/10.2217/imt-2016-0031
PT - Journal Article
PT - Review
ID - 10.2217/imt-2016-0031 [doi]
PP - ppublish
LG - English
DP - 2016 Nov
DC - 20161220
EZ - 2016/12/21 06:00
DA - 2017/07/06 06:00
DT - 2016/12/21 06:00
YR - 2016
ED - 20170705
RD - 20170705
UP - 20170706
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27993090
<2. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27892744
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Abdel-Rahman O
FA - Abdel-Rahman, Omar
IN - Abdel-Rahman, Omar. Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
TI - Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [Review]
SO - Immunotherapy. 8(12):1383-1391, 2016 Dec
AS - Immunotherapy. 8(12):1383-1391, 2016 Dec
NJ - Immunotherapy
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101485158
IO - Immunotherapy
SB - Index Medicus
CP - England
MH - *Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Clinical Protocols
MH - Clinical Trials as Topic
MH - Drug-Related Side Effects and Adverse Reactions
MH - Humans
MH - *Melanoma/dh [Diet Therapy]
MH - *Programmed Cell Death 1 Receptor/im [Immunology]
MH - Treatment Outcome
KW - NSCLC; dose; melanoma; pembrolizumab
AB - AIM: Pembrolizumab is a fully humanized anti-PD-1 agent currently approved for the treatment of advanced melanoma and pretreated non-small-cell lung cancer (NSCLC).
AB - OBJECTIVE: To assess the efficacy and safety of different dose schedules of pembrolizumab in the treatment of patients with advanced NSCLC and melanoma. Search method: MEDLINE database has been searched. Reference lists of original studies and review articles were checked for other related articles.
AB - SELECTION CRITERIA: Prospective clinical trials reporting the outcomes of more than one dose schedule of pembrolizumab in the treatment of advanced NSCLC and melanoma.
AB - DATA COLLECTION & ANALYSIS: The review author extracted information on the outcomes of the study for this review, and presented the results.
AB - MAIN RESULTS: Four trials with 3425 patients were included in this systematic review. Pooled analysis for the odds ratio of objective response rate comparing 2 versus 10 mg/kg every 3 weeks in advanced melanoma was 1.03 (95% CI: 0.71-1.49; p = 0.89), while for advanced NSCLC, it was 0.97 (95% CI: 0.66-1.43; p = 0.87). Moreover, odds ratio for selected side effects between the two doses was as follows: rash: 0.83 (95 CI: 0.58-1.18; p = 0.29); vitiligo: 1.27 (95% CI: 0.62-2.61; p = 0.52); diarrhea: 0.94 (95% CI: 0.63-1.42; p = 0.79); hypothyroidism: 0.97 (95% CI: 0.63-1.50; p = 0.90); hepatitis/elevated transaminases: 1.86 (95% CI: 0.91-3.79; p = 0.09); nephritis: 0.88 (95% CI: 0.32-2.44; p = 0.80); pneumonitis: 1.17 (95% CI: 0.62-2.23; p = 0.63).
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - DPT0O3T46P (pembrolizumab)
ES - 1750-7448
IL - 1750-743X
DO - https://dx.doi.org/10.2217/imt-2016-0075
PT - Journal Article
PT - Meta-Analysis
PT - Review
ID - 10.2217/imt-2016-0075 [doi]
PP - ppublish
LG - English
EP - 20161128
DP - 2016 Dec
DC - 20161128
EZ - 2016/11/29 06:00
DA - 2017/07/06 06:00
DT - 2016/11/29 06:00
YR - 2016
ED - 20170705
RD - 20170705
UP - 20170706
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27892744
<3. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27045886
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Bastman JJ
AU - Serracino HS
AU - Zhu Y
AU - Koenig MR
AU - Mateescu V
AU - Sams SB
AU - Davies KD
AU - Raeburn CD
AU - McIntyre RC Jr
AU - Haugen BR
AU - French JD
FA - Bastman, Jill J
FA - Serracino, Hilary S
FA - Zhu, Yuwen
FA - Koenig, Michelle R
FA - Mateescu, Valerica
FA - Sams, Sharon B
FA - Davies, Kurtis D
FA - Raeburn, Christopher D
FA - McIntyre, Robert C Jr
FA - Haugen, Bryan R
FA - French, Jena D
IN - Bastman, Jill J. Department of Medicine (J.J.B., B.R.H., J.D.F.), Division of Endocrinology, Metabolism, and Diabetes, Departments of Pathology (H.S.S., V.M., S.B.S., K.D.D., B.R.H.) and Surgery (Y.Z., M.R.K., R.C.M., C.D.R.), and University of Colorado Cancer Center (B.R.H., J.D.F.), University of Colorado Denver, Aurora, Colorado 80045.
IN - Serracino, Hilary S. Department of Medicine (J.J.B., B.R.H., J.D.F.), Division of Endocrinology, Metabolism, and Diabetes, Departments of Pathology (H.S.S., V.M., S.B.S., K.D.D., B.R.H.) and Surgery (Y.Z., M.R.K., R.C.M., C.D.R.), and University of Colorado Cancer Center (B.R.H., J.D.F.), University of Colorado Denver, Aurora, Colorado 80045.
IN - Zhu, Yuwen. Department of Medicine (J.J.B., B.R.H., J.D.F.), Division of Endocrinology, Metabolism, and Diabetes, Departments of Pathology (H.S.S., V.M., S.B.S., K.D.D., B.R.H.) and Surgery (Y.Z., M.R.K., R.C.M., C.D.R.), and University of Colorado Cancer Center (B.R.H., J.D.F.), University of Colorado Denver, Aurora, Colorado 80045.
IN - Koenig, Michelle R. Department of Medicine (J.J.B., B.R.H., J.D.F.), Division of Endocrinology, Metabolism, and Diabetes, Departments of Pathology (H.S.S., V.M., S.B.S., K.D.D., B.R.H.) and Surgery (Y.Z., M.R.K., R.C.M., C.D.R.), and University of Colorado Cancer Center (B.R.H., J.D.F.), University of Colorado Denver, Aurora, Colorado 80045.
IN - Mateescu, Valerica. Department of Medicine (J.J.B., B.R.H., J.D.F.), Division of Endocrinology, Metabolism, and Diabetes, Departments of Pathology (H.S.S., V.M., S.B.S., K.D.D., B.R.H.) and Surgery (Y.Z., M.R.K., R.C.M., C.D.R.), and University of Colorado Cancer Center (B.R.H., J.D.F.), University of Colorado Denver, Aurora, Colorado 80045.
IN - Sams, Sharon B. Department of Medicine (J.J.B., B.R.H., J.D.F.), Division of Endocrinology, Metabolism, and Diabetes, Departments of Pathology (H.S.S., V.M., S.B.S., K.D.D., B.R.H.) and Surgery (Y.Z., M.R.K., R.C.M., C.D.R.), and University of Colorado Cancer Center (B.R.H., J.D.F.), University of Colorado Denver, Aurora, Colorado 80045.
IN - Davies, Kurtis D. Department of Medicine (J.J.B., B.R.H., J.D.F.), Division of Endocrinology, Metabolism, and Diabetes, Departments of Pathology (H.S.S., V.M., S.B.S., K.D.D., B.R.H.) and Surgery (Y.Z., M.R.K., R.C.M., C.D.R.), and University of Colorado Cancer Center (B.R.H., J.D.F.), University of Colorado Denver, Aurora, Colorado 80045.
IN - Raeburn, Christopher D. Department of Medicine (J.J.B., B.R.H., J.D.F.), Division of Endocrinology, Metabolism, and Diabetes, Departments of Pathology (H.S.S., V.M., S.B.S., K.D.D., B.R.H.) and Surgery (Y.Z., M.R.K., R.C.M., C.D.R.), and University of Colorado Cancer Center (B.R.H., J.D.F.), University of Colorado Denver, Aurora, Colorado 80045.
IN - McIntyre, Robert C Jr. Department of Medicine (J.J.B., B.R.H., J.D.F.), Division of Endocrinology, Metabolism, and Diabetes, Departments of Pathology (H.S.S., V.M., S.B.S., K.D.D., B.R.H.) and Surgery (Y.Z., M.R.K., R.C.M., C.D.R.), and University of Colorado Cancer Center (B.R.H., J.D.F.), University of Colorado Denver, Aurora, Colorado 80045.
IN - Haugen, Bryan R. Department of Medicine (J.J.B., B.R.H., J.D.F.), Division of Endocrinology, Metabolism, and Diabetes, Departments of Pathology (H.S.S., V.M., S.B.S., K.D.D., B.R.H.) and Surgery (Y.Z., M.R.K., R.C.M., C.D.R.), and University of Colorado Cancer Center (B.R.H., J.D.F.), University of Colorado Denver, Aurora, Colorado 80045.
IN - French, Jena D. Department of Medicine (J.J.B., B.R.H., J.D.F.), Division of Endocrinology, Metabolism, and Diabetes, Departments of Pathology (H.S.S., V.M., S.B.S., K.D.D., B.R.H.) and Surgery (Y.Z., M.R.K., R.C.M., C.D.R.), and University of Colorado Cancer Center (B.R.H., J.D.F.), University of Colorado Denver, Aurora, Colorado 80045.
TI - Tumor-Infiltrating T Cells and the PD-1 Checkpoint Pathway in Advanced Differentiated and Anaplastic Thyroid Cancer.
SO - Journal of Clinical Endocrinology & Metabolism. 101(7):2863-73, 2016 Jul
AS - J Clin Endocrinol Metab. 101(7):2863-73, 2016 Jul
NJ - The Journal of clinical endocrinology and metabolism
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - hrb, 0375362
IO - J. Clin. Endocrinol. Metab.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929840
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Biomarkers, Tumor/ge [Genetics]
MH - CD8-Positive T-Lymphocytes/im [Immunology]
MH - CD8-Positive T-Lymphocytes/pa [Pathology]
MH - Cell Cycle Checkpoints/ge [Genetics]
MH - Female
MH - Gene Expression Regulation, Neoplastic
MH - Humans
MH - *Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Lymphocytes, Tumor-Infiltrating/pa [Pathology]
MH - Male
MH - Middle Aged
MH - Neoplasm Invasiveness
MH - Prognosis
MH - *Programmed Cell Death 1 Receptor/ge [Genetics]
MH - Programmed Cell Death 1 Receptor/ph [Physiology]
MH - Signal Transduction/ge [Genetics]
MH - Thyroid Carcinoma, Anaplastic/di [Diagnosis]
MH - *Thyroid Carcinoma, Anaplastic/ge [Genetics]
MH - *Thyroid Carcinoma, Anaplastic/im [Immunology]
MH - Thyroid Carcinoma, Anaplastic/pa [Pathology]
MH - Thyroid Neoplasms/di [Diagnosis]
MH - *Thyroid Neoplasms/ge [Genetics]
MH - *Thyroid Neoplasms/im [Immunology]
MH - Thyroid Neoplasms/pa [Pathology]
AB - CONTEXT: Five to 10% of patients with differentiated thyroid cancers (DTC) develop invasive and/or distant metastatic disease that is marginally improved with standard therapies. Prognosis is poor for patients with anaplastic thyroid cancer, with a median survival of 3-5 months. We suggest that a paradigm shift is necessary in the treatment of advanced cases.
AB - OBJECTIVE: We hypothesized that a T-cell response is generated in advanced thyroid cancer and may be a viable therapeutic target.
AB - DESIGN: Primary DTCs were analyzed by quantitative RT-PCR (n = 92) for expression of CD3, CD8, forkhead box (Fox)-P3, programmed death (PD)-1, PD-1 ligand-1, and PD-1 ligand-2 and biopsied for cellular analysis by flow cytometry (n = 11). Advanced pT4 cases (n = 22) and metastases (n = 5) were analyzed by immunohistochemistry.
AB - SETTING: The study was conducted at the University of Colorado Hospital.
AB - PATIENTS: Thyroid cancer patients undergoing thyroidectomy or completion surgery for advanced disease between 2002 and 2013 participated in the study.
AB - INTERVENTION: There were no interventions.
AB - MAIN OUTCOME MEASURE: Immune markers were analyzed for association with disease severity.
AB - RESULTS: Immune markers were commonly expressed at the RNA level. PD-L1 was higher (P = .0443) in patients with nodal metastases. FoxP3(+) (P < .0001), PD-1(+)CD8(+) (P = .0058), and PD-1(+)CD4(+) (P = .0104) T cells were enriched in DTC biopsies. CD8(+) and FoxP3(+) T cells were detected by immunohistochemistry in all pT4 tumors and a subset of metastases. PD-1(+) lymphocytes were found in 50% of DTCs. PD-L1 was expressed by tumor and associated leukocytes in 13 of 22 cases, and expression was more diffuse in anaplastic thyroid cancer (P = .0373). BRAF(V600E) mutation was associated with higher frequencies of tumor-associated lymphocytes (P = .0095) but not PD-L1 expression.
AB - CONCLUSIONS: PD-1 checkpoint blockades may have therapeutic efficacy in patients with aggressive forms of thyroid cancer.
RN - 0 (Biomarkers, Tumor)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1945-7197
IL - 0021-972X
DO - https://dx.doi.org/10.1210/jc.2015-4227
PT - Journal Article
ID - 10.1210/jc.2015-4227 [doi]
ID - PMC4929840 [pmc]
PP - ppublish
PH - 2017/07/01 [pmc-release]
GI - No: P30 CA046934
Organization: (CA) *NCI NIH HHS*
Country: United States
No: UL1 RR025780
Organization: (RR) *NCRR NIH HHS*
Country: United States
LG - English
EP - 20160405
DP - 2016 Jul
DC - 20160706
EZ - 2016/04/06 06:00
DA - 2017/07/06 06:00
DT - 2016/04/06 06:00
YR - 2016
ED - 20170705
RD - 20170705
UP - 20170706
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27045886
<4. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28106152
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Byun DJ
AU - Wolchok JD
AU - Rosenberg LM
AU - Girotra M
FA - Byun, David J
FA - Wolchok, Jedd D
FA - Rosenberg, Lynne M
FA - Girotra, Monica
IN - Byun, David J. Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, 10065 New York, USA.
IN - Byun, David J. Weill Cornell Medical College, 1300 York Avenue, New York, 10065 New York, USA.
IN - Wolchok, Jedd D. Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, 10065 New York, USA.
IN - Wolchok, Jedd D. Weill Cornell Medical College, 1300 York Avenue, New York, 10065 New York, USA.
IN - Rosenberg, Lynne M. Weill Cornell Medical College, 1300 York Avenue, New York, 10065 New York, USA.
IN - Girotra, Monica. Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, 10065 New York, USA.
IN - Girotra, Monica. Weill Cornell Medical College, 1300 York Avenue, New York, 10065 New York, USA.
TI - Cancer immunotherapy - immune checkpoint blockade and associated endocrinopathies. [Review]
SO - Nature Reviews Endocrinology. 13(4):195-207, 2017 Apr
AS - Nat Rev Endocrinol. 13(4):195-207, 2017 Apr
NJ - Nature reviews. Endocrinology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101500078
IO - Nat Rev Endocrinol
SB - Index Medicus
CP - England
MH - Animals
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - CTLA-4 Antigen/bi [Biosynthesis]
MH - *Endocrine System Diseases/ci [Chemically Induced]
MH - *Endocrine System Diseases/im [Immunology]
MH - Endocrine System Diseases/me [Metabolism]
MH - Humans
MH - Immunotherapy/ae [Adverse Effects]
MH - *Neoplasms/dt [Drug Therapy]
MH - *Neoplasms/im [Immunology]
MH - Neoplasms/me [Metabolism]
MH - Programmed Cell Death 1 Receptor/bi [Biosynthesis]
AB - Advances in cancer therapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (IRAEs), which resemble autoimmune disease. In this Review, we describe the current data regarding immune-related endocrinopathies, including hypophysitis, thyroid dysfunction and diabetes mellitus. We discuss the clinical management of these endocrinopathies within the context of our current understanding of the mechanisms of IRAEs.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 6T8C155666 (ipilimumab)
ES - 1759-5037
IL - 1759-5029
DI - nrendo.2016.205
DO - https://dx.doi.org/10.1038/nrendo.2016.205
PT - Journal Article
PT - Review
ID - nrendo.2016.205 [pii]
ID - 10.1038/nrendo.2016.205 [doi]
PP - ppublish
GI - No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20170120
DP - 2017 Apr
DC - 20170120
EZ - 2017/01/21 06:00
DA - 2017/07/04 06:00
DT - 2017/01/21 06:00
YR - 2017
ED - 20170703
RD - 20170703
UP - 20170705
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28106152
<5. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27085692
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Hofmann L
AU - Forschner A
AU - Loquai C
AU - Goldinger SM
AU - Zimmer L
AU - Ugurel S
AU - Schmidgen MI
AU - Gutzmer R
AU - Utikal JS
AU - Goppner D
AU - Hassel JC
AU - Meier F
AU - Tietze JK
AU - Thomas I
AU - Weishaupt C
AU - Leverkus M
AU - Wahl R
AU - Dietrich U
AU - Garbe C
AU - Kirchberger MC
AU - Eigentler T
AU - Berking C
AU - Gesierich A
AU - Krackhardt AM
AU - Schadendorf D
AU - Schuler G
AU - Dummer R
AU - Heinzerling LM
FA - Hofmann, Lars
FA - Forschner, Andrea
FA - Loquai, Carmen
FA - Goldinger, Simone M
FA - Zimmer, Lisa
FA - Ugurel, Selma
FA - Schmidgen, Maria I
FA - Gutzmer, Ralf
FA - Utikal, Jochen S
FA - Goppner, Daniela
FA - Hassel, Jessica C
FA - Meier, Friedegund
FA - Tietze, Julia K
FA - Thomas, Ioannis
FA - Weishaupt, Carsten
FA - Leverkus, Martin
FA - Wahl, Renate
FA - Dietrich, Ursula
FA - Garbe, Claus
FA - Kirchberger, Michael C
FA - Eigentler, Thomas
FA - Berking, Carola
FA - Gesierich, Anja
FA - Krackhardt, Angela M
FA - Schadendorf, Dirk
FA - Schuler, Gerold
FA - Dummer, Reinhard
FA - Heinzerling, Lucie M
IN - Hofmann, Lars. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nurnberg (FAU), Germany.
IN - Forschner, Andrea. Department of Dermatology, University Hospital Tubingen, Germany.
IN - Loquai, Carmen. Department of Dermatology, University Hospital Mainz, Germany.
IN - Goldinger, Simone M. Department of Dermatology, University Hospital Zurich, Switzerland.
IN - Zimmer, Lisa. Department of Dermatology, University Hospital, University Duisburg-Essen, Germany.
IN - Ugurel, Selma. Department of Dermatology, University Hospital, University Duisburg-Essen, Germany.
IN - Schmidgen, Maria I. Department of Dermatology, University Hospital Mainz, Germany.
IN - Gutzmer, Ralf. Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Germany.
IN - Utikal, Jochen S. Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
IN - Goppner, Daniela. Department of Dermatology, University Hospital Magdeburg, Germany.
IN - Hassel, Jessica C. Department of Dermatology, University Hospital Heidelberg, Germany.
IN - Meier, Friedegund. Department of Dermatology, University Hospital Dresden, Germany.
IN - Tietze, Julia K. Department of Dermatology and Allergology, Ludwig-Maximilian-University (LMU) Munich, Germany.
IN - Thomas, Ioannis. Department of Dermatology, University Hospital Tubingen, Germany.
IN - Weishaupt, Carsten. Department of Dermatology, University Hospital Munster, Munster, Germany.
IN - Leverkus, Martin. Department of Dermatology, University Hospital RWTH Aachen, Germany.
IN - Wahl, Renate. Department of Dermatology, University Hospital RWTH Aachen, Germany.
IN - Dietrich, Ursula. Department of Dermatology, University Hospital Dresden, Germany.
IN - Garbe, Claus. Department of Dermatology, University Hospital Tubingen, Germany.
IN - Kirchberger, Michael C. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nurnberg (FAU), Germany.
IN - Eigentler, Thomas. Department of Dermatology, University Hospital Tubingen, Germany.
IN - Berking, Carola. Department of Dermatology and Allergology, Ludwig-Maximilian-University (LMU) Munich, Germany.
IN - Gesierich, Anja. Department of Dermatology, University Hospital Wurzburg, Germany.
IN - Krackhardt, Angela M. III. Medical Department, Technische Universitat Munchen (TUM), Munich, Germany.
IN - Schadendorf, Dirk. Department of Dermatology, University Hospital, University Duisburg-Essen, Germany.
IN - Schuler, Gerold. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nurnberg (FAU), Germany.
IN - Dummer, Reinhard. Department of Dermatology, University Hospital Zurich, Switzerland.
IN - Heinzerling, Lucie M. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nurnberg (FAU), Germany. Electronic address: Lucie.Heinzerling@uk-erlangen.de.
TI - Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy.
SO - European Journal of Cancer. 60:190-209, 2016 Jun
AS - Eur J Cancer. 60:190-209, 2016 Jun
NJ - European journal of cancer (Oxford, England : 1990)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - arv, 9005373
IO - Eur. J. Cancer
SB - Index Medicus
CP - England
MH - Adult
MH - Aged
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Chemical and Drug Induced Liver Injury/et [Etiology]
MH - Drug Eruptions/et [Etiology]
MH - Endocrine System Diseases/ci [Chemically Induced]
MH - Female
MH - Gastrointestinal Diseases/ci [Chemically Induced]
MH - Humans
MH - Kidney Diseases/ci [Chemically Induced]
MH - *Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Retrospective Studies
MH - *Skin Neoplasms/dt [Drug Therapy]
KW - Adverse event; Anti-PD-1; Checkpoint inhibitors; Immune-related; Nivolumab; Pembrolizumab; Side-effect; Tolerability; Toxicity
AB - BACKGROUND: Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma as well as for other cancer entities. They act via blockade of the PD-1 receptor, an inhibitor of the T-cell effector mechanisms that limit immune responses against tumours. As reported for ipilimumab, the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential.
AB - METHODS AND FINDINGS: In total, 496 patients with metastatic melanoma from 15 skin cancer centers were treated with pembrolizumab or nivolumab; 242 side-effects were described in 138 patients. In 116 of the 138 patients, side-effects affected the skin, gastrointestinal tract, liver, endocrine, and renal system. Rare side-effects included diabetes mellitus, lichen planus, and pancreas insufficiency due to pancreatitis.
AB - CONCLUSION: Anti-PD1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity.
Copyright © 2016 Elsevier Ltd. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 31YO63LBSN (nivolumab)
RN - 6T8C155666 (ipilimumab)
RN - DPT0O3T46P (pembrolizumab)
ES - 1879-0852
IL - 0959-8049
DI - S0959-8049(16)00151-9
DO - https://dx.doi.org/10.1016/j.ejca.2016.02.025
PT - Journal Article
PT - Multicenter Study
ID - S0959-8049(16)00151-9 [pii]
ID - 10.1016/j.ejca.2016.02.025 [doi]
PP - ppublish
PH - 2016/02/22 [received]
PH - 2016/02/25 [accepted]
LG - English
EP - 20160413
DP - 2016 Jun
DC - 20160516
EZ - 2016/04/18 06:00
DA - 2017/07/04 06:00
DT - 2016/04/18 06:00
YR - 2016
ED - 20170703
RD - 20170703
UP - 20170705
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27085692
<6. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27084345
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Zimmer L
AU - Goldinger SM
AU - Hofmann L
AU - Loquai C
AU - Ugurel S
AU - Thomas I
AU - Schmidgen MI
AU - Gutzmer R
AU - Utikal JS
AU - Goppner D
AU - Hassel JC
AU - Meier F
AU - Tietze JK
AU - Forschner A
AU - Weishaupt C
AU - Leverkus M
AU - Wahl R
AU - Dietrich U
AU - Garbe C
AU - Kirchberger MC
AU - Eigentler T
AU - Berking C
AU - Gesierich A
AU - Krackhardt AM
AU - Schadendorf D
AU - Schuler G
AU - Dummer R
AU - Heinzerling LM
FA - Zimmer, Lisa
FA - Goldinger, Simone M
FA - Hofmann, Lars
FA - Loquai, Carmen
FA - Ugurel, Selma
FA - Thomas, Ioannis
FA - Schmidgen, Maria I
FA - Gutzmer, Ralf
FA - Utikal, Jochen S
FA - Goppner, Daniela
FA - Hassel, Jessica C
FA - Meier, Friedegund
FA - Tietze, Julia K
FA - Forschner, Andrea
FA - Weishaupt, Carsten
FA - Leverkus, Martin
FA - Wahl, Renate
FA - Dietrich, Ursula
FA - Garbe, Claus
FA - Kirchberger, Michael C
FA - Eigentler, Thomas
FA - Berking, Carola
FA - Gesierich, Anja
FA - Krackhardt, Angela M
FA - Schadendorf, Dirk
FA - Schuler, Gerold
FA - Dummer, Reinhard
FA - Heinzerling, Lucie M
IN - Zimmer, Lisa. Department of Dermatology, University Hospital, University Duisburg-Essen, Germany.
IN - Goldinger, Simone M. Department of Dermatology, University Hospital Zurich, Switzerland.
IN - Hofmann, Lars. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nurnberg (FAU), Germany.
IN - Loquai, Carmen. Department of Dermatology, University Hospital Mainz, Germany.
IN - Ugurel, Selma. Department of Dermatology, University Hospital, University Duisburg-Essen, Germany.
IN - Thomas, Ioannis. Department of Dermatology, University Hospital Tubingen, Germany.
IN - Schmidgen, Maria I. Department of Dermatology, University Hospital Mainz, Germany.
IN - Gutzmer, Ralf. Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Germany.
IN - Utikal, Jochen S. Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
IN - Goppner, Daniela. Department of Dermatology, University Hospital Magdeburg, Germany.
IN - Hassel, Jessica C. Department of Dermatology, University Hospital Heidelberg, Germany.
IN - Meier, Friedegund. Department of Dermatology, University Hospital Dresden, Germany.
IN - Tietze, Julia K. Department of Dermatology and Allergology, University Hospital Munich (LMU), Germany.
IN - Forschner, Andrea. Department of Dermatology, University Hospital Tubingen, Germany.
IN - Weishaupt, Carsten. Department of Dermatology, University Hospital Munster, Germany.
IN - Leverkus, Martin. Department of Dermatology, University Hospital RWTH Aachen, Germany.
IN - Wahl, Renate. Department of Dermatology, University Hospital RWTH Aachen, Germany.
IN - Dietrich, Ursula. Department of Dermatology, University Hospital Dresden, Germany.
IN - Garbe, Claus. Department of Dermatology, University Hospital Tubingen, Germany.
IN - Kirchberger, Michael C. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nurnberg (FAU), Germany.
IN - Eigentler, Thomas. Department of Dermatology, University Hospital Tubingen, Germany.
IN - Berking, Carola. Department of Dermatology and Allergology, University Hospital Munich (LMU), Germany.
IN - Gesierich, Anja. Department of Dermatology, University Hospital Wurzburg, Germany.
IN - Krackhardt, Angela M. III. Medical Department, Technische Universitat Munchen (TUM) Munich, Germany.
IN - Schadendorf, Dirk. Department of Dermatology, University Hospital, University Duisburg-Essen, Germany.
IN - Schuler, Gerold. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nurnberg (FAU), Germany.
IN - Dummer, Reinhard. Department of Dermatology, University Hospital Zurich, Switzerland.
IN - Heinzerling, Lucie M. Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nurnberg (FAU), Germany. Electronic address: Lucie.Heinzerling@uk-erlangen.de.
TI - Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy.
SO - European Journal of Cancer. 60:210-25, 2016 Jun
AS - Eur J Cancer. 60:210-25, 2016 Jun
NJ - European journal of cancer (Oxford, England : 1990)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - arv, 9005373
IO - Eur. J. Cancer
SB - Index Medicus
CP - England
MH - Adult
MH - Aged
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Cell Cycle Checkpoints
MH - Eye Diseases/ci [Chemically Induced]
MH - Female
MH - Heart Diseases/ci [Chemically Induced]
MH - Humans
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - Musculoskeletal Diseases/ci [Chemically Induced]
MH - Nervous System Diseases/ci [Chemically Induced]
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Respiratory Tract Diseases/ci [Chemically Induced]
MH - Retrospective Studies
MH - *Skin Neoplasms/dt [Drug Therapy]
KW - Adverse event; Anti-PD-1; Checkpoint inhibitors; Immune-related; Nivolumab; Pembrolizumab; Side-effect; Tolerability; Toxicity
AB - BACKGROUND: Anti-programmed cell death 1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma and other cancer entities. They act via blockade of the PD-1 receptor, an inhibitor of the T-cell effector mechanisms that limit immune responses against tumours. As reported for ipilimumab, the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects can involve skin, gastrointestinal tract, liver, the endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential.
AB - METHODS AND FINDINGS: In total, 496 patients with metastatic melanoma from 15 skin cancer centres were treated with pembrolizumab or nivolumab. Two hundred forty two side-effects in 138 patients have been analysed. In 77 of the 138 patients side-effects affected the nervous system, respiratory tract, musculoskeletal system, heart, blood and eyes. Not yet reported side-effects such as meningo-(radiculitis), polyradiculitis, cardiac arrhythmia, asystolia, and paresis have been observed. Rare and difficult to manage side-effects such as myasthenia gravis are described in detail.
AB - CONCLUSION: Anti-PD-1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity.
Copyright © 2016. Published by Elsevier Ltd.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 31YO63LBSN (nivolumab)
RN - 6T8C155666 (ipilimumab)
RN - DPT0O3T46P (pembrolizumab)
ES - 1879-0852
IL - 0959-8049
DI - S0959-8049(16)00150-7
DO - https://dx.doi.org/10.1016/j.ejca.2016.02.024
PT - Journal Article
PT - Multicenter Study
ID - S0959-8049(16)00150-7 [pii]
ID - 10.1016/j.ejca.2016.02.024 [doi]
PP - ppublish
PH - 2016/02/22 [received]
PH - 2016/02/25 [accepted]
LG - English
EP - 20160413
DP - 2016 Jun
DC - 20160516
EZ - 2016/04/17 06:00
DA - 2017/07/04 06:00
DT - 2016/04/17 06:00
YR - 2016
ED - 20170703
RD - 20170703
UP - 20170705
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27084345
<7. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27571185
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - de Filette J
AU - Jansen Y
AU - Schreuer M
AU - Everaert H
AU - Velkeniers B
AU - Neyns B
AU - Bravenboer B
FA - de Filette, Jeroen
FA - Jansen, Yanina
FA - Schreuer, Max
FA - Everaert, Hendrik
FA - Velkeniers, Brigitte
FA - Neyns, Bart
FA - Bravenboer, Bert
IN - de Filette, Jeroen. Departments of Endocrinology (J.d.F., B.V., B.B.), Medical Oncology (Y.J., M.S., B.N.), and Nuclear Medicine (H.E.), Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
IN - Jansen, Yanina. Departments of Endocrinology (J.d.F., B.V., B.B.), Medical Oncology (Y.J., M.S., B.N.), and Nuclear Medicine (H.E.), Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
IN - Schreuer, Max. Departments of Endocrinology (J.d.F., B.V., B.B.), Medical Oncology (Y.J., M.S., B.N.), and Nuclear Medicine (H.E.), Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
IN - Everaert, Hendrik. Departments of Endocrinology (J.d.F., B.V., B.B.), Medical Oncology (Y.J., M.S., B.N.), and Nuclear Medicine (H.E.), Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
IN - Velkeniers, Brigitte. Departments of Endocrinology (J.d.F., B.V., B.B.), Medical Oncology (Y.J., M.S., B.N.), and Nuclear Medicine (H.E.), Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
IN - Neyns, Bart. Departments of Endocrinology (J.d.F., B.V., B.B.), Medical Oncology (Y.J., M.S., B.N.), and Nuclear Medicine (H.E.), Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
IN - Bravenboer, Bert. Departments of Endocrinology (J.d.F., B.V., B.B.), Medical Oncology (Y.J., M.S., B.N.), and Nuclear Medicine (H.E.), Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
TI - Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab.
SO - Journal of Clinical Endocrinology & Metabolism. 101(11):4431-4439, 2016 Nov
AS - J Clin Endocrinol Metab. 101(11):4431-4439, 2016 Nov
NJ - The Journal of clinical endocrinology and metabolism
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - hrb, 0375362
IO - J. Clin. Endocrinol. Metab.
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - *Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Female
MH - Humans
MH - Hypothyroidism/bl [Blood]
MH - *Hypothyroidism/ci [Chemically Induced]
MH - Hypothyroidism/dg [Diagnostic Imaging]
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - Positron Emission Tomography Computed Tomography
MH - *Thyroiditis/ci [Chemically Induced]
MH - Thyroiditis/dg [Diagnostic Imaging]
MH - Thyrotoxicosis/bl [Blood]
MH - *Thyrotoxicosis/ci [Chemically Induced]
MH - Thyrotoxicosis/dg [Diagnostic Imaging]
AB - CONTEXT: Immune checkpoint blockade is associated with endocrine-related adverse events. Thyroid dysfunction during pembrolizumab therapy, an anti-programmed cell death 1 (PD-1) receptor monoclonal antibody, remains to be fully characterized.
AB - OBJECTIVE: To assess the incidence and characteristics of pembrolizumab-associated thyroid dysfunction.
AB - DESIGN AND SETTING: Thyroid function was monitored prospectively in melanoma patients who initiated pembrolizumab within an expanded access program at a referral oncology center. 18Fluorodeoxyglucose uptake on positron emission tomography/computed tomography (18FDG-PET/CT) was reviewed in cases compatible with inflammatory thyroiditis.
AB - PATIENTS: Ninety-nine patients with advanced melanoma (age, 26.3-93.6 years; 63.6% females) who received at least one administration of pembrolizumab.
AB - MAIN OUTCOME MEASURES: Patient characteristics, thyroid function (TSH, free T4), thyroid autoantibodies, and 18FDG-PET/CT.
AB - RESULTS: Eighteen adverse events of thyroid dysfunction were observed in 17 patients. Thyrotoxicosis occurred in 12 patients, of which nine evolved to hypothyroidism. Isolated hypothyroidism was present in six patients. Levothyroxine therapy was required in 10 of 15 hypothyroid patients. Thyroid autoantibodies were elevated during thyroid dysfunction in four of 10 cases. Diffuse increased 18FDG uptake by the thyroid gland was observed in all seven thyrotoxic patients who progressed to hypothyroidism.
AB - CONCLUSIONS: Thyroid dysfunction is common in melanoma patients treated with pembrolizumab. Hypothyroidism and thyrotoxicosis related to inflammatory thyroiditis are the most frequent presentations. Serial measurements of thyroid function tests are indicated during anti-PD-1 monoclonal antibody therapy. Thyrotoxicosis compatible with inflammatory thyroiditis was associated with diffuse increased 18FDG uptake by the thyroid gland. The prospective role of thyroid autoantibodies should be further investigated, together with the histopathological correlates.
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - DPT0O3T46P (pembrolizumab)
ES - 1945-7197
IL - 0021-972X
DO - https://dx.doi.org/10.1210/jc.2016-2300
PT - Journal Article
ID - 10.1210/jc.2016-2300 [doi]
ID - PMC5095250 [pmc]
PP - ppublish
LG - English
EP - 20160829
DP - 2016 Nov
DC - 20160829
EZ - 2016/08/30 06:00
DA - 2017/07/01 06:00
DT - 2016/11/05 06:00
YR - 2016
ED - 20170630
RD - 20170630
UP - 20170703
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27571185
<8. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27221508
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Lin HY
AU - Chin YT
AU - Nana AW
AU - Shih YJ
AU - Lai HY
AU - Tang HY
AU - Leinung M
AU - Mousa SA
AU - Davis PJ
FA - Lin, Hung-Yun
FA - Chin, Yu-Tang
FA - Nana, Andre Wendindonde
FA - Shih, Ya-Jung
FA - Lai, Hsuan-Yu
FA - Tang, Heng-Yuan
FA - Leinung, Matthew
FA - Mousa, Shaker A
FA - Davis, Paul J
IN - Lin, Hung-Yun. PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
IN - Chin, Yu-Tang. Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan; Department of Dentistry, Wan-Fang Medical Center, Taipei Medical University, Taipei, Taiwan.
IN - Nana, Andre Wendindonde. PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
IN - Shih, Ya-Jung. Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
IN - Lai, Hsuan-Yu. Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
IN - Tang, Heng-Yuan. Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; NanoPharmaceuticals LLC, Rensselaer, NY, USA.
IN - Leinung, Matthew. Department of Medicine, Albany Medical College, Albany, NY, USA.
IN - Mousa, Shaker A. Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; NanoPharmaceuticals LLC, Rensselaer, NY, USA.
IN - Davis, Paul J. Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA; NanoPharmaceuticals LLC, Rensselaer, NY, USA; Department of Medicine, Albany Medical College, Albany, NY, USA. Electronic address: pdavis.ordwayst@gmail.com.
TI - Actions of l-thyroxine and Nano-diamino-tetrac (Nanotetrac) on PD-L1 in cancer cells.
SO - Steroids. 114:59-67, 2016 Oct
AS - Steroids. 114:59-67, 2016 Oct
NJ - Steroids
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - v10, 0404536
IO - Steroids
SB - Index Medicus
CP - United States
MH - Antigens, CD274/ge [Genetics]
MH - *Antigens, CD274/me [Metabolism]
MH - Antineoplastic Agents/ch [Chemistry]
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - Breast Neoplasms/me [Metabolism]
MH - Cell Line, Tumor
MH - HCT116 Cells
MH - HT29 Cells
MH - Humans
MH - Phosphorylation/de [Drug Effects]
MH - RNA, Messenger
MH - Signal Transduction/de [Drug Effects]
MH - Signal Transduction/ge [Genetics]
MH - Thyroxine/aa [Analogs & Derivatives]
MH - Thyroxine/ch [Chemistry]
MH - *Thyroxine/pd [Pharmacology]
KW - Breast carcinoma; Cancer immunotherapy; Colon carcinoma; Programmed death ligand 1; l-Thyroxine (T(4))
AB - The PD-1 (programmed death-1)/PD-L1 (PD-ligand 1) checkpoint is a critical regulator of activated T cell-cancer cell interactions, defending tumor cells against immune destruction. Nano-diamino-tetrac (NDAT; Nanotetrac) is an anticancer/anti-angiogenic agent targeted to the thyroid hormone-tetrac receptor on the extracellular domain of integrin alphavbeta3. NDAT inhibits the cancer cell PI3-K and MAPK signal transduction pathways that are critical to PD-L1 gene expression. We examined actions in vitro of thyroid hormone (l-thyroxine, T4) and NDAT on PD-L1 mRNA abundance (qPCR) and PD-L1 protein content in human breast cancer (MDA-MB-231) cells and colon carcinoma (HCT116 and HT-29) cells. In MDA-MB-231 cells, a physiological concentration of T4 (10-7M total; 10-10M free hormone) stimulated PD-L1 gene expression by 38% and increased PD-L1 protein by 2.7-fold (p<0.05, all changes). NDAT (10-7M) reduced PD-L1 in T4-exposed cells by 21% (mRNA) and 39% (protein) (p<0.05, all changes). In HCT116 cells, T4 enhanced PD-L1 gene expression by 17% and protein content by 24% (p<0.05). NDAT reduced basal PD-L1 mRNA by 35% and protein by 31% and in T4-treated cells lowered mRNA by 33% and protein by 66%. In HT-29 cells, T4 increased PD-L1 mRNA by 62% and protein by 27%. NDAT lowered basal and T4-stimulated responses in PD-L1 mRNA and protein by 35-40% (p<0.05). Activation of ERK1/2 was involved in T4-induced PD-L1 accumulation. We propose that, by a nongenomic mechanism, endogenous T4 may clinically support activity of the defensive PD-1/PD-L1 checkpoint in tumor cells. NDAT non-immunologically suppresses basal and T4-induced PD-L1 gene expression and protein accumulation in cancer cells.
Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (CD274 protein, human)
RN - 0 (RNA, Messenger)
RN - PA7UX1FFYQ (tetraiodothyroacetic acid)
RN - Q51BO43MG4 (Thyroxine)
ES - 1878-5867
IL - 0039-128X
DI - S0039-128X(16)30038-1
DO - https://dx.doi.org/10.1016/j.steroids.2016.05.006
PT - Journal Article
ID - S0039-128X(16)30038-1 [pii]
ID - 10.1016/j.steroids.2016.05.006 [doi]
PP - ppublish
PH - 2016/01/28 [received]
PH - 2016/05/13 [revised]
PH - 2016/05/19 [accepted]
LG - English
EP - 20160521
DP - 2016 Oct
DC - 20160603
EZ - 2016/05/26 06:00
DA - 2017/06/27 06:00
DT - 2016/05/26 06:00
YR - 2016
ED - 20170626
RD - 20170626
UP - 20170627
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27221508
<9. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28564739
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Micheel A
AU - Aigner F
AU - Henke O
FA - Micheel, Anita
FA - Aigner, Felix
FA - Henke, Oliver
IN - Micheel, Anita. Bundeswehrkrankenhaus Berlin, Abteilung fur Innere Medizin, Berlin.
IN - Aigner, Felix. Charite - Universitatsmedizin Berlin, Chirurgische Klinik, Campus Virchow Klinikum, Berlin.
IN - Henke, Oliver. Bundeswehrkrankenhaus Berlin, Abteilung fur Innere Medizin, Berlin.
TI - [Histologic Remission following Neoadjuvant Immunotherapy in a Patient with Lynch-Syndrome and Primarily Unresectable Relapse of Rectum Carcinoma]. [German]
OT - Histologische Vollremission nach neoadjuvanter Immuntherapie bei einem Patienten mit Lynch-Syndrom und primar inoperablem Rezidiv eines Rektumkarzinoms.
SO - Deutsche Medizinische Wochenschrift. 142(11):842-846, 2017 Jun
AS - Dtsch Med Wochenschr. 142(11):842-846, 2017 Jun
NJ - Deutsche medizinische Wochenschrift (1946)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ecl, 0006723
IO - Dtsch. Med. Wochenschr.
SB - Index Medicus
CP - Germany
MH - Adult
MH - Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Colorectal Neoplasms, Hereditary Nonpolyposis/pa [Pathology]
MH - Colorectal Neoplasms, Hereditary Nonpolyposis/th [Therapy]
MH - *Colorectal Neoplasms, Hereditary Nonpolyposis
MH - Humans
MH - Immunotherapy
MH - Male
MH - Neoadjuvant Therapy
MH - Neoplasm Recurrence, Local
MH - Off-Label Use
MH - Rectal Neoplasms/pa [Pathology]
MH - Rectal Neoplasms/th [Therapy]
MH - *Rectal Neoplasms
MH - Recurrence
AB - Clinical History A 43-year-old male patient was diagnosed to have rectum carcinoma cT4N2M0 with underlying Lynch-Syndrome. After initializing neoadjuvant radio-chemotherapy followed by operation, the patient presents with an extensive locoregional relapse within a short time. In order to achieve resectability, a second line treatment with FOLFOXIRI protocol in addition to Bevacizumab was conducted. However, after completing six cycles of this intensiv treatment protocol, the tumour showed further progression. Clinical Course Having no evidence of distance metastasis, we decided to initiate off-label use of Pembrolizumab, a PD-1-receptor inhibitor. Clinical symptoms decreased rapidly and after receiving six cycles, PET/CT imaging showed regression. The side effects were limited to subclinical autoimmune thyroiditis. After re-operation no evidence of malignancy were found in the resectates of exenteration of the pelvis. Currently the patient is capable of working with only limited symptoms. Conclusion Pembrolizumab offers new treatment options for patients with DNA-repair-deficiency mismatch, e. g. Lynch-Syndrome. A phase II study already showed effectiveness in this particular group of patients. The striking and unexpected histo-pathologic results showing full remission should draw attention to the use of Pembrolizumab in neoadjuvant settings.
Copyright © Georg Thieme Verlag KG Stuttgart . New York.
OA - Publisher: Anamnese Bei dem 43-jahrigen mannlichen Patienten wurde ein Rektumkarzinom mit zugrundeliegendem Lynch-Syndrom im Stadium cT4N2M0 diagnostiziert. Nach leitliniengerechter neoadjuvanter Radiochemotherapie und Rektumexstirpation entwickelte sich innerhalb weniger Monate ein ausgedehntes lokoregionares Rezidiv. Es erfolgte eine erneute Polychemotherapie nach dem FOLFOXIRI-Protokoll in Kombination mit Bevacizumab fur sechs Zyklen, um erneute Resektabilitat zu erreichen. Trotz dieser intensiven Therapie zeigte sich der Befund progredient. Weiterer Verlauf Angesichts fehlender Fernmetastasierung wurde ein Off-label-Therapieversuch mit dem PD-1-Rezeptor Inhibitor Pembrolizumab begonnen. Klinisch profitierte der Patient rasch, auch die Bildgebung zeigte nach sechs Zyklen eine Regression des Tumors, die Nebenwirkungen der Therapie beschrankten sich auf eine subklinische Autoimmunthyreoiditis. Die histopathologische Aufarbeitung der anschliesenden ausgedehnten operativen Beckenexenteration konnte keinen Malignitatsnachweis mehr erbringen. Mittlerweile ist der Patient wieder dienstfahig mit geringer Symptomenlast. Folgerung Die Therapie mit Pembrolizumab eroffnet fur Patienten mit einem DNA-repair-deficiency mismatch, wie z. B. dem Lynch-Syndrom, eine Therapiealternative, wie bereits eine Phase-II-Studie zeigen konnte. Bemerkenswert ist in dem vorliegenden Fall die komplette histopathologische Vollremission, die bislang in der Literatur nicht beschrieben wurde und ein besonderes Augenmerk auf die Verwendung des Antikorpers Pembrolizumab auf den neoadjuvanten Einsatz legt.; Language: German
CI - Disclosure The authors report no conflicts of interest in this work.
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - DPT0O3T46P (pembrolizumab)
ES - 1439-4413
IL - 0012-0472
DO - https://dx.doi.org/10.1055/s-0043-101212
PT - Journal Article
ID - 10.1055/s-0043-101212 [doi]
PP - ppublish
LG - German
EP - 20170531
DP - 2017 Jun
DC - 20170531
EZ - 2017/06/01 06:00
DA - 2017/06/01 06:00
DT - 2017/06/01 06:00
YR - 2017
ED - 20170622
RD - 20170622
UP - 20170623
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28564739
<10. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27734691
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Cap J
FA - Cap, Jan
TI - [Endocrine complications of modern cancer therapy]. [Czech]
OT - Endokrinni komplikace moderni onkologicke lecby.
SO - Vnitrni Lekarstvi. 62(9 Suppl 3):45-49, Fall 2016
AS - Vnitr Lek. 62(9 Suppl 3):45-49, Fall 2016
NJ - Vnitrni lekarstvi
PI - Journal available in: Print
PI - Citation processed from: Print
JC - xfy, 0413602
IO - Vnitr Lek
SB - Index Medicus
CP - Czech Republic
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Anticarcinogenic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Humans
MH - *Hypophysitis/ci [Chemically Induced]
MH - *Hypothyroidism/ci [Chemically Induced]
MH - Immunotherapy
MH - *Neoplasms/dt [Drug Therapy]
MH - *Protein Kinase Inhibitors/ae [Adverse Effects]
MH - *Tetrahydronaphthalenes/ae [Adverse Effects]
MH - Thyroid Diseases/ci [Chemically Induced]
MH - *Thyroiditis, Autoimmune/ci [Chemically Induced]
MH - Thyroxine/me [Metabolism]
AB - Treatment with tyrosine kinase inhibitors leads to thyroid dysfunction in up to one half of treated patients, hypothyroidism being the most common. It is caused by destructive thyroiditis, impaired transport of T4 into the cell and deiodinase induction. Bexarotene is a nuclear retinoid X receptor agonist. Its application is accompanied with central hypothyroidism and hypertriglyceriaemia in virtually all patients and it also increases thyroxin metabolism. Autoimmune endocrine side effects are common in cancer immunotherapy. Cytokines (interpheron alpha and interleukin 2) cause autoimmune thyroiditis in 2-10 % of treated patients. Therapy with immune checkpoints inhibitors is connected with a variety of immune-related adverse events (irAE). Endocrine irAE include hypophysitis and thyroiditis during treatment with monoclonal antibodies against CTLA4 and thyroid dysfunction during therapy with antibody against CD1 receptor and its ligand. Knowledge, early recognition and management of these side effects is crucial.Key words: bexarotene - endocrine complication - hypophysitis - immune checkpoint inhibitors - immunotherapy.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Anticarcinogenic Agents)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (Protein Kinase Inhibitors)
RN - 0 (Tetrahydronaphthalenes)
RN - 6T8C155666 (ipilimumab)
RN - A61RXM4375 (bexarotene)
RN - Q51BO43MG4 (Thyroxine)
IS - 0042-773X
IL - 0042-773X
DI - 59243
PT - Journal Article
ID - 59243 [pii]
PP - ppublish
LG - Czech
DP - Fall 2016
DC - 20161013
EZ - 2016/10/14 06:00
DA - 2016/10/14 06:00
DT - 2016/10/14 06:00
YR - Fall
ED - 20170622
RD - 20170622
UP - 20170623
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27734691
<11. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28564739
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Micheel A
AU - Aigner F
AU - Henke O
FA - Micheel, Anita
FA - Aigner, Felix
FA - Henke, Oliver
IN - Micheel, Anita. Bundeswehrkrankenhaus Berlin, Abteilung fur Innere Medizin, Berlin.
IN - Aigner, Felix. Charite - Universitatsmedizin Berlin, Chirurgische Klinik, Campus Virchow Klinikum, Berlin.
IN - Henke, Oliver. Bundeswehrkrankenhaus Berlin, Abteilung fur Innere Medizin, Berlin.
TI - [Histologic Remission following Neoadjuvant Immunotherapy in a Patient with Lynch-Syndrome and Primarily Unresectable Relapse of Rectum Carcinoma]. [German]
OT - Histologische Vollremission nach neoadjuvanter Immuntherapie bei einem Patienten mit Lynch-Syndrom und primar inoperablem Rezidiv eines Rektumkarzinoms.
SO - Deutsche Medizinische Wochenschrift. 142(11):842-846, 2017 Jun
AS - Dtsch Med Wochenschr. 142(11):842-846, 2017 Jun
NJ - Deutsche medizinische Wochenschrift (1946)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ecl, 0006723
IO - Dtsch. Med. Wochenschr.
SB - Index Medicus
CP - Germany
MH - Adult
MH - Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Colorectal Neoplasms, Hereditary Nonpolyposis/pa [Pathology]
MH - Colorectal Neoplasms, Hereditary Nonpolyposis/th [Therapy]
MH - *Colorectal Neoplasms, Hereditary Nonpolyposis
MH - Humans
MH - Immunotherapy
MH - Male
MH - Neoadjuvant Therapy
MH - Neoplasm Recurrence, Local
MH - Off-Label Use
MH - Rectal Neoplasms/pa [Pathology]
MH - Rectal Neoplasms/th [Therapy]
MH - *Rectal Neoplasms
MH - Recurrence
AB - Clinical History A 43-year-old male patient was diagnosed to have rectum carcinoma cT4N2M0 with underlying Lynch-Syndrome. After initializing neoadjuvant radio-chemotherapy followed by operation, the patient presents with an extensive locoregional relapse within a short time. In order to achieve resectability, a second line treatment with FOLFOXIRI protocol in addition to Bevacizumab was conducted. However, after completing six cycles of this intensiv treatment protocol, the tumour showed further progression. Clinical Course Having no evidence of distance metastasis, we decided to initiate off-label use of Pembrolizumab, a PD-1-receptor inhibitor. Clinical symptoms decreased rapidly and after receiving six cycles, PET/CT imaging showed regression. The side effects were limited to subclinical autoimmune thyroiditis. After re-operation no evidence of malignancy were found in the resectates of exenteration of the pelvis. Currently the patient is capable of working with only limited symptoms. Conclusion Pembrolizumab offers new treatment options for patients with DNA-repair-deficiency mismatch, e. g. Lynch-Syndrome. A phase II study already showed effectiveness in this particular group of patients. The striking and unexpected histo-pathologic results showing full remission should draw attention to the use of Pembrolizumab in neoadjuvant settings.
Copyright © Georg Thieme Verlag KG Stuttgart . New York.
OA - Publisher: Anamnese Bei dem 43-jahrigen mannlichen Patienten wurde ein Rektumkarzinom mit zugrundeliegendem Lynch-Syndrom im Stadium cT4N2M0 diagnostiziert. Nach leitliniengerechter neoadjuvanter Radiochemotherapie und Rektumexstirpation entwickelte sich innerhalb weniger Monate ein ausgedehntes lokoregionares Rezidiv. Es erfolgte eine erneute Polychemotherapie nach dem FOLFOXIRI-Protokoll in Kombination mit Bevacizumab fur sechs Zyklen, um erneute Resektabilitat zu erreichen. Trotz dieser intensiven Therapie zeigte sich der Befund progredient. Weiterer Verlauf Angesichts fehlender Fernmetastasierung wurde ein Off-label-Therapieversuch mit dem PD-1-Rezeptor Inhibitor Pembrolizumab begonnen. Klinisch profitierte der Patient rasch, auch die Bildgebung zeigte nach sechs Zyklen eine Regression des Tumors, die Nebenwirkungen der Therapie beschrankten sich auf eine subklinische Autoimmunthyreoiditis. Die histopathologische Aufarbeitung der anschliesenden ausgedehnten operativen Beckenexenteration konnte keinen Malignitatsnachweis mehr erbringen. Mittlerweile ist der Patient wieder dienstfahig mit geringer Symptomenlast. Folgerung Die Therapie mit Pembrolizumab eroffnet fur Patienten mit einem DNA-repair-deficiency mismatch, wie z. B. dem Lynch-Syndrom, eine Therapiealternative, wie bereits eine Phase-II-Studie zeigen konnte. Bemerkenswert ist in dem vorliegenden Fall die komplette histopathologische Vollremission, die bislang in der Literatur nicht beschrieben wurde und ein besonderes Augenmerk auf die Verwendung des Antikorpers Pembrolizumab auf den neoadjuvanten Einsatz legt.; Language: German
CI - Disclosure The authors report no conflicts of interest in this work.
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - DPT0O3T46P (pembrolizumab)
ES - 1439-4413
IL - 0012-0472
DO - https://dx.doi.org/10.1055/s-0043-101212
PT - Journal Article
ID - 10.1055/s-0043-101212 [doi]
PP - ppublish
LG - German
EP - 20170531
DP - 2017 Jun
DC - 20170531
EZ - 2017/06/01 06:00
DA - 2017/06/24 06:00
DT - 2017/06/01 06:00
YR - 2017
ED - 20170622
RD - 20170622
UP - 20170626
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=28564739
<12. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27734691
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Cap J
FA - Cap, Jan
TI - [Endocrine complications of modern cancer therapy]. [Czech]
OT - Endokrinni komplikace moderni onkologicke lecby.
SO - Vnitrni Lekarstvi. 62(9 Suppl 3):45-49, Fall 2016
AS - Vnitr Lek. 62(9 Suppl 3):45-49, Fall 2016
NJ - Vnitrni lekarstvi
PI - Journal available in: Print
PI - Citation processed from: Print
JC - xfy, 0413602
IO - Vnitr Lek
SB - Index Medicus
CP - Czech Republic
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Anticarcinogenic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Humans
MH - *Hypophysitis/ci [Chemically Induced]
MH - *Hypothyroidism/ci [Chemically Induced]
MH - Immunotherapy
MH - *Neoplasms/dt [Drug Therapy]
MH - *Protein Kinase Inhibitors/ae [Adverse Effects]
MH - *Tetrahydronaphthalenes/ae [Adverse Effects]
MH - Thyroid Diseases/ci [Chemically Induced]
MH - *Thyroiditis, Autoimmune/ci [Chemically Induced]
MH - Thyroxine/me [Metabolism]
AB - Treatment with tyrosine kinase inhibitors leads to thyroid dysfunction in up to one half of treated patients, hypothyroidism being the most common. It is caused by destructive thyroiditis, impaired transport of T4 into the cell and deiodinase induction. Bexarotene is a nuclear retinoid X receptor agonist. Its application is accompanied with central hypothyroidism and hypertriglyceriaemia in virtually all patients and it also increases thyroxin metabolism. Autoimmune endocrine side effects are common in cancer immunotherapy. Cytokines (interpheron alpha and interleukin 2) cause autoimmune thyroiditis in 2-10 % of treated patients. Therapy with immune checkpoints inhibitors is connected with a variety of immune-related adverse events (irAE). Endocrine irAE include hypophysitis and thyroiditis during treatment with monoclonal antibodies against CTLA4 and thyroid dysfunction during therapy with antibody against CD1 receptor and its ligand. Knowledge, early recognition and management of these side effects is crucial.Key words: bexarotene - endocrine complication - hypophysitis - immune checkpoint inhibitors - immunotherapy.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Anticarcinogenic Agents)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (Protein Kinase Inhibitors)
RN - 0 (Tetrahydronaphthalenes)
RN - 6T8C155666 (ipilimumab)
RN - A61RXM4375 (bexarotene)
RN - Q51BO43MG4 (Thyroxine)
IS - 0042-773X
IL - 0042-773X
DI - 59243
PT - Journal Article
ID - 59243 [pii]
PP - ppublish
LG - Czech
DP - Fall 2016
DC - 20161013
EZ - 2016/10/14 06:00
DA - 2017/06/24 06:00
DT - 2016/10/14 06:00
YR - Fall
ED - 20170622
RD - 20170622
UP - 20170626
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=27734691
<13. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28065619
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Gottlieb CE
AU - Mills AM
AU - Cross JV
AU - Ring KL
FA - Gottlieb, Chelsea E
FA - Mills, Anne M
FA - Cross, Janet V
FA - Ring, Kari L
IN - Gottlieb, Chelsea E. Department of Pathology, University of Virginia Health System, PO Box 800712, Charlottesville, VA, United States. Electronic address: CEG2KC@hscmail.mcc.virginia.edu.
IN - Mills, Anne M. Department of Pathology, University of Virginia Health System, PO Box 800712, Charlottesville, VA, United States. Electronic address: AMM7R@hscmail.mcc.virginia.edu.
IN - Cross, Janet V. Department of Pathology, University of Virginia Health System, PO Box 800712, Charlottesville, VA, United States. Electronic address: jvc5b@eservices.virginia.edu.
IN - Ring, Kari L. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Virginia Health System, PO Box 800712, Charlottesville, VA, United States. Electronic address: kel7j@hscmail.mcc.virginia.edu.
TI - Tumor-associated macrophage expression of PD-L1 in implants of high grade serous ovarian carcinoma: A comparison of matched primary and metastatic tumors.
SO - Gynecologic Oncology. 144(3):607-612, 2017 Mar
AS - Gynecol Oncol. 144(3):607-612, 2017 Mar
NJ - Gynecologic oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - fxc, 0365304
IO - Gynecol. Oncol.
SB - Index Medicus
CP - United States
MH - *Antigens, CD274/bi [Biosynthesis]
MH - Antigens, CD274/ge [Genetics]
MH - Cystadenocarcinoma, Serous/ge [Genetics]
MH - *Cystadenocarcinoma, Serous/me [Metabolism]
MH - Female
MH - Humans
MH - Immunohistochemistry
MH - *Macrophages/me [Metabolism]
MH - Middle Aged
MH - Neoplasm Grading
MH - Ovarian Neoplasms/ge [Genetics]
MH - *Ovarian Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/pa [Pathology]
KW - BRCA; High grade serous ovarian cancer; PD-L1; Treatment naive; Tumor-associated macrophages
AB - OBJECTIVE: Data on PD-L1 expression in high grade serous ovarian carcinoma (HGSOC) is mixed. Some studies report robust tumor staining and others identify expression limited to tumor-associated macrophages (TAM). TAM PD-L1 expression is induced in HGSOC metastatic implants from patients who have undergone chemotherapy. However, it is unclear whether TAM acquisition of PD-L1 plays a role in treatment naive tumors. We investigated PD-L1 expression in primary ovarian tumors and matched metastatic implants from predominantly treatment-naive HGSOC.
AB - METHODS: Sixty one primary HGSOC were evaluated with PD-L1 and CD68 IHC: 40 on TMA and 21 on whole section. Whole section cases were matched to a metastatic implant. TAM were delineated by CD68. Membranous PD-L1 staining was scored separately for tumor cells and TAM.
AB - RESULTS: Eight percent of primary HGSOC demonstrated PD-L1 expression. In contrast, 74% showed PD-L1+ TAM. In the 16 treatment naive cases, 13 (81.3%) demonstrated fidelity in intratumoral PD-L1 expression between the primary and metastatic site. Of the 21 matched pairs, only one case (4.8%) did not exhibit PD-L1 positive TAM in the metastatic implant and 19 (90.5%) showed fidelity across both locations. Intratumoral and immune infiltrate PD-L1 expression was not different in cases who received neoadjuvant chemotherapy compared to treatment naive cases.
AB - CONCLUSIONS: PD-L1+ TAM are common in both primary and metastatic HGSOC however tumoral PD-L1 staining is rare. There was high fidelity of PD-L1 expression when comparing primary tumors and metastatic implants in treatment naive specimens. Clinical trials are needed to determine whether tumor-associated staining correlates with clinical response to PD-1/PD-L1 inhibition.
Copyright A© 2016 Elsevier Inc. All rights reserved.
RN - 0 (Antigens, CD274)
RN - 0 (CD274 protein, human)
ES - 1095-6859
IL - 0090-8258
DI - S0090-8258(16)31685-7
DO - https://dx.doi.org/10.1016/j.ygyno.2016.12.021
PT - Journal Article
ID - S0090-8258(16)31685-7 [pii]
ID - 10.1016/j.ygyno.2016.12.021 [doi]
PP - ppublish
PH - 2016/11/29 [received]
PH - 2016/12/21 [revised]
PH - 2016/12/22 [accepted]
LG - English
EP - 20170105
DP - 2017 Mar
DC - 20170109
EZ - 2017/01/10 06:00
DA - 2017/06/22 06:00
DT - 2017/01/10 06:00
YR - 2017
ED - 20170621
RD - 20170621
UP - 20170622
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28065619
<14. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28253833
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Andrikou K
AU - Peterle C
AU - Pipitone S
AU - Salati M
AU - Cascinu S
FA - Andrikou, Kalliopi
FA - Peterle, Chiara
FA - Pipitone, Stefania
FA - Salati, Massimiliano
FA - Cascinu, Stefano
IN - Andrikou, Kalliopi. a Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults , University Hospital of Modena , Modena , Italy.
IN - Peterle, Chiara. a Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults , University Hospital of Modena , Modena , Italy.
IN - Pipitone, Stefania. a Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults , University Hospital of Modena , Modena , Italy.
IN - Salati, Massimiliano. a Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults , University Hospital of Modena , Modena , Italy.
IN - Cascinu, Stefano. a Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults , University Hospital of Modena , Modena , Italy.
TI - Emerging antibodies for the treatment of pancreatic cancer. [Review]
SO - Expert Opinion on Emerging Drugs. 22(1):39-51, 2017 Mar
AS - Expert Opin Emerg Drugs. 22(1):39-51, 2017 Mar
NJ - Expert opinion on emerging drugs
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101135662
IO - Expert Opin Emerg Drugs
SB - Index Medicus
CP - England
MH - *Adenocarcinoma/dt [Drug Therapy]
MH - Adenocarcinoma/pa [Pathology]
MH - Animals
MH - *Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/pd [Pharmacology]
MH - Antineoplastic Combined Chemotherapy Protocols/ad [Administration & Dosage]
MH - Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
MH - Antineoplastic Combined Chemotherapy Protocols/pd [Pharmacology]
MH - Biomarkers, Tumor/me [Metabolism]
MH - *Carcinoma, Pancreatic Ductal/dt [Drug Therapy]
MH - Carcinoma, Pancreatic Ductal/pa [Pathology]
MH - Drug Design
MH - Humans
MH - Molecular Targeted Therapy
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Patient Selection
MH - Tumor Microenvironment
KW - Biomarkers; immunotherapy; monoclonal antibodies; pancreatic cancer; targeted therapies
AB - INTRODUCTION: Pancreatic ductal adenocarcinoma cancer (PDAC) is the fourth leading cause of cancer death worldwide. Recently, two chemotherapy regimens have proven to improve median overall survival in comparison with gemcitabine. Based on better understanding of tumor molecular biology and of the role of tumor microenvironment, monoclonal antibodies (mAbs) could be an interesting and new type of targeted treatment of PDAC. Areas covered: Preclinical and clinical trials have evaluated the efficacy of several mAbs in pancreatic cancer treatment. This review will underline the most important targeted pathways by mAbs involved in this disease, including EGFR, HER-2, IGF-1 R, VEGF/VEGFR, NOTCH, WNT and immune checkpoints. Expert opinion: Despite the promising results of preclinical and phase I trials, the addition of mAbs to standard chemotherapy or in association with other target agents seems not to confirm these results in the following phase II and III trials in pancreatic cancer patients. However, an improved patient selection before treatment based on molecular characteristics in association with reliable predictive biomarkers can identified more efficacious treatment approaches, minimizing toxicity profile of these drugs.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Biomarkers, Tumor)
ES - 1744-7623
IL - 1472-8214
DO - https://dx.doi.org/10.1080/14728214.2017.1293649
PT - Journal Article
PT - Review
ID - 10.1080/14728214.2017.1293649 [doi]
PP - ppublish
LG - English
EP - 20170228
DP - 2017 Mar
DC - 20170303
EZ - 2017/03/04 06:00
DA - 2017/06/20 06:00
DT - 2017/03/04 06:00
YR - 2017
ED - 20170619
RD - 20170619
UP - 20170620
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28253833
<15. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28283736
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Yamazaki N
AU - Takenouchi T
AU - Fujimoto M
AU - Ihn H
AU - Uchi H
AU - Inozume T
AU - Kiyohara Y
AU - Uhara H
AU - Nakagawa K
AU - Furukawa H
AU - Wada H
AU - Noguchi K
AU - Shimamoto T
AU - Yokota K
FA - Yamazaki, Naoya
FA - Takenouchi, Tatsuya
FA - Fujimoto, Manabu
FA - Ihn, Hironobu
FA - Uchi, Hiroshi
FA - Inozume, Takashi
FA - Kiyohara, Yoshio
FA - Uhara, Hisashi
FA - Nakagawa, Kazuhiko
FA - Furukawa, Hiroshi
FA - Wada, Hidefumi
FA - Noguchi, Kazuo
FA - Shimamoto, Takashi
FA - Yokota, Kenji
IN - Yamazaki, Naoya. Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. nyamazaki@ncc.go.jp.
IN - Takenouchi, Tatsuya. Department of Dermatology, Niigata Cancer Center Hospital, Niigata, Japan.
IN - Fujimoto, Manabu. Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
IN - Ihn, Hironobu. Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
IN - Uchi, Hiroshi. Department of Dermatology, Kyushu University School of Medicine, Fukuoka, Japan.
IN - Inozume, Takashi. Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
IN - Kiyohara, Yoshio. Department of Dermatology, Shizuoka Cancer Center, Shizuoka, Japan.
IN - Uhara, Hisashi. Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
IN - Nakagawa, Kazuhiko. Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-sayama, Japan.
IN - Furukawa, Hiroshi. Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
IN - Wada, Hidefumi. Department of Dermatology, Yokohama City University School of Medicine, Yokohama, Japan.
IN - Noguchi, Kazuo. MSD K.K., Tokyo, Japan.
IN - Shimamoto, Takashi. MSD K.K., Tokyo, Japan.
IN - Yokota, Kenji. Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
TI - Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041).
SO - Cancer Chemotherapy & Pharmacology. 79(4):651-660, 2017 Apr
AS - Cancer Chemother Pharmacol. 79(4):651-660, 2017 Apr
NJ - Cancer chemotherapy and pharmacology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c9s, 7806519
IO - Cancer Chemother. Pharmacol.
SB - Index Medicus
CP - Germany
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - *Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Asian Continental Ancestry Group
MH - Disease-Free Survival
MH - Female
MH - Humans
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/ge [Genetics]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - *Programmed Cell Death 1 Receptor/im [Immunology]
MH - Skin/pa [Pathology]
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/ge [Genetics]
MH - Skin Neoplasms/pa [Pathology]
MH - Survival Analysis
KW - Anti-PD-1 therapy; Immunotherapy; Japanese patients; Melanoma; Pembrolizumab
AB - PURPOSE: This phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma.
AB - METHODS: Pembrolizumab (2 mg/kg) was given every 3 weeks (Q3W) for up to 2 years or until confirmed progression or unacceptable toxicity. The tumor response was assessed as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by both investigator review and central review.
AB - RESULTS: Forty-two patients with advanced melanoma received pembrolizumab. A primary cutaneous histology was observed in 34 patients (81.0%), while a primary mucosal histology was observed in 8 patients (19.0%). Thirty-four patients (81.0%) experienced treatment-related adverse events (AEs). The most common treatment-related AEs were pruritus, maculopapular rash, malaise, and hypothyroidism. Grade 3-5 treatment-related AEs occurred in 8 patients (19.0%). The only grade 3-5 treatment-related AE reported in at least two patients was anemia. There were two treatment-related deaths (unknown cause and cerebral hemorrhage). Among the 37 evaluable patients, the confirmed overall response rates (ORRs) determined by central review were 24.1% (95% CI 10.3-43.5) for cutaneous melanoma and 25.0% (95% CI 3.2-65.1) for mucosal melanoma. The responses were durable, and the median duration of response was not reached in either population. The median overall survival (OS) was not reached, with a 12-month OS of 82.7% for cutaneous melanoma and 51.4% for mucosal melanoma.
AB - CONCLUSION: The safety profile of pembrolizumab in Japanese patients was similar to that reported in the previous clinical studies. Pembrolizumab provided promising anti-tumor activity in Japanese patients with advanced melanoma.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - DPT0O3T46P (pembrolizumab)
RS - Melanoma, Cutaneous Malignant
ES - 1432-0843
IL - 0344-5704
DI - 10.1007/s00280-016-3237-x
DO - https://dx.doi.org/10.1007/s00280-016-3237-x
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Multicenter Study
ID - 10.1007/s00280-016-3237-x [doi]
ID - 10.1007/s00280-016-3237-x [pii]
ID - PMC5364262 [pmc]
PP - ppublish
PH - 2016/12/02 [received]
PH - 2016/12/28 [accepted]
LG - English
EP - 20170311
DP - 2017 Apr
DC - 20170311
EZ - 2017/03/12 06:00
DA - 2017/06/14 06:00
DT - 2017/03/12 06:00
YR - 2017
ED - 20170613
RD - 20170613
UP - 20170614
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28283736
<16. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27932067
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Hellmann MD
AU - Rizvi NA
AU - Goldman JW
AU - Gettinger SN
AU - Borghaei H
AU - Brahmer JR
AU - Ready NE
AU - Gerber DE
AU - Chow LQ
AU - Juergens RA
AU - Shepherd FA
AU - Laurie SA
AU - Geese WJ
AU - Agrawal S
AU - Young TC
AU - Li X
AU - Antonia SJ
FA - Hellmann, Matthew D
FA - Rizvi, Naiyer A
FA - Goldman, Jonathan W
FA - Gettinger, Scott N
FA - Borghaei, Hossein
FA - Brahmer, Julie R
FA - Ready, Neal E
FA - Gerber, David E
FA - Chow, Laura Q
FA - Juergens, Rosalyn A
FA - Shepherd, Frances A
FA - Laurie, Scott A
FA - Geese, William J
FA - Agrawal, Shruti
FA - Young, Tina C
FA - Li, Xuemei
FA - Antonia, Scott J
IN - Hellmann, Matthew D. Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: hellmanm@mskcc.org.
IN - Rizvi, Naiyer A. Memorial Sloan Kettering Cancer Center, New York, NY, USA.
IN - Goldman, Jonathan W. UCLA, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
IN - Gettinger, Scott N. Yale Comprehensive Cancer Center, New Haven, CT, USA.
IN - Borghaei, Hossein. Fox Chase Cancer Center, Philadelphia, PA, USA.
IN - Brahmer, Julie R. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
IN - Ready, Neal E. Duke University Medical Center, Durham, NC, USA.
IN - Gerber, David E. UT Southwestern Medical Center, Dallas, TX, USA.
IN - Chow, Laura Q. University of Washington, Seattle, WA, USA.
IN - Juergens, Rosalyn A. Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada.
IN - Shepherd, Frances A. Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
IN - Laurie, Scott A. Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada.
IN - Geese, William J. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Agrawal, Shruti. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Young, Tina C. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Li, Xuemei. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Antonia, Scott J. H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
TI - Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study.
SO - Lancet Oncology. 18(1):31-41, 2017 Jan
AS - Lancet Oncol. 18(1):31-41, 2017 Jan
NJ - The Lancet. Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 100957246
IO - Lancet Oncol.
SB - Index Medicus
CP - England
MH - *Adenocarcinoma/dt [Drug Therapy]
MH - Adenocarcinoma/pa [Pathology]
MH - Aged
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - *Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Carcinoma, Non-Small-Cell Lung/pa [Pathology]
MH - *Carcinoma, Squamous Cell/dt [Drug Therapy]
MH - Carcinoma, Squamous Cell/pa [Pathology]
MH - Cohort Studies
MH - Female
MH - Follow-Up Studies
MH - Humans
MH - *Lung Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/pa [Pathology]
MH - Male
MH - Middle Aged
MH - Neoplasm Staging
MH - Prognosis
MH - Survival Rate
AB - BACKGROUND: Nivolumab has shown improved survival in the treatment of advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy. We assessed the safety and activity of combination nivolumab plus ipilimumab as first-line therapy for NSCLC.
AB - METHODS: The open-label, phase 1, multicohort study (CheckMate 012) cohorts reported here were enrolled at eight US academic centres. Eligible patients were aged 18 years or older with histologically or cytologically confirmed recurrent stage IIIb or stage IV, chemotherapy-naive NSCLC. Patients were randomly assigned (1:1:1) by an interactive voice response system to receive nivolumab 1 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks, nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 12 weeks, or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks until disease progression, unacceptable toxicities, or withdrawal of consent. Data from the latter two cohorts, which were considered potentially suitable for further clinical development, are presented in this report; data from the other cohort (as well as several earlier cohorts) are described in the appendix. The primary outcome was safety and tolerability, assessed in all treated patients. This ongoing study is registered with ClinicalTrials.gov, number NCT01454102.
AB - FINDINGS: Between May 15, 2014, and March 25, 2015, 78 patients were randomly assigned to receive nivolumab every 2 weeks plus ipilimumab every 12 weeks (n=38) or nivolumab every 2 weeks plus ipilimumab every 6 weeks (n=40). One patient in the ipilimumab every-6-weeks cohort was excluded before treatment; therefore 77 patients actually received treatment (38 in the ipilimumab every-12-weeks cohort; 39 in the ipilimumab every-6-weeks cohort). At data cut-off on Jan 7, 2016, 29 (76%) patients in the ipilimumab every-12-weeks cohort and 32 (82%) in the ipilimumab every-6-weeks cohort had discontinued treatment. Grade 3-4 treatment-related adverse events occurred in 14 (37%) patients in the ipilimumab every-12-weeks cohort and 13 (33%) patients in the every-6-weeks cohort; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase (three [8%] and no patients), pneumonitis (two [5%] and one [3%] patients), adrenal insufficiency (one [3%] and two [5%] patients), and colitis (one [3%] and two [5%] patients). Treatment-related serious adverse events were reported in 12 (32%) patients in the ipilimumab every-12-weeks cohort and 11 (28%) patients in the every-6-weeks cohort. Treatment-related adverse events (any grade) prompted treatment discontinuation in four (11%) patients in the every-12-weeks cohort and five (13%) patients in the every-6-weeks cohort. No treatment-related deaths occurred. Confirmed objective responses were achieved in 18 (47% [95% CI 31-64]) patients in the ipilimumab every-12-weeks cohort and 15 (38% [95% CI 23-55]) patients in the ipilimumab every-6-weeks cohort; median duration of response was not reached in either cohort, with median follow-up times of 12.8 months (IQR 9.3-15.5) in the ipilimumab every-12-weeks cohort and 11.8 months (6.7-15.9) in the ipilimumab every-6-weeks cohort. In patients with PD-L1 of 1% or greater, confirmed objective responses were achieved in 12 (57%) of 21 patients in the ipilimumab every-12-weeks cohort and 13 (57%) of 23 patients in the ipilimumab every-6-weeks cohort.
AB - INTERPRETATION: In NSCLC, first-line nivolumab plus ipilimumab had a tolerable safety profile and showed encouraging clinical activity characterised by a high response rate and durable response. To our knowledge, the results of this study are the first suggestion of improved benefit compared with anti-PD-1 monotherapy in patients with NSCLC, supporting further assessment of this combination in a phase 3 study.
AB - FUNDING: Bristol-Myers Squibb.
AB - Copyright © 2017 Elsevier Ltd. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 31YO63LBSN (nivolumab)
RN - 6T8C155666 (ipilimumab)
ES - 1474-5488
IL - 1470-2045
DI - S1470-2045(16)30624-6
DO - https://dx.doi.org/10.1016/S1470-2045(16)30624-6
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Multicenter Study
PT - Randomized Controlled Trial
ID - S1470-2045(16)30624-6 [pii]
ID - 10.1016/S1470-2045(16)30624-6 [doi]
PP - ppublish
PH - 2016/09/07 [received]
PH - 2016/10/01 [revised]
PH - 2016/10/05 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01454102
SL - https://clinicaltrials.gov/search/term=NCT01454102
GI - No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20161205
DP - 2017 Jan
DC - 20161209
EZ - 2016/12/10 06:00
DA - 2017/06/14 06:00
DT - 2016/12/10 06:00
YR - 2017
ED - 20170613
RD - 20170613
UP - 20170614
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27932067
<17. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27856273
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Humphris JL
AU - Patch AM
AU - Nones K
AU - Bailey PJ
AU - Johns AL
AU - McKay S
AU - Chang DK
AU - Miller DK
AU - Pajic M
AU - Kassahn KS
AU - Quinn MC
AU - Bruxner TJ
AU - Christ AN
AU - Harliwong I
AU - Idrisoglu S
AU - Manning S
AU - Nourse C
AU - Nourbakhsh E
AU - Stone A
AU - Wilson PJ
AU - Anderson M
AU - Fink JL
AU - Holmes O
AU - Kazakoff S
AU - Leonard C
AU - Newell F
AU - Waddell N
AU - Wood S
AU - Mead RS
AU - Xu Q
AU - Wu J
AU - Pinese M
AU - Cowley MJ
AU - Jones MD
AU - Nagrial AM
AU - Chin VT
AU - Chantrill LA
AU - Mawson A
AU - Chou A
AU - Scarlett CJ
AU - Pinho AV
AU - Rooman I
AU - Giry-Laterriere M
AU - Samra JS
AU - Kench JG
AU - Merrett ND
AU - Toon CW
AU - Epari K
AU - Nguyen NQ
AU - Barbour A
AU - Zeps N
AU - Jamieson NB
AU - McKay CJ
AU - Carter CR
AU - Dickson EJ
AU - Graham JS
AU - Duthie F
AU - Oien K
AU - Hair J
AU - Morton JP
AU - Sansom OJ
AU - Grutzmann R
AU - Hruban RH
AU - Maitra A
AU - Iacobuzio-Donahue CA
AU - Schulick RD
AU - Wolfgang CL
AU - Morgan RA
AU - Lawlor RT
AU - Rusev B
AU - Corbo V
AU - Salvia R
AU - Cataldo I
AU - Tortora G
AU - Tempero MA
AU - Australian Pancreatic Cancer Genome Initiative
AU - Hofmann O
AU - Eshleman JR
AU - Pilarsky C
AU - Scarpa A
AU - Musgrove EA
AU - Gill AJ
AU - Pearson JV
AU - Grimmond SM
AU - Waddell N
AU - Biankin AV
FA - Humphris, Jeremy L
FA - Patch, Ann-Marie
FA - Nones, Katia
FA - Bailey, Peter J
FA - Johns, Amber L
FA - McKay, Skye
FA - Chang, David K
FA - Miller, David K
FA - Pajic, Marina
FA - Kassahn, Karin S
FA - Quinn, Michael C J
FA - Bruxner, Timothy J C
FA - Christ, Angelika N
FA - Harliwong, Ivon
FA - Idrisoglu, Senel
FA - Manning, Suzanne
FA - Nourse, Craig
FA - Nourbakhsh, Ehsan
FA - Stone, Andrew
FA - Wilson, Peter J
FA - Anderson, Matthew
FA - Fink, J Lynn
FA - Holmes, Oliver
FA - Kazakoff, Stephen
FA - Leonard, Conrad
FA - Newell, Felicity
FA - Waddell, Nick
FA - Wood, Scott
FA - Mead, Ronald S
FA - Xu, Qinying
FA - Wu, Jianmin
FA - Pinese, Mark
FA - Cowley, Mark J
FA - Jones, Marc D
FA - Nagrial, Adnan M
FA - Chin, Venessa T
FA - Chantrill, Lorraine A
FA - Mawson, Amanda
FA - Chou, Angela
FA - Scarlett, Christopher J
FA - Pinho, Andreia V
FA - Rooman, Ilse
FA - Giry-Laterriere, Marc
FA - Samra, Jaswinder S
FA - Kench, James G
FA - Merrett, Neil D
FA - Toon, Christopher W
FA - Epari, Krishna
FA - Nguyen, Nam Q
FA - Barbour, Andrew
FA - Zeps, Nikolajs
FA - Jamieson, Nigel B
FA - McKay, Colin J
FA - Carter, C Ross
FA - Dickson, Euan J
FA - Graham, Janet S
FA - Duthie, Fraser
FA - Oien, Karin
FA - Hair, Jane
FA - Morton, Jennifer P
FA - Sansom, Owen J
FA - Grutzmann, Robert
FA - Hruban, Ralph H
FA - Maitra, Anirban
FA - Iacobuzio-Donahue, Christine A
FA - Schulick, Richard D
FA - Wolfgang, Christopher L
FA - Morgan, Richard A
FA - Lawlor, Rita T
FA - Rusev, Borislav
FA - Corbo, Vincenzo
FA - Salvia, Roberto
FA - Cataldo, Ivana
FA - Tortora, Giampaolo
FA - Tempero, Margaret A
FA - Australian Pancreatic Cancer Genome Initiative
FA - Hofmann, Oliver
FA - Eshleman, James R
FA - Pilarsky, Christian
FA - Scarpa, Aldo
FA - Musgrove, Elizabeth A
FA - Gill, Anthony J
FA - Pearson, John V
FA - Grimmond, Sean M
FA - Waddell, Nicola
FA - Biankin, Andrew V
IN - Humphris, Jeremy L. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
IN - Patch, Ann-Marie. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Nones, Katia. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Bailey, Peter J. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
IN - Johns, Amber L. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
IN - McKay, Skye. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
IN - Chang, David K. Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Department of Surgery, Bankstown Hospital, Bankstown, Sydney, New South Wales, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales Australia, Liverpool, New South Wales, Australia; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
IN - Miller, David K. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Pajic, Marina. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Darlinghurst, New South Wales, Australia.
IN - Kassahn, Karin S. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; Genetic and Molecular Pathology, Adelaide, South Australia, Australia; School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
IN - Quinn, Michael C J. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Bruxner, Timothy J C. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Christ, Angelika N. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Harliwong, Ivon. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Idrisoglu, Senel. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Manning, Suzanne. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Nourse, Craig. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Darlinghurst, New South Wales, Australia.
IN - Nourbakhsh, Ehsan. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Stone, Andrew. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
IN - Wilson, Peter J. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Anderson, Matthew. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Fink, J Lynn. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Holmes, Oliver. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Kazakoff, Stephen. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Leonard, Conrad. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Newell, Felicity. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Waddell, Nick. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Wood, Scott. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Mead, Ronald S. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; South Eastern Area Laboratory Services Pathology, Prince of Wales Hospital, Randwick, New South Wales, Australia; Sonic Genetics, Douglass Hanly Moir Pathology, New South Wales, Australia.
IN - Xu, Qinying. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Wu, Jianmin. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
IN - Pinese, Mark. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
IN - Cowley, Mark J. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Darlinghurst, New South Wales, Australia.
IN - Jones, Marc D. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
IN - Nagrial, Adnan M. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
IN - Chin, Venessa T. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
IN - Chantrill, Lorraine A. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Macarthur Cancer Therapy Centre, Campbelltown Hospital, New South Wales, Australia.
IN - Mawson, Amanda. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
IN - Chou, Angela. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Department of Anatomical Pathology, SydPath, St Vincent's Hospital, New South Wales, Australia.
IN - Scarlett, Christopher J. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; School of Environmental and Life Sciences, University of Newcastle, Ourimbah, New South Wales, Australia.
IN - Pinho, Andreia V. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
IN - Rooman, Ilse. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
IN - Giry-Laterriere, Marc. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
IN - Samra, Jaswinder S. Department of Surgery, Royal North Shore Hospital, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia.
IN - Kench, James G. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
IN - Merrett, Neil D. Department of Surgery, Bankstown Hospital, Bankstown, Sydney, New South Wales, Australia; School of Medicine, Western Sydney University, Penrith, New South Wales, Australia.
IN - Toon, Christopher W. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
IN - Epari, Krishna. Department of Surgery, Fiona Stanley Hospital, Murdoch, Washington.
IN - Nguyen, Nam Q. Department of Gastroenterology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, Australia.
IN - Barbour, Andrew. Department of Surgery, Princess Alexandra Hospital, Woollongabba, Queensland, Australia.
IN - Zeps, Nikolajs. School of Surgery, University of Western Australia, Australia and St John of God Pathology, Subiaco, Washington.
IN - Jamieson, Nigel B. Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom; Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom.
IN - McKay, Colin J. West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
IN - Carter, C Ross. West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
IN - Dickson, Euan J. West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
IN - Graham, Janet S. Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Department of Medical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
IN - Duthie, Fraser. Department of Pathology, Southern General Hospital, Greater Glasgow & Clyde National Health Service, Glasgow, United Kingdom.
IN - Oien, Karin. Department of Pathology, Southern General Hospital, Greater Glasgow & Clyde National Health Service, Glasgow, United Kingdom.
IN - Hair, Jane. Greater Glasgow and Clyde Bio-repository, Pathology Department, Queen Elizabeth University Hospital, Glasgow, United Kingdom.
IN - Morton, Jennifer P. Cancer Research UK Beatson Institute, Glasgow, United Kingdom; Institute for Cancer Science, University of Glasgow, Glasgow, United Kingdom.
IN - Sansom, Owen J. Cancer Research UK Beatson Institute, Glasgow, United Kingdom; Institute for Cancer Science, University of Glasgow, Glasgow, United Kingdom.
IN - Grutzmann, Robert. Universitatsklinikum Erlangen, Erlangen, Germany.
IN - Hruban, Ralph H. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland.
IN - Maitra, Anirban. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland.
IN - Iacobuzio-Donahue, Christine A. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland.
IN - Schulick, Richard D. Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland.
IN - Wolfgang, Christopher L. Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland.
IN - Morgan, Richard A. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland.
IN - Lawlor, Rita T. ARC-NET Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy; Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
IN - Rusev, Borislav. ARC-NET Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy; Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
IN - Corbo, Vincenzo. ARC-NET Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy; Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
IN - Salvia, Roberto. ARC-NET Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy; Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
IN - Cataldo, Ivana. ARC-NET Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy; Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
IN - Tortora, Giampaolo. Department of Medicine, University and Hospital Trust of Verona, Verona, Italy.
IN - Tempero, Margaret A. Division of Hematology and Oncology, University of California, San Francisco, California.
IN - , . Australian Pancreatic Cancer Genome Initiative.
IN - Hofmann, Oliver. Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
IN - Eshleman, James R. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland.
IN - Pilarsky, Christian. Universitatsklinikum Erlangen, Department of Surgery, University of Erlangen-Nueremberg, Germany.
IN - Scarpa, Aldo. ARC-NET Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy; Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
IN - Musgrove, Elizabeth A. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales Australia, Darlinghurst, New South Wales, Australia.
IN - Gill, Anthony J. The Kinghorn Cancer Centre, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia; Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
IN - Pearson, John V. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
IN - Grimmond, Sean M. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia; University of Melbourne Centre for Cancer Research, The University of Melbourne, Melbourne, Victoria, Australia.
IN - Waddell, Nicola. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. Electronic address: nic.waddell@qimrberghofer.edu.au.
IN - Biankin, Andrew V. Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Department of Surgery, Bankstown Hospital, Bankstown, Sydney, New South Wales, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales Australia, Liverpool, New South Wales, Australia; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom. Electronic address: andrew.biankin@glasgow.ac.uk.
TI - Hypermutation In Pancreatic Cancer.
SO - Gastroenterology. 152(1):68-74.e2, 2017 Jan
AS - Gastroenterology. 152(1):68-74.e2, 2017 Jan
NJ - Gastroenterology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - fh3, 0374630
IO - Gastroenterology
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - *Carcinoma, Pancreatic Ductal/ge [Genetics]
MH - *DNA Mismatch Repair/ge [Genetics]
MH - DNA Mutational Analysis
MH - Female
MH - Genome
MH - Humans
MH - Male
MH - Middle Aged
MH - MutL Protein Homolog 1/ge [Genetics]
MH - MutS Homolog 2 Protein/ge [Genetics]
MH - *Mutation
MH - *Pancreatic Neoplasms/ge [Genetics]
MH - Proto-Oncogene Proteins p21(ras)/ge [Genetics]
MH - *Transcriptome
KW - Cancer Genetics; Pancreatic Adenocarcinoma; Sequencing; Somatic Rearrangement
AB - Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.
AB - Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.
RN - 0 (KRAS protein, human)
RN - 0 (MLH1 protein, human)
RN - EC 3-6-1-3 (MSH2 protein, human)
RN - EC 3-6-1-3 (MutL Protein Homolog 1)
RN - EC 3-6-1-3 (MutS Homolog 2 Protein)
RN - EC 3-6-5-2 (Proto-Oncogene Proteins p21(ras))
ES - 1528-0012
IL - 0016-5085
DI - S0016-5085(16)35189-7
DO - https://dx.doi.org/10.1053/j.gastro.2016.09.060
PT - Journal Article
ID - S0016-5085(16)35189-7 [pii]
ID - 10.1053/j.gastro.2016.09.060 [doi]
PP - ppublish
PH - 2016/01/29 [received]
PH - 2016/09/07 [revised]
PH - 2016/09/21 [accepted]
GI - No: 11650
Organization: *Cancer Research UK*
Country: United Kingdom
LG - English
EP - 20161115
DP - 2017 Jan
DC - 20161118
EZ - 2016/11/19 06:00
DA - 2017/06/14 06:00
DT - 2016/11/20 06:00
YR - 2017
ED - 20170613
RD - 20170613
UP - 20170614
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27856273
<18. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27912830
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Kalemkerian GP
AU - Schneider BJ
FA - Kalemkerian, Gregory P
FA - Schneider, Bryan J
IN - Kalemkerian, Gregory P. Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, C350 Med Inn-SPC 5848, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5848, USA. Electronic address: kalemker@umich.edu.
IN - Schneider, Bryan J. Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, C411 Med Inn-SPC 5848, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5848, USA.
TI - Advances in Small Cell Lung Cancer. [Review]
SO - Hematology - Oncology Clinics of North America. 31(1):143-156, 2017 Feb
AS - Hematol Oncol Clin North Am. 31(1):143-156, 2017 Feb
NJ - Hematology/oncology clinics of North America
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - heo, 8709473
IO - Hematol. Oncol. Clin. North Am.
SB - Index Medicus
CP - United States
MH - *Chemoradiotherapy/mt [Methods]
MH - Cranial Irradiation
MH - Disease-Free Survival
MH - Humans
MH - Incidence
MH - Lung Neoplasms/mo [Mortality]
MH - Lung Neoplasms/pa [Pathology]
MH - *Lung Neoplasms/th [Therapy]
MH - Neoplasm Staging
MH - Quality of Life
MH - Small Cell Lung Carcinoma/mo [Mortality]
MH - Small Cell Lung Carcinoma/pa [Pathology]
MH - *Small Cell Lung Carcinoma/th [Therapy]
MH - Smoking/ae [Adverse Effects]
MH - Smoking/mo [Mortality]
MH - Smoking/pa [Pathology]
MH - Survival Rate
KW - Chemotherapy; Genomics; Immunotherapy; Lung cancer; Radiation therapy; Small cell; Targeted therapy
AB - Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by early metastatic spread and responsiveness to initial therapy. The incidence of SCLC has been declining in the United States in parallel with the decreasing prevalence of cigarette smoking. Limited stage disease is potentially curable with chemoradiotherapy followed by cranial irradiation. Extensive stage disease is incurable, but systemic chemotherapy can improve quality of life and prolong survival. Nearly all patients relapse with chemoresistant disease. Molecularly targeted therapy has failed to yield convincing clinical benefits. Nevertheless, many biologically rational strategies, including immune checkpoint inhibition, show promise in ongoing clinical trials.
AB - Copyright A© 2016 Elsevier Inc. All rights reserved.
ES - 1558-1977
IL - 0889-8588
DI - S0889-8588(16)30119-8
DO - https://dx.doi.org/10.1016/j.hoc.2016.08.005
PT - Journal Article
PT - Review
ID - S0889-8588(16)30119-8 [pii]
ID - 10.1016/j.hoc.2016.08.005 [doi]
PP - ppublish
LG - English
DP - 2017 Feb
DC - 20161203
EZ - 2016/12/04 06:00
DA - 2017/06/10 06:00
DT - 2016/12/04 06:00
YR - 2017
ED - 20170609
RD - 20170609
UP - 20170612
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27912830
<19. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28223062
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Morris VK
AU - Salem ME
AU - Nimeiri H
AU - Iqbal S
AU - Singh P
AU - Ciombor K
AU - Polite B
AU - Deming D
AU - Chan E
AU - Wade JL
AU - Xiao L
AU - Bekaii-Saab T
AU - Vence L
AU - Blando J
AU - Mahvash A
AU - Foo WC
AU - Ohaji C
AU - Pasia M
AU - Bland G
AU - Ohinata A
AU - Rogers J
AU - Mehdizadeh A
AU - Banks K
AU - Lanman R
AU - Wolff RA
AU - Streicher H
AU - Allison J
AU - Sharma P
AU - Eng C
FA - Morris, Van K
FA - Salem, Mohamed E
FA - Nimeiri, Halla
FA - Iqbal, Syma
FA - Singh, Preet
FA - Ciombor, Kristen
FA - Polite, Blase
FA - Deming, Dustin
FA - Chan, Emily
FA - Wade, James L
FA - Xiao, Lianchun
FA - Bekaii-Saab, Tanios
FA - Vence, Luis
FA - Blando, Jorge
FA - Mahvash, Armeen
FA - Foo, Wai Chin
FA - Ohaji, Chimela
FA - Pasia, Manolo
FA - Bland, Gail
FA - Ohinata, Aki
FA - Rogers, Jane
FA - Mehdizadeh, Amir
FA - Banks, Kimberly
FA - Lanman, Richard
FA - Wolff, Robert A
FA - Streicher, Howard
FA - Allison, James
FA - Sharma, Padmanee
FA - Eng, Cathy
IN - Morris, Van K. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Salem, Mohamed E. Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
IN - Nimeiri, Halla. Northwestern University, Chicago, IL, USA.
IN - Iqbal, Syma. University of Southern California, Los Angeles, CA, USA.
IN - Singh, Preet. Washington University, St Louis, MO, USA.
IN - Ciombor, Kristen. The Ohio State University, Columbus, OH, USA.
IN - Polite, Blase. University of Chicago, Chicago, IL, USA.
IN - Deming, Dustin. University of Wisconsin, Madison, WI, USA.
IN - Chan, Emily. Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
IN - Wade, James L. Decatur Memorial Hospital, Decatur, IL, USA.
IN - Xiao, Lianchun. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Bekaii-Saab, Tanios. The Ohio State University, Columbus, OH, USA.
IN - Vence, Luis. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Blando, Jorge. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Mahvash, Armeen. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Foo, Wai Chin. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Ohaji, Chimela. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Pasia, Manolo. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Bland, Gail. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Ohinata, Aki. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Rogers, Jane. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Mehdizadeh, Amir. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Banks, Kimberly. Guardant Health, Redwood City, CA, USA.
IN - Lanman, Richard. Guardant Health, Redwood City, CA, USA.
IN - Wolff, Robert A. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Streicher, Howard. National Cancer Institute, Bethesda, MD, USA.
IN - Allison, James. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Sharma, Padmanee. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA.
IN - Eng, Cathy. The University of Texas-MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ceng@mdanderson.org.
TI - Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study.
SO - Lancet Oncology. 18(4):446-453, 2017 Apr
AS - Lancet Oncol. 18(4):446-453, 2017 Apr
NJ - The Lancet. Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 100957246
IO - Lancet Oncol.
SB - Index Medicus
CP - England
MH - Aged
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Anus Neoplasms/dt [Drug Therapy]
MH - Anus Neoplasms/pa [Pathology]
MH - *Carcinoma, Squamous Cell/dt [Drug Therapy]
MH - Carcinoma, Squamous Cell/sc [Secondary]
MH - Case-Control Studies
MH - *Drug Resistance, Neoplasm/de [Drug Effects]
MH - Female
MH - Follow-Up Studies
MH - Humans
MH - Lymphatic Metastasis
MH - Male
MH - Middle Aged
MH - *Neoplasm Recurrence, Local/dt [Drug Therapy]
MH - Neoplasm Recurrence, Local/pa [Pathology]
MH - Neoplasm Staging
MH - Prognosis
MH - Prospective Studies
MH - Response Evaluation Criteria in Solid Tumors
MH - *Salvage Therapy
MH - Survival Rate
AB - BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA.
AB - METHODS: We did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169.
AB - RESULTS: We screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15-33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported.
AB - INTERPRETATION: To our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease.
AB - FUNDING: National Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor.
AB - Copyright © 2017 Elsevier Ltd. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 31YO63LBSN (nivolumab)
ES - 1474-5488
IL - 1470-2045
DI - S1470-2045(17)30104-3
DO - https://dx.doi.org/10.1016/S1470-2045(17)30104-3
PT - Clinical Trial, Phase II
PT - Journal Article
PT - Multicenter Study
ID - S1470-2045(17)30104-3 [pii]
ID - 10.1016/S1470-2045(17)30104-3 [doi]
PP - ppublish
PH - 2016/11/01 [received]
PH - 2016/12/16 [revised]
PH - 2016/12/21 [accepted]
LG - English
EP - 20170218
DP - 2017 Apr
DC - 20170222
EZ - 2017/02/23 06:00
DA - 2017/06/09 06:00
DT - 2017/02/23 06:00
YR - 2017
ED - 20170608
RD - 20170608
UP - 20170609
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28223062
<20. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28162999
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Coens C
AU - Suciu S
AU - Chiarion-Sileni V
AU - Grob JJ
AU - Dummer R
AU - Wolchok JD
AU - Schmidt H
AU - Hamid O
AU - Robert C
AU - Ascierto PA
AU - Richards JM
AU - Lebbe C
AU - Ferraresi V
AU - Smylie M
AU - Weber JS
AU - Maio M
AU - Bottomley A
AU - Kotapati S
AU - de Pril V
AU - Testori A
AU - Eggermont AM
FA - Coens, Corneel
FA - Suciu, Stefan
FA - Chiarion-Sileni, Vanna
FA - Grob, Jean-Jacques
FA - Dummer, Reinhard
FA - Wolchok, Jedd D
FA - Schmidt, Henrik
FA - Hamid, Omid
FA - Robert, Caroline
FA - Ascierto, Paolo A
FA - Richards, Jon M
FA - Lebbe, Celeste
FA - Ferraresi, Virginia
FA - Smylie, Michael
FA - Weber, Jeffrey S
FA - Maio, Michele
FA - Bottomley, Andrew
FA - Kotapati, Srividya
FA - de Pril, Veerle
FA - Testori, Alessandro
FA - Eggermont, Alexander M M
IN - Coens, Corneel. EORTC Headquarters, Brussels, Belgium. Electronic address: corneel.coens@eortc.be.
IN - Suciu, Stefan. EORTC Headquarters, Brussels, Belgium.
IN - Chiarion-Sileni, Vanna. IOV-IRCCS, Melanoma Oncology Unit, Padova, Italy.
IN - Grob, Jean-Jacques. Hopital de la Timone, Marseille, France.
IN - Dummer, Reinhard. University of Zurich Hospital, Zurich, Switzerland.
IN - Wolchok, Jedd D. Memorial Sloan Kettering Cancer Center, New York, NY, USA.
IN - Schmidt, Henrik. Aarhus University Hospital, Aarhus, Denmark.
IN - Hamid, Omid. The Angeles Clinic and Research Institute, Los Angeles, CA, USA.
IN - Robert, Caroline. Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.
IN - Ascierto, Paolo A. Istituto Nazionale Tumori Fondazione "G. Pascale", Naples, Italy.
IN - Richards, Jon M. Oncology Specialists S C, Park Ridge, IL, USA.
IN - Lebbe, Celeste. Assistance Publique des Hopitaux de Paris (AP-HP), Hopital Saint-Louis, Paris.
IN - Ferraresi, Virginia. Istituti Fisioterapici Ospitalieri, Rome, Italy.
IN - Smylie, Michael. Cross Cancer Institute, Edmonton, AB, Canada.
IN - Weber, Jeffrey S. H Lee Moffitt Cancer Center, Tampa, FL, USA.
IN - Maio, Michele. University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy.
IN - Bottomley, Andrew. EORTC Headquarters, Brussels, Belgium.
IN - Kotapati, Srividya. Bristol-Myers Squibb, Wallingford, CT, USA.
IN - de Pril, Veerle. Bristol-Myers Squibb, Braine-l'Alleud, Belgium.
IN - Testori, Alessandro. European Institute of Oncology, Milan, Italy.
IN - Eggermont, Alexander M M. Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.
TI - Health-related quality of life with adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): secondary outcomes of a multinational, randomised, double-blind, phase 3 trial.
SO - Lancet Oncology. 18(3):393-403, 2017 Mar
AS - Lancet Oncol. 18(3):393-403, 2017 Mar
NJ - The Lancet. Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 100957246
IO - Lancet Oncol.
SB - Index Medicus
CP - England
MH - *Adjuvants, Immunologic/tu [Therapeutic Use]
MH - Adolescent
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Double-Blind Method
MH - Female
MH - Follow-Up Studies
MH - Humans
MH - International Agencies
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/pa [Pathology]
MH - Melanoma/su [Surgery]
MH - Middle Aged
MH - Neoplasm Staging
MH - Prognosis
MH - *Quality of Life
MH - Young Adult
AB - BACKGROUND: The EORTC 18071 phase 3 trial compared adjuvant ipilimumab with placebo in patients with stage III melanoma. The primary endpoint, recurrence-free survival, was significantly longer in the ipilimumab group than in the placebo group. Investigator-reported toxic effects of ipilimumab consisted mainly of skin, gastrointestinal, endocrine, and hepatic immune-related adverse events. Adjuvant treatment with ipilimumab in this setting was approved in October, 2014, by the US Food and Drug Administration based on the results of the primary outcome of this trial. Here, we report the results of the secondary endpoint, health-related quality of life (HRQoL), of this trial.
AB - METHODS: EORTC 18071 was a multinational, double-blind, randomised, phase 3 trial in patients with stage III cutaneous melanoma (excluding lymph node metastasis <=1 mm or in-transit metastasis) in 19 countries worldwide. Participants were randomly assigned (1:1) centrally by an interactive voice response system, to receive either ipilimumab 10 mg/kg or placebo every 3 weeks for four doses, then every 3 months for up to 3 years. Using a minimisation technique, randomisation was stratified by disease stage and geographical region. HRQoL was assessed with the EORTC QLQ-C30 quality-of-life instrument at baseline, weeks 4, 7, 10, and 24, and every 12 weeks thereafter up to 2 years, irrespective of disease progression. Results were summarised by timepoint and in a longitudinal manner in the intention-to-treat population. Two summary scores were calculated for each HRQoL scale: the average score reported during induction (ipilimumab or placebo at a dose of 10 mg/kg, administered as one single dose at the start of days 1, 22, 43, and 64-ie, four doses in 3 weeks), and the average score reported after induction. A predefined threshold of a 10 point difference between arms was considered clinically relevant. The primary HRQoL endpoint was the global health scale, with the predefined hypothesis of no clinically relevant differences after induction between groups. This trial is registered with EudraCT, number 2007-001974-10, and ClinicalTrials.gov, number NCT00636168.
AB - FINDINGS: Between July 10, 2008, and Aug 1, 2011, 951 patients were randomly assigned to treatment: 475 in the ipilimumab group and 476 in the placebo group. Compliance with completing the HRQoL questionnaire was 893 (94%) of 951 patients at baseline, 693 (75%) of 924 at week 24, and 354 (51%) of 697 at week 108. Patient mean global health scores during (77.32 [SD 17.36] vs 72.96 [17.82]; p=0.00011) and after induction (76.48 [17.52] vs 72.32 [18.60]; p=0.00067) were statistically significantly different between groups but were not clinically relevant. Mean global health scores differed most between the groups at week 7 (77 [SD 19] in the placebo group vs 72 [22] in the ipilimumab group) and week 10 (77 [20] vs 70 [23]). Mean HRQoL scores differed by more than 10 points at week 10 between treatment groups for diarrhoea (7.67 [SD 17.05] for placebo vs 18.17 [28.35] for ipilimumab) and insomnia (15.17 [22.53] vs 25.60 [29.19]).
AB - INTERPRETATION: Despite increased toxicity, which led to treatment discontinuation for most patients during the induction phase of ipilimumab administration, overall HRQoL, as measured by the EORTC QLQ-C30, was similar between groups, as no clinically relevant differences (10 points or more) in global health status scores were observed during or after induction. Clinically relevant deterioration for some symptoms was observed at week 10, but after induction, no clinically relevant differences remained. Together with the primary analysis, results from this trial show that treatment with ipilimumab results in longer recurrence-free survival compared with that for treatment with placebo, with little impairment in HRQoL despite grade 3-4 investigator-reported adverse events.
AB - FUNDING: Bristol-Myers Squibb.
AB - Copyright © 2017 Elsevier Ltd. All rights reserved.
RN - 0 (Adjuvants, Immunologic)
RN - 0 (Antibodies, Monoclonal)
RN - 6T8C155666 (ipilimumab)
ES - 1474-5488
IL - 1470-2045
DI - S1470-2045(17)30015-3
DO - https://dx.doi.org/10.1016/S1470-2045(17)30015-3
PT - Clinical Trial, Phase III
PT - Comparative Study
PT - Journal Article
PT - Multicenter Study
PT - Randomized Controlled Trial
ID - S1470-2045(17)30015-3 [pii]
ID - 10.1016/S1470-2045(17)30015-3 [doi]
PP - ppublish
PH - 2016/06/09 [received]
PH - 2016/10/17 [revised]
PH - 2016/10/24 [accepted]
GI - No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20170203
DP - 2017 Mar
DC - 20170206
EZ - 2017/02/07 06:00
DA - 2017/06/09 06:00
DT - 2017/02/07 06:00
YR - 2017
ED - 20170608
RD - 20170609
UP - 20170609
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28162999
<21. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28161703
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Rinke A
AU - Gress TM
FA - Rinke, Anja
FA - Gress, Thomas M
IN - Rinke, Anja. Department of Gastroenterology, University Hospital Marburg, Marburg, Germany.
TI - Neuroendocrine Cancer, Therapeutic Strategies in G3 Cancers. [Review]
SO - Digestion. 95(2):109-114, 2017
AS - Digestion. 95(2):109-114, 2017
NJ - Digestion
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - e9a, 0150472
IO - Digestion
SB - Index Medicus
CP - Switzerland
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Antineoplastic Combined Chemotherapy Protocols/ad [Administration & Dosage]
MH - *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - Camptothecin/ad [Administration & Dosage]
MH - Camptothecin/aa [Analogs & Derivatives]
MH - Camptothecin/tu [Therapeutic Use]
MH - Carboplatin/ad [Administration & Dosage]
MH - Carboplatin/tu [Therapeutic Use]
MH - *Carcinoma, Neuroendocrine/dt [Drug Therapy]
MH - Carcinoma, Neuroendocrine/mo [Mortality]
MH - *Carcinoma, Neuroendocrine/pa [Pathology]
MH - Cisplatin/ad [Administration & Dosage]
MH - Cisplatin/tu [Therapeutic Use]
MH - Etoposide/ad [Administration & Dosage]
MH - Etoposide/tu [Therapeutic Use]
MH - *Gastrointestinal Neoplasms/dt [Drug Therapy]
MH - Gastrointestinal Neoplasms/mo [Mortality]
MH - *Gastrointestinal Neoplasms/pa [Pathology]
MH - Humans
MH - Ki-67 Antigen/an [Analysis]
MH - Neoplasm Grading
MH - *Neuroendocrine Tumors/dt [Drug Therapy]
MH - Neuroendocrine Tumors/mo [Mortality]
MH - *Neuroendocrine Tumors/pa [Pathology]
MH - Practice Guidelines as Topic
MH - Prognosis
MH - Treatment Outcome
AB - BACKGROUND: According to the latest WHO classification, neuroendocrine neoplasm (NEN) G3 of the gastrointestinal tract is defined by a proliferation index Ki67 above 20%. Gastrointestinal neuroendocrine carcinoma (NEC) is a rare and highly aggressive malignancy and despite responsiveness to chemotherapy, overall survival is poor. In the last 3-4 years, the heterogeneity of the NEN G3 group has become evident.
AB - SUMMARY: In addition to the proliferative activity, the tumour differentiation seems to play a major role, further dividing the NEN G3 group into neuroendocrine tumour (NET) G3 and NEC. NET G3 often arise in the pancreas, and their median proliferation rate is lower and prognosis is better as compared to NEC. However, NET G3 show a limited response to platinum-based chemotherapy. Lack of specific data for NET G3 hampers clear therapeutic recommendations. Cisplatin combined with etoposide is the established standard regimen for advanced gastrointestinal NEC. Substituting carboplatin for cisplatin or irinotecan for etoposide is considered alternative first-line regimen. There is no standard second-line treatment; options are discussed within this review.
AB - KEY POINTS: (1) In NEN G3, the distinction between NET G3 and NEC G3 is clinically and prognostically meaningful. (2) Platinum-based chemotherapy remains the recommended first-line treatment in metastasized NEC patients. (3) There is no established standard for NET G3; treatments established for NET G2 such as temozolomide-based chemotherapy or peptide receptor radiotherapy may be considered. (4) Specific trials for NET G3 are necessary. (5) New therapies for NEC are urgently needed. Checkpoint inhibitors should be evaluated.
AB - Copyright © 2017 S. Karger AG, Basel.
RN - 0 (Antineoplastic Agents)
RN - 0 (Ki-67 Antigen)
RN - 0H43101T0J (irinotecan)
RN - 6PLQ3CP4P3 (Etoposide)
RN - BG3F62OND5 (Carboplatin)
RN - Q20Q21Q62J (Cisplatin)
RN - XT3Z54Z28A (Camptothecin)
ES - 1421-9867
IL - 0012-2823
DI - 000454761
DO - https://dx.doi.org/10.1159/000454761
PT - Journal Article
PT - Review
ID - 000454761 [pii]
ID - 10.1159/000454761 [doi]
PP - ppublish
PH - 2016/09/26 [received]
PH - 2016/11/25 [accepted]
LG - English
EP - 20170204
DP - 2017
DC - 20170205
EZ - 2017/02/06 06:00
DA - 2017/06/07 06:00
DT - 2017/02/06 06:00
YR - 2017
ED - 20170606
RD - 20170606
UP - 20170608
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28161703
<22. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27307501
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Cappelli LC
AU - Gutierrez AK
AU - Baer AN
AU - Albayda J
AU - Manno RL
AU - Haque U
AU - Lipson EJ
AU - Bleich KB
AU - Shah AA
AU - Naidoo J
AU - Brahmer JR
AU - Le D
AU - Bingham CO 3rd
FA - Cappelli, Laura C
FA - Gutierrez, Anna Kristina
FA - Baer, Alan N
FA - Albayda, Jemima
FA - Manno, Rebecca L
FA - Haque, Uzma
FA - Lipson, Evan J
FA - Bleich, Karen B
FA - Shah, Ami A
FA - Naidoo, Jarushka
FA - Brahmer, Julie R
FA - Le, Dung
FA - Bingham, Clifton O 3rd
IN - Cappelli, Laura C. Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
IN - Gutierrez, Anna Kristina. Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
IN - Baer, Alan N. Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
IN - Albayda, Jemima. Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
IN - Manno, Rebecca L. Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
IN - Haque, Uzma. Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
IN - Lipson, Evan J. Department of Oncology, Johns Hopkins University, Baltimore, Maryland, USA.
IN - Bleich, Karen B. Department of Radiology, Johns Hopkins University, Baltimore, Maryland, USA.
IN - Shah, Ami A. Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
IN - Naidoo, Jarushka. Department of Oncology, Johns Hopkins University, Baltimore, Maryland, USA.
IN - Brahmer, Julie R. Department of Oncology, Johns Hopkins University, Baltimore, Maryland, USA.
IN - Le, Dung. Department of Oncology, Johns Hopkins University, Baltimore, Maryland, USA.
IN - Bingham, Clifton O 3rd. Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
TI - Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab.
SO - Annals of the Rheumatic Diseases. 76(1):43-50, 2017 Jan
AS - Ann Rheum Dis. 76(1):43-50, 2017 Jan
NJ - Annals of the rheumatic diseases
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 0372355, 62w
IO - Ann. Rheum. Dis.
SB - Index Medicus
CP - England
MH - Adult
MH - Aged
MH - Antibodies, Antinuclear/bl [Blood]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - *Arthritis/ci [Chemically Induced]
MH - Arthritis/dt [Drug Therapy]
MH - Female
MH - Humans
MH - Male
MH - Middle Aged
MH - *Sjogren's Syndrome/ci [Chemically Induced]
MH - Sjogren's Syndrome/dt [Drug Therapy]
MH - *Synovitis/ci [Chemically Induced]
MH - Synovitis/dt [Drug Therapy]
KW - *Arthritis; *Autoimmune Diseases; *Inflammation; *Sjogren's Syndrome
AB - OBJECTIVES: Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways have demonstrated survival improvements in multiple advanced cancers, but also cause immune-related adverse events (IRAEs). IRAEs with clinical features similar to rheumatic diseases have not been well described. We report patients with inflammatory arthritis and sicca syndrome secondary to ICIs.
AB - METHODS: We report patients evaluated in the Johns Hopkins Rheumatology clinics from 2012 to 2016 identified as having new rheumatological symptoms in the context of treatment with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) for solid tumours.
AB - RESULTS: We identified 13 patients who received ICIs and developed rheumatological IRAEs. Mean age was 58.7 years. Cancer types included melanoma, non-small cell lung cancer, small cell lung cancer and renal cell carcinoma. ICI regimens included nivolumab or ipilimumab as monotherapy (n=5), or combination nivolumab and ipilimumab (n=8). Nine of 13 patients developed an inflammatory arthritis, 4 with synovitis confirmed on imaging (3 ultrasound, 1 MRI) and 4 with inflammatory synovial fluid. Four patients developed sicca syndrome with severe salivary hypofunction. Other IRAEs included: pneumonitis, colitis, interstitial nephritis and thyroiditis. Antinuclear antibodies were positive in 5 out of 13 patients. All 13 patients were treated with corticosteroids with varying response. Two patients were treated with methotrexate and antitumor necrosis factor therapy for inflammatory arthritis.
AB - CONCLUSIONS: As ICIs are increasingly used for a range of malignancies, new cases of rheumatic IRAEs are likely to emerge. Further research is required to understand mechanisms, determine risk factors and develop management algorithms for rheumatic IRAEs.
AB - Copyright Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
RN - 0 (Antibodies, Antinuclear)
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 31YO63LBSN (nivolumab)
RN - 6T8C155666 (ipilimumab)
ES - 1468-2060
IL - 0003-4967
DI - annrheumdis-2016-209595
DO - https://dx.doi.org/10.1136/annrheumdis-2016-209595
PT - Journal Article
ID - annrheumdis-2016-209595 [pii]
ID - 10.1136/annrheumdis-2016-209595 [doi]
ID - PMC5333990 [pmc]
ID - NIHMS848643 [mid]
PP - ppublish
PH - 2016/03/22 [received]
PH - 2016/05/16 [revised]
PH - 2016/05/27 [accepted]
PH - 2018/01/01 [pmc-release]
GI - No: K23 AR061439
Organization: (AR) *NIAMS NIH HHS*
Country: United States
No: P30 AR053503
Organization: (AR) *NIAMS NIH HHS*
Country: United States
No: P30 AR070254
Organization: (AR) *NIAMS NIH HHS*
Country: United States
No: T35 AG026758
Organization: (AG) *NIA NIH HHS*
Country: United States
LG - English
EP - 20160615
DP - 2017 Jan
DC - 20160623
EZ - 2016/06/17 06:00
DA - 2017/06/07 06:00
DT - 2016/06/17 06:00
YR - 2017
ED - 20170606
RD - 20170606
UP - 20170608
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27307501
<23. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28292987
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Horio Y
FA - Horio, Yoshitsugu
IN - Horio, Yoshitsugu. Dept. of Outpatient Services, Aichi Cancer Center Hospital.
TI - [Management of Toxicities of Immune Checkpoint Inhibitors]. [Review] [Japanese]
SO - Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy]. 44(3):185-190, 2017 Mar
AS - Gan To Kagaku Ryoho. 44(3):185-190, 2017 Mar
NJ - Gan to kagaku ryoho. Cancer & chemotherapy
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 7810034, 6t8
IO - Gan To Kagaku Ryoho
SB - Index Medicus
CP - Japan
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Humans
MH - *Immune System/de [Drug Effects]
MH - *Molecular Targeted Therapy/ae [Adverse Effects]
MH - Neoplasms/dt [Drug Therapy]
MH - *Neoplasms/im [Immunology]
AB - Immune checkpoint inhibitors, including the anti-CTLA-4 antibody ipilimumab, the anti-PD-1 antibodies nivolumab and pembrolizumab, and the anti-PD-L1 antibody atezolizumab had produced long-lasting tumor responses in several malignancies. Immune-related Adverse Events(irAEs)which are different from adverse events of conventional chemotherapy and molecular targeted therapy, occur as a consequence of impaired self-tolerance from loss of T-cell inhibition. The main irAEs of immune checkpoint inhibitors include dermatological, gastrointestinal, pulmonary, hepatic, endocrine, renal toxicities. Every organ system can be potentially involved, but nivolumab, pembrolizumab and atezolizumab have a different toxicity profile with fewer high grade events compared with ipilimumab. In this article, we provide an approach to appropriate management for each class of irAEs.
RN - 0 (Antineoplastic Agents)
IS - 0385-0684
IL - 0385-0684
PT - Journal Article
PT - Review
PP - ppublish
LG - Japanese
DP - 2017 Mar
DC - 20170315
EZ - 2017/03/16 06:00
DA - 2017/03/16 06:00
DT - 2017/03/16 06:00
YR - 2017
ED - 20170605
RD - 20170605
UP - 20170607
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28292987
<24. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27157491
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Muro K
AU - Chung HC
AU - Shankaran V
AU - Geva R
AU - Catenacci D
AU - Gupta S
AU - Eder JP
AU - Golan T
AU - Le DT
AU - Burtness B
AU - McRee AJ
AU - Lin CC
AU - Pathiraja K
AU - Lunceford J
AU - Emancipator K
AU - Juco J
AU - Koshiji M
AU - Bang YJ
FA - Muro, Kei
FA - Chung, Hyun Cheol
FA - Shankaran, Veena
FA - Geva, Ravit
FA - Catenacci, Daniel
FA - Gupta, Shilpa
FA - Eder, Joseph Paul
FA - Golan, Talia
FA - Le, Dung T
FA - Burtness, Barbara
FA - McRee, Autumn J
FA - Lin, Chia-Chi
FA - Pathiraja, Kumudu
FA - Lunceford, Jared
FA - Emancipator, Kenneth
FA - Juco, Jonathan
FA - Koshiji, Minori
FA - Bang, Yung-Jue
IN - Muro, Kei. Aichi Cancer Center Hospital, Nagoya, Japan. Electronic address: kmuro@aichi-cc.jp.
IN - Chung, Hyun Cheol. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
IN - Shankaran, Veena. University of Washington, Seattle, WA, USA.
IN - Geva, Ravit. Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
IN - Catenacci, Daniel. University of Chicago, Chicago, IL, USA.
IN - Gupta, Shilpa. University of Minnesota, Minneapolis, MN, USA.
IN - Eder, Joseph Paul. Yale University, New Haven, CT, USA.
IN - Golan, Talia. Sheba Medical Center, Ramat Gan, Israel.
IN - Le, Dung T. Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
IN - Burtness, Barbara. Fox Chase Cancer Center, Philadelphia, PA, USA.
IN - McRee, Autumn J. University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
IN - Lin, Chia-Chi. National Taiwan University Hospital, Taipei, Taiwan.
IN - Pathiraja, Kumudu. Merck & Co, Kenilworth, NJ, USA.
IN - Lunceford, Jared. Merck & Co, Kenilworth, NJ, USA.
IN - Emancipator, Kenneth. Merck & Co, Kenilworth, NJ, USA.
IN - Juco, Jonathan. Merck & Co, Kenilworth, NJ, USA.
IN - Koshiji, Minori. Merck & Co, Kenilworth, NJ, USA.
IN - Bang, Yung-Jue. Seoul National University College of Medicine, Seoul, South Korea.
TI - Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial.
SO - Lancet Oncology. 17(6):717-26, 2016 Jun
AS - Lancet Oncol. 17(6):717-26, 2016 Jun
NJ - The Lancet. Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 100957246
IO - Lancet Oncol.
SB - Index Medicus
CP - England
MH - *Adenocarcinoma/dt [Drug Therapy]
MH - Adenocarcinoma/me [Metabolism]
MH - Adenocarcinoma/sc [Secondary]
MH - Adult
MH - Aged
MH - *Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - *Antigens, CD274/me [Metabolism]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Biomarkers, Tumor/me [Metabolism]
MH - Female
MH - Follow-Up Studies
MH - Humans
MH - Male
MH - Middle Aged
MH - *Neoplasm Recurrence, Local/dt [Drug Therapy]
MH - Neoplasm Recurrence, Local/me [Metabolism]
MH - Neoplasm Recurrence, Local/pa [Pathology]
MH - Neoplasm Staging
MH - Prognosis
MH - *Stomach Neoplasms/dt [Drug Therapy]
MH - Stomach Neoplasms/me [Metabolism]
MH - Stomach Neoplasms/pa [Pathology]
MH - Survival Rate
AB - BACKGROUND: Expression of PD-L1 has been shown to be upregulated in some patients with gastric cancer. As part of the phase 1b KEYNOTE-012 study, we aimed to assess the safety and activity of the anti-PD-1 antibody pembrolizumab in patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction.
AB - METHODS: This study was a multicentre, open-label, phase 1b trial done at 13 cancer research centres in the USA, Israel, Japan, South Korea, and Taiwan. We enrolled patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Patients received intravenous pembrolizumab at 10 mg/kg once every 2 weeks for 24 months or until progression or unacceptable toxic effects occurred. Response was assessed every 8 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. The primary objectives were safety in patients who received at least one dose of pembrolizumab and the proportion of patients achieving overall responses in patients who received at least one pembrolizumab dose and who either had a post-baseline scan or who discontinued therapy because of clinical disease progression or a treatment-related adverse event before the first post-baseline scan. The study is registered with ClinicalTrials.gov, number NCT01848834, and is ongoing but no longer enrolling patients.
AB - FINDINGS: From Oct 23, 2013, to May 5, 2014, 39 patients were enrolled. 36 were evaluable for response by central assessment. Eight (22%, 95% CI 10-39) patients were judged to have had an overall response at central review; all responses were partial. All 39 patients were included in the safety analyses. Five (13%) patients had a total of six grade 3 or 4 treatment-related adverse events, consisting of two cases of grade 3 fatigue, one case each of grade 3 pemphigoid, grade 3 hypothyroidism, and grade 3 peripheral sensory neuropathy, and one case of grade 4 pneumonitis. No treatment-related deaths occurred.
AB - INTERPRETATION: In this population of patients with recurrent or metastatic PD-L1-positive gastric cancer, pembrolizumab had a manageable toxicity profile and promising antitumour activity, warranting further study in phase 2 and 3 trials.
AB - FUNDING: Merck & Co.
AB - Copyright © 2016 Elsevier Ltd. All rights reserved.
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (Biomarkers, Tumor)
RN - 0 (CD274 protein, human)
RN - DPT0O3T46P (pembrolizumab)
ES - 1474-5488
IL - 1470-2045
DI - S1470-2045(16)00175-3
DO - https://dx.doi.org/10.1016/S1470-2045(16)00175-3
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Multicenter Study
ID - S1470-2045(16)00175-3 [pii]
ID - 10.1016/S1470-2045(16)00175-3 [doi]
PP - ppublish
PH - 2015/12/30 [received]
PH - 2016/02/17 [revised]
PH - 2016/03/11 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01848834
SL - https://clinicaltrials.gov/search/term=NCT01848834
LG - English
EP - 20160503
DP - 2016 Jun
DC - 20160615
EZ - 2016/05/10 06:00
DA - 2016/05/10 06:00
DT - 2016/05/10 06:00
YR - 2016
ED - 20170605
RD - 20170605
UP - 20170607
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27157491
<25. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28292987
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Horio Y
FA - Horio, Yoshitsugu
IN - Horio, Yoshitsugu. Dept. of Outpatient Services, Aichi Cancer Center Hospital.
TI - [Management of Toxicities of Immune Checkpoint Inhibitors]. [Review] [Japanese]
SO - Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy]. 44(3):185-190, 2017 Mar
AS - Gan To Kagaku Ryoho. 44(3):185-190, 2017 Mar
NJ - Gan to kagaku ryoho. Cancer & chemotherapy
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 7810034, 6t8
IO - Gan To Kagaku Ryoho
SB - Index Medicus
CP - Japan
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Humans
MH - *Immune System/de [Drug Effects]
MH - *Molecular Targeted Therapy/ae [Adverse Effects]
MH - Neoplasms/dt [Drug Therapy]
MH - *Neoplasms/im [Immunology]
AB - Immune checkpoint inhibitors, including the anti-CTLA-4 antibody ipilimumab, the anti-PD-1 antibodies nivolumab and pembrolizumab, and the anti-PD-L1 antibody atezolizumab had produced long-lasting tumor responses in several malignancies. Immune-related Adverse Events(irAEs)which are different from adverse events of conventional chemotherapy and molecular targeted therapy, occur as a consequence of impaired self-tolerance from loss of T-cell inhibition. The main irAEs of immune checkpoint inhibitors include dermatological, gastrointestinal, pulmonary, hepatic, endocrine, renal toxicities. Every organ system can be potentially involved, but nivolumab, pembrolizumab and atezolizumab have a different toxicity profile with fewer high grade events compared with ipilimumab. In this article, we provide an approach to appropriate management for each class of irAEs.
RN - 0 (Antineoplastic Agents)
IS - 0385-0684
IL - 0385-0684
PT - Journal Article
PT - Review
PP - ppublish
LG - Japanese
DP - 2017 Mar
DC - 20170315
EZ - 2017/03/16 06:00
DA - 2017/06/06 06:00
DT - 2017/03/16 06:00
YR - 2017
ED - 20170605
RD - 20170605
UP - 20170608
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=28292987
<26. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27157491
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Muro K
AU - Chung HC
AU - Shankaran V
AU - Geva R
AU - Catenacci D
AU - Gupta S
AU - Eder JP
AU - Golan T
AU - Le DT
AU - Burtness B
AU - McRee AJ
AU - Lin CC
AU - Pathiraja K
AU - Lunceford J
AU - Emancipator K
AU - Juco J
AU - Koshiji M
AU - Bang YJ
FA - Muro, Kei
FA - Chung, Hyun Cheol
FA - Shankaran, Veena
FA - Geva, Ravit
FA - Catenacci, Daniel
FA - Gupta, Shilpa
FA - Eder, Joseph Paul
FA - Golan, Talia
FA - Le, Dung T
FA - Burtness, Barbara
FA - McRee, Autumn J
FA - Lin, Chia-Chi
FA - Pathiraja, Kumudu
FA - Lunceford, Jared
FA - Emancipator, Kenneth
FA - Juco, Jonathan
FA - Koshiji, Minori
FA - Bang, Yung-Jue
IN - Muro, Kei. Aichi Cancer Center Hospital, Nagoya, Japan. Electronic address: kmuro@aichi-cc.jp.
IN - Chung, Hyun Cheol. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
IN - Shankaran, Veena. University of Washington, Seattle, WA, USA.
IN - Geva, Ravit. Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
IN - Catenacci, Daniel. University of Chicago, Chicago, IL, USA.
IN - Gupta, Shilpa. University of Minnesota, Minneapolis, MN, USA.
IN - Eder, Joseph Paul. Yale University, New Haven, CT, USA.
IN - Golan, Talia. Sheba Medical Center, Ramat Gan, Israel.
IN - Le, Dung T. Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
IN - Burtness, Barbara. Fox Chase Cancer Center, Philadelphia, PA, USA.
IN - McRee, Autumn J. University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
IN - Lin, Chia-Chi. National Taiwan University Hospital, Taipei, Taiwan.
IN - Pathiraja, Kumudu. Merck & Co, Kenilworth, NJ, USA.
IN - Lunceford, Jared. Merck & Co, Kenilworth, NJ, USA.
IN - Emancipator, Kenneth. Merck & Co, Kenilworth, NJ, USA.
IN - Juco, Jonathan. Merck & Co, Kenilworth, NJ, USA.
IN - Koshiji, Minori. Merck & Co, Kenilworth, NJ, USA.
IN - Bang, Yung-Jue. Seoul National University College of Medicine, Seoul, South Korea.
TI - Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial.
SO - Lancet Oncology. 17(6):717-26, 2016 Jun
AS - Lancet Oncol. 17(6):717-26, 2016 Jun
NJ - The Lancet. Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 100957246
IO - Lancet Oncol.
SB - Index Medicus
CP - England
MH - *Adenocarcinoma/dt [Drug Therapy]
MH - Adenocarcinoma/me [Metabolism]
MH - Adenocarcinoma/sc [Secondary]
MH - Adult
MH - Aged
MH - *Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - *Antigens, CD274/me [Metabolism]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Biomarkers, Tumor/me [Metabolism]
MH - Female
MH - Follow-Up Studies
MH - Humans
MH - Male
MH - Middle Aged
MH - *Neoplasm Recurrence, Local/dt [Drug Therapy]
MH - Neoplasm Recurrence, Local/me [Metabolism]
MH - Neoplasm Recurrence, Local/pa [Pathology]
MH - Neoplasm Staging
MH - Prognosis
MH - *Stomach Neoplasms/dt [Drug Therapy]
MH - Stomach Neoplasms/me [Metabolism]
MH - Stomach Neoplasms/pa [Pathology]
MH - Survival Rate
AB - BACKGROUND: Expression of PD-L1 has been shown to be upregulated in some patients with gastric cancer. As part of the phase 1b KEYNOTE-012 study, we aimed to assess the safety and activity of the anti-PD-1 antibody pembrolizumab in patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction.
AB - METHODS: This study was a multicentre, open-label, phase 1b trial done at 13 cancer research centres in the USA, Israel, Japan, South Korea, and Taiwan. We enrolled patients with PD-L1-positive recurrent or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Patients received intravenous pembrolizumab at 10 mg/kg once every 2 weeks for 24 months or until progression or unacceptable toxic effects occurred. Response was assessed every 8 weeks in accordance with Response Evaluation Criteria in Solid Tumors version 1.1. The primary objectives were safety in patients who received at least one dose of pembrolizumab and the proportion of patients achieving overall responses in patients who received at least one pembrolizumab dose and who either had a post-baseline scan or who discontinued therapy because of clinical disease progression or a treatment-related adverse event before the first post-baseline scan. The study is registered with ClinicalTrials.gov, number NCT01848834, and is ongoing but no longer enrolling patients.
AB - FINDINGS: From Oct 23, 2013, to May 5, 2014, 39 patients were enrolled. 36 were evaluable for response by central assessment. Eight (22%, 95% CI 10-39) patients were judged to have had an overall response at central review; all responses were partial. All 39 patients were included in the safety analyses. Five (13%) patients had a total of six grade 3 or 4 treatment-related adverse events, consisting of two cases of grade 3 fatigue, one case each of grade 3 pemphigoid, grade 3 hypothyroidism, and grade 3 peripheral sensory neuropathy, and one case of grade 4 pneumonitis. No treatment-related deaths occurred.
AB - INTERPRETATION: In this population of patients with recurrent or metastatic PD-L1-positive gastric cancer, pembrolizumab had a manageable toxicity profile and promising antitumour activity, warranting further study in phase 2 and 3 trials.
AB - FUNDING: Merck & Co.
AB - Copyright © 2016 Elsevier Ltd. All rights reserved.
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (Biomarkers, Tumor)
RN - 0 (CD274 protein, human)
RN - DPT0O3T46P (pembrolizumab)
ES - 1474-5488
IL - 1470-2045
DI - S1470-2045(16)00175-3
DO - https://dx.doi.org/10.1016/S1470-2045(16)00175-3
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Multicenter Study
ID - S1470-2045(16)00175-3 [pii]
ID - 10.1016/S1470-2045(16)00175-3 [doi]
PP - ppublish
PH - 2015/12/30 [received]
PH - 2016/02/17 [revised]
PH - 2016/03/11 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01848834
SL - https://clinicaltrials.gov/search/term=NCT01848834
LG - English
EP - 20160503
DP - 2016 Jun
DC - 20160615
EZ - 2016/05/10 06:00
DA - 2017/06/06 06:00
DT - 2016/05/10 06:00
YR - 2016
ED - 20170605
RD - 20170605
UP - 20170608
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=27157491
<27. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27271951
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Williams TJ
AU - Benavides DR
AU - Patrice KA
AU - Dalmau JO
AU - de Avila AL
AU - Le DT
AU - Lipson EJ
AU - Probasco JC
AU - Mowry EM
FA - Williams, Tanya J
FA - Benavides, David R
FA - Patrice, Kelly-Ann
FA - Dalmau, Josep O
FA - de Avila, Alexandre Leon Ribeiro
FA - Le, Dung T
FA - Lipson, Evan J
FA - Probasco, John C
FA - Mowry, Ellen M
IN - Williams, Tanya J. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
IN - Benavides, David R. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
IN - Patrice, Kelly-Ann. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
IN - Dalmau, Josep O. Department of Neurology, Hospital Clinic/Institut d'Investigacio Biomedica August Pi i Sunyer, University of Barcelona, Barcelona, Spain3Institucio Catalana de Recerca i Estudis Avancats, University of Barcelona, Barcelona, Spain.
IN - de Avila, Alexandre Leon Ribeiro. Bristol-Myers Squibb, Plainsboro, New Jersey.
IN - Le, Dung T. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
IN - Lipson, Evan J. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
IN - Probasco, John C. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
IN - Mowry, Ellen M. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
TI - Association of Autoimmune Encephalitis With Combined Immune Checkpoint Inhibitor Treatment for Metastatic Cancer.
SO - JAMA Neurology. 73(8):928-33, 2016 Aug 01
AS - JAMA Neurol. 73(8):928-33, 2016 Aug 01
NJ - JAMA neurology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101589536
IO - JAMA Neurol
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Drug Therapy, Combination/ae [Adverse Effects]
MH - *Encephalitis/ci [Chemically Induced]
MH - Female
MH - *Hashimoto Disease/ci [Chemically Induced]
MH - Humans
MH - *Immunologic Factors/ae [Adverse Effects]
MH - Male
MH - Melanoma/dt [Drug Therapy]
MH - Melanoma/sc [Secondary]
MH - Middle Aged
MH - Retrospective Studies
MH - Small Cell Lung Carcinoma/dt [Drug Therapy]
MH - Small Cell Lung Carcinoma/sc [Secondary]
AB - IMPORTANCE: Paraneoplastic encephalitides usually precede a diagnosis of cancer and are often refractory to immunosuppressive therapy. Conversely, autoimmune encephalitides are reversible conditions that can occur in the presence or absence of cancer.
AB - OBJECTIVE: To report the induction of autoimmune encephalitis in 2 patients after treatment of metastatic cancer with a combination of the immune checkpoint inhibitors nivolumab and ipilimumab.
AB - DESIGN, SETTING, AND PARTICIPANTS: A retrospective case study was conducted of the clinical and management course of 2 patients with progressive, treatment-refractory metastatic cancer who were treated with a single dose each (concomitantly) of the immune checkpoint inhibitors nivolumab, 1 mg/kg, and ipilimumab, 3 mg/kg.
AB - EXPOSURES: Nivolumab and ipilimumab.
AB - MAIN OUTCOMES AND MEASURES: The clinical response to immunosuppressive therapy in suspected autoimmune encephalitis in the setting of immune checkpoint inhibitor use.
AB - RESULTS: Autoantibody testing confirmed identification of anti-N-methyl-D-aspartate receptor antibodies in the cerebrospinal fluid of 1 patient. Withdrawal of immune checkpoint inhibitors and initiation of immunosuppressive therapy, consisting of intravenous methylprednisolone sodium succinate equivalent to 1000 mg of methylprednisolone for 5 days, 0.4 mg/kg/d of intravenous immunoglobulin for 5 days, and 2 doses of rituximab, 1000 mg, in 1 patient and oral prednisone, 60 mg/d, in the other patient, resulted in improved neurologic symptoms.
AB - CONCLUSIONS AND RELEVANCE: Immune checkpoint inhibition may favor the development of immune responses against neuronal antigens, leading to autoimmune encephalitis. Early recognition and treatment of autoimmune encephalitis in patients receiving immune checkpoint blockade therapy will likely be essential for maximizing clinical recovery and minimizing the effect of drug-related toxic effects. The mechanisms by which immune checkpoint inhibition may contribute to autoimmune encephalitis require further study.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Immunologic Factors)
RN - 31YO63LBSN (nivolumab)
RN - 6T8C155666 (ipilimumab)
RS - Hashimoto's encephalitis
ES - 2168-6157
IL - 2168-6149
DI - 2526493
DO - https://dx.doi.org/10.1001/jamaneurol.2016.1399
PT - Case Reports
PT - Journal Article
ID - 2526493 [pii]
ID - 10.1001/jamaneurol.2016.1399 [doi]
PP - ppublish
LG - English
DP - 2016 Aug 01
DC - 20160809
EZ - 2016/06/09 06:00
DA - 2017/05/31 06:00
DT - 2016/06/09 06:00
YR - 2016
ED - 20170530
RD - 20170530
UP - 20170601
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27271951
<28. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27622997
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Hodi FS
AU - Chesney J
AU - Pavlick AC
AU - Robert C
AU - Grossmann KF
AU - McDermott DF
AU - Linette GP
AU - Meyer N
AU - Giguere JK
AU - Agarwala SS
AU - Shaheen M
AU - Ernstoff MS
AU - Minor DR
AU - Salama AK
AU - Taylor MH
AU - Ott PA
AU - Horak C
AU - Gagnier P
AU - Jiang J
AU - Wolchok JD
AU - Postow MA
FA - Hodi, F Stephen
FA - Chesney, Jason
FA - Pavlick, Anna C
FA - Robert, Caroline
FA - Grossmann, Kenneth F
FA - McDermott, David F
FA - Linette, Gerald P
FA - Meyer, Nicolas
FA - Giguere, Jeffrey K
FA - Agarwala, Sanjiv S
FA - Shaheen, Montaser
FA - Ernstoff, Marc S
FA - Minor, David R
FA - Salama, April K
FA - Taylor, Matthew H
FA - Ott, Patrick A
FA - Horak, Christine
FA - Gagnier, Paul
FA - Jiang, Joel
FA - Wolchok, Jedd D
FA - Postow, Michael A
IN - Hodi, F Stephen. Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: stephen_hodi@dfci.harvard.edu.
IN - Chesney, Jason. University of Louisville, Louisville, KY, USA.
IN - Pavlick, Anna C. New York University, New York, NY, USA.
IN - Robert, Caroline. Gustave Roussy, INSERM U981, Paris, France.
IN - Grossmann, Kenneth F. Huntsman Cancer Institute, Salt Lake City, UT, USA.
IN - McDermott, David F. Beth Israel Deaconess Medical Center, Boston, MA, USA.
IN - Linette, Gerald P. Washington University School of Medicine, St Louis, MO, USA.
IN - Meyer, Nicolas. Institut Universitaire du Cancer, Toulouse, France.
IN - Giguere, Jeffrey K. Greenville Health System Cancer Institute, Greenville, SC, USA.
IN - Agarwala, Sanjiv S. St Luke's Cancer Center and Temple University, Bethlehem, PA, USA.
IN - Shaheen, Montaser. University of New Mexico, Albuquerque, NM, USA.
IN - Ernstoff, Marc S. Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
IN - Minor, David R. California Pacific Center for Melanoma Research, San Francisco, CA, USA.
IN - Salama, April K. Duke University Medical Center, Durham, NC, USA.
IN - Taylor, Matthew H. Oregon Health & Science University, Portland, OR, USA.
IN - Ott, Patrick A. Dana-Farber Cancer Institute, Boston, MA, USA.
IN - Horak, Christine. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Gagnier, Paul. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Jiang, Joel. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Wolchok, Jedd D. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
IN - Postow, Michael A. Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
TI - Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial.
SO - Lancet Oncology. 17(11):1558-1568, 2016 Nov
AS - Lancet Oncol. 17(11):1558-1568, 2016 Nov
NJ - The Lancet. Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 100957246
IO - Lancet Oncol.
SB - Index Medicus
CP - England
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - Double-Blind Method
MH - Humans
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/ge [Genetics]
MH - Melanoma/mo [Mortality]
MH - Mutation
MH - Proto-Oncogene Proteins B-raf/ge [Genetics]
AB - BACKGROUND: Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab (an anti-PD-1 antibody) plus ipilimumab (an anti-CTLA-4 antibody) compared with ipilimumab alone. We report 2-year overall survival data from a randomised controlled trial assessing this treatment in previously untreated advanced melanoma.
AB - METHODS: In this multicentre, double-blind, randomised, controlled, phase 2 trial (CheckMate 069) we recruited patients from 19 specialist cancer centres in two countries (France and the USA). Eligible patients were aged 18 years or older with previously untreated, unresectable stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned 2:1 to receive an intravenous infusion of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or ipilimumab 3 mg/kg plus placebo, every 3 weeks for four doses. Subsequently, patients assigned to nivolumab plus ipilimumab received nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity, whereas patients allocated to ipilimumab alone received placebo every 2 weeks during this phase. Randomisation was done via an interactive voice response system with a permuted block schedule (block size of six) and stratification by BRAF mutation status. The study funder, patients, investigators, and study site staff were masked to treatment assignment. The primary endpoint, which has been reported previously, was the proportion of patients with BRAFV600 wild-type melanoma achieving an investigator-assessed objective response. Overall survival was an exploratory endpoint and is reported in this Article. Efficacy analyses were done on the intention-to-treat population, whereas safety was assessed in all treated patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01927419, and is ongoing but no longer enrolling patients.
AB - FINDINGS: Between Sept 16, 2013, and Feb 6, 2014, we screened 179 patients and enrolled 142, randomly assigning 95 patients to nivolumab plus ipilimumab and 47 to ipilimumab alone. In each treatment group, one patient no longer met the study criteria following randomisation and thus did not receive study drug. At a median follow-up of 24.5 months (IQR 9.1-25.7), 2-year overall survival was 63.8% (95% CI 53.3-72.6) for those assigned to nivolumab plus ipilimumab and 53.6% (95% CI 38.1-66.8) for those assigned to ipilimumab alone; median overall survival had not been reached in either group (hazard ratio 0.74, 95% CI 0.43-1.26; p=0.26). Treatment-related grade 3-4 adverse events were reported in 51 (54%) of 94 patients who received nivolumab plus ipilimumab compared with nine (20%) of 46 patients who received ipilimumab alone. The most common treatment-related grade 3-4 adverse events were colitis (12 [13%] of 94 patients) and increased alanine aminotransferase (ten [11%]) in the combination group and diarrhoea (five [11%] of 46 patients) and hypophysitis (two [4%]) in the ipilimumab alone group. Serious grade 3-4 treatment-related adverse events were reported in 34 (36%) of 94 patients who received nivolumab plus ipilimumab (including colitis in ten [11%] of 94 patients, and diarrhoea in five [5%]) compared with four (9%) of 46 patients who received ipilimumab alone (including diarrhoea in two [4%] of 46 patients, colitis in one [2%], and hypophysitis in one [2%]). No new types of treatment-related adverse events or treatment-related deaths occurred in this updated analysis.
AB - INTERPRETATION: Although follow-up of the patients in this study is ongoing, the results of this analysis suggest that the combination of first-line nivolumab plus ipilimumab might lead to improved outcomes compared with first-line ipilimumab alone in patients with advanced melanoma. The results suggest encouraging survival outcomes with immunotherapy in this population of patients.
AB - FUNDING: Bristol-Myers Squibb.
AB - Copyright © 2016 Elsevier Ltd. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 31YO63LBSN (nivolumab)
RN - 6T8C155666 (ipilimumab)
RN - EC 2-7-11-1 (BRAF protein, human)
RN - EC 2-7-11-1 (Proto-Oncogene Proteins B-raf)
ES - 1474-5488
IL - 1470-2045
DI - S1470-2045(16)30366-7
DO - https://dx.doi.org/10.1016/S1470-2045(16)30366-7
PT - Clinical Trial, Phase II
PT - Journal Article
PT - Multicenter Study
PT - Randomized Controlled Trial
ID - S1470-2045(16)30366-7 [pii]
ID - 10.1016/S1470-2045(16)30366-7 [doi]
PP - ppublish
PH - 2016/05/26 [received]
PH - 2016/07/07 [revised]
PH - 2016/07/12 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01927419
SL - https://clinicaltrials.gov/search/term=NCT01927419
LG - English
EP - 20160909
DP - 2016 Nov
DC - 20160913
EZ - 2016/09/14 06:00
DA - 2017/05/27 06:00
DT - 2016/09/14 06:00
YR - 2016
ED - 20170526
RD - 20170526
UP - 20170530
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27622997
<29. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27141885
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Boutros C
AU - Tarhini A
AU - Routier E
AU - Lambotte O
AU - Ladurie FL
AU - Carbonnel F
AU - Izzeddine H
AU - Marabelle A
AU - Champiat S
AU - Berdelou A
AU - Lanoy E
AU - Texier M
AU - Libenciuc C
AU - Eggermont AM
AU - Soria JC
AU - Mateus C
AU - Robert C
FA - Boutros, Celine
FA - Tarhini, Ahmad
FA - Routier, Emilie
FA - Lambotte, Olivier
FA - Ladurie, Francois Leroy
FA - Carbonnel, Franck
FA - Izzeddine, Hassane
FA - Marabelle, Aurelien
FA - Champiat, Stephane
FA - Berdelou, Armandine
FA - Lanoy, Emilie
FA - Texier, Matthieu
FA - Libenciuc, Cristina
FA - Eggermont, Alexander M M
FA - Soria, Jean-Charles
FA - Mateus, Christine
FA - Robert, Caroline
IN - Boutros, Celine. Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Tarhini, Ahmad. University of Pittsburgh, 4200 Fifth Avenue, Pittsburgh, Pennsylvania 15260, USA.
IN - Routier, Emilie. Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Lambotte, Olivier. AP-HP, Internal Medicine Department, University Hospital of Bicetre, 78 Rue du General Leclerc, 94270 Le Kremlin-Bicetre, France.
IN - Lambotte, Olivier. Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicetre, France.
IN - Lambotte, Olivier. INSERM Unit U1184, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicetre, France.
IN - Ladurie, Francois Leroy. Thoracic and Vascular Surgery Service, Centre Chirurgical Marie Lannelongue, 133 Avenue de la Resistance, 92350 Le Plessis-Robinson, France.
IN - Carbonnel, Franck. Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicetre, France.
IN - Carbonnel, Franck. AP-HP, Department of Gastroenterology, University Hospital of Bicetre, Paris Sud University, 78 Rue du General Leclerc, 94270 Le Kremlin-Bicetre, France.
IN - Izzeddine, Hassane. Department of Nephrology, Pitie-Salpetriere Hospital, 47-83 Boulevard de l'hopital, 75013 Paris, France.
IN - Marabelle, Aurelien. Drug Development Department (DITEP), Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Champiat, Stephane. INSERM Unit U981, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Berdelou, Armandine. Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Lanoy, Emilie. Biostatistic and Epidemiology Unit, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Texier, Matthieu. Biostatistic and Epidemiology Unit, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Libenciuc, Cristina. Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Eggermont, Alexander M M. Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Eggermont, Alexander M M. Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicetre, France.
IN - Soria, Jean-Charles. Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicetre, France.
IN - Soria, Jean-Charles. Drug Development Department (DITEP), Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Soria, Jean-Charles. INSERM Unit U981, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Mateus, Christine. Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Robert, Caroline. Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Robert, Caroline. Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicetre, France.
IN - Robert, Caroline. INSERM Unit U981, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
TI - Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. [Review]
SO - Nature Reviews Clinical Oncology. 13(8):473-86, 2016 Aug
AS - Nat Rev Clin Oncol. 13(8):473-86, 2016 Aug
NJ - Nature reviews. Clinical oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101500077
IO - Nat Rev Clin Oncol
SB - Index Medicus
CP - England
MH - *Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - *CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Lymphocyte Activation/im [Immunology]
MH - *Melanoma/dt [Drug Therapy]
MH - Molecular Targeted Therapy/mt [Methods]
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - *Skin Neoplasms/dt [Drug Therapy]
AB - Inhibition of immune checkpoints using anti-programmed cell death-1 (PD-1) or anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibodies has revolutionized the management of patients with advanced-stage melanoma and is among the most promising treatment approaches for many other cancers. Use of CTLA-4 and PD-1 inhibitors, either as single agents, or in combination, has been approved by the US FDA for the treatment of metastatic melanoma. Treatment with these novel immunotherapies results in a unique and distinct spectrum of adverse events, which are mostly related to activation of the immune system and are, therefore, an unwanted consequence of their mechanisms of action. Adverse effects of CTLA-4 and/or PD-1 inhibition are most commonly observed in the skin, gastrointestinal tract, liver and endocrine systems and include pruritus, rash, nausea, diarrhoea and thyroid disorders. In this Review, the authors describe the adverse event profile of checkpoint inhibitors targeting CTLA-4 and PD-1, used both as monotherapies and in combination and aim to provide some general guidelines, based upon the mechanisms of action of these therapies and on the management of these immune-related adverse events.
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1759-4782
IL - 1759-4774
DI - nrclinonc.2016.58
DO - https://dx.doi.org/10.1038/nrclinonc.2016.58
PT - Journal Article
PT - Review
ID - nrclinonc.2016.58 [pii]
ID - 10.1038/nrclinonc.2016.58 [doi]
PP - ppublish
LG - English
EP - 20160504
DP - 2016 Aug
DC - 20160720
EZ - 2016/05/05 06:00
DA - 2017/05/23 06:00
DT - 2016/05/05 06:00
YR - 2016
ED - 20170522
RD - 20170522
UP - 20170524
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27141885
<30. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27141885
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Boutros C
AU - Tarhini A
AU - Routier E
AU - Lambotte O
AU - Ladurie FL
AU - Carbonnel F
AU - Izzeddine H
AU - Marabelle A
AU - Champiat S
AU - Berdelou A
AU - Lanoy E
AU - Texier M
AU - Libenciuc C
AU - Eggermont AM
AU - Soria JC
AU - Mateus C
AU - Robert C
FA - Boutros, Celine
FA - Tarhini, Ahmad
FA - Routier, Emilie
FA - Lambotte, Olivier
FA - Ladurie, Francois Leroy
FA - Carbonnel, Franck
FA - Izzeddine, Hassane
FA - Marabelle, Aurelien
FA - Champiat, Stephane
FA - Berdelou, Armandine
FA - Lanoy, Emilie
FA - Texier, Matthieu
FA - Libenciuc, Cristina
FA - Eggermont, Alexander M M
FA - Soria, Jean-Charles
FA - Mateus, Christine
FA - Robert, Caroline
IN - Boutros, Celine. Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Tarhini, Ahmad. University of Pittsburgh, 4200 Fifth Avenue, Pittsburgh, Pennsylvania 15260, USA.
IN - Routier, Emilie. Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Lambotte, Olivier. AP-HP, Internal Medicine Department, University Hospital of Bicetre, 78 Rue du General Leclerc, 94270 Le Kremlin-Bicetre, France.
IN - Lambotte, Olivier. Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicetre, France.
IN - Lambotte, Olivier. INSERM Unit U1184, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicetre, France.
IN - Ladurie, Francois Leroy. Thoracic and Vascular Surgery Service, Centre Chirurgical Marie Lannelongue, 133 Avenue de la Resistance, 92350 Le Plessis-Robinson, France.
IN - Carbonnel, Franck. Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicetre, France.
IN - Carbonnel, Franck. AP-HP, Department of Gastroenterology, University Hospital of Bicetre, Paris Sud University, 78 Rue du General Leclerc, 94270 Le Kremlin-Bicetre, France.
IN - Izzeddine, Hassane. Department of Nephrology, Pitie-Salpetriere Hospital, 47-83 Boulevard de l'hopital, 75013 Paris, France.
IN - Marabelle, Aurelien. Drug Development Department (DITEP), Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Champiat, Stephane. INSERM Unit U981, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Berdelou, Armandine. Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Lanoy, Emilie. Biostatistic and Epidemiology Unit, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Texier, Matthieu. Biostatistic and Epidemiology Unit, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Libenciuc, Cristina. Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Eggermont, Alexander M M. Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Eggermont, Alexander M M. Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicetre, France.
IN - Soria, Jean-Charles. Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicetre, France.
IN - Soria, Jean-Charles. Drug Development Department (DITEP), Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Soria, Jean-Charles. INSERM Unit U981, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Mateus, Christine. Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Robert, Caroline. Dermatology Service, Department of Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
IN - Robert, Caroline. Paris Sud University, 63 Rue Gabriel Peri, 94270 Le Kremlin Bicetre, France.
IN - Robert, Caroline. INSERM Unit U981, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
TI - Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. [Review]
SO - Nature Reviews Clinical Oncology. 13(8):473-86, 2016 Aug
AS - Nat Rev Clin Oncol. 13(8):473-86, 2016 Aug
NJ - Nature reviews. Clinical oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101500077
IO - Nat Rev Clin Oncol
SB - Index Medicus
CP - England
MH - *Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - *CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Lymphocyte Activation/im [Immunology]
MH - *Melanoma/dt [Drug Therapy]
MH - Molecular Targeted Therapy/mt [Methods]
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - *Skin Neoplasms/dt [Drug Therapy]
AB - Inhibition of immune checkpoints using anti-programmed cell death-1 (PD-1) or anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibodies has revolutionized the management of patients with advanced-stage melanoma and is among the most promising treatment approaches for many other cancers. Use of CTLA-4 and PD-1 inhibitors, either as single agents, or in combination, has been approved by the US FDA for the treatment of metastatic melanoma. Treatment with these novel immunotherapies results in a unique and distinct spectrum of adverse events, which are mostly related to activation of the immune system and are, therefore, an unwanted consequence of their mechanisms of action. Adverse effects of CTLA-4 and/or PD-1 inhibition are most commonly observed in the skin, gastrointestinal tract, liver and endocrine systems and include pruritus, rash, nausea, diarrhoea and thyroid disorders. In this Review, the authors describe the adverse event profile of checkpoint inhibitors targeting CTLA-4 and PD-1, used both as monotherapies and in combination and aim to provide some general guidelines, based upon the mechanisms of action of these therapies and on the management of these immune-related adverse events.
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1759-4782
IL - 1759-4774
DI - nrclinonc.2016.58
DO - https://dx.doi.org/10.1038/nrclinonc.2016.58
PT - Journal Article
PT - Review
ID - nrclinonc.2016.58 [pii]
ID - 10.1038/nrclinonc.2016.58 [doi]
PP - ppublish
LG - English
EP - 20160504
DP - 2016 Aug
DC - 20160720
EZ - 2016/05/05 06:00
DA - 2017/05/23 06:00
DT - 2016/05/05 06:00
YR - 2016
ED - 20170522
RD - 20170606
UP - 20170608
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=27141885
<31. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27672267
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Kimbara S
AU - Kondo S
FA - Kimbara, Shiro
FA - Kondo, Shunsuke
IN - Kimbara, Shiro. Shiro Kimbara, Shunsuke Kondo, Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo 104-0045, Japan.
IN - Kondo, Shunsuke. Shiro Kimbara, Shunsuke Kondo, Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo 104-0045, Japan.
TI - Immune checkpoint and inflammation as therapeutic targets in pancreatic carcinoma. [Review]
SO - World Journal of Gastroenterology. 22(33):7440-52, 2016 Sep 07
AS - World J Gastroenterol. 22(33):7440-52, 2016 Sep 07
NJ - World journal of gastroenterology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 100883448
IO - World J. Gastroenterol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011660
SB - Index Medicus
CP - United States
MH - Adenocarcinoma/im [Immunology]
MH - *Adenocarcinoma/th [Therapy]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Cancer Vaccines/me [Metabolism]
MH - Combined Modality Therapy
MH - Humans
MH - *Immunotherapy/mt [Methods]
MH - Inflammation/dt [Drug Therapy]
MH - Interleukin-6/me [Metabolism]
MH - Janus Kinases/me [Metabolism]
MH - NF-kappa B/me [Metabolism]
MH - Pancreatic Neoplasms/im [Immunology]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - Randomized Controlled Trials as Topic
MH - Receptors, Interleukin-8B/me [Metabolism]
MH - Signal Transduction
MH - T-Lymphocytes, Cytotoxic/me [Metabolism]
KW - Immune checkpoint; Inflammation; Pancreatic adenocarcinoma; Randomized clinical trial; Therapeutic anticancer target
AB - Pancreatic adenocarcinoma (PAC) is one of the most deadly malignant neoplasms, and the efficacy of conventional cytotoxic chemotherapy is far from satisfactory. Recent research studies have revealed that immunosuppression and inflammation are associated with oncogenesis, as well as tumor development, invasion, and metastasis in PAC. Thus, immunosuppression-related signaling, especially that involving immune checkpoint and inflammation, has emerged as novel treatment targets for PAC. However, PAC is an immune-resistant tumor, and it is still unclear whether immune checkpoint or anti-inflammation therapies would be an ideal strategy. In this article, we will review immune checkpoint and inflammation as potential targets, as well as clinical trials and the prospects for immunotherapy in PAC.
CI - Conflict-of-interest statement: Shiro Kimbara have no conflict of interest associated with this manuscript. Shunsuke Kondo received research funding from AstraZeneca, Eli Lilly and Company, and Bayer AG.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Cancer Vaccines)
RN - 0 (IL6 protein, human)
RN - 0 (Interleukin-6)
RN - 0 (NF-kappa B)
RN - 0 (Receptors, Interleukin-8B)
RN - EC 2-7-10-2 (Janus Kinases)
RS - Pancreatic Carcinoma
ES - 2219-2840
IL - 1007-9327
DO - https://dx.doi.org/10.3748/wjg.v22.i33.7440
PT - Journal Article
PT - Review
ID - 10.3748/wjg.v22.i33.7440 [doi]
ID - PMC5011660 [pmc]
PP - ppublish
PH - 2016/03/26 [received]
PH - 2016/06/30 [revised]
PH - 2016/08/01 [accepted]
LG - English
DP - 2016 Sep 07
DC - 20160927
EZ - 2016/09/28 06:00
DA - 2017/05/20 06:00
DT - 2016/09/28 06:00
YR - 2016
ED - 20170519
RD - 20170519
UP - 20170522
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27672267
<32. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27753448
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Rodrigues DN
AU - Boysen G
AU - Sumanasuriya S
AU - Seed G
AU - Marzo AM
AU - de Bono J
FA - Rodrigues, Daniel Nava
FA - Boysen, Gunther
FA - Sumanasuriya, Semini
FA - Seed, George
FA - Marzo, Angelo M De
FA - de Bono, Johann
IN - Rodrigues, Daniel Nava. The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
IN - Rodrigues, Daniel Nava. Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.
IN - Boysen, Gunther. The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
IN - Boysen, Gunther. Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.
IN - Sumanasuriya, Semini. The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
IN - Sumanasuriya, Semini. Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.
IN - Seed, George. The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
IN - Marzo, Angelo M De. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
IN - de Bono, Johann. The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
IN - de Bono, Johann. Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.
TI - The molecular underpinnings of prostate cancer: impacts on management and pathology practice. [Review]
SO - Journal of Pathology. 241(2):173-182, 2017 Jan
AS - J Pathol. 241(2):173-182, 2017 Jan
NJ - The Journal of pathology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - jlb, 0204634
IO - J. Pathol.
SB - Index Medicus
CP - England
MH - Androstenes/tu [Therapeutic Use]
MH - Animals
MH - *Biomarkers/an [Analysis]
MH - Humans
MH - Male
MH - Phosphatidylinositol 3-Kinases/me [Metabolism]
MH - *Prostatic Neoplasms/dt [Drug Therapy]
MH - Prostatic Neoplasms/me [Metabolism]
MH - *Prostatic Neoplasms/pa [Pathology]
MH - *Receptors, Androgen/me [Metabolism]
MH - *Signal Transduction/de [Drug Effects]
KW - *DNA sequencing; *FISH; *neoplasia; *prostate
AB - Prostate cancer (PCa) is a clinically heterogeneous disease and current treatment strategies are based largely on anatomical and pathological parameters. In the recent past, several DNA sequencing studies of primary and advanced PCa have revealed recurrent patterns of genomic aberrations that expose mechanisms of resistance to available therapies and potential new drug targets. Suppression of androgen receptor (AR) signalling is the cornerstone of advanced prostate cancer treatment. Genomic aberrations of the androgen receptor or alternative splicing of its mRNA are increasingly recognised as biomarkers of resistance to AR-targeted therapies such as abiraterone or enzalutamide. Genomic aberrations of the PI3K-AKT axis, in particular affecting PTEN, are common in PCa, and compounds targeting different kinases in this pathway are showing promise in clinical trials. Both germline and somatic defects in DNA repair genes have been shown to sensitise some patients to therapy with PARP inhibition. In addition, abnormalities in mismatch-repair genes are associated with response to immune checkpoint inhibition in other solid tumours and present a tantalising therapeutic avenue to be pursued. Aberrations in CDK4/6-RB1 pathway genes occur in a subset of PCas, may associate with differential sensitivity to treatment, and are likely to have clinical implications beyond prognostication. Inhibitors of CDK4/6 are already being tested in prostate cancer clinical trials. Furthermore, deletions of RB1 are strongly associated with a neuroendocrine phenotype, a rare condition characterized by a non-AR-driven transcriptomic profile. Finally, aberrations in genes involved in regulating the chromatin structure are an emerging area of interest. Deletions of CHD1 are not infrequent in PCa and may associate with increased AR activity and genomic instability, and these tumours could benefit from DNA-damaging therapies. This review summarises how genomic discoveries in PCa are changing the treatment landscape of advanced CRPC, both by identifying biomarkers of resistance and by identifying vulnerabilities to be targeted. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
AB - Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
RN - 0 (Androstenes)
RN - 0 (Biomarkers)
RN - 0 (Receptors, Androgen)
RN - EC 2-7-1 (Phosphatidylinositol 3-Kinases)
RN - G819A456D0 (abiraterone)
ES - 1096-9896
IL - 0022-3417
DO - https://dx.doi.org/10.1002/path.4826
PT - Journal Article
PT - Review
ID - 10.1002/path.4826 [doi]
PP - ppublish
PH - 2016/09/14 [received]
PH - 2016/09/29 [revised]
PH - 2016/10/01 [accepted]
LG - English
EP - 20161201
DP - 2017 Jan
DC - 20161018
EZ - 2016/10/19 06:00
DA - 2017/05/17 06:00
DT - 2016/10/19 06:00
YR - 2017
ED - 20170516
RD - 20170516
UP - 20170518
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27753448
<33. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27170616
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Marrone KA
AU - Ying W
AU - Naidoo J
FA - Marrone, K A
FA - Ying, W
FA - Naidoo, J
IN - Marrone, K A. Department of Oncology, Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
IN - Ying, W. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
IN - Naidoo, J. Department of Oncology, Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
TI - Immune-Related Adverse Events From Immune Checkpoint Inhibitors. [Review]
SO - Clinical Pharmacology & Therapeutics. 100(3):242-51, 2016 Sep
AS - Clin Pharmacol Ther. 100(3):242-51, 2016 Sep
NJ - Clinical pharmacology and therapeutics
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dhr, 0372741
IO - Clin. Pharmacol. Ther.
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antigens, CD/im [Immunology]
MH - *Antigens, CD274/ai [Antagonists & Inhibitors]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - *CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Drug Therapy, Combination
MH - Endocrine System Diseases/im [Immunology]
MH - Gastrointestinal Diseases/im [Immunology]
MH - Humans
MH - Immunotherapy, Adoptive/ae [Adverse Effects]
MH - Immunotherapy, Adoptive/mt [Methods]
MH - Molecular Targeted Therapy
MH - *Neoplasms/dt [Drug Therapy]
MH - Programmed Cell Death 1 Receptor
MH - Receptors, KIR/im [Immunology]
MH - Receptors, OX40/im [Immunology]
MH - Skin Diseases/im [Immunology]
MH - Time Factors
AB - Immunotherapy for cancer treatment has come of age, specifically with the use of immune checkpoint antibodies directed against molecules such as CTLA-4, PD-1, and PD-L1. Single-agent and combinatorial approaches utilizing these agents and other immunotherapies that may enhance antitumor effects are under investigation. With increasing clinical use of these agents, an appreciation for their toxicities comes to the fore. Adverse events that occur as a result of the immunologic effects of these therapies are termed "immune-related adverse events" (irAEs), and range in both frequency and severity in reported single-agent and combination studies. Improvements in our understanding of how and why irAEs develop and how to effectively manage them are needed. Herein we provide a state-of-the-art synopsis of the incidence, clinical features, mechanisms, and management of selected irAEs with immune checkpoint inhibitors currently in use.
AB - Copyright © 2016 American Society for Clinical Pharmacology and Therapeutics.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (CD223 antigen)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 0 (Receptors, KIR)
RN - 0 (Receptors, OX40)
RN - 0 (TNFRSF4 protein, human)
ES - 1532-6535
IL - 0009-9236
DO - https://dx.doi.org/10.1002/cpt.394
PT - Journal Article
PT - Review
ID - 10.1002/cpt.394 [doi]
PP - ppublish
PH - 2016/03/21 [received]
PH - 2016/05/06 [revised]
PH - 2016/05/07 [accepted]
LG - English
EP - 20160729
DP - 2016 Sep
DC - 20160812
EZ - 2016/05/13 06:00
DA - 2017/05/16 06:00
DT - 2016/05/14 06:00
YR - 2016
ED - 20170515
RD - 20170515
UP - 20170517
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27170616
<34. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28094061
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Larsabal M
AU - Marti A
AU - Jacquemin C
AU - Rambert J
AU - Thiolat D
AU - Dousset L
AU - Taieb A
AU - Dutriaux C
AU - Prey S
AU - Boniface K
AU - Seneschal J
FA - Larsabal, Maiana
FA - Marti, Aurelie
FA - Jacquemin, Clement
FA - Rambert, Jerome
FA - Thiolat, Denis
FA - Dousset, Lea
FA - Taieb, Alain
FA - Dutriaux, Caroline
FA - Prey, Sorilla
FA - Boniface, Katia
FA - Seneschal, Julien
IN - Larsabal, Maiana. Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hopital Saint-Andre, Bordeaux, France.
IN - Marti, Aurelie. Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hopital Saint-Andre, Bordeaux, France.
IN - Jacquemin, Clement. Institut National de la Sante Et de la Recherche Medicale (INSERM) U1035, Biotherapies de Maladies Genetiques, Inflammatoires et Cancers (BMGIC), Immuno-dermatology ATIP-AVENIR, University of Bordeaux, Bordeaux, France.
IN - Rambert, Jerome. Institut National de la Sante Et de la Recherche Medicale (INSERM) U1035, Biotherapies de Maladies Genetiques, Inflammatoires et Cancers (BMGIC), Immuno-dermatology ATIP-AVENIR, University of Bordeaux, Bordeaux, France.
IN - Thiolat, Denis. Institut National de la Sante Et de la Recherche Medicale (INSERM) U1035, Biotherapies de Maladies Genetiques, Inflammatoires et Cancers (BMGIC), Immuno-dermatology ATIP-AVENIR, University of Bordeaux, Bordeaux, France.
IN - Dousset, Lea. Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hopital Saint-Andre, Bordeaux, France.
IN - Taieb, Alain. Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hopital Saint-Andre, Bordeaux, France; Institut National de la Sante Et de la Recherche Medicale (INSERM) U1035, Biotherapies de Maladies Genetiques, Inflammatoires et Cancers (BMGIC), Immuno-dermatology ATIP-AVENIR, University of Bordeaux, Bordeaux, France.
IN - Dutriaux, Caroline. Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hopital Saint-Andre, Bordeaux, France.
IN - Prey, Sorilla. Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hopital Saint-Andre, Bordeaux, France.
IN - Boniface, Katia. Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hopital Saint-Andre, Bordeaux, France; Institut National de la Sante Et de la Recherche Medicale (INSERM) U1035, Biotherapies de Maladies Genetiques, Inflammatoires et Cancers (BMGIC), Immuno-dermatology ATIP-AVENIR, University of Bordeaux, Bordeaux, France.
IN - Seneschal, Julien. Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin Disorders, Hopital Saint-Andre, Bordeaux, France; Institut National de la Sante Et de la Recherche Medicale (INSERM) U1035, Biotherapies de Maladies Genetiques, Inflammatoires et Cancers (BMGIC), Immuno-dermatology ATIP-AVENIR, University of Bordeaux, Bordeaux, France. Electronic address: julien.seneschal@chu-bordeaux.fr.
TI - Vitiligo-like lesions occurring in patients receiving anti-programmed cell death-1 therapies are clinically and biologically distinct from vitiligo.
SO - Journal of the American Academy of Dermatology. 76(5):863-870, 2017 May
AS - J Am Acad Dermatol. 76(5):863-870, 2017 May
NJ - Journal of the American Academy of Dermatology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - hvg, 7907132
IO - J. Am. Acad. Dermatol.
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - CD8-Positive T-Lymphocytes
MH - Case-Control Studies
MH - *Chemokine CXCL10/bl [Blood]
MH - Drug Eruptions/et [Etiology]
MH - *Drug Eruptions/me [Metabolism]
MH - *Drug Eruptions/pa [Pathology]
MH - Female
MH - Humans
MH - Interferon-gamma/me [Metabolism]
MH - Male
MH - Middle Aged
MH - Photography
MH - Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Prospective Studies
MH - Receptors, CXCR3/me [Metabolism]
MH - Tumor Necrosis Factor-alpha/me [Metabolism]
MH - Vitiligo/ge [Genetics]
MH - *Vitiligo/me [Metabolism]
MH - *Vitiligo/pa [Pathology]
MH - Young Adult
KW - anti-programmed cell death-1 therapy; nivolumab; pembrolizumab; vitiligo; vitiligo-like lesions
AB - BACKGROUND: The use of anti-programmed cell death (PD)-1 therapies in metastatic tumors is associated with cutaneous side effects including vitiligo-like lesions.
AB - OBJECTIVE: We sought to characterize clinically and biologically vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies by studying a case series of 8 patients with metastatic tumors and 30 control subjects with vitiligo.
AB - METHODS: Eight patients receiving anti-PD-1 therapies with features of vitiligo-like lesions seen in our department were recruited. Clinical features and photographs were analyzed. For some patients, skin and blood samples were obtained. Results were compared with the vitiligo group.
AB - RESULTS: All patients developed lesions localized on photoexposed areas with a specific depigmentation pattern consisting of multiple flecked lesions without Koebner phenomenon. In contrast to vitiligo, patients receiving anti-PD-1 therapies who developed vitiligo-like lesions did not report any personal or family histories of vitiligo, thyroiditis, or other autoimmune disorders. Analysis of blood and skin samples revealed increased C-X-C motif ligand 10 levels in serum of patients developing vitiligo-like lesions, associated with skin infiltration of CD8 T-cells expressing C-X-C motif receptor 3 and producing elevated levels of interferon-gamma and tumor necrosis factor-alfa.
AB - LIMITATIONS: This cross-sectional study concerned a single center.
AB - CONCLUSIONS: Clinical and biological patterns of vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies differ from vitiligo, suggesting a different mechanism.
AB - Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (CXCL10 protein, human)
RN - 0 (CXCR3 protein, human)
RN - 0 (Chemokine CXCL10)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 0 (Receptors, CXCR3)
RN - 0 (Tumor Necrosis Factor-alpha)
RN - 31YO63LBSN (nivolumab)
RN - 82115-62-6 (Interferon-gamma)
RN - DPT0O3T46P (pembrolizumab)
ES - 1097-6787
IL - 0190-9622
DI - S0190-9622(16)31020-9
DO - https://dx.doi.org/10.1016/j.jaad.2016.10.044
PT - Journal Article
ID - S0190-9622(16)31020-9 [pii]
ID - 10.1016/j.jaad.2016.10.044 [doi]
PP - ppublish
PH - 2016/07/26 [received]
PH - 2016/10/27 [revised]
PH - 2016/10/31 [accepted]
LG - English
EP - 20170113
DP - 2017 May
DC - 20170117
EZ - 2017/01/18 06:00
DA - 2017/05/04 06:00
DT - 2017/01/18 06:00
YR - 2017
ED - 20170503
RD - 20170503
UP - 20170505
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28094061
<35. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27920468
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Johansson H
AU - Andersson R
AU - Bauden M
AU - Hammes S
AU - Holdenrieder S
AU - Ansari D
FA - Johansson, Henrik
FA - Andersson, Roland
FA - Bauden, Monika
FA - Hammes, Sarah
FA - Holdenrieder, Stefan
FA - Ansari, Daniel
IN - Johansson, Henrik. Henrik Johansson, Roland Andersson, Monika Bauden, Daniel Ansari, Department of Surgery, Clinical Sciences Lund, Lund University, and Skane University Hospital, SE-221 85 Lund, Sweden.
IN - Andersson, Roland. Henrik Johansson, Roland Andersson, Monika Bauden, Daniel Ansari, Department of Surgery, Clinical Sciences Lund, Lund University, and Skane University Hospital, SE-221 85 Lund, Sweden.
IN - Bauden, Monika. Henrik Johansson, Roland Andersson, Monika Bauden, Daniel Ansari, Department of Surgery, Clinical Sciences Lund, Lund University, and Skane University Hospital, SE-221 85 Lund, Sweden.
IN - Hammes, Sarah. Henrik Johansson, Roland Andersson, Monika Bauden, Daniel Ansari, Department of Surgery, Clinical Sciences Lund, Lund University, and Skane University Hospital, SE-221 85 Lund, Sweden.
IN - Holdenrieder, Stefan. Henrik Johansson, Roland Andersson, Monika Bauden, Daniel Ansari, Department of Surgery, Clinical Sciences Lund, Lund University, and Skane University Hospital, SE-221 85 Lund, Sweden.
IN - Ansari, Daniel. Henrik Johansson, Roland Andersson, Monika Bauden, Daniel Ansari, Department of Surgery, Clinical Sciences Lund, Lund University, and Skane University Hospital, SE-221 85 Lund, Sweden.
TI - Immune checkpoint therapy for pancreatic cancer. [Review]
SO - World Journal of Gastroenterology. 22(43):9457-9476, 2016 Nov 21
AS - World J Gastroenterol. 22(43):9457-9476, 2016 Nov 21
NJ - World journal of gastroenterology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 100883448
IO - World J. Gastroenterol.
SB - Index Medicus
CP - United States
MH - Animals
MH - *Antibodies/tu [Therapeutic Use]
MH - Antigens, CD274/ai [Antagonists & Inhibitors]
MH - Antigens, CD274/im [Immunology]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - Clinical Trials as Topic
MH - Humans
MH - *Immunotherapy/mt [Methods]
MH - Molecular Targeted Therapy
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/im [Immunology]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - Signal Transduction/de [Drug Effects]
KW - *Clinical trials; *Immune checkpoint inhibitors; *Pancreatic cancer
AB - Novel treatment modalities are necessary for pancreatic cancer. Immunotherapy with immune checkpoint inhibition has shown effect in other solid tumors, and could have a place in pancreatic cancer treatment. Most available clinical studies on immune checkpoint inhibitors for pancreatic cancer are not yet completed and are still recruiting patients. Among the completed trials, there have been findings of a preliminary nature such as delayed disease progression and enhanced overall survival after treatment with immune checkpoint inhibitors in mono- or combination therapy. However, due to small sample sizes, major results are not yet identifiable. The present article provides a clinical overview of immune checkpoint inhibition in pancreatic cancer. PubMed, ClinicalTrials.gov and American Society of Clinical Oncology's meeting abstracts were systematically searched for relevant clinical studies. Four articles, five abstracts and 25 clinical trials were identified and analyzed in detail.
CI - Conflict-of-interest statement: No potential conflicts of interest. No financial support.
RN - 0 (Antibodies)
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (CD274 protein, human)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 2219-2840
IL - 1007-9327
DO - https://dx.doi.org/10.3748/wjg.v22.i43.9457
PT - Journal Article
PT - Review
ID - 10.3748/wjg.v22.i43.9457 [doi]
ID - PMC5116591 [pmc]
PP - ppublish
PH - 2016/07/24 [received]
PH - 2016/09/18 [revised]
PH - 2016/10/19 [accepted]
LG - English
DP - 2016 Nov 21
DC - 20161206
EZ - 2016/12/07 06:00
DA - 2017/05/04 06:00
DT - 2016/12/07 06:00
YR - 2016
ED - 20170503
RD - 20170503
UP - 20170505
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27920468
<36. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28230773
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Botti G
AU - Collina F
AU - Scognamiglio G
AU - Rao F
AU - Peluso V
AU - De Cecio R
AU - Piezzo M
AU - Landi G
AU - De Laurentiis M
AU - Cantile M
AU - Di Bonito M
FA - Botti, Gerardo
FA - Collina, Francesca
FA - Scognamiglio, Giosue
FA - Rao, Federica
FA - Peluso, Valentina
FA - De Cecio, Rossella
FA - Piezzo, Michela
FA - Landi, Gabriella
FA - De Laurentiis, Michelino
FA - Cantile, Monica
FA - Di Bonito, Maurizio
IN - Botti, Gerardo. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. g.botti@istitutotumori.na.it.
IN - Collina, Francesca. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. francescacollina84@gmail.com.
IN - Scognamiglio, Giosue. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. giosco80@gmail.com.
IN - Rao, Federica. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. federica.rao@gmail.com.
IN - Peluso, Valentina. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. valent.peluso@gmail.com.
IN - De Cecio, Rossella. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. r.dececio@istitutotumori.na.it.
IN - Piezzo, Michela. Department of Breast Surgery and Cancer Prevention, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. m.piezzo@breastunit.org.
IN - Landi, Gabriella. Department of Breast Surgery and Cancer Prevention, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. g.landi@istitutotumori.na.it.
IN - De Laurentiis, Michelino. Department of Breast Surgery and Cancer Prevention, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. m.delaurentiis@istitutotumori.na.it.
IN - Cantile, Monica. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. m.cantile@istitutotumori.na.it.
IN - Di Bonito, Maurizio. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. mauriziodibonito@libero.it.
TI - Programmed Death Ligand 1 (PD-L1) Tumor Expression Is Associated with a Better Prognosis and Diabetic Disease in Triple Negative Breast Cancer Patients.
SO - International Journal of Molecular Sciences. 18(2), 2017 Feb 21
AS - Int. j. mol. sci.. 18(2), 2017 Feb 21
NJ - International journal of molecular sciences
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101092791
IO - Int J Mol Sci
SB - Index Medicus
CP - Switzerland
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - Antigens, CD274/ge [Genetics]
MH - *Antigens, CD274/me [Metabolism]
MH - Biomarkers, Tumor
MH - *Diabetes Mellitus/me [Metabolism]
MH - Female
MH - Humans
MH - Immunohistochemistry
MH - Kaplan-Meier Estimate
MH - Ki-67 Antigen/me [Metabolism]
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Lymphocytes, Tumor-Infiltrating/me [Metabolism]
MH - Middle Aged
MH - Neoplasm Grading
MH - Neoplasm Metastasis
MH - Neoplasm Staging
MH - Prognosis
MH - Risk Factors
MH - *Triple Negative Breast Neoplasms/me [Metabolism]
MH - *Triple Negative Breast Neoplasms/mo [Mortality]
MH - Triple Negative Breast Neoplasms/pa [Pathology]
MH - Tumor Burden
MH - Young Adult
KW - PD-L1; TNBC; diabetes
AB - Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value. However, data available in the literature about PD-L1 immunohistochemical expression in breast cancer are often discordant and not uniform, probably for the use of different antibodies clones and the high molecular heterogeneity of the different tumor types. The absence of target therapies, in particular for TNBC, has shifted the clinical attention mainly on the role of PD-L1 in this subtype of breast cancer. In this study, we evaluated tumor and TIL (tumor infiltrating lymphocytes) PDL-1 expression in a series of TNBC, included in Tissue Micro Arrays (TMAs), to define its real prognostic value, optimizing immunohistochemistry method with an "approved for diagnostic assay" antibody. PD-L1 expression directly correlated with proliferation index (Ki-67), glycemia, the presence of diabetes and indirectly with menopausal status, presence of lymph node metastasis and relapse. The analysis of Kaplan-Meier showed that an increased PD-L1 expression was strongly associated with better disease-free survival (DFS) but not correlated with overall survival (OS). Our data confirmed that PD-L1 could be an important marker for prognostic stratification and for planning immune checkpoint inhibitors therapies in patients with TNBC.
RN - 0 (Antigens, CD274)
RN - 0 (Biomarkers, Tumor)
RN - 0 (Ki-67 Antigen)
ES - 1422-0067
IL - 1422-0067
DI - E459
DI - ijms18020459
DO - https://dx.doi.org/10.3390/ijms18020459
PT - Journal Article
ID - ijms18020459 [pii]
ID - 10.3390/ijms18020459 [doi]
ID - PMC5343992 [pmc]
PP - epublish
PH - 2016/12/28 [received]
PH - 2017/02/06 [revised]
PH - 2017/02/15 [accepted]
LG - English
EP - 20170221
DP - 2017 Feb 21
DC - 20170223
EZ - 2017/02/24 06:00
DA - 2017/02/24 06:00
DT - 2017/02/24 06:00
YR - 2017
ED - 20170428
RD - 20170428
UP - 20170501
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28230773
<37. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28230773
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Botti G
AU - Collina F
AU - Scognamiglio G
AU - Rao F
AU - Peluso V
AU - De Cecio R
AU - Piezzo M
AU - Landi G
AU - De Laurentiis M
AU - Cantile M
AU - Di Bonito M
FA - Botti, Gerardo
FA - Collina, Francesca
FA - Scognamiglio, Giosue
FA - Rao, Federica
FA - Peluso, Valentina
FA - De Cecio, Rossella
FA - Piezzo, Michela
FA - Landi, Gabriella
FA - De Laurentiis, Michelino
FA - Cantile, Monica
FA - Di Bonito, Maurizio
IN - Botti, Gerardo. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. g.botti@istitutotumori.na.it.
IN - Collina, Francesca. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. francescacollina84@gmail.com.
IN - Scognamiglio, Giosue. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. giosco80@gmail.com.
IN - Rao, Federica. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. federica.rao@gmail.com.
IN - Peluso, Valentina. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. valent.peluso@gmail.com.
IN - De Cecio, Rossella. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. r.dececio@istitutotumori.na.it.
IN - Piezzo, Michela. Department of Breast Surgery and Cancer Prevention, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. m.piezzo@breastunit.org.
IN - Landi, Gabriella. Department of Breast Surgery and Cancer Prevention, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. g.landi@istitutotumori.na.it.
IN - De Laurentiis, Michelino. Department of Breast Surgery and Cancer Prevention, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. m.delaurentiis@istitutotumori.na.it.
IN - Cantile, Monica. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. m.cantile@istitutotumori.na.it.
IN - Di Bonito, Maurizio. Pathology Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", via Mariano Semmola, 80131 Napoli, Italy. mauriziodibonito@libero.it.
TI - Programmed Death Ligand 1 (PD-L1) Tumor Expression Is Associated with a Better Prognosis and Diabetic Disease in Triple Negative Breast Cancer Patients.
SO - International Journal of Molecular Sciences. 18(2), 2017 Feb 21
AS - Int. j. mol. sci.. 18(2), 2017 Feb 21
NJ - International journal of molecular sciences
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101092791
IO - Int J Mol Sci
SB - Index Medicus
CP - Switzerland
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - Antigens, CD274/ge [Genetics]
MH - *Antigens, CD274/me [Metabolism]
MH - Biomarkers, Tumor
MH - *Diabetes Mellitus/me [Metabolism]
MH - Female
MH - Humans
MH - Immunohistochemistry
MH - Kaplan-Meier Estimate
MH - Ki-67 Antigen/me [Metabolism]
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Lymphocytes, Tumor-Infiltrating/me [Metabolism]
MH - Middle Aged
MH - Neoplasm Grading
MH - Neoplasm Metastasis
MH - Neoplasm Staging
MH - Prognosis
MH - Risk Factors
MH - *Triple Negative Breast Neoplasms/me [Metabolism]
MH - *Triple Negative Breast Neoplasms/mo [Mortality]
MH - Triple Negative Breast Neoplasms/pa [Pathology]
MH - Tumor Burden
MH - Young Adult
KW - PD-L1; TNBC; diabetes
AB - Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value. However, data available in the literature about PD-L1 immunohistochemical expression in breast cancer are often discordant and not uniform, probably for the use of different antibodies clones and the high molecular heterogeneity of the different tumor types. The absence of target therapies, in particular for TNBC, has shifted the clinical attention mainly on the role of PD-L1 in this subtype of breast cancer. In this study, we evaluated tumor and TIL (tumor infiltrating lymphocytes) PDL-1 expression in a series of TNBC, included in Tissue Micro Arrays (TMAs), to define its real prognostic value, optimizing immunohistochemistry method with an "approved for diagnostic assay" antibody. PD-L1 expression directly correlated with proliferation index (Ki-67), glycemia, the presence of diabetes and indirectly with menopausal status, presence of lymph node metastasis and relapse. The analysis of Kaplan-Meier showed that an increased PD-L1 expression was strongly associated with better disease-free survival (DFS) but not correlated with overall survival (OS). Our data confirmed that PD-L1 could be an important marker for prognostic stratification and for planning immune checkpoint inhibitors therapies in patients with TNBC.
RN - 0 (Antigens, CD274)
RN - 0 (Biomarkers, Tumor)
RN - 0 (Ki-67 Antigen)
ES - 1422-0067
IL - 1422-0067
DI - E459
DI - ijms18020459
DO - https://dx.doi.org/10.3390/ijms18020459
PT - Journal Article
ID - ijms18020459 [pii]
ID - 10.3390/ijms18020459 [doi]
ID - PMC5343992 [pmc]
PP - epublish
PH - 2016/12/28 [received]
PH - 2017/02/06 [revised]
PH - 2017/02/15 [accepted]
LG - English
EP - 20170221
DP - 2017 Feb 21
DC - 20170223
EZ - 2017/02/24 06:00
DA - 2017/04/30 06:00
DT - 2017/02/24 06:00
YR - 2017
ED - 20170428
RD - 20170428
UP - 20170502
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=28230773
<38. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27696192
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Munakata W
AU - Ohashi K
AU - Yamauchi N
AU - Tobinai K
AI - Munakata, Wataru; ORCID: http://orcid.org/0000-0002-4679-0656
FA - Munakata, Wataru
FA - Ohashi, Ken
FA - Yamauchi, Nobuhiko
FA - Tobinai, Kensei
IN - Munakata, Wataru. Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. wmunakat@ncc.go.jp.
IN - Ohashi, Ken. Department of General Internal Medicine, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
IN - Yamauchi, Nobuhiko. Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
IN - Tobinai, Kensei. Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
TI - Fulminant type I diabetes mellitus associated with nivolumab in a patient with relapsed classical Hodgkin lymphoma.
SO - International Journal of Hematology. 105(3):383-386, 2017 Mar
AS - Int J Hematol. 105(3):383-386, 2017 Mar
NJ - International journal of hematology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - a7f, 9111627
IO - Int. J. Hematol.
SB - Index Medicus
CP - Japan
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Diabetes Mellitus, Type 1/ci [Chemically Induced]
MH - Diabetes Mellitus, Type 1/di [Diagnosis]
MH - Diabetes Mellitus, Type 1/ge [Genetics]
MH - Genetic Predisposition to Disease
MH - HLA-B Antigens/an [Analysis]
MH - HLA-B Antigens/ge [Genetics]
MH - *Hodgkin Disease/co [Complications]
MH - Hodgkin Disease/dt [Drug Therapy]
MH - Humans
MH - Male
MH - Recurrence
KW - *Anti-PD-1 antibody; *Fulminant type I diabetes mellitus; *Immune-related adverse events; *Nivolumab
AB - We report the case of a patient with relapsed classical Hodgkin lymphoma who developed fulminant type I diabetes mellitus as a severe adverse event of treatment with the anti-programmed cell death-1 (PD-1) antibody, nivolumab. On the first day of the sixth cycle, the blood glucose level was markedly elevated (375 mg/dL). Although neither ketoacidosis nor ketonuria was detected, the markedly acute onset of the hyperglycemia was consistent with the typical clinical course of fulminant type I diabetes mellitus, and this diagnosis was supported by clinical data. All autoantibodies associated with type I diabetes mellitus were negative. The endogenous insulin secretion ceased completely within 2 weeks. After the blood glucose level was brought under control, nivolumab was resumed and continued without other major adverse events. Human leukocyte antigen (HLA) analysis revealed that the patient carried the HLA-B*4002 haplotype, a susceptibility allele for this type of diabetes mellitus. This case suggests that fulminant type I diabetes mellitus may be triggered by nivolumab in patients with a genetic background associated with the condition, warranting careful future consideration of this particular adverse event.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (HLA-B Antigens)
RN - 31YO63LBSN (nivolumab)
ES - 1865-3774
IL - 0925-5710
DI - 10.1007/s12185-016-2101-4
DO - https://dx.doi.org/10.1007/s12185-016-2101-4
PT - Case Reports
PT - Journal Article
ID - 10.1007/s12185-016-2101-4 [doi]
ID - 10.1007/s12185-016-2101-4 [pii]
PP - ppublish
PH - 2016/07/11 [received]
PH - 2016/09/26 [accepted]
PH - 2016/09/20 [revised]
LG - English
EP - 20161001
DP - 2017 Mar
DC - 20161003
EZ - 2016/10/04 06:00
DA - 2017/04/27 06:00
DT - 2016/10/04 06:00
YR - 2017
ED - 20170426
RD - 20170426
UP - 20170428
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27696192
<39. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28112370
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Doi T
AU - Ishikawa T
AU - Okayama T
AU - Oka K
AU - Mizushima K
AU - Yasuda T
AU - Sakamoto N
AU - Katada K
AU - Kamada K
AU - Uchiyama K
AU - Handa O
AU - Takagi T
AU - Naito Y
AU - Itoh Y
FA - Doi, Toshifumi
FA - Ishikawa, Takeshi
FA - Okayama, Tetsuya
FA - Oka, Kaname
FA - Mizushima, Katsura
FA - Yasuda, Tomoyo
FA - Sakamoto, Naoyuki
FA - Katada, Kazuhiro
FA - Kamada, Kazuhiro
FA - Uchiyama, Kazuhiko
FA - Handa, Osamu
FA - Takagi, Tomohisa
FA - Naito, Yuji
FA - Itoh, Yoshito
IN - Doi, Toshifumi. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
IN - Ishikawa, Takeshi. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
IN - Okayama, Tetsuya. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
IN - Oka, Kaname. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
IN - Mizushima, Katsura. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
IN - Yasuda, Tomoyo. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
IN - Sakamoto, Naoyuki. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
IN - Katada, Kazuhiro. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
IN - Kamada, Kazuhiro. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
IN - Uchiyama, Kazuhiko. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
IN - Handa, Osamu. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
IN - Takagi, Tomohisa. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
IN - Naito, Yuji. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
IN - Itoh, Yoshito. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
TI - The JAK/STAT pathway is involved in the upregulation of PD-L1 expression in pancreatic cancer cell lines.
SO - Oncology Reports. 37(3):1545-1554, 2017 Mar
AS - Oncol Rep. 37(3):1545-1554, 2017 Mar
NJ - Oncology reports
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c1f, 9422756
IO - Oncol. Rep.
SB - Index Medicus
CP - Greece
MH - Antigens, CD274/ge [Genetics]
MH - *Antigens, CD274/me [Metabolism]
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - Apoptosis/de [Drug Effects]
MH - Blotting, Western
MH - Cell Proliferation/de [Drug Effects]
MH - Flow Cytometry
MH - *Gene Expression Regulation, Neoplastic/de [Drug Effects]
MH - Humans
MH - Janus Kinase 2/ge [Genetics]
MH - *Janus Kinase 2/me [Metabolism]
MH - Pancreatic Neoplasms/dt [Drug Therapy]
MH - *Pancreatic Neoplasms/me [Metabolism]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - RNA, Messenger/ge [Genetics]
MH - Real-Time Polymerase Chain Reaction
MH - Reverse Transcriptase Polymerase Chain Reaction
MH - STAT1 Transcription Factor/ge [Genetics]
MH - *STAT1 Transcription Factor/me [Metabolism]
MH - Signal Transduction
MH - Tumor Cells, Cultured
AB - Although improvements in the chemotherapy modalities for pancreatic cancer have been realized, pancreatic cancer remains one of the most lethal malignancies. New-generation cancer immunotherapy methods, such as blocking of the PD-1/PD-L1 pathway, are consistently being investigated to improve the survival of pancreatic cancer patients. In the present study, we evaluated the influence of anticancer agents 5-fluorouracil, gemcitabine and paclitaxel on PD-L1 expression in human pancreatic cancer cell lines MIA PaCa-2 and AsPC-1 and in murine pancreatic cancer cell line Pan02. Additionally, we analyzed the molecular mechanisms that facilitated the regulation of PD-L1 expression in these cell lines. We observed that when AsPC-1, MIA PaCa-2 and Pan02 cells were stimulated by 5-fluorouracil, gemcitabine or paclitaxel, PD-L1 surface protein expression was enhanced. Similarly, the mRNA level of PD-L1 was upregulated in the AsPC-1 and Pan02 cells when stimulated by each of the three anticancer agents. The phosphorylation of STAT1 and an increase in total STAT1 were also observed in the AsPC-1 cells when stimulated by each anticancer agent. In response to JAK2 inhibitor treatment, PD-L1 upregulation induced by the anticancer agents was reduced in a dose-dependent manner. These results suggest that i) the JAK2/STAT1 pathway is involved in the anticancer agent-mediated PD-L1 transcription; and ii) the anticancer agents altered the tumor immune response which may induce tumor immune escape. These findings can have an influence on the design of treatments that combine chemotherapy and immunotherapy.
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (CD274 protein, human)
RN - 0 (RNA, Messenger)
RN - 0 (STAT1 Transcription Factor)
RN - 0 (STAT1 protein, human)
RN - EC 2-7-10-2 (JAK2 protein, human)
RN - EC 2-7-10-2 (Janus Kinase 2)
ES - 1791-2431
IL - 1021-335X
DO - https://dx.doi.org/10.3892/or.2017.5399
PT - Journal Article
ID - 10.3892/or.2017.5399 [doi]
PP - ppublish
PH - 2016/03/28 [received]
PH - 2016/12/28 [accepted]
LG - English
EP - 20170123
DP - 2017 Mar
DC - 20170123
EZ - 2017/01/24 06:00
DA - 2017/04/26 06:00
DT - 2017/01/24 06:00
YR - 2017
ED - 20170425
RD - 20170425
UP - 20170427
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28112370
<40. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27416087
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Gonzalez N
AU - Ratner D
FA - Gonzalez, Noelani
FA - Ratner, Desiree
IN - Gonzalez, Noelani. Icahn School of Medicine at Mount Sinai, New York, New York, USA.
IN - Ratner, Desiree. Icahn School of Medicine at Mount Sinai and Mount Sinai Beth Israel, New York, New York, USA.
TI - Novel melanoma therapies and their side effects. [Review]
SO - Cutis. 97(6):426-8, 2016 Jun
AS - Cutis. 97(6):426-8, 2016 Jun
NJ - Cutis
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - dxb, 0006440
IO - Cutis
SB - Index Medicus
CP - United States
MH - Adrenal Cortex Hormones/tu [Therapeutic Use]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Chemical and Drug Induced Liver Injury/dt [Drug Therapy]
MH - Chemical and Drug Induced Liver Injury/et [Etiology]
MH - Drug Eruptions/et [Etiology]
MH - Gastrointestinal Diseases/ci [Chemically Induced]
MH - Gastrointestinal Diseases/dt [Drug Therapy]
MH - Humans
MH - Hypophysitis/ci [Chemically Induced]
MH - Hypophysitis/dt [Drug Therapy]
MH - Hypothyroidism/ci [Chemically Induced]
MH - Hypothyroidism/dt [Drug Therapy]
MH - Imidazoles/ae [Adverse Effects]
MH - Immunosuppressive Agents/tu [Therapeutic Use]
MH - Indoles/ae [Adverse Effects]
MH - *Melanoma/dt [Drug Therapy]
MH - Mycophenolic Acid/tu [Therapeutic Use]
MH - Oximes/ae [Adverse Effects]
MH - Pyridones/ae [Adverse Effects]
MH - Pyrimidinones/ae [Adverse Effects]
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Sulfonamides/ae [Adverse Effects]
MH - Sweet Syndrome/ci [Chemically Induced]
MH - Thyrotoxicosis/ci [Chemically Induced]
MH - Thyrotoxicosis/dt [Drug Therapy]
MH - Tumor Necrosis Factor-alpha/ai [Antagonists & Inhibitors]
MH - Vitiligo/ci [Chemically Induced]
AB - In the last few years, melanoma treatment has been revolutionized by the development of immune checkpoint-blocking antibodies or immune checkpoint inhibitors including ipilimumab, vemurafenib, dabrafenib, trametinib, nivolumab, and pembrolizumab. Although they have shown promising results, they also have caused multiple adverse events (AEs), particularly immune-related AEs (irAEs). Specialists should be familiar with these AEs.
RN - 0 (Adrenal Cortex Hormones)
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (Imidazoles)
RN - 0 (Immunosuppressive Agents)
RN - 0 (Indoles)
RN - 0 (Oximes)
RN - 0 (Pyridones)
RN - 0 (Pyrimidinones)
RN - 0 (Sulfonamides)
RN - 0 (Tumor Necrosis Factor-alpha)
RN - 207SMY3FQT (vemurafenib)
RN - 31YO63LBSN (nivolumab)
RN - 33E86K87QN (trametinib)
RN - 6T8C155666 (ipilimumab)
RN - DPT0O3T46P (pembrolizumab)
RN - HU9DX48N0T (Mycophenolic Acid)
RN - QGP4HA4G1B (dabrafenib)
ES - 2326-6929
IL - 0011-4162
PT - Journal Article
PT - Review
PP - ppublish
LG - English
DP - 2016 Jun
DC - 20160715
EZ - 2016/07/15 06:00
DA - 2017/04/19 06:00
DT - 2016/07/16 06:00
YR - 2016
ED - 20170418
RD - 20170418
UP - 20170420
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27416087
<41. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27809739
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Bourke JM
AU - O'Sullivan M
AU - Khattak MA
FA - Bourke, Jack M
FA - O'Sullivan, Michael
FA - Khattak, Muhammad A
IN - Bourke, Jack M. Fiona Stanley Hospital, Perth, WA Jack.Bourke@health.wa.gov.au.
IN - O'Sullivan, Michael. Fiona Stanley Hospital, Perth, WA.
IN - Khattak, Muhammad A. Fiona Stanley Hospital, Perth, WA.
TI - Management of adverse events related to new cancer immunotherapy (immune checkpoint inhibitors). [Review]
SO - Medical Journal of Australia. 205(9):418-424, 2016 Nov 07
AS - Med J Aust. 205(9):418-424, 2016 Nov 07
NJ - The Medical journal of Australia
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 0400714, m26
IO - Med. J. Aust.
SB - Index Medicus
CP - Australia
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/ad [Administration & Dosage]
MH - *Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - *Cell Cycle Checkpoints
MH - Drug Eruptions/et [Etiology]
MH - Humans
MH - Immunosuppressive Agents/ad [Administration & Dosage]
MH - *Immunosuppressive Agents/ae [Adverse Effects]
MH - *Lung Neoplasms/dt [Drug Therapy]
MH - *Melanoma/dt [Drug Therapy]
MH - Pituitary Diseases/et [Etiology]
AB - New immunotherapies have significantly improved survival in certain advanced cancers in recent years, particularly metastatic melanoma and lung cancer. The most effective of these therapies are the immune checkpoint inhibitors (ICIs) such as ipilimumab, nivolumab and pembrolizumab. The use of ICIs will continue to increase in the coming years as evidence of their benefit in a range of other cancers builds. ICIs are associated with novel immune-related adverse events (irAEs), which can involve a wide range of organs. The most common irAEs involve the skin (rash, pruritus), gastrointestinal tract (diarrhoea, colitis) and endocrine system (thyroid, pituitary). While severity is generally mild, life-threatening complications can occur if not recognised and treated promptly. Due to the diverse manifestations of irAEs, patients may present to doctors who are not familiar with these drugs, which creates the potential for delays in management. Management of irAEs depends on severity and the organ affected. Systemic steroids are often required and ICI therapy may be withheld or discontinued. Additional immunosuppressive medications may be necessary in steroid-refractory cases. This review provides an overview of the potential toxicities and their management for general clinicians. Broader awareness of these issues among medical professionals will hopefully reduce unnecessary delays in diagnosis and treatment. Patient and carer education regarding irAEs is extremely important; patients and carers should be advised to seek urgent medical attention if required.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Immunosuppressive Agents)
RN - 31YO63LBSN (nivolumab)
RN - 6T8C155666 (ipilimumab)
RN - DPT0O3T46P (pembrolizumab)
ES - 1326-5377
IL - 0025-729X
DI - 10.5694/mja16.00586
PT - Journal Article
PT - Review
ID - 10.5694/mja16.00586 [pii]
PP - ppublish
PH - 2016/05/17 [received]
PH - 2016/07/20 [accepted]
LG - English
DP - 2016 Nov 07
DC - 20161104
EZ - 2016/11/05 06:00
DA - 2017/04/13 06:00
DT - 2016/11/05 06:00
YR - 2016
ED - 20170412
RD - 20170412
UP - 20170414
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27809739
<42. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27297738
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Miyoshi Y
AU - Ogawa O
AU - Oyama Y
FA - Miyoshi, Yuka
FA - Ogawa, Osamu
FA - Oyama, Yu
IN - Miyoshi, Yuka. Department of Diabetes and Endocrinology, Kameda Medical Center.
TI - Nivolumab, an Anti-Programmed Cell Death-1 Antibody, Induces Fulminant Type 1 Diabetes.
SO - Tohoku Journal of Experimental Medicine. 239(2):155-8, 2016
AS - Tohoku J Exp Med. 239(2):155-8, 2016
NJ - The Tohoku journal of experimental medicine
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - vtf, 0417355
IO - Tohoku J. Exp. Med.
SB - Index Medicus
CP - Japan
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Diabetes Mellitus, Type 1/ci [Chemically Induced]
MH - Diabetes Mellitus, Type 1/dt [Drug Therapy]
MH - Female
MH - Hemoglobin A, Glycosylated/me [Metabolism]
MH - Humans
MH - Insulin/me [Metabolism]
MH - *Programmed Cell Death 1 Receptor/im [Immunology]
AB - Programmed cell death-1 (PD-1), an immunoreceptor, is located on T cells and pro-B cells and interacts with its ligands to inhibit T cell activation and proliferation, thereby promoting immunological self-tolerance. Nivolumab, an anti-PD1 antibody, blocks PD-1 and can restore anticancer immune responses by abrogating PD-1 pathway-mediated T-cell inhibition. Autoimmune adverse events are expected with PD-1 therapy. Fulminant type 1 diabetes is the subtype of type 1 diabetes. The clinical feature is the extremely rapid progression of hyperglycemia and ketoacidosis. Here we describe a 66-year-old woman with advanced melanoma who was treated with nivolumab. After 4 months and six doses of the medicine, the patient was admitted to the hospital with complaints of nausea and vomiting. The laboratory data showed ketonuria, hyperglycemia (531 mg/dl), high anion gap metabolic acidosis, HbA1c (7.3%), and absence of insulin-secreting capacity. These data are compatible with the criteria of fulminant type 1 diabetes. The patient was diagnosed with diabetic ketoacidosis because of fulminant type 1 diabetes. The findings of this case indicated that nivolumab can cause fulminant type 1 diabetes. Diabetic ketoacidosis due to fulminant type 1 diabetes is potentially fatal condition. Thus, diabetic ketoacidosis due to fulminant type 1 diabetes should be considered in the differential diagnosis when patients treated with nivolumab complain of gastrointestinal symptoms.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Hemoglobin A, Glycosylated)
RN - 0 (Insulin)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 31YO63LBSN (nivolumab)
ES - 1349-3329
IL - 0040-8727
DO - https://dx.doi.org/10.1620/tjem.239.155
PT - Case Reports
PT - Journal Article
ID - 10.1620/tjem.239.155 [doi]
PP - ppublish
LG - English
DP - 2016
DC - 20160614
EZ - 2016/06/15 06:00
DA - 2017/04/04 06:00
DT - 2016/06/15 06:00
YR - 2016
ED - 20170403
RD - 20170403
UP - 20170405
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27297738
<43. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27447625
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Mittica G
AU - Genta S
AU - Aglietta M
AU - Valabrega G
FA - Mittica, Gloria
FA - Genta, Sofia
FA - Aglietta, Massimo
FA - Valabrega, Giorgio
IN - Mittica, Gloria. Candiolo Cancer Institute-FPO-IRCCS, Candiolo, Turin 10060, Italy. gloria.mittica@ircc.it.
IN - Mittica, Gloria. Department of Oncology, University of Torino, Turin 10060, Italy. gloria.mittica@ircc.it.
IN - Genta, Sofia. Candiolo Cancer Institute-FPO-IRCCS, Candiolo, Turin 10060, Italy. sofia.genta@ircc.it.
IN - Genta, Sofia. Department of Oncology, University of Torino, Turin 10060, Italy. sofia.genta@ircc.it.
IN - Aglietta, Massimo. Candiolo Cancer Institute-FPO-IRCCS, Candiolo, Turin 10060, Italy. massimo.aglietta@ircc.it.
IN - Aglietta, Massimo. Department of Oncology, University of Torino, Turin 10060, Italy. massimo.aglietta@ircc.it.
IN - Valabrega, Giorgio. Candiolo Cancer Institute-FPO-IRCCS, Candiolo, Turin 10060, Italy. giorgio.valabrega@ircc.it.
IN - Valabrega, Giorgio. Department of Oncology, University of Torino, Turin 10060, Italy. giorgio.valabrega@ircc.it.
TI - Immune Checkpoint Inhibitors: A New Opportunity in the Treatment of Ovarian Cancer?. [Review]
SO - International Journal of Molecular Sciences. 17(7), 2016 Jul 20
AS - Int. j. mol. sci.. 17(7), 2016 Jul 20
NJ - International journal of molecular sciences
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101092791
IO - Int J Mol Sci
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964540
SB - Index Medicus
CP - Switzerland
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Cell Cycle Checkpoints/de [Drug Effects]
MH - Female
MH - Humans
MH - *Immunotherapy
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - Ovarian Neoplasms/im [Immunology]
KW - cytotoxic T-lymphocyte-associated protein 4 (CTLA-4); immune checkpoint inhibitor; ipilimumab; nivolumab; ovarian cancer; pembrolizumab; programmed cell death ligand-1 (PD-L1); programmed cell death-1 (PD-1); tumor infiltrating lymphocytes (TILs)
AB - Epithelial ovarian cancer (EOC) is the leading cause of death for gynecological cancer. The standard treatment for advanced stage is the combination of optimal debulking surgery and platinum-based chemotherapy. Nevertheless, recurrence is frequent (around 70%) and prognosis is globally poor. New therapeutic agents are needed to improve survival. Since EOC is strongly immunogenic, immune checkpoint inhibitors are under evaluation for their capacity to contrast the "turn off" signals expressed by the tumor to escape the immune system and usually responsible for self-tolerance maintenance. This article reviews the literature on anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies in EOC and highlights their possible lines of development. Further studies are needed to better define the prognostic role of the immune checkpoint inhibitors, to identify predictors of response and the optimal clinical setting in EOC.
RN - 0 (Antineoplastic Agents)
ES - 1422-0067
IL - 1422-0067
DI - E1169
DI - ijms17071169
DO - https://dx.doi.org/10.3390/ijms17071169
PT - Journal Article
PT - Review
ID - ijms17071169 [pii]
ID - 10.3390/ijms17071169 [doi]
ID - PMC4964540 [pmc]
PP - epublish
PH - 2016/06/20 [received]
PH - 2016/07/08 [revised]
PH - 2016/07/14 [accepted]
LG - English
EP - 20160720
DP - 2016 Jul 20
DC - 20160724
EZ - 2016/07/23 06:00
DA - 2016/07/23 06:00
DT - 2016/07/23 06:00
YR - 2016
ED - 20170328
RD - 20170328
UP - 20170330
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27447625
<44. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27012985
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Tanaka R
AU - Fujisawa Y
AU - Maruyama H
AU - Nakamura Y
AU - Yoshino K
AU - Ohtsuka M
AU - Fujimoto M
FA - Tanaka, Ryota
FA - Fujisawa, Yasuhiro
FA - Maruyama, Hiroshi
FA - Nakamura, Yasuhiro
FA - Yoshino, Koji
FA - Ohtsuka, Mikio
FA - Fujimoto, Manabu
IN - Tanaka, Ryota. Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki ryota621@hotmail.co.jp.
IN - Fujisawa, Yasuhiro. Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki.
IN - Maruyama, Hiroshi. Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki.
IN - Nakamura, Yasuhiro. Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center, Saitama.
IN - Yoshino, Koji. Department of Dermatology, Tokyo Metropolitan Komagome Hospital, Tokyo.
IN - Ohtsuka, Mikio. Department of Dermatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
IN - Fujimoto, Manabu. Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki.
TI - Nivolumab-induced thyroid dysfunction.
SO - Japanese Journal of Clinical Oncology. 46(6):575-9, 2016 Jun
AS - Jpn J Clin Oncol. 46(6):575-9, 2016 Jun
NJ - Japanese journal of clinical oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - kin, 0313225
IO - Jpn. J. Clin. Oncol.
SB - Index Medicus
CP - England
MH - Aged
MH - Aged, 80 and over
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Female
MH - Hormone Replacement Therapy
MH - Humans
MH - *Hypothyroidism/et [Etiology]
MH - Hypothyroidism/th [Therapy]
MH - Male
MH - Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - Quality of Life
MH - Thyrotropin/an [Analysis]
MH - Thyroxine/an [Analysis]
MH - Triiodothyronine/an [Analysis]
KW - *endocrine-med; *immunotherapy; *skin
AB - Nivolumab (ONO-4538) is an anti-programmed death-1 specific monoclonal antibody, which has become a standard treatment for metastatic malignant melanoma. Nivolumab induces autoimmune adverse events, defined as immune-related adverse events. Herein, we report a case of nivolumab-induced thyroid dysfunction in the clinical setting. Fourteen patients were treated with nivolumab at our institute, of which three developed thyroid dysfunction, an incidence higher than previously reported in the initial clinical trials. Interestingly, one patient achieved complete remission; suggesting that in some patients, the occurrence of immune-related adverse events, including thyroid dysfunction, might reflect the drug's antitumour efficacy. No patient died or discontinued nivolumab treatment owing to thyroid dysfunction. Although thyroid dysfunction first appeared to be asymptomatic, two of the three patients developed symptoms related to hypothyroidism soon after, requiring hormone replacement therapy. Another patient developed hyperthyroidism that was initially asymptomatic; the patient subsequently developed myalgia with fever >39.5degreeC after two additional courses of nivolumab. Treatment with nivolumab was therefore discontinued, and treatment with prednisolone was initiated. Symptoms resolved within a few days, and thyroid function normalized. Thyroid dysfunction is sometimes difficult to diagnose because its symptoms similar to those of many other diseases. In addition, thyroid-related immune-related adverse events may present with unique symptoms such as myalgia with high fever, abruptly worsening patients' quality of life. Consequently, thyroid dysfunction should be considered as a possible immune-related adverse event. Thus, it is important to test for thyroid dysfunction at baseline and before the administration of each nivolumab dose if possible.
AB - Copyright © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 06LU7C9H1V (Triiodothyronine)
RN - 31YO63LBSN (nivolumab)
RN - 9002-71-5 (Thyrotropin)
RN - Q51BO43MG4 (Thyroxine)
ES - 1465-3621
IL - 0368-2811
DI - hyw036
DO - https://dx.doi.org/10.1093/jjco/hyw036
PT - Case Reports
PT - Journal Article
ID - hyw036 [pii]
ID - 10.1093/jjco/hyw036 [doi]
PP - ppublish
PH - 2015/08/31 [received]
PH - 2016/02/20 [accepted]
LG - English
EP - 20160323
DP - 2016 Jun
DC - 20160702
EZ - 2016/03/26 06:00
DA - 2016/03/26 06:00
DT - 2016/03/26 06:00
YR - 2016
ED - 20170328
RD - 20170328
UP - 20170330
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27012985
<45. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27447625
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Mittica G
AU - Genta S
AU - Aglietta M
AU - Valabrega G
FA - Mittica, Gloria
FA - Genta, Sofia
FA - Aglietta, Massimo
FA - Valabrega, Giorgio
IN - Mittica, Gloria. Candiolo Cancer Institute-FPO-IRCCS, Candiolo, Turin 10060, Italy. gloria.mittica@ircc.it.
IN - Mittica, Gloria. Department of Oncology, University of Torino, Turin 10060, Italy. gloria.mittica@ircc.it.
IN - Genta, Sofia. Candiolo Cancer Institute-FPO-IRCCS, Candiolo, Turin 10060, Italy. sofia.genta@ircc.it.
IN - Genta, Sofia. Department of Oncology, University of Torino, Turin 10060, Italy. sofia.genta@ircc.it.
IN - Aglietta, Massimo. Candiolo Cancer Institute-FPO-IRCCS, Candiolo, Turin 10060, Italy. massimo.aglietta@ircc.it.
IN - Aglietta, Massimo. Department of Oncology, University of Torino, Turin 10060, Italy. massimo.aglietta@ircc.it.
IN - Valabrega, Giorgio. Candiolo Cancer Institute-FPO-IRCCS, Candiolo, Turin 10060, Italy. giorgio.valabrega@ircc.it.
IN - Valabrega, Giorgio. Department of Oncology, University of Torino, Turin 10060, Italy. giorgio.valabrega@ircc.it.
TI - Immune Checkpoint Inhibitors: A New Opportunity in the Treatment of Ovarian Cancer?. [Review]
SO - International Journal of Molecular Sciences. 17(7), 2016 Jul 20
AS - Int. j. mol. sci.. 17(7), 2016 Jul 20
NJ - International journal of molecular sciences
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101092791
IO - Int J Mol Sci
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964540
SB - Index Medicus
CP - Switzerland
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Cell Cycle Checkpoints/de [Drug Effects]
MH - Female
MH - Humans
MH - *Immunotherapy
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - Ovarian Neoplasms/im [Immunology]
KW - cytotoxic T-lymphocyte-associated protein 4 (CTLA-4); immune checkpoint inhibitor; ipilimumab; nivolumab; ovarian cancer; pembrolizumab; programmed cell death ligand-1 (PD-L1); programmed cell death-1 (PD-1); tumor infiltrating lymphocytes (TILs)
AB - Epithelial ovarian cancer (EOC) is the leading cause of death for gynecological cancer. The standard treatment for advanced stage is the combination of optimal debulking surgery and platinum-based chemotherapy. Nevertheless, recurrence is frequent (around 70%) and prognosis is globally poor. New therapeutic agents are needed to improve survival. Since EOC is strongly immunogenic, immune checkpoint inhibitors are under evaluation for their capacity to contrast the "turn off" signals expressed by the tumor to escape the immune system and usually responsible for self-tolerance maintenance. This article reviews the literature on anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies in EOC and highlights their possible lines of development. Further studies are needed to better define the prognostic role of the immune checkpoint inhibitors, to identify predictors of response and the optimal clinical setting in EOC.
RN - 0 (Antineoplastic Agents)
ES - 1422-0067
IL - 1422-0067
DI - E1169
DI - ijms17071169
DO - https://dx.doi.org/10.3390/ijms17071169
PT - Journal Article
PT - Review
ID - ijms17071169 [pii]
ID - 10.3390/ijms17071169 [doi]
ID - PMC4964540 [pmc]
PP - epublish
PH - 2016/06/20 [received]
PH - 2016/07/08 [revised]
PH - 2016/07/14 [accepted]
LG - English
EP - 20160720
DP - 2016 Jul 20
DC - 20160724
EZ - 2016/07/23 06:00
DA - 2017/03/30 06:00
DT - 2016/07/23 06:00
YR - 2016
ED - 20170328
RD - 20170328
UP - 20170331
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=27447625
<46. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27012985
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Tanaka R
AU - Fujisawa Y
AU - Maruyama H
AU - Nakamura Y
AU - Yoshino K
AU - Ohtsuka M
AU - Fujimoto M
FA - Tanaka, Ryota
FA - Fujisawa, Yasuhiro
FA - Maruyama, Hiroshi
FA - Nakamura, Yasuhiro
FA - Yoshino, Koji
FA - Ohtsuka, Mikio
FA - Fujimoto, Manabu
IN - Tanaka, Ryota. Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki ryota621@hotmail.co.jp.
IN - Fujisawa, Yasuhiro. Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki.
IN - Maruyama, Hiroshi. Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki.
IN - Nakamura, Yasuhiro. Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center, Saitama.
IN - Yoshino, Koji. Department of Dermatology, Tokyo Metropolitan Komagome Hospital, Tokyo.
IN - Ohtsuka, Mikio. Department of Dermatology, Fukushima Medical University School of Medicine, Fukushima, Japan.
IN - Fujimoto, Manabu. Department of Dermatology, Faculty of Medicine, University of Tsukuba, Ibaraki.
TI - Nivolumab-induced thyroid dysfunction.
SO - Japanese Journal of Clinical Oncology. 46(6):575-9, 2016 Jun
AS - Jpn J Clin Oncol. 46(6):575-9, 2016 Jun
NJ - Japanese journal of clinical oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - kin, 0313225
IO - Jpn. J. Clin. Oncol.
SB - Index Medicus
CP - England
MH - Aged
MH - Aged, 80 and over
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Female
MH - Hormone Replacement Therapy
MH - Humans
MH - *Hypothyroidism/et [Etiology]
MH - Hypothyroidism/th [Therapy]
MH - Male
MH - Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - Quality of Life
MH - Thyrotropin/an [Analysis]
MH - Thyroxine/an [Analysis]
MH - Triiodothyronine/an [Analysis]
KW - *endocrine-med; *immunotherapy; *skin
AB - Nivolumab (ONO-4538) is an anti-programmed death-1 specific monoclonal antibody, which has become a standard treatment for metastatic malignant melanoma. Nivolumab induces autoimmune adverse events, defined as immune-related adverse events. Herein, we report a case of nivolumab-induced thyroid dysfunction in the clinical setting. Fourteen patients were treated with nivolumab at our institute, of which three developed thyroid dysfunction, an incidence higher than previously reported in the initial clinical trials. Interestingly, one patient achieved complete remission; suggesting that in some patients, the occurrence of immune-related adverse events, including thyroid dysfunction, might reflect the drug's antitumour efficacy. No patient died or discontinued nivolumab treatment owing to thyroid dysfunction. Although thyroid dysfunction first appeared to be asymptomatic, two of the three patients developed symptoms related to hypothyroidism soon after, requiring hormone replacement therapy. Another patient developed hyperthyroidism that was initially asymptomatic; the patient subsequently developed myalgia with fever >39.5degreeC after two additional courses of nivolumab. Treatment with nivolumab was therefore discontinued, and treatment with prednisolone was initiated. Symptoms resolved within a few days, and thyroid function normalized. Thyroid dysfunction is sometimes difficult to diagnose because its symptoms similar to those of many other diseases. In addition, thyroid-related immune-related adverse events may present with unique symptoms such as myalgia with high fever, abruptly worsening patients' quality of life. Consequently, thyroid dysfunction should be considered as a possible immune-related adverse event. Thus, it is important to test for thyroid dysfunction at baseline and before the administration of each nivolumab dose if possible.
AB - Copyright © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 06LU7C9H1V (Triiodothyronine)
RN - 31YO63LBSN (nivolumab)
RN - 9002-71-5 (Thyrotropin)
RN - Q51BO43MG4 (Thyroxine)
ES - 1465-3621
IL - 0368-2811
DI - hyw036
DO - https://dx.doi.org/10.1093/jjco/hyw036
PT - Case Reports
PT - Journal Article
ID - hyw036 [pii]
ID - 10.1093/jjco/hyw036 [doi]
PP - ppublish
PH - 2015/08/31 [received]
PH - 2016/02/20 [accepted]
LG - English
EP - 20160323
DP - 2016 Jun
DC - 20160702
EZ - 2016/03/26 06:00
DA - 2017/03/30 06:00
DT - 2016/03/26 06:00
YR - 2016
ED - 20170328
RD - 20170328
UP - 20170331
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=27012985
<47. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27881588
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Aleksova J
AU - Lau PK
AU - Soldatos G
AU - McArthur G
FA - Aleksova, Jasna
FA - Lau, Peter K H
FA - Soldatos, Georgia
FA - McArthur, Grant
IN - Aleksova, Jasna. Monash Health, Clayton, Victoria, Australia.
IN - Lau, Peter K H. Peter MacCallum Cancer Institute, Cancer Medicine, East Melbourne, Victoria, Australia.
IN - Soldatos, Georgia. Peter MacCallum Cancer Institute, Cancer Medicine, East Melbourne, Victoria, Australia.
IN - Soldatos, Georgia. Monash Centre for Health Research and Implementation, Melbourne, Victoria, Australia.
IN - McArthur, Grant. Department of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
IN - McArthur, Grant. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
TI - Glucocorticoids did not reverse type 1 diabetes mellitus secondary to pembrolizumab in a patient with metastatic melanoma.
SO - BMJ Case Reports. 2016, 2016 Nov 23
AS - BMJ Case Rep. 2016, 2016 Nov 23
NJ - BMJ case reports
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101526291
IO - BMJ Case Rep
SB - Index Medicus
CP - England
MH - *Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - *Diabetes Mellitus, Type 1/ci [Chemically Induced]
MH - *Diabetes Mellitus, Type 1/dt [Drug Therapy]
MH - *Glucocorticoids/tu [Therapeutic Use]
MH - Humans
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - *Melanoma/pa [Pathology]
MH - Middle Aged
MH - Treatment Outcome
AB - Immune checkpoint inhibitors offer patients with advanced melanoma substantial improvements in survival. Unlike chemotherapy, immune checkpoint inhibitors such as ipilimumab and pembrolizumab cause unique immune-related adverse events (irAEs), including the development of endocrinopathies. We report a case of a man aged 60 years who developed diabetic ketoacidosis (DKA) following the use of pembrolizumab for the treatment of metastatic melanoma. He received four cycles of ipilimumab, before proceeding to pembrolizumab. Five weeks after initiating pembrolizumab, he presented in DKA with a pH of 7.0, bicarbonate of 7 mmol/L, blood glucose of 27 mmol/L and serum ketones of 5.9 mmol/L. Antibodies to glutamic acid decarboxylase (anti-GAD) and Islet antigen 2 (IA-2) were negative and C-peptide was low at 57 pmol/L (300-2350 pmol/L). There was no personal or family history of autoimmune conditions. Standard immunosuppression for irAEs was started using prednisolone in an attempt to salvage beta cell function but was unsuccessful. To the best of our knowledge, this is the first reported attempt at reversing pembrolizumab-induced type 1 diabetes using glucocorticoids.
AB - Copyright 2016 BMJ Publishing Group Ltd.
CI - PL has received honoraria and travel funding from Bristol Myers Squibb.
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Glucocorticoids)
RN - DPT0O3T46P (pembrolizumab)
ES - 1757-790X
IL - 1757-790X
DI - bcr2016217454
DI - bcr-2016-217454
DO - https://dx.doi.org/10.1136/bcr-2016-217454
PT - Case Reports
PT - Journal Article
ID - bcr-2016-217454 [pii]
ID - 10.1136/bcr-2016-217454 [doi]
PP - epublish
LG - English
EP - 20161123
DP - 2016 Nov 23
DC - 20161124
EZ - 2016/11/25 06:00
DA - 2017/03/18 06:00
DT - 2016/11/25 06:00
YR - 2016
ED - 20170317
RD - 20170317
UP - 20170320
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27881588
<48. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27181232
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Fukushima S
FA - Fukushima, Satoshi
IN - Fukushima, Satoshi. Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University.
TI - A review of adverse events caused by immune checkpoint inhibitors. [Review]
SO - Nihon Rinsho Meneki Gakkai Kaishi. 39(1):30-6, 2016
AS - Nihon Rinsho Meneki Gakkai Kaishi. 39(1):30-6, 2016
NJ - Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - ccm, 9505992
IO - Nihon Rinsho Meneki Gakkai Kaishi
SB - Index Medicus
CP - Japan
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Autoimmune Diseases/ci [Chemically Induced]
MH - Chemical and Drug Induced Liver Injury/et [Etiology]
MH - Colitis/ci [Chemically Induced]
MH - Endocrine System Diseases/ci [Chemically Induced]
MH - Humans
MH - Lung Diseases, Interstitial/ci [Chemically Induced]
MH - Melanoma/dt [Drug Therapy]
MH - *Membrane Transport Proteins/im [Immunology]
MH - Myasthenia Gravis/ci [Chemically Induced]
MH - *Programmed Cell Death 1 Receptor/im [Immunology]
MH - Skin Diseases/ci [Chemically Induced]
AB - There has been no effective therapy in the unresectable melanoma for more than 40 years. Anti-PD-1 antibody and anti-CTLA-4 antibody have totally changed the situation. They have clearly shown the survival benefits of the patients with metastatic melanoma. However, immune checkpoint inhibitors sometimes induce various kinds of immune-related adverse events (irAEs). It is very important for the clinicians to know the reported cases of irAEs and to keep in mind the symptoms of irAEs for the early detection. This review describes the previously reported irAEs and adequate managements for irAEs induced by immune checkpoint inhibitors.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Membrane Transport Proteins)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 0 (choline transporter-like protein 4, human)
RN - 31YO63LBSN (nivolumab)
RN - 6T8C155666 (ipilimumab)
ES - 1349-7413
IL - 0911-4300
DO - https://dx.doi.org/10.2177/jsci.39.30
PT - Journal Article
PT - Review
ID - 10.2177/jsci.39.30 [doi]
PP - ppublish
LG - English
DP - 2016
DC - 20160516
EZ - 2016/05/17 06:00
DA - 2017/03/17 06:00
DT - 2016/05/18 06:00
YR - 2016
ED - 20170316
RD - 20170316
UP - 20170320
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27181232
<49. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27286362
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Oing C
AU - Kollmannsberger C
AU - Oechsle K
AU - Bokemeyer C
FA - Oing, Christoph
FA - Kollmannsberger, Christian
FA - Oechsle, Karin
FA - Bokemeyer, Carsten
IN - Oing, Christoph. a Department of Oncology, Hematology and Bone Marrow Transplantation , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
IN - Kollmannsberger, Christian. b Division of Medical Oncology, British Columbia Cancer Agency Vancouver Cancer Center , University of British Columbia , Vancouver , Canada.
IN - Oechsle, Karin. a Department of Oncology, Hematology and Bone Marrow Transplantation , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
IN - Bokemeyer, Carsten. a Department of Oncology, Hematology and Bone Marrow Transplantation , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
TI - Investigational targeted therapies for the treatment of testicular germ cell tumors. [Review]
SO - Expert Opinion on Investigational Drugs. 25(9):1033-43, 2016 Sep
AS - Expert Opin Investig Drugs. 25(9):1033-43, 2016 Sep
NJ - Expert opinion on investigational drugs
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9434197
IO - Expert Opin Investig Drugs
SB - Index Medicus
CP - England
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Clinical Trials as Topic
MH - Drug Resistance, Neoplasm/de [Drug Effects]
MH - Humans
MH - Male
MH - *Molecular Targeted Therapy/mt [Methods]
MH - *Neoplasms, Germ Cell and Embryonal/dt [Drug Therapy]
MH - Neoplasms, Germ Cell and Embryonal/ge [Genetics]
MH - Neoplasms, Germ Cell and Embryonal/me [Metabolism]
MH - Neoplasms, Germ Cell and Embryonal/pa [Pathology]
MH - Taxoids/ad [Administration & Dosage]
MH - *Taxoids/tu [Therapeutic Use]
MH - *Testicular Neoplasms/dt [Drug Therapy]
MH - Testicular Neoplasms/ge [Genetics]
MH - Testicular Neoplasms/me [Metabolism]
MH - Testicular Neoplasms/pa [Pathology]
MH - Treatment Outcome
KW - *Germ cell tumor; *platinum-refractory disease; *targeted therapy; *testicular cancer
AB - INTRODUCTION: Germ cell tumors (GCTs) are the most common malignancy among men aged between 15 to 45. Despite high cure rates of >90% over all GCTs, 3 to 5% of patients will still die of platinum-refractory disease. New systemic treatment options are needed to improve treatment success in this challenging setting.
AB - AREAS COVERED: To review targeted treatment options and preclinical developments in platinum-refractory GCTs, a comprehensive literature search of PubMed, Medline and scientific meeting abstracts on published clinical trials and reports on molecularly targeted approaches was conducted. Outcomes of platinum-refractory disease and of patients failing high-dose chemotherapy remain poor. Currently, no molecularly targeted treatment has shown clinically meaningful activity in unselected patient populations in clinical trials, but individual patients may achieve short-lived objective responses by treatment with sunitinib, brentuximab vedotin or imatinib. Targeted trials based on molecular selection of patients have not yet been performed.
AB - EXPERT OPINION: The limited activity of targeted agents in refractory GCT is disappointing. Assessment of druggable biomarkers and marker-stratified treatment may help individual patients, but is largely lacking. The low incidence and high curability of GCTs make the design of larger clinical trials difficult. The potential of novel agents, i.e. immune-checkpoint inhibitors, remains to be elucidated.
RN - 0 (Antineoplastic Agents)
RN - 0 (Taxoids)
RN - 51F690397J (cabazitaxel)
ES - 1744-7658
IL - 1354-3784
DO - https://dx.doi.org/10.1080/13543784.2016.1195808
PT - Journal Article
PT - Review
ID - 10.1080/13543784.2016.1195808 [doi]
PP - ppublish
LG - English
EP - 20160610
DP - 2016 Sep
DC - 20160819
EZ - 2016/06/11 06:00
DA - 2016/06/11 06:00
DT - 2016/06/11 06:00
YR - 2016
ED - 20170314
RD - 20170314
UP - 20170316
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27286362
<50. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27286362
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Oing C
AU - Kollmannsberger C
AU - Oechsle K
AU - Bokemeyer C
FA - Oing, Christoph
FA - Kollmannsberger, Christian
FA - Oechsle, Karin
FA - Bokemeyer, Carsten
IN - Oing, Christoph. a Department of Oncology, Hematology and Bone Marrow Transplantation , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
IN - Kollmannsberger, Christian. b Division of Medical Oncology, British Columbia Cancer Agency Vancouver Cancer Center , University of British Columbia , Vancouver , Canada.
IN - Oechsle, Karin. a Department of Oncology, Hematology and Bone Marrow Transplantation , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
IN - Bokemeyer, Carsten. a Department of Oncology, Hematology and Bone Marrow Transplantation , University Medical Center Hamburg-Eppendorf , Hamburg , Germany.
TI - Investigational targeted therapies for the treatment of testicular germ cell tumors. [Review]
SO - Expert Opinion on Investigational Drugs. 25(9):1033-43, 2016 Sep
AS - Expert Opin Investig Drugs. 25(9):1033-43, 2016 Sep
NJ - Expert opinion on investigational drugs
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9434197
IO - Expert Opin Investig Drugs
SB - Index Medicus
CP - England
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Clinical Trials as Topic
MH - Drug Resistance, Neoplasm/de [Drug Effects]
MH - Humans
MH - Male
MH - *Molecular Targeted Therapy/mt [Methods]
MH - *Neoplasms, Germ Cell and Embryonal/dt [Drug Therapy]
MH - Neoplasms, Germ Cell and Embryonal/ge [Genetics]
MH - Neoplasms, Germ Cell and Embryonal/me [Metabolism]
MH - Neoplasms, Germ Cell and Embryonal/pa [Pathology]
MH - Taxoids/ad [Administration & Dosage]
MH - *Taxoids/tu [Therapeutic Use]
MH - *Testicular Neoplasms/dt [Drug Therapy]
MH - Testicular Neoplasms/ge [Genetics]
MH - Testicular Neoplasms/me [Metabolism]
MH - Testicular Neoplasms/pa [Pathology]
MH - Treatment Outcome
KW - *Germ cell tumor; *platinum-refractory disease; *targeted therapy; *testicular cancer
AB - INTRODUCTION: Germ cell tumors (GCTs) are the most common malignancy among men aged between 15 to 45. Despite high cure rates of >90% over all GCTs, 3 to 5% of patients will still die of platinum-refractory disease. New systemic treatment options are needed to improve treatment success in this challenging setting.
AB - AREAS COVERED: To review targeted treatment options and preclinical developments in platinum-refractory GCTs, a comprehensive literature search of PubMed, Medline and scientific meeting abstracts on published clinical trials and reports on molecularly targeted approaches was conducted. Outcomes of platinum-refractory disease and of patients failing high-dose chemotherapy remain poor. Currently, no molecularly targeted treatment has shown clinically meaningful activity in unselected patient populations in clinical trials, but individual patients may achieve short-lived objective responses by treatment with sunitinib, brentuximab vedotin or imatinib. Targeted trials based on molecular selection of patients have not yet been performed.
AB - EXPERT OPINION: The limited activity of targeted agents in refractory GCT is disappointing. Assessment of druggable biomarkers and marker-stratified treatment may help individual patients, but is largely lacking. The low incidence and high curability of GCTs make the design of larger clinical trials difficult. The potential of novel agents, i.e. immune-checkpoint inhibitors, remains to be elucidated.
RN - 0 (Antineoplastic Agents)
RN - 0 (Taxoids)
RN - 51F690397J (cabazitaxel)
ES - 1744-7658
IL - 1354-3784
DO - https://dx.doi.org/10.1080/13543784.2016.1195808
PT - Journal Article
PT - Review
ID - 10.1080/13543784.2016.1195808 [doi]
PP - ppublish
LG - English
EP - 20160610
DP - 2016 Sep
DC - 20160819
EZ - 2016/06/11 06:00
DA - 2017/03/16 06:00
DT - 2016/06/11 06:00
YR - 2016
ED - 20170314
RD - 20170314
UP - 20170317
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=27286362
<51. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27438590
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Ellenrieder V
AU - Konig A
AU - Seufferlein T
FA - Ellenrieder, Volker
FA - Konig, Alexander
FA - Seufferlein, Thomas
IN - Ellenrieder, Volker. Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Gottingen, Gottingen, Germany.
TI - Current Standard and Future Perspectives in First- and Second-Line Treatment of Metastatic Pancreatic Adenocarcinoma. [Review]
SO - Digestion. 94(1):44-9, 2016
AS - Digestion. 94(1):44-9, 2016
NJ - Digestion
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - e9a, 0150472
IO - Digestion
SB - Index Medicus
CP - Switzerland
MH - Aged
MH - Albumins/ad [Administration & Dosage]
MH - Albumins/tu [Therapeutic Use]
MH - *Antineoplastic Combined Chemotherapy Protocols/st [Standards]
MH - *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - Camptothecin/ad [Administration & Dosage]
MH - Camptothecin/aa [Analogs & Derivatives]
MH - Camptothecin/tu [Therapeutic Use]
MH - *Carcinoma, Pancreatic Ductal/dt [Drug Therapy]
MH - Carcinoma, Pancreatic Ductal/mo [Mortality]
MH - Clinical Trials as Topic
MH - Deoxycytidine/ad [Administration & Dosage]
MH - Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/tu [Therapeutic Use]
MH - Disease-Free Survival
MH - Fluorouracil/ad [Administration & Dosage]
MH - Fluorouracil/tu [Therapeutic Use]
MH - Humans
MH - Leucovorin/ad [Administration & Dosage]
MH - Leucovorin/tu [Therapeutic Use]
MH - Male
MH - Middle Aged
MH - Nanoparticles/ad [Administration & Dosage]
MH - Nanoparticles/tu [Therapeutic Use]
MH - Organoplatinum Compounds/ad [Administration & Dosage]
MH - Organoplatinum Compounds/tu [Therapeutic Use]
MH - Paclitaxel/ad [Administration & Dosage]
MH - Paclitaxel/tu [Therapeutic Use]
MH - Palliative Care/mt [Methods]
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a median 5-year survival of <8%. At the time of diagnosis, a vast majority of pancreatic cancer patients were found to be with either metastatic spread of the disease or locally advanced tumors. Despite relatively low efficacy, gemcitabine administration was the first choice chemotherapeutic strategy in advanced PDAC for many years. In the last 5 years, however, our understanding of pancreatic carcinogenesis has improved dramatically and with this our therapeutic options have expanded significantly.
AB - SUMMARY: With the FOLFIRINOX protocol or the combination of gemcitabine and nab-paclitaxel, 2 novel and more effective chemotherapeutic regimens have been introduced in clinical routine, which increased the overall survival by 4-5 months in the palliative situation. Most recently, we learned that both regimens can be modified and dosages can be adapted in older patients without significant loss of efficacy. Additionally, novel application strategies such as nanoparticle fused liposomal irinotecan along with 5-FU/LV provided convincing results in patients previously treated with gemcitabine. Current preclinical and clinical trials investigate efficacy and tolerability of novel drugs aiming at the inhibition of key inflammatory pathways, for example, JAK-STAT signaling, or the tumor surrounding desmoplasia. Prospectively, immunovaccination approaches or immune checkpoint inhibition appears as promising strategies in the near future, particularly when combined with epigenetic drugs in advanced PDAC patients. In this 'to-the-point' article, we review the current standard and summarize the most recent and encouraging advances in cytostatic PDAC treatment.
AB - KEY POINTS: (1) FOLFIRINOX and nab-paclitaxel/gemcitabine as first-line treatment regime significantly increase survival in patients with advanced PDAC; (2) Selection of appropriate treatment regime depends on patient performance, comorbidity, and toxicity; (3) PDAC patients will benefit from second-line chemotherapy and selection of appropriate regimes depends on first line therapy and patient criteria; (4) Future therapeutic strategies in advanced PDAC will respect molecular tumor profiling and other biomarkers.
AB - Copyright © 2016 S. Karger AG, Basel.
RN - 0 (130-nm albumin-bound paclitaxel)
RN - 0 (Albumins)
RN - 0 (Organoplatinum Compounds)
RN - 04ZR38536J (oxaliplatin)
RN - 0H43101T0J (irinotecan)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
RN - P88XT4IS4D (Paclitaxel)
RN - Q573I9DVLP (Leucovorin)
RN - U3P01618RT (Fluorouracil)
RN - XT3Z54Z28A (Camptothecin)
ES - 1421-9867
IL - 0012-2823
DI - 000447739
DO - https://dx.doi.org/10.1159/000447739
PT - Journal Article
PT - Review
ID - 000447739 [pii]
ID - 10.1159/000447739 [doi]
PP - ppublish
PH - 2016/03/17 [received]
PH - 2016/06/11 [accepted]
LG - English
EP - 20160721
DP - 2016
DC - 20160831
EZ - 2016/07/21 06:00
DA - 2017/03/08 06:00
DT - 2016/07/21 06:00
YR - 2016
ED - 20170307
RD - 20170307
UP - 20170309
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27438590
<52. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28148549
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Hsieh AH
AU - Faithfull S
AU - Brown MP
FA - Hsieh, Amy Hsin-Chieh
FA - Faithfull, Sarah
FA - Brown, Michael P
IN - Hsieh, Amy Hsin-Chieh. Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
IN - Faithfull, Sarah. Radiology Department, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
IN - Brown, Michael P. Department of Medical Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
TI - Risk of cumulative toxicity after complete melanoma response with pembrolizumab.
SO - BMJ Case Reports. 2017, 2017 Feb 01
AS - BMJ Case Rep. 2017, 2017 Feb 01
NJ - BMJ case reports
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101526291
IO - BMJ Case Rep
SB - Index Medicus
CP - England
MH - Aged
MH - *Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - *Drug Eruptions/et [Etiology]
MH - Groin
MH - Hormone Replacement Therapy
MH - Humans
MH - Hydrocortisone/tu [Therapeutic Use]
MH - *Hypopituitarism/ci [Chemically Induced]
MH - Hypopituitarism/dt [Drug Therapy]
MH - *Limbic Encephalitis/ci [Chemically Induced]
MH - Limbic Encephalitis/dg [Diagnostic Imaging]
MH - Lymphatic Metastasis
MH - Magnetic Resonance Imaging
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Pelvis
MH - Thyroxine/tu [Therapeutic Use]
AB - Pembrolizumab is an approved first-line systemic therapy for unresectable metastatic melanoma. Despite the achievement of complete and durable responses in a small subgroup of patients, it is standard practice that pembrolizumab therapy continues beyond complete response. Nevertheless, the incidence of immune-related toxicities gradually increases with continuing pembrolizumab therapy. We report a case highlighting the occurrence of serious induced immune-related adverse events, which were attributed to pembrolizumab in a patient with metastatic melanoma who obtained a complete response (CR) after receiving pembrolizumab for a total of 6.5 months. Although mild pembrolizumab-related toxicity persists, the patient remains disease-free 5.5 months after discontinuation of pembrolizumab. Accordingly, we believe that cessation of pembrolizumab should be considered in patients who achieve a CR because of the ongoing risk of toxicity with extended pembrolizumab administration.
AB - Copyright 2017 BMJ Publishing Group Ltd.
CI - Competing interests: None declared.
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - DPT0O3T46P (pembrolizumab)
RN - Q51BO43MG4 (Thyroxine)
RN - WI4X0X7BPJ (Hydrocortisone)
RS - Combined Pituitary Hormone Deficiency
ES - 1757-790X
IL - 1757-790X
DI - bcr2016218308
DI - bcr-2016-218308
DO - https://dx.doi.org/10.1136/bcr-2016-218308
PT - Case Reports
PT - Journal Article
ID - 28148549 [pubmed]
ID - bcr-2016-218308 [pii]
ID - 10.1136/bcr-2016-218308 [doi]
PP - epublish
LG - English
EP - 20170201
DP - 2017 Feb 01
DC - 20170202
EZ - 2017/02/03 06:00
DA - 2017/03/07 06:00
DT - 2017/02/06 06:00
YR - 2017
ED - 20170306
RD - 20170306
UP - 20170308
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28148549
<53. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27245147
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Katoh M
FA - Katoh, Masaru
IN - Katoh, Masaru. Department of Omics Network, National Cancer Center, Tokyo 104-0045, Japan.
TI - FGFR inhibitors: Effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review). [Review]
SO - International Journal of Molecular Medicine. 38(1):3-15, 2016 Jul
AS - Int J Mol Med. 38(1):3-15, 2016 Jul
NJ - International journal of molecular medicine
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c8h, 9810955
IO - Int. J. Mol. Med.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899036
SB - Index Medicus
CP - Greece
MH - Animals
MH - Drug Delivery Systems
MH - *Homeostasis/de [Drug Effects]
MH - Humans
MH - *Neoplasms/pa [Pathology]
MH - *Protein Kinase Inhibitors/pd [Pharmacology]
MH - *Receptor Protein-Tyrosine Kinases/ai [Antagonists & Inhibitors]
MH - Receptor Protein-Tyrosine Kinases/ge [Genetics]
MH - Receptor Protein-Tyrosine Kinases/me [Metabolism]
MH - *Tumor Microenvironment/de [Drug Effects]
AB - Fibroblast growth factor (FGF)2, FGF4, FGF7 and FGF20 are representative paracrine FGFs binding to heparan-sulfate proteoglycan and fibroblast growth factor receptors (FGFRs), whereas FGF19, FGF21 and FGF23 are endocrine FGFs binding to Klotho and FGFRs. FGFR1 is relatively frequently amplified and overexpressed in breast and lung cancer, and FGFR2 in gastric cancer. BCR-FGFR1, CNTRL-FGFR1, CUX1-FGFR1, FGFR1OP-FGFR1, MYO18A-FGFR1 and ZMYM2-FGFR1 fusions in myeloproliferative neoplasms are non-receptor-type FGFR kinases, whereas FGFR1-TACC1, FGFR2-AFF3, FGFR2-BICC1, FGFR2-PPHLN1, FGFR3-BAIAP2L1 and FGFR3-TACC3 fusions in solid tumors are transmembrane-type FGFRs with C-terminal alterations. AZD4547, BGJ398 (infigratinib), Debio-1347 and dovitinib are FGFR1/2/3 inhibitors; BLU9931 is a selective FGFR4 inhibitor; FIIN-2, JNJ-42756493, LY2874455 and ponatinib are pan-FGFR inhibitors. AZD4547, dovitinib and ponatinib are multi-kinase inhibitors targeting FGFRs, colony stimulating factor 1 receptor (CSF1R), vascular endothelial growth factor (VEGF)R2, and others. The tumor microenvironment consists of cancer cells and stromal/immune cells, such as cancer-associated fibroblasts (CAFs), endothelial cells, M2-type tumor-associating macrophages (M2-TAMs), myeloid-derived suppressor cells (MDSCs) and regulatory T cells. FGFR inhibitors elicit antitumor effects directly on cancer cells, as well as indirectly through the blockade of paracrine signaling. The dual inhibition of FGF and CSF1 or VEGF signaling is expected to enhance the antitumor effects through the targeting of immune evasion and angiogenesis in the tumor microenvironment. Combination therapy using tyrosine kinase inhibitors (FGFR or CSF1R inhibitors) and immune checkpoint blockers (anti-PD-1 or anti-CTLA-4 monoclonal antibodies) may be a promising choice for cancer patients. The inhibition of FGF19-FGFR4 signaling is associated with a risk of liver toxicity, whereas the activation of FGF23-FGFR4 signaling is associated with a risk of heart toxicity. Endocrine FGF signaling affects the pathophysiology of cancer patients who are prescribed FGFR inhibitors. Whole-genome sequencing is necessary for the detection of promoter/enhancer alterations of FGFR genes and rare alterations of other genes causing FGFR overexpression. To sustain the health care system in an aging society, a benefit-cost analysis should be performed with a focus on disease-free survival and the total medical cost before implementing genome-based precision medicine for cancer patients.
RN - 0 (Protein Kinase Inhibitors)
RN - EC 2-7-10-1 (Receptor Protein-Tyrosine Kinases)
ES - 1791-244X
IL - 1107-3756
DO - https://dx.doi.org/10.3892/ijmm.2016.2620
PT - Journal Article
PT - Review
ID - 27245147 [pubmed]
ID - 10.3892/ijmm.2016.2620 [doi]
ID - PMC4899036 [pmc]
PP - ppublish
PH - 2016/02/29 [received]
PH - 2016/05/23 [accepted]
LG - English
EP - 20160531
DP - 2016 Jul
DC - 20160618
EZ - 2016/06/02 06:00
DA - 2017/03/07 06:00
DT - 2016/06/02 06:00
YR - 2016
ED - 20170306
RD - 20170306
UP - 20170308
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27245147
<54. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28174381
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Daido W
AU - Yamasaki M
AU - Saito N
AU - Ishiyama S
AU - Deguchi N
AU - Taniwaki M
AU - Daga H
AU - Ohashi N
FA - Daido, Wakako
FA - Yamasaki, Masahiro
FA - Saito, Naomi
FA - Ishiyama, Sayaka
FA - Deguchi, Naoko
FA - Taniwaki, Masaya
FA - Daga, Haruko
FA - Ohashi, Nobuyuki
IN - Daido, Wakako. Dept. of Respiratory Disease, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital.
TI - [Effectiveness of Nivolumab in Large-Cell Neuroendocrine Carcinoma of the Lung - A Report of Two Cases]. [Review] [Japanese]
SO - Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy]. 44(1):59-62, 2017 Jan
AS - Gan To Kagaku Ryoho. 44(1):59-62, 2017 Jan
NJ - Gan to kagaku ryoho. Cancer & chemotherapy
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 7810034, 6t8
IO - Gan To Kagaku Ryoho
SB - Index Medicus
CP - Japan
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Biomarkers, Tumor/bl [Blood]
MH - Carcinoma, Large Cell/ch [Chemistry]
MH - Carcinoma, Large Cell/dg [Diagnostic Imaging]
MH - *Carcinoma, Large Cell/dt [Drug Therapy]
MH - Carcinoma, Neuroendocrine/ch [Chemistry]
MH - Carcinoma, Neuroendocrine/dg [Diagnostic Imaging]
MH - *Carcinoma, Neuroendocrine/dt [Drug Therapy]
MH - Humans
MH - Lung Neoplasms/ch [Chemistry]
MH - Lung Neoplasms/dg [Diagnostic Imaging]
MH - *Lung Neoplasms/dt [Drug Therapy]
MH - Male
MH - Middle Aged
MH - Tomography, X-Ray Computed
MH - Treatment Outcome
AB - BACKGROUND: The anti-programmed death-1 antibody nivolumab is an important treatment option for non-small-cell lung carcinoma.However, its effectiveness for large-cell neuroendocrine carcinomas(LCNEC)is still controversial.Here, we report 2 cases of LCNECs that responded to nivolumab.Case 1: A 62-year-old man received chemotherapy and radiotherapy for stage III A lung adenocarcinoma.One year later, another lung lesion was observed and diagnosed as LCNEC using surgical lung biopsy.Although he subsequently received some chemotherapy regimens, the patient developed new brain metastasis, expanded mediastinal lesion, and increased levels of the tumor marker pro-gastrin releasing peptide(ProGRP).We started nivolumab as the sixth-line treatment.In response, ProGRP levels significantly decreased and the mediastinal lesion became smaller.Case 2: A 55-year-old man was diagnosed with stage III A LCNEC and received chemotherapy and radiotherapy.The primary lesion was controlled; however, lung metastases developed and chemotherapy was unable to control them.We provided treatment with nivolumab as the third-line therapy.The tumor marker ProGRP decreased and the lung metastases became smaller.
AB - CONCLUSION: Nivolumab can be a valuable treatment option for LCNEC.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (Biomarkers, Tumor)
RN - 31YO63LBSN (nivolumab)
IS - 0385-0684
IL - 0385-0684
PT - Case Reports
PT - Journal Article
PT - Review
ID - 28174381 [pubmed]
PP - ppublish
LG - Japanese
DP - 2017 Jan
DC - 20170208
EZ - 2017/02/09 06:00
DA - 2017/02/09 06:00
DT - 2017/02/09 06:00
YR - 2017
ED - 20170301
RD - 20170302
UP - 20170303
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28174381
<55. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28174381
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Daido W
AU - Yamasaki M
AU - Saito N
AU - Ishiyama S
AU - Deguchi N
AU - Taniwaki M
AU - Daga H
AU - Ohashi N
FA - Daido, Wakako
FA - Yamasaki, Masahiro
FA - Saito, Naomi
FA - Ishiyama, Sayaka
FA - Deguchi, Naoko
FA - Taniwaki, Masaya
FA - Daga, Haruko
FA - Ohashi, Nobuyuki
IN - Daido, Wakako. Dept. of Respiratory Disease, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital.
TI - [Effectiveness of Nivolumab in Large-Cell Neuroendocrine Carcinoma of the Lung - A Report of Two Cases]. [Review] [Japanese]
SO - Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy]. 44(1):59-62, 2017 Jan
AS - Gan To Kagaku Ryoho. 44(1):59-62, 2017 Jan
NJ - Gan to kagaku ryoho. Cancer & chemotherapy
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 7810034, 6t8
IO - Gan To Kagaku Ryoho
SB - Index Medicus
CP - Japan
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Biomarkers, Tumor/bl [Blood]
MH - Carcinoma, Large Cell/ch [Chemistry]
MH - Carcinoma, Large Cell/dg [Diagnostic Imaging]
MH - *Carcinoma, Large Cell/dt [Drug Therapy]
MH - Carcinoma, Neuroendocrine/ch [Chemistry]
MH - Carcinoma, Neuroendocrine/dg [Diagnostic Imaging]
MH - *Carcinoma, Neuroendocrine/dt [Drug Therapy]
MH - Humans
MH - Lung Neoplasms/ch [Chemistry]
MH - Lung Neoplasms/dg [Diagnostic Imaging]
MH - *Lung Neoplasms/dt [Drug Therapy]
MH - Male
MH - Middle Aged
MH - Tomography, X-Ray Computed
MH - Treatment Outcome
AB - BACKGROUND: The anti-programmed death-1 antibody nivolumab is an important treatment option for non-small-cell lung carcinoma.However, its effectiveness for large-cell neuroendocrine carcinomas(LCNEC)is still controversial.Here, we report 2 cases of LCNECs that responded to nivolumab.Case 1: A 62-year-old man received chemotherapy and radiotherapy for stage III A lung adenocarcinoma.One year later, another lung lesion was observed and diagnosed as LCNEC using surgical lung biopsy.Although he subsequently received some chemotherapy regimens, the patient developed new brain metastasis, expanded mediastinal lesion, and increased levels of the tumor marker pro-gastrin releasing peptide(ProGRP).We started nivolumab as the sixth-line treatment.In response, ProGRP levels significantly decreased and the mediastinal lesion became smaller.Case 2: A 55-year-old man was diagnosed with stage III A LCNEC and received chemotherapy and radiotherapy.The primary lesion was controlled; however, lung metastases developed and chemotherapy was unable to control them.We provided treatment with nivolumab as the third-line therapy.The tumor marker ProGRP decreased and the lung metastases became smaller.
AB - CONCLUSION: Nivolumab can be a valuable treatment option for LCNEC.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (Biomarkers, Tumor)
RN - 31YO63LBSN (nivolumab)
IS - 0385-0684
IL - 0385-0684
PT - Case Reports
PT - Journal Article
PT - Review
ID - 28174381 [pubmed]
PP - ppublish
LG - Japanese
DP - 2017 Jan
DC - 20170208
EZ - 2017/02/09 06:00
DA - 2017/03/03 06:00
DT - 2017/02/09 06:00
YR - 2017
ED - 20170301
RD - 20170302
UP - 20170306
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=28174381
<56. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27367787
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Friedman CF
AU - Proverbs-Singh TA
AU - Postow MA
FA - Friedman, Claire F
FA - Proverbs-Singh, Tracy A
FA - Postow, Michael A
IN - Friedman, Claire F. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York2Weill Cornell Medical College, New York, New York.
IN - Proverbs-Singh, Tracy A. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York2Weill Cornell Medical College, New York, New York.
IN - Postow, Michael A. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York2Weill Cornell Medical College, New York, New York.
TI - Treatment of the Immune-Related Adverse Effects of Immune Checkpoint Inhibitors: A Review. [Review]
SO - JAMA Oncology. 2(10):1346-1353, 2016 Oct 01
AS - JAMA Oncol. 2(10):1346-1353, 2016 Oct 01
NJ - JAMA oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101652861
IO - JAMA Oncol
SB - Index Medicus
CP - United States
MH - Adrenal Cortex Hormones/tu [Therapeutic Use]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Chemical and Drug Induced Liver Injury/et [Etiology]
MH - Colitis/ci [Chemically Induced]
MH - Colitis/dt [Drug Therapy]
MH - Exanthema/ci [Chemically Induced]
MH - Exanthema/dt [Drug Therapy]
MH - Humans
MH - Immunosuppressive Agents/tu [Therapeutic Use]
MH - Pneumonia/ci [Chemically Induced]
MH - Pneumonia/dt [Drug Therapy]
AB - Importance: The development of immune checkpoint inhibitors targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) has significantly improved the treatment of a variety of cancers and led to US Food and Drug Administration approvals for patients with a variety of malignant neoplasms. Immune checkpoint inhibitors enhance antitumor immunity by blocking negative regulators of T-cell function that exist both on immune cells and on tumor cells. Although these agents can lead to remarkable responses, their use can also be associated with unique immune-related adverse effects (irAEs).
AB - Observations: In general, use of PD-1 inhibitors such as nivolumab and pembrolizumab has a lower incidence of irAEs compared with those that block CTLA-4 such as ipilimumab. The combination of nivolumab and ipilimumab has a higher rate of irAEs than either approach as monotherapy. Consensus guidelines regarding the treatment of the most common irAEs including rash, colitis, hepatitis, endocrinopathies, and pneumonitis have been established. The mainstay of irAE treatment consists of immunosuppression with corticosteroids or other immunosuppressant agents such as infliximab; most irAEs will resolve with appropriate management.
AB - Conclusions and Relevance: The clinical use of immune checkpoint inhibitors is expanding rapidly. Oncology practitioners will therefore be required to recognize and manage irAEs in a growing patient population. Early recognition and treatment are essential to prevent patient morbidity and mortality, and adherence to established algorithms is recommended.
RN - 0 (Adrenal Cortex Hormones)
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (Immunosuppressive Agents)
RN - 6T8C155666 (ipilimumab)
RN - DPT0O3T46P (pembrolizumab)
ES - 2374-2445
IL - 2374-2437
DI - 2531472
DO - https://dx.doi.org/10.1001/jamaoncol.2016.1051
PT - Journal Article
PT - Review
ID - 27367787 [pubmed]
ID - 2531472 [pii]
ID - 10.1001/jamaoncol.2016.1051 [doi]
PP - ppublish
LG - English
DP - 2016 Oct 01
DC - 20160701
EZ - 2016/07/02 06:00
DA - 2017/02/22 06:00
DT - 2016/07/02 06:00
YR - 2016
ED - 20170221
RD - 20170221
UP - 20170222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27367787
<57. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27305306
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Besemer B
AU - Mussig K
FA - Besemer, Britta
FA - Mussig, Karsten
TI - [Rare differential diagnosis of hyperthyroidism]. [German]
OT - Seltene Ursache einer Hyperthyreose - Fall 4 / 2016.
SO - Deutsche Medizinische Wochenschrift. 141(12):889, 2016 Jun
AS - Dtsch Med Wochenschr. 141(12):889, 2016 Jun
NJ - Deutsche medizinische Wochenschrift (1946)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ecl, 0006723
IO - Dtsch. Med. Wochenschr.
SB - Index Medicus
CP - Germany
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Diagnosis, Differential
MH - Female
MH - Humans
MH - *Hyperthyroidism/ci [Chemically Induced]
MH - *Hyperthyroidism/di [Diagnosis]
MH - *Lung Neoplasms/dt [Drug Therapy]
MH - *Lung Neoplasms/sc [Secondary]
MH - *Melanoma/dt [Drug Therapy]
MH - *Melanoma/sc [Secondary]
MH - *Membrane Transport Proteins/de [Drug Effects]
MH - Middle Aged
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Thyroid Function Tests
MH - *Thyroiditis, Autoimmune/ci [Chemically Induced]
MH - *Thyroiditis, Autoimmune/di [Diagnosis]
AB - HISTORY AND ADMISSION FINDINGS: A 54-year-old female patient is admitted for evaluation of her thyroid function after two cycles of ipilimumab therapy. The decision for the anti-cytotoxic-T-lymphocyte-antigen-4-therapy (anti-CTLA-4) was made two months earlier because of malignant melanoma with pulmonary metastases. The patient was euthyroid before initiation of treatment and without known thyroid disease.
AB - INVESTIGATIONS: The laboratory reveals thyrotoxicosis with elevated anti-thyroid peroxidase and anti-thyroglobulin antibody levels. The anti-thyroid stimulating hormone receptor antibody levels are within the normal range. Thyroid ultrasound shows a normal-sized, inhomogenous, hypoechogenic thyroid gland, consistent with autoimmune thyroiditis.
AB - DIAGNOSIS, TREATMENT AND COURSE: Diagnosis of hyperthyroidism due to ipilimumab-induced autoimmune thyroiditis is made. The patient does not receive any thyroid-specific medication, with regular control of the thyroid hormone levels. When the patient becomes euthyroid, the ipilimumab therapy is continued. Three weeks later, the patient develops hypothyroidism and a supplementation with L-thyroxine is initiated.
AB - CONCLUSIONS: An anti-CTLA-4 therapy may cause thyroid dysfunction. Therefore, before initiation and in the course of the treatment, regular controls of the thyroid hormone levels are required.
AB - Copyright © Georg Thieme Verlag KG Stuttgart . New York.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Membrane Transport Proteins)
RN - 0 (choline transporter-like protein 4, human)
RN - 6T8C155666 (ipilimumab)
ES - 1439-4413
IL - 0012-0472
DO - https://dx.doi.org/10.1055/s-0041-104686
PT - Case Reports
PT - Journal Article
ID - 27305306 [pubmed]
ID - 10.1055/s-0041-104686 [doi]
PP - ppublish
LG - German
EP - 20160615
DP - 2016 Jun
DC - 20160616
EZ - 2016/06/16 06:00
DA - 2017/02/22 06:00
DT - 2016/06/16 06:00
YR - 2016
ED - 20170221
RD - 20170221
UP - 20170222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27305306
<58. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27440480
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Okano Y
AU - Satoh T
AU - Horiguchi K
AU - Toyoda M
AU - Osaki A
AU - Matsumoto S
AU - Tomaru T
AU - Nakajima Y
AU - Ishii S
AU - Ozawa A
AU - Shibusawa N
AU - Shimada T
AU - Higuchi T
AU - Chikamatsu K
AU - Yamada M
FA - Okano, Yudai
FA - Satoh, Tetsurou
FA - Horiguchi, Kazuhiko
FA - Toyoda, Minoru
FA - Osaki, Aya
FA - Matsumoto, Shunichi
FA - Tomaru, Takuya
FA - Nakajima, Yasuyo
FA - Ishii, Sumiyasu
FA - Ozawa, Atsushi
FA - Shibusawa, Nobuyuki
FA - Shimada, Takehiro
FA - Higuchi, Tetsuya
FA - Chikamatsu, Kazuaki
FA - Yamada, Masanobu
IN - Okano, Yudai. Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.
TI - Nivolumab-induced hypophysitis in a patient with advanced malignant melanoma.
SO - Endocrine Journal. 63(10):905-912, 2016 Oct 29
AS - Endocr J. 63(10):905-912, 2016 Oct 29
NJ - Endocrine journal
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - bt5, 9313485
IO - Endocr. J.
SB - Index Medicus
CP - Japan
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Disease Progression
MH - Humans
MH - *Hypophysitis/ci [Chemically Induced]
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - *Oropharyngeal Neoplasms/dt [Drug Therapy]
MH - Oropharyngeal Neoplasms/pa [Pathology]
AB - The anti-programmed cell death-1 monoclonal antibody (mab), nivolumab has recently been approved for the treatment of unresectable or metastatic malignant melanoma and non-small-cell lung cancers in Japan. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 mab for malignant melanoma that was approved earlier than nivolumab in Western countries, is known to frequently cause endocrine immune-related adverse events such as hypophysitis and thyroid dysfunction. We herein report a patient with advanced melanoma who appeared to develop hypophysitis as a consequence of the inhibition of PD-1 by nivolumab. One week after the 6th administration of nivolumab, the patient developed progressive fatigue and appetite loss. Laboratory data on admission for the 7th administration of nivolumab showed eosinophilia and hyponatremia. Since ACTH and cortisol levels were low, nivolumab was discontinued and a large dose of hydrocortisone (100 mg/d) was promptly administered intravenously. A magnetic resonance imaging scan revealed the mild enlargement of the anterior pituitary gland and thickening of the stalk with homogenous contrast. A detailed assessment of anterior pituitary functions with hypothalamic hormone challenges showed that hormonal secretions other than ACTH and TSH were normal. With a replacement dose of hydrocortisone (20 mg/d), the 7th administration of nivolumab was completed without exacerbating the patient's general condition. The present report provides the first detailed endocrinological presentation of nivolumab-induced hypophysitis showing the enlargement of the pituitary gland and stalk in a malignant melanoma patient in Japan. Oncologists and endocrinologists need to be familiar with potentially life-threatening hypophysitis induced by immune-checkpoint inhibitors.
RN - 0 (Antibodies, Monoclonal)
RN - 31YO63LBSN (nivolumab)
ES - 1348-4540
IL - 0918-8959
DO - https://dx.doi.org/10.1507/endocrj.EJ16-0161
PT - Case Reports
PT - Journal Article
ID - 27440480 [pubmed]
ID - 10.1507/endocrj.EJ16-0161 [doi]
PP - ppublish
LG - English
EP - 20160720
DP - 2016 Oct 29
DC - 20160721
EZ - 2016/07/22 06:00
DA - 2017/02/18 06:00
DT - 2016/11/01 06:00
YR - 2016
ED - 20170217
RD - 20170217
UP - 20170221
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27440480
<59. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27930550
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Chang JH
AU - Jiang Y
AU - Pillarisetty VG
FA - Chang, Jae Hyuck
FA - Jiang, Yongjian
FA - Pillarisetty, Venu G
IN - Chang, Jae Hyuck. aDepartment of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea bDepartment of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai, China cDepartment of Surgery, University of Washington Medical Center, Seattle, University of Washington, Seattle, WA.
TI - Role of immune cells in pancreatic cancer from bench to clinical application: An updated review. [Review]
SO - Medicine. 95(49):e5541, 2016 Dec
AS - Medicine (Baltimore). 95(49):e5541, 2016 Dec
NJ - Medicine
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - mny, 2985248r
IO - Medicine (Baltimore)
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Cancer Vaccines/tu [Therapeutic Use]
MH - Humans
MH - Immune Tolerance
MH - Immunotherapy
MH - *Pancreatic Neoplasms/im [Immunology]
MH - Pancreatic Neoplasms/th [Therapy]
AB - BACKGROUND: Pancreatic cancer (PC) remains difficult to treat, despite the recent advances in various anticancer therapies. Immuno-inflammatory response is considered to be a major risk factor for the development of PC in addition to a combination of genetic background and environmental factors. Although patients with PC exhibit evidence of systemic immune dysfunction, the PC microenvironment is replete with immune cells.
AB - METHODS: We searched PubMed for all relevant English language articles published up to March 2016. They included clinical trials, experimental studies, observational studies, and reviews. Trials enrolled at Clinical trial.gov were also searched.
AB - RESULTS: PC induces an immunosuppressive microenvironment, and intratumoral activation of immunity in PC is attenuated by inhibitory signals that limit immune effector function. Multiple types of immune responses can promote an immunosuppressive microenvironment; key regulators of the host tumor immune response are dendritic cells, natural killer cells, macrophages, myeloid derived suppressor cells, and T cells. The function of these immune cells in PC is also influenced by chemotherapeutic agents and the components in tumor microenvironment such as pancreatic stellate cells. Immunotherapy of PC employs monoclonal antibodies/effector cells generated in vitro or vaccination to stimulate antitumor response. Immune therapy in PC has failed to improve overall survival; however, combination therapies comprising immune checkpoint inhibitors and vaccines have been attempted to increase the response.
AB - CONCLUSION: A number of studies have begun to elucidate the roles of immune cell subtypes and their capacity to function or dysfunction in the tumor microenvironment of PC. It will not be long before immune therapy for PC becomes a clinical reality.
RN - 0 (Cancer Vaccines)
ES - 1536-5964
IL - 0025-7974
DI - 00005792-201612060-00047
DO - https://dx.doi.org/10.1097/MD.0000000000005541
PT - Journal Article
PT - Review
ID - 27930550 [pubmed]
ID - 10.1097/MD.0000000000005541 [doi]
ID - 00005792-201612060-00047 [pii]
ID - PMC5266022 [pmc]
PP - ppublish
LG - English
DP - 2016 Dec
DC - 20161208
EZ - 2016/12/09 06:00
DA - 2017/02/16 06:00
DT - 2016/12/09 06:00
YR - 2016
ED - 20170215
RD - 20170215
UP - 20170217
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27930550
<60. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27181090
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Okamoto M
AU - Okamoto M
AU - Gotoh K
AU - Masaki T
AU - Ozeki Y
AU - Ando H
AU - Anai M
AU - Sato A
AU - Yoshida Y
AU - Ueda S
AU - Kakuma T
AU - Shibata H
FA - Okamoto, Masahide
FA - Okamoto, Mitsuhiro
FA - Gotoh, Koro
FA - Masaki, Takayuki
FA - Ozeki, Yoshinori
FA - Ando, Hisae
FA - Anai, Manabu
FA - Sato, Asami
FA - Yoshida, Yuichi
FA - Ueda, So
FA - Kakuma, Tetsuya
FA - Shibata, Hirotaka
IN - Okamoto, Masahide. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan.
IN - Okamoto, Mitsuhiro. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan.
IN - Gotoh, Koro. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan.
IN - Masaki, Takayuki. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan.
IN - Ozeki, Yoshinori. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan.
IN - Ando, Hisae. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan.
IN - Anai, Manabu. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan.
IN - Sato, Asami. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan.
IN - Yoshida, Yuichi. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan.
IN - Ueda, So. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan.
IN - Kakuma, Tetsuya. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan.
IN - Shibata, Hirotaka. Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Oita, Japan. hiro-405@cb3.so-net.ne.jp.
TI - Fulminant type 1 diabetes mellitus with anti-programmed cell death-1 therapy.
SO - Journal of Diabetes Investigation. 7(6):915-918, 2016 Nov
AS - J. diabetes investig.. 7(6):915-918, 2016 Nov
NJ - Journal of diabetes investigation
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101520702
IO - J Diabetes Investig
SB - Index Medicus
CP - Japan
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - *Diabetes Mellitus, Type 1/ci [Chemically Induced]
MH - Diabetes Mellitus, Type 1/im [Immunology]
MH - Female
MH - Humans
MH - Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - *Programmed Cell Death 1 Receptor/im [Immunology]
MH - Treatment Outcome
KW - Anti-programmed cell death-1 antibodies; Fulminant type 1 diabetes; Nivolumab
AB - Anti-programmed cell death-1 (PD-1) antibodies are regarded as a risk factor for insulin-dependent diabetes mellitus as a side-effect. While a small number of cases have been reported, evidence remains limited. This is the first report of an Asian patient developing insulin-dependent diabetes during anti-PD-1 therapy. A 55-year-old euglycemic woman receiving nivolumab for malignant melanoma showed abrupt onset of ketonuria, and elevated levels of plasma glucose (580 mg/dL) and hemoglobin A1c (7.0%). Over the next 2 weeks, serum C-peptide levels fell below the limit of detection. Islet autoantibodies were negative, and the patient showed a human leukocyte antigen haplotype associated with type 1 diabetes. Anti-PD-1 therapy can cause rapid onset of insulin-dependent diabetes, possibly because of inappropriate activation of T cells. Human leukocyte antigen haplotypes might be related to the onset of this disease. Physicians should be aware of this serious adverse event and carry out routine blood glucose testing during anti-PD-1 therapy.
AB - Copyright © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 31YO63LBSN (nivolumab)
ES - 2040-1124
IL - 2040-1116
DO - https://dx.doi.org/10.1111/jdi.12531
PT - Case Reports
ID - 27181090 [pubmed]
ID - 10.1111/jdi.12531 [doi]
ID - PMC5089956 [pmc]
PP - ppublish
PH - 2015/12/16 [received]
PH - 2016/03/14 [revised]
PH - 2016/04/11 [accepted]
LG - English
EP - 20160531
DP - 2016 Nov
DC - 20160516
EZ - 2016/05/17 06:00
DA - 2017/02/16 06:00
DT - 2016/11/03 06:00
YR - 2016
ED - 20170215
RD - 20170215
UP - 20170217
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27181090
<61. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27930550
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Chang JH
AU - Jiang Y
AU - Pillarisetty VG
FA - Chang, Jae Hyuck
FA - Jiang, Yongjian
FA - Pillarisetty, Venu G
IN - Chang, Jae Hyuck. aDepartment of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea bDepartment of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai, China cDepartment of Surgery, University of Washington Medical Center, Seattle, University of Washington, Seattle, WA.
TI - Role of immune cells in pancreatic cancer from bench to clinical application: An updated review. [Review]
SO - Medicine. 95(49):e5541, 2016 Dec
AS - Medicine (Baltimore). 95(49):e5541, 2016 Dec
NJ - Medicine
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - mny, 2985248r
IO - Medicine (Baltimore)
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Cancer Vaccines/tu [Therapeutic Use]
MH - Humans
MH - Immune Tolerance
MH - Immunotherapy
MH - *Pancreatic Neoplasms/im [Immunology]
MH - Pancreatic Neoplasms/th [Therapy]
AB - BACKGROUND: Pancreatic cancer (PC) remains difficult to treat, despite the recent advances in various anticancer therapies. Immuno-inflammatory response is considered to be a major risk factor for the development of PC in addition to a combination of genetic background and environmental factors. Although patients with PC exhibit evidence of systemic immune dysfunction, the PC microenvironment is replete with immune cells.
AB - METHODS: We searched PubMed for all relevant English language articles published up to March 2016. They included clinical trials, experimental studies, observational studies, and reviews. Trials enrolled at Clinical trial.gov were also searched.
AB - RESULTS: PC induces an immunosuppressive microenvironment, and intratumoral activation of immunity in PC is attenuated by inhibitory signals that limit immune effector function. Multiple types of immune responses can promote an immunosuppressive microenvironment; key regulators of the host tumor immune response are dendritic cells, natural killer cells, macrophages, myeloid derived suppressor cells, and T cells. The function of these immune cells in PC is also influenced by chemotherapeutic agents and the components in tumor microenvironment such as pancreatic stellate cells. Immunotherapy of PC employs monoclonal antibodies/effector cells generated in vitro or vaccination to stimulate antitumor response. Immune therapy in PC has failed to improve overall survival; however, combination therapies comprising immune checkpoint inhibitors and vaccines have been attempted to increase the response.
AB - CONCLUSION: A number of studies have begun to elucidate the roles of immune cell subtypes and their capacity to function or dysfunction in the tumor microenvironment of PC. It will not be long before immune therapy for PC becomes a clinical reality.
CI - The authors have no conflicts of interest to disclose.
RN - 0 (Cancer Vaccines)
ES - 1536-5964
IL - 0025-7974
DI - 00005792-201612060-00047
DO - https://dx.doi.org/10.1097/MD.0000000000005541
PT - Journal Article
PT - Review
ID - 27930550 [pubmed]
ID - 10.1097/MD.0000000000005541 [doi]
ID - 00005792-201612060-00047 [pii]
ID - PMC5266022 [pmc]
PP - ppublish
LG - English
DP - 2016 Dec
DC - 20161208
EZ - 2016/12/09 06:00
DA - 2017/02/16 06:00
DT - 2016/12/09 06:00
YR - 2016
ED - 20170215
RD - 20170224
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=27930550
<62. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28113097
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Solinas C
AU - Chanza NM
AU - Awada A
AU - Scartozzi M
FA - Solinas, Cinzia
FA - Chanza, Nieves Martinez
FA - Awada, Ahmad
FA - Scartozzi, Mario
IN - Solinas, Cinzia. Molecular Immunology Unit, Universite Libre de Bruxelles, Institut Jules Bordet, Brussels, Belgium. Electronic address: czsolinas@gmail.com.
IN - Chanza, Nieves Martinez. Medical Oncology, Universite Libre de Bruxelles, Institut Jules Bordet, Brussels, Belgium; Medical Oncology, Universite Libre de Bruxelles, Erasme Hospital, Brussels, Belgium. Electronic address: nieves.martinez-chanza@bordet.be.
IN - Awada, Ahmad. Medical Oncology, Universite Libre de Bruxelles, Institut Jules Bordet, Brussels, Belgium. Electronic address: ahmad.awada@bordet.be.
IN - Scartozzi, Mario. Medical Oncology, University of Cagliari, Cagliari, Italy. Electronic address: marioscartozzi@gmail.com.
TI - The immune infiltrate in prostate, bladder and testicular tumors: An old friend for new challenges. [Review]
SO - Cancer Treatment Reviews. 53:138-145, 2017 Feb
AS - Cancer Treat Rev. 53:138-145, 2017 Feb
NJ - Cancer treatment reviews
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cnn, 7502030
IO - Cancer Treat. Rev.
SB - Index Medicus
CP - Netherlands
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Lymphocytes, Tumor-Infiltrating
MH - Male
MH - Prostatic Neoplasms/im [Immunology]
MH - *Prostatic Neoplasms/th [Therapy]
MH - Prostatic Neoplasms, Castration-Resistant/im [Immunology]
MH - Prostatic Neoplasms, Castration-Resistant/th [Therapy]
MH - Testicular Neoplasms/im [Immunology]
MH - *Testicular Neoplasms/th [Therapy]
MH - Urinary Bladder Neoplasms/im [Immunology]
MH - Urinary Bladder Neoplasms/pa [Pathology]
MH - *Urinary Bladder Neoplasms/th [Therapy]
KW - Bladder cancer; Immune checkpoint molecules; Immunotherapy; Prostate cancer; TIL; Testicular tumors
AB - In genito-urinary tumors immunotherapy has been administered for a long time: Calmette-Guerin Bacillus as adjuvant treatment in high risk patients with non muscle invasive urothelial bladder cancer and interleukin-2 and interferon-alpha in metastatic kidney cancer. The vaccine Sipuleucel-T has been approved by United States Food and Drug Administration for the treatment of castration resistant prostate cancer patients with asymptomatic or minimally symptomatic disease, given the 22% reduction of mortality risk in this group. Recently immunotherapeutic agents targeting inhibitory immune checkpoint molecules lead to improved outcomes and lasting anti-tumor effects in a variety of hematological and solid malignancies, including urogenital tumors. The benefit from these treatments has been observed only in a proportion of subjects, raising a need in optimizing patients' selection for immune checkpoint blockade. The composition and activity of a pre-existing immune infiltrate may aid in identifying ideal candidates to immunotherapy, with possible implications for the clinical management of neoplastic diseases from earlier to later stages.
AB - Copyright © 2017 Elsevier Ltd. All rights reserved.
ES - 1532-1967
IL - 0305-7372
DI - S0305-7372(16)30152-9
DO - https://dx.doi.org/10.1016/j.ctrv.2016.12.004
PT - Journal Article
PT - Review
ID - 28113097 [pubmed]
ID - S0305-7372(16)30152-9 [pii]
ID - 10.1016/j.ctrv.2016.12.004 [doi]
PP - ppublish
PH - 2016/12/09 [received]
PH - 2016/12/16 [revised]
PH - 2016/12/18 [accepted]
LG - English
EP - 20161230
DP - 2017 Feb
DC - 20170123
EZ - 2017/01/24 06:00
DA - 2017/02/12 06:00
DT - 2017/01/24 06:00
YR - 2017
ED - 20170210
RD - 20170210
UP - 20170214
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=28113097
<63. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27583876
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Zhou GW
AU - Xiong Y
AU - Chen S
AU - Xia F
AU - Li Q
AU - Hu J
FA - Zhou, Guo-Wu
FA - Xiong, Ye
FA - Chen, Si
FA - Xia, Fan
FA - Li, Qiang
FA - Hu, Jia
IN - Zhou, Guo-Wu. aDepartment of Respiratory and Critical Care Medicine, Changhai Hospital, Second Military Medical University bDepartment of Pulmonary Medicine, Medicine, 85 Hospital of People's Liberation Army, Shanghai cDepartment of Oncology, The First Affiliated Hospital to PLA General Hospital, Beijing, P.R. China.
TI - Anti-PD-1/PD-L1 antibody therapy for pretreated advanced nonsmall-cell lung cancer: A meta-analysis of randomized clinical trials. [Review]
SO - Medicine. 95(35):e4611, 2016 Aug
AS - Medicine (Baltimore). 95(35):e4611, 2016 Aug
NJ - Medicine
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - mny, 2985248r
IO - Medicine (Baltimore)
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008560
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antigens, CD274/an [Analysis]
MH - Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
MH - *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - Carcinoma, Non-Small-Cell Lung/ch [Chemistry]
MH - *Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Disease-Free Survival
MH - Humans
MH - Lung Neoplasms/ch [Chemistry]
MH - *Lung Neoplasms/dt [Drug Therapy]
MH - *Programmed Cell Death 1 Receptor/an [Analysis]
MH - Randomized Controlled Trials as Topic
MH - Retreatment
MH - Survival Rate
MH - Taxoids/ad [Administration & Dosage]
AB - BACKGROUND: Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC.
AB - METHODS: Randomized clinical trials were retrieved by searching the PubMed, EMBASE, ASCO meeting abstract, clinicaltrial.gov, and Cochrane library databases. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the overall response rate and adverse events (AEs) were calculated by STATA software.
AB - RESULTS: Three randomized clinical trials involving 1141 pretreated patients with advanced NSCLC were included. These trials all compared the efficacy and safety of anti-PD-1/PD-L1 antibodies (nivolumab and MPDL3280A) with docetaxel. The results suggested that, for all patients, anti-PD-1/PD-L1 therapy could acquire a greater overall response (odds ratio = 1.50, 95% CI: 1.08-2.07, P = 0.015, P for heterogeneity [Ph] = 0.620) and longer OS (HR = 0.71, 95% CI: 0.61-0.81, P < 0.001, Ph = 0.361) than docetaxel, but not PFS (HR = 0.83, 95% CI: 0.65-1.06, P = 0.134; Ph = 0.031). Subgroup analyses according to the tumor PD-L1 expression level showed that anti-PD-1/PD-L1 therapy could significantly improve both OS and PFS in patients with high expressions of PD-L1, but not in those with low expressions. Generally, the rates of grade 3 or 4 AEs of anti-PD-1/PD-L1 therapy were significantly lower than that of docetaxel. However, the risks of pneumonitis and hypothyroidism were significantly higher.
AB - CONCLUSION: Anti-PD-1/PD-L1 antibody therapy may significantly improve the outcomes for pretreated advanced NSCLC patients, with a better safety profile than docetaxel.
CI - The authors have no conflicts of interest to disclose.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD274)
RN - 0 (CD274 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 0 (Taxoids)
RN - 15H5577CQD (docetaxel)
RN - 31YO63LBSN (nivolumab)
RN - 52CMI0WC3Y (atezolizumab)
ES - 1536-5964
IL - 0025-7974
DI - 00005792-201608300-00036
DO - https://dx.doi.org/10.1097/MD.0000000000004611
PT - Journal Article
PT - Meta-Analysis
PT - Review
ID - 27583876 [pubmed]
ID - 10.1097/MD.0000000000004611 [doi]
ID - 00005792-201608300-00036 [pii]
ID - PMC5008560 [pmc]
PP - ppublish
LG - English
DP - 2016 Aug
DC - 20160902
EZ - 2016/09/02 06:00
DA - 2017/02/09 06:00
DT - 2016/09/02 06:00
YR - 2016
ED - 20170208
RD - 20170224
UP - 20170227
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27583876
<64. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26843405
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Kotteas E
AU - Saif MW
AU - Syrigos K
FA - Kotteas, Elias
FA - Saif, Muhammad Wasif
FA - Syrigos, Konstantinos
IN - Kotteas, Elias. Oncology Unit, 3rd Department of Internal Medicine, Sotiria General Hospital, Athens University School of Medicine, 152 Mesogeion Avenue, Athens, Greece. ilkotteas@hotmail.com.
IN - Saif, Muhammad Wasif. Section of GI and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA, USA.
IN - Syrigos, Konstantinos. Oncology Unit, 3rd Department of Internal Medicine, Sotiria General Hospital, Athens University School of Medicine, 152 Mesogeion Avenue, Athens, Greece.
IN - Syrigos, Konstantinos. Yale School of Medicine, New Haven, CT, USA.
TI - Immunotherapy for pancreatic cancer. [Review]
SO - Journal of Cancer Research & Clinical Oncology. 142(8):1795-805, 2016 Aug
AS - J Cancer Res Clin Oncol. 142(8):1795-805, 2016 Aug
NJ - Journal of cancer research and clinical oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - hl5, 7902060
IO - J. Cancer Res. Clin. Oncol.
SB - Index Medicus
CP - Germany
MH - Cancer Vaccines/tu [Therapeutic Use]
MH - Cell Transplantation
MH - Humans
MH - Immunotherapy/ae [Adverse Effects]
MH - *Immunotherapy
MH - Male
MH - *Pancreatic Neoplasms/th [Therapy]
KW - Antibodies; Checkpoint inhibitors; Cytokines; Immunotherapy; Pancreatic cancer; Vaccines
AB - INTRODUCTION: Pancreatic cancer is among the most lethal malignancies resistant to conventional therapies. The vast majority of patients is diagnosed with advanced/metastatic disease and consequently has grim prognosis. Despite the available options with nab-paclitaxel and gemcitabine or 5-fluorouracil/leucovorin/oxaliplatin, chemotherapy offers a modest survival benefit. Targeted therapy in combination with chemotherapy has not shown significant improvement in treatment outcomes. The urgent need for new therapies has turned the spotlights on immunotherapy. Immunotherapy in pancreatic cancer recruits and activates T cells which recognize tumor-specific antigens.
AB - RESULTS: Preclinical models have demonstrated that chemotherapy or targeted therapy works synergistically with immunotherapy. A growing body of evidence has already been gathered regarding the efficacy of checkpoint inhibitors, vaccines, adoptive T cell therapy, monoclonal antibodies, and cytokines in patients with pancreatic cancer.
AB - CONCLUSIONS: Many ongoing trials are aiming to identify treatments which could combine efficacy with limited toxicity. In this article, we review the available data concerning multiple aspects of immunotherapy in pancreatic cancer.
RN - 0 (Cancer Vaccines)
ES - 1432-1335
IL - 0171-5216
DI - 10.1007/s00432-016-2119-2
DO - https://dx.doi.org/10.1007/s00432-016-2119-2
PT - Journal Article
PT - Review
ID - 26843405 [pubmed]
ID - 10.1007/s00432-016-2119-2 [doi]
ID - 10.1007/s00432-016-2119-2 [pii]
PP - ppublish
PH - 2015/12/23 [received]
PH - 2016/01/18 [accepted]
LG - English
EP - 20160203
DP - 2016 Aug
DC - 20160721
EZ - 2016/02/05 06:00
DA - 2017/02/09 06:00
DT - 2016/02/05 06:00
YR - 2016
ED - 20170208
RD - 20170208
UP - 20170210
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26843405
<65. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27583876
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Zhou GW
AU - Xiong Y
AU - Chen S
AU - Xia F
AU - Li Q
AU - Hu J
FA - Zhou, Guo-Wu
FA - Xiong, Ye
FA - Chen, Si
FA - Xia, Fan
FA - Li, Qiang
FA - Hu, Jia
IN - Zhou, Guo-Wu. aDepartment of Respiratory and Critical Care Medicine, Changhai Hospital, Second Military Medical University bDepartment of Pulmonary Medicine, Medicine, 85 Hospital of People's Liberation Army, Shanghai cDepartment of Oncology, The First Affiliated Hospital to PLA General Hospital, Beijing, P.R. China.
TI - Anti-PD-1/PD-L1 antibody therapy for pretreated advanced nonsmall-cell lung cancer: A meta-analysis of randomized clinical trials. [Review]
SO - Medicine. 95(35):e4611, 2016 Aug
AS - Medicine (Baltimore). 95(35):e4611, 2016 Aug
NJ - Medicine
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - mny, 2985248r
IO - Medicine (Baltimore)
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008560
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antigens, CD274/an [Analysis]
MH - Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
MH - *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - Carcinoma, Non-Small-Cell Lung/ch [Chemistry]
MH - *Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Disease-Free Survival
MH - Humans
MH - Lung Neoplasms/ch [Chemistry]
MH - *Lung Neoplasms/dt [Drug Therapy]
MH - *Programmed Cell Death 1 Receptor/an [Analysis]
MH - Randomized Controlled Trials as Topic
MH - Retreatment
MH - Survival Rate
MH - Taxoids/ad [Administration & Dosage]
AB - BACKGROUND: Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC.
AB - METHODS: Randomized clinical trials were retrieved by searching the PubMed, EMBASE, ASCO meeting abstract, clinicaltrial.gov, and Cochrane library databases. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the overall response rate and adverse events (AEs) were calculated by STATA software.
AB - RESULTS: Three randomized clinical trials involving 1141 pretreated patients with advanced NSCLC were included. These trials all compared the efficacy and safety of anti-PD-1/PD-L1 antibodies (nivolumab and MPDL3280A) with docetaxel. The results suggested that, for all patients, anti-PD-1/PD-L1 therapy could acquire a greater overall response (odds ratio = 1.50, 95% CI: 1.08-2.07, P = 0.015, P for heterogeneity [Ph] = 0.620) and longer OS (HR = 0.71, 95% CI: 0.61-0.81, P < 0.001, Ph = 0.361) than docetaxel, but not PFS (HR = 0.83, 95% CI: 0.65-1.06, P = 0.134; Ph = 0.031). Subgroup analyses according to the tumor PD-L1 expression level showed that anti-PD-1/PD-L1 therapy could significantly improve both OS and PFS in patients with high expressions of PD-L1, but not in those with low expressions. Generally, the rates of grade 3 or 4 AEs of anti-PD-1/PD-L1 therapy were significantly lower than that of docetaxel. However, the risks of pneumonitis and hypothyroidism were significantly higher.
AB - CONCLUSION: Anti-PD-1/PD-L1 antibody therapy may significantly improve the outcomes for pretreated advanced NSCLC patients, with a better safety profile than docetaxel.
CI - The authors have no conflicts of interest to disclose.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD274)
RN - 0 (CD274 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 0 (Taxoids)
RN - 15H5577CQD (docetaxel)
RN - 31YO63LBSN (nivolumab)
RN - 52CMI0WC3Y (atezolizumab)
ES - 1536-5964
IL - 0025-7974
DI - 00005792-201608300-00036
DO - https://dx.doi.org/10.1097/MD.0000000000004611
PT - Journal Article
PT - Meta-Analysis
PT - Review
ID - 27583876 [pubmed]
ID - 10.1097/MD.0000000000004611 [doi]
ID - 00005792-201608300-00036 [pii]
ID - PMC5008560 [pmc]
PP - ppublish
LG - English
DP - 2016 Aug
DC - 20160902
EZ - 2016/09/02 06:00
DA - 2017/02/09 06:00
DT - 2016/09/02 06:00
YR - 2016
ED - 20170208
RD - 20170224
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=27583876
<66. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27229364
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Bonnet C
AU - Beinse G
AU - Cabel L
AU - Cochereau D
AU - Lavaud P
AU - Rochefort P
AU - Tabouret E
AU - Turpin A
AU - Verlingue L
AU - Vicier C
AU - Massard C
FA - Bonnet, Clement
FA - Beinse, Guillaume
FA - Cabel, Luc
FA - Cochereau, Delphine
FA - Lavaud, Pernelle
FA - Rochefort, Pauline
FA - Tabouret, Emeline
FA - Turpin, Anthony
FA - Verlingue, Loic
FA - Vicier, Cecile
FA - Massard, Christophe
IN - Bonnet, Clement. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Beinse, Guillaume. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Cabel, Luc. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Cochereau, Delphine. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Lavaud, Pernelle. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Rochefort, Pauline. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Tabouret, Emeline. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Turpin, Anthony. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Verlingue, Loic. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Vicier, Cecile. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Massard, Christophe. AERIO, 149, avenue du Maine, 75014 Paris, France; DITEP, Gustave-Roussy, 94805 Villejuif, France. Electronic address: christophe.massard@gustaveroussy.fr.
TI - [ESMO ECCO 2015: The highlights of immunotherapy and targeted therapies]. [French]
OT - ESMO ECCO 2015 : les temps forts de l'immunotherapie et des therapies ciblees.
SO - Bulletin du Cancer. 103(6):594-603, 2016 Jun
AS - Bull Cancer. 103(6):594-603, 2016 Jun
NJ - Bulletin du cancer
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 0072416
IO - Bull Cancer
SB - Index Medicus
CP - France
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Austria
MH - Europe
MH - Humans
MH - *Immunotherapy
MH - Medical Oncology
MH - *Molecular Targeted Therapy
MH - *Neoplasms/th [Therapy]
KW - Early phase studies; Essai de phases precoces; Immunotherapies; Immunotherapies; Medecine personnalisee; Personalized medicine; Targeted therapies; Therapies ciblees
AB - The ESMO/ECC congress (European Society for Medical Oncology/European Cancer Congress) took place in Vienna, Austria, September 25-29. The main topic of the conference was immunotherapies especially in advanced kidney cancer with nivolumab in phase III and in metastatic lung cancer with atezolizumab in phase II. Targeted therapies were also highlighted with cabozantinib proposed in advanced renal cancer or everolimus in differenciated neuroendocrine tumors grade 1 or 2. Furthermore the current challenges remain unchanged: improving patients' care through better selection and finding biomarkers using simple samples (blood or urine). Also early phases and personalized medicine found their place in the different presentations and were highlighted largely bringing new approaches in the treatment of metastatic patients.
AB - Copyright © 2016.
RN - 0 (Antineoplastic Agents)
ES - 1769-6917
IL - 0007-4551
DI - S0007-4551(16)30039-X
DO - https://dx.doi.org/10.1016/j.bulcan.2016.04.001
PT - Congresses
ID - 27229364 [pubmed]
ID - S0007-4551(16)30039-X [pii]
ID - 10.1016/j.bulcan.2016.04.001 [doi]
PP - ppublish
PH - 2016/04/01 [received]
PH - 2016/04/09 [accepted]
LG - French
EP - 20160524
DP - 2016 Jun
DC - 20160617
EZ - 2016/05/28 06:00
DA - 2017/01/26 06:00
DT - 2016/05/28 06:00
YR - 2016
ED - 20170125
RD - 20170125
UP - 20170127
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27229364
<67. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26811622
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Ibrahim AM
AU - Wang YH
FA - Ibrahim, Andrea Marie
FA - Wang, Yao-He
IN - Ibrahim, Andrea Marie. Andrea Marie Ibrahim, Yao-He Wang, Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, EC1M6BQ London, United Kingdom.
IN - Wang, Yao-He. Andrea Marie Ibrahim, Yao-He Wang, Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, EC1M6BQ London, United Kingdom.
TI - Viro-immune therapy: A new strategy for treatment of pancreatic cancer. [Review]
SO - World Journal of Gastroenterology. 22(2):748-63, 2016 Jan 14
AS - World J Gastroenterol. 22(2):748-63, 2016 Jan 14
NJ - World journal of gastroenterology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 100883448
IO - World J. Gastroenterol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4716074
SB - Index Medicus
CP - United States
MH - Animals
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Cancer Vaccines/tu [Therapeutic Use]
MH - Carcinoma, Pancreatic Ductal/im [Immunology]
MH - *Carcinoma, Pancreatic Ductal/th [Therapy]
MH - Carcinoma, Pancreatic Ductal/vi [Virology]
MH - Combined Modality Therapy
MH - Host-Pathogen Interactions
MH - Humans
MH - *Immunotherapy/mt [Methods]
MH - Molecular Targeted Therapy
MH - *Oncolytic Virotherapy
MH - Oncolytic Viruses/im [Immunology]
MH - *Oncolytic Viruses/py [Pathogenicity]
MH - Pancreatic Neoplasms/im [Immunology]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - *Pancreatic Neoplasms/vi [Virology]
MH - Treatment Outcome
MH - Tumor Escape
MH - Tumor Microenvironment
KW - Anti-cytotoxic T-lymphocyte-associate protein 4; Anti-programmed death receptor 1; Anti-programmed death receptor ligand 1; Cancer vaccine; Immune checkpoint blockade inhibitors; Immunotherapy; Oncolytic viruses; Pancreatic cancer; Pancreatic ductal adenocarcinoma
AB - Pancreatic ductal adenocarcinoma (PDAC) is an almost uniformly lethal disease with less than 5% survival at five years. This is largely due to metastatic disease, which is already present in the majority of patients when diagnosed. Even when the primary cancer can be removed by radical surgery, local recurrence occurs within one year in 50%-80% of cases. Therefore, it is imperative to develop new approaches for the treatment of advanced cancer and the prevention of recurrence after surgery. Tumour-targeted oncolytic viruses (TOVs) have become an attractive therapeutic agent as TOVs can kill cancer cells through multiple mechanisms of action, especially via virus-induced engagement of the immune response specifically against tumour cells. To attack tumour cells effectively, tumour-specific T cells need to overcome negative regulatory signals that suppress their activation or that induce tolerance programmes such as anergy or exhaustion in the tumour microenvironment. In this regard, the recent breakthrough in immunotherapy achieved with immune checkpoint blockade agents, such as anti-cytotoxic T-lymphocyte-associate protein 4, programmed death 1 (PD-1) or PD-L1 antibodies, has demonstrated the possibility of relieving immune suppression in PDAC. Therefore, the combination of oncolytic virotherapy and immune checkpoint blockade agents may synergistically function to enhance the antitumour response, lending the opportunity to be the future for treatment of pancreatic cancer.
RN - 0 (Antineoplastic Agents)
RN - 0 (Cancer Vaccines)
ES - 2219-2840
IL - 1007-9327
DO - https://dx.doi.org/10.3748/wjg.v22.i2.748
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 26811622 [pubmed]
ID - 10.3748/wjg.v22.i2.748 [doi]
ID - PMC4716074 [pmc]
PP - ppublish
PH - 2015/07/29 [received]
PH - 2015/10/26 [revised]
PH - 2015/12/12 [accepted]
LG - English
DP - 2016 Jan 14
DC - 20160126
EZ - 2016/01/27 06:00
DA - 2016/01/27 06:00
DT - 2016/01/27 06:00
YR - 2016
ED - 20170117
RD - 20170117
UP - 20170119
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26811622
<68. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26198822
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Narita T
AU - Oiso N
AU - Taketomo Y
AU - Okahashi K
AU - Yamauchi K
AU - Sato M
AU - Uchida S
AU - Matsuda H
AU - Kawada A
FA - Narita, Tomohiko
FA - Oiso, Naoki
FA - Taketomo, Yasunori
FA - Okahashi, Kazunori
FA - Yamauchi, Kohei
FA - Sato, Masako
FA - Uchida, Shusuke
FA - Matsuda, Hiromasa
FA - Kawada, Akira
IN - Narita, Tomohiko. Department of Dermatology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
IN - Oiso, Naoki. Department of Dermatology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
IN - Taketomo, Yasunori. Department of Endocrinology, Metabolism and Diabetes, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
IN - Okahashi, Kazunori. Department of Dermatology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
IN - Yamauchi, Kohei. Department of Dermatology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
IN - Sato, Masako. Department of Dermatology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
IN - Uchida, Shusuke. Department of Dermatology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
IN - Matsuda, Hiromasa. Department of Dermatology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
IN - Kawada, Akira. Department of Dermatology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
TI - Serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab.
SO - Journal of Dermatology. 43(2):210-4, 2016 Feb
AS - J Dermatol. 43(2):210-4, 2016 Feb
NJ - The Journal of dermatology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - hz7, 7600545
IO - J. Dermatol.
SB - Index Medicus
CP - England
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Female
MH - Hashimoto Disease/bl [Blood]
MH - *Hashimoto Disease/et [Etiology]
MH - Hashimoto Disease/im [Immunology]
MH - Humans
MH - Male
MH - Melanoma/sc [Secondary]
MH - Melanoma/th [Therapy]
MH - Thyroid Gland/dg [Diagnostic Imaging]
MH - Thyroid Hormones/bl [Blood]
MH - Ultrasonography
KW - Hashimoto disease; insulin-dependent diabetes; malignant melanoma; nivolumab; ultrasonography; vitiligo
AB - Nivolumab, a blockade of programmed cell death 1, is now administrated for advanced malignant melanomas. Nivolumab-associated adverse events include organ-specific autoimmune disorders; autoimmune thyroid disease, vitiligo and insulin-dependent diabetes. However, predisposed persons are currently unknown. Here, we report serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab: one with Hashimoto disease and another with probable subclinical Hashimoto disease. We should verify if nivolumab-related hypothyroidism and hyperthyroidism are predisposed to occur in euthyroid individuals with subclinical autoimmune thyroid disease.
AB - Copyright © 2015 Japanese Dermatological Association.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Thyroid Hormones)
RN - 31YO63LBSN (nivolumab)
ES - 1346-8138
IL - 0385-2407
DO - https://dx.doi.org/10.1111/1346-8138.13028
PT - Case Reports
PT - Journal Article
ID - 26198822 [pubmed]
ID - 10.1111/1346-8138.13028 [doi]
PP - ppublish
PH - 2015/04/22 [received]
PH - 2015/06/12 [accepted]
LG - English
EP - 20150722
DP - 2016 Feb
DC - 20160127
EZ - 2015/07/23 06:00
DA - 2015/07/23 06:00
DT - 2015/07/23 06:00
YR - 2016
ED - 20170117
RD - 20170117
UP - 20170119
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26198822
<69. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26968587
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Mandai M
AU - Hamanishi J
AU - Abiko K
AU - Matsumura N
AU - Baba T
AU - Konishi I
FA - Mandai, Masaki
FA - Hamanishi, Junzo
FA - Abiko, Kaoru
FA - Matsumura, Noriomi
FA - Baba, Tsukasa
FA - Konishi, Ikuo
IN - Mandai, Masaki. Department of Obstetrics and Gynecology, Faculty of Medicine, Kinki University, Osaka-Sayama, Japan. mandai@med.kindai.ac.jp.
IN - Hamanishi, Junzo. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
IN - Abiko, Kaoru. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
IN - Matsumura, Noriomi. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
IN - Baba, Tsukasa. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
IN - Konishi, Ikuo. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
TI - Anti-PD-L1/PD-1 immune therapies in ovarian cancer: basic mechanism and future clinical application. [Review]
SO - International Journal of Clinical Oncology. 21(3):456-61, 2016 Jun
AS - Int J Clin Oncol. 21(3):456-61, 2016 Jun
NJ - International journal of clinical oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9616295
IO - Int. J. Clin. Oncol.
SB - Index Medicus
CP - Japan
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antigens, CD274/im [Immunology]
MH - Antigens, CD274/me [Metabolism]
MH - Female
MH - Humans
MH - *Immunotherapy
MH - *Ovarian Neoplasms/th [Therapy]
MH - *Programmed Cell Death 1 Receptor/im [Immunology]
MH - Programmed Cell Death 1 Receptor/me [Metabolism]
MH - Signal Transduction
MH - Tumor Escape/im [Immunology]
MH - Tumor Microenvironment/im [Immunology]
KW - Immune checkpoint inhibitor; Immunotherapy; Ovarian cancer; PD-L1/PD-1
AB - Tumor immune therapy, especially anti-programmed cell death ligand-1/programmed cell death-1 (PD-L1/PD-1) treatment, is currently the focus of substantial attention. Ovarian cancer is the leading cause of mortality from gynecological malignancies, and novel treatment modalities, including immune therapy, are needed. However, a basic understanding of tumor immunity associated with the PD-L1/PD-1 signal has only recently emerged. In this review, we first discuss the importance of local tumor immunity, which affects the clinical outcome of ovarian cancer. We subsequently provide an overview of the basic findings regarding how the PD-L1/PD-1 signal influences local tumor immunity in ovarian cancer. Finally, we discuss what is needed to apply immune therapy in future clinical medicine.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD274)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1437-7772
IL - 1341-9625
DI - 10.1007/s10147-016-0968-y
DO - https://dx.doi.org/10.1007/s10147-016-0968-y
PT - Journal Article
PT - Review
ID - 26968587 [pubmed]
ID - 10.1007/s10147-016-0968-y [doi]
ID - 10.1007/s10147-016-0968-y [pii]
PP - ppublish
PH - 2016/02/02 [received]
PH - 2016/02/22 [accepted]
LG - English
EP - 20160311
DP - 2016 Jun
DC - 20160610
EZ - 2016/03/13 06:00
DA - 2017/01/12 06:00
DT - 2016/03/13 06:00
YR - 2016
ED - 20170111
RD - 20170112
UP - 20170113
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26968587
<70. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27090545
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - McMillen B
AU - Dhillon MS
AU - Yong-Yow S
FA - McMillen, Brock
FA - Dhillon, Manvinder Shelley
FA - Yong-Yow, Sabrina
IN - McMillen, Brock. Department of Family Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
IN - Dhillon, Manvinder Shelley. Department of Family Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
IN - Yong-Yow, Sabrina. Department of Family Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
TI - A rare case of thyroid storm.
SO - BMJ Case Reports. 2016:10.1136/bcr-2016-214603, 2016 Apr 18
AS - BMJ Case Rep. 2016:10.1136/bcr-2016-214603, 2016 Apr 18
NJ - BMJ case reports
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101526291
IO - BMJ Case Rep
SB - Index Medicus
CP - England
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - *Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
MH - Female
MH - Humans
MH - *Melanoma/dt [Drug Therapy]
MH - *Thyroid Crisis/ci [Chemically Induced]
MH - Young Adult
AB - Thyroid storm is a rare and life-threatening state of thyroid hormone excess. Rapid recognition of thyroid storm is key to decreasing the morbidity and mortality of this condition. Clinical manifestations of thyroid storm include unexplained weight loss, hyperactivity and irritability. The most common causes of thyrotoxicosis are Graves' disease, toxic multinodular goitre and toxic adenoma. We present a rare case of thyroid storm induced by dual nivolumab and ipilimumab immunotherapy in a patient receiving treatment for advanced melanoma. In this case, our patient was admitted for thyroid storm 1 month after initiating treatment with nivolumab and ipilimumab immunotherapy. The patient was treated with beta-blockers, antithyroid medications and systemic steroids resulting in an improvement in thyroid function testing and symptoms.
AB - Copyright 2016 BMJ Publishing Group Ltd.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 31YO63LBSN (nivolumab)
RN - 6T8C155666 (ipilimumab)
ES - 1757-790X
IL - 1757-790X
DI - bcr2016214603
DI - bcr-2016-214603
DO - https://dx.doi.org/10.1136/bcr-2016-214603
PT - Case Reports
PT - Journal Article
ID - 27090545 [pubmed]
ID - bcr-2016-214603 [pii]
ID - 10.1136/bcr-2016-214603 [doi]
PP - epublish
LG - English
EP - 20160418
DP - 2016 Apr 18
DC - 20160419
EZ - 2016/04/20 06:00
DA - 2017/01/05 06:00
DT - 2016/04/20 06:00
YR - 2016
ED - 20170104
RD - 20170105
UP - 20170106
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27090545
<71. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27628544
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Nakamura Y
AU - Teramoto Y
AU - Asami Y
AU - Matsuya T
AU - Yamamoto A
FA - Nakamura, Yasuhiro
FA - Teramoto, Yukiko
FA - Asami, Yuri
FA - Matsuya, Taisuke
FA - Yamamoto, Akifumi
IN - Nakamura, Yasuhiro. Dept. of Skin Oncology/Dermatology, Saitama Medical University International Medical Center.
TI - [Immune Checkpoint Inhibitors for Advanced Melanoma - Evidences and Future Perspectives]. [Japanese]
SO - Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy]. 43(9):1036-40, 2016 Sep
AS - Gan To Kagaku Ryoho. 43(9):1036-40, 2016 Sep
NJ - Gan to kagaku ryoho. Cancer & chemotherapy
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 7810034, 6t8
IO - Gan To Kagaku Ryoho
SB - Index Medicus
CP - Japan
MH - Antigens, CD274/im [Immunology]
MH - Clinical Trials as Topic
MH - Humans
MH - *Melanoma/im [Immunology]
MH - Molecular Targeted Therapy
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - Signal Transduction
AB - Recently developed immune checkpoint inhibitors, such as anti-PD-1 antibodies, have shown a clear improvement in clinical efficacy compared with conventional cytotoxic chemotherapy in the treatment of patients with advanced melanoma. Treatment with anti-PD-1 antibodies has resulted in improved objective response rates, longer durations of response, and longer overall survival rates. Although the incidence rate of adverse events associated with anti-PD-1 antibodies is lower than that associated with cytotoxic agents, characteristic severe adverse events such as pneumonia, endocrinopathy, and colitis can occur. A recent clinical trial that evaluated the utility of an anti-PD-1 antibody in combination with an anti-CTLA-4 antibody reported that the treatment enhanced clinical efficacy in terms of response rate and progression-free survival. However, the incidence of adverse events and treatment discontinuation also increased. For optimal selection of immune checkpoint inhibitors for treating patients with advanced melanoma, biomarkers capable of predicting clinical efficacy, prognosis, and adverse events in each patient need to be identified. In addition, novel combination therapies, including immune checkpoint inhibitors and MAP kinase pathway-targeting agents, should result in more favorable clinical responses and prolonged overall survival rates.
RN - 0 (Antigens, CD274)
RN - 0 (CD274 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
IS - 0385-0684
IL - 0385-0684
PT - Journal Article
ID - 27628544 [pubmed]
PP - ppublish
LG - Japanese
DP - 2016 Sep
DC - 20160916
EZ - 2016/09/16 06:00
DA - 2016/12/17 06:00
DT - 2016/09/16 06:00
YR - 2016
ED - 20161216
RD - 20161217
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27628544
<72. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26892612
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Antonilli M
AU - Rahimi H
AU - Visconti V
AU - Napoletano C
AU - Ruscito I
AU - Zizzari IG
AU - Caponnetto S
AU - Barchiesi G
AU - Iadarola R
AU - Pierelli L
AU - Rughetti A
AU - Bellati F
AU - Panici PB
AU - Nuti M
FA - Antonilli, Morena
FA - Rahimi, Hassan
FA - Visconti, Valeria
FA - Napoletano, Chiara
FA - Ruscito, Ilary
FA - Zizzari, Ilaria Grazia
FA - Caponnetto, Salvatore
FA - Barchiesi, Giacomo
FA - Iadarola, Roberta
FA - Pierelli, Luca
FA - Rughetti, Aurelia
FA - Bellati, Filippo
FA - Panici, Pierluigi Benedetti
FA - Nuti, Marianna
IN - Antonilli, Morena. Department of Gynecology, Obstetrics and Urology, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
IN - Rahimi, Hassan. Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
IN - Visconti, Valeria. Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
IN - Napoletano, Chiara. Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
IN - Ruscito, Ilary. Department of Gynecology, Obstetrics and Urology, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
IN - Zizzari, Ilaria Grazia. Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
IN - Caponnetto, Salvatore. Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
IN - Barchiesi, Giacomo. Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
IN - Iadarola, Roberta. Department of Gynecology, Obstetrics and Urology, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
IN - Pierelli, Luca. Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
IN - Rughetti, Aurelia. Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
IN - Bellati, Filippo. Department of Gynecology, Obstetrics and Urology, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
IN - Panici, Pierluigi Benedetti. Department of Gynecology, Obstetrics and Urology, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
IN - Nuti, Marianna. Department of Experimental Medicine, 'Sapienza' University of Rome, Policlinico Umberto I, 00161 Rome, Italy.
TI - Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: Clinical and immunological data of a phase I/II clinical trial.
SO - International Journal of Oncology. 48(4):1369-78, 2016 Apr
AS - Int J Oncol. 48(4):1369-78, 2016 Apr
NJ - International journal of oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cx5, 9306042
IO - Int. J. Oncol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4777599
SB - Index Medicus
CP - Greece
MH - Adult
MH - Aged
MH - *Breast Neoplasms/dt [Drug Therapy]
MH - Breast Neoplasms/im [Immunology]
MH - Breast Neoplasms/pa [Pathology]
MH - Cancer Vaccines/ad [Administration & Dosage]
MH - Cancer Vaccines/im [Immunology]
MH - *Carcinoembryonic Antigen/ad [Administration & Dosage]
MH - Carcinoembryonic Antigen/im [Immunology]
MH - Disease-Free Survival
MH - Female
MH - Flow Cytometry
MH - HLA-A2 Antigen/ge [Genetics]
MH - HLA-A2 Antigen/im [Immunology]
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Lymph Nodes/im [Immunology]
MH - Lymph Nodes/pa [Pathology]
MH - Middle Aged
MH - *Mucin-1/ad [Administration & Dosage]
MH - Mucin-1/im [Immunology]
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/pa [Pathology]
MH - Peptide Fragments/ad [Administration & Dosage]
MH - Peptide Fragments/im [Immunology]
MH - *Receptor, ErbB-2/ad [Administration & Dosage]
MH - Receptor, ErbB-2/im [Immunology]
MH - T-Lymphocytes/im [Immunology]
AB - Vaccination with priming and expansion of tumour reacting T cells is an important therapeutic option to be used in combination with novel checkpoint inhibitors to increase the specificity of the T cell infiltrate and the efficacy of the treatment. In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide. Patients were subjected to 6 doses of vaccine every two weeks and a recall dose after 3 months. ECOG grade 2 toxicity was observed at the injection site. Eight out of 14 patients showed specific CD8+ T cells to at least one antigen. None of 4 patients vaccinated for compassionate use showed a CD8 activation. An OC patient who suffered from a lymph nodal recurrence, showed specific anti-ErbB2 CD8+ T cells in the bulky aortic lymph nodes suggesting homing of the activated T cells. Results confirm that peptide vaccination strategy is feasible, safe and well tolerated. In particular OC patients appear to show a higher response rate compared to BC patients. Vaccination generates a long-lasting immune response, which is strongly enhanced by recall administrations. The clinical outcome of patients enrolled in the trial appears favourable, having registered no deceased patients with a minimum follow-up of 8 years. These promising data, in line with the results of similar studies, the high compliance of patients observed and the favourable toxicity profile, support future trials of peptide vaccination in clinically disease-free patients who have completed standard treatments.
RN - 0 (Cancer Vaccines)
RN - 0 (Carcinoembryonic Antigen)
RN - 0 (HLA-A2 Antigen)
RN - 0 (MUC1 protein, human)
RN - 0 (Mucin-1)
RN - 0 (Peptide Fragments)
RN - EC 2-7-10-1 (ERBB2 protein, human)
RN - EC 2-7-10-1 (Receptor, ErbB-2)
ES - 1791-2423
IL - 1019-6439
DO - https://dx.doi.org/10.3892/ijo.2016.3386
PT - Clinical Trial, Phase I
PT - Clinical Trial, Phase II
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26892612 [pubmed]
ID - 10.3892/ijo.2016.3386 [doi]
ID - PMC4777599 [pmc]
PP - ppublish
PH - 2015/11/05 [received]
PH - 2016/01/13 [accepted]
LG - English
EP - 20160208
DP - 2016 Apr
DC - 20160407
EZ - 2016/02/20 06:00
DA - 2016/12/17 06:00
DT - 2016/02/20 06:00
YR - 2016
ED - 20161216
RD - 20161217
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26892612
<73. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26890478
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Parsels LA
AU - Tanska DM
AU - Parsels JD
AU - Zabludoff SD
AU - Cuneo KC
AU - Lawrence TS
AU - Maybaum J
AU - Morgan MA
FA - Parsels, Leslie A
FA - Tanska, Daria M
FA - Parsels, Joshua D
FA - Zabludoff, Sonya D
FA - Cuneo, Kyle C
FA - Lawrence, Theodore S
FA - Maybaum, Jonathan
FA - Morgan, Meredith A
IN - Parsels, Leslie A. a Department of Radiation Oncology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Parsels, Leslie A. b Department of Pharmacology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Tanska, Daria M. b Department of Pharmacology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Parsels, Joshua D. a Department of Radiation Oncology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Parsels, Joshua D. b Department of Pharmacology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Zabludoff, Sonya D. c AstraZeneca R&D Boston , Waltham , MA , USA.
IN - Zabludoff, Sonya D. d Zabludoff Consulting San Diego , CA , USA.
IN - Cuneo, Kyle C. a Department of Radiation Oncology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Lawrence, Theodore S. a Department of Radiation Oncology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Maybaum, Jonathan. a Department of Radiation Oncology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Maybaum, Jonathan. b Department of Pharmacology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Morgan, Meredith A. a Department of Radiation Oncology , University of Michigan Medical School , Ann Arbor , MI , USA.
TI - Dissociation of gemcitabine chemosensitization by CHK1 inhibition from cell cycle checkpoint abrogation and aberrant mitotic entry.
SO - Cell Cycle. 15(5):730-9, 2016
AS - Cell Cycle. 15(5):730-9, 2016
NJ - Cell cycle (Georgetown, Tex.)
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101137841
IO - Cell Cycle
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845922
SB - Index Medicus
CP - United States
MH - *Antimetabolites, Antineoplastic/pd [Pharmacology]
MH - Cell Cycle Checkpoints
MH - Cell Line, Tumor
MH - *Checkpoint Kinase 1/ai [Antagonists & Inhibitors]
MH - Cyclin B1/me [Metabolism]
MH - DNA Damage
MH - *Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Drug Screening Assays, Antitumor
MH - G2 Phase Cell Cycle Checkpoints
MH - Humans
MH - Mitosis
MH - Nocodazole/pd [Pharmacology]
MH - Pancreatic Neoplasms/dt [Drug Therapy]
MH - *Thiophenes/pd [Pharmacology]
MH - *Urea/aa [Analogs & Derivatives]
MH - Urea/pd [Pharmacology]
KW - AZD7762; CHK1; aberrant mitotic entry; checkpoint abrogation; gemcitabine; pancreatic cancer
AB - In order to determine the relative contribution of checkpoint abrogation and subsequent aberrant mitotic entry to gemcitabine chemosensitization by CHK1 inhibition, we established a model utilizing the CDK inhibitors roscovitine or purvalanol A to re-establish cell cycle arrest and prevent aberrant mitotic entry in pancreatic cancer cells treated with gemcitabine and the CHK inhibitor AZD7762. In this study, we report that the extent of aberrant mitotic entry, as determined by flow cytometry for the mitotic marker phospho-Histone H3 (Ser10), did not reflect the relative sensitivities of pancreatic cancer cell lines to gemcitabine chemosensitization by AZD7762. In addition, re-establishing gemcitabine-induced cell cycle arrest either pharmacologically, with roscovitine or purvalanol A, or genetically, with cyclin B1 siRNA, did not inhibit chemosensitization uniformly across the cell lines. Furthermore, we found that AZD7762 augmented high-intensity gammaH2AX signaling in gemcitabine-treated cells, suggesting the presence of replication stress when CHK1 is inhibited. Finally, the ability of roscovitine to prevent chemosensitization correlated with its ability to inhibit AZD7762-induced high-intensity gammaH2AX, but not aberrant pHH3, suggesting that the effects of AZD7762 on DNA replication or repair rather than aberrant mitotic entry determine gemcitabine chemosensitization in pancreatic cancer cells.
RN - 0 (3-(carbamoylamino)-5-(3-fluorophenyl)-N-(3-piperidyl)thiophene-2-carboxamide)
RN - 0 (Antimetabolites, Antineoplastic)
RN - 0 (CCNB1 protein, human)
RN - 0 (Cyclin B1)
RN - 0 (Thiophenes)
RN - 0W860991D6 (Deoxycytidine)
RN - 8W8T17847W (Urea)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
RN - SH1WY3R615 (Nocodazole)
ES - 1551-4005
IL - 1551-4005
DO - https://dx.doi.org/10.1080/15384101.2016.1148841
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 26890478 [pubmed]
ID - 10.1080/15384101.2016.1148841 [doi]
ID - PMC4845922 [pmc]
PP - ppublish
PH - 2017/02/18 [pmc-release]
GI - No: R01 CA163895
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50CA130810
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01CA138723
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01CA163895
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2016
DC - 20160331
EZ - 2016/02/19 06:00
DA - 2016/12/16 06:00
DT - 2016/02/19 06:00
YR - 2016
ED - 20161215
RD - 20161230
UP - 20161230
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26890478
<74. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26890478
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Parsels LA
AU - Tanska DM
AU - Parsels JD
AU - Zabludoff SD
AU - Cuneo KC
AU - Lawrence TS
AU - Maybaum J
AU - Morgan MA
FA - Parsels, Leslie A
FA - Tanska, Daria M
FA - Parsels, Joshua D
FA - Zabludoff, Sonya D
FA - Cuneo, Kyle C
FA - Lawrence, Theodore S
FA - Maybaum, Jonathan
FA - Morgan, Meredith A
IN - Parsels, Leslie A. a Department of Radiation Oncology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Parsels, Leslie A. b Department of Pharmacology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Tanska, Daria M. b Department of Pharmacology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Parsels, Joshua D. a Department of Radiation Oncology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Parsels, Joshua D. b Department of Pharmacology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Zabludoff, Sonya D. c AstraZeneca R&D Boston , Waltham , MA , USA.
IN - Zabludoff, Sonya D. d Zabludoff Consulting San Diego , CA , USA.
IN - Cuneo, Kyle C. a Department of Radiation Oncology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Lawrence, Theodore S. a Department of Radiation Oncology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Maybaum, Jonathan. a Department of Radiation Oncology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Maybaum, Jonathan. b Department of Pharmacology , University of Michigan Medical School , Ann Arbor , MI , USA.
IN - Morgan, Meredith A. a Department of Radiation Oncology , University of Michigan Medical School , Ann Arbor , MI , USA.
TI - Dissociation of gemcitabine chemosensitization by CHK1 inhibition from cell cycle checkpoint abrogation and aberrant mitotic entry.
SO - Cell Cycle. 15(5):730-9, 2016
AS - Cell Cycle. 15(5):730-9, 2016
NJ - Cell cycle (Georgetown, Tex.)
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101137841
IO - Cell Cycle
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845922
SB - Index Medicus
CP - United States
MH - *Antimetabolites, Antineoplastic/pd [Pharmacology]
MH - Cell Cycle Checkpoints
MH - Cell Line, Tumor
MH - *Checkpoint Kinase 1/ai [Antagonists & Inhibitors]
MH - Cyclin B1/me [Metabolism]
MH - DNA Damage
MH - *Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Drug Screening Assays, Antitumor
MH - G2 Phase Cell Cycle Checkpoints
MH - Humans
MH - Mitosis
MH - Nocodazole/pd [Pharmacology]
MH - Pancreatic Neoplasms/dt [Drug Therapy]
MH - *Thiophenes/pd [Pharmacology]
MH - *Urea/aa [Analogs & Derivatives]
MH - Urea/pd [Pharmacology]
KW - AZD7762; CHK1; aberrant mitotic entry; checkpoint abrogation; gemcitabine; pancreatic cancer
AB - In order to determine the relative contribution of checkpoint abrogation and subsequent aberrant mitotic entry to gemcitabine chemosensitization by CHK1 inhibition, we established a model utilizing the CDK inhibitors roscovitine or purvalanol A to re-establish cell cycle arrest and prevent aberrant mitotic entry in pancreatic cancer cells treated with gemcitabine and the CHK inhibitor AZD7762. In this study, we report that the extent of aberrant mitotic entry, as determined by flow cytometry for the mitotic marker phospho-Histone H3 (Ser10), did not reflect the relative sensitivities of pancreatic cancer cell lines to gemcitabine chemosensitization by AZD7762. In addition, re-establishing gemcitabine-induced cell cycle arrest either pharmacologically, with roscovitine or purvalanol A, or genetically, with cyclin B1 siRNA, did not inhibit chemosensitization uniformly across the cell lines. Furthermore, we found that AZD7762 augmented high-intensity gammaH2AX signaling in gemcitabine-treated cells, suggesting the presence of replication stress when CHK1 is inhibited. Finally, the ability of roscovitine to prevent chemosensitization correlated with its ability to inhibit AZD7762-induced high-intensity gammaH2AX, but not aberrant pHH3, suggesting that the effects of AZD7762 on DNA replication or repair rather than aberrant mitotic entry determine gemcitabine chemosensitization in pancreatic cancer cells.
RN - 0 (3-(carbamoylamino)-5-(3-fluorophenyl)-N-(3-piperidyl)thiophene-2-carboxamide)
RN - 0 (Antimetabolites, Antineoplastic)
RN - 0 (CCNB1 protein, human)
RN - 0 (Cyclin B1)
RN - 0 (Thiophenes)
RN - 0W860991D6 (Deoxycytidine)
RN - 8W8T17847W (Urea)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
RN - SH1WY3R615 (Nocodazole)
ES - 1551-4005
IL - 1551-4005
DO - https://dx.doi.org/10.1080/15384101.2016.1148841
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 26890478 [pubmed]
ID - 10.1080/15384101.2016.1148841 [doi]
ID - PMC4845922 [pmc]
PP - ppublish
GI - No: R01 CA163895
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50CA130810
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01CA138723
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01CA163895
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2016
DC - 20160331
EZ - 2016/02/19 06:00
DA - 2016/12/16 06:00
DT - 2016/02/19 06:00
YR - 2016
ED - 20161215
RD - 20170218
UP - 20170221
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26890478
<75. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25760920
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Papavasileiou E
AU - Prasad S
AU - Freitag SK
AU - Sobrin L
AU - Lobo AM
FA - Papavasileiou, Evangelia
FA - Prasad, Sashank
FA - Freitag, Suzanne K
FA - Sobrin, Lucia
FA - Lobo, Ann-Marie
IN - Papavasileiou, Evangelia. a Department of Ophthalmology , Harvard Medical School, Massachusetts Eye and Ear Infirmary , Boston , Massachusetts , USA and.
IN - Prasad, Sashank. b Department of Neurology , Harvard Medical School, Brigham and Women's Hospital , Boston , Massachusetts , USA.
IN - Freitag, Suzanne K. a Department of Ophthalmology , Harvard Medical School, Massachusetts Eye and Ear Infirmary , Boston , Massachusetts , USA and.
IN - Sobrin, Lucia. a Department of Ophthalmology , Harvard Medical School, Massachusetts Eye and Ear Infirmary , Boston , Massachusetts , USA and.
IN - Lobo, Ann-Marie. a Department of Ophthalmology , Harvard Medical School, Massachusetts Eye and Ear Infirmary , Boston , Massachusetts , USA and.
TI - Ipilimumab-induced Ocular and Orbital Inflammation--A Case Series and Review of the Literature. [Review]
SO - Ocular Immunology & Inflammation. 24(2):140-6, 2016
AS - Ocul Immunol Inflamm. 24(2):140-6, 2016
NJ - Ocular immunology and inflammation
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cq1, 9312169
IO - Ocul. Immunol. Inflamm.
SB - Index Medicus
CP - England
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - CTLA-4 Antigen/im [Immunology]
MH - *Corneal Ulcer/ci [Chemically Induced]
MH - Corneal Ulcer/di [Diagnosis]
MH - Corneal Ulcer/dt [Drug Therapy]
MH - Female
MH - Glucocorticoids/tu [Therapeutic Use]
MH - Humans
MH - Male
MH - Middle Aged
MH - *Orbital Cellulitis/ci [Chemically Induced]
MH - Orbital Cellulitis/di [Diagnosis]
MH - Orbital Cellulitis/dt [Drug Therapy]
MH - Retrospective Studies
MH - Tomography, X-Ray Computed
MH - *Uveitis/ci [Chemically Induced]
MH - Uveitis/di [Diagnosis]
MH - Uveitis/dt [Drug Therapy]
KW - Autoimmune adverse events; CTLA-4 inhibitors; eye and orbit complications; ipilimumab; melanoma
AB - PURPOSE: Ipilimumab, a monoclonal antibody directed against the immune protein cytotoxic T-lymphocyte antigen-4 (CTLA-4), characteristically induces side effects called "immune-related adverse events" (IRAE). Although ophthalmic involvement is rare, we report 7 cases of eye and orbit complications related to ipilimumab therapy.
AB - METHODS: We performed a retrospective review of patients with metastatic melanoma who developed ipilimumab-related ocular or orbital inflammation who were seen at our institutions.
AB - RESULTS: Seven patients were identified: 4 patients had orbital inflammation, 2 had uveitis, and 1 had peripheral ulcerative keratitis. Four patients developed inflammation after the second ipilimumab infusion, 2 after the third infusion and 1 after the first infusion. All 4 patients with orbital inflammation were treated with systemic corticosteroids. Two patients with uveitis were treated with topical steroids, but were also treated with systemic corticosteroids for other IRAE, including colitis and hypophysitis. The patient with keratitis was treated with topical corticosteroids alone with resolution of inflammation. All 7 patients discontinued ipilimumab therapy, 5 due to systemic IRAE and 2 due to tumor progression. Five of 7 patients had tumor progression on ipilimumab therapy.
AB - CONCLUSIONS: Ocular and orbital inflammation may occur in patients with metastatic melanoma receiving ipilimumab, is frequently accompanied by other IRAEs, and resolves with corticosteroid treatment, often leaving no long-term sequelae.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (Glucocorticoids)
RN - 6T8C155666 (ipilimumab)
ES - 1744-5078
IL - 0927-3948
DO - https://dx.doi.org/10.3109/09273948.2014.1001858
PT - Case Reports
PT - Journal Article
PT - Review
ID - 25760920 [pubmed]
ID - 10.3109/09273948.2014.1001858 [doi]
PP - ppublish
LG - English
EP - 20150311
DP - 2016
DC - 20160414
EZ - 2015/03/12 06:00
DA - 2016/12/15 06:00
DT - 2015/03/12 06:00
YR - 2016
ED - 20161214
RD - 20161230
UP - 20161230
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25760920
<76. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26186958
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Faje A
FA - Faje, Alexander
IN - Faje, Alexander. BUL 457, Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. afaje@partners.org.
TI - Immunotherapy and hypophysitis: clinical presentation, treatment, and biologic insights. [Review]
SO - Pituitary. 19(1):82-92, 2016 Feb
AS - Pituitary. 19(1):82-92, 2016 Feb
NJ - Pituitary
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - dsi, 9814578
IO - Pituitary
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - CTLA-4 Antigen/me [Metabolism]
MH - Humans
MH - *Hypophysitis/me [Metabolism]
MH - *Hypophysitis/th [Therapy]
MH - *Immunotherapy/mt [Methods]
KW - CTLA-4; Hypophysitis; Hypopituitarism; Ipilimumab
AB - INTRODUCTION: Advances in immunotherapy have transformed the management of metastatic melanoma and generated encouraging results in the treatment of other malignancies. Autoimmune side effects from these agents, termed immune-related adverse events (IRAEs), are diverse and can include multiple endocrinopathies. Ipilimumab-induced hypophysitis (IH) is a recently recognized endocrine IRAE.
AB - METHODS: This review summarizes published data and experience from our center on the incidence, presentation and management, and proposed mechanisms for immunotherapy-related hypophysitis, with a focus on patients treated with ipilimumab (Ipi).
AB - CONCLUSION: Hypophysitis occurs in a significant minority of patients treated with Ipi, in contrast to the relative rarity of idiopathic autoimmune hypophysitis or hypophysitis after treatment with other immunotherapies. Recently published cohorts have described the clinical presentation and management of IH and longitudinal outcomes in these patients. Additional studies with Ipi and other emerging agents have helped identify potential risk factors for the development of immunotherapy-related hypophysitis and possible underlying mechanisms for IH. Clarification of the mechanism(s) for IH may enhance our understanding of idiopathic autoimmune hypophysitis and could have potential therapeutic applications.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
ES - 1573-7403
IL - 1386-341X
DI - 10.1007/s11102-015-0671-4
DO - https://dx.doi.org/10.1007/s11102-015-0671-4
PT - Journal Article
PT - Review
ID - 26186958 [pubmed]
ID - 10.1007/s11102-015-0671-4 [doi]
ID - 10.1007/s11102-015-0671-4 [pii]
PP - ppublish
LG - English
DP - 2016 Feb
DC - 20160113
EZ - 2015/07/19 06:00
DA - 2016/12/15 06:00
DT - 2015/07/19 06:00
YR - 2016
ED - 20161213
RD - 20161230
UP - 20161230
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26186958
<77. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26942589
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Hardwick N
AU - Frankel PH
AU - Cristea M
FA - Hardwick, Nicola
FA - Frankel, Paul H
FA - Cristea, Mihaela
IN - Hardwick, Nicola. Department of Experimental Therapeutics, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA.
IN - Frankel, Paul H. Division of Biostatistics, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA.
IN - Cristea, Mihaela. Department of Medical Oncology, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA. mcristea@coh.org.
TI - New Approaches for Immune Directed Treatment for Ovarian Cancer. [Review]
SO - Current Treatment Options in Oncology. 17(3):14, 2016 Mar
AS - Curr Treat Options Oncol. 17(3):14, 2016 Mar
NJ - Current treatment options in oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 100900946
IO - Curr Treat Options Oncol
SB - Index Medicus
CP - United States
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antigens, CD274/ai [Antagonists & Inhibitors]
MH - Antigens, CD274/im [Immunology]
MH - Cancer Vaccines/im [Immunology]
MH - *Cancer Vaccines/tu [Therapeutic Use]
MH - Clinical Trials as Topic
MH - Disease-Free Survival
MH - Female
MH - Humans
MH - Immunosuppression
MH - *Immunotherapy
MH - Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Ovarian Neoplasms/th [Therapy]
MH - Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - T-Lymphocytes/de [Drug Effects]
MH - T-Lymphocytes/im [Immunology]
KW - Adoptive T cell transfer; Cancer vaccine; Immunotherapy; Monoclonal antibodies check point inhibitors; Ovarian cancer
AB - OPINION STATEMENT: The immune system plays an active role in the pathogenesis of ovarian cancer (OC), as well as in the mechanisms of disease progression and overall survival (OS). Immunotherapy in gynecological cancers could help to revert immunosuppression and lymphocyte depletion due to prior treatments. Current immunotherapies for ovarian cancer, like all cancer immunotherapy, are based on either stimulating the immune system or reverting immune suppression. Several approaches have been used, including therapeutic vaccines, monoclonal antibodies; checkpoint inhibitors and adoptive T cell transfer. Most of these therapies are still in early-phase testing (phase I and II) for ovarian cancer, but the initial data in ovarian cancer and successful use in other types of cancers suggests some of these approaches may ultimately prove useful for ovarian cancer as well. Ovarian cancer vaccines have shown only a modest benefit in ovarian cancer when used as monotherapy, but these agents may be able to enhance antitumor activity when combined with chemotherapy, checkpoint inhibitors, or other immunotherapies. Monoclonal antibodies have been explored in ovarian cancer but despite encouraging phase II data, randomized studies failed to demonstrate significant clinical benefit. Check point inhibitors have promising activity in several solid tumors and have demonstrated a favorable toxicity profile. Data from early clinical trials utilizing PD1 and PD-L1 inhibitors showed encouraging results. Ongoing clinical trials are evaluating the role of check point inhibitors in combination with chemotherapy. Adoptive T cell transfer involves the infusion of ex vivo activated and expanded tumor specific T cells, using various sources and types of T cells. While this approach has been explored in several hematologic malignancies, it constitutes early research in ovarian cancer. Immunotherapy remains investigational in ovarian cancer and the benefit of this approach in improving progression-free survival (PFS) or OS is unknown. Previous clinical trials have not selected patients based on biomarkers and this may explain the negative results. We expect to discover that tumor response will relate to the patient's immune features and specific tumor characteristics. We are only beginning to realize the potential of immunotherapy for ovarian cancer patients, and one goal of future clinical trials will be to identify subsets of patient based on histologic, molecular, and immune characteristics.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD274)
RN - 0 (CD274 protein, human)
RN - 0 (Cancer Vaccines)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1534-6277
IL - 1534-6277
DI - 10.1007/s11864-016-0389-1
DO - https://dx.doi.org/10.1007/s11864-016-0389-1
PT - Journal Article
PT - Review
ID - 26942589 [pubmed]
ID - 10.1007/s11864-016-0389-1 [doi]
ID - 10.1007/s11864-016-0389-1 [pii]
PP - ppublish
LG - English
DP - 2016 Mar
DC - 20160305
EZ - 2016/03/05 06:00
DA - 2016/12/15 06:00
DT - 2016/03/05 06:00
YR - 2016
ED - 20161213
RD - 20161230
UP - 20161230
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26942589
<78. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26534966
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Merchant MS
AU - Wright M
AU - Baird K
AU - Wexler LH
AU - Rodriguez-Galindo C
AU - Bernstein D
AU - Delbrook C
AU - Lodish M
AU - Bishop R
AU - Wolchok JD
AU - Streicher H
AU - Mackall CL
FA - Merchant, Melinda S
FA - Wright, Matthew
FA - Baird, Kristin
FA - Wexler, Leonard H
FA - Rodriguez-Galindo, Carlos
FA - Bernstein, Donna
FA - Delbrook, Cindy
FA - Lodish, Maya
FA - Bishop, Rachel
FA - Wolchok, Jedd D
FA - Streicher, Howard
FA - Mackall, Crystal L
IN - Merchant, Melinda S. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. mackallc@mail.nih.gov.
IN - Wright, Matthew. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
IN - Baird, Kristin. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
IN - Wexler, Leonard H. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY and Weill-Cornell Medical College, New York, NY.
IN - Rodriguez-Galindo, Carlos. Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA.
IN - Bernstein, Donna. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
IN - Delbrook, Cindy. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
IN - Lodish, Maya. National Institute of Child Health and Human Development, NIH, Bethesda, MD.
IN - Bishop, Rachel. National Eye Institute, NIH, Bethesda, MD.
IN - Wolchok, Jedd D. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. Weill-Cornell Medical College, New York, NY.
IN - Streicher, Howard. Investigational Drug Branch, National Cancer Institute, NIH, Bethesda, MD.
IN - Mackall, Crystal L. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
TI - Phase I Clinical Trial of Ipilimumab in Pediatric Patients with Advanced Solid Tumors.
SO - Clinical Cancer Research. 22(6):1364-70, 2016 Mar 15
AS - Clin Cancer Res. 22(6):1364-70, 2016 Mar 15
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c2h, 9502500
IO - Clin. Cancer Res.
SB - Index Medicus
CP - United States
MH - Adolescent
MH - Adult
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Brain/pa [Pathology]
MH - Child
MH - Child, Preschool
MH - Combined Modality Therapy
MH - Drug Monitoring
MH - Female
MH - Humans
MH - Immunomodulation
MH - Magnetic Resonance Imaging
MH - Male
MH - Neoplasms/di [Diagnosis]
MH - *Neoplasms/dt [Drug Therapy]
MH - Neoplasms/im [Immunology]
MH - Neoplasms/me [Metabolism]
MH - Retreatment
MH - Treatment Outcome
MH - Young Adult
AB - PURPOSE: Ipilimumab is a first-in-class immune checkpoint inhibitor approved for treatment of metastatic melanoma but not studied in children until this phase I protocol.
AB - EXPERIMENTAL DESIGN: This study examined safety, pharmacokinetics, and immunogenicity, and immune correlates of ipilimumab administered to subjects <=21 years old with recurrent or progressive solid tumors. Dose escalation cohorts received 1, 3, 5, or 10 mg/m(2) intravenously every 3 weeks in a 3 + 3 design. Response was assessed after 6 weeks and 12 weeks, and then every 3 months. Treatment was continued until disease progression or unacceptable toxicity.
AB - RESULTS: Thirty-three patients received 72 doses of ipilimumab. Patients enrolled had melanoma (n = 12), sarcoma (n = 17), or other refractory solid tumors (n = 4). Immune-related adverse events included pancreatitis, pneumonitis, colitis, endocrinopathies, and transaminitis with dose-limiting toxicities observed at 5 and 10 mg/kg dose levels. Pharmacokinetics revealed a half-life of 8 to 15 days. At day 21, subjects had increased levels of cycling T cells, but no change in regulatory T-cell populations. Six subjects had confirmed stable disease for 4 to 10 cycles (melanoma, osteosarcoma, clear cell sarcoma, and synovial sarcoma).
AB - CONCLUSIONS: Ipilimumab was safely administered to pediatric patients using management algorithms for immune-related toxicities. The spectrum of immune-related adverse events is similar to those described in adults; however, many of the pediatric toxicities were evident after a single dose. Although no objective tumor regressions were observed with ipilimumab as a single agent, subjects with immune-related toxicities had an increased overall survival compared with those who showed no evidence of breaking tolerance.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
IS - 1078-0432
IL - 1078-0432
DI - 1078-0432.CCR-15-0491
DO - https://dx.doi.org/10.1158/1078-0432.CCR-15-0491
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Multicenter Study
PT - Research Support, N.I.H., Intramural
ID - 26534966 [pubmed]
ID - 1078-0432.CCR-15-0491 [pii]
ID - 10.1158/1078-0432.CCR-15-0491 [doi]
ID - PMC5027962 [pmc]
ID - NIHMS735794 [mid]
PP - ppublish
PH - 2015/03/02 [received]
PH - 2015/10/14 [accepted]
PH - 2017/03/15 [pmc-release]
GI - No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
No: Z99 CA999999
Organization: *Intramural NIH HHS*
Country: United States
LG - English
EP - 20151103
DP - 2016 Mar 15
DC - 20160316
EZ - 2015/11/05 06:00
DA - 2016/12/15 06:00
DT - 2015/11/05 06:00
YR - 2016
ED - 20161213
RD - 20161230
UP - 20161230
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26534966
<79. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26655088
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Goh G
AU - Walradt T
AU - Markarov V
AU - Blom A
AU - Riaz N
AU - Doumani R
AU - Stafstrom K
AU - Moshiri A
AU - Yelistratova L
AU - Levinsohn J
AU - Chan TA
AU - Nghiem P
AU - Lifton RP
AU - Choi J
FA - Goh, Gerald
FA - Walradt, Trent
FA - Markarov, Vladimir
FA - Blom, Astrid
FA - Riaz, Nadeem
FA - Doumani, Ryan
FA - Stafstrom, Krista
FA - Moshiri, Ata
FA - Yelistratova, Lola
FA - Levinsohn, Jonathan
FA - Chan, Timothy A
FA - Nghiem, Paul
FA - Lifton, Richard P
FA - Choi, Jaehyuk
IN - Goh, Gerald. Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
IN - Goh, Gerald. Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT, USA.
IN - Walradt, Trent. Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
IN - Markarov, Vladimir. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
IN - Blom, Astrid. Department of Dermatology, University of Washington, Seattle, WA, USA.
IN - Riaz, Nadeem. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
IN - Riaz, Nadeem. Department of Pathology, University of Washington, Seattle, WA, USA.
IN - Doumani, Ryan. Department of Dermatology, University of Washington, Seattle, WA, USA.
IN - Stafstrom, Krista. Department of Dermatology, University of Washington, Seattle, WA, USA.
IN - Moshiri, Ata. Department of Dermatology, University of Washington, Seattle, WA, USA.
IN - Yelistratova, Lola. Department of Dermatology, University of Washington, Seattle, WA, USA.
IN - Levinsohn, Jonathan. Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
IN - Chan, Timothy A. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
IN - Chan, Timothy A. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
IN - Nghiem, Paul. Department of Dermatology, University of Washington, Seattle, WA, USA.
IN - Nghiem, Paul. Department of Pathology, University of Washington, Seattle, WA, USA.
IN - Nghiem, Paul. Fred Hutchinson Cancer Center, Seattle, WA, USA.
IN - Lifton, Richard P. Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
IN - Lifton, Richard P. Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT, USA.
IN - Choi, Jaehyuk. Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
IN - Choi, Jaehyuk. Department of Dermatology, Veterans Affairs Healthcare, West Haven, CT, USA.
IN - Choi, Jaehyuk. Current address: Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
TI - Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy.
SO - Oncotarget. 7(3):3403-15, 2016 Jan 19
AS - Oncotarget. 7(3):3403-15, 2016 Jan 19
NJ - Oncotarget
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101532965
IO - Oncotarget
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823115
SB - Index Medicus
CP - United States
MH - *Biomarkers, Tumor/ge [Genetics]
MH - *Carcinoma, Merkel Cell/ge [Genetics]
MH - Carcinoma, Merkel Cell/im [Immunology]
MH - Carcinoma, Merkel Cell/vi [Virology]
MH - Exome/ge [Genetics]
MH - Genes, Tumor Suppressor
MH - Humans
MH - Immunotherapy
MH - *Merkel cell polyomavirus/im [Immunology]
MH - *Mutation/ge [Genetics]
MH - Oncogenes/ge [Genetics]
MH - RNA, Messenger/ge [Genetics]
MH - Real-Time Polymerase Chain Reaction
MH - Reverse Transcriptase Polymerase Chain Reaction
MH - *Skin Neoplasms/ge [Genetics]
MH - Skin Neoplasms/im [Immunology]
MH - Skin Neoplasms/vi [Virology]
MH - *Tumor Virus Infections/ge [Genetics]
MH - Tumor Virus Infections/im [Immunology]
MH - Tumor Virus Infections/vi [Virology]
KW - Merkel cell carcinoma; Merkel cell polyomavirus; TP53; cancer genetics; tumor neoantigens
AB - Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous neuroendocrine carcinoma, associated with the Merkel cell polyomavirus (MCPyV) in 80% of cases. To define the genetic basis of MCCs, we performed exome sequencing of 49 MCCs. We show that MCPyV-negative MCCs have a high mutation burden (median of 1121 somatic single nucleotide variants (SSNVs) per-exome with frequent mutations in RB1 and TP53 and additional damaging mutations in genes in the chromatin modification (ASXL1, MLL2, and MLL3), JNK (MAP3K1 and TRAF7), and DNA-damage pathways (ATM, MSH2, and BRCA1). In contrast, MCPyV-positive MCCs harbor few SSNVs (median of 12.5 SSNVs/tumor) with none in the genes listed above. In both subgroups, there are rare cancer-promoting mutations predicted to activate the PI3K pathway (HRAS, KRAS, PIK3CA, PTEN, and TSC1) and to inactivate the Notch pathway (Notch1 and Notch2). TP53 mutations appear to be clinically relevant in virus-negative MCCs as 37% of these tumors harbor potentially targetable gain-of-function mutations in TP53 at p.R248 and p.P278. Moreover, TP53 mutational status predicts death in early stage MCC (5-year survival in TP53 mutant vs wild-type stage I and II MCCs is 20% vs. 92%, respectively; P = 0.0036). Lastly, we identified the tumor neoantigens in MCPyV-negative and MCPyV-positive MCCs. We found that virus-negative MCCs harbor more tumor neoantigens than melanomas or non-small cell lung cancers (median of 173, 65, and 111 neoantigens/sample, respectively), two cancers for which immune checkpoint blockade can produce durable clinical responses. Collectively, these data support the use of immunotherapies for virus-negative MCCs.
RN - 0 (Biomarkers, Tumor)
RN - 0 (RNA, Messenger)
ES - 1949-2553
IL - 1949-2553
DI - 6494
DO - https://dx.doi.org/10.18632/oncotarget.6494
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 26655088 [pubmed]
ID - 6494 [pii]
ID - 10.18632/oncotarget.6494 [doi]
ID - PMC4823115 [pmc]
PP - ppublish
PH - 2015/08/27 [received]
PH - 2015/11/20 [accepted]
GI - No: K08 CA191019
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA162522
Organization: (CA) *NCI NIH HHS*
Country: United States
No: T32 AR007016
Organization: (AR) *NIAMS NIH HHS*
Country: United States
No: K24 CA139052
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA060553
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA176841
Organization: (CA) *NCI NIH HHS*
Country: United States
Organization: *Howard Hughes Medical Institute*
Country: United States
LG - English
DP - 2016 Jan 19
DC - 20160216
EZ - 2015/12/15 06:00
DA - 2016/12/15 06:00
DT - 2015/12/15 06:00
YR - 2016
ED - 20161213
RD - 20161230
UP - 20161230
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26655088
<80. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26881392
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Emens LA
AU - Kok M
AU - Ojalvo LS
FA - Emens, Leisha A
FA - Kok, Marleen
FA - Ojalvo, Laureen S
IN - Emens, Leisha A. aDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA bThe Netherlands Cancer Institute, Amsterdam, the Netherlands cThe Kelly Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
TI - Targeting the programmed cell death-1 pathway in breast and ovarian cancer.
SO - Current Opinion in Obstetrics & Gynecology. 28(2):142-7, 2016 Apr
AS - Curr Opin Obstet Gynecol. 28(2):142-7, 2016 Apr
NJ - Current opinion in obstetrics & gynecology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - a50, 9007264
IO - Curr. Opin. Obstet. Gynecol.
SB - Index Medicus
CP - England
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antigens, CD274/ai [Antagonists & Inhibitors]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Apoptosis
MH - Breast Neoplasms/im [Immunology]
MH - *Breast Neoplasms/th [Therapy]
MH - Female
MH - Humans
MH - *Immunotherapy
MH - Ovarian Neoplasms/im [Immunology]
MH - *Ovarian Neoplasms/th [Therapy]
AB - PURPOSE OF REVIEW: Immune checkpoint blockade is changing cancer therapy. Targeting the programmed cell death-1 (PD-1) pathway releases T cells from inhibitory signals within the tumor microenvironment, thereby activating a latent antitumor immune response. Here, we review the biology underlying the activity of PD-1/programmed cell death-ligand 1 (PD-L1) antagonists, and data describing their clinical activity in breast and ovarian cancer.
AB - RECENT FINDINGS: Several antagonists of PD-1 and PD-L1 have been tested in breast and ovarian cancer. These drugs are generally well tolerated, with some immune-related adverse events that are typically easily managed. Objective response rates generally range from about 10 to 20% in both breast cancer and ovarian cancer, with durable responses noted in multiple trials. Selecting patients with PD-L1 expression by cells within the tumor microenvironment appears to enrich for responses. These agents are under accelerated development based on these promising early data.
AB - SUMMARY: Monoclonal antibody-based blockade of the PD-1 pathway results in objective and durable clinical responses in a subset of patients with breast or ovarian cancers, particularly those with PD-L1-positive cells within the tumor microenvironment. Current priorities are to refine biomarkers of therapeutic response, and to develop combination immunotherapy strategies that integrate PD-1/PD-L1 antagonists with both standard and immune-based cancer therapies to increase efficacy.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
ES - 1473-656X
IL - 1040-872X
DO - https://dx.doi.org/10.1097/GCO.0000000000000257
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26881392 [pubmed]
ID - 10.1097/GCO.0000000000000257 [doi]
PP - ppublish
LG - English
DP - 2016 Apr
DC - 20160304
EZ - 2016/02/17 06:00
DA - 2016/12/15 06:00
DT - 2016/02/18 06:00
YR - 2016
ED - 20161213
RD - 20161230
UP - 20161230
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26881392
<81. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26625204
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Darb-Esfahani S
AU - Kunze CA
AU - Kulbe H
AU - Sehouli J
AU - Wienert S
AU - Lindner J
AU - Budczies J
AU - Bockmayr M
AU - Dietel M
AU - Denkert C
AU - Braicu I
AU - Johrens K
FA - Darb-Esfahani, Silvia
FA - Kunze, Catarina Alisa
FA - Kulbe, Hagen
FA - Sehouli, Jalid
FA - Wienert, Stephan
FA - Lindner, Judith
FA - Budczies, Jan
FA - Bockmayr, Michael
FA - Dietel, Manfred
FA - Denkert, Carsten
FA - Braicu, Ioana
FA - Johrens, Korinna
IN - Darb-Esfahani, Silvia. Institute of Pathology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Darb-Esfahani, Silvia. Tumorbank Ovarian Cancer Network, Department of Gynecology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Kunze, Catarina Alisa. Institute of Pathology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Kulbe, Hagen. Tumorbank Ovarian Cancer Network, Department of Gynecology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Kulbe, Hagen. Department of Gynecology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Sehouli, Jalid. Tumorbank Ovarian Cancer Network, Department of Gynecology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Sehouli, Jalid. Department of Gynecology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Wienert, Stephan. Institute of Pathology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Wienert, Stephan. VM Scope GmbH, Berlin, Germany.
IN - Lindner, Judith. Institute of Pathology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Budczies, Jan. Institute of Pathology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Bockmayr, Michael. Institute of Pathology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Dietel, Manfred. Institute of Pathology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Denkert, Carsten. Institute of Pathology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Denkert, Carsten. Tumorbank Ovarian Cancer Network, Department of Gynecology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Braicu, Ioana. Tumorbank Ovarian Cancer Network, Department of Gynecology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Braicu, Ioana. Department of Gynecology, Charite Universitatsmedizin Berlin, Berlin, Germany.
IN - Johrens, Korinna. Institute of Pathology, Charite Universitatsmedizin Berlin, Berlin, Germany.
TI - Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma.
SO - Oncotarget. 7(2):1486-99, 2016 Jan 12
AS - Oncotarget. 7(2):1486-99, 2016 Jan 12
NJ - Oncotarget
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101532965
IO - Oncotarget
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811475
SB - Index Medicus
CP - United States
MH - *Antigens, CD274/an [Analysis]
MH - Antigens, CD274/ge [Genetics]
MH - *Biomarkers, Tumor/an [Analysis]
MH - Biomarkers, Tumor/ge [Genetics]
MH - *Carcinoma/ch [Chemistry]
MH - Carcinoma/ge [Genetics]
MH - Carcinoma/im [Immunology]
MH - Carcinoma/th [Therapy]
MH - Databases, Genetic
MH - Disease-Free Survival
MH - Female
MH - Gene Expression Regulation, Neoplastic
MH - Humans
MH - Immunohistochemistry
MH - Kaplan-Meier Estimate
MH - *Lymphocytes, Tumor-Infiltrating/ch [Chemistry]
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Lymphocytes, Tumor-Infiltrating/pa [Pathology]
MH - Middle Aged
MH - Neoplasm Grading
MH - *Neoplasms, Cystic, Mucinous, and Serous/ch [Chemistry]
MH - Neoplasms, Cystic, Mucinous, and Serous/ge [Genetics]
MH - Neoplasms, Cystic, Mucinous, and Serous/im [Immunology]
MH - Neoplasms, Cystic, Mucinous, and Serous/th [Therapy]
MH - *Ovarian Neoplasms/ch [Chemistry]
MH - Ovarian Neoplasms/ge [Genetics]
MH - Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/th [Therapy]
MH - *Programmed Cell Death 1 Receptor/an [Analysis]
MH - Programmed Cell Death 1 Receptor/ge [Genetics]
MH - RNA, Messenger/ge [Genetics]
MH - Reverse Transcriptase Polymerase Chain Reaction
MH - Time Factors
MH - Tissue Array Analysis
KW - PD-1; PD-L1; high grade serous carcinoma; ovarian; tumor-infiltrating lymphocytes
AB - AIMS: Antibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma.
AB - METHODS: PD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measured by quantitative reverse transcription PCR. An in silico validation of mRNA data was performed in The Cancer Genome Atlas (TCGA) dataset.
AB - RESULTS: PD-1 and PD-L1 expression in cancer cells, CD3+, PD-1+, and PD-L1+ TILs densities as well as PD-1 and PD-L1 mRNA levels were positive prognostic factors for progression-free (PFS) and overall survival (OS), with all factors being significant for PFS (p < 0.035 each), and most being significant for OS. Most factors also had prognostic value that was independent from age, stage, and residual tumor. Moreover, high PD-1+ TILs as well as PD-L1+ TILs densities added prognostic value to CD3+TILs (PD-1+: p = 0.002,; PD-L1+: p = 0.002). The significant positive prognostic impact of PD-1 and PD-L1 mRNA expression could be reproduced in the TCGA gene expression datasets (p = 0.02 and p < 0.0001, respectively).
AB - CONCLUSIONS: Despite their reported immune-modulatory function, high PD-1 and PD-L1 levels are indicators of a favorable prognosis in ovarian cancer. Our data indicate that PD-1 and PD-L1 molecules are biologically relevant regulators of the immune response in high-grade serous ovarian carcinoma, which is an argument for the evaluation of immune checkpoint inhibiting drugs in this tumor entity.
RN - 0 (Antigens, CD274)
RN - 0 (Biomarkers, Tumor)
RN - 0 (CD274 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 0 (RNA, Messenger)
ES - 1949-2553
IL - 1949-2553
DI - 6429
DO - https://dx.doi.org/10.18632/oncotarget.6429
PT - Journal Article
ID - 26625204 [pubmed]
ID - 6429 [pii]
ID - 10.18632/oncotarget.6429 [doi]
ID - PMC4811475 [pmc]
PP - ppublish
PH - 2015/06/12 [received]
PH - 2015/11/15 [accepted]
LG - English
DP - 2016 Jan 12
DC - 20160216
EZ - 2015/12/02 06:00
DA - 2016/12/15 06:00
DT - 2015/12/02 06:00
YR - 2016
ED - 20161213
RD - 20161230
UP - 20161230
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26625204
<82. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26655088
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Goh G
AU - Walradt T
AU - Markarov V
AU - Blom A
AU - Riaz N
AU - Doumani R
AU - Stafstrom K
AU - Moshiri A
AU - Yelistratova L
AU - Levinsohn J
AU - Chan TA
AU - Nghiem P
AU - Lifton RP
AU - Choi J
FA - Goh, Gerald
FA - Walradt, Trent
FA - Markarov, Vladimir
FA - Blom, Astrid
FA - Riaz, Nadeem
FA - Doumani, Ryan
FA - Stafstrom, Krista
FA - Moshiri, Ata
FA - Yelistratova, Lola
FA - Levinsohn, Jonathan
FA - Chan, Timothy A
FA - Nghiem, Paul
FA - Lifton, Richard P
FA - Choi, Jaehyuk
IN - Goh, Gerald. Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
IN - Goh, Gerald. Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT, USA.
IN - Walradt, Trent. Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
IN - Markarov, Vladimir. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
IN - Blom, Astrid. Department of Dermatology, University of Washington, Seattle, WA, USA.
IN - Riaz, Nadeem. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
IN - Riaz, Nadeem. Department of Pathology, University of Washington, Seattle, WA, USA.
IN - Doumani, Ryan. Department of Dermatology, University of Washington, Seattle, WA, USA.
IN - Stafstrom, Krista. Department of Dermatology, University of Washington, Seattle, WA, USA.
IN - Moshiri, Ata. Department of Dermatology, University of Washington, Seattle, WA, USA.
IN - Yelistratova, Lola. Department of Dermatology, University of Washington, Seattle, WA, USA.
IN - Levinsohn, Jonathan. Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
IN - Chan, Timothy A. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
IN - Chan, Timothy A. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
IN - Nghiem, Paul. Department of Dermatology, University of Washington, Seattle, WA, USA.
IN - Nghiem, Paul. Department of Pathology, University of Washington, Seattle, WA, USA.
IN - Nghiem, Paul. Fred Hutchinson Cancer Center, Seattle, WA, USA.
IN - Lifton, Richard P. Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
IN - Lifton, Richard P. Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT, USA.
IN - Choi, Jaehyuk. Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
IN - Choi, Jaehyuk. Department of Dermatology, Veterans Affairs Healthcare, West Haven, CT, USA.
IN - Choi, Jaehyuk. Current address: Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
TI - Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy.
SO - Oncotarget. 7(3):3403-15, 2016 Jan 19
AS - Oncotarget. 7(3):3403-15, 2016 Jan 19
NJ - Oncotarget
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101532965
IO - Oncotarget
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823115
SB - Index Medicus
CP - United States
MH - *Biomarkers, Tumor/ge [Genetics]
MH - *Carcinoma, Merkel Cell/ge [Genetics]
MH - Carcinoma, Merkel Cell/im [Immunology]
MH - Carcinoma, Merkel Cell/vi [Virology]
MH - Exome/ge [Genetics]
MH - Genes, Tumor Suppressor
MH - Humans
MH - Immunotherapy
MH - *Merkel cell polyomavirus/im [Immunology]
MH - *Mutation/ge [Genetics]
MH - Oncogenes/ge [Genetics]
MH - RNA, Messenger/ge [Genetics]
MH - Real-Time Polymerase Chain Reaction
MH - Reverse Transcriptase Polymerase Chain Reaction
MH - *Skin Neoplasms/ge [Genetics]
MH - Skin Neoplasms/im [Immunology]
MH - Skin Neoplasms/vi [Virology]
MH - *Tumor Virus Infections/ge [Genetics]
MH - Tumor Virus Infections/im [Immunology]
MH - Tumor Virus Infections/vi [Virology]
KW - Merkel cell carcinoma; Merkel cell polyomavirus; TP53; cancer genetics; tumor neoantigens
AB - Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous neuroendocrine carcinoma, associated with the Merkel cell polyomavirus (MCPyV) in 80% of cases. To define the genetic basis of MCCs, we performed exome sequencing of 49 MCCs. We show that MCPyV-negative MCCs have a high mutation burden (median of 1121 somatic single nucleotide variants (SSNVs) per-exome with frequent mutations in RB1 and TP53 and additional damaging mutations in genes in the chromatin modification (ASXL1, MLL2, and MLL3), JNK (MAP3K1 and TRAF7), and DNA-damage pathways (ATM, MSH2, and BRCA1). In contrast, MCPyV-positive MCCs harbor few SSNVs (median of 12.5 SSNVs/tumor) with none in the genes listed above. In both subgroups, there are rare cancer-promoting mutations predicted to activate the PI3K pathway (HRAS, KRAS, PIK3CA, PTEN, and TSC1) and to inactivate the Notch pathway (Notch1 and Notch2). TP53 mutations appear to be clinically relevant in virus-negative MCCs as 37% of these tumors harbor potentially targetable gain-of-function mutations in TP53 at p.R248 and p.P278. Moreover, TP53 mutational status predicts death in early stage MCC (5-year survival in TP53 mutant vs wild-type stage I and II MCCs is 20% vs. 92%, respectively; P = 0.0036). Lastly, we identified the tumor neoantigens in MCPyV-negative and MCPyV-positive MCCs. We found that virus-negative MCCs harbor more tumor neoantigens than melanomas or non-small cell lung cancers (median of 173, 65, and 111 neoantigens/sample, respectively), two cancers for which immune checkpoint blockade can produce durable clinical responses. Collectively, these data support the use of immunotherapies for virus-negative MCCs.
RN - 0 (Biomarkers, Tumor)
RN - 0 (RNA, Messenger)
ES - 1949-2553
IL - 1949-2553
DI - 6494
DO - https://dx.doi.org/10.18632/oncotarget.6494
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 6494 [pii]
ID - 10.18632/oncotarget.6494 [doi]
ID - PMC4823115 [pmc]
PP - ppublish
PH - 2015/08/27 [received]
PH - 2015/11/20 [accepted]
GI - No: K08 CA191019
Organization: (CA) *NCI NIH HHS*
Country: United States
No: UL1 TR001863
Organization: (TR) *NCATS NIH HHS*
Country: United States
No: R01 CA162522
Organization: (CA) *NCI NIH HHS*
Country: United States
No: T32 AR007016
Organization: (AR) *NIAMS NIH HHS*
Country: United States
No: K24 CA139052
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA060553
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA176841
Organization: (CA) *NCI NIH HHS*
Country: United States
Organization: *Howard Hughes Medical Institute*
Country: United States
LG - English
DP - 2016 Jan 19
DC - 20160216
EZ - 2015/12/15 06:00
DA - 2016/12/15 06:00
DT - 2015/12/15 06:00
YR - 2016
ED - 20161213
RD - 20170412
UP - 20170414
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26655088
<83. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26534966
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Merchant MS
AU - Wright M
AU - Baird K
AU - Wexler LH
AU - Rodriguez-Galindo C
AU - Bernstein D
AU - Delbrook C
AU - Lodish M
AU - Bishop R
AU - Wolchok JD
AU - Streicher H
AU - Mackall CL
FA - Merchant, Melinda S
FA - Wright, Matthew
FA - Baird, Kristin
FA - Wexler, Leonard H
FA - Rodriguez-Galindo, Carlos
FA - Bernstein, Donna
FA - Delbrook, Cindy
FA - Lodish, Maya
FA - Bishop, Rachel
FA - Wolchok, Jedd D
FA - Streicher, Howard
FA - Mackall, Crystal L
IN - Merchant, Melinda S. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. mackallc@mail.nih.gov.
IN - Wright, Matthew. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
IN - Baird, Kristin. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
IN - Wexler, Leonard H. Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY and Weill-Cornell Medical College, New York, NY.
IN - Rodriguez-Galindo, Carlos. Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA.
IN - Bernstein, Donna. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
IN - Delbrook, Cindy. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
IN - Lodish, Maya. National Institute of Child Health and Human Development, NIH, Bethesda, MD.
IN - Bishop, Rachel. National Eye Institute, NIH, Bethesda, MD.
IN - Wolchok, Jedd D. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. Weill-Cornell Medical College, New York, NY.
IN - Streicher, Howard. Investigational Drug Branch, National Cancer Institute, NIH, Bethesda, MD.
IN - Mackall, Crystal L. Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
TI - Phase I Clinical Trial of Ipilimumab in Pediatric Patients with Advanced Solid Tumors.
SO - Clinical Cancer Research. 22(6):1364-70, 2016 Mar 15
AS - Clin Cancer Res. 22(6):1364-70, 2016 Mar 15
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c2h, 9502500
IO - Clin. Cancer Res.
SB - Index Medicus
CP - United States
MH - Adolescent
MH - Adult
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Brain/pa [Pathology]
MH - Child
MH - Child, Preschool
MH - Combined Modality Therapy
MH - Drug Monitoring
MH - Female
MH - Humans
MH - Immunomodulation
MH - Magnetic Resonance Imaging
MH - Male
MH - Neoplasms/di [Diagnosis]
MH - *Neoplasms/dt [Drug Therapy]
MH - Neoplasms/im [Immunology]
MH - Neoplasms/me [Metabolism]
MH - Retreatment
MH - Treatment Outcome
MH - Young Adult
AB - PURPOSE: Ipilimumab is a first-in-class immune checkpoint inhibitor approved for treatment of metastatic melanoma but not studied in children until this phase I protocol.
AB - EXPERIMENTAL DESIGN: This study examined safety, pharmacokinetics, and immunogenicity, and immune correlates of ipilimumab administered to subjects <=21 years old with recurrent or progressive solid tumors. Dose escalation cohorts received 1, 3, 5, or 10 mg/m(2) intravenously every 3 weeks in a 3 + 3 design. Response was assessed after 6 weeks and 12 weeks, and then every 3 months. Treatment was continued until disease progression or unacceptable toxicity.
AB - RESULTS: Thirty-three patients received 72 doses of ipilimumab. Patients enrolled had melanoma (n = 12), sarcoma (n = 17), or other refractory solid tumors (n = 4). Immune-related adverse events included pancreatitis, pneumonitis, colitis, endocrinopathies, and transaminitis with dose-limiting toxicities observed at 5 and 10 mg/kg dose levels. Pharmacokinetics revealed a half-life of 8 to 15 days. At day 21, subjects had increased levels of cycling T cells, but no change in regulatory T-cell populations. Six subjects had confirmed stable disease for 4 to 10 cycles (melanoma, osteosarcoma, clear cell sarcoma, and synovial sarcoma).
AB - CONCLUSIONS: Ipilimumab was safely administered to pediatric patients using management algorithms for immune-related toxicities. The spectrum of immune-related adverse events is similar to those described in adults; however, many of the pediatric toxicities were evident after a single dose. Although no objective tumor regressions were observed with ipilimumab as a single agent, subjects with immune-related toxicities had an increased overall survival compared with those who showed no evidence of breaking tolerance.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
IS - 1078-0432
IL - 1078-0432
DI - 1078-0432.CCR-15-0491
DO - https://dx.doi.org/10.1158/1078-0432.CCR-15-0491
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Multicenter Study
PT - Research Support, N.I.H., Intramural
ID - 1078-0432.CCR-15-0491 [pii]
ID - 10.1158/1078-0432.CCR-15-0491 [doi]
ID - PMC5027962 [pmc]
ID - NIHMS735794 [mid]
PP - ppublish
PH - 2015/03/02 [received]
PH - 2015/10/14 [accepted]
GI - No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
No: Z99 CA999999
Organization: *Intramural NIH HHS*
Country: United States
LG - English
EP - 20151103
DP - 2016 Mar 15
DC - 20160316
EZ - 2015/11/05 06:00
DA - 2016/12/15 06:00
DT - 2015/11/05 06:00
YR - 2016
ED - 20161213
RD - 20170315
UP - 20170317
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26534966
<84. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26598537
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Cierna Z
AU - Mego M
AU - Miskovska V
AU - Machalekova K
AU - Chovanec M
AU - Svetlovska D
AU - Hainova K
AU - Rejlekova K
AU - Macak D
AU - Spanik S
AU - Ondrus D
AU - Kajo K
AU - Mardiak J
AU - Babal P
FA - Cierna, Z
FA - Mego, M
FA - Miskovska, V
FA - Machalekova, K
FA - Chovanec, M
FA - Svetlovska, D
FA - Hainova, K
FA - Rejlekova, K
FA - Macak, D
FA - Spanik, S
FA - Ondrus, D
FA - Kajo, K
FA - Mardiak, J
FA - Babal, P
IN - Cierna, Z. Department of Pathology, Faculty of Medicine.
IN - Mego, M. 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava misomego@gmail.com.
IN - Miskovska, V. Faculty of Medicine, St Elisabeth Cancer Institute, Bratislava.
IN - Machalekova, K. Department of Pathology, Slovak Medical University and St Elisabeth Cancer Institute, Bratislava.
IN - Chovanec, M. 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava.
IN - Svetlovska, D. Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute.
IN - Hainova, K. Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute Cancer Research Institute, Slovak, Academy of Sciences, Bratislava.
IN - Rejlekova, K. 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava.
IN - Macak, D. Department of Pathology, National Cancer Institute, Bratislava.
IN - Spanik, S. Faculty of Medicine, St Elisabeth Cancer Institute, Bratislava.
IN - Ondrus, D. Faculty of Medicine, St Elisabeth Cancer Institute, Bratislava.
IN - Kajo, K. Department of Pathology, Slovak Medical University and St Elisabeth Cancer Institute, Bratislava.
IN - Mardiak, J. 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava.
IN - Babal, P. Department of Pathology, Faculty of Medicine Faculty Hospital with Policlinics Skalica, a.s., Skalica, Slovak Republic.
TI - Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors.
CM - Comment in: Nat Rev Urol. 2016 Feb;13(2):62; PMID: 26666362
SO - Annals of Oncology. 27(2):300-5, 2016 Feb
AS - Ann Oncol. 27(2):300-5, 2016 Feb
NJ - Annals of oncology : official journal of the European Society for Medical Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ayf, 9007735
IO - Ann. Oncol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751222
SB - Index Medicus
CP - England
MH - Adolescent
MH - Adult
MH - Aged
MH - Antibodies, Monoclonal/im [Immunology]
MH - Antigens, CD274/ai [Antagonists & Inhibitors]
MH - *Antigens, CD274/me [Metabolism]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - *Biomarkers, Tumor/bl [Blood]
MH - *Choriocarcinoma/pa [Pathology]
MH - Cisplatin/tu [Therapeutic Use]
MH - Disease-Free Survival
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Male
MH - Middle Aged
MH - Neoplasms, Germ Cell and Embryonal/dt [Drug Therapy]
MH - Neoplasms, Germ Cell and Embryonal/mo [Mortality]
MH - *Neoplasms, Germ Cell and Embryonal/pa [Pathology]
MH - Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - *Programmed Cell Death 1 Receptor/me [Metabolism]
MH - Testicular Neoplasms/dt [Drug Therapy]
MH - Testicular Neoplasms/mo [Mortality]
MH - *Testicular Neoplasms/pa [Pathology]
MH - Translational Medical Research
MH - Young Adult
KW - immunotherapy; prognosis; programmed death receptor 1; programmed death-ligand 1; testicular germ cell tumors
AB - BACKGROUND: Testicular germ cell tumors (TGCTs) belong to the most chemosensitive solid tumors; however, a small proportion of patients fail to be cured with cisplatin-based chemotherapy. Inhibitors of PD-1/PD-L1 pathways represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate expression and prognostic value of PD-1 and PD-L1 in TGCTs.
AB - PATIENTS AND METHODS: Surgical specimens from 140 patients with TGCTs (131 with primary testicular tumor and 9 with extragonadal GCTs) were included into the translational study. PD-1 and PD-L1 expression was detected in the tumor tissue by immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method, compared with their expression in normal testicular tissue and correlated with clinicopathological characteristics and clinical outcome.
AB - RESULTS: None of the GCTs exhibited PD-1 protein, although expression of PD-L1 was significantly higher in GCTs in comparison with normal testicular tissue (mean QS = 5.29 versus 0.32, P < 0.0001). Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and seminoma. PD-L1 expression was associated with poor prognostic features, including >=3 metastatic sites, increased serum tumor markers and/or non-pulmonary visceral metastases. Patients with low PD-L1 expression had significantly better progression-free survival [hazard ratio (HR) = 0.40, 95% confidence interval (CI) 0.16-1.01, P = 0.008] and overall survival (HR = 0.43, 95% CI 0.15-1.23, P = 0.040) compared with patients with high PD-L1 expression.
AB - CONCLUSIONS: In this translational study, we showed, for the first time, the prognostic value of PD-L1 expression in TGCTs and our data imply that the PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs.
AB - Copyright © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (Biomarkers, Tumor)
RN - 0 (CD274 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - Q20Q21Q62J (Cisplatin)
RS - Testicular Germ Cell Tumor
ES - 1569-8041
IL - 0923-7534
DI - mdv574
DO - https://dx.doi.org/10.1093/annonc/mdv574
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26598537 [pubmed]
ID - mdv574 [pii]
ID - 10.1093/annonc/mdv574 [doi]
ID - PMC4751222 [pmc]
PP - ppublish
PH - 2015/09/06 [received]
PH - 2015/11/09 [accepted]
PH - 2017/02/01 [pmc-release]
LG - English
EP - 20151123
DP - 2016 Feb
DC - 20160123
EZ - 2015/11/25 06:00
DA - 2016/11/12 06:00
DT - 2015/11/26 06:00
YR - 2016
ED - 20161111
RD - 20161112
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26598537
<85. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26598537
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Cierna Z
AU - Mego M
AU - Miskovska V
AU - Machalekova K
AU - Chovanec M
AU - Svetlovska D
AU - Hainova K
AU - Rejlekova K
AU - Macak D
AU - Spanik S
AU - Ondrus D
AU - Kajo K
AU - Mardiak J
AU - Babal P
FA - Cierna, Z
FA - Mego, M
FA - Miskovska, V
FA - Machalekova, K
FA - Chovanec, M
FA - Svetlovska, D
FA - Hainova, K
FA - Rejlekova, K
FA - Macak, D
FA - Spanik, S
FA - Ondrus, D
FA - Kajo, K
FA - Mardiak, J
FA - Babal, P
IN - Cierna, Z. Department of Pathology, Faculty of Medicine.
IN - Mego, M. 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava misomego@gmail.com.
IN - Miskovska, V. Faculty of Medicine, St Elisabeth Cancer Institute, Bratislava.
IN - Machalekova, K. Department of Pathology, Slovak Medical University and St Elisabeth Cancer Institute, Bratislava.
IN - Chovanec, M. 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava.
IN - Svetlovska, D. Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute.
IN - Hainova, K. Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute Cancer Research Institute, Slovak, Academy of Sciences, Bratislava.
IN - Rejlekova, K. 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava.
IN - Macak, D. Department of Pathology, National Cancer Institute, Bratislava.
IN - Spanik, S. Faculty of Medicine, St Elisabeth Cancer Institute, Bratislava.
IN - Ondrus, D. Faculty of Medicine, St Elisabeth Cancer Institute, Bratislava.
IN - Kajo, K. Department of Pathology, Slovak Medical University and St Elisabeth Cancer Institute, Bratislava.
IN - Mardiak, J. 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava.
IN - Babal, P. Department of Pathology, Faculty of Medicine Faculty Hospital with Policlinics Skalica, a.s., Skalica, Slovak Republic.
TI - Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors.
CM - Comment in: Nat Rev Urol. 2016 Feb;13(2):62; PMID: 26666362
SO - Annals of Oncology. 27(2):300-5, 2016 Feb
AS - Ann Oncol. 27(2):300-5, 2016 Feb
NJ - Annals of oncology : official journal of the European Society for Medical Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ayf, 9007735
IO - Ann. Oncol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751222
SB - Index Medicus
CP - England
MH - Adolescent
MH - Adult
MH - Aged
MH - Antibodies, Monoclonal/im [Immunology]
MH - Antigens, CD274/ai [Antagonists & Inhibitors]
MH - *Antigens, CD274/me [Metabolism]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - *Biomarkers, Tumor/bl [Blood]
MH - *Choriocarcinoma/pa [Pathology]
MH - Cisplatin/tu [Therapeutic Use]
MH - Disease-Free Survival
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Male
MH - Middle Aged
MH - Neoplasms, Germ Cell and Embryonal/dt [Drug Therapy]
MH - Neoplasms, Germ Cell and Embryonal/mo [Mortality]
MH - *Neoplasms, Germ Cell and Embryonal/pa [Pathology]
MH - Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - *Programmed Cell Death 1 Receptor/me [Metabolism]
MH - Testicular Neoplasms/dt [Drug Therapy]
MH - Testicular Neoplasms/mo [Mortality]
MH - *Testicular Neoplasms/pa [Pathology]
MH - Translational Medical Research
MH - Young Adult
KW - immunotherapy; prognosis; programmed death receptor 1; programmed death-ligand 1; testicular germ cell tumors
AB - BACKGROUND: Testicular germ cell tumors (TGCTs) belong to the most chemosensitive solid tumors; however, a small proportion of patients fail to be cured with cisplatin-based chemotherapy. Inhibitors of PD-1/PD-L1 pathways represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate expression and prognostic value of PD-1 and PD-L1 in TGCTs.
AB - PATIENTS AND METHODS: Surgical specimens from 140 patients with TGCTs (131 with primary testicular tumor and 9 with extragonadal GCTs) were included into the translational study. PD-1 and PD-L1 expression was detected in the tumor tissue by immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method, compared with their expression in normal testicular tissue and correlated with clinicopathological characteristics and clinical outcome.
AB - RESULTS: None of the GCTs exhibited PD-1 protein, although expression of PD-L1 was significantly higher in GCTs in comparison with normal testicular tissue (mean QS = 5.29 versus 0.32, P < 0.0001). Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and seminoma. PD-L1 expression was associated with poor prognostic features, including >=3 metastatic sites, increased serum tumor markers and/or non-pulmonary visceral metastases. Patients with low PD-L1 expression had significantly better progression-free survival [hazard ratio (HR) = 0.40, 95% confidence interval (CI) 0.16-1.01, P = 0.008] and overall survival (HR = 0.43, 95% CI 0.15-1.23, P = 0.040) compared with patients with high PD-L1 expression.
AB - CONCLUSIONS: In this translational study, we showed, for the first time, the prognostic value of PD-L1 expression in TGCTs and our data imply that the PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs.
AB - Copyright © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (Biomarkers, Tumor)
RN - 0 (CD274 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - Q20Q21Q62J (Cisplatin)
RS - Testicular Germ Cell Tumor
ES - 1569-8041
IL - 0923-7534
DI - mdv574
DO - https://dx.doi.org/10.1093/annonc/mdv574
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26598537 [pubmed]
ID - mdv574 [pii]
ID - 10.1093/annonc/mdv574 [doi]
ID - PMC4751222 [pmc]
PP - ppublish
PH - 2015/09/06 [received]
PH - 2015/11/09 [accepted]
LG - English
EP - 20151123
DP - 2016 Feb
DC - 20160123
EZ - 2015/11/25 06:00
DA - 2016/11/12 06:00
DT - 2015/11/26 06:00
YR - 2016
ED - 20161111
RD - 20170201
UP - 20170202
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26598537
<86. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27569912
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Daley D
AU - Zambirinis CP
AU - Seifert L
AU - Akkad N
AU - Mohan N
AU - Werba G
AU - Barilla R
AU - Torres-Hernandez A
AU - Hundeyin M
AU - Mani VR
AU - Avanzi A
AU - Tippens D
AU - Narayanan R
AU - Jang JE
AU - Newman E
AU - Pillarisetty VG
AU - Dustin ML
AU - Bar-Sagi D
AU - Hajdu C
AU - Miller G
FA - Daley, Donnele
FA - Zambirinis, Constantinos Pantelis
FA - Seifert, Lena
FA - Akkad, Neha
FA - Mohan, Navyatha
FA - Werba, Gregor
FA - Barilla, Rocky
FA - Torres-Hernandez, Alejandro
FA - Hundeyin, Mautin
FA - Mani, Vishnu Raj Kumar
FA - Avanzi, Antonina
FA - Tippens, Daniel
FA - Narayanan, Rajkishen
FA - Jang, Jung-Eun
FA - Newman, Elliot
FA - Pillarisetty, Venu Gopal
FA - Dustin, Michael Loran
FA - Bar-Sagi, Dafna
FA - Hajdu, Cristina
FA - Miller, George
IN - Daley, Donnele. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Zambirinis, Constantinos Pantelis. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Seifert, Lena. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Akkad, Neha. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Mohan, Navyatha. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Werba, Gregor. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Barilla, Rocky. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Torres-Hernandez, Alejandro. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Hundeyin, Mautin. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Mani, Vishnu Raj Kumar. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Avanzi, Antonina. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Tippens, Daniel. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Narayanan, Rajkishen. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Jang, Jung-Eun. Department of Biochemistry, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Pathology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Newman, Elliot. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Pillarisetty, Venu Gopal. Department of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA.
IN - Dustin, Michael Loran. Department of Pathology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; The Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington Oxford OX3 7FY, UK.
IN - Bar-Sagi, Dafna. Department of Biochemistry, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Hajdu, Cristina. Department of Pathology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Miller, George. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA. Electronic address: george.miller@nyumc.org.
TI - gammadelta T Cells Support Pancreatic Oncogenesis by Restraining alphabeta T Cell Activation.
SO - Cell. 166(6):1485-1499.e15, 2016 Sep 08
AS - Cell. 166(6):1485-1499.e15, 2016 Sep 08
NJ - Cell
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cq4, 0413066
IO - Cell
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017923
OI - Source: NLM. NIHMS812937 [Available on 09/08/17]
SB - Index Medicus
CP - United States
MH - Adaptive Immunity
MH - Animals
MH - *Carcinogenesis/im [Immunology]
MH - Carcinogenesis/pa [Pathology]
MH - *Carcinoma, Pancreatic Ductal/im [Immunology]
MH - *Carcinoma, Pancreatic Ductal/pp [Physiopathology]
MH - Cells, Cultured
MH - Chemokines/im [Immunology]
MH - Epithelial Cells/ph [Physiology]
MH - Female
MH - Humans
MH - Ligands
MH - *Lymphocyte Activation/im [Immunology]
MH - Male
MH - Mice
MH - Mice, Inbred C57BL
MH - Signal Transduction/im [Immunology]
MH - *T-Lymphocytes/im [Immunology]
MH - Tumor Microenvironment/im [Immunology]
KW - Kras; cancer; checkpoint ligands
AB - Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated gammadeltaT cell population, which constituted ~40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of gammadeltaT cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of gammadeltaT cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of alphabetaT cells. Although alphabetaT cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon gammadeltaT cell ablation. PDA-infiltrating gammadeltaT cells expressed high levels of exhaustion ligands and thereby negated adaptive anti-tumor immunity. Blockade of PD-L1 in gammadeltaT cells enhanced CD4(+) and CD8(+) T cell infiltration and immunogenicity and induced tumor protection suggesting that gammadeltaT cells are critical sources of immune-suppressive checkpoint ligands in PDA. We describe gammadeltaT cells as central regulators of effector T cell activation in cancer via novel cross-talk.
AB - Copyright © 2016 Elsevier Inc. All rights reserved.
RN - 0 (Chemokines)
RN - 0 (Ligands)
ES - 1097-4172
IL - 0092-8674
DI - S0092-8674(16)30996-5
DO - https://dx.doi.org/10.1016/j.cell.2016.07.046
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 27569912 [pubmed]
ID - S0092-8674(16)30996-5 [pii]
ID - 10.1016/j.cell.2016.07.046 [doi]
ID - PMC5017923 [pmc]
ID - NIHMS812937 [mid]
PP - ppublish
PH - 2015/07/16 [received]
PH - 2016/02/16 [revised]
PH - 2016/07/27 [accepted]
PH - 2017/09/08 [pmc-release]
GI - Organization: (PCAN) *Pancreatic Cancer Action Network*
Country: United States
No: P30 CA016087
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA168611
Organization: (CA) *NCI NIH HHS*
Country: United States
No: T32 CA193111
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA155649
Organization: (CA) *NCI NIH HHS*
Country: United States
No: UL1 TR000038
Organization: (TR) *NCATS NIH HHS*
Country: United States
LG - English
EP - 20160825
DP - 2016 Sep 08
DC - 20160910
EZ - 2016/08/30 06:00
DA - 2016/11/05 06:00
DT - 2016/08/30 06:00
YR - 2016
ED - 20161104
RD - 20161202
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27569912
<87. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27569912
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Daley D
AU - Zambirinis CP
AU - Seifert L
AU - Akkad N
AU - Mohan N
AU - Werba G
AU - Barilla R
AU - Torres-Hernandez A
AU - Hundeyin M
AU - Mani VR
AU - Avanzi A
AU - Tippens D
AU - Narayanan R
AU - Jang JE
AU - Newman E
AU - Pillarisetty VG
AU - Dustin ML
AU - Bar-Sagi D
AU - Hajdu C
AU - Miller G
FA - Daley, Donnele
FA - Zambirinis, Constantinos Pantelis
FA - Seifert, Lena
FA - Akkad, Neha
FA - Mohan, Navyatha
FA - Werba, Gregor
FA - Barilla, Rocky
FA - Torres-Hernandez, Alejandro
FA - Hundeyin, Mautin
FA - Mani, Vishnu Raj Kumar
FA - Avanzi, Antonina
FA - Tippens, Daniel
FA - Narayanan, Rajkishen
FA - Jang, Jung-Eun
FA - Newman, Elliot
FA - Pillarisetty, Venu Gopal
FA - Dustin, Michael Loran
FA - Bar-Sagi, Dafna
FA - Hajdu, Cristina
FA - Miller, George
IN - Daley, Donnele. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Zambirinis, Constantinos Pantelis. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Seifert, Lena. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Akkad, Neha. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Mohan, Navyatha. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Werba, Gregor. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Barilla, Rocky. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Torres-Hernandez, Alejandro. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Hundeyin, Mautin. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Mani, Vishnu Raj Kumar. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Avanzi, Antonina. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Tippens, Daniel. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Narayanan, Rajkishen. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Jang, Jung-Eun. Department of Biochemistry, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Pathology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Newman, Elliot. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Pillarisetty, Venu Gopal. Department of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA.
IN - Dustin, Michael Loran. Department of Pathology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; The Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington Oxford OX3 7FY, UK.
IN - Bar-Sagi, Dafna. Department of Biochemistry, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Hajdu, Cristina. Department of Pathology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA.
IN - Miller, George. S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Department of Cell Biology, New York University School of Medicine, 430 East 29th Street, New York, NY 10016, USA. Electronic address: george.miller@nyumc.org.
TI - gammadelta T Cells Support Pancreatic Oncogenesis by Restraining alphabeta T Cell Activation.
SO - Cell. 166(6):1485-1499.e15, 2016 Sep 08
AS - Cell. 166(6):1485-1499.e15, 2016 Sep 08
NJ - Cell
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cq4, 0413066
IO - Cell
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5017923
OI - Source: NLM. NIHMS812937 [Available on 09/08/17]
SB - Index Medicus
CP - United States
MH - Adaptive Immunity
MH - Animals
MH - *Carcinogenesis/im [Immunology]
MH - Carcinogenesis/pa [Pathology]
MH - *Carcinoma, Pancreatic Ductal/im [Immunology]
MH - *Carcinoma, Pancreatic Ductal/pp [Physiopathology]
MH - Cells, Cultured
MH - Chemokines/im [Immunology]
MH - Epithelial Cells/ph [Physiology]
MH - Female
MH - Humans
MH - Ligands
MH - *Lymphocyte Activation/im [Immunology]
MH - Male
MH - Mice
MH - Mice, Inbred C57BL
MH - Signal Transduction/im [Immunology]
MH - *T-Lymphocytes/im [Immunology]
MH - Tumor Microenvironment/im [Immunology]
KW - Kras; cancer; checkpoint ligands
AB - Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated gammadeltaT cell population, which constituted ~40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of gammadeltaT cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of gammadeltaT cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of alphabetaT cells. Although alphabetaT cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon gammadeltaT cell ablation. PDA-infiltrating gammadeltaT cells expressed high levels of exhaustion ligands and thereby negated adaptive anti-tumor immunity. Blockade of PD-L1 in gammadeltaT cells enhanced CD4(+) and CD8(+) T cell infiltration and immunogenicity and induced tumor protection suggesting that gammadeltaT cells are critical sources of immune-suppressive checkpoint ligands in PDA. We describe gammadeltaT cells as central regulators of effector T cell activation in cancer via novel cross-talk.
AB - Copyright © 2016 Elsevier Inc. All rights reserved.
RN - 0 (Chemokines)
RN - 0 (Ligands)
ES - 1097-4172
IL - 0092-8674
DI - S0092-8674(16)30996-5
DO - https://dx.doi.org/10.1016/j.cell.2016.07.046
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 27569912 [pubmed]
ID - S0092-8674(16)30996-5 [pii]
ID - 10.1016/j.cell.2016.07.046 [doi]
ID - PMC5017923 [pmc]
ID - NIHMS812937 [mid]
PP - ppublish
PH - 2015/07/16 [received]
PH - 2016/02/16 [revised]
PH - 2016/07/27 [accepted]
PH - 2017/09/08 [pmc-release]
GI - No: UL1 TR001445
Organization: (TR) *NCATS NIH HHS*
Country: United States
Organization: (PCAN) *Pancreatic Cancer Action Network*
Country: United States
No: P30 CA016087
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA168611
Organization: (CA) *NCI NIH HHS*
Country: United States
No: T32 CA193111
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA155649
Organization: (CA) *NCI NIH HHS*
Country: United States
No: UL1 TR000038
Organization: (TR) *NCATS NIH HHS*
Country: United States
LG - English
EP - 20160825
DP - 2016 Sep 08
DC - 20160910
EZ - 2016/08/30 06:00
DA - 2016/11/05 06:00
DT - 2016/08/30 06:00
YR - 2016
ED - 20161104
RD - 20170125
UP - 20170126
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=27569912
<88. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26446948
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Freeman-Keller M
AU - Kim Y
AU - Cronin H
AU - Richards A
AU - Gibney G
AU - Weber JS
FA - Freeman-Keller, Morganna
FA - Kim, Youngchul
FA - Cronin, Heather
FA - Richards, Allison
FA - Gibney, Geoffrey
FA - Weber, Jeffrey S
IN - Freeman-Keller, Morganna. Department of Graduate Medical Education, University of South Florida, Tampa, Florida. morganna.freemankeller@moffitt.org.
IN - Kim, Youngchul. Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.
IN - Cronin, Heather. Clinical Trials Office, Moffitt Cancer Center, Tampa, Florida.
IN - Richards, Allison. Clinical Trials Office, Moffitt Cancer Center, Tampa, Florida.
IN - Gibney, Geoffrey. Department of Cutaneous Oncology, Lombardi Comprehensive Cancer Center, Washington, DC.
IN - Weber, Jeffrey S. Donald A. Adam Comprehensive Melanoma Research Center, Moffitt Cancer Center, Tampa, Florida.
TI - Nivolumab in Resected and Unresectable Metastatic Melanoma: Characteristics of Immune-Related Adverse Events and Association with Outcomes.
SO - Clinical Cancer Research. 22(4):886-94, 2016 Feb 15
AS - Clin Cancer Res. 22(4):886-94, 2016 Feb 15
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c2h, 9502500
IO - Clin. Cancer Res.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755809
OI - Source: NLM. NIHMS729897 [Available on 02/15/17]
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Exanthema/ci [Chemically Induced]
MH - Humans
MH - Hypothyroidism/ci [Chemically Induced]
MH - Kaplan-Meier Estimate
MH - Melanoma/im [Immunology]
MH - Melanoma/mo [Mortality]
MH - *Melanoma/th [Therapy]
MH - Mucositis/ci [Chemically Induced]
MH - Multivariate Analysis
MH - Pneumonia/ci [Chemically Induced]
MH - Proportional Hazards Models
MH - Skin Neoplasms/im [Immunology]
MH - Skin Neoplasms/mo [Mortality]
MH - *Skin Neoplasms/th [Therapy]
MH - Treatment Outcome
AB - PURPOSE: Retrospective analysis of irAEs in melanoma patients treated with nivolumab.
AB - EXPERIMENTAL DESIGN: Data were pooled from 148 patients (33 resected, 115 unresectable) treated with nivolumab plus peptide vaccine or nivolumab alone every 2 weeks for 12 weeks. Patients with stable disease or regression received an additional 12-week cycle, then nivolumab alone every 12 weeks for up to 2 additional years. Frequency, grade, and characteristics of immune-related adverse events (irAE) were analyzed. A 12-week landmark survival analysis using a multivariate time-dependent Cox proportional hazard model assessed difference in overall survival (OS) in the presence or absence of irAEs.
AB - RESULTS: IrAEs of any grade were observed in 68.2% of patients (101 of 148). Grade III/IV irAEs were infrequent: 3 (2%) had grade III rash, 2 (1.35%) had asymptomatic grade III elevation in amylase/lipase, and 2 (1.35%) had grade III colitis. A statistically significant OS difference was noted among patients with any grade of irAE versus those without (P <= 0.001), and OS benefit was noted in patients who reported three or more irAE events (P <= 0.001). Subset analyses showed statistically significant OS differences with rash [P = 0.001; HR, 0.423; 95% confidence interval (CI), 0.243-0.735] and vitiligo (P = 0.012; HR, 0.184; 95% CI, 0.036-0.94). Rash and vitiligo also correlated with statistically significant OS differences in patients with metastatic disease (P = 0.004 and P = 0.028, respectively). No significant survival differences were seen with other irAEs (endocrinopathies, colitis, or pneumonitis).
AB - CONCLUSIONS: Cutaneous irAEs are associated with improved survival in melanoma patients treated with nivolumab, and clinical benefit should be validated in larger prospective analyses.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 31YO63LBSN (nivolumab)
IS - 1078-0432
IL - 1078-0432
DI - 1078-0432.CCR-15-1136
DO - https://dx.doi.org/10.1158/1078-0432.CCR-15-1136
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, U.S. Gov't, P.H.S.
ID - 26446948 [pubmed]
ID - 1078-0432.CCR-15-1136 [pii]
ID - 10.1158/1078-0432.CCR-15-1136 [doi]
ID - PMC4755809 [pmc]
ID - NIHMS729897 [mid]
PP - ppublish
PH - 2015/06/05 [received]
PH - 2015/09/28 [accepted]
PH - 2017/02/15 [pmc-release]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01176461
SA - ClinicalTrials.gov/NCT01176474
SL - https://clinicaltrials.gov/search/term=NCT01176461
SL - https://clinicaltrials.gov/search/term=NCT01176474
GI - No: FDA RO1 FD-003511
Organization: *PHS HHS*
Country: United States
No: R01 FD003511
Organization: (FD) *FDA HHS*
Country: United States
No: NCI P30 CA076292
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA076292
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA129594
Organization: (CA) *NCI NIH HHS*
Country: United States
No: NCI RO1 CA129594
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA168536
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20151007
DP - 2016 Feb 15
DC - 20160216
EZ - 2015/10/09 06:00
DA - 2016/11/04 06:00
DT - 2015/10/09 06:00
YR - 2016
ED - 20161103
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26446948
<89. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26446948
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Freeman-Keller M
AU - Kim Y
AU - Cronin H
AU - Richards A
AU - Gibney G
AU - Weber JS
FA - Freeman-Keller, Morganna
FA - Kim, Youngchul
FA - Cronin, Heather
FA - Richards, Allison
FA - Gibney, Geoffrey
FA - Weber, Jeffrey S
IN - Freeman-Keller, Morganna. Department of Graduate Medical Education, University of South Florida, Tampa, Florida. morganna.freemankeller@moffitt.org.
IN - Kim, Youngchul. Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.
IN - Cronin, Heather. Clinical Trials Office, Moffitt Cancer Center, Tampa, Florida.
IN - Richards, Allison. Clinical Trials Office, Moffitt Cancer Center, Tampa, Florida.
IN - Gibney, Geoffrey. Department of Cutaneous Oncology, Lombardi Comprehensive Cancer Center, Washington, DC.
IN - Weber, Jeffrey S. Donald A. Adam Comprehensive Melanoma Research Center, Moffitt Cancer Center, Tampa, Florida.
TI - Nivolumab in Resected and Unresectable Metastatic Melanoma: Characteristics of Immune-Related Adverse Events and Association with Outcomes.
SO - Clinical Cancer Research. 22(4):886-94, 2016 Feb 15
AS - Clin Cancer Res. 22(4):886-94, 2016 Feb 15
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c2h, 9502500
IO - Clin. Cancer Res.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755809
OI - Source: NLM. NIHMS729897 [Available on 02/15/17]
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Exanthema/ci [Chemically Induced]
MH - Humans
MH - Hypothyroidism/ci [Chemically Induced]
MH - Kaplan-Meier Estimate
MH - Melanoma/im [Immunology]
MH - Melanoma/mo [Mortality]
MH - *Melanoma/th [Therapy]
MH - Mucositis/ci [Chemically Induced]
MH - Multivariate Analysis
MH - Pneumonia/ci [Chemically Induced]
MH - Proportional Hazards Models
MH - Skin Neoplasms/im [Immunology]
MH - Skin Neoplasms/mo [Mortality]
MH - *Skin Neoplasms/th [Therapy]
MH - Treatment Outcome
AB - PURPOSE: Retrospective analysis of irAEs in melanoma patients treated with nivolumab.
AB - EXPERIMENTAL DESIGN: Data were pooled from 148 patients (33 resected, 115 unresectable) treated with nivolumab plus peptide vaccine or nivolumab alone every 2 weeks for 12 weeks. Patients with stable disease or regression received an additional 12-week cycle, then nivolumab alone every 12 weeks for up to 2 additional years. Frequency, grade, and characteristics of immune-related adverse events (irAE) were analyzed. A 12-week landmark survival analysis using a multivariate time-dependent Cox proportional hazard model assessed difference in overall survival (OS) in the presence or absence of irAEs.
AB - RESULTS: IrAEs of any grade were observed in 68.2% of patients (101 of 148). Grade III/IV irAEs were infrequent: 3 (2%) had grade III rash, 2 (1.35%) had asymptomatic grade III elevation in amylase/lipase, and 2 (1.35%) had grade III colitis. A statistically significant OS difference was noted among patients with any grade of irAE versus those without (P <= 0.001), and OS benefit was noted in patients who reported three or more irAE events (P <= 0.001). Subset analyses showed statistically significant OS differences with rash [P = 0.001; HR, 0.423; 95% confidence interval (CI), 0.243-0.735] and vitiligo (P = 0.012; HR, 0.184; 95% CI, 0.036-0.94). Rash and vitiligo also correlated with statistically significant OS differences in patients with metastatic disease (P = 0.004 and P = 0.028, respectively). No significant survival differences were seen with other irAEs (endocrinopathies, colitis, or pneumonitis).
AB - CONCLUSIONS: Cutaneous irAEs are associated with improved survival in melanoma patients treated with nivolumab, and clinical benefit should be validated in larger prospective analyses.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 31YO63LBSN (nivolumab)
IS - 1078-0432
IL - 1078-0432
DI - 1078-0432.CCR-15-1136
DO - https://dx.doi.org/10.1158/1078-0432.CCR-15-1136
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, U.S. Gov't, P.H.S.
ID - 26446948 [pubmed]
ID - 1078-0432.CCR-15-1136 [pii]
ID - 10.1158/1078-0432.CCR-15-1136 [doi]
ID - PMC4755809 [pmc]
ID - NIHMS729897 [mid]
PP - ppublish
PH - 2015/06/05 [received]
PH - 2015/09/28 [accepted]
GI - No: FDA RO1 FD-003511
Organization: *PHS HHS*
Country: United States
No: R01 FD003511
Organization: (FD) *FDA HHS*
Country: United States
No: NCI P30 CA076292
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA076292
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA129594
Organization: (CA) *NCI NIH HHS*
Country: United States
No: NCI RO1 CA129594
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA168536
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20151007
DP - 2016 Feb 15
DC - 20160216
EZ - 2015/10/09 06:00
DA - 2016/11/04 06:00
DT - 2015/10/09 06:00
YR - 2016
ED - 20161103
RD - 20170215
UP - 20170216
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26446948
<90. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26775673
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Abdel-Rahman O
AU - ElHalawani H
AU - Fouad M
FA - Abdel-Rahman, Omar
FA - ElHalawani, Hesham
FA - Fouad, Mona
IN - Abdel-Rahman, Omar. Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
IN - ElHalawani, Hesham. Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
IN - Fouad, Mona. Medical Microbiology & Immunology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
TI - Risk of endocrine complications in cancer patients treated with immune check point inhibitors: a meta-analysis. [Review]
SO - Future Oncology. 12(3):413-25, 2016 Feb
AS - Fut Oncol. 12(3):413-25, 2016 Feb
NJ - Future oncology (London, England)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101256629
IO - Future Oncol
SB - Index Medicus
CP - England
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - *Endocrine System Diseases/ci [Chemically Induced]
MH - Humans
MH - *Neoplasms/dt [Drug Therapy]
MH - Neoplasms/im [Immunology]
MH - Randomized Controlled Trials as Topic
MH - Risk
KW - adrenal insufficiency; hypothyroidism; ipilimumab; nivolumab
AB - BACKGROUND: We performed a meta-analysis of the risk of endocrine adverse events associated with immune check point inhibitors.
AB - METHODS: Eligible studies included randomized trials of cancer patients on immune checkpoint inhibitors; describing events of hypothyroidism, hyperthyroidism, hypophysitis and adrenal insufficiency.
AB - RESULTS: A total of ten clinical trials were eligible for the meta-analysis. The relative risk of all-grade hypothyroidism, hyperthyroidism, hypophyisitis and adrenal insufficiency were 8.26 (95% CI: 4.67-14.62; p < 0.00001), 5.48 (95% CI: 1.33-22.53; p = 0.02); 22.03 (95% CI: 8.52-56.94; p < 0.00001), 3.87 (95% CI: 1.12-13.41; p = 0.03), respectively.
AB - CONCLUSION: Our meta-analysis has demonstrated that the use of immune check point inhibitors is associated with an increased risk of hypothyroidism, hyperthyroidism, hypophysitis and adrenal insufficiency compared with control.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (pidilizumab)
RN - 31YO63LBSN (nivolumab)
RN - 6T8C155666 (ipilimumab)
RN - DPT0O3T46P (pembrolizumab)
RN - QEN1X95CIX (tremelimumab)
ES - 1744-8301
IL - 1479-6694
DO - https://dx.doi.org/10.2217/fon.15.222
PT - Journal Article
PT - Meta-Analysis
PT - Review
ID - 26775673 [pubmed]
ID - 10.2217/fon.15.222 [doi]
PP - ppublish
LG - English
EP - 20160118
DP - 2016 Feb
DC - 20160128
EZ - 2016/01/19 06:00
DA - 2016/11/27 06:00
DT - 2016/01/19 06:00
YR - 2016
ED - 20161019
RD - 20161127
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26775673
<91. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26775673
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Abdel-Rahman O
AU - ElHalawani H
AU - Fouad M
FA - Abdel-Rahman, Omar
FA - ElHalawani, Hesham
FA - Fouad, Mona
IN - Abdel-Rahman, Omar. Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
IN - ElHalawani, Hesham. Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
IN - Fouad, Mona. Medical Microbiology & Immunology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
TI - Risk of endocrine complications in cancer patients treated with immune check point inhibitors: a meta-analysis. [Review]
SO - Future Oncology. 12(3):413-25, 2016 Feb
AS - Fut Oncol. 12(3):413-25, 2016 Feb
NJ - Future oncology (London, England)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101256629
IO - Future Oncol
SB - Index Medicus
CP - England
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - *Endocrine System Diseases/ci [Chemically Induced]
MH - Humans
MH - *Neoplasms/dt [Drug Therapy]
MH - Neoplasms/im [Immunology]
MH - Randomized Controlled Trials as Topic
MH - Risk
KW - adrenal insufficiency; hypothyroidism; ipilimumab; nivolumab
AB - BACKGROUND: We performed a meta-analysis of the risk of endocrine adverse events associated with immune check point inhibitors.
AB - METHODS: Eligible studies included randomized trials of cancer patients on immune checkpoint inhibitors; describing events of hypothyroidism, hyperthyroidism, hypophysitis and adrenal insufficiency.
AB - RESULTS: A total of ten clinical trials were eligible for the meta-analysis. The relative risk of all-grade hypothyroidism, hyperthyroidism, hypophyisitis and adrenal insufficiency were 8.26 (95% CI: 4.67-14.62; p < 0.00001), 5.48 (95% CI: 1.33-22.53; p = 0.02); 22.03 (95% CI: 8.52-56.94; p < 0.00001), 3.87 (95% CI: 1.12-13.41; p = 0.03), respectively.
AB - CONCLUSION: Our meta-analysis has demonstrated that the use of immune check point inhibitors is associated with an increased risk of hypothyroidism, hyperthyroidism, hypophysitis and adrenal insufficiency compared with control.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (pidilizumab)
RN - 31YO63LBSN (nivolumab)
RN - 6T8C155666 (ipilimumab)
RN - DPT0O3T46P (pembrolizumab)
RN - QEN1X95CIX (tremelimumab)
ES - 1744-8301
IL - 1479-6694
DO - https://dx.doi.org/10.2217/fon.15.222
PT - Journal Article
PT - Meta-Analysis
PT - Review
ID - 26775673 [pubmed]
ID - 10.2217/fon.15.222 [doi]
PP - ppublish
LG - English
EP - 20160118
DP - 2016 Feb
DC - 20160128
EZ - 2016/01/19 06:00
DA - 2016/11/27 06:00
DT - 2016/01/19 06:00
YR - 2016
ED - 20161019
RD - 20170103
UP - 20170103
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26775673
<92. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26733436
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Verma I
AU - Modi A
AU - Tripathi H
AU - Agrawal A
AI - Agrawal, Abhinav; ORCID: http://orcid.org/0000-0003-1080-6449
FA - Verma, Isha
FA - Modi, Anar
FA - Tripathi, Hemantkumar
FA - Agrawal, Abhinav
IN - Verma, Isha. Department of Medicine, Monmouth Medical Center, Long Branch, New Jersey, USA.
IN - Modi, Anar. Division of Endocrinology, Diabetes & Metabolism, Cooper University Hospital, Camden, New Jersey, USA.
IN - Tripathi, Hemantkumar. Mower Central Research Lab, Sinai Hospital of Baltimore, Baltimore, Maryland, USA.
IN - Agrawal, Abhinav. Department of Medicine, Monmouth Medical Center, Long Branch, New Jersey, USA.
TI - Nivolumab causing painless thyroiditis in a patient with adenocarcinoma of the lung.
SO - BMJ Case Reports. 2016, 2016 Jan 05
AS - BMJ Case Rep. 2016, 2016 Jan 05
NJ - BMJ case reports
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101526291
IO - BMJ Case Rep
SB - Index Medicus
CP - England
MH - *Adenocarcinoma/co [Complications]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Female
MH - Humans
MH - *Lung Neoplasms/co [Complications]
MH - Middle Aged
MH - *Thyroiditis/ci [Chemically Induced]
MH - Thyrotoxicosis/et [Etiology]
AB - Thyroiditis is characterised by transient hyperthyroidism, followed sometimes by hypothyroidism, and then recovery. We report a case of painless drug-induced thyroiditis-in a patient with no history of any thyroid disorder-treated with Nivolumab (an IgG4 monoclonal antibody against Programmed Death Receptor 1). The purpose of this case report is to increase awareness among clinicians regarding this possible adverse effect from Nivolumab, and discuss the possible pathophysiology and management strategies in such patients.
AB - Copyright 2016 BMJ Publishing Group Ltd.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 31YO63LBSN (nivolumab)
ES - 1757-790X
IL - 1757-790X
DI - bcr2015213692
DI - bcr-2015-213692
DO - https://dx.doi.org/10.1136/bcr-2015-213692
PT - Case Reports
PT - Journal Article
ID - 26733436 [pubmed]
ID - bcr-2015-213692 [pii]
ID - 10.1136/bcr-2015-213692 [doi]
PP - epublish
LG - English
EP - 20160105
DP - 2016 Jan 05
DC - 20160106
EZ - 2016/01/07 06:00
DA - 2016/10/11 06:00
DT - 2016/01/07 06:00
YR - 2016
ED - 20161010
RD - 20161117
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26733436
<93. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26733436
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Verma I
AU - Modi A
AU - Tripathi H
AU - Agrawal A
AI - Agrawal, Abhinav; ORCID: http://orcid.org/0000-0003-1080-6449
FA - Verma, Isha
FA - Modi, Anar
FA - Tripathi, Hemantkumar
FA - Agrawal, Abhinav
IN - Verma, Isha. Department of Medicine, Monmouth Medical Center, Long Branch, New Jersey, USA.
IN - Modi, Anar. Division of Endocrinology, Diabetes & Metabolism, Cooper University Hospital, Camden, New Jersey, USA.
IN - Tripathi, Hemantkumar. Mower Central Research Lab, Sinai Hospital of Baltimore, Baltimore, Maryland, USA.
IN - Agrawal, Abhinav. Department of Medicine, Monmouth Medical Center, Long Branch, New Jersey, USA.
TI - Nivolumab causing painless thyroiditis in a patient with adenocarcinoma of the lung.
SO - BMJ Case Reports. 2016, 2016 Jan 05
AS - BMJ Case Rep. 2016, 2016 Jan 05
NJ - BMJ case reports
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101526291
IO - BMJ Case Rep
SB - Index Medicus
CP - England
MH - *Adenocarcinoma/co [Complications]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Female
MH - Humans
MH - *Lung Neoplasms/co [Complications]
MH - Middle Aged
MH - *Thyroiditis/ci [Chemically Induced]
MH - Thyrotoxicosis/et [Etiology]
AB - Thyroiditis is characterised by transient hyperthyroidism, followed sometimes by hypothyroidism, and then recovery. We report a case of painless drug-induced thyroiditis-in a patient with no history of any thyroid disorder-treated with Nivolumab (an IgG4 monoclonal antibody against Programmed Death Receptor 1). The purpose of this case report is to increase awareness among clinicians regarding this possible adverse effect from Nivolumab, and discuss the possible pathophysiology and management strategies in such patients.
AB - Copyright 2016 BMJ Publishing Group Ltd.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 31YO63LBSN (nivolumab)
ES - 1757-790X
IL - 1757-790X
DI - bcr2015213692
DI - bcr-2015-213692
DO - https://dx.doi.org/10.1136/bcr-2015-213692
PT - Case Reports
PT - Journal Article
ID - 26733436 [pubmed]
ID - bcr-2015-213692 [pii]
ID - 10.1136/bcr-2015-213692 [doi]
PP - epublish
LG - English
EP - 20160105
DP - 2016 Jan 05
DC - 20160106
EZ - 2016/01/07 06:00
DA - 2016/10/11 06:00
DT - 2016/01/07 06:00
YR - 2016
ED - 20161010
RD - 20161230
UP - 20161230
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26733436
<94. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26681547
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Rossi E
AU - Sgambato A
AU - De Chiara G
AU - Casaluce F
AU - Losanno T
AU - Sacco PC
AU - Santabarbara G
AU - Gridelli C
FA - Rossi, Emanuela
FA - Sgambato, Assunta
FA - De Chiara, Giovanni
FA - Casaluce, Francesca
FA - Losanno, Tania
FA - Sacco, Paola Claudia
FA - Santabarbara, Giuseppe
FA - Gridelli, Cesare
IN - Rossi, Emanuela. a Division of Medical Oncology , "S. G. Moscati" Hospital , Avellino , Italy.
IN - Sgambato, Assunta. b Department of Clinical and Experimental Medicine , Second University of Naples , Naples , Italy.
IN - De Chiara, Giovanni. c Division of Pathologic Anatomy , "S. G. Moscati" Hospital , Avellino , Italy.
IN - Casaluce, Francesca. b Department of Clinical and Experimental Medicine , Second University of Naples , Naples , Italy.
IN - Losanno, Tania. d Department of Experimental Medicine , "Sapienza" University , Rome , Italy.
IN - Sacco, Paola Claudia. a Division of Medical Oncology , "S. G. Moscati" Hospital , Avellino , Italy.
IN - Santabarbara, Giuseppe. a Division of Medical Oncology , "S. G. Moscati" Hospital , Avellino , Italy.
IN - Gridelli, Cesare. a Division of Medical Oncology , "S. G. Moscati" Hospital , Avellino , Italy.
TI - Endocrinopathies induced by immune-checkpoint inhibitors in advanced non-small cell lung cancer. [Review]
SO - Expert Review of Clinical Pharmacology. 9(3):419-28, 2016
AS - Expert Rev Clin Pharmacol. 9(3):419-28, 2016
NJ - Expert review of clinical pharmacology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101278296
IO - Expert Rev Clin Pharmacol
SB - Index Medicus
CP - England
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/pd [Pharmacology]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/pd [Pharmacology]
MH - Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - Antigens, CD274/ai [Antagonists & Inhibitors]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/pd [Pharmacology]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Carcinoma, Non-Small-Cell Lung/im [Immunology]
MH - Carcinoma, Non-Small-Cell Lung/pa [Pathology]
MH - *Endocrine System Diseases/ci [Chemically Induced]
MH - Endocrine System Diseases/di [Diagnosis]
MH - Endocrine System Diseases/th [Therapy]
MH - Humans
MH - *Immunotherapy/ae [Adverse Effects]
MH - Immunotherapy/mt [Methods]
MH - Lung Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/im [Immunology]
MH - Lung Neoplasms/pa [Pathology]
MH - Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
KW - CTLA-4; NSCLC; PD-1; PD-L1; endocrine toxicities; immunotherapy
AB - The advent of immunotherapy has recently expanded the therapeutic options in advanced non-small cell lung cancer (NSCLC). In these patients, the recent efficacy demonstration of antibodies against immune checkpoints: the anti-programmed death-1 (PD-1) and anti-programmed death ligand-1 (PD-L1), has led to approval of nivolumab and pembrolizumab (anti-PD-1) in the treatment of advanced NSCLC. The mechanism of action of checkpoint inhibitors explains the development of autoimmune diseases as a side-effect of these medications. Among these, a spectrum of endocrine disorders has been also reported. This manuscript focuses particularly on endocrine disorders induced by immuno-checkpoint inhibitors employed in NSCLC, in order to suggest the strategies for their diagnosis and effective management.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (CD274 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 31YO63LBSN (nivolumab)
RN - DPT0O3T46P (pembrolizumab)
ES - 1751-2441
IL - 1751-2433
DO - https://dx.doi.org/10.1586/17512433.2016.1133289
PT - Journal Article
PT - Review
ID - 26681547 [pubmed]
ID - 10.1586/17512433.2016.1133289 [doi]
PP - ppublish
LG - English
EP - 20160206
DP - 2016
DC - 20160225
EZ - 2015/12/19 06:00
DA - 2016/10/08 06:00
DT - 2015/12/19 06:00
YR - 2016
ED - 20161007
RD - 20161008
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26681547
<95. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26681547
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Rossi E
AU - Sgambato A
AU - De Chiara G
AU - Casaluce F
AU - Losanno T
AU - Sacco PC
AU - Santabarbara G
AU - Gridelli C
FA - Rossi, Emanuela
FA - Sgambato, Assunta
FA - De Chiara, Giovanni
FA - Casaluce, Francesca
FA - Losanno, Tania
FA - Sacco, Paola Claudia
FA - Santabarbara, Giuseppe
FA - Gridelli, Cesare
IN - Rossi, Emanuela. a Division of Medical Oncology , "S. G. Moscati" Hospital , Avellino , Italy.
IN - Sgambato, Assunta. b Department of Clinical and Experimental Medicine , Second University of Naples , Naples , Italy.
IN - De Chiara, Giovanni. c Division of Pathologic Anatomy , "S. G. Moscati" Hospital , Avellino , Italy.
IN - Casaluce, Francesca. b Department of Clinical and Experimental Medicine , Second University of Naples , Naples , Italy.
IN - Losanno, Tania. d Department of Experimental Medicine , "Sapienza" University , Rome , Italy.
IN - Sacco, Paola Claudia. a Division of Medical Oncology , "S. G. Moscati" Hospital , Avellino , Italy.
IN - Santabarbara, Giuseppe. a Division of Medical Oncology , "S. G. Moscati" Hospital , Avellino , Italy.
IN - Gridelli, Cesare. a Division of Medical Oncology , "S. G. Moscati" Hospital , Avellino , Italy.
TI - Endocrinopathies induced by immune-checkpoint inhibitors in advanced non-small cell lung cancer. [Review]
SO - Expert Review of Clinical Pharmacology. 9(3):419-28, 2016
AS - Expert Rev Clin Pharmacol. 9(3):419-28, 2016
NJ - Expert review of clinical pharmacology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101278296
IO - Expert Rev Clin Pharmacol
SB - Index Medicus
CP - England
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/pd [Pharmacology]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/pd [Pharmacology]
MH - Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - Antigens, CD274/ai [Antagonists & Inhibitors]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/pd [Pharmacology]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Carcinoma, Non-Small-Cell Lung/im [Immunology]
MH - Carcinoma, Non-Small-Cell Lung/pa [Pathology]
MH - *Endocrine System Diseases/ci [Chemically Induced]
MH - Endocrine System Diseases/di [Diagnosis]
MH - Endocrine System Diseases/th [Therapy]
MH - Humans
MH - *Immunotherapy/ae [Adverse Effects]
MH - Immunotherapy/mt [Methods]
MH - Lung Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/im [Immunology]
MH - Lung Neoplasms/pa [Pathology]
MH - Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
KW - CTLA-4; NSCLC; PD-1; PD-L1; endocrine toxicities; immunotherapy
AB - The advent of immunotherapy has recently expanded the therapeutic options in advanced non-small cell lung cancer (NSCLC). In these patients, the recent efficacy demonstration of antibodies against immune checkpoints: the anti-programmed death-1 (PD-1) and anti-programmed death ligand-1 (PD-L1), has led to approval of nivolumab and pembrolizumab (anti-PD-1) in the treatment of advanced NSCLC. The mechanism of action of checkpoint inhibitors explains the development of autoimmune diseases as a side-effect of these medications. Among these, a spectrum of endocrine disorders has been also reported. This manuscript focuses particularly on endocrine disorders induced by immuno-checkpoint inhibitors employed in NSCLC, in order to suggest the strategies for their diagnosis and effective management.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (CD274 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 31YO63LBSN (nivolumab)
RN - DPT0O3T46P (pembrolizumab)
ES - 1751-2441
IL - 1751-2433
DO - https://dx.doi.org/10.1586/17512433.2016.1133289
PT - Journal Article
PT - Review
ID - 26681547 [pubmed]
ID - 10.1586/17512433.2016.1133289 [doi]
PP - ppublish
LG - English
EP - 20160206
DP - 2016
DC - 20160225
EZ - 2015/12/19 06:00
DA - 2016/10/08 06:00
DT - 2015/12/19 06:00
YR - 2016
ED - 20161007
RD - 20161230
UP - 20161230
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26681547
<96. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27688833
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Bilir SP
AU - Ma Q
AU - Zhao Z
AU - Wehler E
AU - Munakata J
AU - Barber B
FA - Bilir, S Pinar
FA - Ma, Qiufei
FA - Zhao, Zhongyun
FA - Wehler, Elizabeth
FA - Munakata, Julie
FA - Barber, Beth
IN - Bilir, S Pinar. Director, Health Economics and Outcomes Research, IMS Health, San Francisco, CA.
IN - Ma, Qiufei. Senior Manager, Amgen, Thousand Oaks, CA.
IN - Zhao, Zhongyun. Director, Amgen.
IN - Wehler, Elizabeth. Senior Consultant, Health Economics and Outcomes Research, IMS Health, Plymouth Meeting, PA.
IN - Munakata, Julie. General Manager, Medical and Scientific Services, Health Economics and Outcomes Research, IMS Health, San Francisco.
IN - Barber, Beth. Executive Director, Amgen.
TI - Economic Burden of Toxicities Associated with Treating Metastatic Melanoma in the United States.
SO - American Health & Drug Benefits. 9(4):203-13, 2016 Jun
AS - Am. health drug benefits. 9(4):203-13, 2016 Jun
NJ - American health & drug benefits
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 101479877
IO - Am Health Drug Benefits
CP - United States
KW - adverse events; chemotherapy; cost analysis; cost of illness; dabrafenib; dacarbazine; drug-related side effects; interleukin-2; ipilimumab; metastatic melanoma; talimogene laherparepvec; temozolomide; toxicities; trametinib; vemurafenib
AB - BACKGROUND: Little has been reported on the costs of managing the adverse events (AEs) associated with current therapies for patients with regional or distant metastatic melanoma.
AB - OBJECTIVES: To identify treatment-related AEs in patients with metastatic melanoma and to estimate the associated costs of treating these AEs in the United States.
AB - METHODS: A cost-estimation study for AEs associated with treatment of metastatic melanoma was conducted from 2012 to 2013 by identifying grades 3 and 4 AEs through the use of a comprehensive search of drug labels and English-language, published phase 2/3 studies in PubMed, conference abstracts, and the National Comprehensive Cancer Network guidelines. Resource utilization for the management of each type of AE in the outpatient setting was obtained via interviews with 5 melanoma specialists in the United States. Unit costs for an AE associated with melanoma treatment in the outpatient setting were assigned using Medicare reimbursement rates to obtain these costs. Hospitalization and length-of-stay costs were estimated for each associated AE using the large national claims database Optum Clinformatics Data Mart for the period of July 1, 2004, to November 30, 2012.
AB - RESULTS: The most common AEs associated with chemotherapies used for melanoma were neutropenia, vomiting, and anemia. The most common AEs associated with vemurafenib were cutaneous squamous-cell carcinoma or keratoacanthoma, rash, and elevated liver enzymes; the most common AEs associated with dabrafenib were cutaneous squamous-cell carcinoma and pyrexia. Trametinib was most often associated with hypertension and rash. The most common AEs with ipilimumab were immune-related diarrhea or colitis, dyspnea, anemia, vomiting, and, less frequently, hypophysitis. The most common grade 3/4 AE with talimogene laherparepvec was cellulitis. The highest treatment costs for an AE in the outpatient setting were for neutropenia ($2092), headache ($609), and peripheral neuropathy ($539). The highest mean inpatient costs for an AE were for acute myocardial infarction, sepsis, and coma, which ranged from $31,682 to $47,069. Colitis or diarrhea, cutaneous squamous-cell carcinoma, thrombocytopenia, hyponatremia, oliguria or anuria, hypertension, anemia, and elevated liver enzymes were associated with mean costs for hospitalization ranging from $19,122 to $26,861.
AB - CONCLUSION: The costs of managing treatment-related AEs in patients with metastatic melanoma are substantial. Effective treatments with improved safety profiles may help to reduce these costs. Until real-world evidence for the costs associated with treatment toxicity is available in the outpatient and inpatient settings, the costs estimated in this study can help inform decision makers about the cost-effectiveness of managing patients with metastatic melanoma.
IS - 1942-2962
IL - 1942-2962
PT - Journal Article
ID - 27688833 [pubmed]
ID - PMC5004818 [pmc]
PP - ppublish
LG - English
DP - 2016 Jun
DC - 20160930
EZ - 2016/10/01 06:00
DA - 2016/10/01 06:01
DT - 2016/10/01 06:00
YR - 2016
ED - 20160930
RD - 20161011
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27688833
<97. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26691441
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Katsuta E
AU - Tanaka S
AU - Mogushi K
AU - Shimada S
AU - Akiyama Y
AU - Aihara A
AU - Matsumura S
AU - Mitsunori Y
AU - Ban D
AU - Ochiai T
AU - Kudo A
AU - Fukamachi H
AU - Tanaka H
AU - Nakayama K
AU - Arii S
AU - Tanabe M
FA - Katsuta, Eriko
FA - Tanaka, Shinji
FA - Mogushi, Kaoru
FA - Shimada, Shu
FA - Akiyama, Yoshimitsu
FA - Aihara, Arihiro
FA - Matsumura, Satoshi
FA - Mitsunori, Yusuke
FA - Ban, Daisuke
FA - Ochiai, Takanori
FA - Kudo, Atsushi
FA - Fukamachi, Hiroshi
FA - Tanaka, Hiroshi
FA - Nakayama, Koh
FA - Arii, Shigeki
FA - Tanabe, Minoru
IN - Katsuta, Eriko. Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Tanaka, Shinji. Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Mogushi, Kaoru. Department of Bioinformatics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Shimada, Shu. Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Akiyama, Yoshimitsu. Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Aihara, Arihiro. Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Matsumura, Satoshi. Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Mitsunori, Yusuke. Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Ban, Daisuke. Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Ochiai, Takanori. Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Kudo, Atsushi. Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Fukamachi, Hiroshi. Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Tanaka, Hiroshi. Department of Bioinformatics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Nakayama, Koh. Oxygen Biology Unit, Frontier Research Laboratory, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Arii, Shigeki. Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Tanabe, Minoru. Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
TI - CD73 as a therapeutic target for pancreatic neuroendocrine tumor stem cells.
SO - International Journal of Oncology. 48(2):657-69, 2016 Feb
AS - Int J Oncol. 48(2):657-69, 2016 Feb
NJ - International journal of oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cx5, 9306042
IO - Int. J. Oncol.
SB - Index Medicus
CP - Greece
MH - *5'-Nucleotidase/me [Metabolism]
MH - Animals
MH - Biomarkers, Tumor/me [Metabolism]
MH - Cell Line, Tumor
MH - Cell Movement/ph [Physiology]
MH - Female
MH - GPI-Linked Proteins/me [Metabolism]
MH - Gene Expression/ph [Physiology]
MH - Humans
MH - Mice
MH - *Neoplastic Stem Cells/me [Metabolism]
MH - *Neuroendocrine Tumors/me [Metabolism]
MH - *Pancreatic Neoplasms/me [Metabolism]
AB - Identification and purification of cancer stem cells (CSCs) lead to the discovery of novel therapeutic targets; however, there has been no study on isolation of the CSC population among pancreatic neuroendocrine tumors (pNETs). This study aimed to identify pNET CSCs and to characterize a therapeutic candidate for pNET CSCs. We identified CSCs by aldehyde dehydrogenase (ALDH) activity in pNET clinical specimens and cell lines. We verified whether or not these cells have the stemness property in vivo and in vitro. ALDHhigh cells, but not control bulk cells, formed spheres, proliferated under hypoxic condition as well as normoxic condition and promoted cell motility, which are features of CSCs. Injection of as few as 10 ALDHhigh cells led to subcutaneous tumor formation, and 105 ALDHhigh cells, but not control bulk cells, established metastases in mice. Comprehensive gene expression analysis revealed that genes associated with mesenchymal stem cells, including CD73, were overexpressed in ALDHhigh cells. Additionally, the in vitro and in vivo effects of an inhibitor of CD73 were investigated. The CD73 inhibitor APCP significantly attenuated in vitro sphere formation and cell motility, as well as in vivo tumor growth observed for ALDHhigh cells. Finally, its expression was evaluated using clinical pNET tissue samples. Immunohistochemical analysis of clinical tissue samples demonstrated CD73 expression was significantly correlated with the invasion into adjacent organs. Since recent studies revealed CD73 as a potential biomarker of anti-PD-1 immune checkpoint therapy, CD73 might be a promising therapeutic target for pNET CSCs.
RN - 0 (Biomarkers, Tumor)
RN - 0 (GPI-Linked Proteins)
RN - EC 3-1-3-5 (5'-Nucleotidase)
RN - EC 3-1-3-5 (NT5E protein, human)
ES - 1791-2423
IL - 1019-6439
DO - https://dx.doi.org/10.3892/ijo.2015.3299
PT - Journal Article
ID - 26691441 [pubmed]
ID - 10.3892/ijo.2015.3299 [doi]
PP - ppublish
PH - 2015/09/26 [received]
PH - 2015/11/05 [accepted]
LG - English
EP - 20151218
DP - 2016 Feb
DC - 20151228
EZ - 2015/12/23 06:00
DA - 2016/09/28 06:00
DT - 2015/12/23 06:00
YR - 2016
ED - 20160927
RD - 20151228
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26691441
<98. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26926680
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wilgenhof S
AU - Corthals J
AU - Heirman C
AU - van Baren N
AU - Lucas S
AU - Kvistborg P
AU - Thielemans K
AU - Neyns B
FA - Wilgenhof, Sofie
FA - Corthals, Jurgen
FA - Heirman, Carlo
FA - van Baren, Nicolas
FA - Lucas, Sophie
FA - Kvistborg, Pia
FA - Thielemans, Kris
FA - Neyns, Bart
IN - Wilgenhof, Sofie. Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Universite Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
IN - Corthals, Jurgen. Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Universite Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
IN - Heirman, Carlo. Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Universite Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
IN - van Baren, Nicolas. Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Universite Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
IN - Lucas, Sophie. Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Universite Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
IN - Kvistborg, Pia. Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Universite Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
IN - Thielemans, Kris. Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Universite Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
IN - Neyns, Bart. Sofie Wilgenhof, Kris Thielemans, and Bart Neyns, Universitair Ziekenhuis Brussel; Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Kris Thielemans, and Bart Neyns, Vrije Universiteit Brussel; Nicolas van Baren, Ludwig Institute for Cancer Research; Sophie Lucas, de Duve Institute, Universite Catholique de Louvain, Brussels, Belgium; and Pia Kvistborg, The Netherlands Cancer Institute, Amsterdam, the Netherlands. Bart.Neyns@uzbrussel.be.
TI - Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma.
SO - Journal of Clinical Oncology. 34(12):1330-8, 2016 Apr 20
AS - J Clin Oncol. 34(12):1330-8, 2016 Apr 20
NJ - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - jco, 8309333
IO - J. Clin. Oncol.
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Cells, Cultured
MH - Chemotherapy, Adjuvant
MH - Dendritic Cells/im [Immunology]
MH - Dendritic Cells/me [Metabolism]
MH - *Dendritic Cells/tr [Transplantation]
MH - Disease Progression
MH - Disease-Free Survival
MH - Drug Administration Schedule
MH - *Electroporation
MH - Female
MH - Genetic Therapy/ae [Adverse Effects]
MH - *Genetic Therapy/mt [Methods]
MH - Genetic Therapy/mo [Mortality]
MH - Humans
MH - Kaplan-Meier Estimate
MH - Male
MH - Melanoma/ge [Genetics]
MH - Melanoma/im [Immunology]
MH - Melanoma/mo [Mortality]
MH - *Melanoma/th [Therapy]
MH - Middle Aged
MH - Proportional Hazards Models
MH - *RNA, Messenger/ge [Genetics]
MH - RNA, Messenger/me [Metabolism]
MH - Skin Neoplasms/ge [Genetics]
MH - Skin Neoplasms/im [Immunology]
MH - Skin Neoplasms/mo [Mortality]
MH - *Skin Neoplasms/th [Therapy]
MH - Time Factors
MH - Transplantation, Autologous
MH - Treatment Outcome
MH - Young Adult
AB - PURPOSE: Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic mRNA (TriMixDC-MEL) are immunogenic and have antitumor activity as a monotherapy in patients with pretreated advanced melanoma. Ipilimumab, an immunoglobulin G1 monoclonal antibody directed against the cytotoxic T-lymphocyte-associated protein 4 receptor that counteracts physiologic suppression of T-cell function, improves the overall survival of patients with advanced melanoma. This phase II study investigated the combination of TriMixDC-MEL and ipilimumab in patients with pretreated advanced melanoma.
AB - PATIENTS AND METHODS: Thirty-nine patients were treated with TriMixDC-MEL (4 x 10(6) cells administered intradermally and 20 x 10(6) cells administered intravenously) plus ipilimumab (10 mg/kg every 3 weeks for a total of four administrations, followed by maintenance therapy every 12 weeks in patients who remained progression free). Six-month disease control rate according to the immune-related response criteria served as the primary end point.
AB - RESULTS: The 6-month disease control rate was 51% (95% CI, 36% to 67%), and the overall tumor response rate was 38% (including eight complete and seven partial responses). Seven complete responses and one partial tumor response are ongoing after a median follow-up time of 36 months (range, 22 to 43 months). The most common treatment-related adverse events (all grades) consisted of local DC injection site skin reactions (100%), transient post-DC infusion chills (38%) and flu-like symptoms (84%), dermatitis (64%), hepatitis (13%), hypophysitis (15%), and diarrhea/colitis (15%). Grade 3 or 4 immune-related adverse events occurred in 36% of patients. There was no grade 5 adverse event.
AB - CONCLUSION: The combination of TriMixDC-MEL and ipilimumab is tolerable and results in an encouraging rate of highly durable tumor responses in patients with pretreated advanced melanoma.
AB - Copyright © 2016 by American Society of Clinical Oncology.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (RNA, Messenger)
RN - 6T8C155666 (ipilimumab)
ES - 1527-7755
IL - 0732-183X
DI - JCO.2015.63.4121
DO - https://dx.doi.org/10.1200/JCO.2015.63.4121
PT - Clinical Trial, Phase II
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26926680 [pubmed]
ID - JCO.2015.63.4121 [pii]
ID - 10.1200/JCO.2015.63.4121 [doi]
PP - ppublish
LG - English
EP - 20160229
DP - 2016 Apr 20
DC - 20160414
EZ - 2016/03/02 06:00
DA - 2016/09/07 06:00
DT - 2016/03/02 06:00
YR - 2016
ED - 20160906
RD - 20161126
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26926680
<99. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27555886
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Iyevleva AG
AU - Imyanitov EN
FA - Iyevleva, Aglaya G
FA - Imyanitov, Evgeny N
IN - Iyevleva, Aglaya G. N.N. Petrov Institute of Oncology, Pesochny-2, St. Petersburg, 197758 Russia ; St. Petersburg Pediatric Medical University, St. Petersburg, 194100 Russia.
IN - Imyanitov, Evgeny N. N.N. Petrov Institute of Oncology, Pesochny-2, St. Petersburg, 197758 Russia ; St. Petersburg Pediatric Medical University, St. Petersburg, 194100 Russia ; I.I. Mechnikov North-Western Medical University, St. Petersburg, 191015 Russia ; St. Petersburg State University, St. Petersburg, 199034 Russia.
TI - Cytotoxic and targeted therapy for hereditary cancers. [Review]
SO - Hereditary Cancer in Clinical Practice. 14(1):17, 2016
AS - Hered. Cancer Clin. Pract.. 14(1):17, 2016
NJ - Hereditary cancer in clinical practice
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101231179
IO - Hered Cancer Clin Pract
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994296
CP - Poland
KW - BRCA1; BRCA2; Breast cancer; Colorectal cancer; Cytotoxic therapy; Familial cancer; Hereditary cancer syndromes; Ovarian cancer; Predictive markers; Targeted therapy
AB - There is a number of drugs demonstrating specific activity towards hereditary cancers. For example, tumors in BRCA1/2 mutation carriers usually arise via somatic inactivation of the remaining BRCA allele, which makes them particularly sensitive to platinum-based drugs, PARP inhibitors (PARPi), mitomycin C, liposomal doxorubicin, etc. There are several molecular assays for BRCA-ness, which permit to reveal BRCA-like phenocopies among sporadic tumors and thus extend clinical indications for the use of BRCA-specific therapies. Retrospective data on high-dose chemotherapy deserve consideration given some unexpected instances of cure from metastatic disease among BRCA1/2-mutated patients. Hereditary non-polyposis colorectal cancer (HNPCC) is characterized by high-level microsatellite instability (MSI-H), increased antigenicity and elevated expression of immunosuppressive molecules. Recent clinical trial demonstrated tumor responses in HNPCC patients treated by the immune checkpoint inhibitor pembrolizumab. There are successful clinical trials on the use of novel targeted agents for the treatment or rare cancer syndromes, e.g. RET inhibitors for hereditary medullary thyroid cancer, mTOR inhibitors for tumors arising in patients with tuberous sclerosis (TSC), and SMO inhibitors for basal-cell nevus syndrome. Germ-line mutation tests will be increasingly used in the future for the choice of the optimal therapy, therefore turnaround time for these laboratory procedures needs to be significantly reduced to ensure proper treatment planning.
IS - 1731-2302
IL - 1731-2302
DI - 57
DO - https://dx.doi.org/10.1186/s13053-016-0057-2
PT - Journal Article
PT - Review
ID - 27555886 [pubmed]
ID - 10.1186/s13053-016-0057-2 [doi]
ID - 57 [pii]
ID - PMC4994296 [pmc]
PP - epublish
PH - 2016/05/12 [received]
PH - 2016/06/27 [accepted]
LG - English
EP - 20160823
DP - 2016
DC - 20160824
EZ - 2016/08/25 06:00
DA - 2016/08/25 06:01
DT - 2016/08/25 06:00
YR - 2016
ED - 20160824
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27555886
<100. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26585231
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Kausar T
AU - Schreiber JS
AU - Karnak D
AU - Parsels LA
AU - Parsels JD
AU - Davis MA
AU - Zhao L
AU - Maybaum J
AU - Lawrence TS
AU - Morgan MA
FA - Kausar, Tasneem
FA - Schreiber, Jason S
FA - Karnak, David
FA - Parsels, Leslie A
FA - Parsels, Joshua D
FA - Davis, Mary A
FA - Zhao, Lili
FA - Maybaum, Jonathan
FA - Lawrence, Theodore S
FA - Morgan, Meredith A
IN - Kausar, Tasneem. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Schreiber, Jason S. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Karnak, David. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Parsels, Leslie A. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Parsels, Joshua D. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Davis, Mary A. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Zhao, Lili. Biostatistics Unit, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109.
IN - Maybaum, Jonathan. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Lawrence, Theodore S. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Morgan, Meredith A. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109. Electronic address: mmccrack@med.umich.edu.
TI - Sensitization of Pancreatic Cancers to Gemcitabine Chemoradiation by WEE1 Kinase Inhibition Depends on Homologous Recombination Repair.
SO - Neoplasia (New York). 17(10):757-66, 2015 Oct
AS - Neoplasia. 17(10):757-66, 2015 Oct
NJ - Neoplasia (New York, N.Y.)
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - dru, 100886622
IO - Neoplasia
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4656803
SB - Index Medicus
CP - United States
MH - Animals
MH - Apoptosis/de [Drug Effects]
MH - Blotting, Western
MH - *Cell Cycle Proteins/ai [Antagonists & Inhibitors]
MH - Cell Cycle Proteins/me [Metabolism]
MH - Cell Proliferation/de [Drug Effects]
MH - Chemoradiotherapy
MH - DNA Damage/de [Drug Effects]
MH - *Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Female
MH - Flow Cytometry
MH - Fluorescent Antibody Technique
MH - Humans
MH - Immunoenzyme Techniques
MH - Mice
MH - Mice, Nude
MH - *Nuclear Proteins/ai [Antagonists & Inhibitors]
MH - Nuclear Proteins/me [Metabolism]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - Phosphorylation/de [Drug Effects]
MH - *Protein Kinase Inhibitors/pd [Pharmacology]
MH - *Protein-Tyrosine Kinases/ai [Antagonists & Inhibitors]
MH - Protein-Tyrosine Kinases/me [Metabolism]
MH - *Radiation-Sensitizing Agents/pd [Pharmacology]
MH - *Recombinational DNA Repair/de [Drug Effects]
MH - Tumor Cells, Cultured
MH - Xenograft Model Antitumor Assays
AB - To improve the efficacy of chemoradiation therapy for locally advanced pancreatic cancer and begin to establish patient selection criteria, we investigated the combination of the WEE1 inhibitor AZD1775 with gemcitabine-radiation in homologous recombination (HR) repair proficient and deficient pancreatic cancers. Sensitization to gemcitabine-radiation by AZD1775 was assessed in pancreatic cancer cells by clonogenic survival and in patient-derived xenografts by tumor growth. The contributions of HR repair inhibition and G2 checkpoint abrogation to sensitization were assessed by gammaH2AX, BRCA2 manipulation, and RAD51 focus formation and pHistone H3 flow cytometry, respectively. We found that AZD1775 sensitized to gemcitabine-radiation in BRCA2 wild-type but not BRCA2 mutant pancreatic cancer cells. In all cells, AZD1775 caused inhibition of CDK1 phosphorylation and G2 checkpoint abrogation. However, sensitization by AZD1775 was associated with persistent gammaH2AX and inhibition of RAD51 focus formation. In HR-proficient (BRCA2 wild-type) or -deficient (BRAC2 null) isogenic cells, AZD1775 sensitized to gemcitabine-radiation in BRCA2 wild-type, but not in BRCA2 null cells, despite significant G2 checkpoint abrogation. In patient-derived pancreatic tumor xenografts, AZD1775 significantly inhibited tumor growth and impaired RAD51 focus formation in response to gemcitabine-radiation. In conclusion, WEE1 inhibition by AZD1775 is an effective strategy for sensitizing pancreatic cancers to gemcitabine chemoradiation. Although this sensitization is accompanied by inhibition of CDK1 phosphorylation and G2 checkpoint abrogation, this mechanism is not sufficient for sensitization. Our findings demonstrate that sensitization to chemoradiation by WEE1 inhibition results from inhibition of HR repair and suggest that patient tumors without underlying HR defects would benefit most from this therapy.
AB - Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
RN - 0 (Cell Cycle Proteins)
RN - 0 (Nuclear Proteins)
RN - 0 (Protein Kinase Inhibitors)
RN - 0 (Radiation-Sensitizing Agents)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7-10-1 (Protein-Tyrosine Kinases)
RN - EC 2-7-10-2 (WEE1 protein, human)
ES - 1476-5586
IL - 1476-5586
DI - S1476-5586(15)00119-0
DO - https://dx.doi.org/10.1016/j.neo.2015.09.006
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 26585231 [pubmed]
ID - S1476-5586(15)00119-0 [pii]
ID - 10.1016/j.neo.2015.09.006 [doi]
ID - PMC4656803 [pmc]
PP - ppublish
PH - 2015/08/14 [received]
PH - 2015/09/18 [revised]
PH - 2015/09/24 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT02037230
SL - https://clinicaltrials.gov/search/term=NCT02037230
GI - No: R01CA163895
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA046592
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01CA138723
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA138723
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA130810
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA163895
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50CA130810
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2015 Oct
DC - 20151120
EZ - 2015/11/21 06:00
DA - 2016/08/24 06:00
DT - 2015/11/21 06:00
YR - 2015
ED - 20160823
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26585231
<101. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26585231
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Kausar T
AU - Schreiber JS
AU - Karnak D
AU - Parsels LA
AU - Parsels JD
AU - Davis MA
AU - Zhao L
AU - Maybaum J
AU - Lawrence TS
AU - Morgan MA
FA - Kausar, Tasneem
FA - Schreiber, Jason S
FA - Karnak, David
FA - Parsels, Leslie A
FA - Parsels, Joshua D
FA - Davis, Mary A
FA - Zhao, Lili
FA - Maybaum, Jonathan
FA - Lawrence, Theodore S
FA - Morgan, Meredith A
IN - Kausar, Tasneem. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Schreiber, Jason S. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Karnak, David. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Parsels, Leslie A. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Parsels, Joshua D. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Davis, Mary A. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Zhao, Lili. Biostatistics Unit, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109.
IN - Maybaum, Jonathan. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Lawrence, Theodore S. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109.
IN - Morgan, Meredith A. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109. Electronic address: mmccrack@med.umich.edu.
TI - Sensitization of Pancreatic Cancers to Gemcitabine Chemoradiation by WEE1 Kinase Inhibition Depends on Homologous Recombination Repair.
SO - Neoplasia (New York). 17(10):757-66, 2015 Oct
AS - Neoplasia. 17(10):757-66, 2015 Oct
NJ - Neoplasia (New York, N.Y.)
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - dru, 100886622
IO - Neoplasia
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4656803
SB - Index Medicus
CP - United States
MH - Animals
MH - Apoptosis/de [Drug Effects]
MH - Blotting, Western
MH - *Cell Cycle Proteins/ai [Antagonists & Inhibitors]
MH - Cell Cycle Proteins/me [Metabolism]
MH - Cell Proliferation/de [Drug Effects]
MH - Chemoradiotherapy
MH - DNA Damage/de [Drug Effects]
MH - *Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Female
MH - Flow Cytometry
MH - Fluorescent Antibody Technique
MH - Humans
MH - Immunoenzyme Techniques
MH - Mice
MH - Mice, Nude
MH - *Nuclear Proteins/ai [Antagonists & Inhibitors]
MH - Nuclear Proteins/me [Metabolism]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - Phosphorylation/de [Drug Effects]
MH - *Protein Kinase Inhibitors/pd [Pharmacology]
MH - *Protein-Tyrosine Kinases/ai [Antagonists & Inhibitors]
MH - Protein-Tyrosine Kinases/me [Metabolism]
MH - *Radiation-Sensitizing Agents/pd [Pharmacology]
MH - *Recombinational DNA Repair/de [Drug Effects]
MH - Tumor Cells, Cultured
MH - Xenograft Model Antitumor Assays
AB - To improve the efficacy of chemoradiation therapy for locally advanced pancreatic cancer and begin to establish patient selection criteria, we investigated the combination of the WEE1 inhibitor AZD1775 with gemcitabine-radiation in homologous recombination (HR) repair proficient and deficient pancreatic cancers. Sensitization to gemcitabine-radiation by AZD1775 was assessed in pancreatic cancer cells by clonogenic survival and in patient-derived xenografts by tumor growth. The contributions of HR repair inhibition and G2 checkpoint abrogation to sensitization were assessed by gammaH2AX, BRCA2 manipulation, and RAD51 focus formation and pHistone H3 flow cytometry, respectively. We found that AZD1775 sensitized to gemcitabine-radiation in BRCA2 wild-type but not BRCA2 mutant pancreatic cancer cells. In all cells, AZD1775 caused inhibition of CDK1 phosphorylation and G2 checkpoint abrogation. However, sensitization by AZD1775 was associated with persistent gammaH2AX and inhibition of RAD51 focus formation. In HR-proficient (BRCA2 wild-type) or -deficient (BRAC2 null) isogenic cells, AZD1775 sensitized to gemcitabine-radiation in BRCA2 wild-type, but not in BRCA2 null cells, despite significant G2 checkpoint abrogation. In patient-derived pancreatic tumor xenografts, AZD1775 significantly inhibited tumor growth and impaired RAD51 focus formation in response to gemcitabine-radiation. In conclusion, WEE1 inhibition by AZD1775 is an effective strategy for sensitizing pancreatic cancers to gemcitabine chemoradiation. Although this sensitization is accompanied by inhibition of CDK1 phosphorylation and G2 checkpoint abrogation, this mechanism is not sufficient for sensitization. Our findings demonstrate that sensitization to chemoradiation by WEE1 inhibition results from inhibition of HR repair and suggest that patient tumors without underlying HR defects would benefit most from this therapy.
AB - Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
RN - 0 (Cell Cycle Proteins)
RN - 0 (Nuclear Proteins)
RN - 0 (Protein Kinase Inhibitors)
RN - 0 (Radiation-Sensitizing Agents)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7-10-1 (Protein-Tyrosine Kinases)
RN - EC 2-7-10-2 (WEE1 protein, human)
ES - 1476-5586
IL - 1476-5586
DI - S1476-5586(15)00119-0
DO - https://dx.doi.org/10.1016/j.neo.2015.09.006
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 26585231 [pubmed]
ID - S1476-5586(15)00119-0 [pii]
ID - 10.1016/j.neo.2015.09.006 [doi]
ID - PMC4656803 [pmc]
PP - ppublish
PH - 2015/08/14 [received]
PH - 2015/09/18 [revised]
PH - 2015/09/24 [accepted]
GI - No: R01CA163895
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA046592
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01CA138723
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA138723
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA130810
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA163895
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50CA130810
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2015 Oct
DC - 20151120
EZ - 2015/11/21 06:00
DA - 2016/08/24 06:00
DT - 2015/11/21 06:00
YR - 2015
ED - 20160823
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26585231
<102. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26561720
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Awuah SG
AU - Zheng YR
AU - Bruno PM
AU - Hemann MT
AU - Lippard SJ
FA - Awuah, Samuel G
FA - Zheng, Yao-Rong
FA - Bruno, Peter M
FA - Hemann, Michael T
FA - Lippard, Stephen J
IN - Awuah, Samuel G. Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
IN - Zheng, Yao-Rong. Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
IN - Bruno, Peter M. The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
IN - Hemann, Michael T. The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
IN - Lippard, Stephen J. Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
IN - Lippard, Stephen J. The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
TI - A Pt(IV) Pro-drug Preferentially Targets Indoleamine-2,3-dioxygenase, Providing Enhanced Ovarian Cancer Immuno-Chemotherapy.[Erratum appears in J Am Chem Soc. 2016 Mar 9;138(9):3250; PMID: 26916820]
SO - Journal of the American Chemical Society. 137(47):14854-7, 2015 Dec 02
AS - J Am Chem Soc. 137(47):14854-7, 2015 Dec 02
NJ - Journal of the American Chemical Society
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - h59, 7503056
IO - J. Am. Chem. Soc.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772771
OI - Source: NLM. NIHMS757395
SB - Index Medicus
CP - United States
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Female
MH - Humans
MH - *Immunotherapy
MH - *Indoleamine-Pyrrole 2,3,-Dioxygenase/me [Metabolism]
MH - Ovarian Neoplasms/dt [Drug Therapy]
MH - *Ovarian Neoplasms/th [Therapy]
AB - Expression of indoleamine-2,3-dioxygenase (IDO), an immunosuppressive enzyme in human tumors, leads to immune evasion and tumor tolerance. IDO is therefore a tumor immunotherapeutic target, and several IDO inhibitors are currently undergoing clinical trials. IDO inhibitors can enhance the efficacy of common cancer chemotherapeutics. Here we investigate Pt(IV)-(D)-1-methyltryptophan conjugates 1 and 2 for combined immunomodulation and DNA cross-link-triggered apoptosis for cancer "immuno-chemotherapy". Compound 2 effectively kills hormone-dependent, cisplatin-resistant human ovarian cancer cells, inhibiting IDO by transcriptional deregulation of the autocrine-signaling loop IDO-AHR-IL6, which blocks kynurenine production and promotes T-cell proliferation. Additionally, 1 and 2 display low toxicity in mice and are stable in blood. To our knowledge, this construct is the first Pt drug candidate with immune checkpoint blockade properties.
RN - 0 (Antineoplastic Agents)
RN - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
ES - 1520-5126
IL - 0002-7863
DO - https://dx.doi.org/10.1021/jacs.5b10182
PT - Journal Article
PT - Research Support, N.I.H., Extramural
ID - 26561720 [pubmed]
ID - 10.1021/jacs.5b10182 [doi]
ID - PMC4772771 [pmc]
ID - NIHMS757395 [mid]
PP - ppublish
GI - No: R01 CA034992
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R37 CA034992
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA034992
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20151118
DP - 2015 Dec 02
DC - 20151202
EZ - 2015/11/13 06:00
DA - 2016/08/23 06:00
DT - 2015/11/13 06:00
YR - 2015
ED - 20160822
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26561720
<103. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26922661
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Eigentler TK
AU - Hassel JC
AU - Berking C
AU - Aberle J
AU - Bachmann O
AU - Grunwald V
AU - Kahler KC
AU - Loquai C
AU - Reinmuth N
AU - Steins M
AU - Zimmer L
AU - Sendl A
AU - Gutzmer R
FA - Eigentler, Thomas K
FA - Hassel, Jessica C
FA - Berking, Carola
FA - Aberle, Jens
FA - Bachmann, Oliver
FA - Grunwald, Viktor
FA - Kahler, Katharina C
FA - Loquai, Carmen
FA - Reinmuth, Niels
FA - Steins, Martin
FA - Zimmer, Lisa
FA - Sendl, Anna
FA - Gutzmer, Ralf
IN - Eigentler, Thomas K. Department of Dermatology, Center for Dermatooncology, University Medical Center Tubingen, Germany. Electronic address: thomas.eigentler@med.uni-tuebingen.de.
IN - Hassel, Jessica C. Department of Dermatology, University Hospital Heidelberg, Germany. Electronic address: jessica.hassel@med.uni-heidelberg.de.
IN - Berking, Carola. Department of Dermatology and Allergy, University Hospital Munich, Munich, Germany. Electronic address: carola.berking@med.uni-muenchen.de.
IN - Aberle, Jens. Department of Internal Medicine III, University Hospital Hamburg Eppendorf, Germany. Electronic address: aberle@uke.de.
IN - Bachmann, Oliver. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany. Electronic address: bachmann.oliver@mh-hannover.de.
IN - Grunwald, Viktor. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Germany. Electronic address: Gruenwald.Victor@mh-hannover.de.
IN - Kahler, Katharina C. Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Germany. Electronic address: kckaehler@dermatology.uni-kiel.de.
IN - Loquai, Carmen. Department of Dermatology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany. Electronic address: Carmen.Loquai@unimedizin-mainz.de.
IN - Reinmuth, Niels. Department of Thoracic Oncology, LungenClinic Grosshansdorf, Germany. Electronic address: n.reinmuth@lungenclinic.de.
IN - Steins, Martin. Department of Thoracic Oncology, Thoraxklinik, University of Heidelberg, Germany. Electronic address: martin.steins@med.uni-heidelberg.de.
IN - Zimmer, Lisa. Department of Dermatology, University Hospital, University Essen-Duisburg, Germany. Electronic address: lisa.zimmer@uk-essen.de.
IN - Sendl, Anna. Bristol-Myers Squibb GmbH&KGaA, Munich, Germany. Electronic address: anna.sendl@bms.com.
IN - Gutzmer, Ralf. Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Germany. Electronic address: gutzmer.ralf@mh-hannover.de.
TI - Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. [Review]
SO - Cancer Treatment Reviews. 45:7-18, 2016 Apr
AS - Cancer Treat Rev. 45:7-18, 2016 Apr
NJ - Cancer treatment reviews
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cnn, 7502030
IO - Cancer Treat. Rev.
SB - Index Medicus
CP - Netherlands
MH - Antibodies, Monoclonal/im [Immunology]
MH - Antibodies, Monoclonal/pd [Pharmacology]
MH - *Antibodies, Monoclonal
MH - Antibodies, Monoclonal, Humanized/im [Immunology]
MH - Antibodies, Monoclonal, Humanized/pd [Pharmacology]
MH - *Antibodies, Monoclonal, Humanized
MH - *Antigens, CD274/ai [Antagonists & Inhibitors]
MH - Antineoplastic Agents/im [Immunology]
MH - Antineoplastic Agents/pd [Pharmacology]
MH - Disease Management
MH - Drug-Related Side Effects and Adverse Reactions/dt [Drug Therapy]
MH - Drug-Related Side Effects and Adverse Reactions/et [Etiology]
MH - Drug-Related Side Effects and Adverse Reactions/im [Immunology]
MH - *Drug-Related Side Effects and Adverse Reactions
MH - Early Diagnosis
MH - Humans
MH - *Immunosuppressive Agents/tu [Therapeutic Use]
MH - Monitoring, Immunologic
MH - *Neoplasms/dt [Drug Therapy]
MH - *Programmed Cell Death 1 Receptor/im [Immunology]
KW - Adverse drug reaction; Immune-related adverse events; Immunotherapy; Nivolumab; PD-1; Pembrolizumab
AB - PD-1 checkpoint inhibitors are associated with a specific spectrum of immune-related adverse events. This spectrum is different from toxicities known for kinase inhibitors or cytotoxic drugs. Since PD-1 directed therapies show effectivity in an increasing number of malignant diseases, their clinical usage will increase rapidly. Therefore clinicians from different specialities such as medical oncology, internal medicine, family doctors and emergency unit staff should be aware of the adverse effects of PD-1 checkpoint inhibitors to avoid delays in diagnosis and treatment. Based on pooled data from pivotal trials as reported by the European Medicines Agency, the present paper reviews incidences and kinetics of onset and resolution of immune-mediated "adverse events of specific interest" (AEOSI) of both approved PD-1 inhibitors nivolumab and pembrolizumab. In general, the severity of AEOSI is mild to moderate (grade 1-2); the frequency of immune-mediated but also idiopathic grade 3-4 adverse drug reactions is 2% for any event term. Recommendations for the diagnosis, monitoring and management of the relevant dermatological, gastrointestinal, pulmonary, endocrine, renal and hepatic toxicities are convened by an expert panel that consolidated and clarified treatment recommendations after the onset of AEOSI. Although the time of onset is not predictable - the medians range from 1 to 6months - the huge majority of events is reversible, with no impact of the time of onset. By the systemic use of glucocorticoids, notably methylprednisolone or equivalents, most AEOSI are well manageable. Non-steroidal immunosuppressants may be used in certain cases of refractory/recalcitrant, long-lasting immune toxicities. With regard to the outstanding clinical activity of the anti-PD-1 antibodies, therapy restart is the principal therapeutic option after recovery of grade 2 AEOSI, or diminution of higher grade skin or endocrine events to mild severity. Early diagnosis and close clinical monitoring are essential for successful management of immune-related adverse events.
AB - Copyright © 2016 Elsevier Ltd. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (Immunosuppressive Agents)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 31YO63LBSN (nivolumab)
RN - DPT0O3T46P (pembrolizumab)
ES - 1532-1967
IL - 0305-7372
DI - S0305-7372(16)00018-9
DO - https://dx.doi.org/10.1016/j.ctrv.2016.02.003
PT - Journal Article
PT - Review
ID - 26922661 [pubmed]
ID - S0305-7372(16)00018-9 [pii]
ID - 10.1016/j.ctrv.2016.02.003 [doi]
PP - ppublish
PH - 2015/12/17 [received]
PH - 2016/02/12 [revised]
PH - 2016/02/13 [accepted]
LG - English
EP - 20160218
DP - 2016 Apr
DC - 20160409
EZ - 2016/02/29 06:00
DA - 2016/08/20 06:00
DT - 2016/02/29 06:00
YR - 2016
ED - 20160819
RD - 20160409
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26922661
<104. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26374557
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Zhang Y
AU - Choi M
FA - Zhang, Yue
FA - Choi, Minsig
IN - Choi, Minsig. Stony Brook University, HSC 15-053C, 101 Nicholls Rd. Stony Brook, New York 11794-8151.
TI - Immune Therapy in Pancreatic Cancer: Now and the Future?. [Review]
SO - Reviews on Recent Clinical Trials. 10(4):317-25, 2015
AS - Rev Recent Clin Trials. 10(4):317-25, 2015
NJ - Reviews on recent clinical trials
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101270873
IO - Rev Recent Clin Trials
SB - Index Medicus
CP - United Arab Emirates
MH - Adult
MH - Aged
MH - *Cancer Vaccines/tu [Therapeutic Use]
MH - Clinical Trials, Phase III as Topic
MH - Disease-Free Survival
MH - Female
MH - Forecasting
MH - Humans
MH - *Immunotherapy/st [Standards]
MH - *Immunotherapy/td [Trends]
MH - Male
MH - Middle Aged
MH - Neoplasm Invasiveness/pa [Pathology]
MH - Neoplasm Recurrence, Local/mo [Mortality]
MH - *Neoplasm Recurrence, Local/pa [Pathology]
MH - Neoplasm Staging
MH - Pancreatic Neoplasms/mo [Mortality]
MH - *Pancreatic Neoplasms/pa [Pathology]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - Risk Assessment
MH - Survival Analysis
MH - Treatment Outcome
AB - Pancreatic cancer continues to be the most lethal malignancy with rising incidence. Traditional chemotherapy remains the standard treatment for advanced pancreatic cancer. Regimens like FOLFIRINOX (5-FU, leucovorin, irinotecan, and oxaliplatin) or gemcitabine and nab-paclitaxel have been used to palliate symptoms and prolong survival. Immune therapy is changing the current treatment paradigm for malignancy, especially with the recent development of antibodies that can modulate immune checkpoint pathways. Immunotherapy to treat pancreatic cancer is a promising approach due to its low toxicity and potential for creating life- long immune response. Multiple large phase III trials using simple vaccination strategies have failed to modulate the immune response in pancreatic cancer. However novel strategies with whole cell vaccines using hyperacute rejections (Algenpantucel- L) immunotherapy demonstrated 62% and 86% 12-month disease free survival and overall survival in resected pancreatic cancer patients. Combination of whole cell vaccine GVAX and mesothelin-secreting vaccine CRS-207 demonstrated an overall survival benefit in metastatic refractory pancreatic cancer patients. In the paper, we review the recently published and ongoing clinical trials using immune based treatment for pancreatic cancer.
RN - 0 (Cancer Vaccines)
ES - 1876-1038
IL - 1574-8871
DI - RRCT-EPUB-70454
PT - Journal Article
PT - Review
ID - 26374557 [pubmed]
ID - RRCT-EPUB-70454 [pii]
PP - ppublish
PH - 2015/06/05 [received]
PH - 2015/07/28 [revised]
PH - 2015/07/31 [accepted]
LG - English
DP - 2015
DC - 20151103
EZ - 2015/09/17 06:00
DA - 2016/08/19 06:00
DT - 2015/09/17 06:00
YR - 2015
ED - 20160818
RD - 20151103
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26374557
<105. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24917416
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Lu J
AU - Lee-Gabel L
AU - Nadeau MC
AU - Ferencz TM
AU - Soefje SA
FA - Lu, Jing
FA - Lee-Gabel, Linda
FA - Nadeau, Michelle C
FA - Ferencz, Thomas M
FA - Soefje, Scott A
IN - Lu, Jing. Department of Pharmacy, Smilow Cancer Hospital at Yale-New Haven, New Haven, USA jing.lu@ynhh.org.
IN - Lee-Gabel, Linda. Department of Pharmacy, Smilow Cancer Hospital at Yale-New Haven, New Haven, USA.
IN - Nadeau, Michelle C. Department of Pharmacy, Smilow Cancer Hospital at Yale-New Haven, New Haven, USA.
IN - Ferencz, Thomas M. Department of Pharmacy, Smilow Cancer Hospital at Yale-New Haven, New Haven, USA.
IN - Soefje, Scott A. Department of Pharmacy, University Medical Center Brackenridge, Seton Healthcare Family, Austin, USA.
TI - Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer immunotherapy. [Review]
SO - Journal of Oncology Pharmacy Practice. 21(6):451-67, 2015 Dec
AS - J Oncol Pharm Pract. 21(6):451-67, 2015 Dec
NJ - Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9511372
IO - J Oncol Pharm Pract
SB - Index Medicus
CP - England
MH - Animals
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Humans
MH - *Immunotherapy/mt [Methods]
MH - Immunotherapy/td [Trends]
MH - *Neoplasms/th [Therapy]
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - *Signal Transduction/de [Drug Effects]
MH - T-Lymphocytes/de [Drug Effects]
KW - Antiprogrammed death-1/programmed death-ligand 1; BMS-936559; CTLA-4 blockade; MEDI4736; MK-3475; MPDL3280A; MSB0010718C; immune-related adverse event; ipilimumab; management of adverse events; nivolumab; pidilizumab
AB - Significant enthusiasm currently exists for new immunotherapeutic strategies: blocking the interaction between programmed death-1 receptor on T-cells and programmed death-ligand 1 on tumor cells to boost immune system stimulation to fight cancer. Immunomodulation with the antiprogrammed death-1/programmed death-ligand 1 monoclonal antibodies has shown to mediate tumor shrinkage and extend overall survival from several pivotal phase I/II studies in melanoma, renal cell carcinoma, and non-small cell lung cancer. This has prompted multiple large ongoing phase III trials with the expectation for fast-track FDA approvals to satisfy unmet medical needs. Compounds targeting the programmed death-1 pathway that are in clinical trials fall into two major categories, namely antiprogrammed death-1 antibodies: Nivolumab, MK-3475, and pidilizumab; and antiprogrammed death-ligand 1 antibodies: MPDL3280A, BMS-936559, MEDI4736, and MSB0010718C. We reviewed the clinical efficacy and safety of each compound based upon major registered clinical trials and published clinical data. Overall, response rate of more than 20% is consistently seen across all these trials, with maximal response of approximately 50% achieved by certain single antiprogrammed death-1 agents or when used in combination with cytotoxic T-lymphocyte antigen-4 blockade. The responses seen are early, durable, and have continued after treatment discontinuation. Immune-related adverse events are the most common side effects seen in these clinical trials. Overall, the skin and gastrointestinal tract are the most common organ systems affected by these compounds while hepatic, endocrine, and neurologic events are less frequent. These side effects are low grade, manageable, and typically resolve within a relatively short time frame with a predictable resolution pattern given proper management. We therefore propose detailed guidelines for management of major immune-related adverse events that are anticipated with antiprogrammed death-1/programmed death-ligand 1 therapies based on general experience with other monoclonal antibodies and the established management algorithms for immune-related adverse events for cytotoxic T-lymphocyte antigen-4 blockade with ipilimumab. We anticipate that the antiprogrammed death-1 strategy will become a viable and crucial clinical strategy for cancer therapy.
AB - Copyright © The Author(s) 2014.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1477-092X
IL - 1078-1552
DI - 1078155214538087
DO - https://dx.doi.org/10.1177/1078155214538087
PT - Journal Article
PT - Review
ID - 24917416 [pubmed]
ID - 1078155214538087 [pii]
ID - 10.1177/1078155214538087 [doi]
PP - ppublish
LG - English
EP - 20140609
DP - 2015 Dec
DC - 20151027
EZ - 2014/06/12 06:00
DA - 2016/08/17 06:00
DT - 2014/06/12 06:00
YR - 2015
ED - 20160816
RD - 20151027
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24917416
<106. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26463091
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Ojalvo LS
AU - Nichols PE
AU - Jelovac D
AU - Emens LA
FA - Ojalvo, Laureen S
FA - Nichols, Paige E
FA - Jelovac, Danijela
FA - Emens, Leisha A
IN - Ojalvo, Laureen S. The Kelly Gynecologic Oncology Service, Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, Baltimore, MD 21202, USA.
IN - Nichols, Paige E. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21202, USA.
IN - Jelovac, Danijela. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21202, USA.
IN - Emens, Leisha A. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21202, USA.
TI - Emerging immunotherapies in ovarian cancer. [Review]
SO - Discovery Medicine. 20(109):97-109, 2015 Sep
AS - Discov. medicin.. 20(109):97-109, 2015 Sep
NJ - Discovery medicine
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101250006
IO - Discov Med
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ch [Chemistry]
MH - Antigens, CD274/ch [Chemistry]
MH - Antigens, Neoplasm/ch [Chemistry]
MH - Antineoplastic Agents/ch [Chemistry]
MH - Cancer Vaccines/ch [Chemistry]
MH - Clinical Trials as Topic
MH - Dendritic Cells/cy [Cytology]
MH - Epitopes/ch [Chemistry]
MH - Female
MH - Humans
MH - Immune System
MH - *Immunotherapy/mt [Methods]
MH - *Immunotherapy/td [Trends]
MH - *Ovarian Neoplasms/im [Immunology]
MH - *Ovarian Neoplasms/th [Therapy]
MH - T-Lymphocytes/im [Immunology]
MH - Treatment Outcome
MH - Tumor Microenvironment
MH - United States
AB - Despite a global effort to significantly reduce mortality, ovarian cancer remains the fifth leading cause of cancer death among American women, and five-year survival rates remain discouragingly low at 45%. Novel therapies are urgently needed. Notably, higher infiltration of activated immune cells into the tumor microenvironment correlates with improved ovarian cancer survival, suggesting that promoting their activity could favorably impact clinical outcomes. Immunotherapy has recently demonstrated impressive clinical benefit in a variety of solid tumors. Immunotherapy strategies tested in ovarian cancer include vaccines, adoptive T cell therapy, and immune checkpoint blockade. Ultimately, a combination immunotherapy approach that integrates immunotherapy with other cancer treatment modalities in additive or synergistic ways will most effectively improve survival.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD274)
RN - 0 (Antigens, Neoplasm)
RN - 0 (Antineoplastic Agents)
RN - 0 (CD274 protein, human)
RN - 0 (Cancer Vaccines)
RN - 0 (Epitopes)
ES - 1944-7930
IL - 1539-6509
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 26463091 [pubmed]
PP - ppublish
LG - English
DP - 2015 Sep
DC - 20151014
EZ - 2015/10/15 06:00
DA - 2016/08/12 06:00
DT - 2015/10/16 06:00
YR - 2015
ED - 20160811
RD - 20151014
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26463091
<107. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26138335
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Higuchi T
AU - Flies DB
AU - Marjon NA
AU - Mantia-Smaldone G
AU - Ronner L
AU - Gimotty PA
AU - Adams SF
FA - Higuchi, Tomoe
FA - Flies, Dallas B
FA - Marjon, Nicole A
FA - Mantia-Smaldone, Gina
FA - Ronner, Lukas
FA - Gimotty, Phyllis A
FA - Adams, Sarah F
IN - Higuchi, Tomoe. The University of New Mexico Cancer Center, Albuquerque, New Mexico.
IN - Flies, Dallas B. The University of New Mexico Cancer Center, Albuquerque, New Mexico.
IN - Marjon, Nicole A. The University of New Mexico Cancer Center, Albuquerque, New Mexico.
IN - Mantia-Smaldone, Gina. Fox Chase Cancer Center, Philadelphia, Pennsylvania.
IN - Ronner, Lukas. Carnegie Mellon University, Pittsburgh, Pennsylvania.
IN - Gimotty, Phyllis A. The University of Pennsylvania, Philadelphia, Pennsylvania.
IN - Adams, Sarah F. The University of New Mexico Cancer Center, Albuquerque, New Mexico. SAdams@salud.unm.edu.
TI - CTLA-4 Blockade Synergizes Therapeutically with PARP Inhibition in BRCA1-Deficient Ovarian Cancer.
SO - Cancer Immunology Research. 3(11):1257-68, 2015 Nov
AS - Cancer Immunol Res. 3(11):1257-68, 2015 Nov
NJ - Cancer immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101614637
IO - Cancer Immunol Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984269
OI - Source: NLM. NIHMS807483 [Available on 11/01/16]
SB - Index Medicus
CP - United States
MH - Animals
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Combined Modality Therapy
MH - Cytotoxicity, Immunologic
MH - Dose-Response Relationship, Drug
MH - Drug Evaluation, Preclinical/mt [Methods]
MH - Female
MH - Humans
MH - Immunologic Memory
MH - Immunotherapy/mt [Methods]
MH - Interferon-gamma/bi [Biosynthesis]
MH - Interferon-gamma/im [Immunology]
MH - Mice, Inbred C57BL
MH - Neoplasm Transplantation
MH - Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Ovarian Neoplasms/th [Therapy]
MH - Poly(ADP-ribose) Polymerase Inhibitors/ad [Administration & Dosage]
MH - *Poly(ADP-ribose) Polymerase Inhibitors/tu [Therapeutic Use]
MH - T-Lymphocyte Subsets/im [Immunology]
MH - Tumor Cells, Cultured
MH - *Ubiquitin-Protein Ligases/df [Deficiency]
AB - Immune checkpoint blockade has shown significant therapeutic efficacy in melanoma and other solid tumors, but results in ovarian cancer have been limited. With evidence that tumor immunogenicity modulates the response to checkpoint blockade, and data indicating that BRCA-deficient ovarian cancers express higher levels of immune response genes, we hypothesized that BRCA(-) ovarian tumors would be vulnerable to checkpoint blockade. To test this hypothesis, we used an immunocompetent BRCA1-deficient murine ovarian cancer model to compare treatment with CTLA-4 or PD-1/PD-L1 antibodies alone or combined with targeted cytotoxic therapy using a PARP inhibitor. Correlative studies were performed in vitro using human BRCA1(-) cells. We found that CTLA-4 antibody, but not PD-1/PD-L1 blockade, synergized therapeutically with the PARP inhibitor, resulting in immune-mediated tumor clearance and long-term survival in a majority of animals (P < 0.0001). The survival benefit of this combination was T-cell mediated and dependent on increases in local IFNgamma production in the peritoneal tumor environment. Evidence of protective immune memory was observed more than 60 days after completion of therapy. Similar increases in the cytotoxic effect of PARP inhibition in the presence of elevated levels of IFNgamma in human BRCA1(-) cancer cells support the translational potential of this treatment protocol. These results demonstrate that CTLA-4 blockade combined with PARP inhibition induces protective antitumor immunity and significant survival benefit in the BRCA1(-) tumor model, and support clinical testing of this regimen to improve outcomes for women with hereditary ovarian cancer.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN - 82115-62-6 (Interferon-gamma)
RN - EC 2-3-2-27 (Brap protein, mouse)
RN - EC 2-3-2-27 (Ubiquitin-Protein Ligases)
ES - 2326-6074
IL - 2326-6066
DI - 2326-6066.CIR-15-0044
DO - https://dx.doi.org/10.1158/2326-6066.CIR-15-0044
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26138335 [pubmed]
ID - 2326-6066.CIR-15-0044 [pii]
ID - 10.1158/2326-6066.CIR-15-0044 [doi]
ID - PMC4984269 [pmc]
ID - NIHMS807483 [mid]
PP - ppublish
PH - 2015/02/10 [received]
PH - 2015/06/13 [accepted]
GI - No: P30 CA016520
Organization: (CA) *NCI NIH HHS*
Country: United States
No: T32 AI007538
Organization: (AI) *NIAID NIH HHS*
Country: United States
LG - English
EP - 20150702
DP - 2015 Nov
DC - 20151106
EZ - 2015/07/04 06:00
DA - 2016/08/11 06:00
DT - 2015/07/04 06:00
YR - 2015
ED - 20160810
RD - 20161126
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26138335
<108. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27306803
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Miyauchi E
AU - Inoue A
FA - Miyauchi, Eisaku
FA - Inoue, Akira
IN - Miyauchi, Eisaku. Dept. of Respiratory Medicine, Tohoku University Hospital.
TI - [Immune Checkpoint Therapy for Non-Small-Cell Lung Cancer]. [Japanese]
SO - Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy]. 43(6):666-71, 2016 Jun
AS - Gan To Kagaku Ryoho. 43(6):666-71, 2016 Jun
NJ - Gan to kagaku ryoho. Cancer & chemotherapy
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 7810034, 6t8
IO - Gan To Kagaku Ryoho
SB - Index Medicus
CP - Japan
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - CTLA-4 Antigen/im [Immunology]
MH - *Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Carcinoma, Non-Small-Cell Lung/im [Immunology]
MH - Humans
MH - *Lung Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/im [Immunology]
MH - Molecular Targeted Therapy
MH - Neoplasm Proteins/im [Immunology]
MH - Transcription Factors/im [Immunology]
AB - Nivolumab is an anti-PD-1 antibody that has recently been approved in Japan, and has shown high response rates and more favorable safety profiles in 2 phase III clinical trials. Accordingly, immune checkpoint therapy has now been included as a new standard treatment for non-small-cell lung cancer. These immune checkpoints are receptors expressed on T cells that regulate the immune response. The PD-1/PD-L1 signal inhibits cytotoxic T lymphocyte proliferation and survival, induces apoptosis of infiltrative T cells, and increases the amount of regulatory T cells in the tumor microenvironment. Therefore, severe immune-related adverse event(irAE)have been observed, including enterocolitis, neuropathies, and endocrinopathies. There are different management approaches to irAEs with conventional cytotoxic drugs. This article reviews the available data regarding immune checkpoint therapy for patients with non-small-cell lung cancer.
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (Neoplasm Proteins)
RN - 0 (PCD1 protein, human)
RN - 0 (Transcription Factors)
IS - 0385-0684
IL - 0385-0684
PT - English Abstract
PT - Journal Article
ID - 27306803 [pubmed]
PP - ppublish
LG - Japanese
DP - 2016 Jun
DC - 20160616
EZ - 2016/06/17 06:00
DA - 2016/08/06 06:00
DT - 2016/06/17 06:00
YR - 2016
ED - 20160805
RD - 20160616
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27306803
<109. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27467964
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Karydis I
AU - Chan PY
AU - Wheater M
AU - Arriola E
AU - Szlosarek PW
AU - Ottensmeier CH
FA - Karydis, Ioannis
FA - Chan, Pui Ying
FA - Wheater, Matthew
FA - Arriola, Edurne
FA - Szlosarek, Peter W
FA - Ottensmeier, Christian H
IN - Karydis, Ioannis. Cancer Sciences Academic Unit, University of Southampton , Southampton, United Kingdom.
IN - Chan, Pui Ying. Department of Medical Oncology, St Bartholomew's Hospital , London.
IN - Wheater, Matthew. Medical Oncology, University Hospital Southampton , Southampton, United Kingdom.
IN - Arriola, Edurne. Medical Oncology, University Hospital Southampton , Southampton, United Kingdom.
IN - Szlosarek, Peter W. Department of Medical Oncology, St Bartholomew's Hospital, London; Barts Cancer Institute, Queen Mary University of London, London.
IN - Ottensmeier, Christian H. Cancer Sciences Academic Unit, University of Southampton , Southampton, United Kingdom.
TI - Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma.
SO - Oncoimmunology. 5(5):e1143997, 2016 May
AS - Oncoimmunology. 5(5):e1143997, 2016 May
NJ - Oncoimmunology
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101570526
IO - Oncoimmunology
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910726
CP - United States
KW - Anti-PD-1; Pembrolizumab; immuno-oncology; metastases; uveal melanoma
AB - BACKGROUND: Untreated metastatic uveal melanoma (UM) carries a grave prognosis. Unlike cutaneous melanoma (CM), there are no established treatments known to significantly improve outcomes for a meaningful proportion of patients. Inhibition of the PD1-PDL1 axis has shown promise in the management of CM and we here report a two center experience of UM patients receiving pembrolizumab.
AB - METHODS: To assess the efficacy and safety of pembrolizumab, we retrospectively analyzed outcome data of 25 consecutive UM patients participating in the MK3475 expanded access program (EAP) who received pembrolizumab at 2 mg/kg 3 weekly. Tumor assessment was evaluated using RECIST 1.1 and immune-related Response Criteria (irRC) by CT scanning. Toxicity was recorded utilizing Common Terminology Criteria for Adverse Events ("CTCAE") v4.03.
AB - RESULTS: Twenty-five patients were identified receiving a median of six cycles of treatment. Two patients achieved a partial response and six patients stable disease. After a median follow-up of 225 d median progression free survival (PFS) was 91 d and overall survival (OS) was not reached. There was a significant trend for improved outcomes in patients with extrahepatic disease progression as opposed to liver only progression at the outset. Five patients experienced grade 3 or 4 adverse events (AEs); there were no treatment related deaths.
AB - CONCLUSIONS: Pembrolizumab 2mg/kg q3w is a safe option in UM patients. Disease control rates, particularly in the subgroup of patients without progressive liver disease at the outset are promising; these results merit further investigation in clinical trials possibly incorporating liver targeted treatment modalities.
IS - 2162-4011
IL - 2162-4011
DI - 1143997
DO - https://dx.doi.org/10.1080/2162402X.2016.1143997
PT - Journal Article
ID - 27467964 [pubmed]
ID - 10.1080/2162402X.2016.1143997 [doi]
ID - 1143997 [pii]
ID - PMC4910726 [pmc]
PP - epublish
PH - 2015/10/02 [received]
PH - 2016/01/12 [revised]
PH - 2016/01/14 [accepted]
LG - English
EP - 20160218
DP - 2016 May
DC - 20160729
EZ - 2016/07/29 06:00
DA - 2016/07/29 06:01
DT - 2016/07/29 06:00
YR - 2016
ED - 20160729
RD - 20160730
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27467964
<110. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26574148
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Guibert N
AU - Mazieres J
FA - Guibert, Nicolas
FA - Mazieres, Julien
IN - Guibert, Nicolas. a Centre Hospitalier Universitaire, Thoracic Oncology Unit, Respiratory Disease Department , Hopital Larrey, Universite Paul Sabatier , CHU Toulouse, Chemin de Pouvourville, Toulouse , Toulouse Cedex 31059 , France.
IN - Mazieres, Julien. a Centre Hospitalier Universitaire, Thoracic Oncology Unit, Respiratory Disease Department , Hopital Larrey, Universite Paul Sabatier , CHU Toulouse, Chemin de Pouvourville, Toulouse , Toulouse Cedex 31059 , France.
IN - Mazieres, Julien. b Hopital Larrey , Institut Universitaire du Cancer , Toulouse , Toulouse Cedex 31059 , France.
TI - Nivolumab for treating non-small cell lung cancer. [Review]
SO - Expert Opinion on Biological Therapy. 15(12):1789-97, 2015
AS - Expert Opin Biol Ther. 15(12):1789-97, 2015
NJ - Expert opinion on biological therapy
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101125414
IO - Expert Opin Biol Ther
SB - Index Medicus
CP - England
MH - Animals
MH - Antibodies, Monoclonal/pd [Pharmacology]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antigens, CD274/ai [Antagonists & Inhibitors]
MH - Antigens, CD274/im [Immunology]
MH - Antineoplastic Agents/pd [Pharmacology]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Biomarkers
MH - *Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Carcinoma, Non-Small-Cell Lung/im [Immunology]
MH - Clinical Trials as Topic/mt [Methods]
MH - Humans
MH - *Lung Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/im [Immunology]
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - Treatment Outcome
KW - PD-1; PD-1 inhibitor; PD-L1; antitumor immunotherapy; immune checkpoint inhibitors; nivolumab
AB - INTRODUCTION: Diversion of the immune checkpoint PD-1/PD-L1 by a tumor in order to escape antitumor immunity is a hallmark of NSCLC, but offers promising new strategies. Nivolumab, a fully human monoclonal antibody, is the first PD-1 inhibitor to be approved to treat metastatic NSCLC after exciting results obtained from clinical trials.
AB - AREAS COVERED: This review aims to:) clarify the mechanism of action and toxicities of PD-1 inhibitors; recapitulate the results from various clinical trials that have evaluated nivolumab as a monotherapy for metastatic NSCLC; discuss the clinical and translational research axes to better use this molecule; and summarize the therapeutic combinations currently under evaluation.
AB - EXPERT OPINION: The contribution of this molecule to treat NSCLC is undeniable, making it a new standard of care after prior chemotherapy. Its toxicity profile is favorable but a good knowledge of new and potentially severe immune-related adverse effects such as endocrinopathy or interstitial pneumonitis is essential for its early detection and management. Better selection of patients is needed, particularly based on the discovery of predictive biomarkers, such as PD-L1 expression. Multiple associations with other checkpoint inhibitors, chemotherapy and targeted therapies are currently being studied and should pave the way toward new uses for this drug.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (Biomarkers)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 31YO63LBSN (nivolumab)
ES - 1744-7682
IL - 1471-2598
DO - https://dx.doi.org/10.1517/14712598.2015.1114097
PT - Journal Article
PT - Review
ID - 26574148 [pubmed]
ID - 10.1517/14712598.2015.1114097 [doi]
PP - ppublish
LG - English
EP - 20151116
DP - 2015
DC - 20151215
EZ - 2015/11/18 06:00
DA - 2016/07/29 06:00
DT - 2015/11/18 06:00
YR - 2015
ED - 20160728
RD - 20151215
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26574148
<111. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26317899
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Barrett MT
AU - Anderson KS
AU - Lenkiewicz E
AU - Andreozzi M
AU - Cunliffe HE
AU - Klassen CL
AU - Dueck AC
AU - McCullough AE
AU - Reddy SK
AU - Ramanathan RK
AU - Northfelt DW
AU - Pockaj BA
FA - Barrett, Michael T
FA - Anderson, Karen S
FA - Lenkiewicz, Elizabeth
FA - Andreozzi, Mariacarla
FA - Cunliffe, Heather E
FA - Klassen, Christine L
FA - Dueck, Amylou C
FA - McCullough, Ann E
FA - Reddy, Srikanth K
FA - Ramanathan, Ramesh K
FA - Northfelt, Donald W
FA - Pockaj, Barbara A
IN - Barrett, Michael T. Department of Research, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
IN - Anderson, Karen S. Biodesign Institute, Arizona State University, Tempe, Arizona, United States of America.
IN - Lenkiewicz, Elizabeth. Department of Research, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
IN - Andreozzi, Mariacarla. Department of Research, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
IN - Cunliffe, Heather E. Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
IN - Klassen, Christine L. Division of General Surgery, Section of Surgical Oncology, Mayo Clinic in Arizona, Phoenix, Arizona, United States of America.
IN - Dueck, Amylou C. Section of Biostatistics, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
IN - McCullough, Ann E. Department of Pathology and Laboratory Medicine, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
IN - Reddy, Srikanth K. Vanderbilt University, Nashville, Tennessee, United States of America.
IN - Ramanathan, Ramesh K. Division of Hematology-Oncology, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
IN - Northfelt, Donald W. Division of Hematology-Oncology, Mayo Clinic in Arizona, Scottsdale, Arizona, United States of America.
IN - Pockaj, Barbara A. Division of General Surgery, Section of Surgical Oncology, Mayo Clinic in Arizona, Phoenix, Arizona, United States of America.
TI - Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer.
SO - Oncotarget. 6(28):26483-93, 2015 Sep 22
AS - Oncotarget. 6(28):26483-93, 2015 Sep 22
NJ - Oncotarget
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101532965
IO - Oncotarget
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694916
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - *Antigens, CD274/ge [Genetics]
MH - *Biomarkers, Tumor/ge [Genetics]
MH - Carcinoma, Pancreatic Ductal/ge [Genetics]
MH - *Chromosomes, Human, Pair 9
MH - Colorectal Neoplasms/ge [Genetics]
MH - Comparative Genomic Hybridization
MH - Disease-Free Survival
MH - Female
MH - Flow Cytometry
MH - Gene Dosage
MH - Gene Expression Profiling
MH - Gene Expression Regulation, Enzymologic
MH - Gene Expression Regulation, Neoplastic
MH - *Genetic Loci
MH - Genetic Predisposition to Disease
MH - Glioblastoma/ge [Genetics]
MH - Humans
MH - *Janus Kinase 2/ge [Genetics]
MH - Kaplan-Meier Estimate
MH - Male
MH - Middle Aged
MH - Oligonucleotide Array Sequence Analysis
MH - Pancreatic Neoplasms/ge [Genetics]
MH - Phenotype
MH - *Programmed Cell Death 1 Ligand 2 Protein/ge [Genetics]
MH - Time Factors
MH - Treatment Outcome
MH - Triple Negative Breast Neoplasms/en [Enzymology]
MH - *Triple Negative Breast Neoplasms/ge [Genetics]
MH - Triple Negative Breast Neoplasms/mo [Mortality]
MH - Triple Negative Breast Neoplasms/pa [Pathology]
MH - Triple Negative Breast Neoplasms/th [Therapy]
MH - Up-Regulation
KW - 9p24.1 amplicon; JAK2; PD-L1; flow sorting; triple negative breast cancer
AB - We used DNA content flow cytometry followed by oligonucleotide array based comparative genomic hybridization to survey the genomes of 326 tumors, including 41 untreated surgically resected triple negative breast cancers (TNBC). A high level (log2ratio >= 1) 9p24 amplicon was found in TNBC (12/41), glioblastomas (2/44), and colon carcinomas (2/68). The shortest region of overlap for the amplicon targets 9p24.1 and includes the loci for PD-L1, PD-L2, and JAK2 (PDJ amplicon). In contrast this amplicon was absent in ER+ (0/8) and HER2+ (0/15) breast tumors, and in pancreatic ductal adenocarcinomas (0/150). The PDJ amplicon in TNBCs was correlated with clinical outcomes in group comparisons by two-sample t-tests for continuous variables and chi-squared tests for categorical variables. TNBC patients with the PDJ amplicon had a worse outcome with worse disease-free and overall survival. Quantitative RT-PCR confirmed that the PDJ amplicon in TNBC is associated with elevated expression of JAK2 and of the PD-1 ligands. These initial findings demonstrate that the PDJ amplicon is enriched in TNBC, targets signaling pathways that activate the PD-1 mediated immune checkpoint, and identifies patients with a poor prognosis.
RN - 0 (Antigens, CD274)
RN - 0 (Biomarkers, Tumor)
RN - 0 (CD274 protein, human)
RN - 0 (PDCD1LG2 protein, human)
RN - 0 (Programmed Cell Death 1 Ligand 2 Protein)
RN - EC 2-7-10-2 (JAK2 protein, human)
RN - EC 2-7-10-2 (Janus Kinase 2)
ES - 1949-2553
IL - 1949-2553
DI - 4494
DO - https://dx.doi.org/10.18632/oncotarget.4494
PT - Comparative Study
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26317899 [pubmed]
ID - 4494 [pii]
ID - 10.18632/oncotarget.4494 [doi]
ID - PMC4694916 [pmc]
PP - ppublish
PH - 2015/05/05 [received]
PH - 2015/06/22 [accepted]
LG - English
DP - 2015 Sep 22
DC - 20151005
EZ - 2015/08/29 06:00
DA - 2016/07/23 06:00
DT - 2015/09/01 06:00
YR - 2015
ED - 20160722
RD - 20160122
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26317899
<112. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26010858
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Lam T
AU - Chan MM
AU - Sweeting AN
AU - De Sousa SM
AU - Clements A
AU - Carlino MS
AU - Long GV
AU - Tonks K
AU - Chua E
AU - Kefford RF
AU - Chipps DR
AI - De Sousa, S M C; ORCID: http://orcid.org/0000-0003-0127-6482
FA - Lam, T
FA - Chan, M M K
FA - Sweeting, A N
FA - De Sousa, S M C
FA - Clements, A
FA - Carlino, M S
FA - Long, G V
FA - Tonks, K
FA - Chua, E
FA - Kefford, R F
FA - Chipps, D R
IN - Lam, T. Department of Diabetes and Endocrinology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.
IN - Chan, M M K. Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.
IN - Chan, M M K. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
IN - Chan, M M K. Central Coast Cancer Centre, Gosford Hospital, Gosford, New South Wales, Australia.
IN - Sweeting, A N. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
IN - Sweeting, A N. Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
IN - De Sousa, S M C. Department of Endocrinology, St Vincent's Hospital, Sydney, New South Wales, Australia.
IN - De Sousa, S M C. Hormones and Cancer Group, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
IN - Clements, A. Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.
IN - Clements, A. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
IN - Carlino, M S. Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.
IN - Carlino, M S. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
IN - Carlino, M S. Melanoma Institute of Australia, Sydney, New South Wales, Australia.
IN - Long, G V. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
IN - Long, G V. Melanoma Institute of Australia, Sydney, New South Wales, Australia.
IN - Tonks, K. Department of Endocrinology, St Vincent's Hospital, Sydney, New South Wales, Australia.
IN - Tonks, K. Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
IN - Chua, E. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
IN - Chua, E. Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
IN - Kefford, R F. Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.
IN - Kefford, R F. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
IN - Kefford, R F. Melanoma Institute of Australia, Sydney, New South Wales, Australia.
IN - Kefford, R F. Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia.
IN - Chipps, D R. Department of Diabetes and Endocrinology, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.
IN - Chipps, D R. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
TI - Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series.[Erratum appears in Intern Med J. 2015 Dec;45(12):1318; PMID: 26648200]
SO - Internal Medicine Journal. 45(10):1066-73, 2015 Oct
AS - Intern Med J. 45(10):1066-73, 2015 Oct
NJ - Internal medicine journal
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - d20, 101092952
IO - Intern Med J
SB - Index Medicus
CP - Australia
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - Australia
MH - CTLA-4 Antigen/im [Immunology]
MH - Female
MH - Hormone Replacement Therapy
MH - Humans
MH - *Hypopituitarism/ci [Chemically Induced]
MH - Hypopituitarism/di [Diagnosis]
MH - Hypopituitarism/dt [Drug Therapy]
MH - Immunotherapy
MH - Magnetic Resonance Imaging
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - *Skin Neoplasms/dt [Drug Therapy]
KW - hypophysitis; hypopituitarism; immune-related adverse event; immunotherapy; ipilimumab; melanoma
AB - BACKGROUND: Ipilimumab (Yervoy; Bristol-Myers Squibb) is a novel fully humanised monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4, an immune checkpoint molecule, to augment anti-tumour T-cell responses. It is associated with significant immune-related side-effects including hypophysitis.
AB - AIM: We reviewed the clinical and biochemical characteristics of 10 patients with ipilimumab-induced hypophysitis (IH), and developed guidelines for the early detection and management of IH based on our experiences at three major teaching hospitals in Sydney.
AB - METHODS: All patients were evaluated at the Crown Princess Mary Cancer Centre and Department of Endocrinology, Westmead Hospital, Department of Endocrinology, Royal Prince Alfred Hospital, the Melanoma Institute Australia and Macarthur Cancer Therapy Centre, Campbelltown Hospital from 2010 to 2014. Relevant data were extracted by review of medical records. Main outcome measures included clinical features, hormone profile and radiological findings associated with IH, and presence of pituitary recovery.
AB - RESULTS: Ten patients were identified with IH. In four patients who underwent monitoring of plasma cortisol, there was a fall in levels in the weeks prior to presentation. The pituitary-adrenal and pituitary-thyroid axes were affected in the majority of patients, with the need for physiological hormone replacement. Imaging abnormalities were identified in five of 10 patients, and resolved without high-dose glucocorticoid therapy. To date, all patients remain on levothyroxine and hydrocortisone replacement, where appropriate.
AB - CONCLUSIONS: There is significant morbidity associated with development of IH. We suggest guidelines to assist with early recognition and therapeutic intervention.
AB - Copyright © 2015 Royal Australasian College of Physicians.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
ES - 1445-5994
IL - 1444-0903
DO - https://dx.doi.org/10.1111/imj.12819
PT - Journal Article
PT - Multicenter Study
ID - 26010858 [pubmed]
ID - 10.1111/imj.12819 [doi]
PP - ppublish
PH - 2015/01/10 [received]
PH - 2015/05/12 [accepted]
LG - English
DP - 2015 Oct
DC - 20151002
EZ - 2015/05/27 06:00
DA - 2016/07/22 06:00
DT - 2015/05/27 06:00
YR - 2015
ED - 20160721
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26010858
<113. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25957829
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Araujo PB
AU - Coelho MC
AU - Arruda M
AU - Gadelha MR
AU - Neto LV
FA - Araujo, P B
FA - Coelho, M C A
FA - Arruda, M
FA - Gadelha, M R
FA - Neto, L V
IN - Araujo, P B. Department of Internal Medicine and Endocrine Unit, Medical School and Hospital Universitario Clementino Fraga Filho, Universidade Federal Do Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255 9degree andar, Servico de Endocrinologia, 21941-913, Rio de Janeiro, RJ, Brazil. paulabruna@gmail.com.
IN - Coelho, M C A. Department of Internal Medicine and Endocrine Unit, Medical School and Hospital Universitario Clementino Fraga Filho, Universidade Federal Do Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255 9degree andar, Servico de Endocrinologia, 21941-913, Rio de Janeiro, RJ, Brazil. carolinealvescoelho@yahoo.com.br.
IN - Coelho, M C A. Endocrinology Unit, Hospital Universitario Pedro Ernesto, Universidade Estadual do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. carolinealvescoelho@yahoo.com.br.
IN - Coelho, M C A. Instituto Estadual de Diabetes e Endocrinologia, Rio de Janeiro, RJ, Brazil. carolinealvescoelho@yahoo.com.br.
IN - Arruda, M. Department of Internal Medicine and Endocrine Unit, Medical School and Hospital Universitario Clementino Fraga Filho, Universidade Federal Do Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255 9degree andar, Servico de Endocrinologia, 21941-913, Rio de Janeiro, RJ, Brazil. mariana.arruda.silva@gmail.com.
IN - Gadelha, M R. Department of Internal Medicine and Endocrine Unit, Medical School and Hospital Universitario Clementino Fraga Filho, Universidade Federal Do Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255 9degree andar, Servico de Endocrinologia, 21941-913, Rio de Janeiro, RJ, Brazil. mgadelha@hucff.ufrj.br.
IN - Neto, L V. Department of Internal Medicine and Endocrine Unit, Medical School and Hospital Universitario Clementino Fraga Filho, Universidade Federal Do Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255 9degree andar, Servico de Endocrinologia, 21941-913, Rio de Janeiro, RJ, Brazil. netolv@gmail.com.
IN - Neto, L V. Endocrinology Unit, Hospital Federal da Lagoa, Rio De Janeiro, RJ, Brazil. netolv@gmail.com.
TI - Ipilimumab-induced hypophysitis: review of the literature. [Review]
SO - Journal of Endocrinological Investigation. 38(11):1159-66, 2015 Nov
AS - J Endocrinol Invest. 38(11):1159-66, 2015 Nov
NJ - Journal of endocrinological investigation
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - iam, 7806594
IO - J. Endocrinol. Invest.
SB - Index Medicus
CP - Italy
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Female
MH - Humans
MH - *Hypopituitarism/ci [Chemically Induced]
MH - *Immunologic Factors/ae [Adverse Effects]
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - *Pituitary Diseases/ci [Chemically Induced]
KW - Hypophysitis; Hypopituitarism; Ipilimumab
AB - PURPOSE: Ipilimumab is a human monoclonal antibody against cytotoxic T-lymphocyte antigen 4 available as an immunotherapy mainly for advanced melanoma. It induces an activation of T cells, resulting in an immune-mediated anti-tumor response and also immune-related adverse events, including hypophysitis. The aim of this review is to identify and discuss features concerning ipilimumab-induced hypophysitis (IIH).
AB - DESIGN: A MEDLINE research of all years of publication of IIH was conducted. We gathered information regarding clinical, radiologic and laboratory features of 71 cases recorded in the literature.
AB - RESULTS: In our review, IIH was more frequent among older and male patients. Fatigue and headache were the most frequent initial clinical manifestations of IIH and enlargement of the pituitary gland at MRI was present in the majority of patients. Those who received more than 3 cycles of ipilimumab had more fatigue (p = 0.04) and arthritis (p = 0.04). Adrenal insufficiency was more prevalent in men (p = 0.007). Glucocorticoid therapy and hormone replacement were required in most patients and pituitary function recovery was uncommon. Low prolactin at diagnosis tended to predict permanent pituitary dysfunction (p = 0.07).
AB - CONCLUSION: Hypopituitarism as a consequence of IIH, if not promptly recognized, can lead to potentially fatal events, such as adrenal insufficiency. IIH can be easily managed with glucocorticoids and hormonal replacement; therefore, physicians should be familiar with the key aspects of this condition. More studies to develop screening protocols and therapeutic intervention algorithms should be performed to decrease morbidity related to IIH.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Immunologic Factors)
RN - 6T8C155666 (ipilimumab)
ES - 1720-8386
IL - 0391-4097
DI - 10.1007/s40618-015-0301-z
DO - https://dx.doi.org/10.1007/s40618-015-0301-z
PT - Case Reports
PT - Journal Article
PT - Meta-Analysis
PT - Review
ID - 25957829 [pubmed]
ID - 10.1007/s40618-015-0301-z [doi]
ID - 10.1007/s40618-015-0301-z [pii]
PP - ppublish
PH - 2015/02/12 [received]
PH - 2015/04/24 [accepted]
LG - English
EP - 20150510
DP - 2015 Nov
DC - 20151012
EZ - 2015/05/11 06:00
DA - 2016/07/21 06:00
DT - 2015/05/11 06:00
YR - 2015
ED - 20160720
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25957829
<114. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26970135
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wojtowicz ME
AU - Dunn BK
AU - Umar A
FA - Wojtowicz, Malgorzata E
FA - Dunn, Barbara K
FA - Umar, Asad
IN - Wojtowicz, Malgorzata E. Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: wojtowim@mail.nih.gov.
IN - Dunn, Barbara K. Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
IN - Umar, Asad. Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
TI - Immunologic approaches to cancer prevention-current status, challenges, and future perspectives. [Review]
SO - Seminars in Oncology. 43(1):161-72, 2016 Feb
AS - Semin Oncol. 43(1):161-72, 2016 Feb
NJ - Seminars in oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - un5, 0420432
IO - Semin. Oncol.
SB - Index Medicus
CP - United States
MH - Adaptive Immunity
MH - Animals
MH - *Antigens, Neoplasm/im [Immunology]
MH - Autoantigens/im [Immunology]
MH - *Breast Neoplasms/im [Immunology]
MH - *Breast Neoplasms/pc [Prevention & Control]
MH - Colorectal Neoplasms/ge [Genetics]
MH - *Colorectal Neoplasms/im [Immunology]
MH - *Colorectal Neoplasms/pc [Prevention & Control]
MH - Female
MH - Frameshift Mutation
MH - Hepatitis B Vaccines/tu [Therapeutic Use]
MH - Humans
MH - Immunity, Innate
MH - Immunologic Surveillance
MH - *Immunotherapy
MH - Lactalbumin/im [Immunology]
MH - Mammaglobin A/im [Immunology]
MH - *Pancreatic Neoplasms/im [Immunology]
MH - Papillomavirus Vaccines/tu [Therapeutic Use]
MH - Receptor, ErbB-2/im [Immunology]
MH - Telomerase/ai [Antagonists & Inhibitors]
MH - Telomerase/im [Immunology]
KW - Cancer immunoprevention; Cancer vaccines; Tumor antigens; Tumor immunity
AB - The potential of the immune system to recognize and reject tumors has been investigated for more than a century. However, only recently impressive breakthroughs in cancer immunotherapy have been seen with the use of checkpoint inhibitors. The experience with various immune-based strategies in the treatment of late cancer highlighted the importance of negative impact advanced disease has on immunity. Consequently, use of immune modulation for cancer prevention rather than therapy has gained considerable attention, with many promising results seen already in preclinical and early clinical studies. Although not without challenges, these results provide much excitement and optimism that successful cancer immunoprevention could be within our reach. In this review we will discuss the current state of predominantly primary and secondary cancer immunoprevention, relevant research, potential barriers, and future directions.
AB - Copyright Published by Elsevier Inc.
RN - 0 (Antigens, Neoplasm)
RN - 0 (Autoantigens)
RN - 0 (Hepatitis B Vaccines)
RN - 0 (Mammaglobin A)
RN - 0 (Papillomavirus Vaccines)
RN - 9013-90-5 (Lactalbumin)
RN - EC 2-7-10-1 (ERBB2 protein, human)
RN - EC 2-7-10-1 (Receptor, ErbB-2)
RN - EC 2-7-7-49 (TERT protein, human)
RN - EC 2-7-7-49 (Telomerase)
ES - 1532-8708
IL - 0093-7754
DI - S0093-7754(15)00243-2
DO - https://dx.doi.org/10.1053/j.seminoncol.2015.11.001
PT - Journal Article
PT - Review
ID - 26970135 [pubmed]
ID - S0093-7754(15)00243-2 [pii]
ID - 10.1053/j.seminoncol.2015.11.001 [doi]
PP - ppublish
LG - English
EP - 20151114
DP - 2016 Feb
DC - 20160313
EZ - 2016/03/13 06:00
DA - 2016/07/20 06:00
DT - 2016/03/13 06:00
YR - 2016
ED - 20160719
RD - 20160313
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26970135
<115. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26100356
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Tirumani SH
AU - Ramaiya NH
AU - Keraliya A
AU - Bailey ND
AU - Ott PA
AU - Hodi FS
AU - Nishino M
FA - Tirumani, Sree Harsha
FA - Ramaiya, Nikhil H
FA - Keraliya, Abhishek
FA - Bailey, Nancy D
FA - Ott, Patrick A
FA - Hodi, F Stephen
FA - Nishino, Mizuki
IN - Tirumani, Sree Harsha. Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Ramaiya, Nikhil H. Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Keraliya, Abhishek. Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Bailey, Nancy D. Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Ott, Patrick A. Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Hodi, F Stephen. Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Nishino, Mizuki. Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts. Mizuki_Nishino@dfci.harvard.edu.
TI - Radiographic Profiling of Immune-Related Adverse Events in Advanced Melanoma Patients Treated with Ipilimumab.
SO - Cancer Immunology Research. 3(10):1185-92, 2015 Oct
AS - Cancer Immunol Res. 3(10):1185-92, 2015 Oct
NJ - Cancer immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101614637
IO - Cancer Immunol Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596761
OI - Source: NLM. NIHMS703148 [Available on 10/01/16]
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Colitis/di [Diagnosis]
MH - Colitis/et [Etiology]
MH - *Drug-Related Side Effects and Adverse Reactions/di [Diagnosis]
MH - Female
MH - Fluorodeoxyglucose F18
MH - Hepatitis/di [Diagnosis]
MH - Hepatitis/et [Etiology]
MH - Humans
MH - Lymphatic Diseases/di [Diagnosis]
MH - Lymphatic Diseases/et [Etiology]
MH - Male
MH - *Melanoma/co [Complications]
MH - Melanoma/dt [Drug Therapy]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - Neoplasm Staging
MH - Organ Specificity
MH - Pancreatitis/di [Diagnosis]
MH - Pancreatitis/et [Etiology]
MH - Pneumonia/di [Diagnosis]
MH - Pneumonia/et [Etiology]
MH - Positron-Emission Tomography
MH - Thyroiditis/di [Diagnosis]
MH - Thyroiditis/et [Etiology]
MH - Tomography, X-Ray Computed
MH - Treatment Outcome
AB - Ipilimumab is a promising novel immunotherapy agent and is associated with a variety of immune-related adverse events (irAE). The purpose of this study was to investigate the manifestations of irAEs on body imaging in patients with advanced melanoma treated with ipilimumab. One-hundred forty-seven patients with advanced melanoma (59 women, 88 men; median age, 64.5 years) treated with ipilimumab were studied. All patients had the baseline and at least one follow-up chest/abdomen/pelvis CT or PET/CT during therapy, which were reviewed by a consensus of two radiologists blinded to the clinical data. Findings indicative of individual types of irAEs were assessed, including thyroiditis, sarcoid-like lymphadenopathy, pneumonitis, hepatitis, pancreatitis, and colitis. Among the 147 patients, 46 (31%) had radiologically identified irAEs. The time interval from the initiation of therapy to the development of irAEs was less than 3 months in 76% (35 of 46) of the patients (range, 0.2-9.1 months). Clinical characteristics did not differ between patients with and without irAEs (P > 0.18). Among the individual types of irAEs, colitis was most common (n = 28; 19%), followed by sarcoid-like lymphadenopathy (n = 8; 5%) and pneumonitis (n = 8; 5%). Hepatitis (n = 3), thyroiditis (n = 2), and pancreatitis (n = 1) were less common. The resolution of irAEs was noted in 32 of 36 patients (89%) with further follow-up scans, with a median time of 2.3 months after the detection of irAE. In conclusion, irAEs were noted on body imaging in 31% of patients with melanoma treated with ipilimumab. Colitis was the most common, followed by sarcoid-like lymphadenopathy and pneumonitis. The results call for an increased awareness of irAEs, given the expanding role of cancer immunotherapy.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN - 6T8C155666 (ipilimumab)
ES - 2326-6074
IL - 2326-6066
DI - 2326-6066.CIR-15-0102
DO - https://dx.doi.org/10.1158/2326-6066.CIR-15-0102
PT - Journal Article
ID - 26100356 [pubmed]
ID - 2326-6066.CIR-15-0102 [pii]
ID - 10.1158/2326-6066.CIR-15-0102 [doi]
ID - PMC4596761 [pmc]
ID - NIHMS703148 [mid]
PP - ppublish
PH - 2015/04/13 [received]
PH - 2015/06/11 [accepted]
GI - No: K23 CA157631
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20150622
DP - 2015 Oct
DC - 20151006
EZ - 2015/06/24 06:00
DA - 2016/07/20 06:00
DT - 2015/06/24 06:00
YR - 2015
ED - 20160719
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26100356
<116. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26429981
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Kurose K
AU - Ohue Y
AU - Wada H
AU - Iida S
AU - Ishida T
AU - Kojima T
AU - Doi T
AU - Suzuki S
AU - Isobe M
AU - Funakoshi T
AU - Kakimi K
AU - Nishikawa H
AU - Udono H
AU - Oka M
AU - Ueda R
AU - Nakayama E
FA - Kurose, Koji
FA - Ohue, Yoshihiro
FA - Wada, Hisashi
FA - Iida, Shinsuke
FA - Ishida, Takashi
FA - Kojima, Takashi
FA - Doi, Toshihiko
FA - Suzuki, Susumu
FA - Isobe, Midori
FA - Funakoshi, Takeru
FA - Kakimi, Kazuhiro
FA - Nishikawa, Hiroyoshi
FA - Udono, Heiichiro
FA - Oka, Mikio
FA - Ueda, Ryuzo
FA - Nakayama, Eiichi
IN - Kurose, Koji. Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
IN - Ohue, Yoshihiro. Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
IN - Wada, Hisashi. Department of Clinical Research in Tumor Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
IN - Iida, Shinsuke. Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
IN - Ishida, Takashi. Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
IN - Kojima, Takashi. Exploratory Oncology Research & Clinical Trial Center, Kashiwa, Chiba, Japan.
IN - Doi, Toshihiko. Exploratory Oncology Research & Clinical Trial Center, Kashiwa, Chiba, Japan.
IN - Suzuki, Susumu. Department of Tumor Immunology, Aichi Medical University, Nagakute, Aichi, Japan.
IN - Isobe, Midori. Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
IN - Funakoshi, Takeru. Department of Dermatology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
IN - Kakimi, Kazuhiro. Department of Immunotherapeutics, The University of Tokyo Hospital, Bunkyo-Ku, Tokyo, Japan.
IN - Nishikawa, Hiroyoshi. Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
IN - Udono, Heiichiro. Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama, Japan.
IN - Oka, Mikio. Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.
IN - Ueda, Ryuzo. Department of Tumor Immunology, Aichi Medical University, Nagakute, Aichi, Japan. nakayama@mw.kawasaki-m.ac.jp uedaryu@aichi-med-u.ac.jp.
IN - Nakayama, Eiichi. Faculty of Health and Welfare, Kawasaki University of Medical Welfare, Kurashiki, Okayama, Japan. nakayama@mw.kawasaki-m.ac.jp uedaryu@aichi-med-u.ac.jp.
TI - Phase Ia Study of FoxP3+ CD4 Treg Depletion by Infusion of a Humanized Anti-CCR4 Antibody, KW-0761, in Cancer Patients.
SO - Clinical Cancer Research. 21(19):4327-36, 2015 Oct 01
AS - Clin Cancer Res. 21(19):4327-36, 2015 Oct 01
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - c2h, 9502500
IO - Clin. Cancer Res.
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal, Humanized/pd [Pharmacology]
MH - *Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - Antineoplastic Agents/pd [Pharmacology]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Carcinoma, Non-Small-Cell Lung/im [Immunology]
MH - Carcinoma, Non-Small-Cell Lung/me [Metabolism]
MH - Female
MH - Forkhead Transcription Factors/me [Metabolism]
MH - Granulocytes/im [Immunology]
MH - Granulocytes/me [Metabolism]
MH - Humans
MH - Immunophenotyping
MH - Lung Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/im [Immunology]
MH - Lung Neoplasms/me [Metabolism]
MH - *Lymphocyte Depletion
MH - Male
MH - *Neoplasms/dt [Drug Therapy]
MH - *Neoplasms/im [Immunology]
MH - Neoplasms/me [Metabolism]
MH - Phenotype
MH - *Receptors, CCR4/ai [Antagonists & Inhibitors]
MH - T-Lymphocyte Subsets/im [Immunology]
MH - T-Lymphocyte Subsets/me [Metabolism]
MH - *T-Lymphocytes, Regulatory/im [Immunology]
MH - T-Lymphocytes, Regulatory/me [Metabolism]
MH - Treatment Outcome
AB - PURPOSE: FoxP3(+) Tregs inhibit immune responses against tumors. KW-0761 is a humanized anti-human CCR4 monoclonal antibody (mAb) that has antibody-dependent cellular cytotoxicity activity. Depletion of CCR4-expressing FoxP3(+) CD4 Tregs by KW-0761 infusion was investigated in solid cancer patients.
AB - EXPERIMENTAL DESIGN: We conducted a phase Ia clinical trial of KW-0761 infusion in 7 lung and 3 esophageal cancer patients. Toxicity, clinical efficacy, changes in lymphocyte subpopulations, including Tregs, and induction of immune responses were analyzed.
AB - RESULTS: The results showed that KW-0761 infusion in a dose range between 0.1 mg/kg and 1.0 mg/kg was safe and well tolerated. No dose-limiting toxicity was observed. Four of 10 patients showed stable disease during treatment and were long survivors. The monitoring of FoxP3(+) Tregs in the peripheral blood mononuclear cells during treatment indicated efficient depletion of those cells, even at the lowest dose of 0.1 mg/kg used. The reduction in Th 1 CD4 T cells and CD8 T cells was limited, whereas a significant reduction was observed with Th 2 and Th 17 CD4 T cells. Immune responses to cancer/testis (CT) antigens and an autoantibody response to thyroid peroxidase were observed in some patients.
AB - CONCLUSIONS: The findings showed Tregs depletion and the possible occurrence of an immune response following KW-0761 infusion. Combined use of KW-0761 to deplete FoxP3(+) Tregs with other immunotherapies, such as cancer vaccines or checkpoint inhibitors, is a promising approach to augment immune responses.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (FOXP3 protein, human)
RN - 0 (Forkhead Transcription Factors)
RN - 0 (Receptors, CCR4)
RN - 0 (mogamulizumab)
IS - 1078-0432
IL - 1078-0432
DI - 21/19/4327
DO - https://dx.doi.org/10.1158/1078-0432.CCR-15-0357
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26429981 [pubmed]
ID - 21/19/4327 [pii]
ID - 10.1158/1078-0432.CCR-15-0357 [doi]
PP - ppublish
LG - English
DP - 2015 Oct 01
DC - 20151002
EZ - 2015/10/03 06:00
DA - 2016/07/12 06:00
DT - 2015/10/03 06:00
YR - 2015
ED - 20160711
RD - 20151002
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26429981
<117. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26924195
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Javle M
AU - Golan T
AU - Maitra A
FA - Javle, Milind
FA - Golan, Talia
FA - Maitra, Anirban
IN - Javle, Milind. MD Anderson Cancer Center, 1515, Holcombe Blvd, Unit 426, Houston, TX 77030, USA.
IN - Golan, Talia. Sheba Medical Center, Tel Hashomer 52621, Israel.
IN - Maitra, Anirban. MD Anderson Cancer Center, 1515, Holcombe Blvd, Unit 426, Houston, TX 77030, USA.
TI - Changing the course of pancreatic cancer--Focus on recent translational advances. [Review]
SO - Cancer Treatment Reviews. 44:17-25, 2016 Mar
AS - Cancer Treat Rev. 44:17-25, 2016 Mar
NJ - Cancer treatment reviews
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cnn, 7502030
IO - Cancer Treat. Rev.
SB - Index Medicus
CP - Netherlands
MH - Cancer Vaccines/tu [Therapeutic Use]
MH - Carcinoma, Pancreatic Ductal/dt [Drug Therapy]
MH - *Carcinoma, Pancreatic Ductal/ge [Genetics]
MH - Carcinoma, Pancreatic Ductal/im [Immunology]
MH - DNA Repair/ge [Genetics]
MH - *Genes, BRCA1
MH - *Genes, BRCA2
MH - Humans
MH - Immunotherapy
MH - Immunotherapy, Adoptive
MH - Molecular Targeted Therapy
MH - Pancreatic Neoplasms/dt [Drug Therapy]
MH - *Pancreatic Neoplasms/ge [Genetics]
MH - Pancreatic Neoplasms/im [Immunology]
MH - Poly(ADP-ribose) Polymerase Inhibitors
MH - *Proto-Oncogene Proteins p21(ras)/ge [Genetics]
MH - T-Lymphocytes/im [Immunology]
MH - T-Lymphocytes, Regulatory/im [Immunology]
MH - Translational Medical Research
MH - Tumor Microenvironment
KW - Carcinoma; Pancreatic ductal; Translational medical research
AB - In the past decade, insightful preclinical research has led to important breakthroughs in our understanding of pancreatic cancer. Even though the vast majority of pancreatic cancers are KRAS mutated, not all pancreatic cancer tumors are "KRAS equal"; there seems to be varying dependencies on the KRAS pathway. While KRAS-targeting therapies have been disappointing in the clinic, 'synthetic lethal' approaches hold promise in this setting. The pancreatic cancer stromal microenvironment appears to have contradictory roles. While there is evidence to suggest that stromal barrier prevents drug delivery, in other circumstances, stroma can play a protective role and its disruption enhances tumor dissemination. Clinical trials aimed at manipulating the various stromal components are in progress. BRCA mutation-related pancreatic tumors illustrate a unique subtype with enhanced susceptibility to DNA damaging agents and PARP-inhibition. DNA repair defects in cancer extend beyond germ line BRCA mutation and may extend the indications for DNA repair-targeting agents. Immune strategies are an area of active investigation in pancreatic cancer. Although the initial trials of single-agent checkpoint inhibitors have been negative, combinational approaches using immune-modifying agents and vaccines appear promising and goal is to identify an 'immune-therapy responsive' profile in pancreatic cancer.
AB - Copyright © 2016 Elsevier Ltd. All rights reserved.
RN - 0 (Cancer Vaccines)
RN - 0 (KRAS protein, human)
RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN - EC 3-6-5-2 (Proto-Oncogene Proteins p21(ras))
ES - 1532-1967
IL - 0305-7372
DI - S0305-7372(16)00012-8
DO - https://dx.doi.org/10.1016/j.ctrv.2016.01.004
PT - Journal Article
PT - Review
ID - 26924195 [pubmed]
ID - S0305-7372(16)00012-8 [pii]
ID - 10.1016/j.ctrv.2016.01.004 [doi]
PP - ppublish
PH - 2015/12/11 [received]
PH - 2016/01/18 [revised]
PH - 2016/01/19 [accepted]
GI - No: P30 CA016672
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20160125
DP - 2016 Mar
DC - 20160229
EZ - 2016/03/01 06:00
DA - 2016/07/07 06:00
DT - 2016/03/01 06:00
YR - 2016
ED - 20160706
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26924195
<118. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26874776
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Spain L
AU - Diem S
AU - Larkin J
FA - Spain, Lavinia
FA - Diem, Stefan
FA - Larkin, James
IN - Spain, Lavinia. Melanoma Unit, Royal Marsden Foundation Trust, Fulham Road, London SW3 6JJ, United Kingdom.
IN - Diem, Stefan. Melanoma Unit, Royal Marsden Foundation Trust, Fulham Road, London SW3 6JJ, United Kingdom.
IN - Larkin, James. Melanoma Unit, Royal Marsden Foundation Trust, Fulham Road, London SW3 6JJ, United Kingdom. Electronic address: james.larkin@rmh.nhs.uk.
TI - Management of toxicities of immune checkpoint inhibitors. [Review]
SO - Cancer Treatment Reviews. 44:51-60, 2016 Mar
AS - Cancer Treat Rev. 44:51-60, 2016 Mar
NJ - Cancer treatment reviews
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cnn, 7502030
IO - Cancer Treat. Rev.
SB - Index Medicus
CP - Netherlands
MH - Adrenal Cortex Hormones/tu [Therapeutic Use]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - Antilymphocyte Serum/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Carcinoma, Renal Cell/dt [Drug Therapy]
MH - Chemical and Drug Induced Liver Injury/dt [Drug Therapy]
MH - *Chemical and Drug Induced Liver Injury/et [Etiology]
MH - *Colitis/ci [Chemically Induced]
MH - Colitis/dt [Drug Therapy]
MH - Cyclosporine/tu [Therapeutic Use]
MH - *Diarrhea/ci [Chemically Induced]
MH - Diarrhea/dt [Drug Therapy]
MH - Drug Eruptions/dt [Drug Therapy]
MH - *Drug Eruptions/et [Etiology]
MH - Humans
MH - *Immunosuppressive Agents/tu [Therapeutic Use]
MH - Infliximab/tu [Therapeutic Use]
MH - Kidney Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/dt [Drug Therapy]
MH - Melanoma/dt [Drug Therapy]
MH - Mycophenolic Acid/aa [Analogs & Derivatives]
MH - Mycophenolic Acid/tu [Therapeutic Use]
MH - *Neoplasms/dt [Drug Therapy]
MH - *Pituitary Diseases/ci [Chemically Induced]
MH - Pituitary Diseases/dt [Drug Therapy]
MH - Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Skin Neoplasms/dt [Drug Therapy]
MH - Tacrolimus/tu [Therapeutic Use]
MH - *Thyroiditis/ci [Chemically Induced]
MH - Thyroiditis/dt [Drug Therapy]
KW - Immune-checkpoint inhibitors; Immune-related adverse events; Ipilimumab; Lung cancer; Melanoma; Nivolumab; Pembrolizumab; Renal cancer
AB - Immune checkpoint inhibition with the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab has improved survival in metastatic melanoma, lung cancer and renal cancer. Use of these agents holds promise in other malignancies. The augmented immune response enabled by these agents has led to a particular group of side effects called immune-related adverse events (irAEs). The main irAEs include diarrhea, colitis, hepatitis, skin toxicities and endocrinopathies such as hypophysitis and thyroid dysfunction. The anti-PD-1 antibodies have a different toxicity profile to ipilimumab with fewer high grade events. This article identifies the rates of common and uncommon irAEs associated with each immune checkpoint inhibitor (ICPI) and their timing of onset, focusing mainly on the experience in melanoma and lung cancer. An approach to management for each class of irAE is provided.
AB - Copyright © 2016 Elsevier Ltd. All rights reserved.
RN - 0 (Adrenal Cortex Hormones)
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antilymphocyte Serum)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (Immunosuppressive Agents)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 31YO63LBSN (nivolumab)
RN - 6T8C155666 (ipilimumab)
RN - 83HN0GTJ6D (Cyclosporine)
RN - B72HH48FLU (Infliximab)
RN - DPT0O3T46P (pembrolizumab)
RN - HU9DX48N0T (Mycophenolic Acid)
RN - WM0HAQ4WNM (Tacrolimus)
ES - 1532-1967
IL - 0305-7372
DI - S0305-7372(16)00016-5
DO - https://dx.doi.org/10.1016/j.ctrv.2016.02.001
PT - Journal Article
PT - Review
ID - 26874776 [pubmed]
ID - S0305-7372(16)00016-5 [pii]
ID - 10.1016/j.ctrv.2016.02.001 [doi]
PP - ppublish
PH - 2015/07/22 [received]
PH - 2016/01/27 [revised]
PH - 2016/02/01 [accepted]
LG - English
EP - 20160206
DP - 2016 Mar
DC - 20160229
EZ - 2016/02/15 06:00
DA - 2016/07/07 06:00
DT - 2016/02/15 06:00
YR - 2016
ED - 20160706
RD - 20161126
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26874776
<119. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26633184
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Johnson DB
AU - Sullivan RJ
AU - Ott PA
AU - Carlino MS
AU - Khushalani NI
AU - Ye F
AU - Guminski A
AU - Puzanov I
AU - Lawrence DP
AU - Buchbinder EI
AU - Mudigonda T
AU - Spencer K
AU - Bender C
AU - Lee J
AU - Kaufman HL
AU - Menzies AM
AU - Hassel JC
AU - Mehnert JM
AU - Sosman JA
AU - Long GV
AU - Clark JI
FA - Johnson, Douglas B
FA - Sullivan, Ryan J
FA - Ott, Patrick A
FA - Carlino, Matteo S
FA - Khushalani, Nikhil I
FA - Ye, Fei
FA - Guminski, Alexander
FA - Puzanov, Igor
FA - Lawrence, Donald P
FA - Buchbinder, Elizabeth I
FA - Mudigonda, Tejaswi
FA - Spencer, Kristen
FA - Bender, Carolin
FA - Lee, Jenny
FA - Kaufman, Howard L
FA - Menzies, Alexander M
FA - Hassel, Jessica C
FA - Mehnert, Janice M
FA - Sosman, Jeffrey A
FA - Long, Georgina V
FA - Clark, Joseph I
IN - Johnson, Douglas B. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Sullivan, Ryan J. Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
IN - Ott, Patrick A. Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Carlino, Matteo S. Department of Medicine, Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia5Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.
IN - Khushalani, Nikhil I. Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York.
IN - Ye, Fei. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Guminski, Alexander. Department of Medicine, University of Sydney, Sydney, New South Wales, Australia8Department of Medicine, Melanoma Institute Australia, Sydney, New South Wales, Australia.
IN - Puzanov, Igor. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Lawrence, Donald P. Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
IN - Buchbinder, Elizabeth I. Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Mudigonda, Tejaswi. medical student at School of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Spencer, Kristen. Department of Medicine, Rutgers Cancer Institute of New Jersey, New Brunswick.
IN - Bender, Carolin. Department of Medicine, Heidelberg University Hospital, Heidelberg, Germany.
IN - Lee, Jenny. Department of Medicine, Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia8Department of Medicine, Melanoma Institute Australia, Sydney, New South Wales, Australia.
IN - Kaufman, Howard L. Department of Surgery, Rutgers Cancer Institute of New Jersey, New Brunswick.
IN - Menzies, Alexander M. Department of Medicine, University of Sydney, Sydney, New South Wales, Australia8Department of Medicine, Melanoma Institute Australia, Sydney, New South Wales, Australia.
IN - Hassel, Jessica C. Department of Medicine, Heidelberg University Hospital, Heidelberg, Germany.
IN - Mehnert, Janice M. Department of Medicine, Rutgers Cancer Institute of New Jersey, New Brunswick.
IN - Sosman, Jeffrey A. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Long, Georgina V. Department of Medicine, University of Sydney, Sydney, New South Wales, Australia8Department of Medicine, Melanoma Institute Australia, Sydney, New South Wales, Australia.
IN - Clark, Joseph I. Department of Medicine, Loyola University Medical Center, Maywood, Illinois.
TI - Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders.
CM - Comment in: JAMA Oncol. 2016 Feb;2(2):241; PMID: 26632762
SO - JAMA Oncology. 2(2):234-40, 2016 Feb
AS - JAMA Oncol. 2(2):234-40, 2016 Feb
NJ - JAMA oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101652861
IO - JAMA Oncol
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Autoimmune Diseases/co [Complications]
MH - Autoimmune Diseases/di [Diagnosis]
MH - Autoimmune Diseases/im [Immunology]
MH - *Autoimmunity
MH - Female
MH - Humans
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - Patient Selection
MH - Retrospective Studies
MH - Risk Assessment
MH - Risk Factors
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/im [Immunology]
MH - Skin Neoplasms/pa [Pathology]
MH - Tertiary Care Centers
MH - Time Factors
MH - Treatment Outcome
AB - IMPORTANCE: Ipilimumab and other immune therapies are effective treatment options for patients with advanced melanoma but cause frequent immune-related toxic effects. Autoimmune diseases are common, and the safety and efficacy of ipilimumab therapy in patients with preexisting autoimmune disorders is not known.
AB - OBJECTIVE: To determine the safety and efficacy of ipilimumab therapy in patients with advanced melanoma with preexisting autoimmune disorders.
AB - DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of patients with advanced melanoma and preexisting autoimmune disorders who received ipilimumab at 9 academic tertiary referral centers from January 1, 2012, through August 1, 2015. The data analysis was performed on August 24, 2015.
AB - EXPOSURE: Ipilimumab therapy.
AB - MAIN OUTCOMES AND MEASURES: Safety, in terms of frequency of autoimmune flares and conventional immune-related adverse events (irAEs), and efficacy, in terms of response rates and overall survival, were evaluated descriptively.
AB - RESULTS: Of the 30 patients who received ipilimumab (17 [57%] male; median [range] age, 59.5 [30-80] y), 6 had rheumatoid arthritis, 5 had psoriasis, 6 had inflammatory bowel disease, 2 had systemic lupus erythematosus, 2 had multiple sclerosis, 2 had autoimmune thyroiditis, and 7 had other conditions. Thirteen patients (43%) were receiving immunosuppressive therapy at the time of initiation of ipilimumab therapy, most commonly low-dose prednisone or hydroxychloroquine. With ipilimumab treatment, 8 patients (27%) experienced exacerbations of their autoimmune condition necessitating systemic treatment; all were managed with corticosteroids. Conventional grade 3 to 5 irAEs occurred in 10 patients (33%) and were reversible with corticosteroids or with infliximab therapy in 2 cases. One patient with baseline psoriasis died of presumed immune-related colitis after a 1-week delay prior to reporting symptoms. Fifteen patients (50%) had neither autoimmune disease flares nor irAEs. Six patients experienced an objective response (20%), including 1 with a durable complete response.
AB - CONCLUSIONS AND RELEVANCE: To our knowledge, this is the largest series of patients with preexisting autoimmune disease treated with immune checkpoint inhibitors. Ipilimumab was clinically active and was associated with exacerbations of autoimmune disease and conventional ipilimumab-induced irAEs that were readily manageable with standard therapies when started in a timely fashion. Ipilimumab therapy may be considered in this setting with vigilant clinical monitoring.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
ES - 2374-2445
IL - 2374-2437
DI - 2473508
DO - https://dx.doi.org/10.1001/jamaoncol.2015.4368
PT - Journal Article
PT - Multicenter Study
PT - Research Support, N.I.H., Extramural
ID - 26633184 [pubmed]
ID - 2473508 [pii]
ID - 10.1001/jamaoncol.2015.4368 [doi]
PP - ppublish
GI - No: K12 CA0906525
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2016 Feb
DC - 20160212
EZ - 2015/12/04 06:00
DA - 2016/06/30 06:00
DT - 2015/12/04 06:00
YR - 2016
ED - 20160629
RD - 20161126
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26633184
<120. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26633184
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Johnson DB
AU - Sullivan RJ
AU - Ott PA
AU - Carlino MS
AU - Khushalani NI
AU - Ye F
AU - Guminski A
AU - Puzanov I
AU - Lawrence DP
AU - Buchbinder EI
AU - Mudigonda T
AU - Spencer K
AU - Bender C
AU - Lee J
AU - Kaufman HL
AU - Menzies AM
AU - Hassel JC
AU - Mehnert JM
AU - Sosman JA
AU - Long GV
AU - Clark JI
FA - Johnson, Douglas B
FA - Sullivan, Ryan J
FA - Ott, Patrick A
FA - Carlino, Matteo S
FA - Khushalani, Nikhil I
FA - Ye, Fei
FA - Guminski, Alexander
FA - Puzanov, Igor
FA - Lawrence, Donald P
FA - Buchbinder, Elizabeth I
FA - Mudigonda, Tejaswi
FA - Spencer, Kristen
FA - Bender, Carolin
FA - Lee, Jenny
FA - Kaufman, Howard L
FA - Menzies, Alexander M
FA - Hassel, Jessica C
FA - Mehnert, Janice M
FA - Sosman, Jeffrey A
FA - Long, Georgina V
FA - Clark, Joseph I
IN - Johnson, Douglas B. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Sullivan, Ryan J. Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
IN - Ott, Patrick A. Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Carlino, Matteo S. Department of Medicine, Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia5Department of Medicine, University of Sydney, Sydney, New South Wales, Australia.
IN - Khushalani, Nikhil I. Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York.
IN - Ye, Fei. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Guminski, Alexander. Department of Medicine, University of Sydney, Sydney, New South Wales, Australia8Department of Medicine, Melanoma Institute Australia, Sydney, New South Wales, Australia.
IN - Puzanov, Igor. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Lawrence, Donald P. Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
IN - Buchbinder, Elizabeth I. Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Mudigonda, Tejaswi. medical student at School of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Spencer, Kristen. Department of Medicine, Rutgers Cancer Institute of New Jersey, New Brunswick.
IN - Bender, Carolin. Department of Medicine, Heidelberg University Hospital, Heidelberg, Germany.
IN - Lee, Jenny. Department of Medicine, Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia8Department of Medicine, Melanoma Institute Australia, Sydney, New South Wales, Australia.
IN - Kaufman, Howard L. Department of Surgery, Rutgers Cancer Institute of New Jersey, New Brunswick.
IN - Menzies, Alexander M. Department of Medicine, University of Sydney, Sydney, New South Wales, Australia8Department of Medicine, Melanoma Institute Australia, Sydney, New South Wales, Australia.
IN - Hassel, Jessica C. Department of Medicine, Heidelberg University Hospital, Heidelberg, Germany.
IN - Mehnert, Janice M. Department of Medicine, Rutgers Cancer Institute of New Jersey, New Brunswick.
IN - Sosman, Jeffrey A. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Long, Georgina V. Department of Medicine, University of Sydney, Sydney, New South Wales, Australia8Department of Medicine, Melanoma Institute Australia, Sydney, New South Wales, Australia.
IN - Clark, Joseph I. Department of Medicine, Loyola University Medical Center, Maywood, Illinois.
TI - Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders.
CM - Comment in: JAMA Oncol. 2016 Feb;2(2):241; PMID: 26632762
SO - JAMA Oncology. 2(2):234-40, 2016 Feb
AS - JAMA Oncol. 2(2):234-40, 2016 Feb
NJ - JAMA oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101652861
IO - JAMA Oncol
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Autoimmune Diseases/co [Complications]
MH - Autoimmune Diseases/di [Diagnosis]
MH - Autoimmune Diseases/im [Immunology]
MH - *Autoimmunity
MH - Female
MH - Humans
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - Patient Selection
MH - Retrospective Studies
MH - Risk Assessment
MH - Risk Factors
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/im [Immunology]
MH - Skin Neoplasms/pa [Pathology]
MH - Tertiary Care Centers
MH - Time Factors
MH - Treatment Outcome
AB - IMPORTANCE: Ipilimumab and other immune therapies are effective treatment options for patients with advanced melanoma but cause frequent immune-related toxic effects. Autoimmune diseases are common, and the safety and efficacy of ipilimumab therapy in patients with preexisting autoimmune disorders is not known.
AB - OBJECTIVE: To determine the safety and efficacy of ipilimumab therapy in patients with advanced melanoma with preexisting autoimmune disorders.
AB - DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of patients with advanced melanoma and preexisting autoimmune disorders who received ipilimumab at 9 academic tertiary referral centers from January 1, 2012, through August 1, 2015. The data analysis was performed on August 24, 2015.
AB - EXPOSURE: Ipilimumab therapy.
AB - MAIN OUTCOMES AND MEASURES: Safety, in terms of frequency of autoimmune flares and conventional immune-related adverse events (irAEs), and efficacy, in terms of response rates and overall survival, were evaluated descriptively.
AB - RESULTS: Of the 30 patients who received ipilimumab (17 [57%] male; median [range] age, 59.5 [30-80] y), 6 had rheumatoid arthritis, 5 had psoriasis, 6 had inflammatory bowel disease, 2 had systemic lupus erythematosus, 2 had multiple sclerosis, 2 had autoimmune thyroiditis, and 7 had other conditions. Thirteen patients (43%) were receiving immunosuppressive therapy at the time of initiation of ipilimumab therapy, most commonly low-dose prednisone or hydroxychloroquine. With ipilimumab treatment, 8 patients (27%) experienced exacerbations of their autoimmune condition necessitating systemic treatment; all were managed with corticosteroids. Conventional grade 3 to 5 irAEs occurred in 10 patients (33%) and were reversible with corticosteroids or with infliximab therapy in 2 cases. One patient with baseline psoriasis died of presumed immune-related colitis after a 1-week delay prior to reporting symptoms. Fifteen patients (50%) had neither autoimmune disease flares nor irAEs. Six patients experienced an objective response (20%), including 1 with a durable complete response.
AB - CONCLUSIONS AND RELEVANCE: To our knowledge, this is the largest series of patients with preexisting autoimmune disease treated with immune checkpoint inhibitors. Ipilimumab was clinically active and was associated with exacerbations of autoimmune disease and conventional ipilimumab-induced irAEs that were readily manageable with standard therapies when started in a timely fashion. Ipilimumab therapy may be considered in this setting with vigilant clinical monitoring.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
ES - 2374-2445
IL - 2374-2437
DI - 2473508
DO - https://dx.doi.org/10.1001/jamaoncol.2015.4368
PT - Journal Article
PT - Multicenter Study
PT - Research Support, N.I.H., Extramural
ID - 26633184 [pubmed]
ID - 2473508 [pii]
ID - 10.1001/jamaoncol.2015.4368 [doi]
PP - ppublish
GI - No: P30 CA072720
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K12 CA0906525
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2016 Feb
DC - 20160212
EZ - 2015/12/04 06:00
DA - 2016/06/30 06:00
DT - 2015/12/04 06:00
YR - 2016
ED - 20160629
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26633184
<121. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26567141
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Karyampudi L
AU - Lamichhane P
AU - Krempski J
AU - Kalli KR
AU - Behrens MD
AU - Vargas DM
AU - Hartmann LC
AU - Janco JM
AU - Dong H
AU - Hedin KE
AU - Dietz AB
AU - Goode EL
AU - Knutson KL
FA - Karyampudi, Lavakumar
FA - Lamichhane, Purushottam
FA - Krempski, James
FA - Kalli, Kimberly R
FA - Behrens, Marshall D
FA - Vargas, Doris M
FA - Hartmann, Lynn C
FA - Janco, Jo Marie T
FA - Dong, Haidong
FA - Hedin, Karen E
FA - Dietz, Allan B
FA - Goode, Ellen L
FA - Knutson, Keith L
IN - Karyampudi, Lavakumar. Vaccine and Gene Therapy Institute, Port St. Lucie, Florida.
IN - Lamichhane, Purushottam. Vaccine and Gene Therapy Institute, Port St. Lucie, Florida. Department of Immunology, Mayo Clinic, Rochester, Minnesota.
IN - Krempski, James. Department of Immunology, Mayo Clinic, Rochester, Minnesota.
IN - Kalli, Kimberly R. Department of Oncology, Mayo Clinic, Rochester, Minnesota.
IN - Behrens, Marshall D. Department of Immunology, Mayo Clinic, Rochester, Minnesota.
IN - Vargas, Doris M. Department of Immunology, Mayo Clinic, Rochester, Minnesota.
IN - Hartmann, Lynn C. Department of Oncology, Mayo Clinic, Rochester, Minnesota.
IN - Janco, Jo Marie T. Department of Gynecologic Surgery Mayo Clinic, Mayo Clinic, Rochester, Minnesota.
IN - Dong, Haidong. Department of Immunology, Mayo Clinic, Rochester, Minnesota.
IN - Hedin, Karen E. Department of Immunology, Mayo Clinic, Rochester, Minnesota.
IN - Dietz, Allan B. Human Cell Therapy Lab, Mayo Clinic, Rochester, Minnesota.
IN - Goode, Ellen L. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
IN - Knutson, Keith L. Vaccine and Gene Therapy Institute, Port St. Lucie, Florida. Department of Immunology, Mayo Clinic, Rochester, Minnesota. knutson.keith@mayo.edu.
TI - PD-1 Blunts the Function of Ovarian Tumor-Infiltrating Dendritic Cells by Inactivating NF-kappaB.
SO - Cancer Research. 76(2):239-50, 2016 Jan 15
AS - Cancer Res. 76(2):239-50, 2016 Jan 15
NJ - Cancer research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cnf, 2984705r
IO - Cancer Res.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715980
OI - Source: NLM. NIHMS737606 [Available on 01/15/17]
SB - Index Medicus
CP - United States
MH - Animals
MH - *Dendritic Cells/im [Immunology]
MH - Female
MH - Humans
MH - Mice
MH - Mice, Inbred C57BL
MH - *NF-kappa B/me [Metabolism]
MH - *Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Programmed Cell Death 1 Receptor/im [Immunology]
MH - Signal Transduction
AB - The PD-1:PD-L1 immune signaling axis mediates suppression of T-cell-dependent tumor immunity. PD-1 expression was recently found to be upregulated on tumor-infiltrating murine (CD11c(+)CD11b(+)CD8(-)CD209a(+)) and human (CD1c(+)CD19(-)) myeloid dendritic cells (TIDC), an innate immune cell type also implicated in immune escape. However, there is little knowledge concerning how PD-1 regulates innate immune cells. In this study, we examined the role of PD-1 in TIDCs derived from mice bearing ovarian tumors. Similar to lymphocytes, TIDC expression of PD-1 was associated with expression of the adapter protein SHP-2, which signals to NF-kappaB; however, in contrast to its role in lymphocytes, we found that expression of PD-1 in TIDC tonically paralyzed NF-kappaB activation. Further mechanistic investigations showed that PD-1 blocked NF-kappaB-dependent cytokine release in a SHP-2-dependent manner. Conversely, inhibition of NF-kappaB-mediated antigen presentation by PD-1 occurred independently of SHP-2. Collectively, our findings revealed that PD-1 acts in a distinct manner in innate immune cells compared with adaptive immune cells, prompting further investigations of the signaling pathways controlled by this central mediator of immune escape in cancer.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (NF-kappa B)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1538-7445
IL - 0008-5472
DI - 0008-5472.CAN-15-0748
DO - https://dx.doi.org/10.1158/0008-5472.CAN-15-0748
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 26567141 [pubmed]
ID - 0008-5472.CAN-15-0748 [pii]
ID - 10.1158/0008-5472.CAN-15-0748 [doi]
ID - PMC4715980 [pmc]
ID - NIHMS737606 [mid]
PP - ppublish
PH - 2015/03/17 [received]
PH - 2015/10/13 [accepted]
PH - 2017/01/15 [pmc-release]
GI - No: P30 CA015083
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA136393
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30-CA015083-25
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50-CA136393
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20151113
DP - 2016 Jan 15
DC - 20160116
EZ - 2015/11/15 06:00
DA - 2016/06/29 06:00
DT - 2015/11/15 06:00
YR - 2016
ED - 20160628
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26567141
<122. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26567141
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Karyampudi L
AU - Lamichhane P
AU - Krempski J
AU - Kalli KR
AU - Behrens MD
AU - Vargas DM
AU - Hartmann LC
AU - Janco JM
AU - Dong H
AU - Hedin KE
AU - Dietz AB
AU - Goode EL
AU - Knutson KL
FA - Karyampudi, Lavakumar
FA - Lamichhane, Purushottam
FA - Krempski, James
FA - Kalli, Kimberly R
FA - Behrens, Marshall D
FA - Vargas, Doris M
FA - Hartmann, Lynn C
FA - Janco, Jo Marie T
FA - Dong, Haidong
FA - Hedin, Karen E
FA - Dietz, Allan B
FA - Goode, Ellen L
FA - Knutson, Keith L
IN - Karyampudi, Lavakumar. Vaccine and Gene Therapy Institute, Port St. Lucie, Florida.
IN - Lamichhane, Purushottam. Vaccine and Gene Therapy Institute, Port St. Lucie, Florida. Department of Immunology, Mayo Clinic, Rochester, Minnesota.
IN - Krempski, James. Department of Immunology, Mayo Clinic, Rochester, Minnesota.
IN - Kalli, Kimberly R. Department of Oncology, Mayo Clinic, Rochester, Minnesota.
IN - Behrens, Marshall D. Department of Immunology, Mayo Clinic, Rochester, Minnesota.
IN - Vargas, Doris M. Department of Immunology, Mayo Clinic, Rochester, Minnesota.
IN - Hartmann, Lynn C. Department of Oncology, Mayo Clinic, Rochester, Minnesota.
IN - Janco, Jo Marie T. Department of Gynecologic Surgery Mayo Clinic, Mayo Clinic, Rochester, Minnesota.
IN - Dong, Haidong. Department of Immunology, Mayo Clinic, Rochester, Minnesota.
IN - Hedin, Karen E. Department of Immunology, Mayo Clinic, Rochester, Minnesota.
IN - Dietz, Allan B. Human Cell Therapy Lab, Mayo Clinic, Rochester, Minnesota.
IN - Goode, Ellen L. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
IN - Knutson, Keith L. Vaccine and Gene Therapy Institute, Port St. Lucie, Florida. Department of Immunology, Mayo Clinic, Rochester, Minnesota. knutson.keith@mayo.edu.
TI - PD-1 Blunts the Function of Ovarian Tumor-Infiltrating Dendritic Cells by Inactivating NF-kappaB.
SO - Cancer Research. 76(2):239-50, 2016 Jan 15
AS - Cancer Res. 76(2):239-50, 2016 Jan 15
NJ - Cancer research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cnf, 2984705r
IO - Cancer Res.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715980
OI - Source: NLM. NIHMS737606 [Available on 01/15/17]
SB - Index Medicus
CP - United States
MH - Animals
MH - *Dendritic Cells/im [Immunology]
MH - Female
MH - Humans
MH - Mice
MH - Mice, Inbred C57BL
MH - *NF-kappa B/me [Metabolism]
MH - *Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Programmed Cell Death 1 Receptor/im [Immunology]
MH - Signal Transduction
AB - The PD-1:PD-L1 immune signaling axis mediates suppression of T-cell-dependent tumor immunity. PD-1 expression was recently found to be upregulated on tumor-infiltrating murine (CD11c(+)CD11b(+)CD8(-)CD209a(+)) and human (CD1c(+)CD19(-)) myeloid dendritic cells (TIDC), an innate immune cell type also implicated in immune escape. However, there is little knowledge concerning how PD-1 regulates innate immune cells. In this study, we examined the role of PD-1 in TIDCs derived from mice bearing ovarian tumors. Similar to lymphocytes, TIDC expression of PD-1 was associated with expression of the adapter protein SHP-2, which signals to NF-kappaB; however, in contrast to its role in lymphocytes, we found that expression of PD-1 in TIDC tonically paralyzed NF-kappaB activation. Further mechanistic investigations showed that PD-1 blocked NF-kappaB-dependent cytokine release in a SHP-2-dependent manner. Conversely, inhibition of NF-kappaB-mediated antigen presentation by PD-1 occurred independently of SHP-2. Collectively, our findings revealed that PD-1 acts in a distinct manner in innate immune cells compared with adaptive immune cells, prompting further investigations of the signaling pathways controlled by this central mediator of immune escape in cancer.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (NF-kappa B)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1538-7445
IL - 0008-5472
DI - 0008-5472.CAN-15-0748
DO - https://dx.doi.org/10.1158/0008-5472.CAN-15-0748
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 26567141 [pubmed]
ID - 0008-5472.CAN-15-0748 [pii]
ID - 10.1158/0008-5472.CAN-15-0748 [doi]
ID - PMC4715980 [pmc]
ID - NIHMS737606 [mid]
PP - ppublish
PH - 2015/03/17 [received]
PH - 2015/10/13 [accepted]
GI - No: P30 CA015083
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA136393
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30-CA015083-25
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50-CA136393
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20151113
DP - 2016 Jan 15
DC - 20160116
EZ - 2015/11/15 06:00
DA - 2016/06/29 06:00
DT - 2015/11/15 06:00
YR - 2016
ED - 20160628
RD - 20170118
UP - 20170119
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26567141
<123. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26642366
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Chamberlain N
AU - Massad C
AU - Oe T
AU - Cantaert T
AU - Herold KC
AU - Meffre E
FA - Chamberlain, Nicolas
FA - Massad, Christopher
FA - Oe, Tyler
FA - Cantaert, Tineke
FA - Herold, Kevan C
FA - Meffre, Eric
TI - Rituximab does not reset defective early B cell tolerance checkpoints.
SO - Journal of Clinical Investigation. 126(1):282-7, 2016 Jan
AS - J Clin Invest. 126(1):282-7, 2016 Jan
NJ - The Journal of clinical investigation
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - hs7, 7802877
IO - J. Clin. Invest.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701568
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - *B-Lymphocytes/de [Drug Effects]
MH - B-Lymphocytes/im [Immunology]
MH - Diabetes Mellitus, Type 1/im [Immunology]
MH - Humans
MH - *Immune Tolerance/de [Drug Effects]
MH - Lymphocyte Depletion
MH - Receptors, Antigen, B-Cell/ph [Physiology]
MH - *Rituximab/pd [Pharmacology]
AB - Type 1 diabetes (T1D) patients show abnormalities in early B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive B cells in their blood. Treatment with rituximab, an anti-CD20 mAb that depletes B cells, has been shown to preserve beta cell function in T1D patients and improve other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. However, it remains largely unknown how anti-B cell therapy thwarts autoimmunity in these pathologies. Here, we analyzed the reactivity of Abs expressed by single, mature naive B cells from 4 patients with T1D before and 52 weeks after treatment to determine whether rituximab resets early B cell tolerance checkpoints. We found that anti-B cell therapy did not alter the frequencies of autoreactive and polyreactive B cells, which remained elevated in the blood of all patients after rituximab treatment. Moreover, the limited proliferative history of autoreactive B cells after treatment revealed that these clones were newly generated B cells and not self-reactive B cells that had escaped depletion and repopulated the periphery through homeostatic expansion. We conclude that anti-B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti-B cell therapy.
RN - 0 (Receptors, Antigen, B-Cell)
RN - 4F4X42SYQ6 (Rituximab)
ES - 1558-8238
IL - 0021-9738
DI - 83840
DO - https://dx.doi.org/10.1172/JCI83840
PT - Journal Article
PT - Research Support, N.I.H., Extramural
ID - 26642366 [pubmed]
ID - 83840 [pii]
ID - 10.1172/JCI83840 [doi]
ID - PMC4701568 [pmc]
PP - ppublish
PH - 2015/07/20 [received]
PH - 2015/11/03 [accepted]
GI - No: AI095848
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: U01 DK061010
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: U01 DK103153
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: R01 AI071087
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: AI071087
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: U01 DK085499
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: U01 DK103266
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: P01 AI061093
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: U01 DK107014
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: AI082713
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: U19 AI082713
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: R21 AI095848
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: AI061093
Organization: (AI) *NIAID NIH HHS*
Country: United States
LG - English
EP - 20151207
DP - 2016 Jan
DC - 20160105
EZ - 2015/12/08 06:00
DA - 2016/06/18 06:00
DT - 2015/12/08 06:00
YR - 2016
ED - 20160617
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26642366
<124. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26164177
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Bacanovic S
AU - Burger IA
AU - Stolzmann P
AU - Hafner J
AU - Huellner MW
FA - Bacanovic, Sara
FA - Burger, Irene A
FA - Stolzmann, Paul
FA - Hafner, Jurg
FA - Huellner, Martin W
IN - Bacanovic, Sara. From the *Department of Medical Radiology, Division of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland; +Department of Medical Radiology, Divisions of Nuclear Medicine and Neuroradiology, University Hospital Zurich, Zurich, Switzerland; and ++Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
TI - Ipilimumab-Induced Adrenalitis: A Possible Pitfall in 18F-FDG-PET/CT.
SO - Clinical Nuclear Medicine. 40(11):e518-9, 2015 Nov
AS - Clin Nucl Med. 40(11):e518-9, 2015 Nov
NJ - Clinical nuclear medicine
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - df6, 7611109
IO - Clin Nucl Med
SB - Index Medicus
CP - United States
MH - Adrenocortical Hyperfunction/ci [Chemically Induced]
MH - *Adrenocortical Hyperfunction/dg [Diagnostic Imaging]
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - False Positive Reactions
MH - Fluorodeoxyglucose F18
MH - Humans
MH - Male
MH - *Melanoma/dg [Diagnostic Imaging]
MH - Melanoma/dt [Drug Therapy]
MH - Melanoma/pa [Pathology]
MH - Multimodal Imaging
MH - Neoplasm Metastasis
MH - *Positron-Emission Tomography
MH - Radiopharmaceuticals
MH - *Tomography, X-Ray Computed
AB - Ipilimumab is a monoclonal antibody against the inhibitory CTLA-4 receptor expressed on T cells. It provokes an upregulation of the immune system. This substance was approved by the US Food and Drug Administration in 2011 and is since increasingly used as a targeted therapeutic approach for metastasized melanoma. Ipilimumab is known to cause neuroendocrine disorders, such as hypophysitis and adrenal insufficiency. Our case of a 79-year-old patient represents an important imaging pitfall. Imaging findings of newly symmetrically and smoothly enlarged, hypermetabolic adrenal glands in the setting of previous ipilimumab therapy represent drug-induced adrenalitis and not metastatic disease.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (Radiopharmaceuticals)
RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN - 6T8C155666 (ipilimumab)
ES - 1536-0229
IL - 0363-9762
DO - https://dx.doi.org/10.1097/RLU.0000000000000887
PT - Case Reports
PT - Journal Article
ID - 26164177 [pubmed]
ID - 10.1097/RLU.0000000000000887 [doi]
PP - ppublish
LG - English
DP - 2015 Nov
DC - 20151007
EZ - 2015/07/13 06:00
DA - 2016/06/18 06:00
DT - 2015/07/15 06:00
YR - 2015
ED - 20160617
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26164177
<125. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26642366
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Chamberlain N
AU - Massad C
AU - Oe T
AU - Cantaert T
AU - Herold KC
AU - Meffre E
FA - Chamberlain, Nicolas
FA - Massad, Christopher
FA - Oe, Tyler
FA - Cantaert, Tineke
FA - Herold, Kevan C
FA - Meffre, Eric
TI - Rituximab does not reset defective early B cell tolerance checkpoints.
SO - Journal of Clinical Investigation. 126(1):282-7, 2016 Jan
AS - J Clin Invest. 126(1):282-7, 2016 Jan
NJ - The Journal of clinical investigation
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - hs7, 7802877
IO - J. Clin. Invest.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701568
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - *B-Lymphocytes/de [Drug Effects]
MH - B-Lymphocytes/im [Immunology]
MH - Diabetes Mellitus, Type 1/im [Immunology]
MH - Humans
MH - *Immune Tolerance/de [Drug Effects]
MH - Lymphocyte Depletion
MH - Receptors, Antigen, B-Cell/ph [Physiology]
MH - *Rituximab/pd [Pharmacology]
AB - Type 1 diabetes (T1D) patients show abnormalities in early B cell tolerance checkpoints, resulting in the accumulation of large numbers of autoreactive B cells in their blood. Treatment with rituximab, an anti-CD20 mAb that depletes B cells, has been shown to preserve beta cell function in T1D patients and improve other autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. However, it remains largely unknown how anti-B cell therapy thwarts autoimmunity in these pathologies. Here, we analyzed the reactivity of Abs expressed by single, mature naive B cells from 4 patients with T1D before and 52 weeks after treatment to determine whether rituximab resets early B cell tolerance checkpoints. We found that anti-B cell therapy did not alter the frequencies of autoreactive and polyreactive B cells, which remained elevated in the blood of all patients after rituximab treatment. Moreover, the limited proliferative history of autoreactive B cells after treatment revealed that these clones were newly generated B cells and not self-reactive B cells that had escaped depletion and repopulated the periphery through homeostatic expansion. We conclude that anti-B cell therapy may provide a temporary dampening of autoimmune processes through B cell depletion. However, repletion with autoreactive B cells may explain the relapse that occurs in many autoimmune patients after anti-B cell therapy.
RN - 0 (Receptors, Antigen, B-Cell)
RN - 4F4X42SYQ6 (Rituximab)
ES - 1558-8238
IL - 0021-9738
DI - 83840
DO - https://dx.doi.org/10.1172/JCI83840
PT - Journal Article
PT - Research Support, N.I.H., Extramural
ID - 26642366 [pubmed]
ID - 83840 [pii]
ID - 10.1172/JCI83840 [doi]
ID - PMC4701568 [pmc]
PP - ppublish
PH - 2015/07/20 [received]
PH - 2015/11/03 [accepted]
GI - No: U01 DK085476
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: AI095848
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: U01 DK061010
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: U01 DK103153
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: U01 DK061058
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: R01 AI071087
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: AI071087
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: U01 DK106984
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: U01 DK085499
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: U01 DK103266
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: P01 AI061093
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: U01 DK107014
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: AI082713
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: U19 AI082713
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: R21 AI095848
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: AI061093
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: U01 DK085465
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG - English
EP - 20151207
DP - 2016 Jan
DC - 20160105
EZ - 2015/12/08 06:00
DA - 2016/06/18 06:00
DT - 2015/12/08 06:00
YR - 2016
ED - 20160617
RD - 20170302
UP - 20170303
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26642366
<126. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27274826
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Murakami N
AU - Borges TJ
AU - Yamashita M
AU - Riella LV
FA - Murakami, Naoka
FA - Borges, Thiago J
FA - Yamashita, Michifumi
FA - Riella, Leonardo V
IN - Murakami, Naoka. Renal Division, Brigham & Women's Hospital , Harvard Medical School , Boston, MA , USA.
IN - Borges, Thiago J. Renal Division, Brigham & Women's Hospital , Harvard Medical School , Boston, MA , USA.
IN - Yamashita, Michifumi. Department of Pathology, Brigham and Women's Hospital , Harvard Medical School , Boston, MA , USA.
IN - Riella, Leonardo V. Renal Division, Brigham& Women's Hospital, Harvard Medical School, Boston, MA, USA; Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
TI - Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma.[Erratum appears in Clin Kidney J. 2016 Aug;9(4):649; PMID: 27478613]
SO - Clinical Kidney Journal. 9(3):411-7, 2016 Jun
AS - Clin Kidney J. 9(3):411-7, 2016 Jun
NJ - Clinical kidney journal
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - 101579321
IO - Clin Kidney J
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886917
CP - England
KW - acute kidney injury; immune-checkpoint blockade; interstitial nephritis
AB - Immune-checkpoint inhibitors are emerging as revolutionary drugs for certain malignancies. However, blocking the co-inhibitory signals may lead to immune-related adverse events, mainly in the spectrum of autoimmune diseases including colitis, endocrinopathies and nephritis. Here, we report a case of a 75-year-old man with metastatic malignant melanoma treated with a combination of nivolumab (anti-PD1-antibody) and ipilimumab (anti-CTLA-4 antibody) who developed systemic rash along with severe acute tubulointerstitial nephritis after two doses of combination therapy. Kidney biopsy and peripheral blood immune profile revealed highly proliferative and cytotoxic T cell features. Herein, we discuss the pathophysiology and management of immune checkpoint blockade-related adverse events.
IS - 2048-8505
IL - 2048-8505
DI - sfw024
DO - https://dx.doi.org/10.1093/ckj/sfw024
PT - Journal Article
ID - 27274826 [pubmed]
ID - 10.1093/ckj/sfw024 [doi]
ID - sfw024 [pii]
ID - PMC4886917 [pmc]
PP - ppublish
PH - 2016/02/16 [received]
PH - 2016/03/08 [accepted]
GI - No: T32 DK007527
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG - English
EP - 20160504
DP - 2016 Jun
DC - 20160609
EZ - 2016/06/09 06:00
DA - 2016/06/09 06:01
DT - 2016/06/09 06:00
YR - 2016
ED - 20160609
RD - 20161025
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27274826
<127. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26765102
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Michot JM
AU - Bigenwald C
AU - Champiat S
AU - Collins M
AU - Carbonnel F
AU - Postel-Vinay S
AU - Berdelou A
AU - Varga A
AU - Bahleda R
AU - Hollebecque A
AU - Massard C
AU - Fuerea A
AU - Ribrag V
AU - Gazzah A
AU - Armand JP
AU - Amellal N
AU - Angevin E
AU - Noel N
AU - Boutros C
AU - Mateus C
AU - Robert C
AU - Soria JC
AU - Marabelle A
AU - Lambotte O
FA - Michot, J M
FA - Bigenwald, C
FA - Champiat, S
FA - Collins, M
FA - Carbonnel, F
FA - Postel-Vinay, S
FA - Berdelou, A
FA - Varga, A
FA - Bahleda, R
FA - Hollebecque, A
FA - Massard, C
FA - Fuerea, A
FA - Ribrag, V
FA - Gazzah, A
FA - Armand, J P
FA - Amellal, N
FA - Angevin, E
FA - Noel, N
FA - Boutros, C
FA - Mateus, C
FA - Robert, C
FA - Soria, J C
FA - Marabelle, A
FA - Lambotte, O
IN - Michot, J M. Department of Medicine Oncology, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Internal Medicine and Clinical Immunology Department, Assistance Publique-Hopitaux de Paris, Hopital Universitaire Bicetre, F-94275 Le Kremlin Bicetre, France. Electronic address: jean-marie.michot@gustaveroussy.fr.
IN - Bigenwald, C. Department of Medicine Oncology, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Champiat, S. Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Collins, M. Gastroenterology Department, Assistance Publique-Hopitaux de Paris, Hopital Universitaire Bicetre, F-94275 Le Kremlin Bicetre, France; Universite Paris Sud 11, F-94275 Le Kremlin-Bicetre, France.
IN - Carbonnel, F. Gastroenterology Department, Assistance Publique-Hopitaux de Paris, Hopital Universitaire Bicetre, F-94275 Le Kremlin Bicetre, France; Universite Paris Sud 11, F-94275 Le Kremlin-Bicetre, France.
IN - Postel-Vinay, S. Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Berdelou, A. Department of Medicine Oncology, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Varga, A. Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Bahleda, R. Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Hollebecque, A. Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Massard, C. Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Fuerea, A. Department of Medicine Oncology, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Ribrag, V. Department of Medicine Oncology, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Gazzah, A. Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Armand, J P. Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Amellal, N. Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Angevin, E. Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Noel, N. Internal Medicine and Clinical Immunology Department, Assistance Publique-Hopitaux de Paris, Hopital Universitaire Bicetre, F-94275 Le Kremlin Bicetre, France; Universite Paris Sud 11, F-94275 Le Kremlin-Bicetre, France; CEA, DSV/iMETI, Division of Immunovirology, IDMIT, F-92265 Fontenay-aux-Roses, France; INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, F-94276 Le Kremlin-Bicetre, France.
IN - Boutros, C. Department of Medicine Oncology, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Internal Medicine and Clinical Immunology Department, Assistance Publique-Hopitaux de Paris, Hopital Universitaire Bicetre, F-94275 Le Kremlin Bicetre, France.
IN - Mateus, C. Department of Medicine Oncology, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Internal Medicine and Clinical Immunology Department, Assistance Publique-Hopitaux de Paris, Hopital Universitaire Bicetre, F-94275 Le Kremlin Bicetre, France.
IN - Robert, C. Department of Medicine Oncology, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France; Internal Medicine and Clinical Immunology Department, Assistance Publique-Hopitaux de Paris, Hopital Universitaire Bicetre, F-94275 Le Kremlin Bicetre, France.
IN - Soria, J C. Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Marabelle, A. Drug Development Department, Gustave Roussy Comprehensive Cancer Center, F-94805 Villejuif, France.
IN - Lambotte, O. Internal Medicine and Clinical Immunology Department, Assistance Publique-Hopitaux de Paris, Hopital Universitaire Bicetre, F-94275 Le Kremlin Bicetre, France; Universite Paris Sud 11, F-94275 Le Kremlin-Bicetre, France; CEA, DSV/iMETI, Division of Immunovirology, IDMIT, F-92265 Fontenay-aux-Roses, France; INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, F-94276 Le Kremlin-Bicetre, France.
TI - Immune-related adverse events with immune checkpoint blockade: a comprehensive review. [Review]
SO - European Journal of Cancer. 54:139-48, 2016 Feb
AS - Eur J Cancer. 54:139-48, 2016 Feb
NJ - European journal of cancer (Oxford, England : 1990)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - arv, 9005373
IO - Eur. J. Cancer
SB - Index Medicus
CP - England
MH - Abatacept/ae [Adverse Effects]
MH - Animals
MH - *Antibodies/ae [Adverse Effects]
MH - Antigens, CD274/ai [Antagonists & Inhibitors]
MH - Antigens, CD274/im [Immunology]
MH - Antigens, CD274/me [Metabolism]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - CTLA-4 Antigen/me [Metabolism]
MH - Drug-Related Side Effects and Adverse Reactions/di [Diagnosis]
MH - *Drug-Related Side Effects and Adverse Reactions/im [Immunology]
MH - Humans
MH - *Immunotherapy/ae [Adverse Effects]
MH - Immunotherapy/mt [Methods]
MH - Molecular Targeted Therapy
MH - *Neoplasms/dt [Drug Therapy]
MH - Neoplasms/im [Immunology]
MH - Neoplasms/me [Metabolism]
MH - Neoplasms/pa [Pathology]
MH - Risk Factors
MH - Signal Transduction/de [Drug Effects]
MH - Treatment Outcome
KW - Anti-PD-1 antibody; Cytotoxic T-lymphocyte-associated antigen 4; Immune checkpoint blockade; Immune-related adverse events; Tumour neoantigen
AB - Cancer immunotherapy is coming of age; it has prompted a paradigm shift in oncology, in which therapeutic agents are used to target immune cells rather than cancer cells. The first generation of new immunotherapies corresponds to antagonistic antibodies that block specific immune checkpoint molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand PD-L1. Targeting these checkpoints in patients living with cancer had led to long-lasting tumour responses. By unbalancing the immune system, these new immunotherapies also generate dysimmune toxicities, called immune-related adverse events (IRAEs) that mainly involve the gut, skin, endocrine glands, liver, and lung but can potentially affect any tissue. In view of their undisputed clinical efficacy, anti-CTLA-4 and anti-PD-1 antibodies are entering in the routine oncological practice, and the number of patients exposed to these drugs will increase dramatically in the near future. Although steroids can be used to treat these IRAEs, the associated immunosuppression may compromise the antitumour response. Oncologists must be ready to detect and manage these new types of adverse events. This review focuses on the mechanisms of IRAE generation, putative relationship between dysimmune toxicity and antitumour efficacy, as a basis for management guidelines.
AB - Copyright © 2015 Elsevier Ltd. All rights reserved.
RN - 0 (Antibodies)
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (CD274 protein, human)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 7D0YB67S97 (Abatacept)
ES - 1879-0852
IL - 0959-8049
DI - S0959-8049(15)01112-0
DO - https://dx.doi.org/10.1016/j.ejca.2015.11.016
PT - Journal Article
PT - Review
ID - 26765102 [pubmed]
ID - S0959-8049(15)01112-0 [pii]
ID - 10.1016/j.ejca.2015.11.016 [doi]
PP - ppublish
PH - 2015/11/11 [received]
PH - 2015/11/15 [accepted]
LG - English
EP - 20160105
DP - 2016 Feb
DC - 20160202
EZ - 2016/01/15 06:00
DA - 2016/06/09 06:00
DT - 2016/01/15 06:00
YR - 2016
ED - 20160606
RD - 20160202
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26765102
<128. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26056145
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wang L
AU - Amoozgar Z
AU - Huang J
AU - Saleh MH
AU - Xing D
AU - Orsulic S
AU - Goldberg MS
FA - Wang, Lei
FA - Amoozgar, Zohreh
FA - Huang, Jing
FA - Saleh, Mohammad H
FA - Xing, Deyin
FA - Orsulic, Sandra
FA - Goldberg, Michael S
IN - Wang, Lei. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Amoozgar, Zohreh. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Huang, Jing. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Saleh, Mohammad H. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Xing, Deyin. Department of Pathology, Johns Hopkins University, Baltimore, Maryland.
IN - Orsulic, Sandra. Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
IN - Goldberg, Michael S. Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts. Michael_Goldberg1@dfci.harvard.edu.
TI - Decitabine Enhances Lymphocyte Migration and Function and Synergizes with CTLA-4 Blockade in a Murine Ovarian Cancer Model.
SO - Cancer Immunology Research. 3(9):1030-41, 2015 Sep
AS - Cancer Immunol Res. 3(9):1030-41, 2015 Sep
NJ - Cancer immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101614637
IO - Cancer Immunol Res
SB - Index Medicus
CP - United States
MH - Animals
MH - Antineoplastic Agents/pd [Pharmacology]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Ascitic Fluid/im [Immunology]
MH - Azacitidine/ad [Administration & Dosage]
MH - *Azacitidine/aa [Analogs & Derivatives]
MH - Azacitidine/pd [Pharmacology]
MH - Azacitidine/tu [Therapeutic Use]
MH - CD8-Positive T-Lymphocytes/im [Immunology]
MH - *CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Cell Movement/de [Drug Effects]
MH - Cell Transformation, Neoplastic/de [Drug Effects]
MH - Cell Transformation, Neoplastic/im [Immunology]
MH - Cytokines/bi [Biosynthesis]
MH - Female
MH - Gene Expression Regulation, Neoplastic/de [Drug Effects]
MH - Gene Expression Regulation, Neoplastic/im [Immunology]
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Killer Cells, Natural/de [Drug Effects]
MH - Killer Cells, Natural/im [Immunology]
MH - Lymph Nodes/im [Immunology]
MH - *Lymphocytes, Tumor-Infiltrating/de [Drug Effects]
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Mice
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - Ovarian Neoplasms/im [Immunology]
MH - Tumor Cells, Cultured
MH - Xenograft Model Antitumor Assays/mt [Methods]
AB - The lack of second-line treatment for relapsed ovarian cancer necessitates the development of improved combination therapies. Targeted therapy and immunotherapy each confer clinical benefit, albeit limited as monotherapies. Ovarian cancer is not particularly responsive to immune checkpoint blockade, so combination with a complementary therapy may be beneficial. Recent studies have revealed that a DNA methyl transferase inhibitor, azacytidine, alters expression of immunoregulatory genes in ovarian cancer. In this study, the antitumor effects of a related DNA methyl transferase inhibitor, decitabine (DAC), were demonstrated in a syngeneic murine ovarian cancer model. Low-dose DAC treatment increases the expression of chemokines that recruit NK cells and CD8(+) T cells, promotes their production of IFNgamma and TNFalpha, and extends the survival of mice bearing subcutaneous or orthotopic tumors. While neither DAC nor immune checkpoint blockade confers durable responses as a monotherapy in this model, the efficacy of anti-CTLA-4 was potentiated by combination with DAC. This combination promotes differentiation of naive T cells into effector T cells and prolongs cytotoxic lymphocyte responses as well as mouse survival. These results suggest that this combination therapy may be worthy of further consideration for improved treatment of drug-resistant ovarian cancer.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (Cytokines)
RN - 776B62CQ27 (decitabine)
RN - M801H13NRU (Azacitidine)
ES - 2326-6074
IL - 2326-6066
DI - 2326-6066.CIR-15-0073
DO - https://dx.doi.org/10.1158/2326-6066.CIR-15-0073
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26056145 [pubmed]
ID - 2326-6066.CIR-15-0073 [pii]
ID - 10.1158/2326-6066.CIR-15-0073 [doi]
PP - ppublish
PH - 2015/03/16 [received]
PH - 2015/05/26 [accepted]
LG - English
EP - 20150608
DP - 2015 Sep
DC - 20150905
EZ - 2015/06/10 06:00
DA - 2016/05/26 06:00
DT - 2015/06/10 06:00
YR - 2015
ED - 20160525
RD - 20150905
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26056145
<129. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25943534
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Stewart R
AU - Morrow M
AU - Hammond SA
AU - Mulgrew K
AU - Marcus D
AU - Poon E
AU - Watkins A
AU - Mullins S
AU - Chodorge M
AU - Andrews J
AU - Bannister D
AU - Dick E
AU - Crawford N
AU - Parmentier J
AU - Alimzhanov M
AU - Babcook JS
AU - Foltz IN
AU - Buchanan A
AU - Bedian V
AU - Wilkinson RW
AU - McCourt M
FA - Stewart, Ross
FA - Morrow, Michelle
FA - Hammond, Scott A
FA - Mulgrew, Kathy
FA - Marcus, Danielle
FA - Poon, Edmund
FA - Watkins, Amanda
FA - Mullins, Stefanie
FA - Chodorge, Matthieu
FA - Andrews, John
FA - Bannister, David
FA - Dick, Emily
FA - Crawford, Nicola
FA - Parmentier, Julie
FA - Alimzhanov, Marat
FA - Babcook, John S
FA - Foltz, Ian N
FA - Buchanan, Andrew
FA - Bedian, Vahe
FA - Wilkinson, Robert W
FA - McCourt, Matthew
IN - Stewart, Ross. MedImmune Ltd, Cambridge, United Kingdom. StewartR@medimmune.com.
IN - Morrow, Michelle. MedImmune Ltd, Cambridge, United Kingdom.
IN - Hammond, Scott A. MedImmune LLC, Gaithersburg, Maryland.
IN - Mulgrew, Kathy. MedImmune LLC, Gaithersburg, Maryland.
IN - Marcus, Danielle. MedImmune Ltd, Cambridge, United Kingdom.
IN - Poon, Edmund. MedImmune Ltd, Cambridge, United Kingdom.
IN - Watkins, Amanda. MedImmune Ltd, Cambridge, United Kingdom.
IN - Mullins, Stefanie. MedImmune Ltd, Cambridge, United Kingdom.
IN - Chodorge, Matthieu. MedImmune Ltd, Cambridge, United Kingdom.
IN - Andrews, John. MedImmune Ltd, Cambridge, United Kingdom.
IN - Bannister, David. MedImmune Ltd, Cambridge, United Kingdom.
IN - Dick, Emily. MedImmune Ltd, Cambridge, United Kingdom.
IN - Crawford, Nicola. MedImmune Ltd, Cambridge, United Kingdom.
IN - Parmentier, Julie. Abbvie Inc, Worcester, Massachusetts. Previously AstraZeneca Ltd.
IN - Alimzhanov, Marat. Acceleron Pharma, Inc, Cambridge, Massachusetts. Previously Astrazeneca Ltd.
IN - Babcook, John S. CDRD, University of British Columbia, Vancouver, British Columbia, Canada. Previously Amgen Inc.
IN - Foltz, Ian N. Amgen Inc, Burnaby, British Columbia, Canada.
IN - Buchanan, Andrew. MedImmune Ltd, Cambridge, United Kingdom.
IN - Bedian, Vahe. AstraZeneca Ltd, Waltham, Massachusetts.
IN - Wilkinson, Robert W. MedImmune Ltd, Cambridge, United Kingdom.
IN - McCourt, Matthew. Kymab Ltd, The Bennet Building, Babraham Research Campus, Cambridge, United Kingdom. Previously MedImmune Ltd.
TI - Identification and Characterization of MEDI4736, an Antagonistic Anti-PD-L1 Monoclonal Antibody.
SO - Cancer Immunology Research. 3(9):1052-62, 2015 Sep
AS - Cancer Immunol Res. 3(9):1052-62, 2015 Sep
NJ - Cancer immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101614637
IO - Cancer Immunol Res
SB - Index Medicus
CP - United States
MH - Animals
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antibodies, Monoclonal/me [Metabolism]
MH - *Antibodies, Monoclonal/pd [Pharmacology]
MH - Antibody-Dependent Cell Cytotoxicity/de [Drug Effects]
MH - *Antigens, CD274/ai [Antagonists & Inhibitors]
MH - Antigens, CD274/me [Metabolism]
MH - Antigens, CD80/me [Metabolism]
MH - Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - Binding, Competitive
MH - Colorectal Neoplasms/dt [Drug Therapy]
MH - Colorectal Neoplasms/pa [Pathology]
MH - Female
MH - Humans
MH - Lymphocyte Activation/de [Drug Effects]
MH - Lymphocyte Culture Test, Mixed
MH - Melanoma/im [Immunology]
MH - Melanoma/pa [Pathology]
MH - Melanoma/pc [Prevention & Control]
MH - Mice, Inbred BALB C
MH - Mice, Inbred C57BL
MH - Mice, Inbred NOD
MH - Organoplatinum Compounds/ad [Administration & Dosage]
MH - Pancreatic Neoplasms/im [Immunology]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Pancreatic Neoplasms/pc [Prevention & Control]
MH - Programmed Cell Death 1 Receptor/me [Metabolism]
MH - T-Lymphocytes/de [Drug Effects]
MH - T-Lymphocytes/im [Immunology]
MH - Tumor Cells, Cultured
MH - Xenograft Model Antitumor Assays
AB - Programmed cell-death 1 ligand 1 (PD-L1) is a member of the B7/CD28 family of proteins that control T-cell activation. Many tumors can upregulate expression of PD-L1, inhibiting antitumor T-cell responses and avoiding immune surveillance and elimination. We have identified and characterized MEDI4736, a human IgG1 monoclonal antibody that binds with high affinity and specificity to PD-L1 and is uniquely engineered to prevent antibody-dependent cell-mediated cytotoxicity. In vitro assays demonstrate that MEDI4736 is a potent antagonist of PD-L1 function, blocking interaction with PD-1 and CD80 to overcome inhibition of primary human T-cell activation. In vivo MEDI4736 significantly inhibits the growth of human tumors in a novel xenograft model containing coimplanted human T cells. This activity is entirely dependent on the presence of transplanted T cells, supporting the immunological mechanism of action for MEDI4736. To further determine the utility of PD-L1 blockade, an anti-mouse PD-L1 antibody was investigated in immunocompetent mice. Here, anti-mouse PD-L1 significantly improved survival of mice implanted with CT26 colorectal cancer cells. The antitumor activity of anti-PD-L1 was enhanced by combination with oxaliplatin, which resulted in increased release of HMGB1 within CT26 tumors. Taken together, our results demonstrate that inhibition of PD-L1 function can have potent antitumor activity when used as monotherapy or in combination in preclinical models, and suggest it may be a promising therapeutic approach for the treatment of cancer. MEDI4736 is currently in several clinical trials both alone and in combination with other agents, including anti-CTLA-4, anti-PD-1, and inhibitors of IDO, MEK, BRAF, and EGFR.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD274)
RN - 0 (Antigens, CD80)
RN - 0 (CD274 protein, human)
RN - 0 (Cd274 protein, mouse)
RN - 0 (MEDI4736)
RN - 0 (Organoplatinum Compounds)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 04ZR38536J (oxaliplatin)
ES - 2326-6074
IL - 2326-6066
DI - 2326-6066.CIR-14-0191
DO - https://dx.doi.org/10.1158/2326-6066.CIR-14-0191
PT - Journal Article
ID - 25943534 [pubmed]
ID - 2326-6066.CIR-14-0191 [pii]
ID - 10.1158/2326-6066.CIR-14-0191 [doi]
PP - ppublish
PH - 2014/11/20 [received]
PH - 2015/04/07 [accepted]
LG - English
EP - 20150505
DP - 2015 Sep
DC - 20150905
EZ - 2015/05/07 06:00
DA - 2016/05/26 06:00
DT - 2015/05/07 06:00
YR - 2015
ED - 20160525
RD - 20150905
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25943534
<130. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27093728
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Hamanishi J
AU - Mandai M
AU - Konishi I
FA - Hamanishi, Junzo
FA - Mandai, Masaki
FA - Konishi, Ikuo
TI - [Future Prospects of Anit-PD-1 or Anti-PD-L1 Antibody Therapy]. [Japanese]
SO - Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy]. 43(2):182-8, 2016 Feb
AS - Gan To Kagaku Ryoho. 43(2):182-8, 2016 Feb
NJ - Gan to kagaku ryoho. Cancer & chemotherapy
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 7810034, 6t8
IO - Gan To Kagaku Ryoho
SB - Index Medicus
CP - Japan
MH - *Antibodies/tu [Therapeutic Use]
MH - *Antigens, CD274/im [Immunology]
MH - Clinical Trials as Topic
MH - Female
MH - Humans
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - Ovarian Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Programmed Cell Death 1 Receptor/im [Immunology]
MH - Recurrence
MH - Signal Transduction/de [Drug Effects]
RN - 0 (Antibodies)
RN - 0 (Antigens, CD274)
RN - 0 (CD274 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
IS - 0385-0684
IL - 0385-0684
PT - Journal Article
ID - 27093728 [pubmed]
PP - ppublish
LG - Japanese
DP - 2016 Feb
DC - 20160419
EZ - 2016/04/21 06:00
DA - 2016/04/29 06:00
DT - 2016/04/21 06:00
YR - 2016
ED - 20160428
RD - 20160419
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=27093728
<131. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26573793
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Peng J
AU - Hamanishi J
AU - Matsumura N
AU - Abiko K
AU - Murat K
AU - Baba T
AU - Yamaguchi K
AU - Horikawa N
AU - Hosoe Y
AU - Murphy SK
AU - Konishi I
AU - Mandai M
FA - Peng, Jin
FA - Hamanishi, Junzo
FA - Matsumura, Noriomi
FA - Abiko, Kaoru
FA - Murat, Kumuruz
FA - Baba, Tsukasa
FA - Yamaguchi, Ken
FA - Horikawa, Naoki
FA - Hosoe, Yuko
FA - Murphy, Susan K
FA - Konishi, Ikuo
FA - Mandai, Masaki
IN - Peng, Jin. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
IN - Hamanishi, Junzo. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan. jnkhmns@kuhp.kyoto-u.ac.jp.
IN - Matsumura, Noriomi. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
IN - Abiko, Kaoru. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
IN - Murat, Kumuruz. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
IN - Baba, Tsukasa. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
IN - Yamaguchi, Ken. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
IN - Horikawa, Naoki. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
IN - Hosoe, Yuko. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
IN - Murphy, Susan K. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina.
IN - Konishi, Ikuo. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
IN - Mandai, Masaki. Department of Obstetrics and Gynecology, Kinki University, Osaka, Japan.
TI - Chemotherapy Induces Programmed Cell Death-Ligand 1 Overexpression via the Nuclear Factor-kappaB to Foster an Immunosuppressive Tumor Microenvironment in Ovarian Cancer.
SO - Cancer Research. 75(23):5034-45, 2015 Dec 01
AS - Cancer Res. 75(23):5034-45, 2015 Dec 01
NJ - Cancer research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cnf, 2984705r
IO - Cancer Res.
SB - Index Medicus
CP - United States
MH - Animals
MH - Antigens, CD274/ai [Antagonists & Inhibitors]
MH - *Antigens, CD274/bi [Biosynthesis]
MH - Antigens, CD274/ge [Genetics]
MH - Antigens, CD274/im [Immunology]
MH - *Antineoplastic Combined Chemotherapy Protocols/pd [Pharmacology]
MH - Capecitabine/ad [Administration & Dosage]
MH - Capecitabine/pd [Pharmacology]
MH - Cell Line, Tumor
MH - Female
MH - Humans
MH - Mice
MH - NF-kappa B/im [Immunology]
MH - *NF-kappa B/me [Metabolism]
MH - Organoplatinum Compounds/ad [Administration & Dosage]
MH - Organoplatinum Compounds/pd [Pharmacology]
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - Ovarian Neoplasms/ge [Genetics]
MH - Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/me [Metabolism]
MH - Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - Taxoids/ad [Administration & Dosage]
MH - Taxoids/pd [Pharmacology]
MH - Transcriptome/de [Drug Effects]
MH - Tumor Microenvironment/de [Drug Effects]
MH - *Tumor Microenvironment/im [Immunology]
MH - Xenograft Model Antitumor Assays
AB - Emerging evidence has highlighted the host immune system in modulating the patient response to chemotherapy, but the mechanism of this modulation remains unclear. The aim of this study was to analyze the effect of chemotherapy on antitumor immunity in the tumor microenvironment of ovarian cancer. Treatment of ovarian cancer cell lines with various chemotherapeutic agents resulted in upregulated expression of MHC class I and programmed cell death 1 ligand 1 (PD-L1) in a NF-kappaB-dependent manner and suppression of antigen-specific T-cell function in vitro. In a mouse model of ovarian cancer, treatment with paclitaxel increased CD8(+) T-cell infiltration into the tumor site, upregulated PD-L1 expression, and activated NF-kappaB signaling. In particular, tumor-bearing mice treated with a combination of paclitaxel and a PD-L1/PD-1 signal blockade survived longer than mice treated with paclitaxel alone. In summary, we found that chemotherapy induces local immune suppression in ovarian cancer through NF-kappaB-mediated PD-L1 upregulation. Thus, a combination of chemotherapy and immunotherapy targeting the PD-L1/PD-1 signaling axis may improve the antitumor response and offers a promising new treatment modality against ovarian cancer.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antigens, CD274)
RN - 0 (CD274 protein, human)
RN - 0 (Cd274 protein, mouse)
RN - 0 (NF-kappa B)
RN - 0 (Organoplatinum Compounds)
RN - 0 (PDCD1 protein, human)
RN - 0 (Pdcd1 protein, mouse)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 0 (Taxoids)
RN - 15H5577CQD (docetaxel)
RN - 6804DJ8Z9U (Capecitabine)
ES - 1538-7445
IL - 0008-5472
DI - 0008-5472.CAN-14-3098
DO - https://dx.doi.org/10.1158/0008-5472.CAN-14-3098
PT - Journal Article
ID - 26573793 [pubmed]
ID - 0008-5472.CAN-14-3098 [pii]
ID - 10.1158/0008-5472.CAN-14-3098 [doi]
PP - ppublish
PH - 2014/10/20 [received]
PH - 2015/09/01 [accepted]
LG - English
EP - 20151116
DP - 2015 Dec 01
DC - 20151202
EZ - 2015/11/18 06:00
DA - 2016/04/27 06:00
DT - 2015/11/18 06:00
YR - 2015
ED - 20160426
RD - 20151202
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26573793
<132. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26615135
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Mills TA
AU - Orloff M
AU - Domingo-Vidal M
AU - Cotzia P
AU - Birbe RC
AU - Draganova-Tacheva R
AU - Martinez Cantarin MP
AU - Tuluc M
AU - Martinez-Outschoorn U
FA - Mills, Teresa Anne
FA - Orloff, Marlana
FA - Domingo-Vidal, Marina
FA - Cotzia, Paolo
FA - Birbe, Ruth C
FA - Draganova-Tacheva, Rossitza
FA - Martinez Cantarin, Maria P
FA - Tuluc, Madalina
FA - Martinez-Outschoorn, Ubaldo
IN - Mills, Teresa Anne. Sidney Kimmel College of Medicine Thomas Jefferson University, Philadelphia, PA.
IN - Orloff, Marlana. Department of Medical Oncology Thomas Jefferson University, Philadelphia, PA.
IN - Domingo-Vidal, Marina. Department of Medical Oncology Thomas Jefferson University, Philadelphia, PA.
IN - Cotzia, Paolo. Department of Pathology Thomas Jefferson University, Philadelphia, PA.
IN - Birbe, Ruth C. Department of Pathology Thomas Jefferson University, Philadelphia, PA.
IN - Draganova-Tacheva, Rossitza. Department of Pathology Thomas Jefferson University, Philadelphia, PA.
IN - Martinez Cantarin, Maria P. Department of Medicine Thomas Jefferson University, Philadelphia, PA.
IN - Tuluc, Madalina. Department of Pathology Thomas Jefferson University, Philadelphia, PA.
IN - Martinez-Outschoorn, Ubaldo. Department of Medical Oncology Thomas Jefferson University, Philadelphia, PA. Electronic address: ubaldo.martinezoutschoorn@jefferson.edu.
TI - Parathyroid Hormone-Related Peptide-Linked Hypercalcemia in a Melanoma Patient Treated With Ipilimumab: Hormone Source and Clinical and Metabolic Correlates.
SO - Seminars in Oncology. 42(6):909-14, 2015 Dec
AS - Semin Oncol. 42(6):909-14, 2015 Dec
NJ - Seminars in oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - un5, 0420432
IO - Semin. Oncol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663680
OI - Source: NLM. NIHMS721618 [Available on 12/01/16]
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Cachexia/ci [Chemically Induced]
MH - Female
MH - Humans
MH - Hypercalcemia/ci [Chemically Induced]
MH - *Hypercalcemia/me [Metabolism]
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - Monocarboxylic Acid Transporters/me [Metabolism]
MH - Paraneoplastic Syndromes/ci [Chemically Induced]
MH - *Parathyroid Hormone-Related Protein/me [Metabolism]
MH - Symporters/me [Metabolism]
AB - A patient diagnosed with metastatic melanoma developed the paraneoplastic syndrome of humoral hypercalcemia of malignancy and cachexia after receiving ipilumumab. The cause of the hypercalcemia was thought to be secondary to parathyroid hormone-related peptide (PTHrP) as plasma levels were found to be elevated. The patient underwent two tumor biopsies: at diagnosis (when calcium levels were normal) and upon development of hypercalcemia and cachexia. PTHrP expression was higher in melanoma cells when hypercalcemia had occurred than prior to its onset. Metabolic characterization of melanoma cells revealed that, with development of hypercalcemia, there was high expression of monocarboxylate transporter 1 (MCT1), which is the main importer of lactate and ketone bodies into cells. MCT1 is associated with high mitochondrial metabolism. Beta-galactosidase (beta-GAL), a marker of senescence, had reduced expression in melanoma cells upon development of hypercalcemia compared to pre-hypercalcemia. In conclusion, PTHrP expression in melanoma is associated with cachexia, increased cancer cell lactate and ketone body import, high mitochondrial metabolism, and reduced senescence. Further studies are required to determine if PTHrP regulates cachexia, lactate and ketone body import, mitochondrial metabolism, and senescence in cancer cells.
AB - Copyright © 2015 Elsevier Inc. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Monocarboxylic Acid Transporters)
RN - 0 (PTHLH protein, human)
RN - 0 (Parathyroid Hormone-Related Protein)
RN - 0 (Symporters)
RN - 0 (monocarboxylate transport protein 1)
RN - 6T8C155666 (ipilimumab)
ES - 1532-8708
IL - 0093-7754
DI - S0093-7754(15)00171-2
DO - https://dx.doi.org/10.1053/j.seminoncol.2015.09.006
PT - Case Reports
PT - Journal Article
ID - 26615135 [pubmed]
ID - S0093-7754(15)00171-2 [pii]
ID - 10.1053/j.seminoncol.2015.09.006 [doi]
ID - PMC4663680 [pmc]
ID - NIHMS721618 [mid]
PP - ppublish
GI - No: K08 CA175193
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA056036
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20150908
DP - 2015 Dec
DC - 20151129
EZ - 2015/11/29 06:00
DA - 2016/04/26 06:00
DT - 2015/11/29 06:00
YR - 2015
ED - 20160425
RD - 20161201
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26615135
<133. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27110415
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Collins DC
AU - Yela R
AU - Horgan N
AU - Power DG
FA - Collins, Dearbhaile Catherine
FA - Yela, Ruben
FA - Horgan, Noel
FA - Power, Derek Gerard
IN - Collins, Dearbhaile Catherine. Department of Medical Oncology, Cork University Hospital, Wilton, Co. Cork, Ireland.
IN - Yela, Ruben. Department of Histopathology, Cork University Hospital, Wilton, Co. Cork, Ireland.
IN - Horgan, Noel. Department of Ophthalmology, Royal Victoria Eye and Ear Hospital, Dublin 2, Ireland.
IN - Power, Derek Gerard. Department of Medical Oncology, Cork University Hospital, Wilton, Co. Cork, Ireland.
TI - A Rare Thyroid Metastasis from Uveal Melanoma and Response to Immunotherapy Agents.
SO - Case Reports in Oncological Medicine. 2016:6564094, 2016
AS - Case Rep Oncol Med. 2016:6564094, 2016
NJ - Case reports in oncological medicine
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - 101581035
IO - Case Rep Oncol Med
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823504
CP - United States
AB - Thyroid metastasis is a rare occurrence with cutaneous melanoma and even more uncommon with uveal melanoma. The management of such metastasis is uncertain due to its infrequency and, in the era of immunotherapy, the effect of these novel drugs on uncommon metastasis, such as to the thyroid, is unknown. We report the rare case of a thyroid metastasis in a patient diagnosed with ocular melanoma initially managed with enucleation. Metastatic disease developed in the lung and thyroid gland. The case patient received the immunotherapy ipilimumab with stable disease in the thyroid and progressive disease elsewhere. The patient was then further treated with a second immunotherapy agent, pembrolizumab, and remains with stable disease one year later. We discuss the current literature on thyroid metastases from all causes and the optimal known management strategies. Furthermore, we provide an original report on the response of this disease to the novel immunomodulators, ipilimumab, and pembrolizumab with stable disease four years after initial diagnosis of ocular melanoma.
IS - 2090-6706
DO - https://dx.doi.org/10.1155/2016/6564094
PT - Journal Article
ID - 27110415 [pubmed]
ID - 10.1155/2016/6564094 [doi]
ID - PMC4823504 [pmc]
PP - ppublish
PH - 2015/10/15 [received]
PH - 2016/03/01 [accepted]
LG - English
EP - 20160324
DP - 2016
DC - 20160425
EZ - 2016/04/26 06:00
DA - 2016/04/26 06:01
DT - 2016/04/26 06:00
YR - 2016
ED - 20160425
RD - 20160427
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27110415
<134. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24451730
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Weber JS
FA - Weber, Jeffrey S
IN - Weber, Jeffrey S. From the Moffitt Cancer Center, Tampa, FL.
TI - Practical management of immune-related adverse events from immune checkpoint protein antibodies for the oncologist.
SO - American Society of Clinical Oncology Educational Book. :174-7, 2012
AS - Am. Soc. Clin. Oncol. educ. book. :174-7, 2012
NJ - American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Meeting
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 101233985
IO - Am Soc Clin Oncol Educ Book
CP - United States
AB - Monoclonal antibodies directed against immune checkpoint proteins, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) or programmed death-1 (PD-1), can boost endogenous immune responses directed against tumor cells. Recently, ipilimumab was approved by the U.S. Food and Drug Administration (FDA) for the treatment of metastatic melanoma, and the anti-PD-1 antibody BMS-936558 has shown promising results in patients with melanoma, non-small cell lung cancer, and renal cell cancer. During treatment with these antibodies, a unique set of toxicities occur called immune-related adverse events (irAEs). These irAEs may occur at any time during treatment and include colitis characterized by a mild to moderate but occasionally severe and persistent diarrhea. Hypophysitis, hepatitis, pancreatitis, iridocyclitis, lymphadenopathy, neuropathies, and nephritis have also been reported with ipilimumab, and a subset of those side effects has also been observed with BMS-936558. Patient and physician education as well as good patient-caretaker communication are keys to limiting the morbidity of irAEs. Early recognition of these irAEs and initiation of treatment are critical to reduce the risk of complications, since virtually all irAEs are reversible with the use of steroids and other immune suppressants. The onset of grade 3 to 4 irAEs correlated with treatment response in some ipilimumab studies. This article provides detailed description and recommendations for practicing oncologists to manage the common irAEs associated with antibodies against immune checkpoint blockade.
IS - 1548-8748
IL - 1548-8748
DI - 79
DO - https://dx.doi.org/10.14694/EdBook_AM.2012.32.174
PT - Journal Article
ID - 24451730 [pubmed]
ID - 79 [pii]
ID - 10.14694/EdBook_AM.2012.32.174 [doi]
PP - ppublish
LG - English
DP - 2012
DC - 20140612
EZ - 2014/01/24 06:00
DA - 2012/01/01 00:01
DT - 2012/01/01 00:00
YR - 2012
ED - 20160415
RD - 20161021
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=24451730
<135. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25855890
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Tiu C
AU - Pezaro C
AU - Davis ID
AU - Grossmann M
AU - Parente P
FA - Tiu, Crescens
FA - Pezaro, Carmel
FA - Davis, Ian D
FA - Grossmann, Mathis
FA - Parente, Phillip
IN - Tiu, Crescens. Department of Medical Oncology, Eastern Health, Box Hill, Victoria, Australia.
TI - Early recognition of ipilimumab-related autoimmune hypophysitis in patients with metastatic melanoma: Case studies and recommendations for management.
SO - Asia-Pacific Journal of Clinical Oncology. 11(2):190-4, 2015 Jun
AS - Asia Pac J Clin Oncol. 11(2):190-4, 2015 Jun
NJ - Asia-Pacific journal of clinical oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101241430
IO - Asia Pac J Clin Oncol
SB - Index Medicus
CP - Australia
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Autoimmune Hypophysitis/ci [Chemically Induced]
MH - Humans
MH - Male
MH - *Melanoma/co [Complications]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
KW - CTLA-4; autoimmune hypophysitis; ipilimumab; melanoma
AB - Ipilimumab is a human anti-CTLA-4 monoclonal antibody recently approved for the treatment of advanced melanoma. Stimulation of T-cell activity unmasks antitumor activity, but can cause immune-related adverse events. Autoimmune hypophysitis is of particular importance because its presentation can be subtle but life threatening. We present two cases where early recognition of ipilimumab-related autoimmune hypophysitis led to timely intervention and low subsequent morbidity, without compromise of antitumor effects. We provide recommendations for detection and management of this potentially life-threatening complication of ipilimumab.
AB - Copyright © 2015 Wiley Publishing Asia Pty Ltd.
RN - 0 (Antibodies, Monoclonal)
RN - 6T8C155666 (ipilimumab)
ES - 1743-7563
IL - 1743-7555
DO - https://dx.doi.org/10.1111/ajco.12348
PT - Case Reports
PT - Journal Article
ID - 25855890 [pubmed]
ID - 10.1111/ajco.12348 [doi]
PP - ppublish
PH - 2015/01/11 [accepted]
LG - English
EP - 20150409
DP - 2015 Jun
DC - 20150507
EZ - 2015/04/10 06:00
DA - 2016/04/15 06:00
DT - 2015/04/10 06:00
YR - 2015
ED - 20160414
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25855890
<136. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25965828
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Saini P
AU - Li Y
AU - Dobbelstein M
FA - Saini, Priyanka
FA - Li, Yizhu
FA - Dobbelstein, Matthias
IN - Saini, Priyanka. Institute of Molecular Oncology, Gottingen Centre of Molecular Biosciences (GZMB), Faculty of Medicine, University of Gottingen, Gottingen, Germany.
IN - Li, Yizhu. Institute of Molecular Oncology, Gottingen Centre of Molecular Biosciences (GZMB), Faculty of Medicine, University of Gottingen, Gottingen, Germany.
IN - Dobbelstein, Matthias. Institute of Molecular Oncology, Gottingen Centre of Molecular Biosciences (GZMB), Faculty of Medicine, University of Gottingen, Gottingen, Germany.
TI - Wee1 is required to sustain ATR/Chk1 signaling upon replicative stress.
SO - Oncotarget. 6(15):13072-87, 2015 May 30
AS - Oncotarget. 6(15):13072-87, 2015 May 30
NJ - Oncotarget
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101532965
IO - Oncotarget
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537000
SB - Index Medicus
CP - United States
MH - Antimetabolites, Antineoplastic/ad [Administration & Dosage]
MH - *Antimetabolites, Antineoplastic/pd [Pharmacology]
MH - *Antineoplastic Combined Chemotherapy Protocols/pd [Pharmacology]
MH - Ataxia Telangiectasia Mutated Proteins/me [Metabolism]
MH - *Cell Cycle Proteins/ai [Antagonists & Inhibitors]
MH - *Cell Cycle Proteins/me [Metabolism]
MH - Cell Line, Tumor
MH - Checkpoint Kinase 1
MH - Deoxycytidine/ad [Administration & Dosage]
MH - Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Drug Synergism
MH - Humans
MH - *Nuclear Proteins/ai [Antagonists & Inhibitors]
MH - *Nuclear Proteins/me [Metabolism]
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/en [Enzymology]
MH - *Pancreatic Neoplasms/me [Metabolism]
MH - Protein Kinase Inhibitors/ad [Administration & Dosage]
MH - *Protein Kinase Inhibitors/pd [Pharmacology]
MH - *Protein Kinases/me [Metabolism]
MH - *Protein-Tyrosine Kinases/ai [Antagonists & Inhibitors]
MH - *Protein-Tyrosine Kinases/me [Metabolism]
MH - Signal Transduction
KW - ATR signaling pathway; Wee1; checkpoint kinases; gemcitabine; replicative stress
AB - The therapeutic efficacy of nucleoside analogues, e.g. gemcitabine, against cancer cells can be augmented by inhibitors of checkpoint kinases, including Wee1, ATR, and Chk1. We have compared the chemosensitizing effect of these inhibitors in cells derived from pancreatic cancer, a tumor entity where gemcitabine is part of the first-line therapeutic regimens, and in osteosarcoma-derived cells. As expected, all three inhibitors rendered cancer cells more sensitive to gemcitabine, but Wee1 inhibition proved to be particularly efficient in this context. Investigating the reasons for this potent sensitizing effect, we found that Wee1 inhibition or knockdown not only blocked Wee1 activity, but also reduced the activation of ATR/Chk1 in gemcitabine-treated cells. Combination of several inhibitors revealed that Wee1 inhibition requires Cyclin-dependent kinases 1 and 2 (Cdk1/2) and Polo-like kinase 1 (Plk1) to reduce ATR/Chk1 activity. Through activation of Cdks and Plk1, Wee1 inhibition reduces Claspin and CtIP levels, explaining the impairment in ATR/Chk1 activity. Taken together, these results confer a consistent signaling pathway reaching from Wee1 inhibition to impaired Chk1 activity, mechanistically dissecting how Wee1 inhibitors not only dysregulate cell cycle progression, but also enhance replicative stress and chemosensitivity towards nucleoside analogues.
RN - 0 (Antimetabolites, Antineoplastic)
RN - 0 (Cell Cycle Proteins)
RN - 0 (Nuclear Proteins)
RN - 0 (Protein Kinase Inhibitors)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7 (Protein Kinases)
RN - EC 2-7-10-1 (Protein-Tyrosine Kinases)
RN - EC 2-7-10-2 (WEE1 protein, human)
RN - EC 2-7-11-1 (ATR protein, human)
RN - EC 2-7-11-1 (Ataxia Telangiectasia Mutated Proteins)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
ES - 1949-2553
IL - 1949-2553
DI - 3865
DO - https://dx.doi.org/10.18632/oncotarget.3865
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 25965828 [pubmed]
ID - 3865 [pii]
ID - PMC4537000 [pmc]
ID - 10.18632/oncotarget.3865 [doi]
PP - ppublish
PH - 2014/12/05 [received]
PH - 2015/03/31 [accepted]
LG - English
DP - 2015 May 30
DC - 20150617
EZ - 2015/05/13 06:00
DA - 2016/04/14 06:00
DT - 2015/05/13 06:00
YR - 2015
ED - 20160412
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25965828
<137. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25444021
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Gedye C
AU - van der Westhuizen A
AU - John T
FA - Gedye, C
FA - van der Westhuizen, A
FA - John, T
IN - Gedye, C. School of Biomedical Sciences and Pharmacy, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
IN - Gedye, C. Department of Medical Oncology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia.
IN - van der Westhuizen, A. Department of Medical Oncology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia.
IN - John, T. Department of Medical Oncology, Olivia Newton John Cancer and Wellness Centre, Austin Hospital, Melbourne, Victoria, Australia.
TI - Checkpoint immunotherapy for cancer: superior survival, unaccustomed toxicities. [Review]
SO - Internal Medicine Journal. 45(7):696-701, 2015 Jul
AS - Intern Med J. 45(7):696-701, 2015 Jul
NJ - Internal medicine journal
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - d20, 101092952
IO - Intern Med J
SB - Index Medicus
CP - Australia
MH - *Genes, cdc/im [Immunology]
MH - Humans
MH - Immunotherapy/ae [Adverse Effects]
MH - *Immunotherapy/mt [Methods]
MH - *Neoplasms/mo [Mortality]
MH - *Neoplasms/th [Therapy]
MH - Survival Rate
KW - cancer; checkpoint protein; immune-related side-effect; immunotherapy; lung cancer; melanoma
AB - Novel cancer immunotherapy antibodies are moving from clinical trials into routine practice, delivering sustained benefits and prolonged survival to patients with melanoma, lung, kidney and other cancers. These immunostimulatory antibodies non-specifically activate the patient's own immune system by inhibiting immune system checkpoint proteins. This mechanism of action is entirely different to traditional cancer treatments, such as chemotherapy. While there are virtually no immediate toxicities, serious life-threatening autoimmune side-effects such as colitis, dermatitis, hypophysitis, pneumonitis and hepatitis can occur, sometimes starting long after the treatment has been given. Recognition, referral and prompt treatment with immunosuppressive drugs like corticosteroids can control these immune-related side-effects without compromising efficacy. This exciting new class of drugs is defining a new paradigm in cancer therapy.
AB - Copyright © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.
ES - 1445-5994
IL - 1444-0903
DO - https://dx.doi.org/10.1111/imj.12653
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 25444021 [pubmed]
ID - 10.1111/imj.12653 [doi]
PP - ppublish
PH - 2014/09/14 [received]
PH - 2014/11/26 [accepted]
LG - English
DP - 2015 Jul
DC - 20150703
EZ - 2014/12/03 06:00
DA - 2016/04/06 06:00
DT - 2014/12/03 06:00
YR - 2015
ED - 20160405
RD - 20150703
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25444021
<138. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25866054
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Teo PY
AU - Yang C
AU - Whilding LM
AU - Parente-Pereira AC
AU - Maher J
AU - George AJ
AU - Hedrick JL
AU - Yang YY
AU - Ghaem-Maghami S
FA - Teo, Pei Yun
FA - Yang, Chuan
FA - Whilding, Lynsey M
FA - Parente-Pereira, Ana C
FA - Maher, John
FA - George, Andrew J T
FA - Hedrick, James L
FA - Yang, Yi Yan
FA - Ghaem-Maghami, Sadaf
IN - Teo, Pei Yun. Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
IN - Teo, Pei Yun. Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
IN - Yang, Chuan. Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
IN - Whilding, Lynsey M. Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
IN - Whilding, Lynsey M. King's College London, Guy's Hospital, St Thomas Street, London, SE1 9RT, UK.
IN - Parente-Pereira, Ana C. King's College London, Guy's Hospital, St Thomas Street, London, SE1 9RT, UK.
IN - Maher, John. King's College London, Guy's Hospital, St Thomas Street, London, SE1 9RT, UK.
IN - George, Andrew J T. Brunel University, Kingston Lane, Uxbridge, Middlesex, UB8 3PH, UK.
IN - Hedrick, James L. IBM Almaden Research Center, 650 Harry Road, San Jose, CA, 95120, USA.
IN - Yang, Yi Yan. Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore, 138669, Singapore.
IN - Ghaem-Maghami, Sadaf. Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
TI - Ovarian cancer immunotherapy using PD-L1 siRNA targeted delivery from folic acid-functionalized polyethylenimine: strategies to enhance T cell killing.
SO - Advanced Healthcare Materials. 4(8):1180-9, 2015 Jun 03
AS - Ad. healthc. mater.. 4(8):1180-9, 2015 Jun 03
NJ - Advanced healthcare materials
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101581613
IO - Adv Healthc Mater
SB - Index Medicus
CP - Germany
MH - *Antigens, CD274/ge [Genetics]
MH - Antigens, CD274/me [Metabolism]
MH - Cell Line, Tumor
MH - Down-Regulation
MH - Female
MH - *Folic Acid/me [Metabolism]
MH - *Gene Expression Regulation, Neoplastic
MH - Genetic Therapy
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Lysosomal-Associated Membrane Protein 1/ge [Genetics]
MH - Lysosomal-Associated Membrane Protein 1/me [Metabolism]
MH - Nanoparticles/ch [Chemistry]
MH - *Neoplasms, Glandular and Epithelial/ge [Genetics]
MH - Neoplasms, Glandular and Epithelial/th [Therapy]
MH - *Ovarian Neoplasms/ge [Genetics]
MH - Ovarian Neoplasms/th [Therapy]
MH - Particle Size
MH - Polyethylene Glycols/ch [Chemistry]
MH - *Polyethyleneimine/me [Metabolism]
MH - Polymers/ch [Chemistry]
MH - *RNA, Small Interfering/ge [Genetics]
MH - T-Lymphocytes/me [Metabolism]
KW - PD-L1 knock-down; T cells; ovarian cancer; polyethylenimine; siRNA delivery
AB - Adoptive T cell immunotherapy is a promising treatment strategy for epithelial ovarian cancer (EOC). However, programmed death ligand-1 (PD-L1), highly expressed on EOC cells, interacts with programmed death-1 (PD-1), expressed on T cells, causing immunosuppression. This study aims to block PD-1/PD-L1 interactions by delivering PD-L1 siRNA, using various folic acid (FA)-functionalized polyethylenimine (PEI) polymers, to SKOV-3-Luc EOC cells, and investigate the sensitization of the EOC cells to T cell killing. To enhance siRNA uptake into EOC cells, which over express folate receptors, PEI is modified with FA or PEG-FA so that siRNA is complexed into nanoparticles with folate molecules on the surface. PEI modification with a single functional group lowers the polymer cytotoxicity compared to unmodified PEI. FA-conjugated polymers increase siRNA uptake into SKOV-3-luc cells and decrease unspecific uptake into monocytes. All polymers result in 40% to 50% PD-L1 protein knockdown. Importantly, SKOV-3-Luc cells treated with either PEI-FA or PEI- polyethylene glycol (PEG)-FA/PD-L1 siRNA complexes are up to twofold more sensitive to T cell killing compared to scrambled siRNA treated controls. These findings are the first to demonstrate that PD-L1 knockdown in EOC cells, via siRNA/FA-targeted delivery, are able to sensitize cancer cells to T cell killing.
AB - Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
RN - 0 (Antigens, CD274)
RN - 0 (CD274 protein, human)
RN - 0 (Lysosomal-Associated Membrane Protein 1)
RN - 0 (Polymers)
RN - 0 (RNA, Small Interfering)
RN - 30IQX730WE (Polyethylene Glycols)
RN - 9002-98-6 (Polyethyleneimine)
RN - 935E97BOY8 (Folic Acid)
RS - Ovarian epithelial cancer
ES - 2192-2659
IL - 2192-2640
DO - https://dx.doi.org/10.1002/adhm.201500089
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 25866054 [pubmed]
ID - 10.1002/adhm.201500089 [doi]
PP - ppublish
PH - 2015/02/07 [received]
PH - 2015/03/17 [revised]
LG - English
EP - 20150411
DP - 2015 Jun 03
DC - 20150604
EZ - 2015/04/14 06:00
DA - 2016/03/26 06:00
DT - 2015/04/14 06:00
YR - 2015
ED - 20160325
RD - 20150604
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25866054
<139. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26236750
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - De Felice F
AU - Marchetti C
AU - Palaia I
AU - Musio D
AU - Muzii L
AU - Tombolini V
AU - Panici PB
FA - De Felice, Francesca
FA - Marchetti, Claudia
FA - Palaia, Innocenza
FA - Musio, Daniela
FA - Muzii, Ludovico
FA - Tombolini, Vincenzo
FA - Panici, Pierluigi Benedetti
IN - De Felice, Francesca. Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Viale Regina Elena 326, 00161 Rome, Italy.
IN - Marchetti, Claudia. Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
IN - Palaia, Innocenza. Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
IN - Musio, Daniela. Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Viale Regina Elena 326, 00161 Rome, Italy.
IN - Muzii, Ludovico. Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
IN - Tombolini, Vincenzo. Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Viale Regina Elena 326, 00161 Rome, Italy.
IN - Panici, Pierluigi Benedetti. Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
TI - Immunotherapy of Ovarian Cancer: The Role of Checkpoint Inhibitors. [Review]
SO - Journal of Immunological Research. 2015:191832, 2015
AS - J. immunol. res.. 2015:191832, 2015
NJ - Journal of immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101627166
IO - J Immunol Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508475
SB - Index Medicus
CP - Egypt
MH - Antibodies, Monoclonal/pd [Pharmacology]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Clinical Trials as Topic
MH - Female
MH - Humans
MH - Immune System
MH - Immunologic Factors/pd [Pharmacology]
MH - Immunologic Factors/tu [Therapeutic Use]
MH - Immunomodulation
MH - Immunotherapy/mt [Methods]
MH - *Immunotherapy
MH - Molecular Targeted Therapy
MH - *Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/me [Metabolism]
MH - *Ovarian Neoplasms/th [Therapy]
MH - Treatment Outcome
AB - Ovarian cancer is the most important cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease. Although surgery and chemotherapy can improve survival rates, it is necessary to integrate alternative strategies to improve the outcomes. Advances in understanding the role of immune system in the pathogenesis of cancer have led to the rapid evolvement of immunotherapy, which might establish a sustained immune system response against recurring cancer cells. Recently, it has emerged that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called "immune checkpoints," which turn off the immune system. Similarly, cancer cells are able to use these checkpoints to avoid immune control and rejection. Inhibition of these inhibitory pathways represents a potent strategy in the fight against cancer and is currently under investigation with encouraging results in some cancers, such as melanoma. In ovarian cancer researches are still in an early phase, but with promising results. In this review we will explore the rationale of immunotherapy in ovarian cancer with a special focus on these emerging molecules.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Immunologic Factors)
ES - 2314-7156
IL - 2314-7156
DO - https://dx.doi.org/10.1155/2015/191832
PT - Journal Article
PT - Review
ID - 26236750 [pubmed]
ID - 10.1155/2015/191832 [doi]
ID - PMC4508475 [pmc]
PP - ppublish
PH - 2015/03/22 [received]
PH - 2015/06/23 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01611558
SL - https://clinicaltrials.gov/search/term=NCT01611558
LG - English
EP - 20150707
DP - 2015
DC - 20150803
EZ - 2015/08/04 06:00
DA - 2016/03/25 06:00
DT - 2015/08/04 06:00
YR - 2015
ED - 20160324
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26236750
<140. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26236750
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - De Felice F
AU - Marchetti C
AU - Palaia I
AU - Musio D
AU - Muzii L
AU - Tombolini V
AU - Panici PB
FA - De Felice, Francesca
FA - Marchetti, Claudia
FA - Palaia, Innocenza
FA - Musio, Daniela
FA - Muzii, Ludovico
FA - Tombolini, Vincenzo
FA - Panici, Pierluigi Benedetti
IN - De Felice, Francesca. Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Viale Regina Elena 326, 00161 Rome, Italy.
IN - Marchetti, Claudia. Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
IN - Palaia, Innocenza. Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
IN - Musio, Daniela. Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Viale Regina Elena 326, 00161 Rome, Italy.
IN - Muzii, Ludovico. Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
IN - Tombolini, Vincenzo. Department of Radiotherapy, Policlinico Umberto I, "Sapienza" University of Rome, Viale Regina Elena 326, 00161 Rome, Italy.
IN - Panici, Pierluigi Benedetti. Department of Gynecological and Obstetrical Sciences and Urological Sciences, "Sapienza" University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
TI - Immunotherapy of Ovarian Cancer: The Role of Checkpoint Inhibitors. [Review]
SO - Journal of Immunological Research. 2015:191832, 2015
AS - J. immunol. res.. 2015:191832, 2015
NJ - Journal of immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101627166
IO - J Immunol Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508475
SB - Index Medicus
CP - Egypt
MH - Antibodies, Monoclonal/pd [Pharmacology]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Clinical Trials as Topic
MH - Female
MH - Humans
MH - Immune System
MH - Immunologic Factors/pd [Pharmacology]
MH - Immunologic Factors/tu [Therapeutic Use]
MH - Immunomodulation
MH - Immunotherapy/mt [Methods]
MH - *Immunotherapy
MH - Molecular Targeted Therapy
MH - *Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/me [Metabolism]
MH - *Ovarian Neoplasms/th [Therapy]
MH - Treatment Outcome
AB - Ovarian cancer is the most important cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease. Although surgery and chemotherapy can improve survival rates, it is necessary to integrate alternative strategies to improve the outcomes. Advances in understanding the role of immune system in the pathogenesis of cancer have led to the rapid evolvement of immunotherapy, which might establish a sustained immune system response against recurring cancer cells. Recently, it has emerged that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called "immune checkpoints," which turn off the immune system. Similarly, cancer cells are able to use these checkpoints to avoid immune control and rejection. Inhibition of these inhibitory pathways represents a potent strategy in the fight against cancer and is currently under investigation with encouraging results in some cancers, such as melanoma. In ovarian cancer researches are still in an early phase, but with promising results. In this review we will explore the rationale of immunotherapy in ovarian cancer with a special focus on these emerging molecules.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Immunologic Factors)
ES - 2314-7156
IL - 2314-7156
DO - https://dx.doi.org/10.1155/2015/191832
PT - Journal Article
PT - Review
ID - 26236750 [pubmed]
ID - 10.1155/2015/191832 [doi]
ID - PMC4508475 [pmc]
PP - ppublish
PH - 2015/03/22 [received]
PH - 2015/06/23 [accepted]
LG - English
EP - 20150707
DP - 2015
DC - 20150803
EZ - 2015/08/04 06:00
DA - 2016/03/25 06:00
DT - 2015/08/04 06:00
YR - 2015
ED - 20160324
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26236750
<141. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26209970
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Carl D
AU - Grullich C
AU - Hering S
AU - Schabet M
FA - Carl, David
FA - Grullich, Carsten
FA - Hering, Steffen
FA - Schabet, Martin
IN - Carl, David. Department of Neurology, Klinikum Ludwigsburg, Posilipostrase 4, Ludwigsburg, Germany. david.carl@mail.klinikum-darmstadt.de.
IN - Grullich, Carsten. National Cent Tumor Diseases (NCT), Heidelberg, Germany. carsten.gruellich@nct-heidelberg.de.
IN - Hering, Steffen. Department of Internal Medicine, Klinikum Bietigheim, Bietigheim-Bissingen, Germany. steffen.hering@kliniken-lb.de.
IN - Schabet, Martin. Department of Neurology, Klinikum Ludwigsburg, Posilipostrase 4, Ludwigsburg, Germany. martin.schabet@kliniken-lb.de.
TI - Steroid responsive encephalopathy associated with autoimmune thyroiditis following ipilimumab therapy: a case report.
SO - BMC Research Notes. 8:316, 2015 Jul 26
AS - BMC Res Notes. 8:316, 2015 Jul 26
NJ - BMC research notes
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101462768
IO - BMC Res Notes
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514969
SB - Index Medicus
CP - England
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Autoantibodies/bi [Biosynthesis]
MH - *Brain Diseases/ci [Chemically Induced]
MH - Brain Diseases/dt [Drug Therapy]
MH - Brain Diseases/pa [Pathology]
MH - Humans
MH - Male
MH - Methylprednisolone/tu [Therapeutic Use]
MH - Middle Aged
MH - Prostatic Neoplasms/dt [Drug Therapy]
MH - Prostatic Neoplasms/pa [Pathology]
MH - *Thyroiditis, Autoimmune/ci [Chemically Induced]
MH - Thyroiditis, Autoimmune/dt [Drug Therapy]
MH - Thyroiditis, Autoimmune/pa [Pathology]
AB - BACKGROUND: Ipilimumab is a cytotoxic T-lymphocyte-associated protein 4 receptor antibody used for immunotherapy in cancer. Several immune-related adverse events are known. Steroid responsive encephalopathy associated with autoimmune thyroiditis is an autoimmune encephalopathy associated with Hashimoto's Disease and elevated serum levels of the related antibodies (anti-thyroid-peroxidase antibody or anti-thyroglobulin antibody). Our case implies that steroid responsive encephalopathy associated with autoimmune thyroiditis may be another previously unreported side effect of ipilimumab therapy.
AB - CASE PRESENTATION: We report the case of a 64 years old caucasian patient with prostatic cancer who received ipilimumab therapy in a clinical trial. He presented with aphasia, tremor and ataxia, myocloni, hallucinations, anxiety and agitation in turns with somnolence. Cranial nerves, deep tendon reflexes, motor and sensory functions were normal. Electroencephalography showed background slowing but no epileptic discharges. Brain magnetic resonance imaging was normal and showed no signs of hypophysitis. Cerebrospinal fluid findings ruled out infection and neoplastic meningitis. Anti-thyroid antibodies (anti-thyroid-peroxidase antibody and anti-thyroglobulin antibody) were heavily increased. Assuming steroid responsive encephalopathy associated with autoimmune thyroiditis the patient was treated with 1,000 mg methylprednisolone i.v. for 3 days and continued with 1 mg/kg orally. On the 3rd day of treatment the patient's condition started to improve. Within the next few days he gradually returned to his previous state, and electroencephalography eventually showed only slight slowing. Seven months later the patient's condition was stable, and anti-thyroid antibodies were no more detectable.
AB - CONCLUSION: Steroid responsive encephalopathy associated with autoimmune thyroiditis may be a hitherto unrecognized complication of ipililumab treatment and should be taken into consideration in patients developing central nervous symptoms undergoing this treatment.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (Autoantibodies)
RN - 0 (anti-thyroglobulin)
RN - 6T8C155666 (ipilimumab)
RN - X4W7ZR7023 (Methylprednisolone)
ES - 1756-0500
IL - 1756-0500
DI - 10.1186/s13104-015-1283-9
DO - https://dx.doi.org/10.1186/s13104-015-1283-9
PT - Case Reports
PT - Journal Article
ID - 26209970 [pubmed]
ID - 10.1186/s13104-015-1283-9 [doi]
ID - 10.1186/s13104-015-1283-9 [pii]
ID - PMC4514969 [pmc]
PP - epublish
PH - 2014/10/11 [received]
PH - 2015/07/16 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01057810
SL - https://clinicaltrials.gov/search/term=NCT01057810
LG - English
EP - 20150726
DP - 2015 Jul 26
DC - 20150727
EZ - 2015/07/27 06:00
DA - 2016/03/18 06:00
DT - 2015/07/27 06:00
YR - 2015
ED - 20160317
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26209970
<142. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26209970
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Carl D
AU - Grullich C
AU - Hering S
AU - Schabet M
FA - Carl, David
FA - Grullich, Carsten
FA - Hering, Steffen
FA - Schabet, Martin
IN - Carl, David. Department of Neurology, Klinikum Ludwigsburg, Posilipostrase 4, Ludwigsburg, Germany. david.carl@mail.klinikum-darmstadt.de.
IN - Grullich, Carsten. National Cent Tumor Diseases (NCT), Heidelberg, Germany. carsten.gruellich@nct-heidelberg.de.
IN - Hering, Steffen. Department of Internal Medicine, Klinikum Bietigheim, Bietigheim-Bissingen, Germany. steffen.hering@kliniken-lb.de.
IN - Schabet, Martin. Department of Neurology, Klinikum Ludwigsburg, Posilipostrase 4, Ludwigsburg, Germany. martin.schabet@kliniken-lb.de.
TI - Steroid responsive encephalopathy associated with autoimmune thyroiditis following ipilimumab therapy: a case report.
SO - BMC Research Notes. 8:316, 2015 Jul 26
AS - BMC Res Notes. 8:316, 2015 Jul 26
NJ - BMC research notes
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101462768
IO - BMC Res Notes
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514969
SB - Index Medicus
CP - England
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Autoantibodies/bi [Biosynthesis]
MH - *Brain Diseases/ci [Chemically Induced]
MH - Brain Diseases/dt [Drug Therapy]
MH - Brain Diseases/pa [Pathology]
MH - Humans
MH - Male
MH - Methylprednisolone/tu [Therapeutic Use]
MH - Middle Aged
MH - Prostatic Neoplasms/dt [Drug Therapy]
MH - Prostatic Neoplasms/pa [Pathology]
MH - *Thyroiditis, Autoimmune/ci [Chemically Induced]
MH - Thyroiditis, Autoimmune/dt [Drug Therapy]
MH - Thyroiditis, Autoimmune/pa [Pathology]
AB - BACKGROUND: Ipilimumab is a cytotoxic T-lymphocyte-associated protein 4 receptor antibody used for immunotherapy in cancer. Several immune-related adverse events are known. Steroid responsive encephalopathy associated with autoimmune thyroiditis is an autoimmune encephalopathy associated with Hashimoto's Disease and elevated serum levels of the related antibodies (anti-thyroid-peroxidase antibody or anti-thyroglobulin antibody). Our case implies that steroid responsive encephalopathy associated with autoimmune thyroiditis may be another previously unreported side effect of ipilimumab therapy.
AB - CASE PRESENTATION: We report the case of a 64 years old caucasian patient with prostatic cancer who received ipilimumab therapy in a clinical trial. He presented with aphasia, tremor and ataxia, myocloni, hallucinations, anxiety and agitation in turns with somnolence. Cranial nerves, deep tendon reflexes, motor and sensory functions were normal. Electroencephalography showed background slowing but no epileptic discharges. Brain magnetic resonance imaging was normal and showed no signs of hypophysitis. Cerebrospinal fluid findings ruled out infection and neoplastic meningitis. Anti-thyroid antibodies (anti-thyroid-peroxidase antibody and anti-thyroglobulin antibody) were heavily increased. Assuming steroid responsive encephalopathy associated with autoimmune thyroiditis the patient was treated with 1,000 mg methylprednisolone i.v. for 3 days and continued with 1 mg/kg orally. On the 3rd day of treatment the patient's condition started to improve. Within the next few days he gradually returned to his previous state, and electroencephalography eventually showed only slight slowing. Seven months later the patient's condition was stable, and anti-thyroid antibodies were no more detectable.
AB - CONCLUSION: Steroid responsive encephalopathy associated with autoimmune thyroiditis may be a hitherto unrecognized complication of ipililumab treatment and should be taken into consideration in patients developing central nervous symptoms undergoing this treatment.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (Autoantibodies)
RN - 0 (anti-thyroglobulin)
RN - 6T8C155666 (ipilimumab)
RN - X4W7ZR7023 (Methylprednisolone)
ES - 1756-0500
IL - 1756-0500
DI - 10.1186/s13104-015-1283-9
DO - https://dx.doi.org/10.1186/s13104-015-1283-9
PT - Case Reports
PT - Journal Article
ID - 26209970 [pubmed]
ID - 10.1186/s13104-015-1283-9 [doi]
ID - 10.1186/s13104-015-1283-9 [pii]
ID - PMC4514969 [pmc]
PP - epublish
PH - 2014/10/11 [received]
PH - 2015/07/16 [accepted]
LG - English
EP - 20150726
DP - 2015 Jul 26
DC - 20150727
EZ - 2015/07/27 06:00
DA - 2016/03/18 06:00
DT - 2015/07/27 06:00
YR - 2015
ED - 20160317
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26209970
<143. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26060068
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Dangaj D
AU - Scholler N
FA - Dangaj, Denarda
FA - Scholler, Nathalie
IN - Dangaj, Denarda. Department of Oncology, Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland.
TI - Isolation and Validation of Anti-B7-H4 scFvs from an Ovarian Cancer scFv Yeast-Display Library.
SO - Methods in Molecular Biology. 1319:37-49, 2015
AS - Methods Mol Biol. 1319:37-49, 2015
NJ - Methods in molecular biology (Clifton, N.J.)
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - bu3, 9214969
IO - Methods Mol. Biol.
SB - Index Medicus
CP - United States
MH - Animals
MH - Antigen Presentation
MH - B-Lymphocytes/im [Immunology]
MH - Female
MH - Gene Library
MH - Humans
MH - Mice
MH - Ovarian Neoplasms/bl [Blood]
MH - *Ovarian Neoplasms/im [Immunology]
MH - *Saccharomyces cerevisiae/ge [Genetics]
MH - Saccharomyces cerevisiae/me [Metabolism]
MH - Single-Chain Antibodies/ge [Genetics]
MH - *Single-Chain Antibodies/ip [Isolation & Purification]
MH - T-Lymphocytes/im [Immunology]
MH - *V-Set Domain-Containing T-Cell Activation Inhibitor 1/me [Metabolism]
MH - Xenograft Model Antitumor Assays
AB - B7-H4 (VTCN1, B7x, B7s) is an inhibitory modulator of T-cell response implicated in antigen tolerization. As such, B7-H4 is an immune checkpoint of potential therapeutic interest. To generate anti-B7-H4 targeting reagents, we isolated antibodies by differential cell screening of a yeast-display library of recombinant antibodies (scFvs) derived from ovarian cancer patients and we screened for functional scFvs capable to interfere with B7-H4-mediated inhibition of antitumor responses. We found one antibody binding to B7-H4 that could restore antitumor T cell responses. This chapter gives an overview of the methods we developed to isolate a functional anti-B7-H4 antibody fragment.
RN - 0 (Single-Chain Antibodies)
RN - 0 (V-Set Domain-Containing T-Cell Activation Inhibitor 1)
RN - 0 (VTCN1 protein, human)
ES - 1940-6029
IL - 1064-3745
DO - https://dx.doi.org/10.1007/978-1-4939-2748-7_2
PT - Journal Article
ID - 26060068 [pubmed]
ID - 10.1007/978-1-4939-2748-7_2 [doi]
PP - ppublish
LG - English
DP - 2015
DC - 20150610
EZ - 2015/06/11 06:00
DA - 2016/03/16 06:00
DT - 2015/06/11 06:00
YR - 2015
ED - 20160315
RD - 20150610
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26060068
<144. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25588542
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wu H
AU - Sun Y
AU - Ye H
AU - Yang S
AU - Lee SL
AU - de las Morenas A
FA - Wu, Hao
FA - Sun, Yue
FA - Ye, Huihui
FA - Yang, Shi
FA - Lee, Stephanie L
FA - de las Morenas, Antonio
IN - Wu, Hao. Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, AB190.11, 6621 Fannin Street, Houston, TX, 77030, USA, hao.wu@bcm.edu.
TI - Anaplastic thyroid cancer: outcome and the mutation/expression profiles of potential targets.
SO - Pathology Oncology Research. 21(3):695-701, 2015 Jul
AS - Pathol Oncol Res. 21(3):695-701, 2015 Jul
NJ - Pathology oncology research : POR
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c3s, 9706087
IO - Pathol. Oncol. Res.
SB - Index Medicus
CP - Netherlands
MH - Adenocarcinoma, Follicular/ge [Genetics]
MH - Adenocarcinoma, Follicular/me [Metabolism]
MH - Adenocarcinoma, Follicular/mo [Mortality]
MH - Adenocarcinoma, Follicular/sc [Secondary]
MH - Adult
MH - Aged
MH - *Antigens, CD274/me [Metabolism]
MH - Biomarkers, Tumor/ge [Genetics]
MH - Biomarkers, Tumor/me [Metabolism]
MH - Female
MH - Follow-Up Studies
MH - Humans
MH - Male
MH - Middle Aged
MH - *Mutation/ge [Genetics]
MH - Neoplasm Metastasis
MH - Neoplasm Staging
MH - Prognosis
MH - *Proto-Oncogene Proteins B-raf/ge [Genetics]
MH - *Proto-Oncogene Proteins c-kit/me [Metabolism]
MH - *Proto-Oncogene Proteins p21(ras)/ge [Genetics]
MH - *Receptor, Epidermal Growth Factor/ge [Genetics]
MH - Retrospective Studies
MH - Survival Rate
MH - Thyroid Carcinoma, Anaplastic/ge [Genetics]
MH - Thyroid Carcinoma, Anaplastic/me [Metabolism]
MH - Thyroid Carcinoma, Anaplastic/mo [Mortality]
MH - *Thyroid Carcinoma, Anaplastic/pa [Pathology]
MH - Thyroid Neoplasms/ge [Genetics]
MH - Thyroid Neoplasms/me [Metabolism]
MH - Thyroid Neoplasms/mo [Mortality]
MH - Thyroid Neoplasms/pa [Pathology]
AB - Anaplastic thyroid cancer (ATC) is a rare but aggressive malignancy of the thyroid. No effective treatment modalities are currently available. Targeted therapy against protein kinases showed promising results in preclinical studies. Our goal was to assess the mutational status of potential therapeutic targets, as well as the biomarker for immunotherapy in the clinical context. Using allele specific PCR, Sanger sequencing, fragment analysis and immunohistochemistry, we assessed BRAF, KRAS, EGFR mutations and protein overexpression of C-KIT and PDL1 in anaplastic thyroid cancer specimens. Results were compared to clinical information and patient outcome to assess the utility of these biomarkers. There were 13 patients in our study with a median overall survival of 19 weeks. Of the 13 ATC patients, 3 (23 %) had BRAF V600E mutation. C-KIT overexpression was found in 1 (8 %) patient who responded well to a tyrosine kinase inhibitor. PDL1 expression was seen in 3 (23 %) patients, none of them were surgical candidates due to unresectability and poor performance status. KRAS codon 12/13 and EGFR exon 18, 19, 20 and 21 were all wild type in our patients. Protein kinase inhibitors and immunotherapy may be useful adjuvant therapies for ATC.
RN - 0 (Antigens, CD274)
RN - 0 (Biomarkers, Tumor)
RN - 0 (CD274 protein, human)
RN - 0 (KRAS protein, human)
RN - EC 2-7-10-1 (EGFR protein, human)
RN - EC 2-7-10-1 (Proto-Oncogene Proteins c-kit)
RN - EC 2-7-10-1 (Receptor, Epidermal Growth Factor)
RN - EC 2-7-11-1 (BRAF protein, human)
RN - EC 2-7-11-1 (Proto-Oncogene Proteins B-raf)
RN - EC 3-6-5-2 (Proto-Oncogene Proteins p21(ras))
ES - 1532-2807
IL - 1219-4956
DO - https://dx.doi.org/10.1007/s12253-014-9876-5
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 25588542 [pubmed]
ID - 10.1007/s12253-014-9876-5 [doi]
PP - ppublish
PH - 2014/10/17 [received]
PH - 2014/12/05 [accepted]
LG - English
EP - 20150115
DP - 2015 Jul
DC - 20150603
EZ - 2015/01/16 06:00
DA - 2016/03/11 06:00
DT - 2015/01/16 06:00
YR - 2015
ED - 20160310
RD - 20150603
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25588542
<145. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26958083
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Kim ST
AU - Ha SY
AU - Lee S
AU - Ahn S
AU - Lee J
AU - Park SH
AU - Park JO
AU - Lim HY
AU - Kang WK
AU - Kim KM
AU - Park YS
FA - Kim, Seung Tae
FA - Ha, Sang Yun
FA - Lee, Sujin
FA - Ahn, Soomin
FA - Lee, Jeeyun
FA - Park, Se Hoon
FA - Park, Joon Oh
FA - Lim, Ho Yeong
FA - Kang, Won Ki
FA - Kim, Kyoung-Mee
FA - Park, Young Suk
IN - Kim, Seung Tae. 1. Division of Hematology-Oncology, Department of Medicine.
IN - Ha, Sang Yun. 2. Department of Pathology & Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
IN - Lee, Sujin. 1. Division of Hematology-Oncology, Department of Medicine.
IN - Ahn, Soomin. 2. Department of Pathology & Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
IN - Lee, Jeeyun. 1. Division of Hematology-Oncology, Department of Medicine.
IN - Park, Se Hoon. 1. Division of Hematology-Oncology, Department of Medicine.
IN - Park, Joon Oh. 1. Division of Hematology-Oncology, Department of Medicine.
IN - Lim, Ho Yeong. 1. Division of Hematology-Oncology, Department of Medicine.
IN - Kang, Won Ki. 1. Division of Hematology-Oncology, Department of Medicine.
IN - Kim, Kyoung-Mee. 2. Department of Pathology & Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
IN - Park, Young Suk. 1. Division of Hematology-Oncology, Department of Medicine.
TI - The Impact of PD-L1 Expression in Patients with Metastatic GEP-NETs.
SO - Journal of Cancer. 7(5):484-9, 2016
AS - J. cancer. 7(5):484-9, 2016
NJ - Journal of Cancer
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101535920
IO - J Cancer
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780123
CP - Australia
KW - Gastroenteropancreatic neuroendocrine tumor (GEP-NET); Programmed death-ligand 1 (PD-L1); WHO classification.
AB - Programmed death-ligand 1 (PD-L1), which is expressed on many cancer cells, interacts with PD1 expressed on the surface of T cells, inhibiting the T cells and blocking the antitumor immune response. Expression of PD-L1 in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has not been studied. We investigated the impact of PD-L1 expression in 32 patients with metastatic GEP-NET. The expression of PD-L1 was evaluated using an anti-PD-L1 immunohistochemistry (IHC) antibody optimized for staining of formalin-fixed paraffin-embedded (FFPE) tissue samples. The correlation between PD-L1 and clinicopathological data including survival and response to systemic treatments was analyzed. Primary sites were 24 foregut-derived GEP-NETs, including stomach (n=1), duodenum (n=2), biliary tract (n=7), and pancreas (n=14), and 8 hindgut-derived GEP-NETs of the distal colon and rectum. Among the 32 patients with metastatic GEP-NET analyzed in this study, 7 (21.9%) had expression of PD-L1 in tumor tissues. Expression of PD-L1 was significantly associated with high-grade WHO classification (grade 3) (p=0.008) but not with gender, primary site, and number of metastatic sites (p>0.05). The status of PD-L1 expression was statistically associated with progression-free survival (PFS) for first-line systemic treatment (p=0.047). Moreover, the status of PD-L1 expression could significantly predict overall survival (p=0.037). The expression of PD-L1 was associated with higher WHO tumor grade (grade 3) in metastatic GEP-NETs. PD-L1 expression had both predictive and prognostic value for survival of patients with metastatic GEP-NETs.
IL - 1837-9664
DI - jcav07p0484
DO - https://dx.doi.org/10.7150/jca.13711
PT - Journal Article
ID - 26958083 [pubmed]
ID - 10.7150/jca.13711 [doi]
ID - jcav07p0484 [pii]
ID - PMC4780123 [pmc]
PP - epublish
PH - 2015/09/01 [received]
PH - 2015/12/08 [accepted]
LG - English
EP - 20160205
DP - 2016
DC - 20160309
EZ - 2016/03/10 06:00
DA - 2016/03/10 06:01
DT - 2016/03/10 06:00
YR - 2016
ED - 20160309
RD - 20160311
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=26958083
<146. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26598057
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Daud A
FA - Daud, Adil
IN - Daud, Adil. HS Clinical Professor, Department of Medicine (Hematology/Oncology), University of California San Francisco, San Francisco, CA; Director, Melanoma Clinical Research, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. Electronic address: Adil.Daud@ucsf.edu.
TI - Current and Emerging Perspectives on Immunotherapy for Melanoma. [Review]
SO - Seminars in Oncology. 42 Suppl 3:S3-S11, 2015 Dec
AS - Semin Oncol. 42 Suppl 3:S3-S11, 2015 Dec
NJ - Seminars in oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - un5, 0420432
IO - Semin. Oncol.
SB - Index Medicus
CP - United States
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Combined Modality Therapy
MH - Humans
MH - Immunotherapy/ae [Adverse Effects]
MH - *Immunotherapy/mt [Methods]
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Signal Transduction
AB - Novel immunotherapeutic treatments are aimed at reversing the action of inhibitory pathways that restrain the T-cell-dominated immune-mediated defense against cancer. The first immune-inhibitory protein to be discovered was cytotoxic T-lymphocyte antigen-4 (CTLA-4). The effectiveness of a CTLA-targeted antibody in treating melanoma was an impetus for the use of programmed cell death-1 (PD-1) inhibitors in cancer treatment. Important differences between the use of CTLA-4 inhibitors and PD-1 inhibitors in treatment include the patterns of expression of each receptor and its ligands and sites of action, as CTLA-4 blockade has been noted to provide more global effects, whereas those of PD-1 inhibition are observed at the tumor site. Although each treatment has been associated with impressive benefits in advanced melanoma, recent comparative studies suggest that PD-1 inhibitors may be more effective than CTLA-4 inhibition and that the most optimal results may be observed using both agents in those who can tolerate the increased toxicity that accompanies combination treatment. The most common adverse reactions include skin effects using either CTLA-4-blocking antibody or PD-1 inhibitors, colitis using CTLA-4 blockade, or thyroid disease using PD-1 inhibitors.
AB - Copyright © 2015 Elsevier Inc. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1532-8708
IL - 0093-7754
DI - S0093-7754(15)00216-X
DO - https://dx.doi.org/10.1053/j.seminoncol.2015.10.003
PT - Journal Article
PT - Review
ID - 26598057 [pubmed]
ID - S0093-7754(15)00216-X [pii]
ID - 10.1053/j.seminoncol.2015.10.003 [doi]
PP - ppublish
LG - English
EP - 20151023
DP - 2015 Dec
DC - 20151124
EZ - 2015/11/25 06:00
DA - 2016/03/10 06:00
DT - 2015/11/26 06:00
YR - 2015
ED - 20160308
RD - 20151124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26598057
<147. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26351349
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Hamanishi J
AU - Mandai M
AU - Ikeda T
AU - Minami M
AU - Kawaguchi A
AU - Murayama T
AU - Kanai M
AU - Mori Y
AU - Matsumoto S
AU - Chikuma S
AU - Matsumura N
AU - Abiko K
AU - Baba T
AU - Yamaguchi K
AU - Ueda A
AU - Hosoe Y
AU - Morita S
AU - Yokode M
AU - Shimizu A
AU - Honjo T
AU - Konishi I
FA - Hamanishi, Junzo
FA - Mandai, Masaki
FA - Ikeda, Takafumi
FA - Minami, Manabu
FA - Kawaguchi, Atsushi
FA - Murayama, Toshinori
FA - Kanai, Masashi
FA - Mori, Yukiko
FA - Matsumoto, Shigemi
FA - Chikuma, Shunsuke
FA - Matsumura, Noriomi
FA - Abiko, Kaoru
FA - Baba, Tsukasa
FA - Yamaguchi, Ken
FA - Ueda, Akihiko
FA - Hosoe, Yuko
FA - Morita, Satoshi
FA - Yokode, Masayuki
FA - Shimizu, Akira
FA - Honjo, Tasuku
FA - Konishi, Ikuo
IN - Hamanishi, Junzo. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan. jnkhmns@kuhp.kyoto-u.ac.jp.
IN - Mandai, Masaki. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Ikeda, Takafumi. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Minami, Manabu. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Kawaguchi, Atsushi. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Murayama, Toshinori. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Kanai, Masashi. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Mori, Yukiko. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Matsumoto, Shigemi. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Chikuma, Shunsuke. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Matsumura, Noriomi. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Abiko, Kaoru. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Baba, Tsukasa. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Yamaguchi, Ken. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Ueda, Akihiko. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Hosoe, Yuko. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Morita, Satoshi. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Yokode, Masayuki. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Shimizu, Akira. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Honjo, Tasuku. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
IN - Konishi, Ikuo. Junzo Hamanishi, Masashi Kanai, Yukiko Mori, Shigemi Matsumoto, Shunsuke Chikuma, Noriomi Matsumura, Kaoru Abiko, Tsukasa Baba, Ken Yamaguchi, Akihiko Ueda, Yuko Hosoe, Tasuku Honjo, and Ikuo Konishi, Kyoto University Graduate School of Medicine, Kyoto, Japan; Masaki Mandai, Kinki University Faculty of Medicine, Osaka, Japan; and Takafumi Ikeda, Manabu Minami, Atsushi Kawaguchi, Toshinori Murayama, Satoshi Morita, Masayuki Yokode, and Akira Shimizu, Kyoto University Hospital, Kyoto, Japan.
TI - Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer.
CM - Comment in: J Clin Oncol. 2015 Dec 1;33(34):3987-9; PMID: 26503205
SO - Journal of Clinical Oncology. 33(34):4015-22, 2015 Dec 01
AS - J Clin Oncol. 33(34):4015-22, 2015 Dec 01
NJ - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - jco, 8309333
IO - J. Clin. Oncol.
SB - Index Medicus
CP - United States
MH - Adenocarcinoma, Clear Cell/dt [Drug Therapy]
MH - Adenocarcinoma, Clear Cell/mo [Mortality]
MH - Adenocarcinoma, Clear Cell/sc [Secondary]
MH - Aged
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Cohort Studies
MH - Cystadenocarcinoma, Serous/dt [Drug Therapy]
MH - Cystadenocarcinoma, Serous/mo [Mortality]
MH - Cystadenocarcinoma, Serous/sc [Secondary]
MH - *Drug Resistance, Neoplasm/de [Drug Effects]
MH - Endometrial Neoplasms/dt [Drug Therapy]
MH - Endometrial Neoplasms/mo [Mortality]
MH - Endometrial Neoplasms/sc [Secondary]
MH - Female
MH - Follow-Up Studies
MH - Humans
MH - Lymphatic Metastasis
MH - Middle Aged
MH - Neoplasm Invasiveness
MH - *Neoplasm Recurrence, Local/dt [Drug Therapy]
MH - Neoplasm Recurrence, Local/mo [Mortality]
MH - Neoplasm Recurrence, Local/pa [Pathology]
MH - Neoplasm Staging
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - Ovarian Neoplasms/mo [Mortality]
MH - Ovarian Neoplasms/pa [Pathology]
MH - Peritoneal Neoplasms/dt [Drug Therapy]
MH - Peritoneal Neoplasms/mo [Mortality]
MH - Peritoneal Neoplasms/sc [Secondary]
MH - Platinum/pd [Pharmacology]
MH - Prognosis
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - *Salvage Therapy
MH - Survival Rate
AB - PURPOSE: Programmed death-1 (PD-1), a coinhibitory immune signal receptor expressed in T cells, binds to PD-1 ligand and regulates antitumor immunity. Nivolumab is an anti-PD-1 antibody that blocks PD-1 signaling. We assessed the safety and antitumor activity of nivolumab in patients with platinum-resistant ovarian cancer.
AB - PATIENTS AND METHODS: Twenty patients with platinum-resistant ovarian cancer were treated with an intravenous infusion of nivolumab every 2 weeks at a dose of 1 or 3 mg/kg (constituting two 10-patient cohorts) from October 21, 2011. This phase II trial defined the primary end point as the best overall response. Patients received up to six cycles (four doses per cycle) of nivolumab treatment or received doses until disease progression occurred. Twenty nivolumab-treated patients were evaluated at the end of the trial on December 7, 2014.
AB - RESULTS: Grade 3 or 4 treatment-related adverse events occurred in eight (40%) of 20 patients. Two patients had severe adverse events. In the 20 patients in whom responses could be evaluated, the best overall response was 15%, which included two patients who had a durable complete response (in the 3-mg/kg cohort). The disease control rate in all 20 patients was 45%. The median progression-free survival time was 3.5 months (95% CI, 1.7 to 3.9 months), and the median overall survival time was 20.0 months (95% CI, 7.0 months to not reached) at study termination.
AB - CONCLUSION: This study, to our knowledge, is the first to explore the effects of nivolumab against ovarian cancer. The encouraging safety and clinical efficacy of nivolumab in patients with platinum-resistant ovarian cancer indicate the merit of additional large-scale investigations (UMIN Clinical Trials Registry UMIN000005714).
AB - Copyright © 2015 by American Society of Clinical Oncology.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 31YO63LBSN (nivolumab)
RN - 49DFR088MY (Platinum)
ES - 1527-7755
IL - 0732-183X
DI - JCO.2015.62.3397
DO - https://dx.doi.org/10.1200/JCO.2015.62.3397
PT - Clinical Trial, Phase II
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26351349 [pubmed]
ID - JCO.2015.62.3397 [pii]
ID - 10.1200/JCO.2015.62.3397 [doi]
PP - ppublish
SI - JPRN
SA - JPRN/UMIN000005714
LG - English
EP - 20150908
DP - 2015 Dec 01
DC - 20151126
EZ - 2015/09/10 06:00
DA - 2016/03/10 06:00
DT - 2015/09/10 06:00
YR - 2015
ED - 20160308
RD - 20151126
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26351349
<148. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25894333
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Santoiemma PP
AU - Powell DJ Jr
FA - Santoiemma, Phillip P
FA - Powell, Daniel J Jr
IN - Santoiemma, Phillip P. a Ovarian Cancer Research Center ; Department of Obstetrics and Gynecology ; Perelman School of Medicine; University of Pennsylvania ; Philadelphia , PA USA.
TI - Tumor infiltrating lymphocytes in ovarian cancer. [Review]
SO - Cancer Biology & Therapy. 16(6):807-20, 2015
AS - Cancer Biol Ther. 16(6):807-20, 2015
NJ - Cancer biology & therapy
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101137842
IO - Cancer Biol. Ther.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622931
SB - Index Medicus
CP - United States
MH - Animals
MH - Cancer Vaccines/im [Immunology]
MH - Clinical Trials as Topic
MH - Female
MH - Humans
MH - Immunomodulation
MH - Immunotherapy, Adoptive
MH - *Lymphocyte Subsets/im [Immunology]
MH - Lymphocyte Subsets/me [Metabolism]
MH - Lymphocyte Subsets/pa [Pathology]
MH - *Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Lymphocytes, Tumor-Infiltrating/me [Metabolism]
MH - Lymphocytes, Tumor-Infiltrating/pa [Pathology]
MH - *Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/mo [Mortality]
MH - *Ovarian Neoplasms/pa [Pathology]
MH - Ovarian Neoplasms/th [Therapy]
MH - Prognosis
MH - Treatment Outcome
MH - Tumor Microenvironment/im [Immunology]
KW - CAR, chimeric antigen receptor; IDO, indoleamine 2,3-dioxygenase; TIL, tumor infiltrating lymphocyte; Tregs, regulatory T-cell; immunosuppression; immunotherapy; ovarian cancer; prognostic factors; regulatory T-cells; tumor infiltrating lymphocytes
AB - The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment.
RN - 0 (Cancer Vaccines)
ES - 1555-8576
IL - 1538-4047
DO - https://dx.doi.org/10.1080/15384047.2015.1040960
PT - Journal Article
PT - Review
ID - 25894333 [pubmed]
ID - 10.1080/15384047.2015.1040960 [doi]
ID - PMC4622931 [pmc]
PP - ppublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01982487
SA - ClinicalTrials.gov/NCT02042430
SL - https://clinicaltrials.gov/search/term=NCT01982487
SL - https://clinicaltrials.gov/search/term=NCT02042430
LG - English
EP - 20150420
DP - 2015
DC - 20150613
EZ - 2015/04/21 06:00
DA - 2016/03/10 06:00
DT - 2015/04/22 06:00
YR - 2015
ED - 20160308
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25894333
<149. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25894333
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Santoiemma PP
AU - Powell DJ Jr
FA - Santoiemma, Phillip P
FA - Powell, Daniel J Jr
IN - Santoiemma, Phillip P. a Ovarian Cancer Research Center ; Department of Obstetrics and Gynecology ; Perelman School of Medicine; University of Pennsylvania ; Philadelphia , PA USA.
TI - Tumor infiltrating lymphocytes in ovarian cancer. [Review]
SO - Cancer Biology & Therapy. 16(6):807-20, 2015
AS - Cancer Biol Ther. 16(6):807-20, 2015
NJ - Cancer biology & therapy
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101137842
IO - Cancer Biol. Ther.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622931
SB - Index Medicus
CP - United States
MH - Animals
MH - Cancer Vaccines/im [Immunology]
MH - Clinical Trials as Topic
MH - Female
MH - Humans
MH - Immunomodulation
MH - Immunotherapy, Adoptive
MH - *Lymphocyte Subsets/im [Immunology]
MH - Lymphocyte Subsets/me [Metabolism]
MH - Lymphocyte Subsets/pa [Pathology]
MH - *Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Lymphocytes, Tumor-Infiltrating/me [Metabolism]
MH - Lymphocytes, Tumor-Infiltrating/pa [Pathology]
MH - *Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/mo [Mortality]
MH - *Ovarian Neoplasms/pa [Pathology]
MH - Ovarian Neoplasms/th [Therapy]
MH - Prognosis
MH - Treatment Outcome
MH - Tumor Microenvironment/im [Immunology]
KW - CAR, chimeric antigen receptor; IDO, indoleamine 2,3-dioxygenase; TIL, tumor infiltrating lymphocyte; Tregs, regulatory T-cell; immunosuppression; immunotherapy; ovarian cancer; prognostic factors; regulatory T-cells; tumor infiltrating lymphocytes
AB - The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment.
RN - 0 (Cancer Vaccines)
ES - 1555-8576
IL - 1538-4047
DO - https://dx.doi.org/10.1080/15384047.2015.1040960
PT - Journal Article
PT - Review
ID - 25894333 [pubmed]
ID - 10.1080/15384047.2015.1040960 [doi]
ID - PMC4622931 [pmc]
PP - ppublish
LG - English
EP - 20150420
DP - 2015
DC - 20150613
EZ - 2015/04/21 06:00
DA - 2016/03/10 06:00
DT - 2015/04/22 06:00
YR - 2015
ED - 20160308
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=25894333
<150. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25806780
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wyluda EJ
AU - Cheng J
AU - Schell TD
AU - Haley JS
AU - Mallon C
AU - Neves RI
AU - Robertson G
AU - Sivik J
AU - Mackley H
AU - Talamo G
AU - Drabick JJ
FA - Wyluda, Edward J
FA - Cheng, Jihua
FA - Schell, Todd D
FA - Haley, Jeremy S
FA - Mallon, Carol
FA - Neves, Rogerio I
FA - Robertson, Gavin
FA - Sivik, Jeffrey
FA - Mackley, Heath
FA - Talamo, Giampaolo
FA - Drabick, Joseph J
IN - Wyluda, Edward J. a Division of Hematology Oncology; Penn State Milton S Hershey Medical Center ; Hershey , PA , USA.
TI - Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy.
SO - Cancer Biology & Therapy. 16(5):662-70, 2015
AS - Cancer Biol Ther. 16(5):662-70, 2015
NJ - Cancer biology & therapy
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101137842
IO - Cancer Biol. Ther.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622667
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Female
MH - Humans
MH - *Immunotherapy/mt [Methods]
MH - *Interleukin-2/me [Metabolism]
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - *Melanoma/im [Immunology]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - Neoplasm Metastasis
MH - *Proto-Oncogene Proteins B-raf/ge [Genetics]
MH - Proto-Oncogene Proteins B-raf/me [Metabolism]
KW - BRAF inhibitor; CBC, complete blood count; CR, complete response; CRP, c-reactive protein; CT, computed tomography; CTL, cytotoxic lymphocyte; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; GrzB, granzyme B; HD, high dose; IFN, interferon; IL-2, interleukin 2; LDH, lactate dehydrogenase; M6P, manose 6 phosphate; MAPK, mitogen-activated protein kinase pathway; PD-1, programmed death 1; PDL-1, programmed death ligand 1; PDL-2, programmed death ligand 2; PET, positron emission tomography; PR, partial response; RT, radiation therapy; SLE, systemic lupus erythematosus; WBC, white blood cell count; cytotoxic therapy, immunotherapy, treatment of melanoma; interleukin-2; ipilimumab; metastatic melanoma
AB - We report 3 cases of durable complete response (CR) in patients with BRAF-mutated metastatic melanoma who were initially treated unsuccessfully with sequential immunotherapies (high dose interleukin 2 followed by ipilimumab with or without concurrent radiation therapy). After progression during or post immunotherapy, these patients were given BRAF inhibitor therapy and developed rapid CRs. Based on the concomitant presence of autoimmune manifestations (including vitiligo and hypophysitis), we postulated that there was a synergistic effect between the prior immune therapy and the BRAF targeting agents. Accordingly, the inhibitors were gradually weaned off beginning at 3 months and were stopped completely at 9-12 months. The three patients remain well and in CR off of all therapy at up to 15 months radiographic follow-up. The institution of the BRAF therapy was associated with development of severe rheumatoid-like arthritis in 2 patients which persisted for months after discontinuation of therapy, suggesting it was not merely a known toxicity of BRAF inhibitors (arthralgias). On immunologic analysis, these patients had high levels of non-T-regulatory, CD4 positive effector phenotype T-cells, which persisted after completion of therapy. Of note, we had previously reported a similar phenomenon in patients with metastatic melanoma who failed high dose interleukin-2 and were then placed on a finite course of temozolomide with rapid complete responses that have remained durable for many years after discontinuation of temozolomide. We postulate that a finite course of cytotoxic or targeted therapy specific for melanoma given after apparent failure of prior immunotherapy can result in complete and durable remissions that may persist long after the specific cytotoxic or targeted agents have been discontinued suggesting the existence of sequence specific synergism between immunotherapy and these agents. Here, we discuss these cases in the context of the literature on synergy between conventional or targeted cytotoxic therapy and immunotherapy in cancer treatment.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Interleukin-2)
RN - 6T8C155666 (ipilimumab)
RN - EC 2-7-11-1 (BRAF protein, human)
RN - EC 2-7-11-1 (Proto-Oncogene Proteins B-raf)
ES - 1555-8576
IL - 1538-4047
DO - https://dx.doi.org/10.1080/15384047.2015.1026507
PT - Case Reports
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 25806780 [pubmed]
ID - 10.1080/15384047.2015.1026507 [doi]
ID - PMC4622667 [pmc]
PP - ppublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT 01124734
SA - ClinicalTrials.gov/NCT01124734
SL - https://clinicaltrials.gov/search/term=NCT 01124734
SL - https://clinicaltrials.gov/search/term=NCT01124734
LG - English
DP - 2015
DC - 20150522
EZ - 2015/03/26 06:00
DA - 2016/03/02 06:00
DT - 2015/03/26 06:00
YR - 2015
ED - 20160301
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25806780
<151. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25806780
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wyluda EJ
AU - Cheng J
AU - Schell TD
AU - Haley JS
AU - Mallon C
AU - Neves RI
AU - Robertson G
AU - Sivik J
AU - Mackley H
AU - Talamo G
AU - Drabick JJ
FA - Wyluda, Edward J
FA - Cheng, Jihua
FA - Schell, Todd D
FA - Haley, Jeremy S
FA - Mallon, Carol
FA - Neves, Rogerio I
FA - Robertson, Gavin
FA - Sivik, Jeffrey
FA - Mackley, Heath
FA - Talamo, Giampaolo
FA - Drabick, Joseph J
IN - Wyluda, Edward J. a Division of Hematology Oncology; Penn State Milton S Hershey Medical Center ; Hershey , PA , USA.
TI - Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy.
SO - Cancer Biology & Therapy. 16(5):662-70, 2015
AS - Cancer Biol Ther. 16(5):662-70, 2015
NJ - Cancer biology & therapy
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101137842
IO - Cancer Biol. Ther.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622667
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Female
MH - Humans
MH - *Immunotherapy/mt [Methods]
MH - *Interleukin-2/me [Metabolism]
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - *Melanoma/im [Immunology]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - Neoplasm Metastasis
MH - *Proto-Oncogene Proteins B-raf/ge [Genetics]
MH - Proto-Oncogene Proteins B-raf/me [Metabolism]
KW - BRAF inhibitor; CBC, complete blood count; CR, complete response; CRP, c-reactive protein; CT, computed tomography; CTL, cytotoxic lymphocyte; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; GrzB, granzyme B; HD, high dose; IFN, interferon; IL-2, interleukin 2; LDH, lactate dehydrogenase; M6P, manose 6 phosphate; MAPK, mitogen-activated protein kinase pathway; PD-1, programmed death 1; PDL-1, programmed death ligand 1; PDL-2, programmed death ligand 2; PET, positron emission tomography; PR, partial response; RT, radiation therapy; SLE, systemic lupus erythematosus; WBC, white blood cell count; cytotoxic therapy, immunotherapy, treatment of melanoma; interleukin-2; ipilimumab; metastatic melanoma
AB - We report 3 cases of durable complete response (CR) in patients with BRAF-mutated metastatic melanoma who were initially treated unsuccessfully with sequential immunotherapies (high dose interleukin 2 followed by ipilimumab with or without concurrent radiation therapy). After progression during or post immunotherapy, these patients were given BRAF inhibitor therapy and developed rapid CRs. Based on the concomitant presence of autoimmune manifestations (including vitiligo and hypophysitis), we postulated that there was a synergistic effect between the prior immune therapy and the BRAF targeting agents. Accordingly, the inhibitors were gradually weaned off beginning at 3 months and were stopped completely at 9-12 months. The three patients remain well and in CR off of all therapy at up to 15 months radiographic follow-up. The institution of the BRAF therapy was associated with development of severe rheumatoid-like arthritis in 2 patients which persisted for months after discontinuation of therapy, suggesting it was not merely a known toxicity of BRAF inhibitors (arthralgias). On immunologic analysis, these patients had high levels of non-T-regulatory, CD4 positive effector phenotype T-cells, which persisted after completion of therapy. Of note, we had previously reported a similar phenomenon in patients with metastatic melanoma who failed high dose interleukin-2 and were then placed on a finite course of temozolomide with rapid complete responses that have remained durable for many years after discontinuation of temozolomide. We postulate that a finite course of cytotoxic or targeted therapy specific for melanoma given after apparent failure of prior immunotherapy can result in complete and durable remissions that may persist long after the specific cytotoxic or targeted agents have been discontinued suggesting the existence of sequence specific synergism between immunotherapy and these agents. Here, we discuss these cases in the context of the literature on synergy between conventional or targeted cytotoxic therapy and immunotherapy in cancer treatment.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Interleukin-2)
RN - 6T8C155666 (ipilimumab)
RN - EC 2-7-11-1 (BRAF protein, human)
RN - EC 2-7-11-1 (Proto-Oncogene Proteins B-raf)
ES - 1555-8576
IL - 1538-4047
DO - https://dx.doi.org/10.1080/15384047.2015.1026507
PT - Case Reports
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 25806780 [pubmed]
ID - 10.1080/15384047.2015.1026507 [doi]
ID - PMC4622667 [pmc]
PP - ppublish
LG - English
DP - 2015
DC - 20150522
EZ - 2015/03/26 06:00
DA - 2016/03/02 06:00
DT - 2015/03/26 06:00
YR - 2015
ED - 20160301
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=25806780
<152. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26423423
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Delitto D
AU - Perez C
AU - Han S
AU - Gonzalo DH
AU - Pham K
AU - Knowlton AE
AU - Graves CL
AU - Behrns KE
AU - Moldawer LL
AU - Thomas RM
AU - Liu C
AU - George TJ Jr
AU - Trevino JG
AU - Wallet SM
AU - Hughes SJ
FA - Delitto, Daniel
FA - Perez, Chelsey
FA - Han, Song
FA - Gonzalo, David H
FA - Pham, Kien
FA - Knowlton, Andrea E
FA - Graves, Christina L
FA - Behrns, Kevin E
FA - Moldawer, Lyle L
FA - Thomas, Ryan M
FA - Liu, Chen
FA - George, Thomas J Jr
FA - Trevino, Jose G
FA - Wallet, Shannon M
FA - Hughes, Steven J
IN - Delitto, Daniel. Department of Surgery, College of Medicine, University of Florida, PO BOX 100109, Gainesville, FL, 32610, USA.
IN - Perez, Chelsey. Department of Surgery, College of Medicine, University of Florida, PO BOX 100109, Gainesville, FL, 32610, USA.
IN - Han, Song. Department of Surgery, College of Medicine, University of Florida, PO BOX 100109, Gainesville, FL, 32610, USA.
IN - Gonzalo, David H. Department of Pathology, Immunology, Laboratory Medicine, University of Florida, Gainesville, FL, USA.
IN - Pham, Kien. Department of Pathology, Immunology, Laboratory Medicine, University of Florida, Gainesville, FL, USA.
IN - Knowlton, Andrea E. Department of Oral Biology, College of Dentistry, University of Florida, PO BOX 100434, Gainesville, FL, 32610, USA.
IN - Graves, Christina L. Department of Oral Biology, College of Dentistry, University of Florida, PO BOX 100434, Gainesville, FL, 32610, USA.
IN - Behrns, Kevin E. Department of Surgery, College of Medicine, University of Florida, PO BOX 100109, Gainesville, FL, 32610, USA.
IN - Moldawer, Lyle L. Department of Surgery, College of Medicine, University of Florida, PO BOX 100109, Gainesville, FL, 32610, USA.
IN - Thomas, Ryan M. Department of Surgery, College of Medicine, University of Florida, PO BOX 100109, Gainesville, FL, 32610, USA.
IN - Liu, Chen. Department of Pathology, Immunology, Laboratory Medicine, University of Florida, Gainesville, FL, USA.
IN - George, Thomas J Jr. Department of Medicine, University of Florida, Gainesville, FL, USA.
IN - Trevino, Jose G. Department of Surgery, College of Medicine, University of Florida, PO BOX 100109, Gainesville, FL, 32610, USA.
IN - Wallet, Shannon M. Department of Oral Biology, College of Dentistry, University of Florida, PO BOX 100434, Gainesville, FL, 32610, USA. swallet@dental.ufl.edu.
IN - Hughes, Steven J. Department of Surgery, College of Medicine, University of Florida, PO BOX 100109, Gainesville, FL, 32610, USA. steven.hughes@surgery.ufl.edu.
TI - Downstream mediators of the intratumoral interferon response suppress antitumor immunity, induce gemcitabine resistance and associate with poor survival in human pancreatic cancer.
SO - Cancer Immunology, Immunotherapy. 64(12):1553-63, 2015 Dec
AS - Cancer Immunol Immunother. 64(12):1553-63, 2015 Dec
NJ - Cancer immunology, immunotherapy : CII
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cn3, 8605732
IO - Cancer Immunol. Immunother.
SB - Index Medicus
CP - Germany
MH - Adaptive Immunity/ge [Genetics]
MH - Adaptive Immunity/im [Immunology]
MH - Cell Line, Tumor
MH - Chemokine CXCL10/ge [Genetics]
MH - Chemokine CXCL10/me [Metabolism]
MH - *Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Drug Resistance, Neoplasm/ge [Genetics]
MH - Enzyme-Linked Immunosorbent Assay
MH - Flow Cytometry
MH - Gene Expression Regulation, Neoplastic/de [Drug Effects]
MH - HLA Antigens/ge [Genetics]
MH - Humans
MH - Interferon-gamma/pd [Pharmacology]
MH - *Interferons/im [Immunology]
MH - Pancreatic Neoplasms/di [Diagnosis]
MH - *Pancreatic Neoplasms/pp [Physiopathology]
MH - Receptors, CXCR3/ge [Genetics]
MH - Tumor Cells, Cultured
MH - *Tumor Microenvironment/ph [Physiology]
KW - CXCL10; Epithelial cell; Immuno-oncology; Interferon-gamma; Pancreatic cancer; Tumor-associated stroma
AB - The cancer microenvironment allows tumor cells to evade immune surveillance through a variety of mechanisms. While interferon-gamma (IFNgamma) is central to effective antitumor immunity, its effects on the microenvironment are not as clear and have in some cancers been shown to induce immune checkpoint ligands. The heterogeneity of these responses to IFNgamma remains poorly characterized in desmoplastic malignancies with minimal inflammatory cell infiltration, such as pancreatic cancer (PC). Thus, the IFNgamma response within and on key cells of the PC microenvironment was evaluated. IFNgamma induced expression of human leukocyte antigen (HLA) class I and II on PC cell lines, primary pancreatic cancer epithelial cells (PPCE) and patient-derived tumor-associated stroma, concomitant with an upregulation of PDL1 in the absence of CD80 and CD86 expression. As expected, IFNgamma also induced high levels of CXCL10 from all cell types. In addition, significantly higher levels of CXCL10 were observed in PC specimens compared to those from chronic pancreatitis, whereby intratumoral CXCL10 concentration was an independent predictor of poor survival. Immunohistochemical analysis revealed a subset of CXCR3-positive cancer cells in over 90 % of PC specimens, as well as on a subset of cultured PC cell lines and PPCE, whereby exposure to CXCL10 induced resistance to the chemotherapeutic gemcitabine. These findings suggest that IFNgamma has multiple effects on many cell types within the PC microenvironment that may lead to immune evasion, chemoresistance and shortened survival.
RN - 0 (Chemokine CXCL10)
RN - 0 (HLA Antigens)
RN - 0 (Receptors, CXCR3)
RN - 0W860991D6 (Deoxycytidine)
RN - 82115-62-6 (Interferon-gamma)
RN - 9008-11-1 (Interferons)
RN - B76N6SBZ8R (gemcitabine)
ES - 1432-0851
IL - 0340-7004
DI - 10.1007/s00262-015-1760-y
DO - https://dx.doi.org/10.1007/s00262-015-1760-y
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 26423423 [pubmed]
ID - 10.1007/s00262-015-1760-y [doi]
ID - 10.1007/s00262-015-1760-y [pii]
ID - PMC5129167 [pmc]
ID - NIHMS830192 [mid]
PP - ppublish
PH - 2015/06/26 [received]
PH - 2015/09/17 [accepted]
GI - No: T90 DE021990
Organization: (DE) *NIDCR NIH HHS*
Country: United States
No: 5T32 CA106493-09
Organization: (CA) *NCI NIH HHS*
Country: United States
No: F31 DK104492-01A
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: T32 CA106493
Organization: (CA) *NCI NIH HHS*
Country: United States
No: T90 DE021990-02
Organization: (DE) *NIDCR NIH HHS*
Country: United States
No: F31 DK104492
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG - English
EP - 20150930
DP - 2015 Dec
DC - 20151113
EZ - 2015/10/02 06:00
DA - 2016/03/02 06:00
DT - 2015/10/02 06:00
YR - 2015
ED - 20160229
RD - 20161201
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26423423
<153. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26337719
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Bertrand A
AU - Kostine M
AU - Barnetche T
AU - Truchetet ME
AU - Schaeverbeke T
FA - Bertrand, Anne
FA - Kostine, Marie
FA - Barnetche, Thomas
FA - Truchetet, Marie-Elise
FA - Schaeverbeke, Thierry
IN - Bertrand, Anne. Departement de Rhumatologie, Hopital Pellegrin, CHU de Bordeaux, Bordeaux, France. anne.bertrand87@gmail.com.
IN - Kostine, Marie. Departement de Rhumatologie, Hopital Pellegrin, CHU de Bordeaux, Bordeaux, France. mariekostine@hotmail.fr.
IN - Barnetche, Thomas. Departement de Rhumatologie, Hopital Pellegrin, CHU de Bordeaux, Bordeaux, France. thomas.barnetche@chu-bordeaux.fr.
IN - Truchetet, Marie-Elise. Departement de Rhumatologie, Hopital Pellegrin, CHU de Bordeaux, Bordeaux, France. marie-elise.truchetet@chu-bordeaux.fr.
IN - Truchetet, Marie-Elise. Laboratoire d'Immunologie, UMR-CNRS 5164, Universite de Bordeaux, Bordeaux, France. marie-elise.truchetet@chu-bordeaux.fr.
IN - Schaeverbeke, Thierry. Departement de Rhumatologie, Hopital Pellegrin, CHU de Bordeaux, Bordeaux, France. thierry.schaeverbeke@chu-bordeaux.fr.
IN - Schaeverbeke, Thierry. Unite sous Contrat, Infections a Mycoplasmes et a Chlamydia chez l'Homme, Universite de Bordeaux, Bordeaux, France. thierry.schaeverbeke@chu-bordeaux.fr.
TI - Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis. [Review]
SO - BMC Medicine. 13:211, 2015 Sep 04
AS - BMC Med. 13:211, 2015 Sep 04
NJ - BMC medicine
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101190723
IO - BMC Med
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559965
SB - Index Medicus
CP - England
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - *CTLA-4 Antigen/im [Immunology]
MH - Humans
MH - *Immunologic Factors/ae [Adverse Effects]
MH - Immunotherapy/ae [Adverse Effects]
MH - *Neoplasms/dt [Drug Therapy]
MH - Neoplasms/im [Immunology]
AB - BACKGROUND: Targeting CTLA-4 is a recent strategic approach in cancer control: blocking CTLA-4 enhances an antitumor immunity by promoting T-cell activation and cytotoxic T-lymphocyte proliferation. This induction of a tolerance break against the tumor may be responsible for immune-related adverse events (irAEs). Our objective was to assess the incidence and nature of irAEs in oncologic patients receiving anti-CTLA-4 antibodies (ipilimumab and tremelimumab).
AB - METHODS: A systematic search of literature up to February 2014 was performed in MEDLINE, EMBASE, and Cochrane databases to identify relevant articles. Paired reviewers independently selected articles for inclusion and extracted data. Pooled incidence was calculated using R(©), package meta.
AB - RESULTS: Overall, 81 articles were included in the study, with a total of 1265 patients from 22 clinical trials included in the meta-analysis. Described irAEs consisted of skin lesions (rash, pruritus, and vitiligo), colitis, and less frequently hepatitis, hypophysitis, thyroiditis, and some rare events such as sarcoidosis, uveitis, Guillain-Barre syndrome, immune-mediated cytopenia and polymyalgia rheumatic/Horton. The overall incidence of all-grade irAEs was 72 % (95 % CI, 65-79 %). The overall incidence of high-grade irAEs was 24 % (95 % CI, 18-30 %). The risk of developing irAEs was dependent of dosage, with incidence of all-grade irAEs being evaluated to 61 % (95 % CI, 56-66 %) for ipilimumab 3 mg/kg and 79 % (95 % CI, 69-89 %) for ipilimumab 10 mg/kg. Death due to irAEs occurred in 0.86 % of patients. The median time of onset of irAEs was about 10 weeks (IQR, 6-12) after the onset of treatment, corresponding with the first three cycles but varied according to the organ system involved. Such immune activation could also be indicative for tumor-specific T-cell activation and irAE occurrence was associated with clinical response to CTLA-4 blocking in 60 % of patients.
AB - CONCLUSION: The price of potential long-term survival to metastatic tumors is an atypical immune toxicity, reflecting the mechanism of action of anti-CTLA-4 antibodies. A better knowledge of these irAEs and its management in a multidisciplinary approach will help to reduce morbidity and therapy interruptions.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (Immunologic Factors)
RN - 6T8C155666 (ipilimumab)
RN - QEN1X95CIX (tremelimumab)
ES - 1741-7015
IL - 1741-7015
DI - 10.1186/s12916-015-0455-8
DO - https://dx.doi.org/10.1186/s12916-015-0455-8
PT - Journal Article
PT - Meta-Analysis
PT - Review
ID - 26337719 [pubmed]
ID - 10.1186/s12916-015-0455-8 [doi]
ID - 10.1186/s12916-015-0455-8 [pii]
ID - PMC4559965 [pmc]
PP - epublish
PH - 2015/04/22 [received]
PH - 2015/08/18 [accepted]
LG - English
EP - 20150904
DP - 2015 Sep 04
DC - 20150904
EZ - 2015/09/05 06:00
DA - 2016/03/02 06:00
DT - 2015/09/05 06:00
YR - 2015
ED - 20160229
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26337719
<154. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25770731
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Schmutz JL
FA - Schmutz, J-L
IN - Schmutz, J-L. Departement de dermatologie et allergologie, batiment des specialites medicales, 6, rue du Morvan, 54500 Vandoeuvre-les-Nancy, France. Electronic address: jl.schmutz@chu-nancy.fr.
TI - [A new form of hypophisitis following ipilimumab therapy]. [French]
OT - Une nouvelle forme d'hypophysite secondaire a l'ipilimumab.
SO - Annales de Dermatologie et de Venereologie. 142(4):307-8, 2015 Apr
AS - Ann Dermatol Venereol. 142(4):307-8, 2015 Apr
NJ - Annales de dermatologie et de venereologie
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 5rc, 7702013
IO - Ann Dermatol Venereol
SB - Index Medicus
CP - France
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - *Autoimmune Hypophysitis/ci [Chemically Induced]
MH - Autoimmune Hypophysitis/co [Complications]
MH - Autoimmune Hypophysitis/dt [Drug Therapy]
MH - Autoimmune Hypophysitis/ep [Epidemiology]
MH - Female
MH - Glucocorticoids/tu [Therapeutic Use]
MH - Humans
MH - Hypopituitarism/et [Etiology]
MH - Incidence
MH - Male
MH - Melanoma/dt [Drug Therapy]
MH - Melanoma/sc [Secondary]
MH - Prognosis
MH - Retrospective Studies
MH - Skin Neoplasms/dt [Drug Therapy]
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (Glucocorticoids)
RN - 6T8C155666 (ipilimumab)
IS - 0151-9638
IL - 0151-9638
DI - S0151-9638(15)00052-6
DO - https://dx.doi.org/10.1016/j.annder.2015.02.001
PT - Journal Article
ID - 25770731 [pubmed]
ID - S0151-9638(15)00052-6 [pii]
ID - 10.1016/j.annder.2015.02.001 [doi]
PP - ppublish
LG - French
EP - 20150312
DP - 2015 Apr
DC - 20150406
EZ - 2015/03/16 06:00
DA - 2016/03/02 06:00
DT - 2015/03/17 06:00
YR - 2015
ED - 20160229
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25770731
<155. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24814274
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Henderson AD
AU - Thomas DA
FA - Henderson, Amanda D
FA - Thomas, Dilip A
IN - Henderson, Amanda D. Department of Ophthalmology, Georgia Regents University, Augusta, Georgia, U.S.A.
TI - A case report of orbital inflammatory syndrome secondary to ipilimumab.
SO - Ophthalmic Plastic & Reconstructive Surgery. 31(3):e68-70, 2015 May-Jun
AS - Ophthal Plast Reconstr Surg. 31(3):e68-70, 2015 May-Jun
NJ - Ophthalmic plastic and reconstructive surgery
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - ay2, 8508431
IO - Ophthal Plast Reconstr Surg
SB - Index Medicus
CP - United States
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - CTLA-4 Antigen/im [Immunology]
MH - Humans
MH - *Immunotherapy/ae [Adverse Effects]
MH - Lymphatic Metastasis
MH - Magnetic Resonance Imaging
MH - Male
MH - Melanoma/dt [Drug Therapy]
MH - Melanoma/sc [Secondary]
MH - Middle Aged
MH - *Orbital Pseudotumor/ci [Chemically Induced]
MH - Orbital Pseudotumor/di [Diagnosis]
MH - Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/pa [Pathology]
AB - Ipilimumab is a monoclonal antibody to cytotoxic T-lymphocyte antigen-4, a negative regulator of T-cell-mediated immune response. Ipilimumab is approved by the US Food and Drug Administration for the treatment of advanced melanoma. However, its use frequently has been associated with immune-related side effects, which can be explained by its mechanism of action. More common adverse effects include dermatitis, colitis, hepatitis, and endocrinopathies, but many less common immune-related adverse effects that involve various tissues and organ systems have been reported with more widespread use of ipilimumab since its approval in 2011. A case of bilateral orbital inflammatory syndrome secondary to ipilimumab, in a patient undergoing adjuvant treatment for metastatic melanoma, is reported.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
ES - 1537-2677
IL - 0740-9303
DO - https://dx.doi.org/10.1097/IOP.0000000000000081
PT - Case Reports
PT - Journal Article
ID - 24814274 [pubmed]
ID - 10.1097/IOP.0000000000000081 [doi]
PP - ppublish
LG - English
DP - 2015 May-Jun
DC - 20150507
EZ - 2014/05/13 06:00
DA - 2016/02/27 06:00
DT - 2014/05/13 06:00
YR - 2015
ED - 20160226
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24814274
<156. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25938471
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Longoria TC
AU - Eskander RN
FA - Longoria, Teresa C
FA - Eskander, Ramez N
IN - Eskander, Ramez N. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California, Irvine-Medical Center, 101 The City Drive, Bldg 56, Ste 800, ZC 3200, Orange, CA 92868 USA. Eskander@uci.edu.
TI - Immune checkpoint inhibition: therapeutic implications in epithelial ovarian cancer. [Review]
SO - Recent Patents on Anti-Cancer Drug Discovery. 10(2):133-44, 2015
AS - Recent Patents Anticancer Drug Discov. 10(2):133-44, 2015
NJ - Recent patents on anti-cancer drug discovery
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101266081
IO - Recent Pat Anticancer Drug Discov
SB - Index Medicus
CP - United Arab Emirates
MH - Animals
MH - Antibodies, Monoclonal/pd [Pharmacology]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Agents/pd [Pharmacology]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Female
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Neoplasm Staging
MH - *Neoplasms, Glandular and Epithelial/dt [Drug Therapy]
MH - Neoplasms, Glandular and Epithelial/im [Immunology]
MH - Neoplasms, Glandular and Epithelial/pa [Pathology]
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/pa [Pathology]
MH - Patents as Topic
MH - Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
AB - Ovarian cancer accounts for more deaths than any other gynecologic malignancy. According to the Ovarian Cancer National Alliance, overall mortality rates due to ovarian cancer have not significantly improved in 40 years, a statistic that highlights the need for innovative treatment strategies. Immune checkpoint inhibitors are part of an emerging immunotherapeutic model that seeks to "inhibit the inhibitors" of adequate cancer immunosurveillance. Immune checkpoints encompass a variety of inhibitory pathways that downregulate an immune response, which allows them to assume an important physiologic role in maintaining homeostasis. While cancer cells are adept at utilizing these pathways to their advantage, basic scientists, translational researchers, and clinical trialists are making great strides in this area of investigation. This review article will focus on the development of anti-CTLA-4 and anti-PD1 monoclonal antibodies, their current role in the treatment of advanced stage EOC, and recently published patents that incorporate the use of immune checkpoint inhibition in the treatment of cancer.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (Programmed Cell Death 1 Receptor)
RS - Ovarian epithelial cancer
ES - 2212-3970
IL - 1574-8928
DI - PRA-EPUB-67005
PT - Journal Article
PT - Review
ID - 25938471 [pubmed]
ID - PRA-EPUB-67005 [pii]
PP - ppublish
PH - 2015/01/19 [received]
PH - 2015/04/28 [revised]
PH - 2015/04/02 [accepted]
LG - English
DP - 2015
DC - 20150518
EZ - 2015/05/05 06:00
DA - 2016/02/19 06:00
DT - 2015/05/06 06:00
YR - 2015
ED - 20160218
RD - 20150518
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25938471
<157. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25993145
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Postow MA
FA - Postow, Michael A
IN - Postow, Michael A. From the Memorial Sloan Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY.
TI - Managing immune checkpoint-blocking antibody side effects. [Review]
SO - American Society of Clinical Oncology Educational Book. :76-83, 2015
AS - Am. Soc. Clin. Oncol. educ. book. :76-83, 2015
NJ - American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Meeting
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101233985
IO - Am Soc Clin Oncol Educ Book
SB - Index Medicus
CP - United States
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - *CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - Chemical and Drug Induced Liver Injury/dt [Drug Therapy]
MH - Chemical and Drug Induced Liver Injury/et [Etiology]
MH - Colitis/ci [Chemically Induced]
MH - Colitis/dt [Drug Therapy]
MH - Diarrhea/ci [Chemically Induced]
MH - Diarrhea/dt [Drug Therapy]
MH - Granulocyte-Macrophage Colony-Stimulating Factor/tu [Therapeutic Use]
MH - Humans
MH - Opportunistic Infections/dt [Drug Therapy]
MH - Opportunistic Infections/et [Etiology]
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - Recombinant Proteins/tu [Therapeutic Use]
AB - Immune checkpoint-blocking antibodies that enhance the immune system's ability to fight cancer are becoming important components of treatment for patients with a variety of malignancies. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) was the first immune checkpoint to be clinically targeted, and ipilimumab, an inhibitor of CTLA-4, was approved by the U.S. Food and Drug Administration (FDA) for patients with advanced melanoma. The programmed cell death-1 (PD-1) receptor and one of its ligands, PD-L1, more recently have shown great promise as therapeutic targets in a variety of malignancies. Nivolumab and pembrolizumab recently have been FDA- approved for patients with melanoma and additional approvals within this therapeutic class are expected. The use of anti-CTLA-4 and anti-PD-1/PD-L1 antibodies is associated with side effects known as immune-related adverse events (irAEs). Immune-related adverse events affect the dermatologic, gastrointestinal, hepatic, endocrine, and other organ systems. Temporary immunosuppression with corticosteroids, tumor necrosis factor-alpha antagonists, mycophenolate mofetil, or other agents can be effective treatment. This article describes the side-effect profile of the checkpoint-blocking antibodies that target CTLA-4 and PD-1/PD-L1 and provides suggestions on how to manage specific irAEs.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 0 (Recombinant Proteins)
RN - 123774-72-1 (sargramostim)
RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
ES - 1548-8756
IL - 1548-8748
DI - 00115000076
DO - https://dx.doi.org/10.14694/EdBook_AM.2015.35.76
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 25993145 [pubmed]
ID - 00115000076 [pii]
ID - 10.14694/EdBook_AM.2015.35.76 [doi]
PP - ppublish
LG - English
DP - 2015
DC - 20150521
EZ - 2015/05/21 06:00
DA - 2016/02/18 06:00
DT - 2015/05/21 06:00
YR - 2015
ED - 20160217
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25993145
<158. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25811348
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Su D
AU - Singer EA
AU - Srinivasan R
FA - Su, Daniel
FA - Singer, Eric A
FA - Srinivasan, Ramaprasad
IN - Su, Daniel. aUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland bSection of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
TI - Molecular pathways in renal cell carcinoma: recent advances in genetics and molecular biology. [Review]
SO - Current Opinion in Oncology. 27(3):217-23, 2015 May
AS - Curr Opin Oncol. 27(3):217-23, 2015 May
NJ - Current opinion in oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - a1v, 9007265
IO - Curr Opin Oncol
SB - Index Medicus
CP - United States
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Carcinoma, Renal Cell/dt [Drug Therapy]
MH - Carcinoma, Renal Cell/ge [Genetics]
MH - Carcinoma, Renal Cell/mo [Mortality]
MH - Carcinoma, Renal Cell/pa [Pathology]
MH - Carrier Proteins
MH - Disease-Free Survival
MH - Humans
MH - *Kidney Neoplasms/dt [Drug Therapy]
MH - Kidney Neoplasms/ge [Genetics]
MH - Kidney Neoplasms/mo [Mortality]
MH - Kidney Neoplasms/pa [Pathology]
MH - Molecular Targeted Therapy/mt [Methods]
MH - *Molecular Targeted Therapy
MH - Vascular Endothelial Growth Factor A
AB - PURPOSE OF REVIEW: Advanced renal cell carcinoma (RCC) remains a largely incurable disease with a grave prognosis despite the availability of a multiplicity of systemic therapies targeted against vascular endothelial growth factor, its receptors, and the mammalian target of rapamycin. Although immune 'checkpoint inhibitors' appear to have activity in clear cell RCC based on recent early phase trials, the true magnitude of the benefit conferred by these agents remains to be fully understood. Given the limitations of existing treatment paradigms, ongoing research into new targetable pathways is critical. This review will highlight some of the more promising avenues of investigation into the molecular biology of RCC.
AB - RECENT FINDINGS: The hypoxia-inducible factor and mammalian target of rapamycin pathways remain critical targets in clear cell RCC. In addition, genes involved in chromatin remodeling such as polybromo 1 (PBRM1), SET domain containing 2 (SETD2), and BRCA-1-associated protein-1 (BAP1) have been shown to influence tumor biology and predict survival. MET alterations and the Krebs cycle enzyme fumarate hydratase are associated with familial type 1 and type 2 papillary RCC (PRCC), respectively. Alterations in nuclear factor (erythroid-derived 2)-like 2, Kelch-like erythroid-derived cap-n-collar homology-associated protein 1, and cullin 3, components of an oxidative stress response pathway, have been recently recognized in some sporadic papillary tumors as well as in fumarate hydratase-deficient tumor and may serve as additional therapeutic targets. In addition, whole-genome sequencing and integrated genomic analysis strategies are beginning to uncover unique molecular signatures associated with distinct subtypes of RCC, laying the foundation for a molecular classification of RCC and more precise, mechanism-based therapeutic intervention.
AB - SUMMARY: The complex molecular changes underlying individual RCC variants are yet to be fully elucidated and remain the subject of ongoing investigation. The findings summarized here further exemplify the diversity of RCC and the need to tailor our therapeutic approaches to the unique genetic alterations specific to individual subtypes of RCC.
RN - 0 (Antineoplastic Agents)
RN - 0 (Carrier Proteins)
RN - 0 (Vascular Endothelial Growth Factor A)
ES - 1531-703X
IL - 1040-8746
DO - https://dx.doi.org/10.1097/CCO.0000000000000186
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, N.I.H., Intramural
PT - Review
ID - 25811348 [pubmed]
ID - 10.1097/CCO.0000000000000186 [doi]
PP - ppublish
GI - No: P30CA072720
Organization: (CA) *NCI NIH HHS*
Country: United States
Organization: *Intramural NIH HHS*
Country: United States
LG - English
DP - 2015 May
DC - 20150408
EZ - 2015/03/27 06:00
DA - 2016/02/18 06:00
DT - 2015/03/27 06:00
YR - 2015
ED - 20160217
RD - 20150408
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25811348
<159. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25811348
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Su D
AU - Singer EA
AU - Srinivasan R
FA - Su, Daniel
FA - Singer, Eric A
FA - Srinivasan, Ramaprasad
IN - Su, Daniel. aUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland bSection of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
TI - Molecular pathways in renal cell carcinoma: recent advances in genetics and molecular biology. [Review]
SO - Current Opinion in Oncology. 27(3):217-23, 2015 May
AS - Curr Opin Oncol. 27(3):217-23, 2015 May
NJ - Current opinion in oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - a1v, 9007265
IO - Curr Opin Oncol
SB - Index Medicus
CP - United States
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Carcinoma, Renal Cell/dt [Drug Therapy]
MH - Carcinoma, Renal Cell/ge [Genetics]
MH - Carcinoma, Renal Cell/mo [Mortality]
MH - Carcinoma, Renal Cell/pa [Pathology]
MH - Carrier Proteins
MH - Disease-Free Survival
MH - Humans
MH - *Kidney Neoplasms/dt [Drug Therapy]
MH - Kidney Neoplasms/ge [Genetics]
MH - Kidney Neoplasms/mo [Mortality]
MH - Kidney Neoplasms/pa [Pathology]
MH - Molecular Targeted Therapy/mt [Methods]
MH - *Molecular Targeted Therapy
MH - Vascular Endothelial Growth Factor A
AB - PURPOSE OF REVIEW: Advanced renal cell carcinoma (RCC) remains a largely incurable disease with a grave prognosis despite the availability of a multiplicity of systemic therapies targeted against vascular endothelial growth factor, its receptors, and the mammalian target of rapamycin. Although immune 'checkpoint inhibitors' appear to have activity in clear cell RCC based on recent early phase trials, the true magnitude of the benefit conferred by these agents remains to be fully understood. Given the limitations of existing treatment paradigms, ongoing research into new targetable pathways is critical. This review will highlight some of the more promising avenues of investigation into the molecular biology of RCC.
AB - RECENT FINDINGS: The hypoxia-inducible factor and mammalian target of rapamycin pathways remain critical targets in clear cell RCC. In addition, genes involved in chromatin remodeling such as polybromo 1 (PBRM1), SET domain containing 2 (SETD2), and BRCA-1-associated protein-1 (BAP1) have been shown to influence tumor biology and predict survival. MET alterations and the Krebs cycle enzyme fumarate hydratase are associated with familial type 1 and type 2 papillary RCC (PRCC), respectively. Alterations in nuclear factor (erythroid-derived 2)-like 2, Kelch-like erythroid-derived cap-n-collar homology-associated protein 1, and cullin 3, components of an oxidative stress response pathway, have been recently recognized in some sporadic papillary tumors as well as in fumarate hydratase-deficient tumor and may serve as additional therapeutic targets. In addition, whole-genome sequencing and integrated genomic analysis strategies are beginning to uncover unique molecular signatures associated with distinct subtypes of RCC, laying the foundation for a molecular classification of RCC and more precise, mechanism-based therapeutic intervention.
AB - SUMMARY: The complex molecular changes underlying individual RCC variants are yet to be fully elucidated and remain the subject of ongoing investigation. The findings summarized here further exemplify the diversity of RCC and the need to tailor our therapeutic approaches to the unique genetic alterations specific to individual subtypes of RCC.
RN - 0 (Antineoplastic Agents)
RN - 0 (Carrier Proteins)
RN - 0 (Vascular Endothelial Growth Factor A)
ES - 1531-703X
IL - 1040-8746
DO - https://dx.doi.org/10.1097/CCO.0000000000000186
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, N.I.H., Intramural
PT - Review
ID - 25811348 [pubmed]
ID - 10.1097/CCO.0000000000000186 [doi]
PP - ppublish
GI - No: P30 CA072720
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30CA072720
Organization: (CA) *NCI NIH HHS*
Country: United States
Organization: *Intramural NIH HHS*
Country: United States
LG - English
DP - 2015 May
DC - 20150408
EZ - 2015/03/27 06:00
DA - 2016/02/18 06:00
DT - 2015/03/27 06:00
YR - 2015
ED - 20160217
RD - 20161214
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=25811348
<160. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26881150
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Azmat U
AU - Liebner D
AU - Joehlin-Price A
AU - Agrawal A
AU - Nabhan F
AI - Agrawal, Amit; ORCID: https://orcid.org/0000-0003-4047-5708
FA - Azmat, Umal
FA - Liebner, David
FA - Joehlin-Price, Amy
FA - Agrawal, Amit
FA - Nabhan, Fadi
IN - Azmat, Umal. Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University, Columbus, OH, USA.
IN - Liebner, David. Division of Medical Oncology and Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA.
IN - Joehlin-Price, Amy. Department of Pathology, The Ohio State University, Columbus, OH, USA.
IN - Agrawal, Amit. Department of Otolaryngology, Head and Neck Surgery, The Ohio State University, Columbus, OH, USA.
IN - Nabhan, Fadi. Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University, Columbus, OH, USA.
TI - Treatment of Ipilimumab Induced Graves' Disease in a Patient with Metastatic Melanoma.
SO - Case Reports in Endocrinology Print. 2016:2087525, 2016
AS - case report. endocrinol.. 2016:2087525, 2016
NJ - Case reports in endocrinology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - 101576457
IO - Case Rep Endocrinol
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737013
CP - United States
AB - Objective. Thyroid disease has been reported among the endocrinopathies that can occur after treatment with ipilimumab. Graves' disease, however, has been rarely reported with this medication. Here we report a case of Graves' disease diagnosed after initiation of ipilimumab in a patient with melanoma. Methods. We present the clinical presentation and management course of this patient followed by a related literature review. Results. A 67-year-old male with metastatic melanoma was started on ipilimumab. He developed hyperthyroidism after two doses of ipilimumab. The cause of hyperthyroidism was determined to be Graves' disease. Ipilimumab was held and the patient was started on methimazole with return to euthyroid status. Ipilimumab was resumed and the patient continued methimazole during the course of ipilimumab therapy, with controlled hyperthyroidism. Restaging studies following four cycles of ipilimumab showed complete response in the lungs, with residual melanoma in the neck. The patient then underwent total thyroidectomy and left neck dissection as a definitive treatment for both hyperthyroidism and residual melanoma. Conclusion. Graves' disease can develop after starting ipilimumab and methimazole can be an effective treatment. For patients whose hyperthyroidism is well-controlled on methimazole, ipilimumab may be resumed with close monitoring.
IS - 2090-6501
IL - 2090-651X
DO - https://dx.doi.org/10.1155/2016/2087525
PT - Journal Article
ID - 26881150 [pubmed]
ID - 10.1155/2016/2087525 [doi]
ID - PMC4737013 [pmc]
PP - ppublish
PH - 2015/09/24 [received]
PH - 2015/12/20 [accepted]
LG - English
EP - 20160111
DP - 2016
DC - 20160216
EZ - 2016/02/17 06:00
DA - 2016/02/18 06:01
DT - 2016/02/18 06:00
YR - 2016
ED - 20160216
RD - 20160219
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=26881150
<161. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26673995
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Kopecky J
AU - Kubecek O
AU - Gabalec F
AU - Hoffmann P
AU - Svilias I
FA - Kopecky, J
FA - Kubecek, O
FA - Gabalec, F
FA - Hoffmann, P
FA - Svilias, I
TI - [Possible Pitfalls of Ipilimumab Therapy in Malignant Melanoma - a Case Report]. [Czech]
OT - Mozna uskali lecby ipilimumabem u maligniho melanomu - kazuistika.
SO - Klinicka Onkologie. 28(6):444-9, 2015
AS - KLIN. ONKOL.. 28(6):444-9, 2015
NJ - Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 9425213
IO - Klin Onkol
SB - Index Medicus
CP - Czech Republic
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Female
MH - Humans
MH - *Melanoma/dt [Drug Therapy]
MH - *Skin Neoplasms/dt [Drug Therapy]
AB - BACKGROUND: Metastatic melanoma is a malignancy with one of the highest mortality rates. However, with the introduction of new drugs during the last decade, the prognosis of patients began to improve. Ipilimumab is one of the first so called modern drugs in melanoma treatment. The therapy is often complicated by adverse effects which are referred as immunerelated adverse events due to its mechanism of action.
AB - CASE: We present a case of 68-year- old women with metastatic melanoma who underwent treatment with ipilimumab. The patient encountered several adverse events during the treatment. Some of them are quite common (e.g. skin affections), others (e.g. endocrinopathies) are less frequent.
AB - CONCLUSION: This case study highlights the need for close observation not only during the actual treatment with ipilimumab, but also several weeks or months after the last dose. This case study also demonstrates further need of education of doctors who do not usually come in to contact with such patients.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
IS - 0862-495X
IL - 0862-495X
DI - 56839
PT - Case Reports
PT - Journal Article
ID - 26673995 [pubmed]
ID - 56839 [pii]
PP - ppublish
LG - Czech
DP - 2015
DC - 20151217
EZ - 2015/12/18 06:00
DA - 2016/02/13 06:00
DT - 2015/12/18 06:00
YR - 2015
ED - 20160211
RD - 20161126
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26673995
<162. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26855529
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Dawood S
FA - Dawood, Shaheenah
IN - Dawood, Shaheenah. Department of Medical Oncology, Dubai Hospital, Dubai, UAE.
TI - Breast and gastrointestinal cancer updates from ASCO 2015.
SO - Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric Oncology. 36(3):189-92, 2015 Jul-Sep
AS - Indian J Med Paediatr Oncol. 36(3):189-92, 2015 Jul-Sep
NJ - Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric Oncology
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 9604571
IO - Indian J Med Paediatr Oncol
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4743179
CP - India
KW - ASCO; breast cancer; colorectal cancer; immunotherapy
AB - This review focuses on the updates presented at the ASCO 2015 symposium in breast and gastrointestinal malignancies. Some were practice changing while others gave us an exciting glimpse into what's to come in the very near future. Immunotherapy was the buzz word this year with data presented on every tumor site. Data on the efficacy of anti PD-1 agents in colorectal, hepatocellular and gastric cancer were presented. In breast cancer we saw data on a new and exciting therapeutic target in the form of androgen receptor among triple receptor negative breast tumors presented. Positive results of the PALOMA 3 trial were presented that has given women with hormone receptor positive metastatic breast cancer another therapeutic option. Furthermore data on strategies to further improve anti her2 therapy, optimizing of chemotherapy in the early and advanced stage and various strategies to improve endocrine therapy among patients with breast cancer were presented.
IS - 0971-5851
IL - 0971-5851
DI - IJMPO-36-189
DO - https://dx.doi.org/10.4103/0971-5851.166757
PT - Journal Article
ID - 26855529 [pubmed]
ID - 10.4103/0971-5851.166757 [doi]
ID - IJMPO-36-189 [pii]
ID - PMC4743179 [pmc]
PP - ppublish
LG - English
DP - 2015 Jul-Sep
DC - 20160209
EZ - 2016/02/09 06:00
DA - 2016/02/09 06:01
DT - 2016/02/09 06:00
YR - 2015
ED - 20160209
RD - 20160210
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=26855529
<163. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25649350
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Johnson DB
AU - Friedman DL
AU - Berry E
AU - Decker I
AU - Ye F
AU - Zhao S
AU - Morgans AK
AU - Puzanov I
AU - Sosman JA
AU - Lovly CM
FA - Johnson, Douglas B
FA - Friedman, Debra L
FA - Berry, Elizabeth
FA - Decker, Ilka
FA - Ye, Fei
FA - Zhao, Shilin
FA - Morgans, Alicia K
FA - Puzanov, Igor
FA - Sosman, Jeffrey A
FA - Lovly, Christine M
IN - Johnson, Douglas B. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. douglas.b.johnson@vanderbilt.edu.
IN - Friedman, Debra L. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Berry, Elizabeth. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Decker, Ilka. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Ye, Fei. Department of Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Zhao, Shilin. Department of Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Morgans, Alicia K. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Puzanov, Igor. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Sosman, Jeffrey A. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Lovly, Christine M. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee.
TI - Survivorship in Immune Therapy: Assessing Chronic Immune Toxicities, Health Outcomes, and Functional Status among Long-term Ipilimumab Survivors at a Single Referral Center.
SO - Cancer Immunology Research. 3(5):464-9, 2015 May
AS - Cancer Immunol Res. 3(5):464-9, 2015 May
NJ - Cancer immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101614637
IO - Cancer Immunol Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420706
OI - Source: NLM. NIHMS661215
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Colitis/ci [Chemically Induced]
MH - Diarrhea/ci [Chemically Induced]
MH - Disease-Free Survival
MH - Exanthema/ci [Chemically Induced]
MH - Humans
MH - Immunotherapy
MH - *Melanoma/dt [Drug Therapy]
MH - Neuralgia/ci [Chemically Induced]
MH - Pituitary Diseases/ci [Chemically Induced]
MH - Pruritus/ci [Chemically Induced]
MH - Treatment Outcome
AB - Ipilimumab, a novel immune checkpoint inhibitor, is associated with long-term survival in approximately 20% of patients with advanced melanoma and is also being evaluated in the adjuvant setting. With this growing cohort of survivors, long-term health outcomes, chronic toxicities, and functional outcomes among survivors treated with ipilimumab need to be defined. Using retrospective medical record abstraction, we evaluated disease status, chronic immune- and non-immune-related health events, pharmacologic management of symptoms, and functional status in patients with melanoma, with overall survival >=2 years following ipilimumab treatment at Vanderbilt University. Ninety patients received ipilimumab for metastatic disease or as adjuvant therapy between January 2006 and September 2012, and 33 patients survived >=2 years, with a median overall survival of 60.1 months. Of these, 24 patients were alive at the last follow-up (73%), with 14 patients free of disease (42%). Gastrointestinal and dermatologic adverse events were frequent but largely transient. By contrast, patients with hypophysitis universally required ongoing corticosteroids, although largely remained asymptomatic with appropriate hormone replacement. Surviving patients generally had excellent performance status (ECOG 0-1 in 23 of 24). Chronic neurologic toxicities caused substantial morbidity and mortality in 2 patients who received whole-brain radiotherapy >5 years before analysis, and in one patient with chronic, painful peripheral neuropathy. No previously undescribed cardiac, pulmonary, gastrointestinal, hematologic, or neoplastic safety signals were identified. In conclusion, ipilimumab was associated with largely excellent functional outcomes among long-term survivors. Chronic endocrine dysfunction and occasional neurologic toxicity (primarily associated with whole-brain radiation) were observed in a small number of patients.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
ES - 2326-6074
IL - 2326-6066
DI - 2326-6066.CIR-14-0217
DO - https://dx.doi.org/10.1158/2326-6066.CIR-14-0217
PT - Clinical Trial
PT - Journal Article
PT - Research Support, N.I.H., Extramural
ID - 25649350 [pubmed]
ID - 2326-6066.CIR-14-0217 [pii]
ID - 10.1158/2326-6066.CIR-14-0217 [doi]
ID - PMC4420706 [pmc]
ID - NIHMS661215 [mid]
PP - ppublish
PH - 2014/11/18 [received]
PH - 2015/01/26 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00094653
SA - ClinicalTrials.gov/NCT00495066
SA - ClinicalTrials.gov/NCT00623766
SA - ClinicalTrials.gov/NCT01274338
SA - ClinicalTrials.gov/NCT00094653
SA - ClinicalTrials.gov/NCT00495066
SA - ClinicalTrials.gov/NCT00623766
SA - ClinicalTrials.gov/NCT01274338
SL - https://clinicaltrials.gov/search/term=NCT00094653
SL - https://clinicaltrials.gov/search/term=NCT00495066
SL - https://clinicaltrials.gov/search/term=NCT00623766
SL - https://clinicaltrials.gov/search/term=NCT01274338
SL - https://clinicaltrials.gov/search/term=NCT00094653
SL - https://clinicaltrials.gov/search/term=NCT00495066
SL - https://clinicaltrials.gov/search/term=NCT00623766
SL - https://clinicaltrials.gov/search/term=NCT01274338
GI - No: K12 CA090625
Organization: (CA) *NCI NIH HHS*
Country: United States
No: UL1 TR000445
Organization: (TR) *NCATS NIH HHS*
Country: United States
No: K12 CA 0906525
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20150203
DP - 2015 May
DC - 20150505
EZ - 2015/02/05 06:00
DA - 2016/02/09 06:00
DT - 2015/02/05 06:00
YR - 2015
ED - 20160208
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25649350
<164. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25649350
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Johnson DB
AU - Friedman DL
AU - Berry E
AU - Decker I
AU - Ye F
AU - Zhao S
AU - Morgans AK
AU - Puzanov I
AU - Sosman JA
AU - Lovly CM
FA - Johnson, Douglas B
FA - Friedman, Debra L
FA - Berry, Elizabeth
FA - Decker, Ilka
FA - Ye, Fei
FA - Zhao, Shilin
FA - Morgans, Alicia K
FA - Puzanov, Igor
FA - Sosman, Jeffrey A
FA - Lovly, Christine M
IN - Johnson, Douglas B. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. douglas.b.johnson@vanderbilt.edu.
IN - Friedman, Debra L. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Berry, Elizabeth. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Decker, Ilka. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Ye, Fei. Department of Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Zhao, Shilin. Department of Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Morgans, Alicia K. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Puzanov, Igor. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Sosman, Jeffrey A. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
IN - Lovly, Christine M. Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee.
TI - Survivorship in Immune Therapy: Assessing Chronic Immune Toxicities, Health Outcomes, and Functional Status among Long-term Ipilimumab Survivors at a Single Referral Center.
SO - Cancer Immunology Research. 3(5):464-9, 2015 May
AS - Cancer Immunol Res. 3(5):464-9, 2015 May
NJ - Cancer immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101614637
IO - Cancer Immunol Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420706
OI - Source: NLM. NIHMS661215
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Colitis/ci [Chemically Induced]
MH - Diarrhea/ci [Chemically Induced]
MH - Disease-Free Survival
MH - Exanthema/ci [Chemically Induced]
MH - Humans
MH - Immunotherapy
MH - *Melanoma/dt [Drug Therapy]
MH - Neuralgia/ci [Chemically Induced]
MH - Pituitary Diseases/ci [Chemically Induced]
MH - Pruritus/ci [Chemically Induced]
MH - Treatment Outcome
AB - Ipilimumab, a novel immune checkpoint inhibitor, is associated with long-term survival in approximately 20% of patients with advanced melanoma and is also being evaluated in the adjuvant setting. With this growing cohort of survivors, long-term health outcomes, chronic toxicities, and functional outcomes among survivors treated with ipilimumab need to be defined. Using retrospective medical record abstraction, we evaluated disease status, chronic immune- and non-immune-related health events, pharmacologic management of symptoms, and functional status in patients with melanoma, with overall survival >=2 years following ipilimumab treatment at Vanderbilt University. Ninety patients received ipilimumab for metastatic disease or as adjuvant therapy between January 2006 and September 2012, and 33 patients survived >=2 years, with a median overall survival of 60.1 months. Of these, 24 patients were alive at the last follow-up (73%), with 14 patients free of disease (42%). Gastrointestinal and dermatologic adverse events were frequent but largely transient. By contrast, patients with hypophysitis universally required ongoing corticosteroids, although largely remained asymptomatic with appropriate hormone replacement. Surviving patients generally had excellent performance status (ECOG 0-1 in 23 of 24). Chronic neurologic toxicities caused substantial morbidity and mortality in 2 patients who received whole-brain radiotherapy >5 years before analysis, and in one patient with chronic, painful peripheral neuropathy. No previously undescribed cardiac, pulmonary, gastrointestinal, hematologic, or neoplastic safety signals were identified. In conclusion, ipilimumab was associated with largely excellent functional outcomes among long-term survivors. Chronic endocrine dysfunction and occasional neurologic toxicity (primarily associated with whole-brain radiation) were observed in a small number of patients.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
ES - 2326-6074
IL - 2326-6066
DI - 2326-6066.CIR-14-0217
DO - https://dx.doi.org/10.1158/2326-6066.CIR-14-0217
PT - Clinical Trial
PT - Journal Article
PT - Research Support, N.I.H., Extramural
ID - 25649350 [pubmed]
ID - 2326-6066.CIR-14-0217 [pii]
ID - 10.1158/2326-6066.CIR-14-0217 [doi]
ID - PMC4420706 [pmc]
ID - NIHMS661215 [mid]
PP - ppublish
PH - 2014/11/18 [received]
PH - 2015/01/26 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00094653
SA - ClinicalTrials.gov/NCT00495066
SA - ClinicalTrials.gov/NCT00623766
SA - ClinicalTrials.gov/NCT01274338
SL - https://clinicaltrials.gov/search/term=NCT00094653
SL - https://clinicaltrials.gov/search/term=NCT00495066
SL - https://clinicaltrials.gov/search/term=NCT00623766
SL - https://clinicaltrials.gov/search/term=NCT01274338
GI - No: K12 CA090625
Organization: (CA) *NCI NIH HHS*
Country: United States
No: UL1 TR000445
Organization: (TR) *NCATS NIH HHS*
Country: United States
No: K12 CA 0906525
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20150203
DP - 2015 May
DC - 20150505
EZ - 2015/02/05 06:00
DA - 2016/02/09 06:00
DT - 2015/02/05 06:00
YR - 2015
ED - 20160208
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=25649350
<165. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25786871
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - El Khatib MM
AU - Sakuma T
AU - Tonne JM
AU - Mohamed MS
AU - Holditch SJ
AU - Lu B
AU - Kudva YC
AU - Ikeda Y
AI - Ikeda, Y; ORCID: https://orcid.org/0000000298747537
FA - El Khatib, M M
FA - Sakuma, T
FA - Tonne, J M
FA - Mohamed, M S
FA - Holditch, S J
FA - Lu, B
FA - Kudva, Y C
FA - Ikeda, Y
IN - El Khatib, M M. Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
IN - Sakuma, T. Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
IN - Tonne, J M. Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
IN - Mohamed, M S. Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
IN - Holditch, S J. Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
IN - Lu, B. Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
IN - Kudva, Y C. Division of Endocrinology, Mayo Clinic College of Medicine, Rochester, MN, USA.
IN - Ikeda, Y. Department of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.
TI - beta-Cell-targeted blockage of PD1 and CTLA4 pathways prevents development of autoimmune diabetes and acute allogeneic islets rejection.
SO - Gene Therapy. 22(5):430-8, 2015 May
AS - Gene Ther. 22(5):430-8, 2015 May
NJ - Gene therapy
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cce, 9421525
IO - Gene Ther.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520544
OI - Source: NLM. NIHMS708388
SB - Index Medicus
CP - England
MH - Animals
MH - *Antigens, CD274/im [Immunology]
MH - *Autoimmunity
MH - *CTLA-4 Antigen/im [Immunology]
MH - *Diabetes Mellitus, Experimental/im [Immunology]
MH - Diabetes Mellitus, Experimental/th [Therapy]
MH - *Graft Rejection
MH - HEK293 Cells
MH - Humans
MH - Immunosuppression
MH - *Insulin-Secreting Cells/im [Immunology]
MH - Insulin-Secreting Cells/tr [Transplantation]
MH - Mice
MH - Mice, Inbred BALB C
MH - Mice, Inbred ICR
MH - Mice, Inbred NOD
MH - Transplantation, Homologous
AB - Protection of beta cells from autoimmune destruction potentially cures type 1 diabetes mellitus (T1D). During antigen presentation, interactions between cytotoxic T-lymphocyte antigen-4 (CTLA4) and B7 molecules, or programmed death 1 (PD1) and its ligand PDL1, negatively regulate immune responses in a non-redundant manner. Here we employed beta-cell-targeted adeno-associated virus serotype 8 (AAV8)-based vectors to overexpress an artificial PDL1-CTLA4Ig polyprotein or interleukin 10 (IL10). beta-Cell-targeted expression of PDL1-CTLA4Ig or IL10 preserved beta-cell mass and protected NOD mice from T1D development. When NOD mice were treated with vectors at early onset of hyperglycemia, PDL1-CTLA4Ig or IL10 alone failed to normalize the early onset of hyperglycemia. When drug-induced diabetic mice received major histocompatibility complex (MHC)-matched allo-islets, with or without pretreatment of the PDL1-CTLA4Ig-expressing vector, PDL1-CTLA4Ig-expressing islets were protected from rejection for at least 120 days. Similarly, transplantation of PDL1-CTLA4Ig-expressing MHC-matched islets into mice with established T1D resulted in protection of allo-islets from acute rejection, although islet grafts were eventually rejected. Thus the present study demonstrates the potent immuno-suppressive effects of beta-cell-targeted PDL1-CTLA4Ig overexpression against T1D development and allo-islet rejection. The gene-based simultaneous inhibition of PD1 and CTLA4 pathways provides a unique strategy for immunosuppression-free tissue/organ transplantation, especially in the setting of no established autoimmunity.
RN - 0 (Antigens, CD274)
RN - 0 (CTLA-4 Antigen)
ES - 1476-5462
IL - 0969-7128
DI - gt201518
DO - https://dx.doi.org/10.1038/gt.2015.18
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 25786871 [pubmed]
ID - gt201518 [pii]
ID - 10.1038/gt.2015.18 [doi]
ID - PMC4520544 [pmc]
ID - NIHMS708388 [mid]
PP - ppublish
PH - 2014/09/03 [received]
PH - 2015/01/07 [revised]
PH - 2015/02/12 [accepted]
GI - No: R01 HL098502
Organization: (HL) *NHLBI NIH HHS*
Country: United States
No: HL098502
Organization: (HL) *NHLBI NIH HHS*
Country: United States
LG - English
EP - 20150319
DP - 2015 May
DC - 20150507
EZ - 2015/03/20 06:00
DA - 2016/02/04 06:00
DT - 2015/03/20 06:00
YR - 2015
ED - 20160203
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25786871
<166. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26304716
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wang Z
AU - Lai ST
AU - Ma NY
AU - Deng Y
AU - Liu Y
AU - Wei DP
AU - Zhao JD
AU - Jiang GL
FA - Wang, Zheng
FA - Lai, Song-Tao
FA - Ma, Ning-Yi
FA - Deng, Yun
FA - Liu, Yong
FA - Wei, Dong-Ping
FA - Zhao, Jian-Dong
FA - Jiang, Guo-Liang
IN - Wang, Zheng. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai 200032, China.
IN - Lai, Song-Tao. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai 200032, China.
IN - Ma, Ning-Yi. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai 200032, China.
IN - Deng, Yun. Cancer Research Institute, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China.
IN - Liu, Yong. Cancer Research Institute, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China.
IN - Wei, Dong-Ping. Cancer Research Institute, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China.
IN - Zhao, Jian-Dong. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai 200032, China.
IN - Jiang, Guo-Liang. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai 200032, China; Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, 4365 Kangxin Road, Shanghai 201321, China. Electronic address: guoliang.jiang@sphic.org.cn.
TI - Radiosensitization of metformin in pancreatic cancer cells via abrogating the G2 checkpoint and inhibiting DNA damage repair.
SO - Cancer Letters. 369(1):192-201, 2015 Dec 01
AS - Cancer Lett. 369(1):192-201, 2015 Dec 01
NJ - Cancer letters
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 7600053, cmx
IO - Cancer Lett.
SB - Index Medicus
CP - Ireland
MH - Apoptosis/re [Radiation Effects]
MH - Cell Cycle Proteins/ai [Antagonists & Inhibitors]
MH - Cell Cycle Proteins/me [Metabolism]
MH - Cell Line, Tumor
MH - Chemoradiotherapy
MH - Cyclin-Dependent Kinases/me [Metabolism]
MH - *DNA Damage
MH - *DNA Repair
MH - *G2 Phase Cell Cycle Checkpoints
MH - Humans
MH - *Metformin/pd [Pharmacology]
MH - Mitosis/de [Drug Effects]
MH - Nuclear Proteins/ai [Antagonists & Inhibitors]
MH - Nuclear Proteins/me [Metabolism]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - Phosphorylation
MH - Protein Biosynthesis/de [Drug Effects]
MH - Protein Processing, Post-Translational/de [Drug Effects]
MH - Protein-Tyrosine Kinases/ai [Antagonists & Inhibitors]
MH - Protein-Tyrosine Kinases/me [Metabolism]
MH - Rad51 Recombinase/me [Metabolism]
MH - Radiation Tolerance
MH - *Radiation-Sensitizing Agents/pd [Pharmacology]
KW - Metformin; Pancreatic cancer; Rad51; Radiosensitizer; Wee1; mTOR
AB - Recent evidences have demonstrated the potential of metformin as a novel agent for cancer prevention and treatment. Here, we investigated its ability of radiosensitization and the underlying mechanisms in human pancreatic cancer cells. In this study, we found that metformin at 5mM concentration enhanced the radiosensitivity of MIA PaCa-2 and PANC-1 cells, with sensitization enhancement ratios of 1.39 and 1.27, respectively. Mechanistically, metformin caused abrogation of the G2 checkpoint and increase of mitotic catastrophe, associated with suppression of Wee1 kinase and in turn CDK1 Tyr15 phosphorylation. Furthermore, metformin inhibited both expression and irradiation-induced foci formation of Rad51, a key player in homologous recombination repair, ultimately leading to persistent DNA damage, as reflected by gamma-H2AX and 53BP1 signaling. Finally, metformin-mediated AMPK/mTOR/p70S6K was identified as a possible upstream pathway controlling translational regulation of Wee1 and Rad51. Our data suggest that metformin radiosensitizes pancreatic cancer cells in vitro via abrogation of the G2 checkpoint and inhibition of DNA damage repair. However, the in vivo study is needed to further confirm the findings from the in vitro study.
AB - Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
RN - 0 (Cell Cycle Proteins)
RN - 0 (Nuclear Proteins)
RN - 0 (Radiation-Sensitizing Agents)
RN - 9100L32L2N (Metformin)
RN - EC 2-7-10-1 (Protein-Tyrosine Kinases)
RN - EC 2-7-10-2 (WEE1 protein, human)
RN - EC 2-7-11-22 (CDK1 protein, human)
RN - EC 2-7-11-22 (Cyclin-Dependent Kinases)
RN - EC 2-7-7 (RAD51 protein, human)
RN - EC 2-7-7 (Rad51 Recombinase)
ES - 1872-7980
IL - 0304-3835
DI - S0304-3835(15)00544-3
DO - https://dx.doi.org/10.1016/j.canlet.2015.08.015
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26304716 [pubmed]
ID - S0304-3835(15)00544-3 [pii]
ID - 10.1016/j.canlet.2015.08.015 [doi]
PP - ppublish
PH - 2015/04/11 [received]
PH - 2015/07/14 [revised]
PH - 2015/08/18 [accepted]
LG - English
EP - 20150821
DP - 2015 Dec 01
DC - 20151010
EZ - 2015/08/26 06:00
DA - 2016/02/02 06:00
DT - 2015/08/26 06:00
YR - 2015
ED - 20160201
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26304716
<167. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25901859
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Grizzi F
AU - Mirandola L
AU - Qehajaj D
AU - Cobos E
AU - Figueroa JA
AU - Chiriva-Internati M
FA - Grizzi, F
FA - Mirandola, L
FA - Qehajaj, D
FA - Cobos, E
FA - Figueroa, J A
FA - Chiriva-Internati, M
IN - Grizzi, F. Humanitas Clinical and Research Center , Rozzano, Milan , Italy.
TI - Cancer-testis antigens and immunotherapy in the light of cancer complexity. [Review]
SO - International Reviews of Immunology. 34(2):143-53, 2015 Mar
AS - Int Rev Immunol. 34(2):143-53, 2015 Mar
NJ - International reviews of immunology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - iri, 8712260
IO - Int. Rev. Immunol.
SB - Index Medicus
CP - England
MH - Animals
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antigens, Neoplasm/im [Immunology]
MH - Drug Approval
MH - Humans
MH - *Immunotherapy, Adoptive
MH - Male
MH - Testicular Neoplasms/im [Immunology]
MH - *Testicular Neoplasms/th [Therapy]
MH - Tissue Extracts/tu [Therapeutic Use]
KW - biomarkers; cancer; cancer-testis antigens; immunotherapy; inflammation; vaccine
AB - The ability of immunotherapy to evoke successful antitumor immune responses has been well documented over the past decade. Despite abundant preclinical data, it is only with the recent approval by the Food and Drug Administration (FDA) of the drugs such as sipuleucel-T and ipilimumab that immunotherapy is finally being recognized as a viable alternative to traditional therapies for treatment of various cancers. Despite the ability of immunotherapy to elicit successful antitumor immune responses, its efficacy is hindered by several factors. Among these are the paucity of tumor-associated antigens (TAA) that can be used as effective targets and the systemic toxicities that often lead to treatment interruption. Indeed, such adverse effects, which can be immunological and/or parenchymal, can be particularly severe and even fatal to some patients. A family of TAA called cancer-testis antigens (CTA) has been identified and their encoding genes have been extensively investigated. CTA expression has been demonstrated in a variety of human cancer tissues, and at least 19 CTA have been found to elicit humoral and/or cellular immune responses in cancer patients. Here we discuss how CTA and immunotherapy will most likely play a major role in the cure of cancer in the light of cancer complexity.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, Neoplasm)
RN - 0 (Tissue Extracts)
RN - 6T8C155666 (ipilimumab)
RN - 8Q622VDR18 (sipuleucel-T)
ES - 1563-5244
IL - 0883-0185
DO - https://dx.doi.org/10.3109/08830185.2015.1018418
PT - Journal Article
PT - Review
ID - 25901859 [pubmed]
ID - 10.3109/08830185.2015.1018418 [doi]
PP - ppublish
LG - English
DP - 2015 Mar
DC - 20150423
EZ - 2015/04/23 06:00
DA - 2016/01/30 06:00
DT - 2015/04/23 06:00
YR - 2015
ED - 20160129
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25901859
<168. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26410424
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Yamazaki N
AU - Kiyohara Y
AU - Uhara H
AU - Fukushima S
AU - Uchi H
AU - Shibagaki N
AU - Tsutsumida A
AU - Yoshikawa S
AU - Okuyama R
AU - Ito Y
AU - Tokudome T
FA - Yamazaki, N
FA - Kiyohara, Y
FA - Uhara, H
FA - Fukushima, S
FA - Uchi, H
FA - Shibagaki, N
FA - Tsutsumida, A
FA - Yoshikawa, S
FA - Okuyama, R
FA - Ito, Y
FA - Tokudome, T
IN - Yamazaki, N. Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
IN - Kiyohara, Y. Dermatology Division, Shizuoka Cancer Center, Shizuoka, Japan.
IN - Uhara, H. Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
IN - Fukushima, S. Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
IN - Uchi, H. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
IN - Shibagaki, N. Department of Dermatology, University of Yamanashi Hospital, Yamanashi, Japan.
IN - Tsutsumida, A. Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
IN - Yoshikawa, S. Dermatology Division, Shizuoka Cancer Center, Shizuoka, Japan.
IN - Okuyama, R. Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
IN - Ito, Y. Research and Development, Bristol-Myers K.K., 6-5-1, Nishishinjuku, Shinjuku-ku, Tokyo, 1631328, Japan.
IN - Tokudome, T. Research and Development, Bristol-Myers K.K., 6-5-1, Nishishinjuku, Shinjuku-ku, Tokyo, 1631328, Japan. takuto0806@gmail.com.
TI - Phase II study of ipilimumab monotherapy in Japanese patients with advanced melanoma.
SO - Cancer Chemotherapy & Pharmacology. 76(5):997-1004, 2015 Nov
AS - Cancer Chemother Pharmacol. 76(5):997-1004, 2015 Nov
NJ - Cancer chemotherapy and pharmacology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c9s, 7806519
IO - Cancer Chemother. Pharmacol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612321
SB - Index Medicus
CP - Germany
MH - Adult
MH - Aged
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/im [Immunology]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antibody Formation
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/im [Immunology]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - Chemical and Drug Induced Liver Injury/et [Etiology]
MH - Disease-Free Survival
MH - Drug Eruptions/et [Etiology]
MH - Exanthema/ci [Chemically Induced]
MH - Female
MH - Fever/ci [Chemically Induced]
MH - Follow-Up Studies
MH - Humans
MH - Immunologic Factors/ae [Adverse Effects]
MH - *Immunologic Factors/tu [Therapeutic Use]
MH - Japan
MH - Kaplan-Meier Estimate
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - Melanoma/sc [Secondary]
MH - Middle Aged
MH - Treatment Outcome
KW - Immune-checkpoint inhibitor; Ipilimumab; Japanese patients; Melanoma; Phase II study
AB - PURPOSE: Ipilimumab is designed to block cytotoxic T-lymphocyte antigen-4 to augment antitumor T cell responses. In studies of predominantly Caucasian patients with advanced melanoma, ipilimumab was associated with durable response, long-term survival benefit, and a manageable safety profile. This phase II study assessed the safety of ipilimumab in Japanese patients with unresectable stage III or IV melanoma.
AB - METHODS: Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. The database lock for the original analysis was in August 2014. Overall survival, progression-free survival, and data on deaths were based on an updated, follow-up analysis (database lock April 2015).
AB - RESULTS: Data are reported from 20 patients. Fifteen patients (75 %) received all four doses of ipilimumab during induction. Twelve patients (60 %) had at least one drug-related adverse event (AE), and no patients discontinued due to a drug-related AE. There were no deaths related to study drug. The most common drug-related AEs were rash (n = 7), pyrexia (n = 3), increased aspartate aminotransferase (AST; n = 3), and increased alanine aminotransferase (ALT; n = 3). Twelve patients (60 %) reported immune-related AEs (irAEs); most frequent were skin (n = 9) and liver (n = 3) disorders. Grade 3 irAEs were ALT and AST elevation (n = 2) and diabetes mellitus (n = 1). Two patients had a partial response and two had stable disease, yielding a 20 % disease control rate. Median overall survival and progression-free survival were 8.71 and 2.74 months, respectively.
AB - CONCLUSION: Ipilimumab 3 mg/kg had a manageable AE profile in this Japanese patient population with clinical outcomes similar to that in Caucasian patients. CLINICALTRIALS.
AB - GOV IDENTIFIER: NCT01990859.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (Immunologic Factors)
RN - 6T8C155666 (ipilimumab)
ES - 1432-0843
IL - 0344-5704
DI - 10.1007/s00280-015-2873-x
DO - https://dx.doi.org/10.1007/s00280-015-2873-x
PT - Clinical Trial, Phase II
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26410424 [pubmed]
ID - 10.1007/s00280-015-2873-x [doi]
ID - 10.1007/s00280-015-2873-x [pii]
ID - PMC4612321 [pmc]
PP - ppublish
PH - 2015/06/30 [received]
PH - 2015/09/09 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01990859
SA - ClinicalTrials.gov/NCT01990859
SL - https://clinicaltrials.gov/search/term=NCT01990859
SL - https://clinicaltrials.gov/search/term=NCT01990859
LG - English
EP - 20150926
DP - 2015 Nov
DC - 20151021
EZ - 2015/09/28 06:00
DA - 2016/01/29 06:00
DT - 2015/09/28 06:00
YR - 2015
ED - 20160128
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26410424
<169. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26407818
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Yamazaki N
AU - Uhara H
AU - Fukushima S
AU - Uchi H
AU - Shibagaki N
AU - Kiyohara Y
AU - Tsutsumida A
AU - Namikawa K
AU - Okuyama R
AU - Otsuka Y
AU - Tokudome T
FA - Yamazaki, N
FA - Uhara, H
FA - Fukushima, S
FA - Uchi, H
FA - Shibagaki, N
FA - Kiyohara, Y
FA - Tsutsumida, A
FA - Namikawa, K
FA - Okuyama, R
FA - Otsuka, Y
FA - Tokudome, T
IN - Yamazaki, N. Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
IN - Uhara, H. Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
IN - Fukushima, S. Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
IN - Uchi, H. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
IN - Shibagaki, N. Department of Dermatology, Yamanashi University Hospital, Yamanashi, Japan.
IN - Kiyohara, Y. Dermatology Division, Shizuoka Cancer Center, Shizuoka, Japan.
IN - Tsutsumida, A. Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
IN - Namikawa, K. Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
IN - Okuyama, R. Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
IN - Otsuka, Y. Research and Development, Bristol-Myers K.K., 6-5-1, Nishishinjuku, Shinjuku-ku, Tokyo, 163-1328, Japan.
IN - Tokudome, T. Research and Development, Bristol-Myers K.K., 6-5-1, Nishishinjuku, Shinjuku-ku, Tokyo, 163-1328, Japan. takuto0806@gmail.com.
TI - Phase II study of the immune-checkpoint inhibitor ipilimumab plus dacarbazine in Japanese patients with previously untreated, unresectable or metastatic melanoma.
SO - Cancer Chemotherapy & Pharmacology. 76(5):969-75, 2015 Nov
AS - Cancer Chemother Pharmacol. 76(5):969-75, 2015 Nov
NJ - Cancer chemotherapy and pharmacology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c9s, 7806519
IO - Cancer Chemother. Pharmacol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612320
SB - Index Medicus
CP - Germany
MH - Adult
MH - Aged
MH - Alanine Transaminase/bl [Blood]
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
MH - *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - Aspartate Aminotransferases/bl [Blood]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - Chemical and Drug Induced Liver Injury/bl [Blood]
MH - *Chemical and Drug Induced Liver Injury/et [Etiology]
MH - Dacarbazine/ad [Administration & Dosage]
MH - Dacarbazine/ae [Adverse Effects]
MH - Disease Progression
MH - Disease-Free Survival
MH - Drug Administration Schedule
MH - Drug Eruptions/et [Etiology]
MH - Endocrine System Diseases/ci [Chemically Induced]
MH - Female
MH - Humans
MH - Immunosuppressive Agents/tu [Therapeutic Use]
MH - Japan
MH - Kaplan-Meier Estimate
MH - Maintenance Chemotherapy
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/sc [Secondary]
MH - Middle Aged
MH - Neoplasm Proteins/ai [Antagonists & Inhibitors]
MH - Neoplasm Proteins/im [Immunology]
MH - Remission Induction
MH - Treatment Outcome
KW - Dacarbazine; Immune-checkpoint inhibitor; Ipilimumab; Japanese patients; Melanoma; Phase 2 study
AB - PURPOSE: Ipilimumab (IPI), a monoclonal antibody against immune-checkpoint receptor cytotoxic T lymphocyte antigen-4, is designed to enhance antitumor T cell function. IPI 10 mg/kg plus dacarbazine (DTIC) significantly improved overall survival in a phase 3 study involving predominantly Caucasian patients, with an adverse event (AE) profile similar to that of IPI monotherapy. We conducted a single-arm, phase 2 study to evaluate the safety and efficacy of IPI plus DTIC in Japanese patients.
AB - METHODS: Previously untreated patients with unresectable stage III or IV melanoma received IPI 10 mg/kg plus DTIC 850 mg/m(2) every 3 weeks for four doses (q3w x 4), followed by DTIC q3w x 4 and then IPI every 12 weeks until disease progression or intolerable toxicity.
AB - RESULTS: All 15 treated patients reported drug-related AEs, the most common of which were increases in alanine aminotransferase (n = 12, 80 %) and aspartate aminotransferase (n = 11, 73 %). Treatment-related serious AEs were reported in 11 (73 %) patients. Nine patients (60 %) discontinued treatment due to drug-related toxicities. Immune-related AEs (irAEs) were reported in 14 patients (93 %). The most frequent irAEs were liver (n = 12, 80 %) and skin (n = 10, 67 %) toxicities. Five deaths were reported; all were caused by progressive disease. Efficacy evaluation showed one complete response, one partial response and four patients with stable disease. Best overall response rate was 13 % (2/15), and the disease control rate was 40 % (6/15). The study was terminated early due to frequent, high-grade liver toxicities.
AB - CONCLUSIONS: IPI 10 mg/kg plus DTIC 850 mg/m(2) was not considered tolerable in the Japanese patient population. ClinicalTrials.gov identifier: NCT01681212.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (Immunosuppressive Agents)
RN - 0 (Neoplasm Proteins)
RN - 6T8C155666 (ipilimumab)
RN - 7GR28W0FJI (Dacarbazine)
RN - EC 2-6-1-1 (Aspartate Aminotransferases)
RN - EC 2-6-1-2 (Alanine Transaminase)
ES - 1432-0843
IL - 0344-5704
DI - 10.1007/s00280-015-2870-0
DO - https://dx.doi.org/10.1007/s00280-015-2870-0
PT - Clinical Trial, Phase II
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26407818 [pubmed]
ID - 10.1007/s00280-015-2870-0 [doi]
ID - 10.1007/s00280-015-2870-0 [pii]
ID - PMC4612320 [pmc]
PP - ppublish
PH - 2015/08/03 [received]
PH - 2015/09/06 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01681212
SA - ClinicalTrials.gov/NCT01681212
SL - https://clinicaltrials.gov/search/term=NCT01681212
SL - https://clinicaltrials.gov/search/term=NCT01681212
LG - English
EP - 20150925
DP - 2015 Nov
DC - 20151021
EZ - 2015/09/27 06:00
DA - 2016/01/29 06:00
DT - 2015/09/27 06:00
YR - 2015
ED - 20160128
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26407818
<170. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26407818
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Yamazaki N
AU - Uhara H
AU - Fukushima S
AU - Uchi H
AU - Shibagaki N
AU - Kiyohara Y
AU - Tsutsumida A
AU - Namikawa K
AU - Okuyama R
AU - Otsuka Y
AU - Tokudome T
FA - Yamazaki, N
FA - Uhara, H
FA - Fukushima, S
FA - Uchi, H
FA - Shibagaki, N
FA - Kiyohara, Y
FA - Tsutsumida, A
FA - Namikawa, K
FA - Okuyama, R
FA - Otsuka, Y
FA - Tokudome, T
IN - Yamazaki, N. Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
IN - Uhara, H. Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
IN - Fukushima, S. Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
IN - Uchi, H. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
IN - Shibagaki, N. Department of Dermatology, Yamanashi University Hospital, Yamanashi, Japan.
IN - Kiyohara, Y. Dermatology Division, Shizuoka Cancer Center, Shizuoka, Japan.
IN - Tsutsumida, A. Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
IN - Namikawa, K. Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
IN - Okuyama, R. Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
IN - Otsuka, Y. Research and Development, Bristol-Myers K.K., 6-5-1, Nishishinjuku, Shinjuku-ku, Tokyo, 163-1328, Japan.
IN - Tokudome, T. Research and Development, Bristol-Myers K.K., 6-5-1, Nishishinjuku, Shinjuku-ku, Tokyo, 163-1328, Japan. takuto0806@gmail.com.
TI - Phase II study of the immune-checkpoint inhibitor ipilimumab plus dacarbazine in Japanese patients with previously untreated, unresectable or metastatic melanoma.
SO - Cancer Chemotherapy & Pharmacology. 76(5):969-75, 2015 Nov
AS - Cancer Chemother Pharmacol. 76(5):969-75, 2015 Nov
NJ - Cancer chemotherapy and pharmacology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c9s, 7806519
IO - Cancer Chemother. Pharmacol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612320
SB - Index Medicus
CP - Germany
MH - Adult
MH - Aged
MH - Alanine Transaminase/bl [Blood]
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
MH - *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - Aspartate Aminotransferases/bl [Blood]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - Chemical and Drug Induced Liver Injury/bl [Blood]
MH - *Chemical and Drug Induced Liver Injury/et [Etiology]
MH - Dacarbazine/ad [Administration & Dosage]
MH - Dacarbazine/ae [Adverse Effects]
MH - Disease Progression
MH - Disease-Free Survival
MH - Drug Administration Schedule
MH - Drug Eruptions/et [Etiology]
MH - Endocrine System Diseases/ci [Chemically Induced]
MH - Female
MH - Humans
MH - Immunosuppressive Agents/tu [Therapeutic Use]
MH - Japan
MH - Kaplan-Meier Estimate
MH - Maintenance Chemotherapy
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/sc [Secondary]
MH - Middle Aged
MH - Neoplasm Proteins/ai [Antagonists & Inhibitors]
MH - Neoplasm Proteins/im [Immunology]
MH - Remission Induction
MH - Treatment Outcome
KW - Dacarbazine; Immune-checkpoint inhibitor; Ipilimumab; Japanese patients; Melanoma; Phase 2 study
AB - PURPOSE: Ipilimumab (IPI), a monoclonal antibody against immune-checkpoint receptor cytotoxic T lymphocyte antigen-4, is designed to enhance antitumor T cell function. IPI 10 mg/kg plus dacarbazine (DTIC) significantly improved overall survival in a phase 3 study involving predominantly Caucasian patients, with an adverse event (AE) profile similar to that of IPI monotherapy. We conducted a single-arm, phase 2 study to evaluate the safety and efficacy of IPI plus DTIC in Japanese patients.
AB - METHODS: Previously untreated patients with unresectable stage III or IV melanoma received IPI 10 mg/kg plus DTIC 850 mg/m(2) every 3 weeks for four doses (q3w x 4), followed by DTIC q3w x 4 and then IPI every 12 weeks until disease progression or intolerable toxicity.
AB - RESULTS: All 15 treated patients reported drug-related AEs, the most common of which were increases in alanine aminotransferase (n = 12, 80 %) and aspartate aminotransferase (n = 11, 73 %). Treatment-related serious AEs were reported in 11 (73 %) patients. Nine patients (60 %) discontinued treatment due to drug-related toxicities. Immune-related AEs (irAEs) were reported in 14 patients (93 %). The most frequent irAEs were liver (n = 12, 80 %) and skin (n = 10, 67 %) toxicities. Five deaths were reported; all were caused by progressive disease. Efficacy evaluation showed one complete response, one partial response and four patients with stable disease. Best overall response rate was 13 % (2/15), and the disease control rate was 40 % (6/15). The study was terminated early due to frequent, high-grade liver toxicities.
AB - CONCLUSIONS: IPI 10 mg/kg plus DTIC 850 mg/m(2) was not considered tolerable in the Japanese patient population. ClinicalTrials.gov identifier: NCT01681212.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (Immunosuppressive Agents)
RN - 0 (Neoplasm Proteins)
RN - 6T8C155666 (ipilimumab)
RN - 7GR28W0FJI (Dacarbazine)
RN - EC 2-6-1-1 (Aspartate Aminotransferases)
RN - EC 2-6-1-2 (Alanine Transaminase)
ES - 1432-0843
IL - 0344-5704
DI - 10.1007/s00280-015-2870-0
DO - https://dx.doi.org/10.1007/s00280-015-2870-0
PT - Clinical Trial, Phase II
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26407818 [pubmed]
ID - 10.1007/s00280-015-2870-0 [doi]
ID - 10.1007/s00280-015-2870-0 [pii]
ID - PMC4612320 [pmc]
PP - ppublish
PH - 2015/08/03 [received]
PH - 2015/09/06 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01681212
SL - https://clinicaltrials.gov/search/term=NCT01681212
LG - English
EP - 20150925
DP - 2015 Nov
DC - 20151021
EZ - 2015/09/27 06:00
DA - 2016/01/29 06:00
DT - 2015/09/27 06:00
YR - 2015
ED - 20160128
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26407818
<171. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26410424
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Yamazaki N
AU - Kiyohara Y
AU - Uhara H
AU - Fukushima S
AU - Uchi H
AU - Shibagaki N
AU - Tsutsumida A
AU - Yoshikawa S
AU - Okuyama R
AU - Ito Y
AU - Tokudome T
FA - Yamazaki, N
FA - Kiyohara, Y
FA - Uhara, H
FA - Fukushima, S
FA - Uchi, H
FA - Shibagaki, N
FA - Tsutsumida, A
FA - Yoshikawa, S
FA - Okuyama, R
FA - Ito, Y
FA - Tokudome, T
IN - Yamazaki, N. Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
IN - Kiyohara, Y. Dermatology Division, Shizuoka Cancer Center, Shizuoka, Japan.
IN - Uhara, H. Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
IN - Fukushima, S. Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
IN - Uchi, H. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
IN - Shibagaki, N. Department of Dermatology, University of Yamanashi Hospital, Yamanashi, Japan.
IN - Tsutsumida, A. Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.
IN - Yoshikawa, S. Dermatology Division, Shizuoka Cancer Center, Shizuoka, Japan.
IN - Okuyama, R. Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
IN - Ito, Y. Research and Development, Bristol-Myers K.K., 6-5-1, Nishishinjuku, Shinjuku-ku, Tokyo, 1631328, Japan.
IN - Tokudome, T. Research and Development, Bristol-Myers K.K., 6-5-1, Nishishinjuku, Shinjuku-ku, Tokyo, 1631328, Japan. takuto0806@gmail.com.
TI - Phase II study of ipilimumab monotherapy in Japanese patients with advanced melanoma.
SO - Cancer Chemotherapy & Pharmacology. 76(5):997-1004, 2015 Nov
AS - Cancer Chemother Pharmacol. 76(5):997-1004, 2015 Nov
NJ - Cancer chemotherapy and pharmacology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c9s, 7806519
IO - Cancer Chemother. Pharmacol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612321
SB - Index Medicus
CP - Germany
MH - Adult
MH - Aged
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/im [Immunology]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antibody Formation
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/im [Immunology]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - Chemical and Drug Induced Liver Injury/et [Etiology]
MH - Disease-Free Survival
MH - Drug Eruptions/et [Etiology]
MH - Exanthema/ci [Chemically Induced]
MH - Female
MH - Fever/ci [Chemically Induced]
MH - Follow-Up Studies
MH - Humans
MH - Immunologic Factors/ae [Adverse Effects]
MH - *Immunologic Factors/tu [Therapeutic Use]
MH - Japan
MH - Kaplan-Meier Estimate
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - Melanoma/sc [Secondary]
MH - Middle Aged
MH - Treatment Outcome
KW - Immune-checkpoint inhibitor; Ipilimumab; Japanese patients; Melanoma; Phase II study
AB - PURPOSE: Ipilimumab is designed to block cytotoxic T-lymphocyte antigen-4 to augment antitumor T cell responses. In studies of predominantly Caucasian patients with advanced melanoma, ipilimumab was associated with durable response, long-term survival benefit, and a manageable safety profile. This phase II study assessed the safety of ipilimumab in Japanese patients with unresectable stage III or IV melanoma.
AB - METHODS: Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. The database lock for the original analysis was in August 2014. Overall survival, progression-free survival, and data on deaths were based on an updated, follow-up analysis (database lock April 2015).
AB - RESULTS: Data are reported from 20 patients. Fifteen patients (75 %) received all four doses of ipilimumab during induction. Twelve patients (60 %) had at least one drug-related adverse event (AE), and no patients discontinued due to a drug-related AE. There were no deaths related to study drug. The most common drug-related AEs were rash (n = 7), pyrexia (n = 3), increased aspartate aminotransferase (AST; n = 3), and increased alanine aminotransferase (ALT; n = 3). Twelve patients (60 %) reported immune-related AEs (irAEs); most frequent were skin (n = 9) and liver (n = 3) disorders. Grade 3 irAEs were ALT and AST elevation (n = 2) and diabetes mellitus (n = 1). Two patients had a partial response and two had stable disease, yielding a 20 % disease control rate. Median overall survival and progression-free survival were 8.71 and 2.74 months, respectively.
AB - CONCLUSION: Ipilimumab 3 mg/kg had a manageable AE profile in this Japanese patient population with clinical outcomes similar to that in Caucasian patients. CLINICALTRIALS.
AB - GOV IDENTIFIER: NCT01990859.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (Immunologic Factors)
RN - 6T8C155666 (ipilimumab)
ES - 1432-0843
IL - 0344-5704
DI - 10.1007/s00280-015-2873-x
DO - https://dx.doi.org/10.1007/s00280-015-2873-x
PT - Clinical Trial, Phase II
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26410424 [pubmed]
ID - 10.1007/s00280-015-2873-x [doi]
ID - 10.1007/s00280-015-2873-x [pii]
ID - PMC4612321 [pmc]
PP - ppublish
PH - 2015/06/30 [received]
PH - 2015/09/09 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01990859
SL - https://clinicaltrials.gov/search/term=NCT01990859
LG - English
EP - 20150926
DP - 2015 Nov
DC - 20151021
EZ - 2015/09/28 06:00
DA - 2016/01/29 06:00
DT - 2015/09/28 06:00
YR - 2015
ED - 20160128
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26410424
<172. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25986891
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wuerkenbieke D
AU - Wang J
AU - Li Y
AU - Ma C
FA - Wuerkenbieke, Delinaer
FA - Wang, Jing
FA - Li, Yan
FA - Ma, Cailing
IN - Wuerkenbieke, Delinaer. Department of Gynecology, The First Teaching Hospital of Xinjiang Medical University, No 137 Liyushan South Road, Urumqi, 830054, Xinjiang, People's Republic of China.
IN - Wang, Jing. Department of Gynecology, The First Teaching Hospital of Xinjiang Medical University, No 137 Liyushan South Road, Urumqi, 830054, Xinjiang, People's Republic of China.
IN - Li, Yan. Department of Gynecology, The First Teaching Hospital of Xinjiang Medical University, No 137 Liyushan South Road, Urumqi, 830054, Xinjiang, People's Republic of China.
IN - Ma, Cailing. Department of Gynecology, The First Teaching Hospital of Xinjiang Medical University, No 137 Liyushan South Road, Urumqi, 830054, Xinjiang, People's Republic of China. cailingma117@126.com.
TI - miRNA-150 downregulation promotes pertuzumab resistance in ovarian cancer cells via AKT activation.
SO - Archives of Gynecology & Obstetrics. 292(5):1109-16, 2015 Nov
AS - Arch Gynecol Obstet. 292(5):1109-16, 2015 Nov
NJ - Archives of gynecology and obstetrics
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 6ys, 8710213
IO - Arch. Gynecol. Obstet.
SB - Index Medicus
CP - Germany
MH - *Antibodies, Monoclonal, Humanized/pd [Pharmacology]
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - Apoptosis/de [Drug Effects]
MH - Breast Neoplasms/dt [Drug Therapy]
MH - Cell Cycle/de [Drug Effects]
MH - Cell Line, Tumor
MH - Chromones
MH - Down-Regulation
MH - *Drug Resistance, Neoplasm/ge [Genetics]
MH - Female
MH - Gene Expression Regulation, Neoplastic/de [Drug Effects]
MH - Gene Expression Regulation, Neoplastic/ge [Genetics]
MH - Humans
MH - *MicroRNAs/ge [Genetics]
MH - Morpholines
MH - Neoplasms, Glandular and Epithelial/me [Metabolism]
MH - Neoplasms, Glandular and Epithelial/pa [Pathology]
MH - *Ovarian Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/pa [Pathology]
MH - Phosphatidylinositol 3-Kinases/ai [Antagonists & Inhibitors]
MH - Phosphatidylinositol 3-Kinases/me [Metabolism]
MH - Proto-Oncogene Proteins c-akt/me [Metabolism]
MH - Receptor, ErbB-2
MH - *Signal Transduction/de [Drug Effects]
KW - Drug resistance; Ovarian cancer; Pertuzumab; miR-150
AB - BACKGROUND: Pertuzumab is a humanized mAb that binds to the extracellular region of HER2/ErbB2 and is approved for treating breast cancer. Although ovarian cancer and breast cancer have comparable levels of HER2/ErbB2 expression, clinical studies of pertuzumab in epithelial ovarian cancer patients have not met the same level of success.
AB - OBJECTIVES: To investigate the molecular mechanisms by which pertuzumab exerts its anti-tumor effects in ovarian cancer and the mechanisms by which cancer cells achieve pertuzumab resistance.
AB - METHODS: We examined expression of miR-150 in ovarian cancer cells treated with pertuzumab or not. miR-150 knockdown impacts on pertuzumab treatment were analyzed by cell proliferation assay, apoptosis analysis and cell cycle analysis. Cell signal pathway was examined by western blot assay.
AB - RESULTS: Pertuzumab induced miRNA-150 expression in SKOV3 and SNU119 cells. Furthermore, suppression of miRNA-150 in both cell lines resulted in decreased drug sensitivity to pertuzumab and cell apoptosis. The blockage of G1/S checkpoint by pertuzumab was rescued as well. miRNA-150 knockdown activated PI3K-Akt pathway and LY294002 reversed the effect of miR-150 knockdown.
AB - CONCLUSIONS: miRNA-150 downregulation may contribute to the pertuzumab resistance in ovarian cancer via, at least in part, PI3K-akt pathway.
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (Chromones)
RN - 0 (MicroRNAs)
RN - 0 (Morpholines)
RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN - EC 2-7-1 (Phosphatidylinositol 3-Kinases)
RN - EC 2-7-10-1 (ERBB2 protein, human)
RN - EC 2-7-10-1 (Receptor, ErbB-2)
RN - EC 2-7-11-1 (Proto-Oncogene Proteins c-akt)
RN - K16AIQ8CTM (pertuzumab)
RS - Ovarian epithelial cancer
ES - 1432-0711
IL - 0932-0067
DI - 10.1007/s00404-015-3742-x
DO - https://dx.doi.org/10.1007/s00404-015-3742-x
PT - Journal Article
ID - 25986891 [pubmed]
ID - 10.1007/s00404-015-3742-x [doi]
ID - 10.1007/s00404-015-3742-x [pii]
PP - ppublish
PH - 2015/03/24 [received]
PH - 2015/04/27 [accepted]
LG - English
EP - 20150519
DP - 2015 Nov
DC - 20150930
EZ - 2015/05/20 06:00
DA - 2016/01/26 06:00
DT - 2015/05/20 06:00
YR - 2015
ED - 20160125
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25986891
<173. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25678581
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Winograd R
AU - Byrne KT
AU - Evans RA
AU - Odorizzi PM
AU - Meyer AR
AU - Bajor DL
AU - Clendenin C
AU - Stanger BZ
AU - Furth EE
AU - Wherry EJ
AU - Vonderheide RH
FA - Winograd, Rafael
FA - Byrne, Katelyn T
FA - Evans, Rebecca A
FA - Odorizzi, Pamela M
FA - Meyer, Anders R L
FA - Bajor, David L
FA - Clendenin, Cynthia
FA - Stanger, Ben Z
FA - Furth, Emma E
FA - Wherry, E John
FA - Vonderheide, Robert H
IN - Winograd, Rafael. Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
IN - Byrne, Katelyn T. Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
IN - Evans, Rebecca A. Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
IN - Odorizzi, Pamela M. Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
IN - Meyer, Anders R L. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
IN - Bajor, David L. Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
IN - Clendenin, Cynthia. Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
IN - Stanger, Ben Z. Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
IN - Furth, Emma E. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
IN - Wherry, E John. Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
IN - Vonderheide, Robert H. Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. rhv@exchange.upenn.edu.
TI - Induction of T-cell Immunity Overcomes Complete Resistance to PD-1 and CTLA-4 Blockade and Improves Survival in Pancreatic Carcinoma.
SO - Cancer Immunology Research. 3(4):399-411, 2015 Apr
AS - Cancer Immunol Res. 3(4):399-411, 2015 Apr
NJ - Cancer immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101614637
IO - Cancer Immunol Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390506
OI - Source: NLM. NIHMS664805
SB - Index Medicus
CP - United States
MH - Animals
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antigens, CD274/ai [Antagonists & Inhibitors]
MH - *Antigens, CD274/im [Immunology]
MH - Antigens, CD40/im [Immunology]
MH - Antimetabolites, Antineoplastic/tu [Therapeutic Use]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - *CTLA-4 Antigen/im [Immunology]
MH - Carcinoma, Pancreatic Ductal/im [Immunology]
MH - *Carcinoma, Pancreatic Ductal/th [Therapy]
MH - Cell Line, Tumor
MH - Combined Modality Therapy
MH - Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/tu [Therapeutic Use]
MH - Female
MH - Genetic Engineering/mt [Methods]
MH - Humans
MH - Immune Tolerance/de [Drug Effects]
MH - Immune Tolerance/im [Immunology]
MH - Immunity, Cellular
MH - Interferon-gamma/im [Immunology]
MH - Lymphocyte Activation/im [Immunology]
MH - Mice, Inbred C57BL
MH - Pancreatic Neoplasms/im [Immunology]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - *T-Lymphocyte Subsets/im [Immunology]
MH - Tumor Microenvironment/im [Immunology]
MH - Xenograft Model Antitumor Assays/mt [Methods]
AB - Disabling the function of immune checkpoint molecules can unlock T-cell immunity against cancer, yet despite remarkable clinical success with monoclonal antibodies (mAb) that block PD-1 or CTLA-4, resistance remains common and essentially unexplained. To date, pancreatic carcinoma is fully refractory to these antibodies. Here, using a genetically engineered mouse model of pancreatic ductal adenocarcinoma in which spontaneous immunity is minimal, we found that PD-L1 is prominent in the tumor microenvironment, a phenotype confirmed in patients; however, tumor PD-L1 was found to be independent of IFNgamma in this model. Tumor T cells expressed PD-1 as prominently as T cells from chronically infected mice, but treatment with alphaPD-1 mAbs, with or without alphaCTLA-4 mAbs, failed in well-established tumors, recapitulating clinical results. Agonist alphaCD40 mAbs with chemotherapy induced T-cell immunity and reversed the complete resistance of pancreatic tumors to alphaPD-1 and alphaCTLA-4. The combination of alphaCD40/chemotherapy plus alphaPD-1 and/or alphaCTLA-4 induced regression of subcutaneous tumors, improved overall survival, and conferred curative protection from multiple tumor rechallenges, consistent with immune memory not otherwise achievable. Combinatorial treatment nearly doubled survival of mice with spontaneous pancreatic cancers, although no cures were observed. Our findings suggest that in pancreatic carcinoma, a nonimmunogenic tumor, baseline refractoriness to checkpoint inhibitors can be rescued by the priming of a T-cell response with alphaCD40/chemotherapy.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD274)
RN - 0 (Antigens, CD40)
RN - 0 (Antimetabolites, Antineoplastic)
RN - 0 (CD274 protein, human)
RN - 0 (CTLA-4 Antigen)
RN - 0W860991D6 (Deoxycytidine)
RN - 82115-62-6 (Interferon-gamma)
RN - B76N6SBZ8R (gemcitabine)
RS - Pancreatic Carcinoma
ES - 2326-6074
IL - 2326-6066
DI - 2326-6066.CIR-14-0215
DO - https://dx.doi.org/10.1158/2326-6066.CIR-14-0215
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 25678581 [pubmed]
ID - 2326-6066.CIR-14-0215 [pii]
ID - 10.1158/2326-6066.CIR-14-0215 [doi]
ID - PMC4390506 [pmc]
ID - NIHMS664805 [mid]
PP - ppublish
PH - 2014/11/16 [received]
PH - 2015/02/06 [accepted]
GI - No: T32 HL007439
Organization: (HL) *NHLBI NIH HHS*
Country: United States
No: T32 CA009140
Organization: (CA) *NCI NIH HHS*
Country: United States
No: U19 AI082630
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: P01 AI112521
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: R01 CA169123
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA016520
Organization: (CA) *NCI NIH HHS*
Country: United States
No: T32 HL007775
Organization: (HL) *NHLBI NIH HHS*
Country: United States
No: U19 AI 082630
Organization: (AI) *NIAID NIH HHS*
Country: United States
LG - English
EP - 20150212
DP - 2015 Apr
DC - 20150407
EZ - 2015/02/14 06:00
DA - 2016/01/26 06:00
DT - 2015/02/14 06:00
YR - 2015
ED - 20160125
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25678581
<174. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26118951
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Quirk SK
AU - Shure AK
AU - Agrawal DK
FA - Quirk, Shannon K
FA - Shure, Anna K
FA - Agrawal, Devendra K
IN - Quirk, Shannon K. Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, Neb.
IN - Shure, Anna K. Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, Neb.
IN - Agrawal, Devendra K. Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, Neb. Electronic address: dkagr@creighton.edu.
TI - Immune-mediated adverse events of anticytotoxic T lymphocyte-associated antigen 4 antibody therapy in metastatic melanoma. [Review]
SO - Translational Research: The Journal Of Laboratory & Clinical Medicine. 166(5):412-24, 2015 Nov
AS - Transl Res. 166(5):412-24, 2015 Nov
NJ - Translational research : the journal of laboratory and clinical medicine
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101280339
IO - Transl Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609598
OI - Source: NLM. NIHMS699615 [Available on 11/01/16]
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/im [Immunology]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *CTLA-4 Antigen/im [Immunology]
MH - Clinical Trials, Phase III as Topic
MH - Drug Therapy, Combination
MH - Humans
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - Melanoma/pa [Pathology]
MH - Neoplasm Metastasis
AB - Ipilimumab, an antibody that blocks cytotoxic T lymphocyte-associated antigen 4 (CTLA-4; CD152), was approved by the Food and Drug Administration in 2011 for the treatment of unresectable stage III or IV malignant melanoma. Although the addition of this particular immunotherapy has broadened treatment options, immune-related adverse events (irAEs) are associated with ipilimumab therapy, including dermatologic effects, colitis and diarrhea, endocrine effects, hepatotoxicity, ocular effects, renal effects, neurologic effects, and others. In this article, a critical evaluation of the underlying mechanisms of irAEs associated with anti-CTLA-4 therapy is presented. Additionally, potentially beneficial effects of combinational therapies to alleviate ipilimumab-induced irAEs in malignant melanoma are discussed. Future research is warranted to elucidate the efficacy of such combination therapies and specific biomarkers that would help to predict a clinical response to ipilimumab in patients with malignant melanoma.
AB - Copyright © 2015 Elsevier Inc. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
RN - QEN1X95CIX (tremelimumab)
ES - 1878-1810
IL - 1878-1810
DI - S1931-5244(15)00210-8
DO - https://dx.doi.org/10.1016/j.trsl.2015.06.005
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Review
ID - 26118951 [pubmed]
ID - S1931-5244(15)00210-8 [pii]
ID - 10.1016/j.trsl.2015.06.005 [doi]
ID - PMC4609598 [pmc]
ID - NIHMS699615 [mid]
PP - ppublish
PH - 2015/04/01 [received]
PH - 2015/06/02 [revised]
PH - 2015/06/04 [accepted]
GI - No: R01HL120659
Organization: (HL) *NHLBI NIH HHS*
Country: United States
No: R01HL112597
Organization: (HL) *NHLBI NIH HHS*
Country: United States
No: R01 HL112597
Organization: (HL) *NHLBI NIH HHS*
Country: United States
No: R01HL116042
Organization: (HL) *NHLBI NIH HHS*
Country: United States
No: R01 HL116042
Organization: (HL) *NHLBI NIH HHS*
Country: United States
No: R01 HL120659
Organization: (HL) *NHLBI NIH HHS*
Country: United States
LG - English
EP - 20150611
DP - 2015 Nov
DC - 20151017
EZ - 2015/06/30 06:00
DA - 2016/01/20 06:00
DT - 2015/06/30 06:00
YR - 2015
ED - 20160119
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26118951
<175. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25641691
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Cheng R
AU - Cooper A
AU - Kench J
AU - Watson G
AU - Bye W
AU - McNeil C
AU - Shackel N
FA - Cheng, Robert
FA - Cooper, Adam
FA - Kench, James
FA - Watson, Geoff
FA - Bye, William
FA - McNeil, Catriona
FA - Shackel, Nicholas
IN - Cheng, Robert. A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
TI - Ipilimumab-induced toxicities and the gastroenterologist. [Review]
SO - Journal of Gastroenterology & Hepatology. 30(4):657-66, 2015 Apr
AS - J Gastroenterol Hepatol. 30(4):657-66, 2015 Apr
NJ - Journal of gastroenterology and hepatology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - a6j, 8607909
IO - J. Gastroenterol. Hepatol.
SB - Index Medicus
CP - Australia
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Azathioprine/ad [Administration & Dosage]
MH - Calcineurin Inhibitors/ad [Administration & Dosage]
MH - *Chemical and Drug Induced Liver Injury/dt [Drug Therapy]
MH - *Colitis/ci [Chemically Induced]
MH - Colitis/dt [Drug Therapy]
MH - Glucocorticoids/ad [Administration & Dosage]
MH - Humans
MH - *Immunosuppressive Agents/ad [Administration & Dosage]
MH - Infliximab/ad [Administration & Dosage]
MH - *Melanoma/dt [Drug Therapy]
MH - *Melanoma/sc [Secondary]
MH - Methylprednisolone/ad [Administration & Dosage]
MH - Mycophenolic Acid/ad [Administration & Dosage]
MH - Mycophenolic Acid/aa [Analogs & Derivatives]
MH - Patient Care Team
MH - Prednisolone/ad [Administration & Dosage]
MH - Pulse Therapy, Drug
KW - CTLA-4 antibody; colitis; hepatitis; immunotherapy; ipilimumab; melanoma
AB - Ipilimumab has been shown to improve overall survival in patients with advanced melanoma. Ipilimumab acts through immune-modulation, and is recognized to cause potentially severe immune-related adverse events (irAEs) including dermatitis, colitis, thyroiditis, hypophysitis, and hepatitis. The acceptance of ipilimumab as a treatment for metastatic melanoma means patients will continue to be treated with this agent and gastroenterologists will be increasingly called upon to assist in managing severe autoimmune-related hepatitis and colitis. To date, the recommendations for managing irAEs secondary to ipilimumab have been steroids at a moderate dose of prednisolone (1mg/kg) as well as immunosuppressive agents such as mycophenolate mofetil (MMF) for steroid-refractory hepatitis and infliximab in the management of corticosteroid-refractory colitis. However, the dosing and the duration of immunosuppressive therapy have not been systematically studied in the setting of treating ipilimumab-induced irAEs. Therefore, additional immune-modifying agents and/or a change in dosing may be required to manage severe irAEs unresponsive to existing treatment recommendations. We describe a treatment paradigm illustrated by a series of five patients who experienced irAEs. In three cases of metastatic melanoma, ipilimumab-induced hepatitis was successfully treated with high-dose parenteral pulsed methylprednisolone. In two other melanoma patients with ipilimumab-induced colitis, one patient had satisfactory resolution of his colitis with high-dose corticosteroid therapy alone and the other patient required infliximab infusion. We have reviewed the current literature and management algorithms for ipilimumab-induced irAEs. Treatment options and the rationale for their use are discussed, including the use of pulsed high-dose steroids, MMF, azathioprine and calcineurin inhibitors.
AB - Copyright © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Calcineurin Inhibitors)
RN - 0 (Glucocorticoids)
RN - 0 (Immunosuppressive Agents)
RN - 6T8C155666 (ipilimumab)
RN - 9PHQ9Y1OLM (Prednisolone)
RN - B72HH48FLU (Infliximab)
RN - HU9DX48N0T (Mycophenolic Acid)
RN - MRK240IY2L (Azathioprine)
RN - X4W7ZR7023 (Methylprednisolone)
ES - 1440-1746
IL - 0815-9319
DO - https://dx.doi.org/10.1111/jgh.12888
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 25641691 [pubmed]
ID - 10.1111/jgh.12888 [doi]
PP - ppublish
PH - 2014/12/29 [accepted]
LG - English
DP - 2015 Apr
DC - 20150317
EZ - 2015/02/03 06:00
DA - 2016/01/15 06:00
DT - 2015/02/03 06:00
YR - 2015
ED - 20160114
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25641691
<176. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25885696
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Venditti O
AU - De Lisi D
AU - Caricato M
AU - Caputo D
AU - Capolupo GT
AU - Taffon C
AU - Pagliara E
AU - Battisi S
AU - Frezza AM
AU - Onetti Muda A
AU - Tonini G
AU - Santini D
FA - Venditti, Olga
FA - De Lisi, Delia
FA - Caricato, Marco
FA - Caputo, Damiano
FA - Capolupo, Gabriella Teresa
FA - Taffon, Chiara
FA - Pagliara, Elisa
FA - Battisi, Sofia
FA - Frezza, Anna Maria
FA - Onetti Muda, Andrea
FA - Tonini, Giuseppe
FA - Santini, Daniele
IN - Venditti, Olga. Department of Medical Oncology, Universita Campus Bio-Medico di Roma, via Alvaro del Portillo 200, 00128, Rome, Italy. o.venditti@unicampus.it.
IN - De Lisi, Delia. Department of Medical Oncology, Universita Campus Bio-Medico di Roma, via Alvaro del Portillo 200, 00128, Rome, Italy. d.delisi@unicampus.it.
IN - Caricato, Marco. Department of General Surgery, Universita Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128, Rome, Italy. m.caricato@unicampus.it.
IN - Caputo, Damiano. Department of General Surgery, Universita Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128, Rome, Italy. d.caputo@unicampus.it.
IN - Capolupo, Gabriella Teresa. Department of General Surgery, Universita Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128, Rome, Italy. g.capolupo@unicampus.it.
IN - Taffon, Chiara. Department of Pathology Universita, Universita Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128, Rome, Italy. c.taffon@unicampus.it.
IN - Pagliara, Elisa. Department of Radiology Universita, Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128, Rome, Italy. e.pagliara@unicampus.it.
IN - Battisi, Sofia. Department of Radiology Universita, Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128, Rome, Italy. s.battisti@unicampus.it.
IN - Frezza, Anna Maria. Department of Medical Oncology, Universita Campus Bio-Medico di Roma, via Alvaro del Portillo 200, 00128, Rome, Italy. a.frezza@unicampus.it.
IN - Onetti Muda, Andrea. Department of Pathology Universita, Universita Campus Bio-Medico di Roma, Via Alvaro del Portillo, 200, 00128, Rome, Italy. a.onetti@unicampus.it.
IN - Tonini, Giuseppe. Department of Medical Oncology, Universita Campus Bio-Medico di Roma, via Alvaro del Portillo 200, 00128, Rome, Italy. g.tonini@unicampus.it.
IN - Santini, Daniele. Department of Medical Oncology, Universita Campus Bio-Medico di Roma, via Alvaro del Portillo 200, 00128, Rome, Italy. d.santini@unicampus.it.
TI - Ipilimumab and immune-mediated adverse events: a case report of anti-CTLA4 induced ileitis.
SO - BMC Cancer. 15:87, 2015 Mar 01
AS - BMC Cancer. 15:87, 2015 Mar 01
NJ - BMC cancer
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 100967800
IO - BMC Cancer
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350587
SB - Index Medicus
CP - England
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Female
MH - Humans
MH - *Ileitis/ci [Chemically Induced]
MH - *Ileitis/pa [Pathology]
MH - Melanoma/dt [Drug Therapy]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - Neoplasm Metastasis
MH - Precision Medicine
MH - Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/pa [Pathology]
AB - BACKGROUND: Ipilimumab is a fully human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 , a key negative regulator of T-cell activation approved by the Food and Drug Administration as of March 2011 for the treatment of metastatic melanoma. As a result of the up-regulation of the immune system, several immune-mediated adverse effects have been reported including colitis, dermatitis, hepatitis and rarely hypophysitis. The most frequent immune-mediated adverse effects described in literature include gastrointestinal toxicity such as diarrhea, colitis and case of colitis and ileitis.
AB - CASE PRESENTATION: In this paper we report an interesting case of immune-mediate ileitis without colitis in a 54 years old woman with metastatic melanoma treated with ipilimumab. We also discuss about case management and the possible pathological mechanisms considering also previous reports.
AB - CONCLUSIONS: The aim of this article is to support further investigations concerning epigenetic and genetic analysis in order to personalize biological therapy and to reduce immune related adverse events observed after ipilimumab administration.
RN - 0 (Antibodies, Monoclonal)
RN - 6T8C155666 (ipilimumab)
ES - 1471-2407
IL - 1471-2407
DI - 10.1186/s12885-015-1074-7
DO - https://dx.doi.org/10.1186/s12885-015-1074-7
PT - Case Reports
PT - Journal Article
ID - 25885696 [pubmed]
ID - 10.1186/s12885-015-1074-7 [doi]
ID - 10.1186/s12885-015-1074-7 [pii]
ID - PMC4350587 [pmc]
PP - epublish
PH - 2014/04/08 [received]
PH - 2015/02/09 [accepted]
LG - English
EP - 20150301
DP - 2015 Mar 01
DC - 20150418
EZ - 2015/04/18 06:00
DA - 2016/01/09 06:00
DT - 2015/04/18 06:00
YR - 2015
ED - 20160108
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25885696
<177. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24955955
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Beeharry N
AU - Banina E
AU - Hittle J
AU - Skobeleva N
AU - Khazak V
AU - Deacon S
AU - Andrake M
AU - Egleston BL
AU - Peterson JR
AU - Astsaturov I
AU - Yen TJ
FA - Beeharry, Neil
FA - Banina, Eugenia
FA - Hittle, James
FA - Skobeleva, Natalia
FA - Khazak, Vladimir
FA - Deacon, Sean
FA - Andrake, Mark
FA - Egleston, Brian L
FA - Peterson, Jeffrey R
FA - Astsaturov, Igor
FA - Yen, Timothy J
IN - Beeharry, Neil. Cancer Biology Program; Fox Chase Cancer Center; Philadelphia, PA USA.
IN - Banina, Eugenia. Program in Developmental Therapeutics; Fox Chase Cancer Center; Philadelphia, PA USA.
IN - Hittle, James. Cancer Biology Program; Fox Chase Cancer Center; Philadelphia, PA USA.
IN - Skobeleva, Natalia. Program in Developmental Therapeutics; Fox Chase Cancer Center; Philadelphia, PA USA.
IN - Khazak, Vladimir. Program in Developmental Therapeutics; Fox Chase Cancer Center; Philadelphia, PA USA.
IN - Deacon, Sean. Reaction Biology Corporation; Malvern, PA USA.
IN - Andrake, Mark. Molecular Modeling Facility; Fox Chase Cancer Center; Philadelphia, PA USA.
IN - Egleston, Brian L. Biostatistics and Bioinformatics Facility; Fox Chase Cancer Center; Philadelphia, PA USA.
IN - Peterson, Jeffrey R. Cancer Biology Program; Fox Chase Cancer Center; Philadelphia, PA USA.
IN - Astsaturov, Igor. Program in Developmental Therapeutics; Fox Chase Cancer Center; Philadelphia, PA USA.
IN - Yen, Timothy J. Cancer Biology Program; Fox Chase Cancer Center; Philadelphia, PA USA.
TI - Re-purposing clinical kinase inhibitors to enhance chemosensitivity by overriding checkpoints.
CM - Comment in: Cell Cycle. 2014;13(18):2810-1; PMID: 25486467
SO - Cell Cycle. 13(14):2172-91, 2014
AS - Cell Cycle. 13(14):2172-91, 2014
NJ - Cell cycle (Georgetown, Tex.)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101137841
IO - Cell Cycle
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111673
SB - Index Medicus
CP - United States
MH - Aniline Compounds/pd [Pharmacology]
MH - Animals
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - *Cell Cycle Checkpoints/de [Drug Effects]
MH - Cell Cycle Proteins/ai [Antagonists & Inhibitors]
MH - Cell Cycle Proteins/me [Metabolism]
MH - Cell Line, Tumor
MH - *Cell Proliferation/de [Drug Effects]
MH - Checkpoint Kinase 1
MH - Cisplatin/pd [Pharmacology]
MH - DNA Damage
MH - DNA Replication
MH - Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Dose-Response Relationship, Drug
MH - Doxorubicin/pd [Pharmacology]
MH - *Drug Repositioning
MH - *Drug Resistance, Neoplasm/de [Drug Effects]
MH - Humans
MH - Male
MH - Mice, Inbred C57BL
MH - Mice, SCID
MH - Models, Molecular
MH - Nitriles/pd [Pharmacology]
MH - Nuclear Proteins/ai [Antagonists & Inhibitors]
MH - Nuclear Proteins/me [Metabolism]
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/en [Enzymology]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Protein Kinase Inhibitors/ch [Chemistry]
MH - *Protein Kinase Inhibitors/pd [Pharmacology]
MH - Protein Kinases/ch [Chemistry]
MH - Protein Kinases/ge [Genetics]
MH - *Protein Kinases/me [Metabolism]
MH - Protein-Tyrosine Kinases/ai [Antagonists & Inhibitors]
MH - Protein-Tyrosine Kinases/me [Metabolism]
MH - Quinolines/pd [Pharmacology]
MH - *Signal Transduction/de [Drug Effects]
MH - Time Factors
MH - Xenograft Model Antitumor Assays
KW - Checkpoint override; DNA damage; Kinase inhibitors; Mitosis; drug repurposing
AB - Inhibitors of the DNA damage checkpoint kinase, Chk1, are highly effective as chemo- and radio-sensitizers in preclinical studies but are not well-tolerated by patients. We exploited the promiscuous nature of kinase inhibitors to screen 9 clinically relevant kinase inhibitors for their ability to sensitize pancreatic cancer cells to a sub-lethal concentration of gemcitabine. Bosutinib, dovitinib, and BEZ-235 were identified as sensitizers that abrogated the DNA damage checkpoint. We further characterized bosutinib, an FDA-approved Src/Abl inhibitor approved for chronic myelogenous leukemia. Unbeknownst to us, we used an isomer (Bos-I) that was unknowingly synthesized and sold to the research community as "authentic" bosutinib. In vitro and cell-based assays showed that both the authentic bosutinib and Bos-I inhibited DNA damage checkpoint kinases Chk1 and Wee1, with Bos-I showing greater potency. Imaging data showed that Bos-I forced cells to override gemcitabine-induced DNA damage checkpoint arrest and destabilized stalled replication forks. These inhibitors enhanced sensitivity to the DNA damaging agents' gemcitabine, cisplatin, and doxorubicin in pancreatic cancer cell lines. The in vivo efficacy of Bos-I was validated using cells derived directly from a pancreatic cancer patient's tumor. Notably, the xenograft studies showed that the combination of gemcitabine and Bos-I was significantly more effective in suppressing tumor growth than either agent alone. Finally, we show that the gatekeeper residue in Wee1 dictates its sensitivity to the 2 compounds. Our strategy to screen clinically relevant kinase inhibitors for off-target effects on cell cycle checkpoints is a promising approach to re-purpose drugs as chemosensitizers.
RN - 0 (Aniline Compounds)
RN - 0 (Antineoplastic Agents)
RN - 0 (Cell Cycle Proteins)
RN - 0 (Nitriles)
RN - 0 (Nuclear Proteins)
RN - 0 (Protein Kinase Inhibitors)
RN - 0 (Quinolines)
RN - 0W860991D6 (Deoxycytidine)
RN - 5018V4AEZ0 (bosutinib)
RN - 80168379AG (Doxorubicin)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7 (Protein Kinases)
RN - EC 2-7-10-1 (Protein-Tyrosine Kinases)
RN - EC 2-7-10-2 (WEE1 protein, human)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
RN - EC 2-7-11-1 (Chek1 protein, mouse)
RN - Q20Q21Q62J (Cisplatin)
ES - 1551-4005
IL - 1551-4005
DI - 29214
DO - https://dx.doi.org/10.4161/cc.29214
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
PT - Research Support, U.S. Gov't, Non-P.H.S.
ID - 24955955 [pubmed]
ID - 29214 [pii]
ID - 10.4161/cc.29214 [doi]
ID - PMC4111673 [pmc]
PP - ppublish
GI - No: R21 CA164205
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA06927
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA169706
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K22 CA160725
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 GM083025
Organization: (GM) *NIGMS NIH HHS*
Country: United States
No: R21 CA169706
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA006927
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20140623
DP - 2014
DC - 20140812
EZ - 2014/06/24 06:00
DA - 2015/12/17 06:00
DT - 2014/06/24 06:00
YR - 2014
ED - 20151215
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24955955
<178. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26503055
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Peng D
AU - Kryczek I
AU - Nagarsheth N
AU - Zhao L
AU - Wei S
AU - Wang W
AU - Sun Y
AU - Zhao E
AU - Vatan L
AU - Szeliga W
AU - Kotarski J
AU - Tarkowski R
AU - Dou Y
AU - Cho K
AU - Hensley-Alford S
AU - Munkarah A
AU - Liu R
AU - Zou W
FA - Peng, Dongjun
FA - Kryczek, Ilona
FA - Nagarsheth, Nisha
FA - Zhao, Lili
FA - Wei, Shuang
FA - Wang, Weimin
FA - Sun, Yuqing
FA - Zhao, Ende
FA - Vatan, Linda
FA - Szeliga, Wojciech
FA - Kotarski, Jan
FA - Tarkowski, Rafal
FA - Dou, Yali
FA - Cho, Kathleen
FA - Hensley-Alford, Sharon
FA - Munkarah, Adnan
FA - Liu, Rebecca
FA - Zou, Weiping
IN - Peng, Dongjun. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Kryczek, Ilona. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Kryczek, Ilona. Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan 48109, USA.
IN - Nagarsheth, Nisha. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Nagarsheth, Nisha. Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan 48109, USA.
IN - Zhao, Lili. Department of Biostatistics, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Wei, Shuang. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Wang, Weimin. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Sun, Yuqing. Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Zhao, Ende. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Vatan, Linda. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Szeliga, Wojciech. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Kotarski, Jan. The First Department of Gynecologic Oncology and Gynecology, Medical University in Lublin, Lublin 20-081, Poland.
IN - Tarkowski, Rafal. The First Department of Gynecologic Oncology and Gynecology, Medical University in Lublin, Lublin 20-081, Poland.
IN - Dou, Yali. Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Cho, Kathleen. Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Cho, Kathleen. The University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
IN - Hensley-Alford, Sharon. Department of Women's Health Services, Henry Ford Health System, Detroit, Michigan 48202, USA.
IN - Munkarah, Adnan. Department of Women's Health Services, Henry Ford Health System, Detroit, Michigan 48202, USA.
IN - Liu, Rebecca. The University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
IN - Liu, Rebecca. Department of Obstetrics and Gynecology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Zou, Weiping. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Zou, Weiping. Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan 48109, USA.
IN - Zou, Weiping. The University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
IN - Zou, Weiping. Graduate Program in Tumor Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
TI - Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy.
CM - Comment in: Nat Rev Immunol. 2015 Dec;15(12):730; PMID: 26542634
SO - Nature. 527(7577):249-53, 2015 Nov 12
AS - Nature. 527(7577):249-53, 2015 Nov 12
NJ - Nature
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 0410462
IO - Nature
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779053
OI - Source: NLM. NIHMS718418
SB - Index Medicus
CP - England
MH - Animals
MH - Antigens, CD274/me [Metabolism]
MH - CD8-Positive T-Lymphocytes/cy [Cytology]
MH - CD8-Positive T-Lymphocytes/im [Immunology]
MH - Chemokine CXCL10/bi [Biosynthesis]
MH - Chemokine CXCL10/ge [Genetics]
MH - Chemokine CXCL10/im [Immunology]
MH - Chemokine CXCL9/bi [Biosynthesis]
MH - Chemokine CXCL9/ge [Genetics]
MH - Chemokine CXCL9/im [Immunology]
MH - Chemokines/bi [Biosynthesis]
MH - *Chemokines/ge [Genetics]
MH - Chemokines/im [Immunology]
MH - DNA (Cytosine-5-)-Methyltransferase/ai [Antagonists & Inhibitors]
MH - DNA (Cytosine-5-)-Methyltransferase/me [Metabolism]
MH - DNA Methylation/de [Drug Effects]
MH - Enhancer of Zeste Homolog 2 Protein
MH - Epigenesis, Genetic/de [Drug Effects]
MH - *Epigenesis, Genetic
MH - Female
MH - *Gene Silencing
MH - Histones/ch [Chemistry]
MH - Histones/me [Metabolism]
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - *Immunotherapy
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Lysine/me [Metabolism]
MH - Mice
MH - Ovarian Neoplasms/en [Enzymology]
MH - *Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Ovarian Neoplasms/th [Therapy]
MH - Polycomb Repressive Complex 2/ai [Antagonists & Inhibitors]
MH - Polycomb Repressive Complex 2/me [Metabolism]
MH - Prognosis
MH - Th1 Cells/im [Immunology]
MH - *Th1 Cells/me [Metabolism]
MH - Tumor Cells, Cultured
MH - Tumor Escape/im [Immunology]
MH - Xenograft Model Antitumor Assays
AB - Epigenetic silencing including histone modifications and DNA methylation is an important tumorigenic mechanism. However, its role in cancer immunopathology and immunotherapy is poorly understood. Using human ovarian cancers as our model, here we show that enhancer of zeste homologue 2 (EZH2)-mediated histone H3 lysine 27 trimethylation (H3K27me3) and DNA methyltransferase 1 (DNMT1)-mediated DNA methylation repress the tumour production of T helper 1 (TH1)-type chemokines CXCL9 and CXCL10, and subsequently determine effector T-cell trafficking to the tumour microenvironment. Treatment with epigenetic modulators removes the repression and increases effector T-cell tumour infiltration, slows down tumour progression, and improves the therapeutic efficacy of programmed death-ligand 1 (PD-L1; also known as B7-H1) checkpoint blockade and adoptive T-cell transfusion in tumour-bearing mice. Moreover, tumour EZH2 and DNMT1 are negatively associated with tumour-infiltrating CD8(+) T cells and patient outcome. Thus, epigenetic silencing of TH1-type chemokines is a novel immune-evasion mechanism of tumours. Selective epigenetic reprogramming alters the T-cell landscape in cancer and may enhance the clinical efficacy of cancer therapy.
RN - 0 (Antigens, CD274)
RN - 0 (CXCL10 protein, human)
RN - 0 (CXCL9 protein, human)
RN - 0 (Chemokine CXCL10)
RN - 0 (Chemokine CXCL9)
RN - 0 (Chemokines)
RN - 0 (Histones)
RN - EC 2-1-1-37 (DNA (Cytosine-5-)-Methyltransferase)
RN - EC 2-1-1-37 (DNA (cytosine-5-)-methyltransferase 1)
RN - EC 2-1-1-43 (EZH2 protein, human)
RN - EC 2-1-1-43 (Enhancer of Zeste Homolog 2 Protein)
RN - EC 2-1-1-43 (Polycomb Repressive Complex 2)
RN - K3Z4F929H6 (Lysine)
ES - 1476-4687
IL - 0028-0836
DI - nature15520
DO - https://dx.doi.org/10.1038/nature15520
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 26503055 [pubmed]
ID - nature15520 [pii]
ID - 10.1038/nature15520 [doi]
ID - PMC4779053 [pmc]
ID - NIHMS718418 [mid]
PP - ppublish
PH - 2014/12/09 [received]
PH - 2015/08/24 [accepted]
GI - No: 5P30CA46592
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA099985
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA190176
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA156685
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA193136
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA046592
Organization: (CA) *NCI NIH HHS*
Country: United States
No: F31 CA189440
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA171306
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA152470
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA171306
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA152470
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA156685
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA190176
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA123088
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA193136
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA123088
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA099985
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20151026
DP - 2015 Nov 12
DC - 20151112
EZ - 2015/10/28 06:00
DA - 2015/12/15 06:00
DT - 2015/10/28 06:00
YR - 2015
ED - 20151214
RD - 20161126
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26503055
<179. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26503055
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Peng D
AU - Kryczek I
AU - Nagarsheth N
AU - Zhao L
AU - Wei S
AU - Wang W
AU - Sun Y
AU - Zhao E
AU - Vatan L
AU - Szeliga W
AU - Kotarski J
AU - Tarkowski R
AU - Dou Y
AU - Cho K
AU - Hensley-Alford S
AU - Munkarah A
AU - Liu R
AU - Zou W
FA - Peng, Dongjun
FA - Kryczek, Ilona
FA - Nagarsheth, Nisha
FA - Zhao, Lili
FA - Wei, Shuang
FA - Wang, Weimin
FA - Sun, Yuqing
FA - Zhao, Ende
FA - Vatan, Linda
FA - Szeliga, Wojciech
FA - Kotarski, Jan
FA - Tarkowski, Rafal
FA - Dou, Yali
FA - Cho, Kathleen
FA - Hensley-Alford, Sharon
FA - Munkarah, Adnan
FA - Liu, Rebecca
FA - Zou, Weiping
IN - Peng, Dongjun. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Kryczek, Ilona. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Kryczek, Ilona. Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan 48109, USA.
IN - Nagarsheth, Nisha. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Nagarsheth, Nisha. Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan 48109, USA.
IN - Zhao, Lili. Department of Biostatistics, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Wei, Shuang. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Wang, Weimin. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Sun, Yuqing. Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Zhao, Ende. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Vatan, Linda. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Szeliga, Wojciech. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Kotarski, Jan. The First Department of Gynecologic Oncology and Gynecology, Medical University in Lublin, Lublin 20-081, Poland.
IN - Tarkowski, Rafal. The First Department of Gynecologic Oncology and Gynecology, Medical University in Lublin, Lublin 20-081, Poland.
IN - Dou, Yali. Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Cho, Kathleen. Department of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Cho, Kathleen. The University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
IN - Hensley-Alford, Sharon. Department of Women's Health Services, Henry Ford Health System, Detroit, Michigan 48202, USA.
IN - Munkarah, Adnan. Department of Women's Health Services, Henry Ford Health System, Detroit, Michigan 48202, USA.
IN - Liu, Rebecca. The University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
IN - Liu, Rebecca. Department of Obstetrics and Gynecology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Zou, Weiping. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
IN - Zou, Weiping. Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan 48109, USA.
IN - Zou, Weiping. The University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
IN - Zou, Weiping. Graduate Program in Tumor Biology, University of Michigan, Ann Arbor, Michigan 48109, USA.
TI - Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy.
CM - Comment in: Nat Rev Immunol. 2015 Dec;15(12):730; PMID: 26542634
SO - Nature. 527(7577):249-53, 2015 Nov 12
AS - Nature. 527(7577):249-53, 2015 Nov 12
NJ - Nature
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 0410462
IO - Nature
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779053
OI - Source: NLM. NIHMS718418
SB - Index Medicus
CP - England
MH - Animals
MH - Antigens, CD274/me [Metabolism]
MH - CD8-Positive T-Lymphocytes/cy [Cytology]
MH - CD8-Positive T-Lymphocytes/im [Immunology]
MH - Chemokine CXCL10/bi [Biosynthesis]
MH - Chemokine CXCL10/ge [Genetics]
MH - Chemokine CXCL10/im [Immunology]
MH - Chemokine CXCL9/bi [Biosynthesis]
MH - Chemokine CXCL9/ge [Genetics]
MH - Chemokine CXCL9/im [Immunology]
MH - Chemokines/bi [Biosynthesis]
MH - *Chemokines/ge [Genetics]
MH - Chemokines/im [Immunology]
MH - DNA (Cytosine-5-)-Methyltransferase/ai [Antagonists & Inhibitors]
MH - DNA (Cytosine-5-)-Methyltransferase/me [Metabolism]
MH - DNA Methylation/de [Drug Effects]
MH - Enhancer of Zeste Homolog 2 Protein
MH - Epigenesis, Genetic/de [Drug Effects]
MH - *Epigenesis, Genetic
MH - Female
MH - *Gene Silencing
MH - Histones/ch [Chemistry]
MH - Histones/me [Metabolism]
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - *Immunotherapy
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Lysine/me [Metabolism]
MH - Mice
MH - Ovarian Neoplasms/en [Enzymology]
MH - *Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Ovarian Neoplasms/th [Therapy]
MH - Polycomb Repressive Complex 2/ai [Antagonists & Inhibitors]
MH - Polycomb Repressive Complex 2/me [Metabolism]
MH - Prognosis
MH - Th1 Cells/im [Immunology]
MH - *Th1 Cells/me [Metabolism]
MH - Tumor Cells, Cultured
MH - Tumor Escape/im [Immunology]
MH - Xenograft Model Antitumor Assays
AB - Epigenetic silencing including histone modifications and DNA methylation is an important tumorigenic mechanism. However, its role in cancer immunopathology and immunotherapy is poorly understood. Using human ovarian cancers as our model, here we show that enhancer of zeste homologue 2 (EZH2)-mediated histone H3 lysine 27 trimethylation (H3K27me3) and DNA methyltransferase 1 (DNMT1)-mediated DNA methylation repress the tumour production of T helper 1 (TH1)-type chemokines CXCL9 and CXCL10, and subsequently determine effector T-cell trafficking to the tumour microenvironment. Treatment with epigenetic modulators removes the repression and increases effector T-cell tumour infiltration, slows down tumour progression, and improves the therapeutic efficacy of programmed death-ligand 1 (PD-L1; also known as B7-H1) checkpoint blockade and adoptive T-cell transfusion in tumour-bearing mice. Moreover, tumour EZH2 and DNMT1 are negatively associated with tumour-infiltrating CD8(+) T cells and patient outcome. Thus, epigenetic silencing of TH1-type chemokines is a novel immune-evasion mechanism of tumours. Selective epigenetic reprogramming alters the T-cell landscape in cancer and may enhance the clinical efficacy of cancer therapy.
RN - 0 (Antigens, CD274)
RN - 0 (CXCL10 protein, human)
RN - 0 (CXCL9 protein, human)
RN - 0 (Chemokine CXCL10)
RN - 0 (Chemokine CXCL9)
RN - 0 (Chemokines)
RN - 0 (Histones)
RN - EC 2-1-1-37 (DNA (Cytosine-5-)-Methyltransferase)
RN - EC 2-1-1-37 (DNA (cytosine-5-)-methyltransferase 1)
RN - EC 2-1-1-43 (EZH2 protein, human)
RN - EC 2-1-1-43 (Enhancer of Zeste Homolog 2 Protein)
RN - EC 2-1-1-43 (Polycomb Repressive Complex 2)
RN - K3Z4F929H6 (Lysine)
ES - 1476-4687
IL - 0028-0836
DI - nature15520
DO - https://dx.doi.org/10.1038/nature15520
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 26503055 [pubmed]
ID - nature15520 [pii]
ID - 10.1038/nature15520 [doi]
ID - PMC4779053 [pmc]
ID - NIHMS718418 [mid]
PP - ppublish
PH - 2014/12/09 [received]
PH - 2015/08/24 [accepted]
GI - No: 5P30CA46592
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA099985
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA190176
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA156685
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA193136
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA046592
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 GM082856
Organization: (GM) *NIGMS NIH HHS*
Country: United States
No: F31 CA189440
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA171306
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA152470
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA171306
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA152470
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA156685
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA190176
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA123088
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA193136
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA123088
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA099985
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20151026
DP - 2015 Nov 12
DC - 20151112
EZ - 2015/10/28 06:00
DA - 2015/12/15 06:00
DT - 2015/10/28 06:00
YR - 2015
ED - 20151214
RD - 20170104
UP - 20170105
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=26503055
<180. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25538262
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Min L
AU - Hodi FS
AU - Giobbie-Hurder A
AU - Ott PA
AU - Luke JJ
AU - Donahue H
AU - Davis M
AU - Carroll RS
AU - Kaiser UB
FA - Min, Le
FA - Hodi, Frank Stephen
FA - Giobbie-Hurder, Anita
FA - Ott, Patrick A
FA - Luke, Jason J
FA - Donahue, Hilary
FA - Davis, Meredith
FA - Carroll, Rona S
FA - Kaiser, Ursula B
IN - Min, Le. Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts. lmin1@partners.org.
IN - Hodi, Frank Stephen. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Giobbie-Hurder, Anita. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Ott, Patrick A. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Luke, Jason J. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Melanoma and Developmental Therapeutics Clinics, University of Chicago, Chicago, Illinois.
IN - Donahue, Hilary. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Davis, Meredith. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
IN - Carroll, Rona S. Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts.
IN - Kaiser, Ursula B. Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts.
TI - Systemic high-dose corticosteroid treatment does not improve the outcome of ipilimumab-related hypophysitis: a retrospective cohort study.
SO - Clinical Cancer Research. 21(4):749-55, 2015 Feb 15
AS - Clin Cancer Res. 21(4):749-55, 2015 Feb 15
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c2h, 9502500
IO - Clin. Cancer Res.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334697
OI - Source: NLM. NIHMS651379
SB - Index Medicus
CP - United States
MH - *Adrenal Cortex Hormones/tu [Therapeutic Use]
MH - Adult
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Cohort Studies
MH - Female
MH - Humans
MH - Kaplan-Meier Estimate
MH - Male
MH - Melanoma/dt [Drug Therapy]
MH - Melanoma/mo [Mortality]
MH - Middle Aged
MH - *Pituitary Diseases/ci [Chemically Induced]
MH - *Pituitary Diseases/dt [Drug Therapy]
MH - Pituitary Diseases/mo [Mortality]
MH - Retrospective Studies
AB - PURPOSE: To examine the onset and outcome of ipilimumab-related hypophysitis and the response to treatment with systemic high-dose corticosteroids (HDS).
AB - EXPERIMENTAL DESIGN: Twenty-five patients who developed ipilimumab-related hypophysitis were analyzed for the incidence, time to onset, time to resolution, frequency of resolution, and the effect of systemic HDS on clinical outcome. To calculate the incidence, the total number (187) of patients with metastatic melanoma treated with ipilimumab at Dana-Farber Cancer Institute (DFCI; Boston, MA) was retrieved from the DFCI oncology database. Comparisons between corticosteroid treatment groups were performed using the Fisher exact test. The distributions of overall survival were based on the method of Kaplan-Meier.
AB - RESULTS: The overall incidence of ipilimumab-related hypophysitis was 13%, with a higher rate in males (16.1%) than females (8.7%). The median time to onset of hypophysitis after initiation of ipilimumab treatment was 9 weeks (range, 5-36 weeks). Resolution of pituitary enlargement, secondary adrenal insufficiency, secondary hypothyroidism, male secondary hypogonadism, and hyponatremia occurred in 73%, 0%, 64%, 45%, and 92% of patients, respectively. Systemic HDS treatment did not improve the outcome of hypophysitis as measured by resolution frequency and time to resolution. One-year overall survival in the cohort of patients was 83%, and while it was slightly higher in patients who did not receive HDS, there was no statistically significant difference between treatment arms.
AB - CONCLUSION: Systemic HDS therapy in patients with ipilimumab-related hypophysitis may not be indicated. Instead, supportive treatment of hypophysitis-related hormone deficiencies with the corresponding hormone replacement should be given.
AB - Copyright ©2014 American Association for Cancer Research.
RN - 0 (Adrenal Cortex Hormones)
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
IS - 1078-0432
IL - 1078-0432
DI - 1078-0432.CCR-14-2353
DO - https://dx.doi.org/10.1158/1078-0432.CCR-14-2353
PT - Journal Article
PT - Research Support, N.I.H., Extramural
ID - 25538262 [pubmed]
ID - 1078-0432.CCR-14-2353 [pii]
ID - 10.1158/1078-0432.CCR-14-2353 [doi]
ID - PMC4334697 [pmc]
ID - NIHMS651379 [mid]
PP - ppublish
GI - No: K08 HD070957
Organization: (HD) *NICHD NIH HHS*
Country: United States
LG - English
EP - 20141223
DP - 2015 Feb 15
DC - 20150218
EZ - 2014/12/25 06:00
DA - 2015/12/15 06:00
DT - 2014/12/30 06:00
YR - 2015
ED - 20151209
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25538262
<181. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25792081
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wozniak S
AU - Mackiewicz-Wysocka M
AU - Krokowicz L
AU - Kwinta L
AU - Mackiewicz J
FA - Wozniak, Sebastian
FA - Mackiewicz-Wysocka, Malgorzata
FA - Krokowicz, Lukasz
FA - Kwinta, Lukasz
FA - Mackiewicz, Jacek
IN - Wozniak, Sebastian. Department of Chemotherapy, Greater Poland Cancer Centre, Poznan, Poland.
TI - Febrile neutropenia in a metastatic melanoma patient treated with ipilimumab - case report.
SO - Oncology Research and Treatment. 38(3):105-8, 2015
AS - Oncol Res Treat. 38(3):105-8, 2015
NJ - Oncology research and treatment
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101627692
IO - Oncol Res Treat
SB - Index Medicus
CP - Netherlands
MH - Adult
MH - Agranulocytosis/et [Etiology]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Axilla
MH - *Febrile Neutropenia/et [Etiology]
MH - Humans
MH - *Immunologic Factors/ae [Adverse Effects]
MH - Lymphatic Metastasis
MH - Lymphocytes/pa [Pathology]
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/sc [Secondary]
MH - Monocytes/pa [Pathology]
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/pa [Pathology]
AB - BACKGROUND: Ipilimumab is a fully human monoclonal antibody (mAb) targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4). Ipilimumab is currently approved in the U.S. and Europe for the treatment of metastatic melanoma in the first- and second-line treatment. Treatment with ipilimumab is linked to immune-related adverse events (irAEs) occurring in the majority of patients. These specific AEs include dermatitis, gastrointestinal disorders (diarrhea, colitis), hepatitis, hypophysitis, hypothyroidism, neuropathy, and iritis/inflammation of the ciliary body.
AB - CASE REPORT: We report a case of febrile neutropenia with agranulocytosis in the blood smear of a 35-year-old metastatic melanoma patient treated with ipilimumab 3 mg/kg.
AB - CONCLUSION: This AE was probably caused by antineutrophil antibodies associated with ipilimumab treatment. To our knowledge this is the first case report of febrile neutropenia in a metastatic melanoma patient treated with ipilimumab 3 mg/kg.
AB - Copyright © 2015 S. Karger GmbH, Freiburg.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Immunologic Factors)
RN - 6T8C155666 (ipilimumab)
ES - 2296-5262
IL - 2296-5270
DI - 000377650
DO - https://dx.doi.org/10.1159/000377650
PT - Case Reports
PT - Journal Article
ID - 25792081 [pubmed]
ID - 000377650 [pii]
ID - 10.1159/000377650 [doi]
PP - ppublish
PH - 2014/03/17 [received]
PH - 2014/09/17 [accepted]
LG - English
EP - 20150220
DP - 2015
DC - 20150320
EZ - 2015/03/21 06:00
DA - 2015/12/15 06:00
DT - 2015/03/21 06:00
YR - 2015
ED - 20151208
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25792081
<182. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26629422
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Mamdani H
AU - Induru R
AU - Jalal SI
FA - Mamdani, Hirva
FA - Induru, Raghava
FA - Jalal, Shadia I
IN - Mamdani, Hirva. 1 Division of Hematology/Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA ; 2 Levine Cancer Institute, Carolinas HealthCare Systems, Albemarle, NC, USA.
IN - Induru, Raghava. 1 Division of Hematology/Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA ; 2 Levine Cancer Institute, Carolinas HealthCare Systems, Albemarle, NC, USA.
IN - Jalal, Shadia I. 1 Division of Hematology/Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA ; 2 Levine Cancer Institute, Carolinas HealthCare Systems, Albemarle, NC, USA.
TI - Novel therapies in small cell lung cancer. [Review]
SO - Translational Lung Cancer Research. 4(5):533-44, 2015 Oct
AS - Transl. lung cancer res.. 4(5):533-44, 2015 Oct
NJ - Translational lung cancer research
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 101646875
IO - Transl Lung Cancer Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630526
CP - China
KW - Notch inhibition; PARP1 inhibition; Small cell lung cancer (SCLC); immune therapy; molecular targeted therapy
AB - Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor of the lung with a tendency to metastasize widely early in the course of the disease. The VA staging system classifies the disease into limited stage (LS) which is confined to one hemithorax and can be included into one radiation field or extensive stage (ES) which extends beyond one hemithorax. Current standard of care is concurrent chemoradiation for LS disease and chemotherapy alone for ES disease. Only a quarter of patients with LS disease will be cured with current standard treatments and majority of the patients ultimately succumb to their disease. A very complex genetic landscape of SCLC accounts for its resistance to conventional therapy and a high recurrence rate, however, at the same time this complexity can form the basis for effective targeted therapy for the disease. In recent years, several different therapeutic strategies and targeted agents have been under investigation for their potential role in SCLC. Several of them including EGFR TKIs, BCR-ABL TKIs, mTOR inhibitors, and VEGF inhibitors have been unsuccessful in showing a survival advantage in this disease. Several others including DNA repair inhibitors, cellular developmental pathway inhibitors, antibody drug conjugates (ADCs), as well as immune therapy with vaccines, immunomodulators, and immune checkpoint inhibitors are being tested. So far, none of these agents are approved for use in SCLC and the majority are in phase I/II clinical trials, with immune checkpoint inhibitors being the most promising therapeutic strategy. In this article, we will discuss these novel therapeutic agents and currently available data in SCLC.
IS - 2218-6751
IL - 2218-6751
DI - tlcr-04-05-533
DO - https://dx.doi.org/10.3978/j.issn.2218-6751.2015.07.20
PT - Journal Article
PT - Review
ID - 26629422 [pubmed]
ID - 10.3978/j.issn.2218-6751.2015.07.20 [doi]
ID - tlcr-04-05-533 [pii]
ID - PMC4630526 [pmc]
PP - ppublish
LG - English
DP - 2015 Oct
DC - 20151202
EZ - 2015/12/03 06:00
DA - 2015/12/03 06:01
DT - 2015/12/03 06:00
YR - 2015
ED - 20151202
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=26629422
<183. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26629425
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Villadolid J
AU - Amin A
FA - Villadolid, Jeryl
FA - Amin, Asim
IN - Villadolid, Jeryl. 1 Department of Pharmacy, 2 Divisions of Immunotherapy and Medical Oncology, Carolinas HealthCare System, Levine Cancer Institute, Charlotte, NC 28204, USA.
IN - Amin, Asim. 1 Department of Pharmacy, 2 Divisions of Immunotherapy and Medical Oncology, Carolinas HealthCare System, Levine Cancer Institute, Charlotte, NC 28204, USA.
TI - Immune checkpoint inhibitors in clinical practice: update on management of immune-related toxicities. [Review]
SO - Translational Lung Cancer Research. 4(5):560-75, 2015 Oct
AS - Transl. lung cancer res.. 4(5):560-75, 2015 Oct
NJ - Translational lung cancer research
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 101646875
IO - Transl Lung Cancer Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630514
CP - China
KW - Immunotherapy; checkpoint inhibition; toxicity
AB - Immune checkpoint blockade using inhibitors of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) has shown clinically significant antitumor response and has been approved for the treatment of malignant melanoma and squamous non-small cell lung cancer (NSCLC). These immunotherapies are associated with unique set of toxicities termed immune-related adverse events (irAEs) that are very different from toxicities observed with conventional cytotoxic chemotherapy. Prompt recognition and initiation of appropriate management, usually in the form of immunosuppression, usually results in complete reversibility, but failing to do so can lead to severe toxicity or even death. Clinical algorithms describing the management of common irAEs have been published based on clinical trial information and experience in metastatic melanoma with ipilimumab, a human IgG1 monoclonal antibody that binds to CTLA-4 and blocks T cell inhibition. The most common irAEs reported with ipilimumab are dermatologic toxicity, diarrhea/colitis, hepatotoxicity, and endocrinopathies, although other sites can also be affected. Similar irAEs have been observed with agents targeting PD-1. Nivolumab and pembrolizumab are humanized monoclonal antibodies that bind to PD-1 and prevent T cell inactivation. Ipilimumab, pembrolizumab, and nivolumab are approved by the Food and Drug Administration (FDA) for the treatment of advanced melanoma; nivolumab was also recently approved for metastatic squamous NSCLC. This review describes the optimal management of toxicities related to immune checkpoint inhibition from FDA-approved agents targeting CTLA-4 and PD-1.
IS - 2218-6751
IL - 2218-6751
DI - tlcr-04-05-560
DO - https://dx.doi.org/10.3978/j.issn.2218-6751.2015.06.06
PT - Journal Article
PT - Review
ID - 26629425 [pubmed]
ID - 10.3978/j.issn.2218-6751.2015.06.06 [doi]
ID - tlcr-04-05-560 [pii]
ID - PMC4630514 [pmc]
PP - ppublish
LG - English
DP - 2015 Oct
DC - 20151202
EZ - 2015/12/03 06:00
DA - 2015/12/03 06:01
DT - 2015/12/03 06:00
YR - 2015
ED - 20151202
RD - 20151214
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=26629425
<184. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26141863
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Koh SB
AU - Courtin A
AU - Boyce RJ
AU - Boyle RG
AU - Richards FM
AU - Jodrell DI
FA - Koh, Siang-Boon
FA - Courtin, Aurelie
FA - Boyce, Richard J
FA - Boyle, Robert G
FA - Richards, Frances M
FA - Jodrell, Duncan I
IN - Koh, Siang-Boon. Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
IN - Courtin, Aurelie. Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
IN - Boyce, Richard J. Sentinel Oncology Limited, Cambridge, United Kingdom.
IN - Boyle, Robert G. Sentinel Oncology Limited, Cambridge, United Kingdom.
IN - Richards, Frances M. Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom. Fran.Richards@cruk.cam.ac.uk.
IN - Jodrell, Duncan I. Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
TI - CHK1 Inhibition Synergizes with Gemcitabine Initially by Destabilizing the DNA Replication Apparatus.
SO - Cancer Research. 75(17):3583-95, 2015 Sep 01
AS - Cancer Res. 75(17):3583-95, 2015 Sep 01
NJ - Cancer research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cnf, 2984705r
IO - Cancer Res.
SB - Index Medicus
CP - United States
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - Cell Division
MH - Cell Line, Tumor
MH - Checkpoint Kinase 1
MH - DNA Damage/de [Drug Effects]
MH - DNA Replication/de [Drug Effects]
MH - Deoxycytidine/ad [Administration & Dosage]
MH - *Deoxycytidine/aa [Analogs & Derivatives]
MH - *Drug Synergism
MH - G2 Phase/de [Drug Effects]
MH - Humans
MH - Mitosis/de [Drug Effects]
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Phosphorylation/de [Drug Effects]
MH - Protein Kinase Inhibitors/ad [Administration & Dosage]
MH - *Protein Kinases/de [Drug Effects]
MH - Tumor Suppressor Protein p53/ge [Genetics]
AB - Combining cell-cycle checkpoint kinase inhibitors with the DNA-damaging chemotherapeutic agent gemcitabine offers clinical appeal, with a mechanistic rationale based chiefly on abrogation of gemcitabine-induced G2-M checkpoint activation. However, evidence supporting this mechanistic rationale from chemosensitization studies has not been consistent. Here we report a systematic definition of how pancreatic cancer cells harboring mutant p53 respond to this combination therapy, by combining mathematical models with large-scale quantitative biologic analyses of single cells and cell populations. Notably, we uncovered a dynamic range of mechanistic effects at different ratios of gemcitabine and CHK1 inhibitors. Remarkably, effective synergy was attained even where cells exhibited an apparently functional G2-M surveillance mechanism, as exemplified by a lack of both overt premature CDK1 activation and S-phase mitotic entry. Consistent with these findings, S-G2 duration was extended in treated cells, leading to a definable set of lineage-dependent catastrophic fates. At synergistic drug concentrations, global replication stress was a distinct indicator of chemosensitization as characterized molecularly by an accumulation of S-phase cells with high levels of hyperphosphorylated RPA-loaded single-stranded DNA. In a fraction of these cells, persistent genomic damage was observed, including chromosomal fragmentation with a loss of centromeric regions that prevented proper kinetochore-microtubule attachment. Together, our results suggested a "foot-in-the-door" mechanism for drug synergy where cells were destroyed not by frank G2-M phase abrogation but rather by initiating a cumulative genotoxicity that deregulated DNA synthesis.
AB - Copyright ©2015 American Association for Cancer Research.
RN - 0 (Antineoplastic Agents)
RN - 0 (Protein Kinase Inhibitors)
RN - 0 (TP53 protein, human)
RN - 0 (Tumor Suppressor Protein p53)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7 (Protein Kinases)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
ES - 1538-7445
IL - 0008-5472
DI - 0008-5472.CAN-14-3347
DO - https://dx.doi.org/10.1158/0008-5472.CAN-14-3347
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26141863 [pubmed]
ID - 0008-5472.CAN-14-3347 [pii]
ID - 10.1158/0008-5472.CAN-14-3347 [doi]
PP - ppublish
PH - 2014/11/13 [received]
PH - 2015/06/01 [accepted]
GI - No: C14303/A17197
Organization: *Cancer Research UK*
Country: United Kingdom
LG - English
EP - 20150703
DP - 2015 Sep 01
DC - 20150902
EZ - 2015/07/05 06:00
DA - 2015/12/15 06:00
DT - 2015/07/05 06:00
YR - 2015
ED - 20151125
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26141863
<185. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26317466
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Chiappinelli KB
AU - Strissel PL
AU - Desrichard A
AU - Li H
AU - Henke C
AU - Akman B
AU - Hein A
AU - Rote NS
AU - Cope LM
AU - Snyder A
AU - Makarov V
AU - Budhu S
AU - Slamon DJ
AU - Wolchok JD
AU - Pardoll DM
AU - Beckmann MW
AU - Zahnow CA
AU - Merghoub T
AU - Chan TA
AU - Baylin SB
AU - Strick R
FA - Chiappinelli, Katherine B
FA - Strissel, Pamela L
FA - Desrichard, Alexis
FA - Li, Huili
FA - Henke, Christine
FA - Akman, Benjamin
FA - Hein, Alexander
FA - Rote, Neal S
FA - Cope, Leslie M
FA - Snyder, Alexandra
FA - Makarov, Vladimir
FA - Budhu, Sadna
FA - Slamon, Dennis J
FA - Wolchok, Jedd D
FA - Pardoll, Drew M
FA - Beckmann, Matthias W
FA - Zahnow, Cynthia A
FA - Merghoub, Taha
FA - Chan, Timothy A
FA - Baylin, Stephen B
FA - Strick, Reiner
IN - Chiappinelli, Katherine B. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
IN - Strissel, Pamela L. Department of Gynaecology and Obstetrics, Laboratory for Molecular Medicine, University-Clinic Erlangen, 91054 Erlangen, Germany.
IN - Desrichard, Alexis. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
IN - Li, Huili. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
IN - Henke, Christine. Department of Gynaecology and Obstetrics, Laboratory for Molecular Medicine, University-Clinic Erlangen, 91054 Erlangen, Germany.
IN - Akman, Benjamin. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
IN - Hein, Alexander. Department of Gynaecology and Obstetrics, Laboratory for Molecular Medicine, University-Clinic Erlangen, 91054 Erlangen, Germany.
IN - Rote, Neal S. Department of Reproductive Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
IN - Cope, Leslie M. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
IN - Snyder, Alexandra. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
IN - Makarov, Vladimir. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
IN - Buhu, Sadna. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
IN - Slamon, Dennis J. The Jonsson Comprehensive Cancer Center, University of California-Los Angeles, Los Angeles, CA 90095, USA.
IN - Wolchok, Jedd D. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
IN - Pardoll, Drew M. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
IN - Beckmann, Matthias W. Department of Gynaecology and Obstetrics, Laboratory for Molecular Medicine, University-Clinic Erlangen, 91054 Erlangen, Germany.
IN - Zahnow, Cynthia A. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.
IN - Mergoub, Taha. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
IN - Chan, Timothy A. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
IN - Baylin, Stephen B. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA. Electronic address: sbaylin@jhmi.edu.
IN - Strick, Reiner. Department of Gynaecology and Obstetrics, Laboratory for Molecular Medicine, University-Clinic Erlangen, 91054 Erlangen, Germany. Electronic address: reiner.strick@uk-erlangen.de.
TI - Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses.[Erratum appears in Cell. 2016 Feb 25;164(5):1073 Note: Buhu, Sadna [corrected to Budhu, Sadna]; Mergoub, Taha [corrected to Merghoub, Taha]; PMID: 27064190]
CM - Comment in: Cell. 2015 Aug 27;162(5):938-9; PMID: 26317460
SO - Cell. 162(5):974-86, 2015 Aug 27
AS - Cell. 162(5):974-86, 2015 Aug 27
NJ - Cell
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - cq4, 0413066
IO - Cell
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556003
OI - Source: NLM. NIHMS707501
SB - Index Medicus
CP - United States
MH - Animals
MH - Azacitidine/pd [Pharmacology]
MH - Cell Line, Tumor
MH - *DNA Methylation/de [Drug Effects]
MH - DNA Modification Methylases/ai [Antagonists & Inhibitors]
MH - Endogenous Retroviruses/ge [Genetics]
MH - Female
MH - Humans
MH - Immunotherapy
MH - *Interferon Type I/im [Immunology]
MH - Lung Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/im [Immunology]
MH - *Melanoma/im [Immunology]
MH - *Melanoma/th [Therapy]
MH - Mice
MH - Mice, Inbred C57BL
MH - Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/th [Therapy]
MH - RNA, Double-Stranded/me [Metabolism]
AB - We show that DNA methyltransferase inhibitors (DNMTis) upregulate immune signaling in cancer through the viral defense pathway. In ovarian cancer (OC), DNMTis trigger cytosolic sensing of double-stranded RNA (dsRNA) causing a type I interferon response and apoptosis. Knocking down dsRNA sensors TLR3 and MAVS reduces this response 2-fold and blocking interferon beta or its receptor abrogates it. Upregulation of hypermethylated endogenous retrovirus (ERV) genes accompanies the response and ERV overexpression activates the response. Basal levels of ERV and viral defense gene expression significantly correlate in primary OC and the latter signature separates primary samples for multiple tumor types from The Cancer Genome Atlas into low versus high expression groups. In melanoma patients treated with an immune checkpoint therapy, high viral defense signature expression in tumors significantly associates with durable clinical response and DNMTi treatment sensitizes to anti-CTLA4 therapy in a pre-clinical melanoma model.
AB - Copyright © 2015 Elsevier Inc. All rights reserved.
RN - 0 (Interferon Type I)
RN - 0 (RNA, Double-Stranded)
RN - EC 2-1-1 (DNA Modification Methylases)
RN - M801H13NRU (Azacitidine)
ES - 1097-4172
IL - 0092-8674
DI - S0092-8674(15)00848-X
DO - https://dx.doi.org/10.1016/j.cell.2015.07.011
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
PT - Research Support, U.S. Gov't, Non-P.H.S.
ID - 26317466 [pubmed]
ID - S0092-8674(15)00848-X [pii]
ID - 10.1016/j.cell.2015.07.011 [doi]
ID - PMC4556003 [pmc]
ID - NIHMS707501 [mid]
PP - ppublish
PH - 2014/12/19 [received]
PH - 2015/05/04 [revised]
PH - 2015/06/26 [accepted]
GI - No: F32CA183214
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA058184
Organization: (CA) *NCI NIH HHS*
Country: United States
No: F32 CA183214
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA058184
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2015 Aug 27
DC - 20150831
EZ - 2015/08/29 06:00
DA - 2015/12/15 06:00
DT - 2015/09/01 06:00
YR - 2015
ED - 20151124
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26317466
<186. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25822767
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Peper JK
AU - Stevanovic S
FA - Peper, Janet Kerstin
FA - Stevanovic, Stefan
IN - Peper, Janet Kerstin. Department of Immunology, Institute of Cell Biology, University of Tubingen, Auf der Morgenstelle 15, 72076, Tubingen, Germany, janet-peper@gmx.de.
TI - A combined approach of human leukocyte antigen ligandomics and immunogenicity analysis to improve peptide-based cancer immunotherapy. [Review]
SO - Cancer Immunology, Immunotherapy. 64(10):1295-303, 2015 Oct
AS - Cancer Immunol Immunother. 64(10):1295-303, 2015 Oct
NJ - Cancer immunology, immunotherapy : CII
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cn3, 8605732
IO - Cancer Immunol. Immunother.
SB - Index Medicus
CP - Germany
MH - Animals
MH - Antigens, Neoplasm/me [Metabolism]
MH - Clinical Trials as Topic
MH - Female
MH - HLA Antigens/me [Metabolism]
MH - Humans
MH - *Immunotherapy/mt [Methods]
MH - Immunotherapy/td [Trends]
MH - Ligands
MH - Molecular Targeted Therapy
MH - Ovarian Neoplasms/im [Immunology]
MH - *Ovarian Neoplasms/th [Therapy]
MH - Peptide Fragments/me [Metabolism]
MH - *Vaccines, Subunit
AB - The breakthrough development of immune checkpoint inhibitors as clinically effective novel therapies demonstrates the potential of cancer immunotherapy. The identification of suitable targets for specific immunotherapy, however, remains a challenging task. Most peptides previously used for vaccination in clinical trials were able to elicit strong immunological responses but failed with regard to clinical benefit. This might, at least partly, be caused by an inadequate peptide selection, usually derived from established tumor-associated antigens which are not necessarily presented as human leukocyte antigen (HLA) ligands. Recently, HLA ligandome analysis revealed cancer-associated peptides, which have been used in clinical trials showing encouraging impact on survival. To improve peptide-based cancer immunotherapy, our group established a combined approach of HLA ligandomics and immunogenicity analysis for the identification of vaccine peptides. This approach is based on the identification of naturally presented HLA ligands on tumor samples, the selection of tumor-associated/tumor-specific HLA ligands and their subsequent testing for immunogenicity in vitro. In this review, we want to present our pipeline for the identification of vaccine peptides, focusing on ovarian cancer, and want to discuss differences to other approaches. Furthermore, we want to give a short outlook of a potential multi-peptide vaccination trial using the novel identified peptides.
RN - 0 (Antigens, Neoplasm)
RN - 0 (HLA Antigens)
RN - 0 (Ligands)
RN - 0 (Peptide Fragments)
RN - 0 (Vaccines, Subunit)
ES - 1432-0851
IL - 0340-7004
DO - https://dx.doi.org/10.1007/s00262-015-1682-8
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 25822767 [pubmed]
ID - 10.1007/s00262-015-1682-8 [doi]
PP - ppublish
PH - 2015/01/30 [received]
PH - 2015/03/10 [accepted]
LG - English
EP - 20150331
DP - 2015 Oct
DC - 20150901
EZ - 2015/03/31 06:00
DA - 2015/11/18 06:00
DT - 2015/03/31 06:00
YR - 2015
ED - 20151117
RD - 20150901
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25822767
<187. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25998800
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Mony JT
AU - Zhang L
AU - Ma T
AU - Grabosch S
AU - Tirodkar TS
AU - Brozick J
AU - Tseng G
AU - Elishaev E
AU - Edwards RP
AU - Huang X
AU - Vlad AM
FA - Mony, Jyothi Thyagabhavan
FA - Zhang, Lixin
FA - Ma, Tianzhou
FA - Grabosch, Shannon
FA - Tirodkar, Tejas S
FA - Brozick, Joan
FA - Tseng, George
FA - Elishaev, Esther
FA - Edwards, Robert P
FA - Huang, Xin
FA - Vlad, Anda M
IN - Mony, Jyothi Thyagabhavan. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, 204 Craft Ave, Pittsburgh, PA, 15213, USA.
TI - Anti-PD-L1 prolongs survival and triggers T cell but not humoral anti-tumor immune responses in a human MUC1-expressing preclinical ovarian cancer model.
SO - Cancer Immunology, Immunotherapy. 64(9):1095-108, 2015 Sep
AS - Cancer Immunol Immunother. 64(9):1095-108, 2015 Sep
NJ - Cancer immunology, immunotherapy : CII
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cn3, 8605732
IO - Cancer Immunol. Immunother.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545381
OI - Source: NLM. NIHMS693558
SB - Index Medicus
CP - Germany
MH - Animals
MH - *Antibodies, Monoclonal/im [Immunology]
MH - *Antibodies, Monoclonal/pd [Pharmacology]
MH - *Antigens, CD274/ai [Antagonists & Inhibitors]
MH - *Antigens, CD274/im [Immunology]
MH - CD8-Positive T-Lymphocytes/im [Immunology]
MH - Disease Models, Animal
MH - Female
MH - Humans
MH - Mice
MH - Mucin-1/bi [Biosynthesis]
MH - Mucin-1/ge [Genetics]
MH - Mucin-1/im [Immunology]
MH - *Ovarian Neoplasms/im [Immunology]
MH - *Ovarian Neoplasms/th [Therapy]
AB - Monoclonal antibodies that block inhibitory immune checkpoint molecules and enhance anti-tumor responses show clinical promise in advanced solid tumors. Most of the preliminary evidence on therapeutic efficacy of immune checkpoint blockers comes from studies in melanoma, lung and renal cancer. To test the in vivo potential of programmed death-ligand 1 (PD-L1) blockade in ovarian cancer, we recently generated a new transplantable tumor model using human mucin 1 (MUC1)-expressing 2F8 cells. The MUC1 transgenic (MUC1.Tg) mice develop large number of intraperitoneal (IP) tumors following IP injection of 8 x 10(5) syngeneic 2F8 cells. The tumors are aggressive and display little T cell infiltration. Anti-PD-L1 antibody was administered IP every 2 weeks (200 mug/dose) for a total of three doses. Treatment was started 21 days post-tumor challenge, a time point which corresponds to late tumor stage. The anti-PD-L1 treatment led to substantial T cell infiltration within the tumor and significantly increased survival (p = 0.001) compared to isotype control-treated mice. When the same therapy was administered to wild-type mice challenged with 2F8 tumors, no survival benefit was observed, despite the presence of high titer anti-MUC1 antibodies. However, earlier treatment (day 11) and higher frequency of IP injections restored the T cell responses and led to prolonged survival. Splenocyte profiling via Nanostring using probes for 511 immune genes revealed a treatment-induced immune gene signature consistent with increased T cell-mediated immunity. These findings strongly support further preclinical and clinical strategies exploring PD-L1 blockade in ovarian cancer.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD274)
RN - 0 (MUC1 protein, human)
RN - 0 (Mucin-1)
ES - 1432-0851
IL - 0340-7004
DO - https://dx.doi.org/10.1007/s00262-015-1712-6
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
PT - Research Support, U.S. Gov't, Non-P.H.S.
ID - 25998800 [pubmed]
ID - 10.1007/s00262-015-1712-6 [doi]
ID - PMC4545381 [pmc]
ID - NIHMS693558 [mid]
PP - ppublish
PH - 2014/10/23 [received]
PH - 2015/05/06 [accepted]
GI - No: UL1 TR000005
Organization: (TR) *NCATS NIH HHS*
Country: United States
No: R01CA163462
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA159981
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA047904
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA163462
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20150522
DP - 2015 Sep
DC - 20150819
EZ - 2015/05/23 06:00
DA - 2015/11/14 06:00
DT - 2015/05/23 06:00
YR - 2015
ED - 20151113
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25998800
<188. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25631244
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Stahl T
AU - Loquai C
FA - Stahl, T
FA - Loquai, C
IN - Stahl, T. Zentralinstitut fur diagnostische und interventionelle Radiologie, Klinikum der Stadt Ludwigshafen gGmbH, Bremserstr. 79, 67063, Ludwigshafen, Deutschland, stahlt@klilu.de.
TI - [Treatment side effects and follow-up of malignant melanoma]. [German]
OT - Therapienebenwirkungen und Nachsorge bei malignem Melanom.
SO - Radiologe. 55(2):136-43, 2015 Feb
AS - Radiologe. 55(2):136-43, 2015 Feb
NJ - Der Radiologe
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - qrl, 0401257
IO - Radiologe
SB - Index Medicus
CP - Germany
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Diagnosis, Differential
MH - *Diagnostic Imaging/mt [Methods]
MH - Drug Monitoring/mt [Methods]
MH - Humans
MH - *Inflammation/ci [Chemically Induced]
MH - *Inflammation/di [Diagnosis]
MH - Melanoma/di [Diagnosis]
MH - *Melanoma/dt [Drug Therapy]
MH - *Melanoma/sc [Secondary]
MH - Treatment Outcome
AB - Side effects in the therapy of malignant melanoma are primarily of importance for radiologists in advanced tumor stages. The available treatment options and their respective side effect profiles have undergone a profound change in recent years after the introduction of modern oncological therapies (e.g. immunotherapy and targeted therapy) with an increasing focus on individual tumor biology and differ significantly from those of classical chemotherapy. The immunotherapeutic agents, in particular ipilimumab, take on a special position because of their specific immune-mediated mechanisms of action and the associated side effects, so-called immune-related adverse events (irAE). The majority of the treatment effects are manifested on the skin (>50%) and are generally not detectable by diagnostic radiology. Only a comparatively small proportion of treatment side effects is detectable with diagnostic imaging (15-20%) but as in the example of therapy-induced colitis with ipilimumab, may be rapidly fatal. In addition to colitis (10-20%) further therapy side effects apparent in diagnostic imaging are hypophysitis (1.8-17%), thyroiditis (0.8%), myositis (1.7%), fasciitis and sarcoid-like lymph node alterations (6.8%). To detect radiologically detectable side effects early on and to delineate them especially from tumor progression and (opportunistic) infections, detailed knowledge of the therapeutic methods for melanoma, the mechanisms of action and in particular the sometimes very specific side effects is imperative for radiologists.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
ES - 1432-2102
IL - 0033-832X
DO - https://dx.doi.org/10.1007/s00117-014-2764-x
PT - English Abstract
PT - Journal Article
ID - 25631244 [pubmed]
ID - 10.1007/s00117-014-2764-x [doi]
PP - ppublish
LG - German
DP - 2015 Feb
DC - 20150219
EZ - 2015/01/30 06:00
DA - 2015/11/11 06:00
DT - 2015/01/30 06:00
YR - 2015
ED - 20151110
RD - 20150219
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25631244
<189. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25589420
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Breckwoldt M
AU - Bendszus M
FA - Breckwoldt, M
FA - Bendszus, M
IN - Breckwoldt, M. Abteilung Neuroradiologie, Neurologische Klinik, Universitatsklinikum Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Deutschland, michael.breckwoldt@med.uni-heidelberg.de.
TI - [Cerebral MR imaging of malignant melanoma]. [German]
OT - Zerebrale MR-Bildgebung beim malignen Melanom.
SO - Radiologe. 55(2):113-9, 2015 Feb
AS - Radiologe. 55(2):113-9, 2015 Feb
NJ - Der Radiologe
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - qrl, 0401257
IO - Radiologe
SB - Index Medicus
CP - Germany
MH - *Brain Neoplasms/di [Diagnosis]
MH - *Brain Neoplasms/sc [Secondary]
MH - Diagnosis, Differential
MH - Humans
MH - Image Enhancement/mt [Methods]
MH - *Magnetic Resonance Imaging/mt [Methods]
MH - *Melanoma/di [Diagnosis]
MH - *Melanoma/sc [Secondary]
MH - *Tomography, X-Ray Computed/mt [Methods]
AB - CLINICAL/METHODICAL ISSUE: Melanoma is the third leading cancer entity to metastasize to the central nervous system (CNS) after lung and breast cancer. This is often an early event in the disease course and limits survival. Metastasis in the CNS is the cause of death in 10-40% of melanoma patients and the incidence of brain metastasis is even higher (50-75%). Cerebral metastases are commonly found in the subcortical white matter. The signal characteristics can vary substantially and may change over time due to hemorrhages or the accumulation of melanin and paramagnetic ions. It is not yet clear whether novel targeted therapies (e.g. immunotherapy and kinase inhibitors) alter imaging characteristics. Also immune-related side effects, such as hypophysitis (in approximately 5% of patients receiving ipilimumab therapy) or granulomatous disease (neurosarcoid) can occur.
AB - STANDARD RADIOLOGICAL METHODS: Melanoma metastases are usually hyperdense in computed tomography (CT). In magnetic resonance imaging (MRI) T2-weighted (T2-w) fluid-attentuated inversion recovery (FLAIR) and T1-w sequences (with and without i.v. contrast) should be obtained. Coronal and axial imaging planes should be scanned to cross-correlate findings.
AB - METHODICAL INNOVATIONS: Susceptibility-weighted imaging is a new sensitive method to detect melanoma metastases. Approximately 66% of melanoma metastases show intratumoral susceptibility signals (ITSS). This sets them apart from other metastases (e.g. lung and breast cancer show less ITSSs, specificity approximately 81-96%). Diffusion imaging plays no major role in melanoma brain imaging.
AB - PERFORMANCE: Susceptibility-weighted imaging increases the sensitivity to detect metastases but lacks specificity. Differentiating metastases, microbleeding or calcification can be impossible. It is controversial how to interpret susceptibility signals without correlative signs on other sequences (differential diagnosis: metastasis, microbleeding and calcification).
AB - PRACTICAL RECOMMENDATIONS: CNS metastases are common in melanoma. MRI screening starting in stage IIc should be considered even in asymptomatic patients. Stage IV requires quarterly MRI examinations. Melanotic and amelanotic metastases show different MRI characteristics. The differentiation between metastasis and microbleeding can be impossible and might require a follow-up scan. Susceptibility-weighted imaging increases the sensitivity of metastases detection but lacks specificity. It can help to differentiate between different metastatic entities.
ES - 1432-2102
IL - 0033-832X
DO - https://dx.doi.org/10.1007/s00117-014-2761-0
PT - English Abstract
PT - Journal Article
ID - 25589420 [pubmed]
ID - 10.1007/s00117-014-2761-0 [doi]
PP - ppublish
LG - German
DP - 2015 Feb
DC - 20150219
EZ - 2015/01/16 06:00
DA - 2015/11/11 06:00
DT - 2015/01/16 06:00
YR - 2015
ED - 20151110
RD - 20150219
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25589420
<190. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23714523
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Chow LQ
FA - Chow, Laura Q M
IN - Chow, Laura Q M. From the Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA.
TI - Exploring novel immune-related toxicities and endpoints with immune-checkpoint inhibitors in non-small cell lung cancer. [Review]
SO - American Society of Clinical Oncology Educational Book. , 2013
AS - Am. Soc. Clin. Oncol. educ. book. , 2013
NJ - American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Meeting
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101233985
IO - Am Soc Clin Oncol Educ Book
SB - Index Medicus
CP - United States
MH - Animals
MH - *Antibodies/ae [Adverse Effects]
MH - *Antigens, CD274/ai [Antagonists & Inhibitors]
MH - Antigens, CD274/im [Immunology]
MH - Antigens, CD274/me [Metabolism]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Apoptosis/de [Drug Effects]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - CTLA-4 Antigen/me [Metabolism]
MH - *Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Carcinoma, Non-Small-Cell Lung/im [Immunology]
MH - Carcinoma, Non-Small-Cell Lung/me [Metabolism]
MH - Carcinoma, Non-Small-Cell Lung/pa [Pathology]
MH - Humans
MH - *Immunotherapy/ae [Adverse Effects]
MH - *Lung Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/im [Immunology]
MH - Lung Neoplasms/me [Metabolism]
MH - Lung Neoplasms/pa [Pathology]
MH - Lymphocyte Activation/de [Drug Effects]
MH - Molecular Targeted Therapy/ae [Adverse Effects]
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - Programmed Cell Death 1 Receptor/me [Metabolism]
MH - Risk Factors
MH - Signal Transduction/de [Drug Effects]
MH - Treatment Outcome
AB - Because of dramatic tumor regressions reported with the anti-programmed death-1 (PD-1) and anti-programmed death ligand-1 (PDL-1) antibodies inhibiting the PD-1 immune checkpoint, non-small cell lung cancer (NSCLC) is now recognized as an immune-modifiable disease. As responses were observed in smaller numbers in phase I trials, the immunologic profiles and unique toxicities of these agents have not been fully established in NSCLC. Moreover, PD-1 checkpoint inhibitors in development by different companies may demonstrate diverse spectrums of activity and toxicity. Although the cytotoxic T-lymphocyte antigen-4 (CTLA-4) checkpoint inhibitors in earlier phase studies appeared to have less impressive responses in NSCLC, their safety profile has been more broadly defined. The anti-CTLA-4 antibody, ipilimumab, has the best characterized immune-related toxicities (predominantly skin, gastrointestinal, hepatic, and endocrine) and management strategies in melanoma. Despite the lack of studies directly comparing these agents, toxicities from PD-1 inhibition seem milder than those of CTLA-4 inhibition, with distinct toxicities of pneumonitis infrequently observed with the BMS-936558 anti-PD-1 antibody, nivolumamb, and frequent mild infusion reactions reported with the BMS-936559 anti-PDL-1 antibody. As lungs are critical organs often already compromised in NSCLC patients, immune-mediated pneumonitis can cause worrisome morbidity and mortality. Even though immune checkpoint inhibitors are being rapidly developed in a multitude of trials, optimal immune-mediated toxicity management has not been determined, is evolving, and will be further explored. Early diagnosis and symptom management with corticosteroids form the basis of treatment. Assessment of new immune-response criteria and use of primary endpoints of overall survival (OS) will be important in the development of these immunotherapies in NSCLC.
RN - 0 (Antibodies)
RN - 0 (Antigens, CD274)
RN - 0 (Antineoplastic Agents)
RN - 0 (CD274 protein, human)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1548-8756
IL - 1548-8748
DI - 0011300280
DO - https://dx.doi.org/10.1200/EdBook_AM.2013.33.e280
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
PT - Video-Audio Media
ID - 23714523 [pubmed]
ID - 0011300280 [pii]
ID - 10.1200/EdBook_AM.2013.33.e280 [doi]
PP - ppublish
LG - English
DP - 2013
DC - 20140219
EZ - 2013/05/30 06:00
DA - 2015/11/04 06:00
DT - 2013/05/30 06:00
YR - 2013
ED - 20151103
RD - 20161021
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23714523
<191. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26171934
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Fankhauser CD
AU - Curioni-Fontecedro A
AU - Allmann V
AU - Beyer J
AU - Tischler V
AU - Sulser T
AU - Moch H
AU - Bode PK
FA - Fankhauser, C D
FA - Curioni-Fontecedro, A
FA - Allmann, V
FA - Beyer, J
FA - Tischler, V
FA - Sulser, T
FA - Moch, H
FA - Bode, P K
IN - Fankhauser, C D. Department of Urology, University Hospital Zurich, Zurich, Switzerland.
IN - Curioni-Fontecedro, A. Department of Oncology, University Hospital Zurich, Zurich, Switzerland.
IN - Allmann, V. Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
IN - Beyer, J. Department of Oncology, University Hospital Zurich, Zurich, Switzerland.
IN - Tischler, V. Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
IN - Sulser, T. Department of Urology, University Hospital Zurich, Zurich, Switzerland.
IN - Moch, H. Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
IN - Bode, P K. Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
TI - Frequent PD-L1 expression in testicular germ cell tumors.
SO - British Journal of Cancer. 113(3):411-3, 2015 Jul 28
AS - Br J Cancer. 113(3):411-3, 2015 Jul 28
NJ - British journal of cancer
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - av4, 0370635
IO - Br. J. Cancer
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522642
SB - Index Medicus
CP - England
MH - Adolescent
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - *Antigens, CD274/me [Metabolism]
MH - Humans
MH - Immunohistochemistry
MH - Male
MH - Middle Aged
MH - *Neoplasms, Germ Cell and Embryonal/ep [Epidemiology]
MH - *Neoplasms, Germ Cell and Embryonal/me [Metabolism]
MH - Neoplasms, Germ Cell and Embryonal/pa [Pathology]
MH - Seminoma/ep [Epidemiology]
MH - Seminoma/me [Metabolism]
MH - Seminoma/pa [Pathology]
MH - *Testicular Neoplasms/ep [Epidemiology]
MH - *Testicular Neoplasms/me [Metabolism]
MH - Testicular Neoplasms/pa [Pathology]
MH - Testis/me [Metabolism]
MH - Testis/pa [Pathology]
MH - Tissue Array Analysis
MH - Young Adult
AB - BACKGROUND: Many testicular germ cell cancers are curable despite metastatic disease, but about 10-15% of patients fail cisplatin-based first-line treatment. Immunotherapy is considered as additional treatment approach for these patients. Inhibition of the interaction between Programmed Death Receptor 1 (PD-1) and Programmed Death Receptor Ligand 1 (PD-L1) enhances T-cell responses in vitro and mediates clinical antitumour activity. We analysed the expression of PD-L1 in testicular germ cell tumours to evaluate its potential as target for immunotherapeutic strategies.
AB - METHODS: Immunohistochemistry was performed in 479 formalin-fixed paraffin-embedded specimens using a rabbit monoclonal antibody (E1L3N). The tissue microarray consisted of 208 pure seminomas, 121 non-seminomas, 20 intratubular germ cell neoplasia unclassified (IGCNU) and 20 specimens of non-neoplastic testicular tissue.
AB - RESULTS: Programmed Death Receptor Ligand-1 expression was found in 73% of all seminomas and in 64% of all non-seminomas. None of 20 IGCNU and none of 20 normal tissue specimens exhibited PD-L1 expression. PD-L1 positive stromal cells were only detected in seminomas, but not in non-seminomas. The anti PD-L1 antibody showed a pre-dominantly membranous staining pattern in testicular tumour cells, as well as expression in stromal cells.
AB - CONCLUSIONS: This frequent expression of PD-L1 in human testicular germ cell tumours suggests that patients with testicular germ cell tumours could profit from immunotherapeutic strategies using anti-PD1 and anti-PDL1 antibodies.
RN - 0 (Antigens, CD274)
RN - 0 (CD274 protein, human)
RS - Testicular Germ Cell Tumor
ES - 1532-1827
IL - 0007-0920
DI - bjc2015244
DO - https://dx.doi.org/10.1038/bjc.2015.244
PT - Journal Article
ID - 26171934 [pubmed]
ID - bjc2015244 [pii]
ID - 10.1038/bjc.2015.244 [doi]
ID - PMC4522642 [pmc]
PP - ppublish
PH - 2015/05/18 [revised]
PH - 2015/06/11 [accepted]
LG - English
EP - 20150714
DP - 2015 Jul 28
DC - 20150729
EZ - 2015/07/15 06:00
DA - 2015/10/16 06:00
DT - 2015/07/15 06:00
YR - 2015
ED - 20151014
RD - 20160728
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26171934
<192. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25751110
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Orlov S
AU - Salari F
AU - Kashat L
AU - Walfish PG
FA - Orlov, Steven
FA - Salari, Farnaz
FA - Kashat, Lawrence
FA - Walfish, Paul G
IN - Orlov, Steven. Department of Medicine (S.O., F.S., L.K., P.G.W.), Endocrine Division, and Otolaryngology-Head and Neck Surgery Program (P.G.W.), Mt. Sinai Hospital, Toronto, ON M5G 1X5, Canada and University of Toronto School of Medicine, Toronto, ON M5S 1A8, Canada.
TI - Induction of painless thyroiditis in patients receiving programmed death 1 receptor immunotherapy for metastatic malignancies.
SO - Journal of Clinical Endocrinology & Metabolism. 100(5):1738-41, 2015 May
AS - J Clin Endocrinol Metab. 100(5):1738-41, 2015 May
NJ - The Journal of clinical endocrinology and metabolism
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - hrb, 0375362
IO - J. Clin. Endocrinol. Metab.
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Female
MH - Humans
MH - *Immunotherapy/ae [Adverse Effects]
MH - Immunotherapy/mt [Methods]
MH - Lung Neoplasms/dt [Drug Therapy]
MH - Male
MH - Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - *Neoplasm Metastasis/dt [Drug Therapy]
MH - *Programmed Cell Death 1 Receptor/im [Immunology]
MH - Skin Neoplasms/dt [Drug Therapy]
MH - *Thyroiditis/ci [Chemically Induced]
MH - Thyroiditis/im [Immunology]
MH - *Thyrotoxicosis/ci [Chemically Induced]
MH - Thyrotoxicosis/im [Immunology]
AB - CONTEXT: Immunotherapies against immune checkpoints that inhibit T cell activation [cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1)] are emerging and promising treatments for several metastatic malignancies. However, the precise adverse effects of these therapies on thyroid gland function have not been well described.
AB - CASE DESCRIPTION: We report on 10 cases of painless thyroiditis syndrome (PTS) from a novel etiology, following immunotherapy with anti-PD-1 monoclonal antibodies (mAb) during treatment for metastatic malignancies. Six patients presented with transient thyrotoxicosis in which thyrotropin binding inhibitory immunoglobulins (TBII) were absent for all, whereas four patients had evidence of positive antithyroid antibodies. All thyrotoxic patients required temporary beta-blocker therapy and had spontaneous resolution of thyrotoxicosis with subsequent hypothyroidism. Four patients presented with hypothyroidism without a detected preceding thyrotoxic phase, occurring 6-8 weeks after initial drug exposure. All of these patients had positive antithyroid antibodies and required thyroid hormone replacement therapy for a minimum of 6 months.
AB - CONCLUSIONS: Patients receiving anti-PD-1 mAb therapy should be monitored for signs and symptoms of PTS which may require supportive treatment with beta-blockers or thyroid hormone replacement. The anti-PD-1 mAb is a novel exogenous cause of PTS and provides new insight into the possible perturbations of the immune network that may modulate the development of endogenous PTS, including cases of sporadic and postpartum thyroiditis.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1945-7197
IL - 0021-972X
DO - https://dx.doi.org/10.1210/jc.2014-4560
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 25751110 [pubmed]
ID - 10.1210/jc.2014-4560 [doi]
PP - ppublish
LG - English
EP - 20150309
DP - 2015 May
DC - 20150509
EZ - 2015/03/10 06:00
DA - 2015/10/01 06:00
DT - 2015/03/10 06:00
YR - 2015
ED - 20150930
RD - 20150509
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25751110
<193. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25828465
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Martin-Liberal J
AU - Furness AJ
AU - Joshi K
AU - Peggs KS
AU - Quezada SA
AU - Larkin J
FA - Martin-Liberal, Juan
FA - Furness, Andrew Js
FA - Joshi, Kroopa
FA - Peggs, Karl S
FA - Quezada, Sergio A
FA - Larkin, James
IN - Martin-Liberal, Juan. Renal and Melanoma Unit, The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK.
TI - Anti-programmed cell death-1 therapy and insulin-dependent diabetes: a case report.
SO - Cancer Immunology, Immunotherapy. 64(6):765-7, 2015 Jun
AS - Cancer Immunol Immunother. 64(6):765-7, 2015 Jun
NJ - Cancer immunology, immunotherapy : CII
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cn3, 8605732
IO - Cancer Immunol. Immunother.
SB - Index Medicus
CP - Germany
MH - *Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - *Diabetes Mellitus, Type 1/ci [Chemically Induced]
MH - Diabetes Mellitus, Type 1/im [Immunology]
MH - Female
MH - Humans
MH - Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Treatment Outcome
AB - The anti programmed cell death-1 (PD-1) antibodies pembrolizumab and nivolumab have been recently licensed by the Food and Drug Administration for the treatment of advanced melanoma. Immune checkpoint inhibitors such as these can induce endocrine adverse events but autoimmune diabetes has not been described to date. However, there is a strong preclinical rationale that supports this autoimmune toxicity. We describe for the first time the case of an adult patient who developed autoimmune diabetes likely as a consequence of PD-1 inhibition with pembrolizumab. The presence of high serum titres of anti-glutamic acid decarboxylase antibodies together with a suggestive clinical presentation, age of the patient and preclinical data strongly support an autoimmune aetiology of the diabetes. Moreover, the patient was found to have a well-known high-risk human leucocyte antigen type for the development of type 1 diabetes in children, so the PD-1 inhibition is very likely to have triggered the autoimmune phenomenon. Our case suggests that insulin-dependent diabetes might be a rare but important anti-PD-1 immune-related adverse event.
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - DPT0O3T46P (pembrolizumab)
ES - 1432-0851
IL - 0340-7004
DO - https://dx.doi.org/10.1007/s00262-015-1689-1
PT - Case Reports
PT - Journal Article
ID - 25828465 [pubmed]
ID - 10.1007/s00262-015-1689-1 [doi]
PP - ppublish
PH - 2015/02/02 [received]
PH - 2015/03/21 [accepted]
GI - No: 12100
Organization: *Cancer Research UK*
Country: United Kingdom
LG - English
EP - 20150401
DP - 2015 Jun
DC - 20150605
EZ - 2015/04/02 06:00
DA - 2015/09/04 06:00
DT - 2015/04/02 06:00
YR - 2015
ED - 20150902
RD - 20161122
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25828465
<194. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25795132
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Aguilar LK
AU - Shirley LA
AU - Chung VM
AU - Marsh CL
AU - Walker J
AU - Coyle W
AU - Marx H
AU - Bekaii-Saab T
AU - Lesinski GB
AU - Swanson B
AU - Sanchez D
AU - Manzanera AG
AU - Aguilar-Cordova E
AU - Bloomston M
FA - Aguilar, Laura K
FA - Shirley, Lawrence A
FA - Chung, Vincent M
FA - Marsh, Christopher L
FA - Walker, Jon
FA - Coyle, Walter
FA - Marx, Howard
FA - Bekaii-Saab, Tanios
FA - Lesinski, Gregory B
FA - Swanson, Benjamin
FA - Sanchez, Daniel
FA - Manzanera, Andrea G
FA - Aguilar-Cordova, Estuardo
FA - Bloomston, Mark
IN - Aguilar, Laura K. Advantagene, Inc., Auburndale, MA, 02466, USA.
TI - Gene-mediated cytotoxic immunotherapy as adjuvant to surgery or chemoradiation for pancreatic adenocarcinoma.
SO - Cancer Immunology, Immunotherapy. 64(6):727-36, 2015 Jun
AS - Cancer Immunol Immunother. 64(6):727-36, 2015 Jun
NJ - Cancer immunology, immunotherapy : CII
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cn3, 8605732
IO - Cancer Immunol. Immunother.
SB - Index Medicus
CP - Germany
MH - Acyclovir/ad [Administration & Dosage]
MH - *Acyclovir/aa [Analogs & Derivatives]
MH - Adenocarcinoma/ge [Genetics]
MH - Adenocarcinoma/im [Immunology]
MH - Adenocarcinoma/pa [Pathology]
MH - Adenocarcinoma/su [Surgery]
MH - *Adenocarcinoma/th [Therapy]
MH - Adenoviridae/ge [Genetics]
MH - Adenoviridae/im [Immunology]
MH - Adult
MH - Aged
MH - Chemoradiotherapy
MH - Combined Modality Therapy
MH - Dose-Response Relationship, Drug
MH - Female
MH - *Genetic Therapy/mt [Methods]
MH - Genetic Vectors/ge [Genetics]
MH - Genetic Vectors/im [Immunology]
MH - Humans
MH - Immunohistochemistry
MH - *Immunotherapy/mt [Methods]
MH - Male
MH - Middle Aged
MH - Neoplasm Recurrence, Local
MH - Pancreatic Neoplasms/ge [Genetics]
MH - Pancreatic Neoplasms/im [Immunology]
MH - Pancreatic Neoplasms/su [Surgery]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - Thymidine Kinase/ge [Genetics]
MH - Valine/ad [Administration & Dosage]
MH - *Valine/aa [Analogs & Derivatives]
AB - BACKGROUND: While surgical resection of pancreatic adenocarcinoma provides the only chance of cure, long-term survival remains poor. Immunotherapy may improve outcomes, especially as adjuvant to local therapies. Gene-mediated cytotoxic immunotherapy (GMCI) generates a systemic anti-tumor response through local delivery of an adenoviral vector expressing the HSV-tk gene (aglatimagene besadenovec, AdV-tk) followed by anti-herpetic prodrug. GMCI has demonstrated synergy with standard of care (SOC) in other tumor types. This is the first application in pancreatic cancer.
AB - METHODS: Four dose levels (3 x 10(10) to 1 x 10(12) vector particles) were evaluated as adjuvant to surgery for resectable disease (Arm A) or to 5-FU chemoradiation for locally advanced disease (Arm B). Each patient received two cycles of AdV-tk + prodrug.
AB - RESULTS: Twenty-four patients completed therapy, 12 per arm, with no dose-limiting toxicities. All Arm A patients were explored, eight were resected, one was locally advanced and three had distant metastases. CD8(+) T cell infiltration increased an average of 22-fold (range sixfold to 75-fold) compared with baseline (p = 0.0021). PD-L1 expression increased in 5/7 samples analyzed. One node-positive resected patient is alive >66 months without recurrence. Arm B RECIST response rate was 25 % with a median OS of 12 months and 1-year survival of 50 %. Patient-reported quality of life showed no evidence of deterioration.
AB - CONCLUSIONS: AdV-tk can be safely combined with pancreatic cancer SOC without added toxicity. Response and survival compare favorably to expected outcomes and immune activity increased. These results support further evaluation of GMCI with more modern chemoradiation and surgery as well as PD-1/PD-L1 inhibitors in pancreatic cancer.
RN - EC 2-7-1-21 (Thymidine Kinase)
RN - HG18B9YRS7 (Valine)
RN - MZ1IW7Q79D (valacyclovir)
RN - X4HES1O11F (Acyclovir)
RS - Pancreatic Carcinoma
ES - 1432-0851
IL - 0340-7004
DO - https://dx.doi.org/10.1007/s00262-015-1679-3
PT - Clinical Trial
PT - Journal Article
PT - Research Support, N.I.H., Extramural
ID - 25795132 [pubmed]
ID - 10.1007/s00262-015-1679-3 [doi]
PP - ppublish
PH - 2014/11/19 [received]
PH - 2015/03/04 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00638612
SL - https://clinicaltrials.gov/search/term=NCT00638612
GI - No: R43CA119847
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20150321
DP - 2015 Jun
DC - 20150605
EZ - 2015/03/22 06:00
DA - 2015/09/04 06:00
DT - 2015/03/22 06:00
YR - 2015
ED - 20150902
RD - 20150605
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25795132
<195. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25742933
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Osada T
AU - Patel SP
AU - Hammond SA
AU - Osada K
AU - Morse MA
AU - Lyerly HK
FA - Osada, Takuya
FA - Patel, Sandip P
FA - Hammond, Scott A
FA - Osada, Koya
FA - Morse, Michael A
FA - Lyerly, H Kim
IN - Osada, Takuya. Section of Applied Therapeutics, Department of Surgery, Duke University Medical Center, 403 MSRB, Research Drive, Durham, NC, 27710, USA, osada001@mc.duke.edu.
TI - CEA/CD3-bispecific T cell-engaging (BiTE) antibody-mediated T lymphocyte cytotoxicity maximized by inhibition of both PD1 and PD-L1.
SO - Cancer Immunology, Immunotherapy. 64(6):677-88, 2015 Jun
AS - Cancer Immunol Immunother. 64(6):677-88, 2015 Jun
NJ - Cancer immunology, immunotherapy : CII
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cn3, 8605732
IO - Cancer Immunol. Immunother.
SB - Index Medicus
CP - Germany
MH - Animals
MH - *Antibodies, Bispecific/im [Immunology]
MH - *Antibodies, Bispecific/pd [Pharmacology]
MH - *Antigens, CD274/ai [Antagonists & Inhibitors]
MH - Antigens, CD274/im [Immunology]
MH - *Antigens, CD3/im [Immunology]
MH - *Carcinoembryonic Antigen/im [Immunology]
MH - Cell Line, Tumor
MH - Colorectal Neoplasms/im [Immunology]
MH - Colorectal Neoplasms/th [Therapy]
MH - HT29 Cells
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Mice
MH - Mice, Inbred NOD
MH - Mice, SCID
MH - Pancreatic Neoplasms/im [Immunology]
MH - Pancreatic Neoplasms/th [Therapy]
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - *T-Lymphocytes, Cytotoxic/im [Immunology]
AB - Bispecific T cell-engaging (BiTE) antibodies recruit polyclonal cytotoxic T cells (CTL) to tumors. One such antibody is carcinoembryonic antigen (CEA) BiTE that mediates T cell/tumor interaction by simultaneously binding CD3 expressed by T cells and CEA expressed by tumor cells. A widely operative mechanism for mitigating cytotoxic T cell-mediated killing is the interaction of tumor-expressed PD-L1 with T cell-expressed PD-1, which may be partly reversed by PD-1/PD-L1 blockade. We hypothesized that PD-1/PD-L1 blockade during BiTE-mediated T cell killing would enhance CTL function. Here, we determined the effects of PD-1 and PD-L1 blockade during initial T cell-mediated killing of CEA-expressing human tumor cell lines in vitro, as well as subsequent T cell-mediated killing by T lymphocytes that had participated in tumor cell killing. We observed a rapid upregulation of PD-1 expression and diminished cytolytic function of T cells after they had engaged in CEA BiTE-mediated killing of tumors. T cell cytolytic activity in vitro could be maximized by administration of anti-PD-1 or anti-PD-L1 antibodies alone or in combination if applied prior to a round of T cell killing, but T cell inhibition could not be fully reversed by this blockade once the T cells had killed tumor. In conclusion, our findings demonstrate that dual blockade of PD-1 and PD-L1 maximizes T cell killing of tumor directed by CEA BiTE in vitro, is more effective if applied early, and provides a rationale for clinical use.
RN - 0 (Antibodies, Bispecific)
RN - 0 (Antigens, CD274)
RN - 0 (Antigens, CD3)
RN - 0 (CD274 protein, human)
RN - 0 (Carcinoembryonic Antigen)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1432-0851
IL - 0340-7004
DO - https://dx.doi.org/10.1007/s00262-015-1671-y
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 25742933 [pubmed]
ID - 10.1007/s00262-015-1671-y [doi]
PP - ppublish
PH - 2014/07/13 [received]
PH - 2015/02/17 [accepted]
LG - English
EP - 20150306
DP - 2015 Jun
DC - 20150605
EZ - 2015/03/07 06:00
DA - 2015/09/04 06:00
DT - 2015/03/07 06:00
YR - 2015
ED - 20150902
RD - 20150605
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25742933
<196. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25964248
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Gibney GT
AU - Atkins MB
FA - Gibney, Geoffrey T
FA - Atkins, Michael B
IN - Gibney, Geoffrey T. Moffitt Cancer Center; and University of South Florida, Tampa, FL geoffrey.gibney@moffitt.org.
IN - Atkins, Michael B. Georgetown-Lombardi Comprehensive Cancer Center; and Medstar-Georgetown University Hospital, Washington, DC.
TI - Swinging for the Fences: Long-Term Survival With Ipilimumab in Metastatic Melanoma.
SO - Journal of Clinical Oncology. 33(17):1873-7, 2015 Jun 10
AS - J Clin Oncol. 33(17):1873-7, 2015 Jun 10
NJ - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - jco, 8309333
IO - J. Clin. Oncol.
SB - Index Medicus
CP - United States
MH - Adrenal Insufficiency/et [Etiology]
MH - Adult
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - Brain Neoplasms/sc [Secondary]
MH - *Brain Neoplasms/th [Therapy]
MH - Cisplatin/ad [Administration & Dosage]
MH - Dacarbazine/ad [Administration & Dosage]
MH - Hormone Replacement Therapy
MH - Humans
MH - Hypopituitarism/ci [Chemically Induced]
MH - *Hypopituitarism/co [Complications]
MH - Hypothyroidism/et [Etiology]
MH - Interferon-alpha/ad [Administration & Dosage]
MH - Interleukin-2/ad [Administration & Dosage]
MH - Lung Neoplasms/sc [Secondary]
MH - *Lung Neoplasms/th [Therapy]
MH - Lymphatic Metastasis
MH - Male
MH - *Melanoma/di [Diagnosis]
MH - Melanoma/dt [Drug Therapy]
MH - Melanoma/sc [Secondary]
MH - Melanoma/su [Surgery]
MH - *Melanoma/th [Therapy]
MH - Neoplasm Staging
MH - Parietal Lobe
MH - *Radiosurgery
MH - Sentinel Lymph Node Biopsy
MH - Shoulder
MH - *Skin Neoplasms/pa [Pathology]
MH - Skin Neoplasms/su [Surgery]
MH - Treatment Outcome
MH - Vinblastine/ad [Administration & Dosage]
AB - A 40-year-old man with stage III melanoma arising from his left shoulder underwent wide local excision, sentinel lymph node biopsy, and lymph node dissection. Nine months after receiving adjuvant biochemotherapy with cisplatin, vinblastine, dacarbazine, interleukin-2 (IL-2), and interferon alfa as part of a clinical trial, he developed headaches and right-hand weakness and was found to have a 2-cm left parietal CNS metastasis. A comprehensive staging workup identified multiple nonspecific subcentimeter pulmonary nodules. The brain mass was resected and confirmed to be metastatic melanoma; the surgical bed was treated with stereotactic radiosurgery. He was monitored off therapy, but 5 months later, he developed a second left parietal CNS metastasis and enlarging lung nodules. The new brain lesion was treated with stereotactic radiosurgery, and he began systemic therapy with ipilimumab on a clinical trial. After the third dose, he presented with headache, nausea, and vomiting; a brain magnetic resonance imaging scan showed left anterior temporal enhancement, possibly representing new disease. His symptoms improved with a course of corticosteroids. Restaging of the chest showed a mixed response among the pulmonary nodules. After tapering off corticosteroids, he received the fourth dose of ipilimumab, which was complicated by grade 3 transaminitis and hypophysitis with documented hypothyroidism and adrenal insufficiency. They were managed with corticosteroids and thyroid and adrenal hormone replacement. Restaging scans showed further disease regression except for new confluent enhancing nodules and edema in the left temporal lobe. Craniotomy and resection of this area showed only necrotic tissue with no viable melanoma cells. Nine years after treatment with ipilimumab, he is alive and shows no evidence of melanoma on the basis of annual computed tomography scans of the chest, abdomen, and pelvis and magnetic resonance imaging scans of the brain. He has full neurologic function but still requires hormone replacement for persistent hypopituitarism.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Interferon-alpha)
RN - 0 (Interleukin-2)
RN - 5V9KLZ54CY (Vinblastine)
RN - 6T8C155666 (ipilimumab)
RN - 7GR28W0FJI (Dacarbazine)
RN - Q20Q21Q62J (Cisplatin)
ES - 1527-7755
IL - 0732-183X
DI - JCO.2014.60.1807
DO - https://dx.doi.org/10.1200/JCO.2014.60.1807
PT - Case Reports
PT - Journal Article
ID - 25964248 [pubmed]
ID - JCO.2014.60.1807 [pii]
ID - 10.1200/JCO.2014.60.1807 [doi]
PP - ppublish
LG - English
EP - 20150511
DP - 2015 Jun 10
DC - 20150609
EZ - 2015/05/13 06:00
DA - 2015/08/22 06:00
DT - 2015/05/13 06:00
YR - 2015
ED - 20150821
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25964248
<197. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26123020
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - McKinney EF
AU - Lee JC
AU - Jayne DR
AU - Lyons PA
AU - Smith KG
FA - McKinney, Eoin F
FA - Lee, James C
FA - Jayne, David R W
FA - Lyons, Paul A
FA - Smith, Kenneth G C
IN - McKinney, Eoin F. 1] Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK [2] Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
IN - Lee, James C. 1] Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK [2] Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
IN - Jayne, David R W. Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
IN - Lyons, Paul A. 1] Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK [2] Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
IN - Smith, Kenneth G C. 1] Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK [2] Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
TI - T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection.
CM - Comment in: Nat Rev Nephrol. 2015 Sep;11(9):503; PMID: 26168738
CM - Comment in: Nat Rev Immunol. 2015 Aug;15(8):468; PMID: 26160615
CM - Comment in: Nat Rev Rheumatol. 2015 Sep;11(9):501; PMID: 26168912
SO - Nature. 523(7562):612-6, 2015 Jul 30
AS - Nature. 523(7562):612-6, 2015 Jul 30
NJ - Nature
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 0410462
IO - Nature
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623162
OI - Source: NLM. EMS62964
SB - Index Medicus
CP - England
MH - Animals
MH - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/ge [Genetics]
MH - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/im [Immunology]
MH - Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pa [Pathology]
MH - Antigens, CD2/im [Immunology]
MH - Autoimmune Diseases/ge [Genetics]
MH - *Autoimmune Diseases/im [Immunology]
MH - Autoimmune Diseases/pa [Pathology]
MH - Autoimmunity/ge [Genetics]
MH - Autoimmunity/im [Immunology]
MH - *CD4-Positive T-Lymphocytes/im [Immunology]
MH - CD4-Positive T-Lymphocytes/me [Metabolism]
MH - *CD8-Positive T-Lymphocytes/im [Immunology]
MH - CD8-Positive T-Lymphocytes/me [Metabolism]
MH - *CD8-Positive T-Lymphocytes/pa [Pathology]
MH - Humans
MH - Infection/ge [Genetics]
MH - *Infection/im [Immunology]
MH - Infection/pa [Pathology]
MH - Infection/vi [Virology]
MH - Inflammation/im [Immunology]
MH - Inflammation/pa [Pathology]
MH - Inflammation/vi [Virology]
MH - Inflammatory Bowel Diseases/ge [Genetics]
MH - Inflammatory Bowel Diseases/im [Immunology]
MH - Inflammatory Bowel Diseases/pa [Pathology]
MH - Lupus Erythematosus, Systemic/ge [Genetics]
MH - Lupus Erythematosus, Systemic/im [Immunology]
MH - Lupus Erythematosus, Systemic/pa [Pathology]
MH - Mice
MH - Phenotype
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - Programmed Cell Death 1 Receptor/me [Metabolism]
MH - Receptors, Antigen, T-Cell/im [Immunology]
MH - Receptors, Interleukin-7/im [Immunology]
MH - Receptors, Interleukin-7/me [Metabolism]
MH - Transcriptome
AB - The clinical course of autoimmune and infectious disease varies greatly, even between individuals with the same condition. An understanding of the molecular basis for this heterogeneity could lead to significant improvements in both monitoring and treatment. During chronic infection the process of T-cell exhaustion inhibits the immune response, facilitating viral persistence. Here we show that a transcriptional signature reflecting CD8 T-cell exhaustion is associated with poor clearance of chronic viral infection, but conversely predicts better prognosis in multiple autoimmune diseases. The development of CD8 T-cell exhaustion during chronic infection is driven both by persistence of antigen and by a lack of accessory 'help' signals. In autoimmunity, we find that where evidence of CD4 T-cell co-stimulation is pronounced, that of CD8 T-cell exhaustion is reduced. We can reproduce the exhaustion signature by modifying the balance of persistent stimulation of T-cell antigen receptors and specific CD2-induced co-stimulation provided to human CD8 T cells in vitro, suggesting that each process plays a role in dictating outcome in autoimmune disease. The 'non-exhausted' T-cell state driven by CD2-induced co-stimulation is reduced by signals through the exhaustion-associated inhibitory receptor PD-1, suggesting that induction of exhaustion may be a therapeutic strategy in autoimmune and inflammatory disease. Using expression of optimal surrogate markers of co-stimulation/exhaustion signatures in independent data sets, we confirm an association with good clinical outcome or response to therapy in infection (hepatitis C virus) and vaccination (yellow fever, malaria, influenza), but poor outcome in autoimmune and inflammatory disease (type 1 diabetes, anti-neutrophil cytoplasmic antibody-associated vasculitis, systemic lupus erythematosus, idiopathic pulmonary fibrosis and dengue haemorrhagic fever). Thus, T-cell exhaustion plays a central role in determining outcome in autoimmune disease and targeted manipulation of this process could lead to new therapeutic opportunities.
RN - 0 (Antigens, CD2)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 0 (Receptors, Antigen, T-Cell)
RN - 0 (Receptors, Interleukin-7)
ES - 1476-4687
IL - 0028-0836
DI - nature14468
DO - https://dx.doi.org/10.1038/nature14468
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 26123020 [pubmed]
ID - nature14468 [pii]
ID - 10.1038/nature14468 [doi]
ID - PMC4623162 [pmc]
ID - EMS62964 [mid]
PP - ppublish
PH - 2014/02/12 [received]
PH - 2015/04/10 [accepted]
GI - No: 104064
Organization: *Wellcome Trust*
Country: United Kingdom
No: 079895
Organization: *Wellcome Trust*
Country: United Kingdom
No: 083650/Z/07/Z
Organization: *Wellcome Trust*
Country: United Kingdom
No: 083650
Organization: *Wellcome Trust*
Country: United Kingdom
No: 094227/Z/10/Z
Organization: *Wellcome Trust*
Country: United Kingdom
No: G0400929
Organization: *Medical Research Council*
Country: United Kingdom
No: 094227
Organization: *Wellcome Trust*
Country: United Kingdom
No: 104064/Z/14/Z
Organization: *Wellcome Trust*
Country: United Kingdom
No: MR/L019027/1
Organization: *Medical Research Council*
Country: United Kingdom
No: 100140
Organization: *Wellcome Trust*
Country: United Kingdom
LG - English
EP - 20150629
DP - 2015 Jul 30
DC - 20150730
EZ - 2015/07/01 06:00
DA - 2015/08/21 06:00
DT - 2015/07/01 06:00
YR - 2015
ED - 20150820
RD - 20161122
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26123020
<198. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25127260
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Chodakiewitz Y
AU - Brown S
AU - Boxerman JL
AU - Brody JM
AU - Rogg JM
FA - Chodakiewitz, Yosef
FA - Brown, Sanford
FA - Boxerman, Jerrold L
FA - Brody, Jeffrey M
FA - Rogg, Jeffrey M
IN - Chodakiewitz, Yosef. Alpert Medical School, Brown University, 222 Richmond St, Providence 02903, USA.
IN - Brown, Sanford. Department of Diagnostic Imaging, Rhode Island Hospital, Alpert Medical School of Brown University, 593 Eddy Street, Providence 02903, USA.
IN - Boxerman, Jerrold L. Department of Diagnostic Imaging, Rhode Island Hospital, Alpert Medical School of Brown University, 593 Eddy Street, Providence 02903, USA.
IN - Brody, Jeffrey M. Department of Diagnostic Imaging, Rhode Island Hospital, Alpert Medical School of Brown University, 593 Eddy Street, Providence 02903, USA.
IN - Rogg, Jeffrey M. Department of Diagnostic Imaging, Rhode Island Hospital, Alpert Medical School of Brown University, 593 Eddy Street, Providence 02903, USA. Electronic address: jrogg@lifespan.org.
TI - Ipilimumab treatment associated pituitary hypophysitis: clinical presentation and imaging diagnosis. [Review]
SO - Clinical Neurology & Neurosurgery. 125:125-30, 2014 Oct
AS - Clin Neurol Neurosurg. 125:125-30, 2014 Oct
NJ - Clinical neurology and neurosurgery
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - df4, 7502039
IO - Clin Neurol Neurosurg
SB - Index Medicus
CP - Netherlands
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Diagnostic Imaging
MH - Humans
MH - Hypopituitarism/di [Diagnosis]
MH - *Hypopituitarism/dt [Drug Therapy]
MH - Magnetic Resonance Imaging/mt [Methods]
MH - Melanoma/di [Diagnosis]
MH - *Melanoma/dt [Drug Therapy]
MH - *Pituitary Gland/pa [Pathology]
KW - Autoimmune lymphocytic hypophysitis; Ipilimumab; MRI; Melanoma; Pituitary
AB - Ipilimumab is an immunomodulating drug for use in treatment of unresectable or metastatic melanoma with autoimmune lymphocytic hypophysitis as a reported complication. We describe three recent cases of ipilimumab associated autoimmune hypophysitis (IAH) at our institution, and provide a selected literature review showing its variable clinical presentation, imaging appearance and treatment in order to expedite early and appropriate IAH management. Patients had variable clinical presentation of hypophysitis, including headache, fatigue, visual changes, endocrinopathy, and/or hyponatremia. Contrast enhanced MRI showed symmetric pituitary gland and stalk enlargement in all of our cases and received a presumptive diagnosis of IAH. Following cessation of therapy and treatment there was normalization of pituitary morphology at follow-up MRI and return to clinical baseline. Varying clinical presentation can complicate the diagnosis of lymphocytic hypophysitis. One must be cognizant of its overall clinical and radiologic picture in patients receiving ipilimumab, now commonly used for the treatment of metastatic melanoma.
AB - Copyright © 2014 Elsevier B.V. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 6T8C155666 (ipilimumab)
ES - 1872-6968
IL - 0303-8467
DI - S0303-8467(14)00215-7
DO - https://dx.doi.org/10.1016/j.clineuro.2014.06.011
PT - Journal Article
PT - Review
ID - 25127260 [pubmed]
ID - S0303-8467(14)00215-7 [pii]
ID - 10.1016/j.clineuro.2014.06.011 [doi]
PP - ppublish
PH - 2014/03/19 [received]
PH - 2014/06/05 [revised]
PH - 2014/06/08 [accepted]
LG - English
EP - 20140729
DP - 2014 Oct
DC - 20140920
EZ - 2014/08/16 06:00
DA - 2015/08/20 06:00
DT - 2014/08/16 06:00
YR - 2014
ED - 20150819
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25127260
<199. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25415283
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Soares KC
AU - Rucki AA
AU - Wu AA
AU - Olino K
AU - Xiao Q
AU - Chai Y
AU - Wamwea A
AU - Bigelow E
AU - Lutz E
AU - Liu L
AU - Yao S
AU - Anders RA
AU - Laheru D
AU - Wolfgang CL
AU - Edil BH
AU - Schulick RD
AU - Jaffee EM
AU - Zheng L
FA - Soares, Kevin C
FA - Rucki, Agnieszka A
FA - Wu, Annie A
FA - Olino, Kelly
FA - Xiao, Qian
FA - Chai, Yi
FA - Wamwea, Anthony
FA - Bigelow, Elaine
FA - Lutz, Eric
FA - Liu, Linda
FA - Yao, Sheng
FA - Anders, Robert A
FA - Laheru, Daniel
FA - Wolfgang, Christopher L
FA - Edil, Barish H
FA - Schulick, Richard D
FA - Jaffee, Elizabeth M
FA - Zheng, Lei
IN - Soares, Kevin C. Departments of *Oncology #Pathology +Surgery ++The Sidney Kimmel Cancer Center The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD PAmplimmune Inc., Gaithersburg, MD **Department of Surgery, University of Colorado School of Medicine, Aurora, CO.
TI - PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors.
SO - Journal of Immunotherapy. 38(1):1-11, 2015 Jan
AS - J Immunother. 38(1):1-11, 2015 Jan
NJ - Journal of immunotherapy (Hagerstown, Md. : 1997)
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - cuq, 9706083
IO - J. Immunother.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4258151
OI - Source: NLM. NIHMS636576
SB - Index Medicus
CP - United States
MH - Animals
MH - *Antigens, CD274/ai [Antagonists & Inhibitors]
MH - *Cancer Vaccines/im [Immunology]
MH - *Carcinoma, Pancreatic Ductal/im [Immunology]
MH - Enzyme-Linked Immunosorbent Assay
MH - Female
MH - Flow Cytometry
MH - Humans
MH - Immunohistochemistry
MH - Immunotherapy/mt [Methods]
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Mice
MH - Mice, Inbred C57BL
MH - *Pancreatic Neoplasms/im [Immunology]
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
AB - Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis due to late detection and resistance to conventional therapies. Published studies show that the PDA tumor microenvironment is predominantly infiltrated with immune suppressive cells and signals that if altered, would allow effective immunotherapy. However, single-agent checkpoint inhibitors including agents that alter immune suppressive signals in other human cancers such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand PD-L1, have failed to demonstrate objective responses when given as single agents to PDA patients. We recently reported that inhibition of the CTLA-4 pathway when given together with a T cell inducing vaccine gives objective responses in metastatic PDA patients. In this study, we evaluated blockade of the PD-1/PD-L1 pathway. We found that PD-L1 is weakly expressed at a low frequency in untreated human and murine PDAs but treatment with a granulocyte macrophage colony-stimulating factor secreting PDA vaccine (GVAX) significantly upregulates PD-L1 membranous expression after treatment of tumor-bearing mice. In addition, combination therapy with vaccine and PD-1 antibody blockade improved murine survival compared with PD-1 antibody monotherapy or GVAX therapy alone. Furthermore, PD-1 blockade increased effector CD8 T lymphocytes and tumor-specific interferon-gamma production of CD8 T cells in the tumor microenvironment. Immunosuppressive pathways, including regulatory T cells and CTLA-4 expression on T cells were overcome by the addition of vaccine and low-dose cyclophosphamide to PD-1 blockade. Collectively, our study supports combining PD-1 or PD-L1 antibody therapy with a T cell inducing agent for PDA treatment.
RN - 0 (Antigens, CD274)
RN - 0 (Cancer Vaccines)
RN - 0 (GVAX vaccine)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1537-4513
IL - 1524-9557
DO - https://dx.doi.org/10.1097/CJI.0000000000000062
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 25415283 [pubmed]
ID - 10.1097/CJI.0000000000000062 [doi]
ID - PMC4258151 [pmc]
ID - NIHMS636576 [mid]
PP - ppublish
GI - No: T32 GM007309
Organization: (GM) *NIGMS NIH HHS*
Country: United States
No: P50 CA062924
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA006973
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA148964
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA148964-01
Organization: (CA) *NCI NIH HHS*
Country: United States
No: T32 DK 7713-18
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: T32 DK007713
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: T32 GM008752
Organization: (GM) *NIGMS NIH HHS*
Country: United States
LG - English
DP - 2015 Jan
DC - 20141206
EZ - 2014/11/22 06:00
DA - 2015/08/01 06:00
DT - 2014/11/22 06:00
YR - 2015
ED - 20150731
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25415283
<200. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25415283
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Soares KC
AU - Rucki AA
AU - Wu AA
AU - Olino K
AU - Xiao Q
AU - Chai Y
AU - Wamwea A
AU - Bigelow E
AU - Lutz E
AU - Liu L
AU - Yao S
AU - Anders RA
AU - Laheru D
AU - Wolfgang CL
AU - Edil BH
AU - Schulick RD
AU - Jaffee EM
AU - Zheng L
FA - Soares, Kevin C
FA - Rucki, Agnieszka A
FA - Wu, Annie A
FA - Olino, Kelly
FA - Xiao, Qian
FA - Chai, Yi
FA - Wamwea, Anthony
FA - Bigelow, Elaine
FA - Lutz, Eric
FA - Liu, Linda
FA - Yao, Sheng
FA - Anders, Robert A
FA - Laheru, Daniel
FA - Wolfgang, Christopher L
FA - Edil, Barish H
FA - Schulick, Richard D
FA - Jaffee, Elizabeth M
FA - Zheng, Lei
IN - Soares, Kevin C. Departments of *Oncology #Pathology +Surgery ++The Sidney Kimmel Cancer Center The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD PAmplimmune Inc., Gaithersburg, MD **Department of Surgery, University of Colorado School of Medicine, Aurora, CO.
TI - PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors.
SO - Journal of Immunotherapy. 38(1):1-11, 2015 Jan
AS - J Immunother. 38(1):1-11, 2015 Jan
NJ - Journal of immunotherapy (Hagerstown, Md. : 1997)
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - cuq, 9706083
IO - J. Immunother.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4258151
OI - Source: NLM. NIHMS636576
SB - Index Medicus
CP - United States
MH - Animals
MH - *Antigens, CD274/ai [Antagonists & Inhibitors]
MH - *Cancer Vaccines/im [Immunology]
MH - *Carcinoma, Pancreatic Ductal/im [Immunology]
MH - Enzyme-Linked Immunosorbent Assay
MH - Female
MH - Flow Cytometry
MH - Humans
MH - Immunohistochemistry
MH - Immunotherapy/mt [Methods]
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Mice
MH - Mice, Inbred C57BL
MH - *Pancreatic Neoplasms/im [Immunology]
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
AB - Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis due to late detection and resistance to conventional therapies. Published studies show that the PDA tumor microenvironment is predominantly infiltrated with immune suppressive cells and signals that if altered, would allow effective immunotherapy. However, single-agent checkpoint inhibitors including agents that alter immune suppressive signals in other human cancers such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand PD-L1, have failed to demonstrate objective responses when given as single agents to PDA patients. We recently reported that inhibition of the CTLA-4 pathway when given together with a T cell inducing vaccine gives objective responses in metastatic PDA patients. In this study, we evaluated blockade of the PD-1/PD-L1 pathway. We found that PD-L1 is weakly expressed at a low frequency in untreated human and murine PDAs but treatment with a granulocyte macrophage colony-stimulating factor secreting PDA vaccine (GVAX) significantly upregulates PD-L1 membranous expression after treatment of tumor-bearing mice. In addition, combination therapy with vaccine and PD-1 antibody blockade improved murine survival compared with PD-1 antibody monotherapy or GVAX therapy alone. Furthermore, PD-1 blockade increased effector CD8 T lymphocytes and tumor-specific interferon-gamma production of CD8 T cells in the tumor microenvironment. Immunosuppressive pathways, including regulatory T cells and CTLA-4 expression on T cells were overcome by the addition of vaccine and low-dose cyclophosphamide to PD-1 blockade. Collectively, our study supports combining PD-1 or PD-L1 antibody therapy with a T cell inducing agent for PDA treatment.
RN - 0 (Antigens, CD274)
RN - 0 (Cancer Vaccines)
RN - 0 (GVAX vaccine)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1537-4513
IL - 1524-9557
DO - https://dx.doi.org/10.1097/CJI.0000000000000062
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 10.1097/CJI.0000000000000062 [doi]
ID - PMC4258151 [pmc]
ID - NIHMS636576 [mid]
PP - ppublish
GI - No: T32 GM007309
Organization: (GM) *NIGMS NIH HHS*
Country: United States
No: P50 CA062924
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA006973
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA148964
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA148964-01
Organization: (CA) *NCI NIH HHS*
Country: United States
No: T32 DK 7713-18
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: T32 DK007713
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: T32 GM008752
Organization: (GM) *NIGMS NIH HHS*
Country: United States
No: R01 CA169702
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2015 Jan
DC - 20141206
EZ - 2014/11/22 06:00
DA - 2015/08/01 06:00
DT - 2014/11/22 06:00
YR - 2015
ED - 20150731
RD - 20170408
UP - 20170410
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=25415283
<201. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24942756
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Lutz ER
AU - Wu AA
AU - Bigelow E
AU - Sharma R
AU - Mo G
AU - Soares K
AU - Solt S
AU - Dorman A
AU - Wamwea A
AU - Yager A
AU - Laheru D
AU - Wolfgang CL
AU - Wang J
AU - Hruban RH
AU - Anders RA
AU - Jaffee EM
AU - Zheng L
FA - Lutz, Eric R
FA - Wu, Annie A
FA - Bigelow, Elaine
FA - Sharma, Rajni
FA - Mo, Guanglan
FA - Soares, Kevin
FA - Solt, Sara
FA - Dorman, Alvin
FA - Wamwea, Anthony
FA - Yager, Allison
FA - Laheru, Daniel
FA - Wolfgang, Christopher L
FA - Wang, Jiang
FA - Hruban, Ralph H
FA - Anders, Robert A
FA - Jaffee, Elizabeth M
FA - Zheng, Lei
IN - Lutz, Eric R. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
IN - Wu, Annie A. Authors' Affiliations: Departments of Oncology, Surgery; The Sidney Kimmel Cancer Center;
IN - Bigelow, Elaine. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center;
IN - Sharma, Rajni. Pathology, and.
IN - Mo, Guanglan. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
IN - Soares, Kevin. Authors' Affiliations: Departments of Oncology, Surgery; The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
IN - Solt, Sara. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
IN - Dorman, Alvin. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
IN - Wamwea, Anthony. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
IN - Yager, Allison. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center;
IN - Laheru, Daniel. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
IN - Wolfgang, Christopher L. Authors' Affiliations: Departments of Oncology, Surgery; The Sidney Kimmel Cancer Center; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
IN - Wang, Jiang. Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
IN - Hruban, Ralph H. Authors' Affiliations: Departments of Oncology, Pathology, and The Sidney Kimmel Cancer Center; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
IN - Anders, Robert A. Authors' Affiliations: Departments of Oncology, Pathology, and The Sidney Kimmel Cancer Center; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
IN - Jaffee, Elizabeth M. Authors' Affiliations: Departments of Oncology, Pathology, and The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and lzheng6@jhmi.edu ejaffee@jhmi.edu.
IN - Zheng, Lei. Authors' Affiliations: Departments of Oncology, Surgery; The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and lzheng6@jhmi.edu ejaffee@jhmi.edu.
TI - Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation.
SO - Cancer Immunology Research. 2(7):616-31, 2014 Jul
AS - Cancer Immunol Res. 2(7):616-31, 2014 Jul
NJ - Cancer immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101614637
IO - Cancer Immunol Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082460
OI - Source: NLM. NIHMS589592
SB - Index Medicus
CP - United States
MH - Adenocarcinoma/ge [Genetics]
MH - Adenocarcinoma/im [Immunology]
MH - *Adenocarcinoma/th [Therapy]
MH - Antineoplastic Agents, Alkylating/ad [Administration & Dosage]
MH - Antineoplastic Agents, Alkylating/tu [Therapeutic Use]
MH - *Cancer Vaccines/tu [Therapeutic Use]
MH - Cell Aggregation/im [Immunology]
MH - Chemotherapy, Adjuvant
MH - Cyclophosphamide/ad [Administration & Dosage]
MH - Cyclophosphamide/tu [Therapeutic Use]
MH - Drug Administration Schedule
MH - Gene Expression Profiling/mt [Methods]
MH - Gene Expression Regulation, Neoplastic/im [Immunology]
MH - Humans
MH - Interferon-gamma/bi [Biosynthesis]
MH - Lymphocyte Activation/im [Immunology]
MH - Lymphocytes, Tumor-Infiltrating/de [Drug Effects]
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - Pancreatic Neoplasms/im [Immunology]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - T-Lymphocytes, Regulatory/im [Immunology]
MH - Up-Regulation/im [Immunology]
AB - Pancreatic ductal adenocarcinoma (PDAC) is considered a "nonimmunogenic" neoplasm. Single-agent immunotherapies have failed to demonstrate significant clinical activity in PDAC and other "nonimmunogenic" tumors, in part due to a complex tumor microenvironment (TME) that provides a formidable barrier to immune infiltration and function. We designed a neoadjuvant and adjuvant clinical trial comparing an irradiated, granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting, allogeneic PDAC vaccine (GVAX) given as a single agent or in combination with low-dose cyclophosphamide to deplete regulatory T cells (Treg) as a means to study how the TME is altered by immunotherapy. Examination of resected PDACs revealed the formation of vaccine-induced intratumoral tertiary lymphoid aggregates in 33 of 39 patients 2 weeks after vaccine treatment. Immunohistochemical analysis showed these aggregates to be regulatory structures of adaptive immunity. Microarray analysis of microdissected aggregates identified gene-expression signatures in five signaling pathways involved in regulating immune-cell activation and trafficking that were associated with improved postvaccination responses. A suppressed Treg pathway and an enhanced Th17 pathway within these aggregates were associated with improved survival, enhanced postvaccination mesothelin-specific T-cell responses, and increased intratumoral Teff:Treg ratios. This study provides the first example of immune-based therapy converting a "nonimmunogenic" neoplasm into an "immunogenic" neoplasm by inducing infiltration of T cells and development of tertiary lymphoid structures in the TME. Post-GVAX T-cell infiltration and aggregate formation resulted in the upregulation of immunosuppressive regulatory mechanisms, including the PD-1-PD-L1 pathway, suggesting that patients with vaccine-primed PDAC may be better candidates than vaccine-naive patients for immune checkpoint and other immunomodulatory therapies.
AB - Copyright ©2014 American Association for Cancer Research.
RN - 0 (Antineoplastic Agents, Alkylating)
RN - 0 (Cancer Vaccines)
RN - 0 (GVAX vaccine)
RN - 82115-62-6 (Interferon-gamma)
RN - 8N3DW7272P (Cyclophosphamide)
RS - Pancreatic Carcinoma
ES - 2326-6074
IL - 2326-6066
DI - 2326-6066.CIR-14-0027
DO - https://dx.doi.org/10.1158/2326-6066.CIR-14-0027
PT - Journal Article
PT - Randomized Controlled Trial
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 24942756 [pubmed]
ID - 2326-6066.CIR-14-0027 [pii]
ID - 10.1158/2326-6066.CIR-14-0027 [doi]
ID - PMC4082460 [pmc]
ID - NIHMS589592 [mid]
PP - ppublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00727441
SL - https://clinicaltrials.gov/search/term=NCT00727441
GI - No: K23 CA148964
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA058236
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA062924
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA148964-01
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20140618
DP - 2014 Jul
DC - 20140703
EZ - 2014/06/20 06:00
DA - 2015/07/24 06:00
DT - 2014/06/20 06:00
YR - 2014
ED - 20150723
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24942756
<202. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24554495
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Marlier J
AU - Cocquyt V
AU - Brochez L
AU - Van Belle S
AU - Kruse V
FA - Marlier, Joke
FA - Cocquyt, Veronique
FA - Brochez, Lieve
FA - Van Belle, Simon
FA - Kruse, Vibeke
IN - Marlier, Joke. Department of Medical Oncology, University Hospital Ghent, De Pintelaan 185, 9000, Ghent, Belgium, Joke.Marlier@ugent.be.
TI - Ipilimumab, not just another anti-cancer therapy: hypophysitis as side effect illustrated by four case-reports.
SO - Endocrine. 47(3):878-83, 2014 Dec
AS - Endocrine. 47(3):878-83, 2014 Dec
NJ - Endocrine
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9434444, CV9
IO - Endocrine
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Female
MH - Humans
MH - *Hypopituitarism/ci [Chemically Induced]
MH - Male
MH - Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - Retrospective Studies
AB - Ipilimumab is a monoclonal antibody that blocks cytotoxic T-lymphocyte antigen4 (CTLA-4), an inhibitory molecule typically expressed on T cells. Blockade of CTLA-4 induces an overall activation of T cells, including an immune-mediated anti-tumour response. Unfortunately, this broad T cell stimulation also causes immune-related adverse events (irAEs), such as dermatitis, colitis, hepatitis and hypophysitis. Ipilimumab is currently available in Belgium as a second line of treatment for patients with advanced melanoma, and is used at a dose of 3 mg/kg of body weight, although higher doses were previously used (up to 10 mg/kg). We performed a retrospective analysis to identify melanoma patients treated with ipilimumab at the Ghent University Hospital between 2010 and 2013. Data on symptoms, stage and timing of ipilimumab, response and adverse events were collected with a special attention to endocrine disturbances, going from a limited involvement of one endocrine axis to development of a hypophysitis. We identified a total of 39 patients with stage III (No. = 7) or stage IV (No. = 32) melanoma, who received a dose of 3 (No. = 31) or 10 (No. = 8) mg/kg. Six patients developed a severe form of irAEs, including one case of colitis (2 %), one case of sarcoidosis (2 %) and 4 cases (10 %) of hypophysitis. Hypophysitis developed between the second and fourth cycle of ipilimumab administration and was independent of the dose used. We describe four cases of involvement of the pituitary gland during treatment with ipilimumab. When managed with vigilant monitoring and high-dose corticosteroids, the acute symptoms resolve, but lifelong hormone substitution therapy can be necessary. Involvement of the pituitary axes is a severe side effect of treatment with ipilimumab with an urgent need for the correct medical intervention.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
ES - 1559-0100
IL - 1355-008X
DO - https://dx.doi.org/10.1007/s12020-014-0199-9
PT - Case Reports
PT - Journal Article
ID - 24554495 [pubmed]
ID - 10.1007/s12020-014-0199-9 [doi]
PP - ppublish
PH - 2013/09/16 [received]
PH - 2014/01/31 [accepted]
LG - English
EP - 20140221
DP - 2014 Dec
DC - 20141121
EZ - 2014/02/21 06:00
DA - 2015/07/24 06:00
DT - 2014/02/21 06:00
YR - 2014
ED - 20150723
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24554495
<203. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24942756
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Lutz ER
AU - Wu AA
AU - Bigelow E
AU - Sharma R
AU - Mo G
AU - Soares K
AU - Solt S
AU - Dorman A
AU - Wamwea A
AU - Yager A
AU - Laheru D
AU - Wolfgang CL
AU - Wang J
AU - Hruban RH
AU - Anders RA
AU - Jaffee EM
AU - Zheng L
FA - Lutz, Eric R
FA - Wu, Annie A
FA - Bigelow, Elaine
FA - Sharma, Rajni
FA - Mo, Guanglan
FA - Soares, Kevin
FA - Solt, Sara
FA - Dorman, Alvin
FA - Wamwea, Anthony
FA - Yager, Allison
FA - Laheru, Daniel
FA - Wolfgang, Christopher L
FA - Wang, Jiang
FA - Hruban, Ralph H
FA - Anders, Robert A
FA - Jaffee, Elizabeth M
FA - Zheng, Lei
IN - Lutz, Eric R. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
IN - Wu, Annie A. Authors' Affiliations: Departments of Oncology, Surgery; The Sidney Kimmel Cancer Center;
IN - Bigelow, Elaine. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center;
IN - Sharma, Rajni. Pathology, and.
IN - Mo, Guanglan. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
IN - Soares, Kevin. Authors' Affiliations: Departments of Oncology, Surgery; The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
IN - Solt, Sara. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
IN - Dorman, Alvin. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
IN - Wamwea, Anthony. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
IN - Yager, Allison. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center;
IN - Laheru, Daniel. Authors' Affiliations: Departments of Oncology, The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care;
IN - Wolfgang, Christopher L. Authors' Affiliations: Departments of Oncology, Surgery; The Sidney Kimmel Cancer Center; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
IN - Wang, Jiang. Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
IN - Hruban, Ralph H. Authors' Affiliations: Departments of Oncology, Pathology, and The Sidney Kimmel Cancer Center; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
IN - Anders, Robert A. Authors' Affiliations: Departments of Oncology, Pathology, and The Sidney Kimmel Cancer Center; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and.
IN - Jaffee, Elizabeth M. Authors' Affiliations: Departments of Oncology, Pathology, and The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and lzheng6@jhmi.edu ejaffee@jhmi.edu.
IN - Zheng, Lei. Authors' Affiliations: Departments of Oncology, Surgery; The Sidney Kimmel Cancer Center; The Skip Viragh Center for Pancreatic Cancer Research and Clinical Care; The Sol Goldman Pancreatic Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; and lzheng6@jhmi.edu ejaffee@jhmi.edu.
TI - Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation.
SO - Cancer Immunology Research. 2(7):616-31, 2014 Jul
AS - Cancer Immunol Res. 2(7):616-31, 2014 Jul
NJ - Cancer immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101614637
IO - Cancer Immunol Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082460
OI - Source: NLM. NIHMS589592
SB - Index Medicus
CP - United States
MH - Adenocarcinoma/ge [Genetics]
MH - Adenocarcinoma/im [Immunology]
MH - *Adenocarcinoma/th [Therapy]
MH - Antineoplastic Agents, Alkylating/ad [Administration & Dosage]
MH - Antineoplastic Agents, Alkylating/tu [Therapeutic Use]
MH - *Cancer Vaccines/tu [Therapeutic Use]
MH - Cell Aggregation/im [Immunology]
MH - Chemotherapy, Adjuvant
MH - Cyclophosphamide/ad [Administration & Dosage]
MH - Cyclophosphamide/tu [Therapeutic Use]
MH - Drug Administration Schedule
MH - Gene Expression Profiling/mt [Methods]
MH - Gene Expression Regulation, Neoplastic/im [Immunology]
MH - Humans
MH - Interferon-gamma/bi [Biosynthesis]
MH - Lymphocyte Activation/im [Immunology]
MH - Lymphocytes, Tumor-Infiltrating/de [Drug Effects]
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - Pancreatic Neoplasms/im [Immunology]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - T-Lymphocytes, Regulatory/im [Immunology]
MH - Up-Regulation/im [Immunology]
AB - Pancreatic ductal adenocarcinoma (PDAC) is considered a "nonimmunogenic" neoplasm. Single-agent immunotherapies have failed to demonstrate significant clinical activity in PDAC and other "nonimmunogenic" tumors, in part due to a complex tumor microenvironment (TME) that provides a formidable barrier to immune infiltration and function. We designed a neoadjuvant and adjuvant clinical trial comparing an irradiated, granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting, allogeneic PDAC vaccine (GVAX) given as a single agent or in combination with low-dose cyclophosphamide to deplete regulatory T cells (Treg) as a means to study how the TME is altered by immunotherapy. Examination of resected PDACs revealed the formation of vaccine-induced intratumoral tertiary lymphoid aggregates in 33 of 39 patients 2 weeks after vaccine treatment. Immunohistochemical analysis showed these aggregates to be regulatory structures of adaptive immunity. Microarray analysis of microdissected aggregates identified gene-expression signatures in five signaling pathways involved in regulating immune-cell activation and trafficking that were associated with improved postvaccination responses. A suppressed Treg pathway and an enhanced Th17 pathway within these aggregates were associated with improved survival, enhanced postvaccination mesothelin-specific T-cell responses, and increased intratumoral Teff:Treg ratios. This study provides the first example of immune-based therapy converting a "nonimmunogenic" neoplasm into an "immunogenic" neoplasm by inducing infiltration of T cells and development of tertiary lymphoid structures in the TME. Post-GVAX T-cell infiltration and aggregate formation resulted in the upregulation of immunosuppressive regulatory mechanisms, including the PD-1-PD-L1 pathway, suggesting that patients with vaccine-primed PDAC may be better candidates than vaccine-naive patients for immune checkpoint and other immunomodulatory therapies.
AB - Copyright ©2014 American Association for Cancer Research.
RN - 0 (Antineoplastic Agents, Alkylating)
RN - 0 (Cancer Vaccines)
RN - 0 (GVAX vaccine)
RN - 82115-62-6 (Interferon-gamma)
RN - 8N3DW7272P (Cyclophosphamide)
RS - Pancreatic Carcinoma
ES - 2326-6074
IL - 2326-6066
DI - 2326-6066.CIR-14-0027
DO - https://dx.doi.org/10.1158/2326-6066.CIR-14-0027
PT - Journal Article
PT - Randomized Controlled Trial
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 2326-6066.CIR-14-0027 [pii]
ID - 10.1158/2326-6066.CIR-14-0027 [doi]
ID - PMC4082460 [pmc]
ID - NIHMS589592 [mid]
PP - ppublish
GI - No: P50 CA058236
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA062924
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA148964
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA148964-01
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA169702
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20140618
DP - 2014 Jul
DC - 20140703
EZ - 2014/06/20 06:00
DA - 2015/07/24 06:00
DT - 2014/06/20 06:00
YR - 2014
ED - 20150723
RD - 20170408
UP - 20170410
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=24942756
<204. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25712539
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Twa DD
AU - Mottok A
AU - Chan FC
AU - Ben-Neriah S
AU - Woolcock BW
AU - Tan KL
AU - Mungall AJ
AU - McDonald H
AU - Zhao Y
AU - Lim RS
AU - Nelson BH
AU - Milne K
AU - Shah SP
AU - Morin RD
AU - Marra MA
AU - Scott DW
AU - Gascoyne RD
AU - Steidl C
FA - Twa, David D W
FA - Mottok, Anja
FA - Chan, Fong Chun
FA - Ben-Neriah, Susana
FA - Woolcock, Bruce W
FA - Tan, King L
FA - Mungall, Andrew J
FA - McDonald, Helen
FA - Zhao, Yongjun
FA - Lim, Raymond S
FA - Nelson, Brad H
FA - Milne, Katy
FA - Shah, Sohrab P
FA - Morin, Ryan D
FA - Marra, Marco A
FA - Scott, David W
FA - Gascoyne, Randy D
FA - Steidl, Christian
IN - Twa, David D W. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Twa, David D W. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
IN - Mottok, Anja. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Mottok, Anja. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
IN - Chan, Fong Chun. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Chan, Fong Chun. Bioinformatics Training Programme, University of British Columbia, Vancouver, BC, Canada.
IN - Ben-Neriah, Susana. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Woolcock, Bruce W. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Tan, King L. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Mungall, Andrew J. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Mungall, Andrew J. Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
IN - McDonald, Helen. Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
IN - Zhao, Yongjun. Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
IN - Lim, Raymond S. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Nelson, Brad H. Deeley Research Centre, BC Cancer Agency, Victoria, BC, Canada.
IN - Nelson, Brad H. Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
IN - Milne, Katy. Deeley Research Centre, BC Cancer Agency, Victoria, BC, Canada.
IN - Shah, Sohrab P. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Shah, Sohrab P. Bioinformatics Training Programme, University of British Columbia, Vancouver, BC, Canada.
IN - Morin, Ryan D. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Morin, Ryan D. Department of Molecular Biology and Biochemistry, Simon Fraser University, Vancouver, BC, Canada.
IN - Marra, Marco A. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Marra, Marco A. Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
IN - Scott, David W. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Gascoyne, Randy D. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Gascoyne, Randy D. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
IN - Steidl, Christian. Department of Lymphoid Cancer Research, BC Cancer Agency, Vancouver, BC, Canada.
IN - Steidl, Christian. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
TI - Recurrent genomic rearrangements in primary testicular lymphoma.
SO - Journal of Pathology. 236(2):136-41, 2015 Jun
AS - J Pathol. 236(2):136-41, 2015 Jun
NJ - The Journal of pathology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - jlb, 0204634
IO - J. Pathol.
SB - Index Medicus
CP - England
MH - *Antigens, CD274/ge [Genetics]
MH - Chromosome Breakpoints
MH - Chromosomes, Artificial, Bacterial
MH - *Forkhead Transcription Factors/ge [Genetics]
MH - Gene Deletion
MH - *Gene Rearrangement, B-Lymphocyte/ge [Genetics]
MH - Humans
MH - Immunohistochemistry
MH - In Situ Hybridization, Fluorescence
MH - *Lymphoma, Large B-Cell, Diffuse/ge [Genetics]
MH - Male
MH - Nuclear Proteins/ge [Genetics]
MH - *Programmed Cell Death 1 Ligand 2 Protein/ge [Genetics]
MH - Recurrence
MH - *Repressor Proteins/ge [Genetics]
MH - *Testicular Neoplasms/ge [Genetics]
MH - Trans-Activators/ge [Genetics]
MH - Translocation, Genetic/ge [Genetics]
KW - CD274; CIITA; FOXP1; PDCD1LG2; capture sequencing; fluorescence in situ hybridization (FISH); genomic rearrangements; primary testicular lymphoma (PTL); programmed death ligands
AB - Primary testicular diffuse large B cell lymphoma (PTL) is an aggressive malignancy that occurs in the immune-privileged anatomical site of the testis. We have previously shown that structural genomic rearrangements involving the MHC class II transactivator CIITA and programmed death ligands (PDLs) 1 and 2 are frequent across multiple B cell lymphoma entities. Specifically in PTL, we found rearrangements in the PDL locus by fluorescence in situ hybridization (FISH). However, breakpoint anatomy and rearrangement partners were undetermined, while CIITA rearrangements had not been reported previously in PTL. Here, we performed bacterial artificial chromosome capture sequencing on three archival, formalin-fixed, paraffin-embedded tissue biopsies, interrogating 20 known rearrangement hotspots in B cell lymphomas. We report novel CIITA, FOXP1 and PDL rearrangements involving IGHG4, FLJ45248, RFX3, SMARCA2 and SNX29. Moreover, we present immunohistochemistry data supporting the association between PDL rearrangements and increased protein expression. Finally, using FISH, we show that CIITA (8/82; 10%) and FOXP1 (5/74; 7%) rearrangements are recurrent in PTL. In summary, we describe rearrangement frequencies and novel rearrangement partners of the CIITA, FOXP1 and PDL loci at base-pair resolution in a rare, aggressive lymphoma. Our data suggest immune-checkpoint inhibitor therapy as a promising intervention for PTL patients harbouring PDL rearrangements.
AB - Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
RN - 0 (Antigens, CD274)
RN - 0 (CD274 protein, human)
RN - 0 (FOXP1 protein, human)
RN - 0 (Forkhead Transcription Factors)
RN - 0 (MHC class II transactivator protein)
RN - 0 (Nuclear Proteins)
RN - 0 (PDCD1LG2 protein, human)
RN - 0 (Programmed Cell Death 1 Ligand 2 Protein)
RN - 0 (Repressor Proteins)
RN - 0 (Trans-Activators)
ES - 1096-9896
IL - 0022-3417
DO - https://dx.doi.org/10.1002/path.4522
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 25712539 [pubmed]
ID - 10.1002/path.4522 [doi]
PP - ppublish
PH - 2014/12/15 [received]
PH - 2015/02/05 [revised]
PH - 2015/02/18 [accepted]
GI - Organization: *Canadian Institutes of Health Research*
Country: Canada
LG - English
EP - 20150326
DP - 2015 Jun
DC - 20150511
EZ - 2015/02/26 06:00
DA - 2015/07/21 06:00
DT - 2015/02/26 06:00
YR - 2015
ED - 20150720
RD - 20150511
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25712539
<205. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25840693
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Eggermont AM
AU - Chiarion-Sileni V
AU - Grob JJ
AU - Dummer R
AU - Wolchok JD
AU - Schmidt H
AU - Hamid O
AU - Robert C
AU - Ascierto PA
AU - Richards JM
AU - Lebbe C
AU - Ferraresi V
AU - Smylie M
AU - Weber JS
AU - Maio M
AU - Konto C
AU - Hoos A
AU - de Pril V
AU - Gurunath RK
AU - de Schaetzen G
AU - Suciu S
AU - Testori A
FA - Eggermont, Alexander M M
FA - Chiarion-Sileni, Vanna
FA - Grob, Jean-Jacques
FA - Dummer, Reinhard
FA - Wolchok, Jedd D
FA - Schmidt, Henrik
FA - Hamid, Omid
FA - Robert, Caroline
FA - Ascierto, Paolo A
FA - Richards, Jon M
FA - Lebbe, Celeste
FA - Ferraresi, Virginia
FA - Smylie, Michael
FA - Weber, Jeffrey S
FA - Maio, Michele
FA - Konto, Cyril
FA - Hoos, Axel
FA - de Pril, Veerle
FA - Gurunath, Ravichandra Karra
FA - de Schaetzen, Gaetan
FA - Suciu, Stefan
FA - Testori, Alessandro
IN - Eggermont, Alexander M M. Gustave Roussy Cancer Campus Grand Paris, Villejuif, France. Electronic address: alexander.eggermont@gustaveroussy.fr.
IN - Chiarion-Sileni, Vanna. IOV-IRCCS, Melanoma Oncology Unit, Padova, Italy.
IN - Grob, Jean-Jacques. Aix-Marseille University, Hopital de La Timone APHM, Marseille, France.
IN - Dummer, Reinhard. University of Zurich Hospital, Zurich, Switzerland.
IN - Wolchok, Jedd D. Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
IN - Schmidt, Henrik. Aarhus University Hospital, Aarhus, Denmark.
IN - Hamid, Omid. The Angeles Clinic and Research Institute, Los Angeles, CA, USA.
IN - Robert, Caroline. Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.
IN - Ascierto, Paolo A. Istituto Nazionale Tumori Fondazione G Pascale, Naples, Italy.
IN - Richards, Jon M. Oncology Specialists SC, Park Ridge, IL, USA.
IN - Lebbe, Celeste. Assistance Publique Hopitaux de Paris, Dermatology and CIC Departments, Hopital Saint Louis, University Paris 7, INSERM U976, France.
IN - Ferraresi, Virginia. Istituti Fisioterapici Ospitalieri, Rome, Italy.
IN - Smylie, Michael. Cross Cancer Institute, Edmonton, Alberta, Canada.
IN - Weber, Jeffrey S. H Lee Moffitt Cancer Center, Tampa, FL, USA.
IN - Maio, Michele. University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy.
IN - Konto, Cyril. Bristol-Myers Squibb, Wallingford, CT, USA.
IN - Hoos, Axel. Bristol-Myers Squibb, Wallingford, CT, USA.
IN - de Pril, Veerle. Bristol-Myers Squibb, Braine-l'Alleud, Belgium.
IN - Gurunath, Ravichandra Karra. EORTC Headquarters, Brussels, Belgium.
IN - de Schaetzen, Gaetan. EORTC Headquarters, Brussels, Belgium.
IN - Suciu, Stefan. EORTC Headquarters, Brussels, Belgium.
IN - Testori, Alessandro. European Institute of Oncology, Milan, Italy.
TI - Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial.[Erratum appears in Lancet Oncol. 2015 Jun;16(6):e262; PMID: 26065611]
CM - Comment in: Lancet Oncol. 2015 May;16(5):478-80; PMID: 25840692
SO - Lancet Oncology. 16(5):522-30, 2015 May
AS - Lancet Oncol. 16(5):522-30, 2015 May
NJ - The Lancet. Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 100957246
IO - Lancet Oncol.
SB - Index Medicus
CP - England
MH - *Adjuvants, Immunologic/ad [Administration & Dosage]
MH - Adult
MH - Aged
MH - *Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Combined Modality Therapy
MH - Disease-Free Survival
MH - Double-Blind Method
MH - Female
MH - Humans
MH - Lymphatic Metastasis
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/pa [Pathology]
MH - Melanoma/su [Surgery]
MH - Middle Aged
MH - *Neoplasm Recurrence, Local/dt [Drug Therapy]
MH - Neoplasm Recurrence, Local/pa [Pathology]
MH - Neoplasm Recurrence, Local/su [Surgery]
AB - BACKGROUND: Ipilimumab is an approved treatment for patients with advanced melanoma. We aimed to assess ipilimumab as adjuvant therapy for patients with completely resected stage III melanoma at high risk of recurrence.
AB - METHODS: We did a double-blind, phase 3 trial in patients with stage III cutaneous melanoma (excluding lymph node metastasis <=1 mm or in-transit metastasis) with adequate resection of lymph nodes (ie, the primary cutaneous melanoma must have been completely excised with adequate surgical margins) who had not received previous systemic therapy for melanoma from 91 hospitals located in 19 countries. Patients were randomly assigned (1:1), centrally by an interactive voice response system, to receive intravenous infusions of 10 mg/kg ipilimumab or placebo every 3 weeks for four doses, then every 3 months for up to 3 years. Using a minimisation technique, randomisation was stratified by disease stage and geographical region. The primary endpoint was recurrence-free survival, assessed by an independent review committee, and analysed by intention to treat. Enrollment is complete but the study is ongoing for follow-up for analysis of secondary endpoints. This trial is registered with EudraCT, number 2007-001974-10, and ClinicalTrials.gov, number NCT00636168.
AB - FINDINGS: Between July 10, 2008, and Aug 1, 2011, 951 patients were randomly assigned to ipilimumab (n=475) or placebo (n=476), all of whom were included in the intention-to-treat analyses. At a median follow-up of 2.74 years (IQR 2.28-3.22), there were 528 recurrence-free survival events (234 in the ipilimumab group vs 294 in the placebo group). Median recurrence-free survival was 26.1 months (95% CI 19.3-39.3) in the ipilimumab group versus 17.1 months (95% CI 13.4-21.6) in the placebo group (hazard ratio 0.75; 95% CI 0.64-0.90; p=0.0013); 3-year recurrence-free survival was 46.5% (95% CI 41.5-51.3) in the ipilimumab group versus 34.8% (30.1-39.5) in the placebo group. The most common grade 3-4 immune-related adverse events in the ipilimumab group were gastrointestinal (75 [16%] vs four [<1%] in the placebo group), hepatic (50 [11%] vs one [<1%]), and endocrine (40 [8%] vs none). Adverse events led to discontinuation of treatment in 245 (52%) of 471 patients who started ipilimumab (182 [39%] during the initial treatment period of four doses). Five patients (1%) died due to drug-related adverse events. Five (1%) participants died because of drug-related adverse events in the ipilimumab group; three patients died because of colitis (two with gastrointestinal perforation), one patient because of myocarditis, and one patient because of multiorgan failure with Guillain-Barre syndrome.
AB - INTERPRETATION: Adjuvant ipilimumab significantly improved recurrence-free survival for patients with completely resected high-risk stage III melanoma. The adverse event profile was consistent with that observed in advanced melanoma, but at higher incidences in particular for endocrinopathies. The risk-benefit ratio of adjuvant ipilimumab at this dose and schedule requires additional assessment based on distant metastasis-free survival and overall survival endpoints to define its definitive value.
AB - FUNDING: Bristol-Myers Squibb.
AB - Copyright © 2015 Elsevier Ltd. All rights reserved.
RN - 0 (Adjuvants, Immunologic)
RN - 0 (Antibodies, Monoclonal)
RN - 6T8C155666 (ipilimumab)
ES - 1474-5488
IL - 1470-2045
DI - S1470-2045(15)70122-1
DO - https://dx.doi.org/10.1016/S1470-2045(15)70122-1
PT - Clinical Trial, Phase III
PT - Journal Article
PT - Randomized Controlled Trial
PT - Research Support, Non-U.S. Gov't
ID - 25840693 [pubmed]
ID - S1470-2045(15)70122-1 [pii]
ID - 10.1016/S1470-2045(15)70122-1 [doi]
PP - ppublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00636168
SL - https://clinicaltrials.gov/search/term=NCT00636168
GI - No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20150331
DP - 2015 May
DC - 20150506
EZ - 2015/04/05 06:00
DA - 2015/07/15 06:00
DT - 2015/04/05 06:00
YR - 2015
ED - 20150714
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25840693
<206. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25765457
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Matsumoto K
AU - Onda T
AU - Yaegashi N
FA - Matsumoto, Koji
FA - Onda, Takashi
FA - Yaegashi, Nobuo
IN - Matsumoto, Koji. Division of Medical Oncology, Hyogo Cancer Center, Akashi kojmatsu@hp.pref.hyogo.jp.
IN - Onda, Takashi. Division of Gynecology and Obstetrics, Kitasato University, Sagamihara.
IN - Yaegashi, Nobuo. Division of Gynecology and Obstetrics, Tohoku University, Sendai, Japan.
TI - Pharmacotherapy for recurrent ovarian cancer: current status and future perspectives. [Review]
SO - Japanese Journal of Clinical Oncology. 45(5):408-10, 2015 May
AS - Jpn J Clin Oncol. 45(5):408-10, 2015 May
NJ - Japanese journal of clinical oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - kin, 0313225
IO - Jpn. J. Clin. Oncol.
SB - Index Medicus
CP - England
MH - Angiogenesis Inhibitors/pd [Pharmacology]
MH - Angiogenesis Inhibitors/tu [Therapeutic Use]
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal, Humanized/ad [Administration & Dosage]
MH - Antimetabolites, Antineoplastic/pd [Pharmacology]
MH - Antimetabolites, Antineoplastic/tu [Therapeutic Use]
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - Benzimidazoles/ad [Administration & Dosage]
MH - Carboplatin/ad [Administration & Dosage]
MH - Deoxycytidine/ad [Administration & Dosage]
MH - Deoxycytidine/aa [Analogs & Derivatives]
MH - Doxorubicin/ad [Administration & Dosage]
MH - Doxorubicin/aa [Analogs & Derivatives]
MH - Everolimus
MH - Female
MH - Folic Acid/ad [Administration & Dosage]
MH - Folic Acid/aa [Analogs & Derivatives]
MH - Humans
MH - *Neoplasm Recurrence, Local/dt [Drug Therapy]
MH - *Neoplasms, Glandular and Epithelial/dt [Drug Therapy]
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - Paclitaxel/ad [Administration & Dosage]
MH - Phthalazines/ad [Administration & Dosage]
MH - Piperazines/ad [Administration & Dosage]
MH - Poly(ADP-ribose) Polymerase Inhibitors
MH - Polyethylene Glycols/ad [Administration & Dosage]
MH - Pyrimidines/ad [Administration & Dosage]
MH - Quinazolines/ad [Administration & Dosage]
MH - Recombinant Fusion Proteins/ad [Administration & Dosage]
MH - Sirolimus/ad [Administration & Dosage]
MH - Sirolimus/aa [Analogs & Derivatives]
MH - Sulfonamides/ad [Administration & Dosage]
MH - TOR Serine-Threonine Kinases/ai [Antagonists & Inhibitors]
MH - Topotecan/ad [Administration & Dosage]
MH - Vinca Alkaloids/ad [Administration & Dosage]
KW - chemo-gynecology; gynecol-med; molecular Dx
AB - Several 'lines of therapy' that utilize cytotoxic agents and are driven by platinum-free intervals are the current standard of care for patients with recurrent ovarian cancer. For patients with platinum-resistant disease, single agent chemotherapy (pegylated liposomal doxorubicin, topotecan, gemcitabine or weekly paclitaxel) is the standard of care. For patients with platinum-sensitive disease, combination chemotherapy (carboplatin plus paclitaxel, pegylated liposomal doxorubicin or gemcitabine) is the standard of care. In addition, antiangiogenic therapy using bevacizumab is an established option. Future directions could include 'lines of therapy' with biologic agents driven by specific biologic targets. Data from antiangiogenic agents (trebananib, pazopanib and cediranib), antifolate drugs (farletuzumab and vintafolide), poly(ADP-ribose) polymerase inhibitors (olaparib and veliparib), mTOR inhibitors (everolimus and temsirolimus) and immune editing agents (nivolumab) have been summarized in this review.
AB - Copyright © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
RN - 0 (Angiogenesis Inhibitors)
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antimetabolites, Antineoplastic)
RN - 0 (Antineoplastic Agents)
RN - 0 (Benzimidazoles)
RN - 0 (EC145)
RN - 0 (Phthalazines)
RN - 0 (Piperazines)
RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN - 0 (Pyrimidines)
RN - 0 (Quinazolines)
RN - 0 (Recombinant Fusion Proteins)
RN - 0 (Sulfonamides)
RN - 0 (Vinca Alkaloids)
RN - 0 (farletuzumab)
RN - 0 (liposomal doxorubicin)
RN - 01O4K0631N (veliparib)
RN - 0W860991D6 (Deoxycytidine)
RN - 30IQX730WE (Polyethylene Glycols)
RN - 31YO63LBSN (nivolumab)
RN - 624KN6GM2T (temsirolimus)
RN - 7M7YKX2N15 (Topotecan)
RN - 7RN5DR86CK (pazopanib)
RN - 80168379AG (Doxorubicin)
RN - 935E97BOY8 (Folic Acid)
RN - 9HW64Q8G6G (Everolimus)
RN - B76N6SBZ8R (gemcitabine)
RN - BG3F62OND5 (Carboplatin)
RN - EC 2-7-1-1 (MTOR protein, human)
RN - EC 2-7-1-1 (TOR Serine-Threonine Kinases)
RN - NQU9IPY4K9 (cediranib)
RN - P88XT4IS4D (Paclitaxel)
RN - W36ZG6FT64 (Sirolimus)
RN - WOH1JD9AR8 (olaparib)
RN - X8Y5U6NC7E (trebananib)
RS - Ovarian epithelial cancer
ES - 1465-3621
IL - 0368-2811
DI - hyv014
DO - https://dx.doi.org/10.1093/jjco/hyv014
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 25765457 [pubmed]
ID - hyv014 [pii]
ID - 10.1093/jjco/hyv014 [doi]
PP - ppublish
PH - 2014/10/31 [received]
PH - 2015/01/05 [accepted]
LG - English
EP - 20150311
DP - 2015 May
DC - 20150429
EZ - 2015/03/14 06:00
DA - 2015/07/15 06:00
DT - 2015/03/15 06:00
YR - 2015
ED - 20150714
RD - 20151119
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25765457
<207. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25867264
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Abiko K
AU - Matsumura N
AU - Hamanishi J
AU - Horikawa N
AU - Murakami R
AU - Yamaguchi K
AU - Yoshioka Y
AU - Baba T
AU - Konishi I
AU - Mandai M
FA - Abiko, K
FA - Matsumura, N
FA - Hamanishi, J
FA - Horikawa, N
FA - Murakami, R
FA - Yamaguchi, K
FA - Yoshioka, Y
FA - Baba, T
FA - Konishi, I
FA - Mandai, M
IN - Abiko, K. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
IN - Matsumura, N. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
IN - Hamanishi, J. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
IN - Horikawa, N. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
IN - Murakami, R. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
IN - Yamaguchi, K. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
IN - Yoshioka, Y. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
IN - Baba, T. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
IN - Konishi, I. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
IN - Mandai, M. Department of Obstetrics and Gynecology, Faculty of Medicine, Kinki University, 377-2 Onohigashi, Osakasayama, Osaka 589-0014, Japan.
TI - IFN-gamma from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer.
SO - British Journal of Cancer. 112(9):1501-9, 2015 Apr 28
AS - Br J Cancer. 112(9):1501-9, 2015 Apr 28
NJ - British journal of cancer
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - av4, 0370635
IO - Br. J. Cancer
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453666
SB - Index Medicus
CP - England
MH - Animals
MH - *Antigens, CD274/me [Metabolism]
MH - Apoptosis
MH - Blotting, Western
MH - CD8-Positive T-Lymphocytes/de [Drug Effects]
MH - *CD8-Positive T-Lymphocytes/im [Immunology]
MH - CD8-Positive T-Lymphocytes/pa [Pathology]
MH - Cell Proliferation
MH - Disease Progression
MH - Female
MH - Flow Cytometry
MH - Humans
MH - Immunoenzyme Techniques
MH - *Interferon-gamma/pd [Pharmacology]
MH - Lymphocytes, Tumor-Infiltrating/de [Drug Effects]
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Lymphocytes, Tumor-Infiltrating/pa [Pathology]
MH - Mice
MH - Mice, Inbred C57BL
MH - Ovarian Neoplasms/dt [Drug Therapy]
MH - Ovarian Neoplasms/im [Immunology]
MH - *Ovarian Neoplasms/me [Metabolism]
MH - *Ovarian Neoplasms/pa [Pathology]
MH - Peritoneal Neoplasms/dt [Drug Therapy]
MH - Peritoneal Neoplasms/im [Immunology]
MH - *Peritoneal Neoplasms/me [Metabolism]
MH - *Peritoneal Neoplasms/sc [Secondary]
MH - Prognosis
MH - Tumor Cells, Cultured
MH - Tumor Microenvironment/de [Drug Effects]
MH - Up-Regulation
MH - Xenograft Model Antitumor Assays
AB - BACKGROUND: PD-L1 (programmed cell death 1 ligand 1) on tumour cells suppresses host immunity through binding to its receptor PD-1 on lymphocytes, and promotes peritoneal dissemination in mouse models of ovarian cancer. However, how PD-L1 expression is regulated in ovarian cancer microenvironment remains unclear.
AB - METHODS: The number of CD8-positive lymphocytes and PD-L1 expression in tumour cells was assessed in ovarian cancer clinical samples. PD-L1 expression and tumour progression in mouse models under conditions of altering IFN-gamma signals was assessed.
AB - RESULTS: The number of CD8-positive cells in cancer stroma was very high in peritoneally disseminated tumours, and was strongly correlated to PD-L1 expression on the tumour cells (P<0.001). In mouse models, depleting IFNGR1 (interferon-gamma receptor 1) resulted in lower level of PD-L1 expression in tumour cells, increased the number of tumour-infiltrating CD8-positive lymphocytes, inhibition of peritoneal disseminated tumour growth and longer survival (P=0.02). The injection of IFN-gamma into subcutaneous tumours induced PD-L1 expression and promoted tumour growth, and PD-L1 depletion completely abrogated tumour growth caused by IFN-gamma injection (P=0.01).
AB - CONCLUSIONS: Interferon-gamma secreted by CD8-positive lymphocytes upregulates PD-L1 on ovarian cancer cells and promotes tumour growth. The lymphocyte infiltration and the IFN-gamma status may be the key to effective anti-PD-1 or anti-PD-L1 therapy in ovarian cancer.
RN - 0 (Antigens, CD274)
RN - 82115-62-6 (Interferon-gamma)
ES - 1532-1827
IL - 0007-0920
DI - bjc2015101
DO - https://dx.doi.org/10.1038/bjc.2015.101
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 25867264 [pubmed]
ID - bjc2015101 [pii]
ID - 10.1038/bjc.2015.101 [doi]
ID - PMC4453666 [pmc]
PP - ppublish
PH - 2014/12/22 [received]
PH - 2015/02/19 [revised]
PH - 2015/02/19 [accepted]
LG - English
EP - 20150331
DP - 2015 Apr 28
DC - 20150429
EZ - 2015/04/14 06:00
DA - 2015/07/15 06:00
DT - 2015/04/14 06:00
YR - 2015
ED - 20150709
RD - 20160428
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25867264
<208. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25801435
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Buddhisa S
AU - Rinchai D
AU - Ato M
AU - Bancroft GJ
AU - Lertmemongkolchai G
FA - Buddhisa, Surachat
FA - Rinchai, Darawan
FA - Ato, Manabu
FA - Bancroft, Gregory J
FA - Lertmemongkolchai, Ganjana
IN - Buddhisa, Surachat. Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand;
IN - Rinchai, Darawan. Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand;
IN - Ato, Manabu. Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; and.
IN - Bancroft, Gregory J. Department of Immunology and Infection, London School of Hygiene & Tropical Medicine, London WC1E 7HT, United Kingdom.
IN - Lertmemongkolchai, Ganjana. Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; ganja_le@kku.ac.th.
TI - Programmed death ligand 1 on Burkholderia pseudomallei-infected human polymorphonuclear neutrophils impairs T cell functions.
SO - Journal of Immunology. 194(9):4413-21, 2015 May 01
AS - J Immunol. 194(9):4413-21, 2015 May 01
NJ - Journal of immunology (Baltimore, Md. : 1950)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ifb, 2985117r
IO - J. Immunol.
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - *Antigens, CD274/me [Metabolism]
MH - *Burkholderia pseudomallei/im [Immunology]
MH - CD4-Positive T-Lymphocytes/im [Immunology]
MH - CD4-Positive T-Lymphocytes/me [Metabolism]
MH - Cell Communication
MH - Diabetes Mellitus, Type 2/im [Immunology]
MH - Diabetes Mellitus, Type 2/me [Metabolism]
MH - Female
MH - Humans
MH - Immunomodulation
MH - Male
MH - Melioidosis/im [Immunology]
MH - Melioidosis/me [Metabolism]
MH - Middle Aged
MH - *Neutrophils/im [Immunology]
MH - *Neutrophils/me [Metabolism]
MH - Neutrophils/mi [Microbiology]
MH - Programmed Cell Death 1 Receptor/me [Metabolism]
MH - Signal Transduction
MH - *T-Lymphocyte Subsets/im [Immunology]
MH - *T-Lymphocyte Subsets/me [Metabolism]
AB - Polymorphonuclear neutrophils (PMNs) are terminally differentiated cells that are involved in innate immune responses and form an early line of defense against pathogens. More recently, it has been shown that PMNs have immunosuppressive abilities on other immune cells. However, the effect of PMNs on T cell responses during bacterial infection remains to be determined. In this report, we examined the interaction of PMNs and T cells in response to infection with Burkholderia pseudomallei, the causative agent of human melioidosis. We observed that CD4(+) T cell proliferation and IFN-gamma production in response to polyclonal activators is significantly inhibited by uninfected PMNs, and to a greater extent B. pseudomallei-infected PMNs. Programmed death ligand 1 (PD-L1), a known regulator of T cell activation, is increased in mRNA expression in the blood of patients and upon infection of PMNs in vitro. The increased expression of PD-L1 was correlated with the degree of T cell inhibition in individuals with type 2 diabetes, a major risk factor of melioidosis. In vitro, addition of anti-PD-L1 Abs blocked this inhibitory activity and restored proliferation of CD4(+) T cells and IFN-gamma production, suggesting that PD-L1 on B. pseudomallei-infected PMNs is a regulatory molecule for the functions of T cells and may be involved in pathogenesis versus control of melioidosis.
AB - Copyright © 2015 by The American Association of Immunologists, Inc.
RN - 0 (Antigens, CD274)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1550-6606
IL - 0022-1767
DI - jimmunol.1402417
DO - https://dx.doi.org/10.4049/jimmunol.1402417
PT - Journal Article
ID - 25801435 [pubmed]
ID - jimmunol.1402417 [pii]
ID - 10.4049/jimmunol.1402417 [doi]
PP - ppublish
PH - 2014/09/23 [received]
PH - 2015/02/18 [accepted]
LG - English
EP - 20150323
DP - 2015 May 01
DC - 20150418
EZ - 2015/03/25 06:00
DA - 2015/07/01 06:00
DT - 2015/03/25 06:00
YR - 2015
ED - 20150630
RD - 20150418
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25801435
<209. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25207976
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - McElnea E
AU - Ni Mhealoid A
AU - Moran S
AU - Kelly R
AU - Fulcher T
FA - McElnea, Elizabeth
FA - Ni Mhealoid, Aine
FA - Moran, Sarah
FA - Kelly, Rory
FA - Fulcher, Tim
IN - McElnea, Elizabeth. Department of Ophthalmology, Mater Misericordiae University Hospital , Dublin , Ireland.
TI - Thyroid-like ophthalmopathy in a euthyroid patient receiving Ipilimumab.
SO - Orbit. 33(6):424-7, 2014 Dec
AS - Orbit. 33(6):424-7, 2014 Dec
NJ - Orbit (Amsterdam, Netherlands)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 8301221
IO - Orbit
SB - Index Medicus
CP - England
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Euthyroid Sick Syndromes/bl [Blood]
MH - *Euthyroid Sick Syndromes/co [Complications]
MH - Exophthalmos/ci [Chemically Induced]
MH - Exophthalmos/di [Diagnosis]
MH - Female
MH - Glucocorticoids/tu [Therapeutic Use]
MH - *Graves Ophthalmopathy/ci [Chemically Induced]
MH - Graves Ophthalmopathy/di [Diagnosis]
MH - Graves Ophthalmopathy/dt [Drug Therapy]
MH - Humans
MH - Melanoma/dt [Drug Therapy]
MH - Melanoma/sc [Secondary]
MH - Methylprednisolone/tu [Therapeutic Use]
MH - Ophthalmoplegia/ci [Chemically Induced]
MH - Ophthalmoplegia/di [Diagnosis]
MH - Thyroid Function Tests
MH - Thyrotropin/bl [Blood]
MH - Thyroxine/bl [Blood]
KW - Ipilimumab; myositis; thyroid eye disease; thyroid orbitopathy
AB - A 68-year-old lady with metastatic malignant melanoma was treated with Ipilimumab. She presented to Eye Casualty unable to move her eyes. Physical examination confirmed ophthalmoplegia and identified proptosis bilaterally. Radiological imaging showed bilateral enlargement of all the extra-ocular muscles suggestive of thyroid eye disease. Laboratory investigations found this patient to be euthyroid. A diagnosis of thyroid-like orbitopathy secondary to Ipilimumab therapy was made. Thyroid function tests should be performed for all patients prior to their commencement of Ipilimumab. Thyroid-like eye disease may develop in patients treated with Ipilimumab even if they remain euthyroid.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Glucocorticoids)
RN - 6T8C155666 (ipilimumab)
RN - 9002-71-5 (Thyrotropin)
RN - Q51BO43MG4 (Thyroxine)
RN - X4W7ZR7023 (Methylprednisolone)
ES - 1744-5108
IL - 0167-6830
DO - https://dx.doi.org/10.3109/01676830.2014.949792
PT - Case Reports
PT - Journal Article
ID - 25207976 [pubmed]
ID - 10.3109/01676830.2014.949792 [doi]
PP - ppublish
LG - English
EP - 20140910
DP - 2014 Dec
DC - 20141028
EZ - 2014/09/11 06:00
DA - 2015/05/20 06:00
DT - 2014/09/11 06:00
YR - 2014
ED - 20150519
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25207976
<210. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25409618
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wang DH
AU - Guo L
AU - Wu XH
FA - Wang, Dong-hui
FA - Guo, Liang
FA - Wu, Xiao-hua
IN - Wang, Dong-hui. First Department of Gynecology, Cangzhou Central Hospital, Cangzhou, 061001, Hebei, China, czwangdonghui@hotmail.com.
TI - Checkpoint inhibitors in immunotherapy of ovarian cancer. [Review]
SO - Tumour Biology. 36(1):33-9, 2015 Jan
AS - Tumour Biol. 36(1):33-9, 2015 Jan
NJ - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - tub, 8409922
IO - Tumour Biol.
SB - Index Medicus
CP - Netherlands
MH - Animals
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Apoptosis/de [Drug Effects]
MH - Cell Cycle Checkpoints/de [Drug Effects]
MH - Female
MH - Humans
MH - *Immunologic Factors/pd [Pharmacology]
MH - Immunologic Factors/tu [Therapeutic Use]
MH - Immunotherapy
MH - *Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/th [Therapy]
MH - T-Lymphocytes, Cytotoxic/de [Drug Effects]
AB - The treatment of ovarian cancer is a major challenge in oncology as mortality from ovarian cancer remains very high. The immune system plays a critical role in controlling cancer through a dynamic relationship with cancer cells. Immunotherapy can establish a sustained immune system response against recurring cancer cells leading to long-term remissions for ovarian cancer patient. The use of immune checkpoint inhibitors, which work by targeting molecules that serve as checks and balances in the regulation of immune responses, might be a promising avenue of immunotherapeutic research in ovarian cancer. In this review, we have focused on the potential of certain immune checkpoint inhibitors, such as anti-cytotoxic T lymphocyte antigens, anti-programmed death agents, and anti-program death ligands against ovarian cancer, with their mechanism of actions. Also, the problems arising due to checkpoint inhibitor immunotherapy have been discussed in this review. Checkpoint inhibitor immunotherapy is still in early-phase testing for ovarian cancer. Understanding the pivotal role of the tumor microenvironment in suppressing anticancer immunity, the unique adverse effects profiles of these agents, and the exploration of combinatorial treatment regimens will ultimately lead to enhance the efficacy of ovarian cancer immunotherapies and improved patient care.
RN - 0 (Antineoplastic Agents)
RN - 0 (Immunologic Factors)
ES - 1423-0380
IL - 1010-4283
DO - https://dx.doi.org/10.1007/s13277-014-2848-2
PT - Journal Article
PT - Review
ID - 25409618 [pubmed]
ID - 10.1007/s13277-014-2848-2 [doi]
PP - ppublish
PH - 2014/10/10 [received]
PH - 2014/11/12 [accepted]
LG - English
EP - 20141120
DP - 2015 Jan
DC - 20150203
EZ - 2014/11/21 06:00
DA - 2015/05/12 06:00
DT - 2014/11/21 06:00
YR - 2015
ED - 20150511
RD - 20150203
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25409618
<211. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25409618
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wang DH
AU - Guo L
AU - Wu XH
FA - Wang, Dong-hui
FA - Guo, Liang
FA - Wu, Xiao-hua
IN - Wang, Dong-hui. First Department of Gynecology, Cangzhou Central Hospital, Cangzhou, 061001, Hebei, China, czwangdonghui@hotmail.com.
TI - Checkpoint inhibitors in immunotherapy of ovarian cancer. [Review]
SO - Tumour Biology. 36(1):33-9, 2015 Jan
AS - Tumour Biol. 36(1):33-9, 2015 Jan
NJ - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - tub, 8409922
IO - Tumour Biol.
SB - Index Medicus
CP - United States
MH - Animals
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Apoptosis/de [Drug Effects]
MH - Cell Cycle Checkpoints/de [Drug Effects]
MH - Female
MH - Humans
MH - *Immunologic Factors/pd [Pharmacology]
MH - Immunologic Factors/tu [Therapeutic Use]
MH - Immunotherapy
MH - *Ovarian Neoplasms/im [Immunology]
MH - Ovarian Neoplasms/th [Therapy]
MH - T-Lymphocytes, Cytotoxic/de [Drug Effects]
AB - The treatment of ovarian cancer is a major challenge in oncology as mortality from ovarian cancer remains very high. The immune system plays a critical role in controlling cancer through a dynamic relationship with cancer cells. Immunotherapy can establish a sustained immune system response against recurring cancer cells leading to long-term remissions for ovarian cancer patient. The use of immune checkpoint inhibitors, which work by targeting molecules that serve as checks and balances in the regulation of immune responses, might be a promising avenue of immunotherapeutic research in ovarian cancer. In this review, we have focused on the potential of certain immune checkpoint inhibitors, such as anti-cytotoxic T lymphocyte antigens, anti-programmed death agents, and anti-program death ligands against ovarian cancer, with their mechanism of actions. Also, the problems arising due to checkpoint inhibitor immunotherapy have been discussed in this review. Checkpoint inhibitor immunotherapy is still in early-phase testing for ovarian cancer. Understanding the pivotal role of the tumor microenvironment in suppressing anticancer immunity, the unique adverse effects profiles of these agents, and the exploration of combinatorial treatment regimens will ultimately lead to enhance the efficacy of ovarian cancer immunotherapies and improved patient care.
RN - 0 (Antineoplastic Agents)
RN - 0 (Immunologic Factors)
ES - 1423-0380
IL - 1010-4283
DO - https://dx.doi.org/10.1007/s13277-014-2848-2
PT - Journal Article
PT - Review
ID - 25409618 [pubmed]
ID - 10.1007/s13277-014-2848-2 [doi]
PP - ppublish
PH - 2014/10/10 [received]
PH - 2014/11/12 [accepted]
LG - English
EP - 20141120
DP - 2015 Jan
DC - 20150203
EZ - 2014/11/21 06:00
DA - 2015/05/12 06:00
DT - 2014/11/21 06:00
YR - 2015
ED - 20150511
RD - 20170124
UP - 20170126
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=25409618
<212. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25918658
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Yun S
AU - Vincelette ND
AU - Mansour I
AU - Hariri D
AU - Motamed S
AI - Yun, Seongseok; ORCID: https://orcid.org/0000-0001-7343-1635
FA - Yun, Seongseok
FA - Vincelette, Nicole D
FA - Mansour, Iyad
FA - Hariri, Dana
FA - Motamed, Sara
IN - Yun, Seongseok. Department of Medicine, University of Arizona, Tucson, AZ 85721, USA.
IN - Vincelette, Nicole D. Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
IN - Mansour, Iyad. Department of Medicine, University of Arizona, Tucson, AZ 85721, USA.
IN - Hariri, Dana. Department of Pathology, University of Arizona, Tucson, AZ 85721, USA.
IN - Motamed, Sara. Midwestern University, Arizona College of Osteopathic Medicine, Glendale, AZ 85308, USA.
TI - Late onset ipilimumab-induced pericarditis and pericardial effusion: a rare but life threatening complication.
SO - Case Reports in Oncological Medicine. 2015:794842, 2015
AS - Case Rep Oncol Med. 2015:794842, 2015
NJ - Case reports in oncological medicine
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - 101581035
IO - Case Rep Oncol Med
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396732
CP - United States
AB - Metastatic cutaneous melanoma has poor prognosis with 2-year survival rate of 10-20%. Melanoma cells express various antigens including gp100, melanoma antigen recognized by T cells 1 (MART-1), and tyrosinase, which can induce immune-mediated anticancer response via T cell activation. Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is an immune check point molecule that negatively regulates T cell activation and proliferation. Accordingly, recent phase III clinical trials demonstrated significant survival benefit with ipilimumab, a human monoclonal antibody (IgG1) that blocks the interaction of CTLA-4 with its ligands. Since the efficacy of ipilimumab depends on T cell activation, it is associated with substantial risk of immune mediated adverse reactions such as colitis, hepatitis, thyroiditis, and hypophysitis. We report the first case of late onset pericarditis and cardiac tamponade associated with ipilimumab treatment in patient with metastatic cutaneous melanoma.
IS - 2090-6706
DO - https://dx.doi.org/10.1155/2015/794842
PT - Journal Article
ID - 25918658 [pubmed]
ID - 10.1155/2015/794842 [doi]
ID - PMC4396732 [pmc]
PP - ppublish
PH - 2015/02/11 [received]
PH - 2015/03/23 [accepted]
LG - English
EP - 20150330
DP - 2015
DC - 20150428
EZ - 2015/04/29 06:00
DA - 2015/04/29 06:01
DT - 2015/04/29 06:00
YR - 2015
ED - 20150428
RD - 20150430
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=25918658
<213. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25582496
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Schultheis AM
AU - Scheel AH
AU - Ozretic L
AU - George J
AU - Thomas RK
AU - Hagemann T
AU - Zander T
AU - Wolf J
AU - Buettner R
FA - Schultheis, Anne M
FA - Scheel, Andreas H
FA - Ozretic, Luka
FA - George, Julie
FA - Thomas, Roman K
FA - Hagemann, Thorsten
FA - Zander, Thomas
FA - Wolf, Jurgen
FA - Buettner, Reinhard
IN - Schultheis, Anne M. Institute of Pathology, University Hospital Cologne, Cologne, Germany. Electronic address: anne.schultheis@uk-koeln.de.
IN - Scheel, Andreas H. Institute of Pathology, University Hospital Cologne, Cologne, Germany.
IN - Ozretic, Luka. Institute of Pathology, University Hospital Cologne, Cologne, Germany.
IN - George, Julie. Department of Translational Genomics, University of Cologne, Cologne, Germany.
IN - Thomas, Roman K. Department of Translational Genomics, University of Cologne, Cologne, Germany.
IN - Hagemann, Thorsten. Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, London, UK.
IN - Zander, Thomas. Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany; Center for Integrated Oncology (CIO) Cologne/Bonn, Germany.
IN - Wolf, Jurgen. Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany; Center for Integrated Oncology (CIO) Cologne/Bonn, Germany.
IN - Buettner, Reinhard. Institute of Pathology, University Hospital Cologne, Cologne, Germany; Center for Integrated Oncology (CIO) Cologne/Bonn, Germany.
TI - PD-L1 expression in small cell neuroendocrine carcinomas.
CM - Comment in: Eur J Cancer. 2015 Sep;51(13):1853-5; PMID: 26148861
SO - European Journal of Cancer. 51(3):421-6, 2015 Feb
AS - Eur J Cancer. 51(3):421-6, 2015 Feb
NJ - European journal of cancer (Oxford, England : 1990)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - arv, 9005373
IO - Eur. J. Cancer
SB - Index Medicus
CP - England
MH - *Antigens, CD274/ge [Genetics]
MH - *Antigens, CD274/me [Metabolism]
MH - *Carcinoma, Small Cell/ge [Genetics]
MH - *Carcinoma, Small Cell/me [Metabolism]
MH - Carcinoma, Small Cell/pa [Pathology]
MH - Gene Expression Regulation, Neoplastic
MH - High-Throughput Nucleotide Sequencing
MH - Humans
MH - Immunohistochemistry
MH - Lung Neoplasms/ge [Genetics]
MH - Lung Neoplasms/me [Metabolism]
MH - Lung Neoplasms/pa [Pathology]
MH - Lymphocytes, Tumor-Infiltrating/me [Metabolism]
MH - Macrophages/me [Metabolism]
MH - Neoplasm Metastasis
MH - *Neuroendocrine Tumors/ge [Genetics]
MH - *Neuroendocrine Tumors/me [Metabolism]
MH - Neuroendocrine Tumors/pa [Pathology]
MH - Programmed Cell Death 1 Ligand 2 Protein/ge [Genetics]
MH - Programmed Cell Death 1 Ligand 2 Protein/me [Metabolism]
MH - Programmed Cell Death 1 Receptor/ge [Genetics]
MH - Programmed Cell Death 1 Receptor/me [Metabolism]
MH - Tissue Array Analysis
KW - Immunohistochemistry; PD-L1; Small cell lung cancer; Small cell neuroendocrine carcinoma
AB - Small cell lung cancer and extrapulmonary small cell carcinomas are the most aggressive type of neuroendocrine carcinomas. Clinical treatment relies on conventional chemotherapy and radiotherapy; relapses are frequent. The PD-1/PD-L1/PD-L2 pathway is a major target of anti-tumour immunotherapy. Aberrant PD-L1 or PD-L2 expression may cause local immune-suppression. Here we investigated expression of PD-1 and its ligands by immunohistochemistry and RNA-seq in small cell carcinomas. PD-L1 and PD-1 protein expression were analysed in 94 clinical cases of small cell carcinomas (61 pulmonary, 33 extrapulmonary) by immunohistochemistry using two different monoclonal antibodies (5H1, E1L3N). RNA expression was profiled by RNA-seq in 43 clinical cases. None of the small cell carcinomas showed PD-L1 protein expression in tumour cells. PD-L1 and PD-1 expression was noticed in the stroma: Using immunohistochemistry, 18.5% of cases (17/92) showed PD-L1 expression in tumour-infiltrating macrophages and 48% showed PD-1 positive lymphocytes (45/94). RNA-seq showed moderate PD-L1 gene expression in 37.2% (16/43). PD-L1 was correlated with macrophage and T-cell markers. The second PD-1 ligand PD-L2 was expressed in 27.9% (12/43) and showed similar correlations. Thus, the PD-1/PD-L1 pathway seems activated in a fraction of small cell carcinomas. The carcinoma cells were negative in all cases, PD-L1 was expressed in tumour-infiltrating macrophages and was correlated with tumour-infiltrating lymphocytes. Patients with stromal PD-L1/PD-L2 expression may respond to anti-PD-1 treatment. Thus, evaluation of the composition of the tumour microenvironment should be included in clinical trials. Besides conventional immunohistochemistry, RNA-seq seems suitable for detection of PD-L1/PD-L2 expression and might prove to be more sensitive.
AB - Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
RN - 0 (Antigens, CD274)
RN - 0 (CD274 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (PDCD1LG2 protein, human)
RN - 0 (Programmed Cell Death 1 Ligand 2 Protein)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1879-0852
IL - 0959-8049
DI - S0959-8049(14)01166-6
DO - https://dx.doi.org/10.1016/j.ejca.2014.12.006
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 25582496 [pubmed]
ID - S0959-8049(14)01166-6 [pii]
ID - 10.1016/j.ejca.2014.12.006 [doi]
PP - ppublish
PH - 2014/07/17 [received]
PH - 2014/10/22 [revised]
PH - 2014/12/11 [accepted]
LG - English
EP - 20150109
DP - 2015 Feb
DC - 20150204
EZ - 2015/01/14 06:00
DA - 2015/04/16 06:00
DT - 2015/01/15 06:00
YR - 2015
ED - 20150415
RD - 20151016
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25582496
<214. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25099440
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Nallapaneni NN
AU - Mourya R
AU - Bhatt VR
AU - Malhotra S
AU - Ganti AK
AU - Tendulkar KK
FA - Nallapaneni, Neelima N
FA - Mourya, Rajesh
FA - Bhatt, Vijaya Raj
FA - Malhotra, Sakshi
FA - Ganti, Apar Kishor
FA - Tendulkar, Ketki K
IN - Nallapaneni, Neelima N. From the University of Nebraska Medical Center, Department of Internal Medicine, Division of Nephrology; Creighton University Medical Center, Department of Internal Medicine; University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology and Oncology; VA Nebraska-Western Iowa Health Care System, Department of Internal Medicine; and VA Nebraska-Western Iowa Health Care System, and University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology and Oncology, Omaha, Nebraska.
IN - Mourya, Rajesh. From the University of Nebraska Medical Center, Department of Internal Medicine, Division of Nephrology; Creighton University Medical Center, Department of Internal Medicine; University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology and Oncology; VA Nebraska-Western Iowa Health Care System, Department of Internal Medicine; and VA Nebraska-Western Iowa Health Care System, and University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology and Oncology, Omaha, Nebraska.
IN - Bhatt, Vijaya Raj. From the University of Nebraska Medical Center, Department of Internal Medicine, Division of Nephrology; Creighton University Medical Center, Department of Internal Medicine; University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology and Oncology; VA Nebraska-Western Iowa Health Care System, Department of Internal Medicine; and VA Nebraska-Western Iowa Health Care System, and University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology and Oncology, Omaha, Nebraska.
IN - Malhotra, Sakshi. From the University of Nebraska Medical Center, Department of Internal Medicine, Division of Nephrology; Creighton University Medical Center, Department of Internal Medicine; University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology and Oncology; VA Nebraska-Western Iowa Health Care System, Department of Internal Medicine; and VA Nebraska-Western Iowa Health Care System, and University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology and Oncology, Omaha, Nebraska.
IN - Ganti, Apar Kishor. From the University of Nebraska Medical Center, Department of Internal Medicine, Division of Nephrology; Creighton University Medical Center, Department of Internal Medicine; University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology and Oncology; VA Nebraska-Western Iowa Health Care System, Department of Internal Medicine; and VA Nebraska-Western Iowa Health Care System, and University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology and Oncology, Omaha, Nebraska.
IN - Tendulkar, Ketki K. From the University of Nebraska Medical Center, Department of Internal Medicine, Division of Nephrology; Creighton University Medical Center, Department of Internal Medicine; University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology and Oncology; VA Nebraska-Western Iowa Health Care System, Department of Internal Medicine; and VA Nebraska-Western Iowa Health Care System, and University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology and Oncology, Omaha, Nebraska.
TI - Ipilimumab-induced hypophysitis and uveitis in a patient with metastatic melanoma and a history of ipilimumab-induced skin rash.
SO - Journal of the National Comprehensive Cancer Network. 12(8):1077-81, 2014 Aug
AS - J. Natl. Compr. Cancer Netw.. 12(8):1077-81, 2014 Aug
NJ - Journal of the National Comprehensive Cancer Network : JNCCN
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101162515
IO - J Natl Compr Canc Netw
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - Drug-Related Side Effects and Adverse Reactions/im [Immunology]
MH - *Drug-Related Side Effects and Adverse Reactions/pa [Pathology]
MH - Exanthema/ci [Chemically Induced]
MH - Exanthema/im [Immunology]
MH - *Exanthema/pa [Pathology]
MH - Humans
MH - Male
MH - Melanoma/co [Complications]
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - Pituitary Diseases/ci [Chemically Induced]
MH - Pituitary Diseases/pa [Pathology]
MH - Uveitis/ci [Chemically Induced]
MH - Uveitis/pa [Pathology]
AB - Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4, leading to enhanced T-cell activation and proliferation, is associated with improved overall survival in melanoma. Its use can result in immune-related adverse events, the most common of which are skin rash, diarrhea, and colitis. Ipilimumab-induced hypophysitis is uncommon, mostly involves anterior pituitary, and is associated with abnormalities in pituitary MRI, whereas uveitis has been rarely reported. These immune-related adverse events occur during therapy. This report describes a patient who developed uveitis and hypophysitis involving both anterior and posterior pituitary, without MRI findings more than 3 weeks after the fourth dose of ipilimumab. This case illustrates the unusual presentation of and diagnostic challenges associated with ipilimumab-induced immune-related adverse events.
AB - Copyright © 2014 by the National Comprehensive Cancer Network.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
ES - 1540-1413
IL - 1540-1405
DI - 12/8/1077
PT - Case Reports
PT - Journal Article
ID - 25099440 [pubmed]
ID - 12/8/1077 [pii]
PP - ppublish
LG - English
DP - 2014 Aug
DC - 20140807
EZ - 2014/08/08 06:00
DA - 2015/04/14 06:00
DT - 2014/08/08 06:00
YR - 2014
ED - 20150413
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25099440
<215. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25861234
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Mahzari M
AU - Liu D
AU - Arnaout A
AU - Lochnan H
FA - Mahzari, Moeber
FA - Liu, Dora
FA - Arnaout, Amel
FA - Lochnan, Heather
IN - Mahzari, Moeber. Division of Endocrinology and Metabolism, Department of Medicine, University of Ottawa and the Ottawa Hospital, Ottawa, Canada.
IN - Liu, Dora. Division of Endocrinology and Metabolism, Department of Medicine, University of Ottawa and the Ottawa Hospital, Ottawa, Canada.
IN - Arnaout, Amel. Division of Endocrinology and Metabolism, Department of Medicine, University of Ottawa and the Ottawa Hospital, Ottawa, Canada.
IN - Lochnan, Heather. Division of Endocrinology and Metabolism, Department of Medicine, University of Ottawa and the Ottawa Hospital, Ottawa, Canada.
TI - Immune checkpoint inhibitor therapy associated hypophysitis. [Review]
SO - Clinical Medicine Insights. 8:21-8, 2015
AS - Clin Med Insights Endocrinol Diabetes. 8:21-8, 2015
NJ - Clinical medicine insights. Endocrinology and diabetes
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101578235
IO - Clin Med Insights Endocrinol Diabetes
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376202
CP - United States
KW - CTLA4; hypoadrenalism; hypophysitis; ipilimumab
AB - Ipilimumab is a monoclonal antibody directed against CTLA4 T-lymphocyte antigen used as cancer therapy. Immune-related adverse events are common side effects and may include hypophysitis-related hypopituitarism. The clinical features of six patients with ipilimumab-induced hypophysitis (IH) are described. The clinical features of IH reported in clinical trials, including the incidence of IH by gender and the likelihood of adrenal axis recovery, are summarized. Following the development of IH, most patients remain on glucocorticoid replacement despite efforts to withdraw therapy. Analysis of gender information in published clinical trials suggests that men are more prone to developing IH than women, and few patients fully recover the pituitary-adrenal axis function. Ipilimumab and other drugs within its class are likely to be used to treat many forms of cancer. Endocrinologists should anticipate a significant increase in the incidence of autoimmune hypophysitis. Strategies for early detection of IH and long-term management should be considered.
IL - 1179-5514
DI - cmed-8-2015-021
DO - https://dx.doi.org/10.4137/CMED.S22469
PT - Journal Article
PT - Review
ID - 25861234 [pubmed]
ID - 10.4137/CMED.S22469 [doi]
ID - cmed-8-2015-021 [pii]
ID - PMC4376202 [pmc]
PP - epublish
PH - 2014/12/05 [received]
PH - 2015/01/26 [revised]
PH - 2015/01/28 [accepted]
LG - English
EP - 20150325
DP - 2015
DC - 20150411
EZ - 2015/04/11 06:00
DA - 2015/04/11 06:01
DT - 2015/04/11 06:00
YR - 2015
ED - 20150411
RD - 20161024
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=25861234
<216. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25104095
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Bryant C
AU - Rawlinson R
AU - Massey AJ
FA - Bryant, Christopher
FA - Rawlinson, Rebecca
FA - Massey, Andrew J
IN - Massey, Andrew J. Vernalis R&D Ltd, Granta Park, Cambridge CB21 6GB, UK. a.massey@vernalis.com.
TI - Chk1 inhibition as a novel therapeutic strategy for treating triple-negative breast and ovarian cancers.
SO - BMC Cancer. 14:570, 2014 Aug 07
AS - BMC Cancer. 14:570, 2014 Aug 07
NJ - BMC cancer
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 100967800
IO - BMC Cancer
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137066
SB - Index Medicus
CP - England
MH - Benzodiazepinones/pd [Pharmacology]
MH - Benzodiazepinones/tu [Therapeutic Use]
MH - *Biomarkers, Tumor/me [Metabolism]
MH - Cell Line, Tumor
MH - Checkpoint Kinase 1
MH - Cisplatin/pd [Pharmacology]
MH - Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Drug Synergism
MH - Female
MH - Gene Expression Regulation, Neoplastic/de [Drug Effects]
MH - HT29 Cells
MH - Humans
MH - *Indoles/pd [Pharmacology]
MH - Indoles/tu [Therapeutic Use]
MH - MCF-7 Cells
MH - *Ovarian Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Protein Kinase Inhibitors/pd [Pharmacology]
MH - Protein Kinase Inhibitors/tu [Therapeutic Use]
MH - *Protein Kinases/me [Metabolism]
MH - Pyrazoles/pd [Pharmacology]
MH - Pyrazoles/tu [Therapeutic Use]
MH - *Pyridones/pd [Pharmacology]
MH - Pyridones/tu [Therapeutic Use]
MH - Thiophenes/pd [Pharmacology]
MH - Thiophenes/tu [Therapeutic Use]
MH - *Triple Negative Breast Neoplasms/me [Metabolism]
MH - Triple Negative Breast Neoplasms/pa [Pathology]
MH - Urea/aa [Analogs & Derivatives]
MH - Urea/pd [Pharmacology]
MH - Urea/tu [Therapeutic Use]
AB - BACKGROUND: Chk1 inhibitors are currently in clinical trials as putative potentiators of cytotoxic chemotherapy drugs. Chk1 inhibitors may exhibit single agent anti-tumor activity in cancers with underlying DNA repair, DNA damage response or DNA replication defects.
AB - METHODS: Here we describe the cellular effects of the pharmacological inhibition of the checkpoint kinase Chk1 by the novel inhibitor V158411 in triple-negative breast cancer and ovarian cancer. Cytotoxicity, the effect on DNA damage response and cell cycle along with the ability to potentiate gemcitabine and cisplatin cytotoxicity in cultured cells was investigated. Western blotting of proteins involved in DNA repair, checkpoint activation, cell cycle and apoptosis was used to identify potential predictive biomarkers of Chk1 inhibitor sensitivity.
AB - RESULTS: The Chk1 inhibitors V158411, PF-477736 and AZD7762 potently inhibited the proliferation of triple-negative breast cancer cells as well as ovarian cancer cells, and these cell lines were sensitive compared to ER positive breast and other solid cancer cells lines. Inhibition of Chk1 in these sensitive cell lines induced DNA damage and caspase-3/7 dependent apoptosis. Western blot profiling identified pChk1 (S296) as a predictive biomarker of Chk1 inhibitor sensitivity in ovarian and triple-negative breast cancer and pH2AX (S139) in luminal breast cancer.
AB - CONCLUSIONS: This finding suggests that Chk1 inhibitors either as single agents or in combination chemotherapy represents a viable therapeutic option for the treatment of triple-negative breast cancer. pChk1 (S296) tumor expression levels could serve as a useful biomarker to stratify patients who might benefit from Chk1 inhibitor therapy.
RN - 0 (3-(carbamoylamino)-5-(3-fluorophenyl)-N-(3-piperidyl)thiophene-2-carboxamide)
RN - 0 (Benzodiazepinones)
RN - 0 (Biomarkers, Tumor)
RN - 0 (Indoles)
RN - 0 (PF 00477736)
RN - 0 (Protein Kinase Inhibitors)
RN - 0 (Pyrazoles)
RN - 0 (Pyridones)
RN - 0 (Thiophenes)
RN - 0 (V158411)
RN - 0W860991D6 (Deoxycytidine)
RN - 8W8T17847W (Urea)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7 (Protein Kinases)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
RN - Q20Q21Q62J (Cisplatin)
ES - 1471-2407
IL - 1471-2407
DI - 1471-2407-14-570
DO - https://dx.doi.org/10.1186/1471-2407-14-570
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 25104095 [pubmed]
ID - 1471-2407-14-570 [pii]
ID - 10.1186/1471-2407-14-570 [doi]
ID - PMC4137066 [pmc]
PP - epublish
PH - 2014/05/01 [received]
PH - 2014/07/28 [accepted]
LG - English
EP - 20140807
DP - 2014 Aug 07
DC - 20140816
EZ - 2014/08/09 06:00
DA - 2015/04/08 06:00
DT - 2014/08/12 06:00
YR - 2014
ED - 20150407
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25104095
<217. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24986059
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Simeone E
AU - Grimaldi AM
AU - Esposito A
AU - Curvietto M
AU - Palla M
AU - Paone M
AU - Mozzillo N
AU - Ascierto PA
FA - Simeone, Ester
FA - Grimaldi, Antonio Maria
FA - Esposito, Assunta
FA - Curvietto, Marcello
FA - Palla, Marco
FA - Paone, Miriam
FA - Mozzillo, Nicola
FA - Ascierto, Paolo Antonio
IN - Ascierto, Paolo Antonio. Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, Istituto Nazionale Tumori Fondazione "G, Pascale", Via Mariano Semmola, 80131 Napoli, Italy. paolo.ascierto@gmail.com.
TI - Serious haematological toxicity during and after ipilimumab treatment: a case series.
SO - Journal of Medical Case Reports [Electronic Resource]. 8:240, 2014 Jul 01
AS - J Med Case Reports. 8:240, 2014 Jul 01
NJ - Journal of medical case reports
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101293382
IO - J Med Case Rep
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090655
SB - Index Medicus
CP - England
MH - Aged
MH - *Anemia/ci [Chemically Induced]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Female
MH - Humans
MH - Male
MH - Middle Aged
MH - Neoplasms/dt [Drug Therapy]
MH - *Neutropenia/ci [Chemically Induced]
MH - Severity of Illness Index
AB - INTRODUCTION: Immunotherapy with the anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody ipilimumab has been shown to improve overall survival in previously treated and treatment-naive patients with unresectable stage III or IV melanoma. Consistent with its proposed immunomodulating mechanism of action, the most common toxicities associated with ipilimumab therapy are immune-related in nature and include those related to the skin and gastrointestinal tract, with endocrine and hepatic events also frequent. Other rare adverse events, including haematological aberrations, may also occur and can have serious consequences if unrecognised. Here we describe three patients who developed serious haematological adverse events during or after treatment with ipilimumab.
AB - CASE PRESENTATION: Three Caucasian patients (two women aged 68 and 49 years and one man aged 70 years) with metastatic melanoma experienced anaemia and/or leukopenia (neutropenia) with toxicity of various grades during or after treatment with ipilimumab, without significant changes to other haematological values. Two of the patients stopped treatment after the third ipilimumab dose, one because of severe anaemia that required blood transfusion and the other due to febrile neutropenia that was treated with antibiotics and granulocyte-macrophage colony-stimulating factor stimulation. The third patient developed anaemia and leukopenia after treatment during the follow-up period. The results of autoimmunity tests performed were positive and corticosteroids were used to treat these events as per side-effects treatment algorithms specifically developed for the management of immune-related adverse events associated with ipilimumab, an approach that was safe and effective.
AB - CONCLUSIONS: Haematological toxicity is a rare but potentially serious immune-related side effect of ipilimumab therapy. However, if promptly recognised and treated, haematological toxicity is manageable and can be reversed with standard corticosteroid treatment as recommended for other ipilimumab immune-related side effects.
RN - 0 (Antibodies, Monoclonal)
RN - 6T8C155666 (ipilimumab)
ES - 1752-1947
IL - 1752-1947
DI - 1752-1947-8-240
DO - https://dx.doi.org/10.1186/1752-1947-8-240
PT - Case Reports
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 24986059 [pubmed]
ID - 1752-1947-8-240 [pii]
ID - 10.1186/1752-1947-8-240 [doi]
ID - PMC4090655 [pmc]
PP - epublish
PH - 2014/02/10 [received]
PH - 2014/04/07 [accepted]
LG - English
EP - 20140701
DP - 2014 Jul 01
DC - 20140711
EZ - 2014/07/03 06:00
DA - 2015/04/01 06:00
DT - 2014/07/06 06:00
YR - 2014
ED - 20150331
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24986059
<218. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24285017
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Tse BW
AU - Collins A
AU - Oehler MK
AU - Zippelius A
AU - Heinzelmann-Schwarz VA
FA - Tse, B W C
FA - Collins, A
FA - Oehler, M K
FA - Zippelius, A
FA - Heinzelmann-Schwarz, V A
IN - Tse, B W C. Ovarian Cancer Group, Lowy Cancer Research Centre, Prince of Wales Clinical School.
TI - Antibody-based immunotherapy for ovarian cancer: where are we at?. [Review]
SO - Annals of Oncology. 25(2):322-31, 2014 Feb
AS - Ann Oncol. 25(2):322-31, 2014 Feb
NJ - Annals of oncology : official journal of the European Society for Medical Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ayf, 9007735
IO - Ann. Oncol.
SB - Index Medicus
CP - England
MH - Animals
MH - Antibodies, Bispecific/tu [Therapeutic Use]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antibodies, Monoclonal, Humanized/tu [Therapeutic Use]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Clinical Trials as Topic
MH - Diphtheria Toxin/tu [Therapeutic Use]
MH - Female
MH - Humans
MH - Immunoglobulin G/tu [Therapeutic Use]
MH - Immunotherapy
MH - Interleukin-2/tu [Therapeutic Use]
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - Recombinant Fusion Proteins/tu [Therapeutic Use]
KW - antibody; clinical trials; diagnosis; gynaecological cancers; immunology; treatment regimens
AB - Cytoreductive surgery and chemotherapy continue to be the mainstay of ovarian cancer treatment. However, as mortality from advanced ovarian cancer remains very high, novel therapies are required to be integrated into existing treatment regimens. Immunotherapy represents an alternative and rational therapeutic approach for ovarian cancer based on a body of evidence supporting a protective role of the immune system against these cancers, and on the clinical success of immunotherapy in other malignancies. Whether or not immunotherapy will have a role in the future management of ovarian cancer is too early to tell, but research in this field is active. This review will discuss recent clinical developments of selected immunotherapies for ovarian cancer which fulfil the following criteria: (i) they are antibody-based, (ii) target a distinct immunological pathway, and (iii) have reached the clinical trial stage. Specifically, the focus is on Catumaxomab (anti-EpCAMxanti-CD3), Abagovomab, Oregovomab (anti-CA125), Daclizumab (anti-CD25), Ipilimumab (anti-CTLA-4), and MXD-1105 (anti-PD-L1). Catumaxomab has reached phase III clinical trials and exhibits promise with reports, showing that it can cause a significant and sustained reduction in ascites. Phase I-III clinical trials continue to be conducted on the other antibodies, some of which have had encouraging reports. We will also provide our perspective on the future of immunotherapy for ovarian cancer, and how it may be best employed in treatment regimens.
RN - 0 (Antibodies, Bispecific)
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (Diphtheria Toxin)
RN - 0 (Immunoglobulin G)
RN - 0 (Interleukin-2)
RN - 0 (Recombinant Fusion Proteins)
RN - 0 (abagovomab)
RN - 0 (catumaxomab)
RN - 25E79B5CTM (denileukin diftitox)
RN - 6T8C155666 (ipilimumab)
RN - CUJ2MVI71Y (daclizumab)
ES - 1569-8041
IL - 0923-7534
DI - mdt405
DO - https://dx.doi.org/10.1093/annonc/mdt405
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 24285017 [pubmed]
ID - mdt405 [pii]
ID - 10.1093/annonc/mdt405 [doi]
PP - ppublish
LG - English
EP - 20131126
DP - 2014 Feb
DC - 20140130
EZ - 2013/11/29 06:00
DA - 2015/03/31 06:00
DT - 2013/11/29 06:00
YR - 2014
ED - 20150330
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24285017
<219. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25416723
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Albarel F
AU - Gaudy C
AU - Castinetti F
AU - Carre T
AU - Morange I
AU - Conte-Devolx B
AU - Grob JJ
AU - Brue T
FA - Albarel, Frederique
FA - Gaudy, Caroline
FA - Castinetti, Frederic
FA - Carre, Tiphaine
FA - Morange, Isabelle
FA - Conte-Devolx, Bernard
FA - Grob, Jean-Jacques
FA - Brue, Thierry
IN - Albarel, Frederique. Assistance Publique - Hopitaux de Marseille (AP-HM)Hopital Timone, Service d'Endocrinologie et Centre de Reference des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteAssistance Publique - Hopitaux de Marseille (AP-HM), Hopital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France Assistance Publique - Hopitaux de Marseille (AP-HM)Hopital Timone, Service d'Endocrinologie et Centre de Reference des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteAssistance Publique - Hopitaux de Marseille (AP-HM), Hopital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France.
IN - Gaudy, Caroline. Assistance Publique - Hopitaux de Marseille (AP-HM)Hopital Timone, Service d'Endocrinologie et Centre de Reference des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteAssistance Publique - Hopitaux de Marseille (AP-HM), Hopital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France.
IN - Castinetti, Frederic. Assistance Publique - Hopitaux de Marseille (AP-HM)Hopital Timone, Service d'Endocrinologie et Centre de Reference des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteAssistance Publique - Hopitaux de Marseille (AP-HM), Hopital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France Assistance Publique - Hopitaux de Marseille (AP-HM)Hopital Timone, Service d'Endocrinologie et Centre de Reference des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteAssistance Publique - Hopitaux de Marseille (AP-HM), Hopital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France.
IN - Carre, Tiphaine. Assistance Publique - Hopitaux de Marseille (AP-HM)Hopital Timone, Service d'Endocrinologie et Centre de Reference des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteAssistance Publique - Hopitaux de Marseille (AP-HM), Hopital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France.
IN - Morange, Isabelle. Assistance Publique - Hopitaux de Marseille (AP-HM)Hopital Timone, Service d'Endocrinologie et Centre de Reference des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteAssistance Publique - Hopitaux de Marseille (AP-HM), Hopital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France Assistance Publique - Hopitaux de Marseille (AP-HM)Hopital Timone, Service d'Endocrinologie et Centre de Reference des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteAssistance Publique - Hopitaux de Marseille (AP-HM), Hopital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France.
IN - Conte-Devolx, Bernard. Assistance Publique - Hopitaux de Marseille (AP-HM)Hopital Timone, Service d'Endocrinologie et Centre de Reference des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteAssistance Publique - Hopitaux de Marseille (AP-HM), Hopital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France Assistance Publique - Hopitaux de Marseille (AP-HM)Hopital Timone, Service d'Endocrinologie et Centre de Reference des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteAssistance Publique - Hopitaux de Marseille (AP-HM), Hopital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France.
IN - Grob, Jean-Jacques. Assistance Publique - Hopitaux de Marseille (AP-HM)Hopital Timone, Service d'Endocrinologie et Centre de Reference des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteAssistance Publique - Hopitaux de Marseille (AP-HM), Hopital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France.
IN - Brue, Thierry. Assistance Publique - Hopitaux de Marseille (AP-HM)Hopital Timone, Service d'Endocrinologie et Centre de Reference des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteAssistance Publique - Hopitaux de Marseille (AP-HM), Hopital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France Assistance Publique - Hopitaux de Marseille (AP-HM)Hopital Timone, Service d'Endocrinologie et Centre de Reference des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversiteAssistance Publique - Hopitaux de Marseille (AP-HM), Hopital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France thierry.brue@univ-amu.fr.
TI - Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma.
SO - European Journal of Endocrinology. 172(2):195-204, 2015 Feb
AS - EUR. J. ENDOCRINOL.. 172(2):195-204, 2015 Feb
NJ - European journal of endocrinology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - bxu, 9423848
IO - Eur. J. Endocrinol.
SB - Index Medicus
CP - England
MH - Adult
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - CTLA-4 Antigen/bl [Blood]
MH - *CTLA-4 Antigen
MH - Double-Blind Method
MH - Female
MH - Follow-Up Studies
MH - Humans
MH - Male
MH - Melanoma/bl [Blood]
MH - *Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - Pituitary Diseases/bl [Blood]
MH - *Pituitary Diseases/ci [Chemically Induced]
MH - *Pituitary Diseases/di [Diagnosis]
MH - Skin Neoplasms/bl [Blood]
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Time Factors
AB - OBJECTIVE: Few data are published on the long-term follow-up of ipilimumab-induced hypophysitis, a cytotoxic T-lymphocyte antigen 4 antibody. We characterized hypophysitis in terms of clinical signs, endocrinological profile, and imaging at diagnosis and during a long-term follow-up.
AB - DESIGN AND PATIENTS: Fifteen patients, treated for malignant melanoma and who presented ipilimumab-induced hypophysitis, were observed between June 2006 and August 2012 in Timone Hospital, Marseille.
AB - METHODS: Symptoms, pituitary function, and pituitary imaging at diagnosis of hypophysitis and during the follow-up were recorded.
AB - RESULTS: Of 131 patients treated with ipilimumab or a placebo, 15 patients (10 mg/kg in 11/15) presented with hypophysitis (>=11.5%) at 9.5+/-5.9 weeks (mean+/-s.d.) after treatment start, occurring in 66% after the third infusion. The main initial symptoms were headache (n=13) and asthenia (n=11). All patients but one had at least one hormonal defect: thyrotroph (n=13), gonadotroph (n=12), or corticotroph (n=11) deficiencies. None had diabetes insipidus. Pituitary imaging showed a moderately enlarged gland in 12 patients. Clinical symptoms improved rapidly on high-dose glucocorticoids (n=11) or physiological replacement doses (n=4). At the end of follow-up (median 33.6 months, range 7-53.5), corticotroph deficiency remained in 13 patients, 11 recovered thyrotroph and ten gonadotroph functions. Pituitary imaging remained abnormal in 11 patients.
AB - CONCLUSION: Ipilimumab-induced hypophysitis is a common side-effect with frequent hormonal deficiencies at diagnosis. Usually, hormonal deficiencies improved, except for corticotroph function. Patients receiving these immunomodulatory therapies should be closely monitored especially by systematic baseline hormone measurements after the third infusion and remain at a risk of adrenal insufficiency in the long-term.
AB - Copyright © 2015 European Society of Endocrinology.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
ES - 1479-683X
IL - 0804-4643
DI - EJE-14-0845
DO - https://dx.doi.org/10.1530/EJE-14-0845
PT - Journal Article
PT - Randomized Controlled Trial
PT - Research Support, Non-U.S. Gov't
ID - 25416723 [pubmed]
ID - EJE-14-0845 [pii]
ID - 10.1530/EJE-14-0845 [doi]
PP - ppublish
LG - English
EP - 20141121
DP - 2015 Feb
DC - 20150110
EZ - 2014/11/23 06:00
DA - 2015/03/21 06:00
DT - 2014/11/25 06:00
YR - 2015
ED - 20150320
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25416723
<220. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25759760
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Yu C
AU - Chopra IJ
AU - Ha E
FA - Yu, Christine
FA - Chopra, Inder J
FA - Ha, Edward
IN - Yu, Christine. Department of Medicine, University of California , Los Angeles, Los Angeles, California, 90095 , USA.
IN - Chopra, Inder J. Division of Endocrinology, Department of Medicine, University of California , 757 Westwood Plaza Blvd, Suite 7501, Los Angeles, CA, 90095 , USA.
IN - Ha, Edward. Department of Medicine, University of California , Los Angeles, Los Angeles, California, 90095 , USA.
TI - A novel melanoma therapy stirs up a storm: ipilimumab-induced thyrotoxicosis.
SO - Endocrinology, Diabetes & Metabolism Case Reports. 2015:140092, 2015
AS - Endocrinol Diabetes Metab Case Rep. 2015:140092, 2015
NJ - Endocrinology, diabetes & metabolism case reports
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - 101618943
IO - Endocrinol Diabetes Metab Case Rep
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330494
CP - England
AB - UNLABELLED: Ipilimumab, a novel therapy for metastatic melanoma, inhibits cytotoxic T-lymphocyte apoptosis, causing both antitumor activity and significant autoimmunity, including autoimmune thyroiditis. Steroids are frequently used in treatment of immune-related adverse events; however, a concern regarding the property of steroids to reduce therapeutic antitumor response exists. This study describes the first reported case of ipilimumab-associated thyroid storm and implicates iopanoic acid as an alternative therapy for immune-mediated adverse effects. An 88-year-old woman with metastatic melanoma presented with fatigue, anorexia, decreased functional status, and intermittent diarrhea for several months, shortly after initiation of ipilimumab - a recombinant human monoclonal antibody to the cytotoxic T-lymphocyte-associated antigen 4 (CTLA4). On arrival, she was febrile, tachycardic, and hypertensive with a wide pulse pressure, yet non-toxic appearing. She had diffuse, non-tender thyromegaly. An electrocardiogram (EKG) revealed supraventricular tachycardia. Blood, urine, and stool cultures were collected, and empiric antibiotics were started. A computed tomography (CT) angiogram of the chest was negative for pulmonary embolism or pneumonia, but confirmed a diffusely enlarged thyroid gland, which prompted thyroid function testing. TSH was decreased at 0.16 muIU/ml (normal 0.3-4.7); free tri-iodothyronine (T3) was markedly elevated at 1031 pg/dl (normal 249-405), as was free thyroxine (T4) at 5.6 ng/dl (normal 0.8-1.6). With iopanoic acid and methimazole therapy, she markedly improved within 48 h, which could be attributed to lowering of serum T3 with iopanoic acid rather than to any effect of the methimazole. Ipilimumab is a cause of overt thyrotoxicosis and its immune-mediated adverse effects can be treated with iopanoic acid, a potent inhibitor of T4-to-T3 conversion.
AB - LEARNING POINTS: While ipilimumab more commonly causes autoimmune thyroiditis, it can also cause thyroid storm and clinicians should include thyroid storm in their differential diagnosis for patients who present with systemic inflammatory response syndrome.Immune-related adverse reactions usually occur after 1-3 months of ipilimumab and baseline thyroid function testing should be completed before initiation with ipilimumab.Conflicting data exist on the use of prednisone for treatment of CTLA4 adverse effects and its attenuation of ipilimumab's antitumor effect. Iopanoic acid may be considered as an alternative therapy in this setting.
IL - 2052-0573
DI - EDM140092
DO - https://dx.doi.org/10.1530/EDM-14-0092
PT - Journal Article
ID - 25759760 [pubmed]
ID - 10.1530/EDM-14-0092 [doi]
ID - EDM140092 [pii]
ID - PMC4330494 [pmc]
PP - ppublish
PH - 2015/01/14 [received]
PH - 2015/01/26 [accepted]
LG - English
EP - 20150201
DP - 2015
DC - 20150311
EZ - 2015/03/12 06:00
DA - 2015/03/12 06:01
DT - 2015/03/12 06:00
YR - 2015
ED - 20150311
RD - 20150313
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=25759760
<221. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25301449
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Xia Y
AU - Lei Q
AU - Zhu Y
AU - Ye T
AU - Wang N
AU - Li G
AU - Shi X
AU - Liu Y
AU - Shao B
AU - Yin T
AU - Zhao L
AU - Wu W
AU - Song X
AU - Xiong Y
AU - Wei Y
AU - Yu L
FA - Xia, Yong
FA - Lei, Qian
FA - Zhu, Yongxia
FA - Ye, Tinghong
FA - Wang, Ningyu
FA - Li, Guobo
FA - Shi, Xuanhong
FA - Liu, Yantong
FA - Shao, Bin
FA - Yin, Tao
FA - Zhao, Lifeng
FA - Wu, Wenshuang
FA - Song, Xuejiao
FA - Xiong, Ying
FA - Wei, Yuquan
FA - Yu, Luoting
IN - Xia, Yong. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Lei, Qian. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Zhu, Yongxia. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Ye, Tinghong. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Wang, Ningyu. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Li, Guobo. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Shi, Xuanhong. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Liu, Yantong. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Shao, Bin. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Yin, Tao. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Zhao, Lifeng. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Wu, Wenshuang. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Song, Xuejiao. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Xiong, Ying. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China; Department of Pharmacy, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
IN - Wei, Yuquan. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
IN - Yu, Luoting. State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. Electronic address: yuluot@scu.edu.cn.
TI - SKLB316, a novel small-molecule inhibitor of cell-cycle progression, induces G2/M phase arrest and apoptosis in vitro and inhibits tumor growth in vivo.
SO - Cancer Letters. 355(2):297-309, 2014 Dec 28
AS - Cancer Lett. 355(2):297-309, 2014 Dec 28
NJ - Cancer letters
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 7600053, cmx
IO - Cancer Lett.
SB - Index Medicus
CP - Ireland
MH - Animals
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - *Apoptosis/de [Drug Effects]
MH - *Benzothiazoles/pd [Pharmacology]
MH - CDC2 Protein Kinase/ge [Genetics]
MH - CDC2 Protein Kinase/me [Metabolism]
MH - Caspase 9/me [Metabolism]
MH - Cell Proliferation/de [Drug Effects]
MH - Checkpoint Kinase 2/me [Metabolism]
MH - *Colorectal Neoplasms/dt [Drug Therapy]
MH - Colorectal Neoplasms/me [Metabolism]
MH - Colorectal Neoplasms/pa [Pathology]
MH - Cyclins/me [Metabolism]
MH - Female
MH - *G2 Phase Cell Cycle Checkpoints/de [Drug Effects]
MH - HCT116 Cells
MH - Humans
MH - Membrane Potential, Mitochondrial/de [Drug Effects]
MH - Mice
MH - Mice, Nude
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/me [Metabolism]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Phosphorylation/de [Drug Effects]
MH - Reactive Oxygen Species/me [Metabolism]
MH - Xenograft Model Antitumor Assays
MH - bcl-2-Associated X Protein/ge [Genetics]
MH - bcl-2-Associated X Protein/me [Metabolism]
MH - cdc25 Phosphatases/me [Metabolism]
KW - Anti-cancer; Apoptosis; Cell cycle arrest; Drug discovery; SKLB316
AB - Benzothiazole derivatives have received considerable attentions for their potencies in cancer therapy. In the present study, we reported that SKLB316, a novel synthesized benzothiazole derivative, exhibits activities to inhibit colorectal and pancreatic cancer in vitro and in vivo by inducing G2/M cell cycle arrest and apoptosis. In vitro, it exhibited significant anti-proliferative activities against human cancer cells derived from different histotypes including the colorectal cancer cell line HCT116 and pancreatic cancer cell line CFPAC-1. We chose these cell lines to study the possible anti-tumor mechanism because they are sensitive to SKLB316 treatment. Flow cytometry assays showed that SKLB316 could induce G2/M cell cycle arrest. Mechanistically, SKLB316 could decrease the activities of cdc2/cyclin B1 complex, including decreasing the synthesis of cyclin B1, cdc2 and cdc25c, while accumulating the levels of phosphorylated cdc2 (Tyr15) and checkpoint kinase 2. SKLB316 could also decrease the level of cyclin E and A2. Moreover, SKLB316 could induce cancer cell apoptosis, which was associated with activation of caspase 9, downregulation of Bcl-2 and upregulation of Bax. SKLB316 could also decrease the mitochondrial membrane potential and induce the generation of reactive oxygen species in cells. The results implied that SKLB316 may induce apoptosis via the mitochondria-mediated apoptotic pathway. Moreover, SKLB316 could suppress the growth of established colorectal and pancreatic cancer tumors in nude mice without causing obvious side effects. TUNEL assays confirmed that SKLB316 could also induce tumor cell apoptosis in vivo. Taken together, these findings demonstrate the potential value of SKLB316 as a novel anti-tumor drug candidate.
AB - Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
RN - 0 (Antineoplastic Agents)
RN - 0 (Benzothiazoles)
RN - 0 (Cyclins)
RN - 0 (Reactive Oxygen Species)
RN - 0 (bcl-2-Associated X Protein)
RN - EC 2-7-1-11 (Checkpoint Kinase 2)
RN - EC 2-7-11-22 (CDC2 Protein Kinase)
RN - EC 3-1-3-48 (CDC25C protein, human)
RN - EC 3-1-3-48 (cdc25 Phosphatases)
RN - EC 3-4-22 (Caspase 9)
ES - 1872-7980
IL - 0304-3835
DI - S0304-3835(14)00583-7
DO - https://dx.doi.org/10.1016/j.canlet.2014.09.042
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 25301449 [pubmed]
ID - S0304-3835(14)00583-7 [pii]
ID - 10.1016/j.canlet.2014.09.042 [doi]
PP - ppublish
PH - 2014/07/22 [received]
PH - 2014/09/28 [revised]
PH - 2014/09/29 [accepted]
LG - English
EP - 20141007
DP - 2014 Dec 28
DC - 20141202
EZ - 2014/10/11 06:00
DA - 2015/03/04 06:00
DT - 2014/10/11 06:00
YR - 2014
ED - 20150303
RD - 20141202
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25301449
<222. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24687600
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Izzedine H
AU - Gueutin V
AU - Gharbi C
AU - Mateus C
AU - Robert C
AU - Routier E
AU - Thomas M
AU - Baumelou A
AU - Rouvier P
FA - Izzedine, Hassane
FA - Gueutin, Victor
FA - Gharbi, Chems
FA - Mateus, Christine
FA - Robert, Caroline
FA - Routier, Emilie
FA - Thomas, Marina
FA - Baumelou, Alain
FA - Rouvier, Philippe
IN - Izzedine, Hassane. Department of Nephrology, Pitie-Salpetriere, 47-80 Boulevard de l'Hopital, 75013, Paris, France, hassan.izzedine@psl.aphp.fr.
TI - Kidney injuries related to ipilimumab.
SO - Investigational New Drugs. 32(4):769-73, 2014 Aug
AS - Invest New Drugs. 32(4):769-73, 2014 Aug
NJ - Investigational new drugs
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - gwj, 8309330
IO - Invest New Drugs
SB - Index Medicus
CP - United States
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Female
MH - Humans
MH - *Kidney Diseases/ci [Chemically Induced]
MH - Male
MH - Middle Aged
AB - Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) have been investigated in metastatic melanoma and other cancers and have shown promising results. Inhibition of CTLA-4 characteristically induces well-known side effects called "immune-related adverse events" (irAEs). IrAEs mainly include colitis, dermatitis, hepatitis, endocrinopathies; uveitis, iridocyclitis, neuropathies, and inflammatory myopathy have occasionally been reported. Kidney involvement is rare. We report 2 cases of acute granulomatous interstitial nephritis and present, based on literature review, renal disorders related to Ipilimumab therapy. Autoimmune symptoms have to be carefully checked for patients treated with CTLA-4 inhibitors. In order to reduce the risk of sequelae, early recognition of irAEs and treatment initiation are crucial.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
ES - 1573-0646
IL - 0167-6997
DO - https://dx.doi.org/10.1007/s10637-014-0092-7
PT - Case Reports
PT - Journal Article
ID - 24687600 [pubmed]
ID - 10.1007/s10637-014-0092-7 [doi]
PP - ppublish
PH - 2014/01/20 [received]
PH - 2014/03/18 [accepted]
LG - English
EP - 20140401
DP - 2014 Aug
DC - 20140717
EZ - 2014/04/02 06:00
DA - 2015/03/03 06:00
DT - 2014/04/02 06:00
YR - 2014
ED - 20150302
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24687600
<223. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24282275
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Slee RB
AU - Grimes BR
AU - Bansal R
AU - Gore J
AU - Blackburn C
AU - Brown L
AU - Gasaway R
AU - Jeong J
AU - Victorino J
AU - March KL
AU - Colombo R
AU - Herbert BS
AU - Korc M
FA - Slee, Roger B
FA - Grimes, Brenda R
FA - Bansal, Ruchi
FA - Gore, Jesse
FA - Blackburn, Corinne
FA - Brown, Lyndsey
FA - Gasaway, Rachel
FA - Jeong, Jaesik
FA - Victorino, Jose
FA - March, Keith L
FA - Colombo, Riccardo
FA - Herbert, Brittney-Shea
FA - Korc, Murray
IN - Slee, Roger B. Corresponding Authors: B.R. Grimes, Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 W. Walnut St, IB30, Indianapolis, IN 46202. brgrimes@iu.edu.
TI - Selective inhibition of pancreatic ductal adenocarcinoma cell growth by the mitotic MPS1 kinase inhibitor NMS-P715.
SO - Molecular Cancer Therapeutics. 13(2):307-15, 2014 Feb
AS - Mol Cancer Ther. 13(2):307-15, 2014 Feb
NJ - Molecular cancer therapeutics
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101132535
IO - Mol. Cancer Ther.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217310
OI - Source: NLM. NIHMS545057
SB - Index Medicus
CP - United States
MH - Adenocarcinoma/ge [Genetics]
MH - Adenocarcinoma/me [Metabolism]
MH - Adenocarcinoma/pa [Pathology]
MH - Animals
MH - Apoptosis/de [Drug Effects]
MH - Apoptosis/ge [Genetics]
MH - Blotting, Western
MH - Carcinoma, Pancreatic Ductal/ge [Genetics]
MH - Carcinoma, Pancreatic Ductal/me [Metabolism]
MH - Carcinoma, Pancreatic Ductal/pa [Pathology]
MH - *Cell Cycle Proteins/ai [Antagonists & Inhibitors]
MH - Cell Cycle Proteins/ge [Genetics]
MH - Cell Cycle Proteins/me [Metabolism]
MH - Cell Line, Tumor
MH - *Cell Proliferation/de [Drug Effects]
MH - Dose-Response Relationship, Drug
MH - Gene Expression Regulation, Neoplastic/de [Drug Effects]
MH - Humans
MH - In Situ Hybridization, Fluorescence
MH - Pancreatic Neoplasms/ge [Genetics]
MH - Pancreatic Neoplasms/me [Metabolism]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Prognosis
MH - Protein Kinase Inhibitors/pd [Pharmacology]
MH - *Protein-Serine-Threonine Kinases/ai [Antagonists & Inhibitors]
MH - Protein-Serine-Threonine Kinases/ge [Genetics]
MH - Protein-Serine-Threonine Kinases/me [Metabolism]
MH - *Protein-Tyrosine Kinases/ai [Antagonists & Inhibitors]
MH - Protein-Tyrosine Kinases/ge [Genetics]
MH - Protein-Tyrosine Kinases/me [Metabolism]
MH - *Pyrazoles/pd [Pharmacology]
MH - *Quinazolines/pd [Pharmacology]
MH - Survival Analysis
MH - Time Factors
MH - Transcriptome
AB - Most solid tumors, including pancreatic ductal adenocarcinoma (PDAC), exhibit structural and numerical chromosome instability (CIN). Although often implicated as a driver of tumor progression and drug resistance, CIN also reduces cell fitness and poses a vulnerability that can be exploited therapeutically. The spindle assembly checkpoint (SAC) ensures correct chromosome-microtubule attachment, thereby minimizing chromosome segregation errors. Many tumors exhibit upregulation of SAC components such as MPS1, which may help contain CIN within survivable limits. Prior studies showed that MPS1 inhibition with the small molecule NMS-P715 limits tumor growth in xenograft models. In cancer cell lines, NMS-P715 causes cell death associated with impaired SAC function and increased chromosome missegregation. Although normal cells appeared more resistant, effects on stem cells, which are the dose-limiting toxicity of most chemotherapeutics, were not examined. Elevated expression of 70 genes (CIN70), including MPS1, provides a surrogate measure of CIN and predicts poor patient survival in multiple tumor types. Our new findings show that the degree of CIN70 upregulation varies considerably among PDAC tumors, with higher CIN70 gene expression predictive of poor outcome. We identified a 25 gene subset (PDAC CIN25) whose overexpression was most strongly correlated with poor survival and included MPS1. In vitro, growth of human and murine PDAC cells is inhibited by NMS-P715 treatment, whereas adipose-derived human mesenchymal stem cells are relatively resistant and maintain chromosome stability upon exposure to NMS-P715. These studies suggest that NMS-P715 could have a favorable therapeutic index and warrant further investigation of MPS1 inhibition as a new PDAC treatment strategy.
RN - 0 (Cell Cycle Proteins)
RN - 0 (N-(2,6-diethylphenyl)-1-methyl-8-((4-((1-methylpiperidin-4-yl)carbamoyl)-2-(trifluoromethoxy)phenyl)amino)-4,5-dihydro-1H-pyrazolo(4,3-h)quinazoline-3-carboxamide)
RN - 0 (Protein Kinase Inhibitors)
RN - 0 (Pyrazoles)
RN - 0 (Quinazolines)
RN - EC 2-7-10-1 (Protein-Tyrosine Kinases)
RN - EC 2-7-11-1 (Protein-Serine-Threonine Kinases)
RN - EC 2-7-12-1 (TTK protein, human)
ES - 1538-8514
IL - 1535-7163
DI - 1535-7163.MCT-13-0324
DO - https://dx.doi.org/10.1158/1535-7163.MCT-13-0324
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 24282275 [pubmed]
ID - 1535-7163.MCT-13-0324 [pii]
ID - 10.1158/1535-7163.MCT-13-0324 [doi]
ID - PMC4217310 [pmc]
ID - NIHMS545057 [mid]
PP - ppublish
GI - No: R25 GM067592
Organization: (GM) *NIGMS NIH HHS*
Country: United States
No: R37 CA075059
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA082709
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R25-GM67592
Organization: (GM) *NIGMS NIH HHS*
Country: United States
No: R37-CA-075059
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA075059
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20131126
DP - 2014 Feb
DC - 20140211
EZ - 2013/11/28 06:00
DA - 2015/02/20 06:00
DT - 2013/11/28 06:00
YR - 2014
ED - 20150219
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24282275
<224. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25694832
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Majchel D
AU - Korytkowski MT
AI - Majchel, Deborah; ORCID: https://orcid.org/0000-0002-4598-9524
FA - Majchel, Deborah
FA - Korytkowski, Mary T
IN - Majchel, Deborah. Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh Medical Center, 3601 Fifth Avenue, Suite 3B, Pittsburgh, PA 15213, USA.
IN - Korytkowski, Mary T. Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh Medical Center, 3601 Fifth Avenue, Suite 3B, Pittsburgh, PA 15213, USA.
TI - Anticytotoxic T-lymphocyte antigen-4 induced autoimmune hypophysitis: a case report and literature review.
SO - Case Reports in Endocrinology Print. 2015:570293, 2015
AS - case report. endocrinol.. 2015:570293, 2015
NJ - Case reports in endocrinology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - 101576457
IO - Case Rep Endocrinol
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324809
CP - United States
AB - Objective. We describe a case of autoimmune hypophysitis induced by the anticytotoxic T-lymphocyte antigen-4 (CTLA-4) agent, ipilimumab. Methods. Case presentation and review of the literature. Results. Autoimmune hypophysitis, a previously described rare disorder, is being recognized more frequently as a side effect of novel immunomodulatory agents used in the treatment of malignancies such as melanoma. CTLA-4 agents are associated with immune-related adverse effects (irAE) which occur as a result of activation (or lack of inactivation) of the immune response. This impacts not only malignant cells but also different host organ-systems. Autoimmune hypophysitis is one of several endocrinopathies associated with these agents. Conclusion. It is important that endocrinologists become familiar with the endocrinopathies, such as autoimmune hypophysitis, associated with new immunomodulator agents which are being used with increasing frequency to treat a variety of malignancies.
IS - 2090-6501
IL - 2090-651X
DO - https://dx.doi.org/10.1155/2015/570293
PT - Journal Article
ID - 25694832 [pubmed]
ID - 10.1155/2015/570293 [doi]
ID - PMC4324809 [pmc]
PP - ppublish
PH - 2014/09/19 [received]
PH - 2015/01/09 [accepted]
LG - English
EP - 20150128
DP - 2015
DC - 20150219
EZ - 2015/02/20 06:00
DA - 2015/02/20 06:01
DT - 2015/02/20 06:00
YR - 2015
ED - 20150219
RD - 20150221
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=25694832
<225. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24622375
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Min L
AU - Ibrahim N
FA - Min, Le
FA - Ibrahim, Nageatte
IN - Min, Le. Brigham and Women's Hospital, Boston MA, USA. Electronic address: lmin1@partners.org.
IN - Ibrahim, Nageatte. Dana-Farber Cancer Institute, Boston, MA, USA.
TI - Ipilimumab-induced autoimmune adrenalitis.
SO - The Lancet Diabetes & Endocrinology. 1(3):e15, 2013 Nov
AS - Lancet Diabetes Endocrinol. 1(3):e15, 2013 Nov
NJ - The lancet. Diabetes & endocrinology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101618821
IO - Lancet Diabetes Endocrinol
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106239
OI - Source: NLM. NIHMS603111
SB - Index Medicus
CP - England
MH - *Adrenal Gland Diseases/ci [Chemically Induced]
MH - Adrenal Gland Diseases/co [Complications]
MH - Adrenal Gland Diseases/dg [Diagnostic Imaging]
MH - Adrenal Insufficiency/et [Etiology]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Autoimmune Diseases/ci [Chemically Induced]
MH - Autoimmune Diseases/co [Complications]
MH - Autoimmune Diseases/dg [Diagnostic Imaging]
MH - Female
MH - Humans
MH - Inflammation
MH - *Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - Tomography, X-Ray Computed
RN - 0 (Antibodies, Monoclonal)
RN - 6T8C155666 (ipilimumab)
ES - 2213-8595
IL - 2213-8587
DI - S2213-8587(13)70031-7
DO - https://dx.doi.org/10.1016/S2213-8587(13)70031-7
PT - Case Reports
PT - Journal Article
ID - 24622375 [pubmed]
ID - S2213-8587(13)70031-7 [pii]
ID - 10.1016/S2213-8587(13)70031-7 [doi]
ID - PMC4106239 [pmc]
ID - NIHMS603111 [mid]
PP - ppublish
GI - No: K08 HD070957
Organization: (HD) *NICHD NIH HHS*
Country: United States
No: T32 DK007529
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG - English
EP - 20130709
DP - 2013 Nov
DC - 20140313
EZ - 2014/03/14 06:00
DA - 2015/02/04 06:00
DT - 2014/03/14 06:00
YR - 2013
ED - 20150203
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24622375
<226. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25430657
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Alonso-Gordoa T
AU - Capdevila J
AU - Grande E
FA - Alonso-Gordoa, T
FA - Capdevila, J
FA - Grande, E
IN - Alonso-Gordoa, T. Medical Oncology DepartmentRamon y Cajal University Hospital, Carretera de Colmenar Km 9,100, 28034 Madrid, SpainMedical Oncology DepartmentVall d'Hebron University Hospital, Passeig de la Vall d'Hebron, 119-129, 08035 Barcelona, Spain.
IN - Capdevila, J. Medical Oncology DepartmentRamon y Cajal University Hospital, Carretera de Colmenar Km 9,100, 28034 Madrid, SpainMedical Oncology DepartmentVall d'Hebron University Hospital, Passeig de la Vall d'Hebron, 119-129, 08035 Barcelona, Spain.
IN - Grande, E. Medical Oncology DepartmentRamon y Cajal University Hospital, Carretera de Colmenar Km 9,100, 28034 Madrid, SpainMedical Oncology DepartmentVall d'Hebron University Hospital, Passeig de la Vall d'Hebron, 119-129, 08035 Barcelona, Spain egrande@oncologiahrc.com.
TI - GEP-NETs update: Biotherapy for neuroendocrine tumours. [Review]
SO - European Journal of Endocrinology. 172(1):R31-46, 2015 Jan
AS - EUR. J. ENDOCRINOL.. 172(1):R31-46, 2015 Jan
NJ - European journal of endocrinology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - bxu, 9423848
IO - Eur. J. Endocrinol.
SB - Index Medicus
CP - England
MH - Amino Acid Sequence
MH - Animals
MH - *Biological Therapy/mt [Methods]
MH - Humans
MH - Molecular Sequence Data
MH - Neuroendocrine Tumors/di [Diagnosis]
MH - Neuroendocrine Tumors/ge [Genetics]
MH - *Neuroendocrine Tumors/th [Therapy]
MH - Receptors, Somatostatin/ge [Genetics]
MH - *Somatostatin/ad [Administration & Dosage]
MH - Somatostatin/ge [Genetics]
AB - Neuroendocrine tumours (NETs) represent a less frequent and heterogeneous group of tumours, which has experienced, in recent years, a significant increase in effective therapeutic possibilities overcoming the disappointing results from chemotherapy. Initial improvements in treatment strategies came from somatostatin analogues (SSAs) that have widely demonstrated a significant improvement in symptomatic relief and tumour control growth by a complex mechanism of action over cell survival, angiogenesis and immunomodulation. Recent investigations have pointed out novel SSAs with a wider binding profile (pasireotide), chimeric molecules against somatostatin receptors and dopamine receptors and the combination with targeted agents, such as mTOR inhibitors or antiangiogenic agents. Immunotherapy is the second cornerstone in NET treatment and has been represented with interferon alpha for a long time, with a demonstrated activity on tumour and clinical response. Its less manageable adverse events have limited its usage. However, different checkpoints in immune system regulation have been effectively targeted in different solid tumours, and novel approaches are currently arising in NETs. In conclusion, biotherapy remains an active treatment strategy for initial approach in patients with NETs. Further investigation on patients' selection, molecular profiles, treatment sequence or combination and optimisation of current and novel biotherapy agents is required.
AB - Copyright © 2015 European Society of Endocrinology.
RN - 0 (Receptors, Somatostatin)
RN - 51110-01-1 (Somatostatin)
ES - 1479-683X
IL - 0804-4643
DI - 172/1/R31
DO - https://dx.doi.org/10.1530/EJE-14-0354
PT - Journal Article
PT - Review
ID - 25430657 [pubmed]
ID - 172/1/R31 [pii]
ID - 10.1530/EJE-14-0354 [doi]
PP - ppublish
LG - English
DP - 2015 Jan
DC - 20141128
EZ - 2014/11/29 06:00
DA - 2015/01/27 06:00
DT - 2014/11/29 06:00
YR - 2015
ED - 20150126
RD - 20161018
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25430657
<227. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25614822
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Rodrigues BT
AU - Otty Z
AU - Sangla K
AU - Shenoy VV
FA - Rodrigues, Beverly T
FA - Otty, Zulfiquer
FA - Sangla, Kunwarjit
FA - Shenoy, Vasant V
IN - Rodrigues, Beverly T. Department of Diabetes and Endocrinology, The Townsville Hospital , Townsville, Queensland , Australia ; School of Medicine and Dentistry, James Cook University , Douglas, Queensland , Australia.
IN - Otty, Zulfiquer. Department of Oncology, The Townsville Hospital , Townsville, Queensland , Australia.
IN - Sangla, Kunwarjit. Department of Diabetes and Endocrinology, The Townsville Hospital , Townsville, Queensland , Australia.
IN - Shenoy, Vasant V. Department of Diabetes and Endocrinology, The Townsville Hospital , Townsville, Queensland , Australia ; School of Medicine and Dentistry, James Cook University , Douglas, Queensland , Australia.
TI - Ipilimumab-induced autoimmune hypophysitis: a differential for sellar mass lesions.
SO - Endocrinology, Diabetes & Metabolism Case Reports. 2014:140098, 2014
AS - Endocrinol Diabetes Metab Case Rep. 2014:140098, 2014
NJ - Endocrinology, diabetes & metabolism case reports
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - 101618943
IO - Endocrinol Diabetes Metab Case Rep
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4276072
CP - England
AB - UNLABELLED: Autoimmune hypophysitis (AH) has been previously described in a typical demographic population, primarily women in the reproductive age group and perinatal period. The era of immune modulation using anti-cytotoxic T-lymphocyte-associated antigen 4 biological therapy (ipilimumab) against advanced cancers like metastatic melanomas has now resulted in a new form of hypophysitis being increasingly recognised under a spectrum of immune-related adverse events. Drug-related AH often presents with subtle symptoms and a pituitary mass, with the potential for fatality necessitating wide awareness and a high index of clinical suspicion given that it is usually treatable. We describe below two cases of AH within the last three months at our centre, which were treated with different regimens and produced good endocrine outcomes.
AB - LEARNING POINTS: AH is a new and defined clinical entity occurring as a side effect of ipilimumab, which enhances immune-mediated destruction of metastatic melanoma.It can present insidiously and have life-threatening complications related to hypocortisolism, hence a high index of clinical suspicion must be exerted by treating physicians, and seems to result in resolution of pituitary masses and variable improvements of pituitary function.Clinical improvement, radiological resolution of pituitary masses and variable normalisation of pituitary function are possible with early treatment with high-dose oral or i.v. steroids and hormone replacement therapy, although duration and dosing protocols are unclear at this stage.Ipilimumab should continue to be prescribed as treatment for metastatic melanoma; however, close clinical observation of patient's progress must be maintained while they are on this drug.Predictive factors for onset of AH remain unclear and it is imperative that AH is distinguished from pituitary metastases.Further studies are required to determine the safety of continuing therapy with ipilimumab in patients who have developed AH while on treatment.
IL - 2052-0573
DI - EDM140098
DO - https://dx.doi.org/10.1530/EDM-14-0098
PT - Journal Article
ID - 25614822 [pubmed]
ID - 10.1530/EDM-14-0098 [doi]
ID - EDM140098 [pii]
ID - PMC4276072 [pmc]
PP - ppublish
PH - 2014/11/16 [received]
PH - 2014/11/21 [accepted]
LG - English
EP - 20141201
DP - 2014
DC - 20150123
EZ - 2015/01/24 06:00
DA - 2015/01/24 06:01
DT - 2015/01/24 06:00
YR - 2014
ED - 20150123
RD - 20150125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=25614822
<228. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25082815
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Zhu Y
AU - Knolhoff BL
AU - Meyer MA
AU - Nywening TM
AU - West BL
AU - Luo J
AU - Wang-Gillam A
AU - Goedegebuure SP
AU - Linehan DC
AU - DeNardo DG
FA - Zhu, Yu
FA - Knolhoff, Brett L
FA - Meyer, Melissa A
FA - Nywening, Timothy M
FA - West, Brian L
FA - Luo, Jingqin
FA - Wang-Gillam, Andrea
FA - Goedegebuure, S Peter
FA - Linehan, David C
FA - DeNardo, David G
IN - Zhu, Yu. Department of Medicine, Washington University School of Medicine, St Louis, Missouri. BRIGHT Institute, Washington University School of Medicine, St Louis, Missouri.
IN - Knolhoff, Brett L. Department of Medicine, Washington University School of Medicine, St Louis, Missouri. BRIGHT Institute, Washington University School of Medicine, St Louis, Missouri.
IN - Meyer, Melissa A. Department of Medicine, Washington University School of Medicine, St Louis, Missouri. BRIGHT Institute, Washington University School of Medicine, St Louis, Missouri.
IN - Nywening, Timothy M. Department of Surgery, Washington University School of Medicine, St Louis, Missouri. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri.
IN - West, Brian L. Plexxikon Inc., Berkeley, California.
IN - Luo, Jingqin. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri. Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri.
IN - Wang-Gillam, Andrea. Department of Medicine, Washington University School of Medicine, St Louis, Missouri.
IN - Goedegebuure, S Peter. Department of Surgery, Washington University School of Medicine, St Louis, Missouri. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri.
IN - Linehan, David C. Department of Surgery, Washington University School of Medicine, St Louis, Missouri. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri.
IN - DeNardo, David G. Department of Medicine, Washington University School of Medicine, St Louis, Missouri. BRIGHT Institute, Washington University School of Medicine, St Louis, Missouri. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri. Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri. ddenardo@dom.wustl.edu.
TI - CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models.
SO - Cancer Research. 74(18):5057-69, 2014 Sep 15
AS - Cancer Res. 74(18):5057-69, 2014 Sep 15
NJ - Cancer research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cnf, 2984705r
IO - Cancer Res.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182950
OI - Source: NLM. NIHMS618198
SB - Index Medicus
CP - United States
MH - *Adenocarcinoma/im [Immunology]
MH - Adenocarcinoma/pa [Pathology]
MH - Animals
MH - Carcinoma, Pancreatic Ductal/im [Immunology]
MH - Carcinoma, Pancreatic Ductal/pa [Pathology]
MH - *Carcinoma, Pancreatic Ductal/th [Therapy]
MH - Cohort Studies
MH - Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Female
MH - Humans
MH - *Immunotherapy/mt [Methods]
MH - Lectins, C-Type/bi [Biosynthesis]
MH - Lectins, C-Type/im [Immunology]
MH - *Macrophage Colony-Stimulating Factor/ai [Antagonists & Inhibitors]
MH - Macrophage Colony-Stimulating Factor/bi [Biosynthesis]
MH - Macrophage Colony-Stimulating Factor/im [Immunology]
MH - *Macrophages/im [Immunology]
MH - Mannose-Binding Lectins/bi [Biosynthesis]
MH - Mannose-Binding Lectins/im [Immunology]
MH - Mice
MH - Mice, Inbred C57BL
MH - Pancreatic Neoplasms/im [Immunology]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - Random Allocation
MH - *Receptor, Macrophage Colony-Stimulating Factor/ai [Antagonists & Inhibitors]
MH - Receptor, Macrophage Colony-Stimulating Factor/im [Immunology]
MH - Receptors, Cell Surface/bi [Biosynthesis]
MH - Receptors, Cell Surface/im [Immunology]
MH - Signal Transduction
MH - *T-Lymphocytes/im [Immunology]
MH - Tissue Array Analysis
MH - Tumor Microenvironment
AB - Cancer immunotherapy generally offers limited clinical benefit without coordinated strategies to mitigate the immunosuppressive nature of the tumor microenvironment. Critical drivers of immune escape in the tumor microenvironment include tumor-associated macrophages and myeloid-derived suppressor cells, which not only mediate immune suppression, but also promote metastatic dissemination and impart resistance to cytotoxic therapies. Thus, strategies to ablate the effects of these myeloid cell populations may offer great therapeutic potential. In this report, we demonstrate in a mouse model of pancreatic ductal adenocarcinoma (PDAC) that inhibiting signaling by the myeloid growth factor receptor CSF1R can functionally reprogram macrophage responses that enhance antigen presentation and productive antitumor T-cell responses. Investigations of this response revealed that CSF1R blockade also upregulated T-cell checkpoint molecules, including PDL1 and CTLA4, thereby restraining beneficial therapeutic effects. We found that PD1 and CTLA4 antagonists showed limited efficacy as single agents to restrain PDAC growth, but that combining these agents with CSF1R blockade potently elicited tumor regressions, even in larger established tumors. Taken together, our findings provide a rationale to reprogram immunosuppressive myeloid cell populations in the tumor microenvironment under conditions that can significantly empower the therapeutic effects of checkpoint-based immunotherapeutics.
AB - Copyright ©2014 American Association for Cancer Research.
RN - 0 (Lectins, C-Type)
RN - 0 (Mannose-Binding Lectins)
RN - 0 (Receptors, Cell Surface)
RN - 0 (mannose receptor)
RN - 0W860991D6 (Deoxycytidine)
RN - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7-10-1 (Receptor, Macrophage Colony-Stimulating Factor)
ES - 1538-7445
IL - 0008-5472
DI - 0008-5472.CAN-13-3723
DO - https://dx.doi.org/10.1158/0008-5472.CAN-13-3723
PT - Journal Article
PT - Research Support, N.I.H., Extramural
ID - 25082815 [pubmed]
ID - 0008-5472.CAN-13-3723 [pii]
ID - 10.1158/0008-5472.CAN-13-3723 [doi]
ID - PMC4182950 [pmc]
ID - NIHMS618198 [mid]
PP - ppublish
GI - No: T32 CA113275
Organization: (CA) *NCI NIH HHS*
Country: United States
No: KL2TR000450
Organization: (TR) *NCATS NIH HHS*
Country: United States
No: T32 CA 009621
Organization: (CA) *NCI NIH HHS*
Country: United States
No: T32 CA009621
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA177670-01
Organization: (CA) *NCI NIH HHS*
Country: United States
No: UL1RR024992
Organization: (RR) *NCRR NIH HHS*
Country: United States
No: UL1 RR024992
Organization: (RR) *NCRR NIH HHS*
Country: United States
No: P30 CA91842
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA168863-01
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA091842
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA177670
Organization: (CA) *NCI NIH HHS*
Country: United States
No: UL1 TR000448
Organization: (TR) *NCATS NIH HHS*
Country: United States
No: KL2 RR024994
Organization: (RR) *NCRR NIH HHS*
Country: United States
No: R01 CA168863
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA182701
Organization: (CA) *NCI NIH HHS*
Country: United States
No: KL2 TR000450
Organization: (TR) *NCATS NIH HHS*
Country: United States
LG - English
EP - 20140731
DP - 2014 Sep 15
DC - 20140916
EZ - 2014/08/02 06:00
DA - 2015/01/21 06:00
DT - 2014/08/02 06:00
YR - 2014
ED - 20150120
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25082815
<229. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25078147
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Faje AT
AU - Sullivan R
AU - Lawrence D
AU - Tritos NA
AU - Fadden R
AU - Klibanski A
AU - Nachtigall L
FA - Faje, Alexander T
FA - Sullivan, Ryan
FA - Lawrence, Donald
FA - Tritos, Nicholas A
FA - Fadden, Riley
FA - Klibanski, Anne
FA - Nachtigall, Lisa
IN - Faje, Alexander T. Neuroendocrine Unit (A.T.F., N.A.T., A.K., L.N.), Massachusetts General Hospital and Harvard Medical School, and Center for Melanoma (R.S., D.L., R.F.), Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114.
TI - Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic melanoma.
SO - Journal of Clinical Endocrinology & Metabolism. 99(11):4078-85, 2014 Nov
AS - J Clin Endocrinol Metab. 99(11):4078-85, 2014 Nov
NJ - The Journal of clinical endocrinology and metabolism
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - hrb, 0375362
IO - J. Clin. Endocrinol. Metab.
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Adult
MH - Age Factors
MH - Aged
MH - Aged, 80 and over
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Female
MH - Humans
MH - *Hypopituitarism/ci [Chemically Induced]
MH - Hypopituitarism/mo [Mortality]
MH - Hypopituitarism/pa [Pathology]
MH - Longitudinal Studies
MH - Magnetic Resonance Imaging
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/mo [Mortality]
MH - Melanoma/sc [Secondary]
MH - Middle Aged
MH - *Pituitary Gland/pa [Pathology]
MH - Prognosis
MH - Retrospective Studies
MH - Risk Factors
MH - Sex Factors
AB - CONTEXT: Ipilimumab (Ipi) is approved by the Food and Drug Administration for the treatment of unresectable or metastatic melanoma. Little is known about Ipi-induced hypophysitis (IH), an important treatment complication.
AB - OBJECTIVE: The objectives of the study were as follows: 1) to examine the prevalence of IH, 2) to characterize the clinical course and treatment outcomes in IH, 3) to identify the risk factors for the development of IH, and 4) to determine optimal strategies for the management of IH.
AB - DESIGN: This was a retrospective review.
AB - SETTING: The study was conducted at a tertiary referral center.
AB - SUBJECTS: One hundred fifty-four adult patients with metastatic melanoma were evaluated at Massachusetts General Hospital and were treated with Ipi between March 2008 and December 2013.
AB - INTERVENTION(S): The intervention included treatment with Ipi.
AB - MAIN OUTCOME MEASURE(S): Pituitary magnetic resonance imaging, pituitary hormone assessment, and patient survival were measured.
AB - RESULTS: IH was diagnosed in 17 patients (11%). Male gender (P = .02) and older age (P = .005), but not the cumulative dose of Ipi, were risk factors for IH. All patients with IH had anterior hypopituitarism (none had diabetes insipidus). Hypopituitarism was persistent in most individuals (76%). Diffuse pituitary enlargement was observed exclusively in all cases of IH and, upon retrospective review of magnetic resonance imaging scans, this finding preceded the clinical diagnosis of hypophysitis in eight patients. Pituitary enlargement resolved rapidly (within 40 d in seven of seven patients). Median survival in patients with IH was 19.4 vs 8.8 months (P = .05) in the remainder of the cohort.
AB - CONCLUSIONS: Male gender and older age are risk factors for IH. Pituitary enlargement is sensitive and specific for IH in the appropriate setting, can precede the clinical diagnosis, and resolves rapidly. Anterior pituitary function recovery is uncommon. The incidence of hypophysitis may positively predict survival in melanoma patients treated with Ipi.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
ES - 1945-7197
IL - 0021-972X
DO - https://dx.doi.org/10.1210/jc.2014-2306
PT - Journal Article
ID - 25078147 [pubmed]
ID - 10.1210/jc.2014-2306 [doi]
PP - ppublish
LG - English
EP - 20140731
DP - 2014 Nov
DC - 20141106
EZ - 2014/08/01 06:00
DA - 2015/01/17 06:00
DT - 2014/08/01 06:00
YR - 2014
ED - 20150116
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25078147
<230. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24804869
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Shigetomi H
AU - Sudo T
AU - Shimada K
AU - Uekuri C
AU - Tsuji Y
AU - Kanayama S
AU - Naruse K
AU - Yamada Y
AU - Konishi N
AU - Kobayashi H
FA - Shigetomi, Hiroshi
FA - Sudo, Tamotsu
FA - Shimada, Keiji
FA - Uekuri, Chiharu
FA - Tsuji, Yoriko
FA - Kanayama, Seiji
FA - Naruse, Katsuhiko
FA - Yamada, Yoshihiko
FA - Konishi, Noboru
FA - Kobayashi, Hiroshi
IN - Shigetomi, Hiroshi. *Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Nara; +Section of Translational Research, Hyogo Cancer Center, Akashi, Hyogo; ++Department of Pathology, Nara Medical University, Kashihara, Nara; and Department of Obstetrics and Gynecology, Yao Municipal Hospital, Yao-city, Osaka, Japan.
TI - Inhibition of cell death and induction of G2 arrest accumulation in human ovarian clear cells by HNF-1beta transcription factor: chemosensitivity is regulated by checkpoint kinase CHK1.
SO - International Journal of Gynecological Cancer. 24(5):838-43, 2014 Jun
AS - Int J Gynecol Cancer. 24(5):838-43, 2014 Jun
NJ - International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - dzp, 9111626
IO - Int. J. Gynecol. Cancer
SB - Index Medicus
CP - United States
MH - Adenocarcinoma, Clear Cell/me [Metabolism]
MH - Adenocarcinoma, Clear Cell/pa [Pathology]
MH - *Apoptosis
MH - Blotting, Western
MH - *Cell Cycle Checkpoints
MH - Cell Proliferation
MH - Checkpoint Kinase 1
MH - *DNA Damage
MH - *Drug Resistance, Neoplasm
MH - Female
MH - Flow Cytometry
MH - *G2 Phase
MH - Hepatocyte Nuclear Factor 1-beta/ai [Antagonists & Inhibitors]
MH - Hepatocyte Nuclear Factor 1-beta/ge [Genetics]
MH - *Hepatocyte Nuclear Factor 1-beta/me [Metabolism]
MH - Humans
MH - *Ovarian Neoplasms/me [Metabolism]
MH - *Ovarian Neoplasms/pa [Pathology]
MH - *Protein Kinases/me [Metabolism]
MH - RNA, Small Interfering/ge [Genetics]
MH - Tumor Cells, Cultured
AB - OBJECTIVE: Appropriate cell cycle checkpoints are essential for the maintenance of normal cells and chemosensitivity of cancer cells. Clear cell adenocarcinoma (CCA) of the ovary is highly resistant to chemotherapy. Hepatocyte nuclear factor-1beta (HNF-1beta) is known to be overexpressed in CCA, but its role and clinical significance is unclear. We investigated the role of HNF-1beta in regulation of the cell cycle in CCA.
AB - METHODS: To clarify the effects of HNF-1beta on cell cycle checkpoints, we compared the cell cycle distribution and the expression of key proteins involved in CCA cells in which HNF-1beta had been stably knocked down and in vector-control cell lines after treatment with bleomycin. HNF-1beta (+) cells were arrested in G2 phase because of DNA damage.
AB - RESULTS: HNF-1beta (-) cells died because of a checkpoint mechanism. G2 arrest of HNF-1beta (+) cells resulted from sustained CHK1 activation, a protein that plays a major role in the checkpoint mechanism. HNF-1beta (+) cells were treated with a CHK1 inhibitor after bleomycin treatment. Flow cytometric analysis of the cell cycle demonstrated that DNA damage-induced G2-arrested cells were released from the checkpoint and killed by a CHK1 inhibitor.
AB - CONCLUSIONS: The chemoresistance of CCA may be due to aberrant retention of the G2 checkpoint through overexpression of HNF-1beta. This is the first study demonstrating cell cycle regulation and chemosensitization by a CHK1 inhibitor in CCA.
RN - 0 (HNF1B protein, human)
RN - 0 (RNA, Small Interfering)
RN - 138674-15-4 (Hepatocyte Nuclear Factor 1-beta)
RN - EC 2-7 (Protein Kinases)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
ES - 1525-1438
IL - 1048-891X
DO - https://dx.doi.org/10.1097/IGC.0000000000000136
PT - Journal Article
ID - 24804869 [pubmed]
ID - 10.1097/IGC.0000000000000136 [doi]
PP - ppublish
LG - English
DP - 2014 Jun
DC - 20140521
EZ - 2014/05/09 06:00
DA - 2015/01/13 06:00
DT - 2014/05/09 06:00
YR - 2014
ED - 20150109
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24804869
<231. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24832153
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - De Remigis A
AU - de Gruijl TD
AU - Uram JN
AU - Tzou SC
AU - Iwama S
AU - Talor MV
AU - Armstrong TD
AU - Santegoets SJ
AU - Slovin SF
AU - Zheng L
AU - Laheru DA
AU - Jaffee EM
AU - Gerritsen WR
AU - van den Eertwegh AJ
AU - Le DT
AU - Caturegli P
FA - De Remigis, Alessandra
FA - de Gruijl, Tanja D
FA - Uram, Jennifer N
FA - Tzou, Schey-Cherng
FA - Iwama, Shintaro
FA - Talor, Monica V
FA - Armstrong, Todd D
FA - Santegoets, Saskia J A M
FA - Slovin, Susan F
FA - Zheng, Lei
FA - Laheru, Daniel A
FA - Jaffee, Elizabeth M
FA - Gerritsen, Winald R
FA - van den Eertwegh, Alfons J M
FA - Le, Dung T
FA - Caturegli, Patrizio
IN - De Remigis, Alessandra. Department of Pathology, Johns Hopkins University, Baltimore, MD.
TI - Development of thyroglobulin antibodies after GVAX immunotherapy is associated with prolonged survival.
SO - International Journal of Cancer. 136(1):127-37, 2015 Jan 01
AS - Int J Cancer. 136(1):127-37, 2015 Jan 01
NJ - International journal of cancer
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - gqu, 0042124
IO - Int. J. Cancer
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199892
OI - Source: NLM. NIHMS596021
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Neoplasm/bl [Blood]
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - Autoantibodies/bl [Blood]
MH - CD4-Positive T-Lymphocytes/im [Immunology]
MH - CD4-Positive T-Lymphocytes/me [Metabolism]
MH - CD8-Positive T-Lymphocytes/im [Immunology]
MH - CD8-Positive T-Lymphocytes/me [Metabolism]
MH - *Cancer Vaccines/ad [Administration & Dosage]
MH - Cancer Vaccines/im [Immunology]
MH - Cell Line, Tumor
MH - Cohort Studies
MH - Colonic Neoplasms/bl [Blood]
MH - Colonic Neoplasms/im [Immunology]
MH - Colonic Neoplasms/mo [Mortality]
MH - *Colonic Neoplasms/th [Therapy]
MH - Combined Modality Therapy
MH - Humans
MH - Male
MH - Pancreatic Neoplasms/bl [Blood]
MH - Pancreatic Neoplasms/im [Immunology]
MH - Pancreatic Neoplasms/mo [Mortality]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - Prostatic Neoplasms/bl [Blood]
MH - Prostatic Neoplasms/im [Immunology]
MH - Prostatic Neoplasms/mo [Mortality]
MH - *Prostatic Neoplasms/th [Therapy]
MH - RNA, Messenger/ge [Genetics]
MH - RNA, Messenger/me [Metabolism]
MH - Survival Analysis
MH - Thyroglobulin/ge [Genetics]
MH - *Thyroglobulin/im [Immunology]
MH - Thyroglobulin/me [Metabolism]
MH - Thyrotropin/bl [Blood]
MH - Vaccination
KW - CTLA-4; GVAX; immunotherapy; thyroglobulin antibodies
AB - Cancer immunotherapy induces a variety of autoinflammatory responses, including those against the thyroid gland, which can be exploited to predict clinical outcomes. Considering the paucity of information about thyroid autoimmunity in patients receiving cancer vaccines, we designed our study to assess the development of thyroglobulin antibodies (TgAbs) in patients treated with GVAX (vaccine made of a tumor cell type transfected with GM-CSF) and/or ipilimumab and correlated seroconversion with survival. Using both in house and commercial ELISA assays, we measured TgAbs in patients with pancreatic (No.=53), prostate (No.=35) or colon (No.=8) cancer, before and after treatment with GVAX only (No.=34), GVAX plus ipilimumab (No.=42) or ipilimumab (No.=20), and correlated their levels with patient's survival, disease status and T-cell surface markers. Antibodies to thyroperoxidase, myeloperoxidase, proteinase 3, insulin and actin were also measured. TgAbs specifically developed after GVAX, independent of the underlying cancer (81% in prostate, 75% colon cancer and 76% pancreatic cancer) and co-administration of ipilimumab (75% in GVAX only and 78% in GVAX plus ipilimumab). This TgAbs seroconversion could be detected mainly by the in house assay, suggesting that the thyroglobulin epitopes recognized by the antibodies induced by GVAX are different from the epitopes seen in the classic form of Hashimoto thyroiditis. Notably, TgAbs seroconversion was associated with significantly prolonged survival (p=0.01 for pancreas and p=0.005 for prostate cancer). In conclusion, GVAX immunotherapy induces the appearance of TgAbs that recognize a unique antigenic repertoire and associate with prolonged survival.
AB - Copyright © 2014 UICC.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Neoplasm)
RN - 0 (Antineoplastic Agents)
RN - 0 (Autoantibodies)
RN - 0 (Cancer Vaccines)
RN - 0 (GVAX vaccine)
RN - 0 (RNA, Messenger)
RN - 6T8C155666 (ipilimumab)
RN - 9002-71-5 (Thyrotropin)
RN - 9010-34-8 (Thyroglobulin)
ES - 1097-0215
IL - 0020-7136
DO - https://dx.doi.org/10.1002/ijc.28973
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 24832153 [pubmed]
ID - 10.1002/ijc.28973 [doi]
ID - PMC4199892 [pmc]
ID - NIHMS596021 [mid]
PP - ppublish
PH - 2013/10/09 [received]
PH - 2014/04/30 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00389610
SA - ClinicalTrials.gov/NCT00656123
SA - ClinicalTrials.gov/NCT00323882
SA - ClinicalTrials.gov/NCT00836407
SA - ClinicalTrials.gov/NCT01510288
SL - https://clinicaltrials.gov/search/term=NCT00389610
SL - https://clinicaltrials.gov/search/term=NCT00656123
SL - https://clinicaltrials.gov/search/term=NCT00323882
SL - https://clinicaltrials.gov/search/term=NCT00836407
SL - https://clinicaltrials.gov/search/term=NCT01510288
GI - No: DK080351
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: P50 CA062924
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA148964
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 DK080351
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: K23 CA148964-01
Organization: (CA) *NCI NIH HHS*
Country: United States
No: 2P50 CA062924
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA1266058
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA126058
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA163672
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20140528
DP - 2015 Jan 01
DC - 20141016
EZ - 2014/05/17 06:00
DA - 2014/12/23 06:00
DT - 2014/05/17 06:00
YR - 2015
ED - 20141222
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24832153
<232. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24832153
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - De Remigis A
AU - de Gruijl TD
AU - Uram JN
AU - Tzou SC
AU - Iwama S
AU - Talor MV
AU - Armstrong TD
AU - Santegoets SJ
AU - Slovin SF
AU - Zheng L
AU - Laheru DA
AU - Jaffee EM
AU - Gerritsen WR
AU - van den Eertwegh AJ
AU - Le DT
AU - Caturegli P
FA - De Remigis, Alessandra
FA - de Gruijl, Tanja D
FA - Uram, Jennifer N
FA - Tzou, Schey-Cherng
FA - Iwama, Shintaro
FA - Talor, Monica V
FA - Armstrong, Todd D
FA - Santegoets, Saskia J A M
FA - Slovin, Susan F
FA - Zheng, Lei
FA - Laheru, Daniel A
FA - Jaffee, Elizabeth M
FA - Gerritsen, Winald R
FA - van den Eertwegh, Alfons J M
FA - Le, Dung T
FA - Caturegli, Patrizio
IN - De Remigis, Alessandra. Department of Pathology, Johns Hopkins University, Baltimore, MD.
TI - Development of thyroglobulin antibodies after GVAX immunotherapy is associated with prolonged survival.
SO - International Journal of Cancer. 136(1):127-37, 2015 Jan 01
AS - Int J Cancer. 136(1):127-37, 2015 Jan 01
NJ - International journal of cancer
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - gqu, 0042124
IO - Int. J. Cancer
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199892
OI - Source: NLM. NIHMS596021
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Neoplasm/bl [Blood]
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - Autoantibodies/bl [Blood]
MH - CD4-Positive T-Lymphocytes/im [Immunology]
MH - CD4-Positive T-Lymphocytes/me [Metabolism]
MH - CD8-Positive T-Lymphocytes/im [Immunology]
MH - CD8-Positive T-Lymphocytes/me [Metabolism]
MH - *Cancer Vaccines/ad [Administration & Dosage]
MH - Cancer Vaccines/im [Immunology]
MH - Cell Line, Tumor
MH - Cohort Studies
MH - Colonic Neoplasms/bl [Blood]
MH - Colonic Neoplasms/im [Immunology]
MH - Colonic Neoplasms/mo [Mortality]
MH - *Colonic Neoplasms/th [Therapy]
MH - Combined Modality Therapy
MH - Humans
MH - Male
MH - Pancreatic Neoplasms/bl [Blood]
MH - Pancreatic Neoplasms/im [Immunology]
MH - Pancreatic Neoplasms/mo [Mortality]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - Prostatic Neoplasms/bl [Blood]
MH - Prostatic Neoplasms/im [Immunology]
MH - Prostatic Neoplasms/mo [Mortality]
MH - *Prostatic Neoplasms/th [Therapy]
MH - RNA, Messenger/ge [Genetics]
MH - RNA, Messenger/me [Metabolism]
MH - Survival Analysis
MH - Thyroglobulin/ge [Genetics]
MH - *Thyroglobulin/im [Immunology]
MH - Thyroglobulin/me [Metabolism]
MH - Thyrotropin/bl [Blood]
MH - Vaccination
KW - CTLA-4; GVAX; immunotherapy; thyroglobulin antibodies
AB - Cancer immunotherapy induces a variety of autoinflammatory responses, including those against the thyroid gland, which can be exploited to predict clinical outcomes. Considering the paucity of information about thyroid autoimmunity in patients receiving cancer vaccines, we designed our study to assess the development of thyroglobulin antibodies (TgAbs) in patients treated with GVAX (vaccine made of a tumor cell type transfected with GM-CSF) and/or ipilimumab and correlated seroconversion with survival. Using both in house and commercial ELISA assays, we measured TgAbs in patients with pancreatic (No.=53), prostate (No.=35) or colon (No.=8) cancer, before and after treatment with GVAX only (No.=34), GVAX plus ipilimumab (No.=42) or ipilimumab (No.=20), and correlated their levels with patient's survival, disease status and T-cell surface markers. Antibodies to thyroperoxidase, myeloperoxidase, proteinase 3, insulin and actin were also measured. TgAbs specifically developed after GVAX, independent of the underlying cancer (81% in prostate, 75% colon cancer and 76% pancreatic cancer) and co-administration of ipilimumab (75% in GVAX only and 78% in GVAX plus ipilimumab). This TgAbs seroconversion could be detected mainly by the in house assay, suggesting that the thyroglobulin epitopes recognized by the antibodies induced by GVAX are different from the epitopes seen in the classic form of Hashimoto thyroiditis. Notably, TgAbs seroconversion was associated with significantly prolonged survival (p=0.01 for pancreas and p=0.005 for prostate cancer). In conclusion, GVAX immunotherapy induces the appearance of TgAbs that recognize a unique antigenic repertoire and associate with prolonged survival.
AB - Copyright © 2014 UICC.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Neoplasm)
RN - 0 (Antineoplastic Agents)
RN - 0 (Autoantibodies)
RN - 0 (Cancer Vaccines)
RN - 0 (GVAX vaccine)
RN - 0 (RNA, Messenger)
RN - 6T8C155666 (ipilimumab)
RN - 9002-71-5 (Thyrotropin)
RN - 9010-34-8 (Thyroglobulin)
ES - 1097-0215
IL - 0020-7136
DO - https://dx.doi.org/10.1002/ijc.28973
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 24832153 [pubmed]
ID - 10.1002/ijc.28973 [doi]
ID - PMC4199892 [pmc]
ID - NIHMS596021 [mid]
PP - ppublish
PH - 2013/10/09 [received]
PH - 2014/04/30 [accepted]
GI - No: DK080351
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: P50 CA062924
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA148964
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 DK080351
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: K23 CA148964-01
Organization: (CA) *NCI NIH HHS*
Country: United States
No: 2P50 CA062924
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA1266058
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA126058
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA163672
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20140528
DP - 2015 Jan 01
DC - 20141016
EZ - 2014/05/17 06:00
DA - 2014/12/23 06:00
DT - 2014/05/17 06:00
YR - 2015
ED - 20141222
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=24832153
<233. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24778161
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Min L
AU - Hodi FS
FA - Min, Le
FA - Hodi, F Stephen
IN - Min, Le. Authors' Affiliations: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
TI - Anti-PD1 following ipilimumab for mucosal melanoma: durable tumor response associated with severe hypothyroidism and rhabdomyolysis.
SO - Cancer Immunology Research. 2(1):15-8, 2014 Jan
AS - Cancer Immunol Res. 2(1):15-8, 2014 Jan
NJ - Cancer immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101614637
IO - Cancer Immunol Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006358
OI - Source: NLM. NIHMS542984
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/pd [Pharmacology]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antibodies, Monoclonal, Humanized
MH - Antineoplastic Agents/pd [Pharmacology]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Humans
MH - Hypothyroidism/di [Diagnosis]
MH - Hypothyroidism/et [Etiology]
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - *Melanoma/pa [Pathology]
MH - Middle Aged
MH - *Mucous Membrane/pa [Pathology]
MH - Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Rhabdomyolysis/di [Diagnosis]
MH - Rhabdomyolysis/et [Etiology]
MH - Treatment Outcome
AB - Treatment with fully human monoclonal antibodies against programmed death 1 (PD1) receptor has shown great promise for a number of advanced malignancies. Although inflammatory adverse events have been well described with anti-CTL antigen 4 (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report on a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near-complete response but developed severe hypothyroidism, rhabdomyolysis, and acute kidney injury. To our knowledge, this is the first case reported of a patient with advanced mucosal melanoma who responded to anti-PD1 therapy. With the promising antitumor effects of anti-PD1 in a wide array of tumors, we expect an increasing number of patients to be exposed to anti-PD1 therapies. Recognition of infrequent presentations of adverse events such as elevated creatine kinase levels and thyroid disorders in patients who receive anti-PD1 therapy is important.
AB - Copyright ©2014 AACR.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 6T8C155666 (ipilimumab)
RN - DPT0O3T46P (pembrolizumab)
ES - 2326-6074
IL - 2326-6066
DI - 2326-6066.CIR-13-0146
DO - https://dx.doi.org/10.1158/2326-6066.CIR-13-0146
PT - Case Reports
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 24778161 [pubmed]
ID - 2326-6066.CIR-13-0146 [pii]
ID - 10.1158/2326-6066.CIR-13-0146 [doi]
ID - PMC4006358 [pmc]
ID - NIHMS542984 [mid]
PP - ppublish
GI - No: K08 HD070957
Organization: (HD) *NICHD NIH HHS*
Country: United States
No: T32 DK007529
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: 5K08HD070957
Organization: (HD) *NICHD NIH HHS*
Country: United States
LG - English
EP - 20131007
DP - 2014 Jan
DC - 20140429
EZ - 2014/04/30 06:00
DA - 2014/12/19 06:00
DT - 2014/04/30 06:00
YR - 2014
ED - 20141218
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24778161
<234. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24778314
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Fearon DT
FA - Fearon, Douglas T
IN - Fearon, Douglas T. Author's Affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
TI - The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillance.
SO - Cancer Immunology Research. 2(3):187-93, 2014 Mar
AS - Cancer Immunol Res. 2(3):187-93, 2014 Mar
NJ - Cancer immunology research
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101614637
IO - Cancer Immunol Res
SB - Index Medicus
CP - United States
MH - Animals
MH - CD8-Positive T-Lymphocytes/im [Immunology]
MH - *Carcinoma, Pancreatic Ductal/im [Immunology]
MH - *Carcinoma, Pancreatic Ductal/pa [Pathology]
MH - Chemokine CXCL12/im [Immunology]
MH - Drug Resistance, Neoplasm
MH - *Fibroblasts/me [Metabolism]
MH - Gelatinases/me [Metabolism]
MH - Humans
MH - Membrane Proteins/me [Metabolism]
MH - Mice
MH - Neoplasms, Experimental
MH - *Pancreatic Neoplasms/im [Immunology]
MH - *Pancreatic Neoplasms/pa [Pathology]
MH - Receptors, CXCR4/im [Immunology]
MH - Serine Endopeptidases/me [Metabolism]
MH - Stromal Cells/ph [Physiology]
MH - *Tumor Escape
MH - Tumor Microenvironment
AB - The fibroblastic element of the tumor microenvironment has been of great interest to cancer biologists but less so to cancer immunologists. Yet, the sharing of a common mesenchymal cell type in the stroma of tumors and at sites of chronic inflammatory lesions, some of which have an autoimmune basis, has been a strong hint that this cellular component of the tumor microenvironment may have an immunologic function. Recent studies have confirmed this possibility. These fibroblast-like cells, which are termed carcinoma-associated fibroblasts (CAF), can be identified by their expression of the membrane protein, fibroblast activation protein-alpha (FAP). The conditional depletion of the FAP(+) CAF permits immune control not only of an artificial, transplanted tumor, but also of an autochthonous model of pancreatic ductal adenocarcinoma (PDA) that replicates the molecular, histologic, clinical, and immunologic characteristics of the human disease. Immune suppression by the FAP(+) CAF is mediated by CXCL12, the chemokine that binds to cancer cells and excludes T cells by a mechanism that depends on signaling by the CXCL12 receptor CXCR4. Inhibition of CXCR4 leads to the elimination of cancer cells by enabling the rapid, intratumoral accumulation of preexisting, PDA-specific CD8(+) T cells, and reveals the antitumor efficacy of the T-cell checkpoint antagonist anti-PD-L1. Recent studies have also shown that the FAP(+) CAF is related to FAP-expressing stromal cells of normal tissues, demonstrating that cancers recruit a member of an essential stromal cell lineage that is involved not only in wound repair but also in normal tissue homeostasis. These findings extend the concept introduced by cancer biologists that the fibroblastic component of tumors has a critical role in the adaptation of the cancer to the host.
AB - Copyright ©2014 AACR.
RN - 0 (Chemokine CXCL12)
RN - 0 (Membrane Proteins)
RN - 0 (Receptors, CXCR4)
RN - EC 3-4-21 (Serine Endopeptidases)
RN - EC 3-4-21 (fibroblast activation protein alpha)
RN - EC 3-4-24 (Gelatinases)
ES - 2326-6074
IL - 2326-6066
DI - 2/3/187
DO - https://dx.doi.org/10.1158/2326-6066.CIR-14-0002
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 24778314 [pubmed]
ID - 2/3/187 [pii]
ID - 10.1158/2326-6066.CIR-14-0002 [doi]
PP - ppublish
LG - English
DP - 2014 Mar
DC - 20140429
EZ - 2014/04/30 06:00
DA - 2014/12/15 06:00
DT - 2014/04/30 06:00
YR - 2014
ED - 20141208
RD - 20160122
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24778314
<235. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24695685
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Iwama S
AU - De Remigis A
AU - Callahan MK
AU - Slovin SF
AU - Wolchok JD
AU - Caturegli P
FA - Iwama, Shintaro
FA - De Remigis, Alessandra
FA - Callahan, Margaret K
FA - Slovin, Susan F
FA - Wolchok, Jedd D
FA - Caturegli, Patrizio
IN - Iwama, Shintaro. Department of Pathology, Johns Hopkins University, Baltimore, MD 21205, USA.
TI - Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody.
SO - Science Translational Medicine. 6(230):230ra45, 2014 Apr 02
AS - Sci Transl Med. 6(230):230ra45, 2014 Apr 02
NJ - Science translational medicine
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101505086
IO - Sci Transl Med
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Animals
MH - *Antibodies, Blocking/ad [Administration & Dosage]
MH - *Antibodies, Blocking/ae [Adverse Effects]
MH - Antibodies, Blocking/bl [Blood]
MH - Antibodies, Blocking/tu [Therapeutic Use]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Autoantibodies/bl [Blood]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - *CTLA-4 Antigen/me [Metabolism]
MH - Complement System Proteins/me [Metabolism]
MH - Disease Models, Animal
MH - Female
MH - Flow Cytometry
MH - Fluorescent Antibody Technique
MH - Hematopoiesis/de [Drug Effects]
MH - Humans
MH - Magnetic Resonance Imaging
MH - Male
MH - Mice
MH - Middle Aged
MH - Pituitary Diseases/bl [Blood]
MH - Pituitary Diseases/dt [Drug Therapy]
MH - *Pituitary Diseases/et [Etiology]
MH - *Pituitary Diseases/im [Immunology]
MH - Pituitary Gland/im [Immunology]
MH - *Pituitary Gland/me [Metabolism]
MH - Pituitary Gland/pa [Pathology]
MH - Pituitary Neoplasms/bl [Blood]
MH - Pituitary Neoplasms/dt [Drug Therapy]
MH - Pituitary Neoplasms/im [Immunology]
MH - Prolactin/se [Secretion]
MH - Thyrotropin/se [Secretion]
AB - Hypophysitis is a chronic inflammation of the pituitary gland of unknown (primary forms) or recognizable (secondary forms) etiology, such as the use of ipilimumab in cancer immunotherapy. Ipilimumab, which blocks the T cell inhibitory molecule CTLA-4 (cytotoxic T lymphocyte antigen-4), induces hypophysitis in about 4% of patients through unknown mechanisms. We first established a model of secondary hypophysitis by repeated injections of a CTLA-4 blocking antibody into SJL/J or C57BL/6J mice, and showed that they developed lymphocytic infiltration of the pituitary gland and circulating pituitary antibodies. We next assessed the prevalence of pituitary antibodies in a cohort of 20 patients with advanced melanoma or prostate cancer, 7 with a clinical diagnosis of hypophysitis, before and after ipilimumab administration. Pituitary antibodies, negative at baseline, developed in the 7 patients with hypophysitis but not in the 13 without it; these antibodies predominantly recognized thyrotropin-, follicle-stimulating hormone-, and corticotropin-secreting cells. We then hypothesized that the injected CTLA-4 antibody could cause pituitary toxicity if bound to CTLA-4 antigen expressed "ectopically" on pituitary endocrine cells. Pituitary glands indeed expressed CTLA-4 at both RNA and protein levels, particularly in a subset of prolactin- and thyrotropin-secreting cells. Notably, these cells became the site of complement activation, featuring deposition of C3d and C4d components and an inflammatory cascade akin to that seen in type II hypersensitivity. In summary, the study offers a mechanism to explain the pituitary toxicity observed in patients receiving ipilimumab, and highlights the utility of measuring pituitary antibodies in this form of secondary hypophysitis.
RN - 0 (Antibodies, Blocking)
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Autoantibodies)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
RN - 9002-62-4 (Prolactin)
RN - 9002-71-5 (Thyrotropin)
RN - 9007-36-7 (Complement System Proteins)
ES - 1946-6242
IL - 1946-6234
DI - 6/230/230ra45
DO - https://dx.doi.org/10.1126/scitranslmed.3008002
PT - Clinical Trial
PT - Journal Article
PT - Multicenter Study
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 24695685 [pubmed]
ID - 6/230/230ra45 [pii]
ID - 10.1126/scitranslmed.3008002 [doi]
PP - ppublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00323882
SA - ClinicalTrials.gov/NCT00495066
SA - ClinicalTrials.gov/NCT00623766
SA - ClinicalTrials.gov/NCT00920907
SL - https://clinicaltrials.gov/search/term=NCT00323882
SL - https://clinicaltrials.gov/search/term=NCT00495066
SL - https://clinicaltrials.gov/search/term=NCT00623766
SL - https://clinicaltrials.gov/search/term=NCT00920907
GI - No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
No: DK080351
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG - English
DP - 2014 Apr 02
DC - 20140403
EZ - 2014/04/04 06:00
DA - 2014/11/19 06:00
DT - 2014/04/04 06:00
YR - 2014
ED - 20141118
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24695685
<236. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24610577
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Ryder M
AU - Callahan M
AU - Postow MA
AU - Wolchok J
AU - Fagin JA
FA - Ryder, Mabel
FA - Callahan, Margaret
FA - Postow, Michael A
FA - Wolchok, Jedd
FA - Fagin, James A
IN - Ryder, Mabel. Human Oncology and Pathogenesis Program, Department of Medicine Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York, USA Weill Cornell Medical College, New York, New York, USA.
TI - Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution. [Review]
SO - Endocrine-Related Cancer. 21(2):371-81, 2014 Apr
AS - Endocr Relat Cancer. 21(2):371-81, 2014 Apr
NJ - Endocrine-related cancer
PI - Journal available in: Electronic-Print
PI - Citation processed from: Internet
JC - 9436481, dgr
IO - Endocr. Relat. Cancer
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573438
OI - Source: NLM. NIHMS616115
SB - Index Medicus
CP - England
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - *Endocrine System Diseases/ci [Chemically Induced]
MH - Endocrine System Diseases/ep [Epidemiology]
MH - Humans
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/ep [Epidemiology]
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/ep [Epidemiology]
MH - Testosterone/bl [Blood]
KW - hypophysitis; immune-related adverse effects; ipilimumab; nivolumab; thyroiditis
AB - Novel immune checkpoint blockade with ipilimumab, an antibody blocking the cytotoxic T-lymphocyte antigen 4 (CTLA4), is revolutionizing cancer therapy. However, ipilimumab induces symptomatic, sometimes severe, endocrine immune-related adverse events (irAEs) that are inconsistently recognized and reported. The objective of this review was to comprehensively characterize the incidence, presentation, and management of endocrinopathies following ipilimumab therapy in a single center that is highly specialized in immune checkpoint blockade. We carried out a retrospective analysis of endocrine irAEs in melanoma patients receiving ipilimumab therapy in clinical trials between 2007 and 2013. A total of 256 patients were included in this analysis. We reviewed pituitary-, thyroid-, and adrenal-related hormone test results, as well as radiographic studies and the clinical histories of patients, to identify and characterize cases of hypophysitis, hypothyroidism, thyroiditis, and adrenal dysfunction. Following ipilimumab therapy, the overall incidence of hypophysitis was 8% and that of hypothyroidism/thyroiditis 6%. Primary adrenal dysfunction was rare. Therapy with a combination of ipilimumab and nivolumab, an anti-programmed cell death 1 (PDCD1, also called PD1) receptor antibody, was associated with a 22% incidence of either thyroiditis or hypothyroidism and a 9% incidence of hypophysitis. Symptomatic relief, in particular, for hypophysitis, was achieved in all patients with hormone replacement, although endogenous hormone secretion rarely recovered. In summary, we observed that CTLA4 blockade alone, and in particular in combination with PD1 blockade, is associated with an increased risk of symptomatic, sometimes severe, hypophysitis as well as thyroid dysfunction. Prompt initiation with hormone replacement reverses symptoms. Evaluation and reporting of endocrine irAEs in clinical trials should be done using standardized diagnostic criteria and terminology.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 3XMK78S47O (Testosterone)
RN - 6T8C155666 (ipilimumab)
ES - 1479-6821
IL - 1351-0088
DI - 21/2/371
DO - https://dx.doi.org/10.1530/ERC-13-0499
PT - Journal Article
PT - Review
ID - 24610577 [pubmed]
ID - 21/2/371 [pii]
ID - 10.1530/ERC-13-0499 [doi]
ID - PMC4573438 [pmc]
ID - NIHMS616115 [mid]
PP - epublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01245556
SA - ClinicalTrials.gov/NCT00920907
SA - ClinicalTrials.gov/NCT00289640
SA - ClinicalTrials.gov/NCT01024231
SA - ClinicalTrials.gov/NCT00324155
SA - ClinicalTrials.gov/NCT00495066
SA - ClinicalTrials.gov/NCT00289627
SA - ClinicalTrials.gov/NCT00162123
SA - ClinicalTrials.gov/NCT01323517
SA - ClinicalTrials.gov/NCT00796991
SL - https://clinicaltrials.gov/search/term=NCT01245556
SL - https://clinicaltrials.gov/search/term=NCT00920907
SL - https://clinicaltrials.gov/search/term=NCT00289640
SL - https://clinicaltrials.gov/search/term=NCT01024231
SL - https://clinicaltrials.gov/search/term=NCT00324155
SL - https://clinicaltrials.gov/search/term=NCT00495066
SL - https://clinicaltrials.gov/search/term=NCT00289627
SL - https://clinicaltrials.gov/search/term=NCT00162123
SL - https://clinicaltrials.gov/search/term=NCT01323517
SL - https://clinicaltrials.gov/search/term=NCT00796991
GI - No: K08 CA133183
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA172012
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20140307
DP - 2014 Apr
DC - 20140310
EZ - 2014/03/11 06:00
DA - 2014/11/15 06:00
DT - 2014/03/13 06:00
YR - 2014
ED - 20141114
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24610577
<237. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24610577
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Ryder M
AU - Callahan M
AU - Postow MA
AU - Wolchok J
AU - Fagin JA
FA - Ryder, Mabel
FA - Callahan, Margaret
FA - Postow, Michael A
FA - Wolchok, Jedd
FA - Fagin, James A
IN - Ryder, Mabel. Human Oncology and Pathogenesis Program, Department of Medicine Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York, USA Weill Cornell Medical College, New York, New York, USA.
TI - Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution. [Review]
SO - Endocrine-Related Cancer. 21(2):371-81, 2014 Apr
AS - Endocr Relat Cancer. 21(2):371-81, 2014 Apr
NJ - Endocrine-related cancer
PI - Journal available in: Electronic-Print
PI - Citation processed from: Internet
JC - 9436481, dgr
IO - Endocr. Relat. Cancer
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573438
OI - Source: NLM. NIHMS616115
SB - Index Medicus
CP - England
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - *Endocrine System Diseases/ci [Chemically Induced]
MH - Endocrine System Diseases/ep [Epidemiology]
MH - Humans
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/ep [Epidemiology]
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/ep [Epidemiology]
MH - Testosterone/bl [Blood]
KW - hypophysitis; immune-related adverse effects; ipilimumab; nivolumab; thyroiditis
AB - Novel immune checkpoint blockade with ipilimumab, an antibody blocking the cytotoxic T-lymphocyte antigen 4 (CTLA4), is revolutionizing cancer therapy. However, ipilimumab induces symptomatic, sometimes severe, endocrine immune-related adverse events (irAEs) that are inconsistently recognized and reported. The objective of this review was to comprehensively characterize the incidence, presentation, and management of endocrinopathies following ipilimumab therapy in a single center that is highly specialized in immune checkpoint blockade. We carried out a retrospective analysis of endocrine irAEs in melanoma patients receiving ipilimumab therapy in clinical trials between 2007 and 2013. A total of 256 patients were included in this analysis. We reviewed pituitary-, thyroid-, and adrenal-related hormone test results, as well as radiographic studies and the clinical histories of patients, to identify and characterize cases of hypophysitis, hypothyroidism, thyroiditis, and adrenal dysfunction. Following ipilimumab therapy, the overall incidence of hypophysitis was 8% and that of hypothyroidism/thyroiditis 6%. Primary adrenal dysfunction was rare. Therapy with a combination of ipilimumab and nivolumab, an anti-programmed cell death 1 (PDCD1, also called PD1) receptor antibody, was associated with a 22% incidence of either thyroiditis or hypothyroidism and a 9% incidence of hypophysitis. Symptomatic relief, in particular, for hypophysitis, was achieved in all patients with hormone replacement, although endogenous hormone secretion rarely recovered. In summary, we observed that CTLA4 blockade alone, and in particular in combination with PD1 blockade, is associated with an increased risk of symptomatic, sometimes severe, hypophysitis as well as thyroid dysfunction. Prompt initiation with hormone replacement reverses symptoms. Evaluation and reporting of endocrine irAEs in clinical trials should be done using standardized diagnostic criteria and terminology.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 3XMK78S47O (Testosterone)
RN - 6T8C155666 (ipilimumab)
ES - 1479-6821
IL - 1351-0088
DI - 21/2/371
DO - https://dx.doi.org/10.1530/ERC-13-0499
PT - Journal Article
PT - Review
ID - 24610577 [pubmed]
ID - 21/2/371 [pii]
ID - 10.1530/ERC-13-0499 [doi]
ID - PMC4573438 [pmc]
ID - NIHMS616115 [mid]
PP - epublish
GI - No: K08 CA133183
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA172012
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20140307
DP - 2014 Apr
DC - 20140310
EZ - 2014/03/11 06:00
DA - 2014/11/15 06:00
DT - 2014/03/13 06:00
YR - 2014
ED - 20141114
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=24610577
<238. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25092294
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Eytan E
AU - Wang K
AU - Miniowitz-Shemtov S
AU - Sitry-Shevah D
AU - Kaisari S
AU - Yen TJ
AU - Liu ST
AU - Hershko A
FA - Eytan, Esther
FA - Wang, Kexi
FA - Miniowitz-Shemtov, Shirly
FA - Sitry-Shevah, Danielle
FA - Kaisari, Sharon
FA - Yen, Tim J
FA - Liu, Song-Tao
FA - Hershko, Avram
IN - Eytan, Esther. Unit of Biochemistry, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel;
IN - Wang, Kexi. Department of Biological Sciences, University of Toledo, Toledo, OH 43606; and.
IN - Miniowitz-Shemtov, Shirly. Unit of Biochemistry, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel;
IN - Sitry-Shevah, Danielle. Unit of Biochemistry, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel;
IN - Kaisari, Sharon. Unit of Biochemistry, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel;
IN - Yen, Tim J. Fox Chase Cancer Center, Philadelphia, PA 19111.
IN - Liu, Song-Tao. Department of Biological Sciences, University of Toledo, Toledo, OH 43606; and.
IN - Hershko, Avram. Unit of Biochemistry, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel; hershko@tx.technion.ac.il.
TI - Disassembly of mitotic checkpoint complexes by the joint action of the AAA-ATPase TRIP13 and p31(comet).
SO - Proceedings of the National Academy of Sciences of the United States of America. 111(33):12019-24, 2014 Aug 19
AS - Proc Natl Acad Sci U S A. 111(33):12019-24, 2014 Aug 19
NJ - Proceedings of the National Academy of Sciences of the United States of America
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - pv3, 7505876
IO - Proc. Natl. Acad. Sci. U.S.A.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142996
SB - Index Medicus
CP - United States
MH - Adaptor Proteins, Signal Transducing/me [Metabolism]
MH - *Adaptor Proteins, Signal Transducing/ph [Physiology]
MH - Carrier Proteins/me [Metabolism]
MH - *Carrier Proteins/ph [Physiology]
MH - Cdc20 Proteins/me [Metabolism]
MH - Cell Cycle Proteins/me [Metabolism]
MH - *Cell Cycle Proteins/ph [Physiology]
MH - HeLa Cells
MH - Humans
MH - Mad2 Proteins/me [Metabolism]
MH - *Mitosis
MH - Nuclear Proteins/me [Metabolism]
MH - *Nuclear Proteins/ph [Physiology]
MH - Protein Binding
KW - mitosis; spindle checkpoint
AB - The mitotic (or spindle assembly) checkpoint system delays anaphase until all chromosomes are correctly attached to the mitotic spindle. When the checkpoint is active, a Mitotic Checkpoint Complex (MCC) assembles and inhibits the ubiquitin ligase Anaphase-Promoting Complex/Cyclosome (APC/C). MCC is composed of the checkpoint proteins Mad2, BubR1, and Bub3 associated with the APC/C activator Cdc20. When the checkpoint signal is turned off, MCC is disassembled and the checkpoint is inactivated. The mechanisms of the disassembly of MCC are not sufficiently understood. We have previously observed that ATP hydrolysis is required for the action of the Mad2-binding protein p31(comet) to disassemble MCC. We now show that HeLa cell extracts contain a factor that promotes ATP- and p31(comet)-dependent disassembly of a Cdc20-Mad2 subcomplex and identify it as Thyroid Receptor Interacting Protein 13 (TRIP13), an AAA-ATPase known to interact with p31(comet). The joint action of TRIP13 and p31(comet) also promotes the release of Mad2 from MCC, participates in the complete disassembly of MCC and abrogates checkpoint inhibition of APC/C. We propose that TRIP13 plays centrally important roles in the sequence of events leading to MCC disassembly and checkpoint inactivation.
RN - 0 (Adaptor Proteins, Signal Transducing)
RN - 0 (Carrier Proteins)
RN - 0 (Cdc20 Proteins)
RN - 0 (Cell Cycle Proteins)
RN - 0 (MAD2L1 protein, human)
RN - 0 (MAD2L1BP protein, human)
RN - 0 (Mad2 Proteins)
RN - 0 (Nuclear Proteins)
RN - 0 (TRIP13 protein, human)
RN - 156288-95-8 (CDC20 protein, human)
ES - 1091-6490
IL - 0027-8424
DI - 1412901111
DO - https://dx.doi.org/10.1073/pnas.1412901111
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
PT - Research Support, U.S. Gov't, Non-P.H.S.
ID - 25092294 [pubmed]
ID - 1412901111 [pii]
ID - 10.1073/pnas.1412901111 [doi]
ID - PMC4142996 [pmc]
PP - ppublish
GI - No: CA06927
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01CA169500
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA169706
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA169500
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA169706
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA006927
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20140804
DP - 2014 Aug 19
DC - 20140820
EZ - 2014/08/06 06:00
DA - 2014/11/05 06:00
DT - 2014/08/06 06:00
YR - 2014
ED - 20141103
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=25092294
<239. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24594636
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Gelao L
AU - Criscitiello C
AU - Esposito A
AU - Goldhirsch A
AU - Curigliano G
FA - Gelao, Lucia
FA - Criscitiello, Carmen
FA - Esposito, Angela
FA - Goldhirsch, Aron
FA - Curigliano, Giuseppe
IN - Gelao, Lucia. Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. lucia.gelao@ieo.it.
IN - Criscitiello, Carmen. Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. carmen.criscitiello@ieo.it.
IN - Esposito, Angela. Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. angela.esposito@ieo.it.
IN - Goldhirsch, Aron. Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. aaron.goldhirsch@ieo.it.
IN - Curigliano, Giuseppe. Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. giuseppe.curigliano@ieo.it.
TI - Immune checkpoint blockade in cancer treatment: a double-edged sword cross-targeting the host as an "innocent bystander". [Review]
SO - Toxins. 6(3):914-33, 2014 Mar 03
AS - Toxins (Basel). 6(3):914-33, 2014 Mar 03
NJ - Toxins
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101530765
IO - Toxins (Basel)
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968368
SB - Index Medicus
CP - Switzerland
MH - Animals
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Humans
MH - Immune Tolerance
MH - Immunologic Factors/ae [Adverse Effects]
MH - Immunologic Factors/tu [Therapeutic Use]
MH - *Immunotherapy/ae [Adverse Effects]
MH - *Neoplasms/th [Therapy]
AB - Targeted immune checkpoint blockade augments anti-tumor immunity and induces durable responses in patients with melanoma and other solid tumors. It also induces specific "immune-related adverse events" (irAEs). IrAEs mainly include gastrointestinal, dermatological, hepatic and endocrinological toxicities. Off-target effects that arise appear to account for much of the toxicity of the immune checkpoint blockade. These unique "innocent bystander" effects are likely a direct result of breaking immune tolerance upon immune check point blockade and require specific treatment guidelines that include symptomatic therapies or systemic corticosteroids. What do we need going forward to limit immune checkpoint blockade-induced toxicity? Most importantly, we need a better understanding of the roles played by these agents in normal tissues, so that we can begin to predict potentially problematic side effects on the basis of their selectivity profile. Second, we need to focus on the predictive factors of the response and toxicity of the host rather than serially focusing on individual agents. Third, rigorous biomarker-driven clinical trials are needed to further elucidate the mechanisms of both the benefit and toxicity. We will summarize the double-edged sword effect of immunotherapeutics in cancer treatment.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Immunologic Factors)
ES - 2072-6651
IL - 2072-6651
DI - toxins6030914
DO - https://dx.doi.org/10.3390/toxins6030914
PT - Journal Article
PT - Review
ID - 24594636 [pubmed]
ID - toxins6030914 [pii]
ID - 10.3390/toxins6030914 [doi]
ID - PMC3968368 [pmc]
PP - epublish
PH - 2013/11/27 [received]
PH - 2014/01/21 [revised]
PH - 2014/02/18 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01454102
SA - ClinicalTrials.gov/NCT01927419
SA - ClinicalTrials.gov/NCT01608594
SA - ClinicalTrials.gov/NCT01750983
SA - ClinicalTrials.gov/NCT01844505
SA - ClinicalTrials.gov/NCT01840579
SA - ClinicalTrials.gov/NCT01822509
SA - ClinicalTrials.gov/NCT01896869
SA - ClinicalTrials.gov/NCT01633970
SA - ClinicalTrials.gov/NCT01846416
SA - ClinicalTrials.gov/NCT00636168
SA - ClinicalTrials.gov/NCT01668784
SA - ClinicalTrials.gov/NCT00836407
SA - ClinicalTrials.gov/NCT01103635
SA - ClinicalTrials.gov/NCT00612664
SA - ClinicalTrials.gov/NCT01832870
SA - ClinicalTrials.gov/NCT01866319
SA - ClinicalTrials.gov/NCT01498978
SA - ClinicalTrials.gov/NCT01750580
SA - ClinicalTrials.gov/NCT01810016
SA - ClinicalTrials.gov/NCT01565837
SA - ClinicalTrials.gov/NCT01590082
SA - ClinicalTrials.gov/NCT01729806
SA - ClinicalTrials.gov/NCT01738139
SA - ClinicalTrials.gov/NCT01024231
SA - ClinicalTrials.gov/NCT01604889
SA - ClinicalTrials.gov/NCT01471210
SA - ClinicalTrials.gov/NCT01473940
SA - ClinicalTrials.gov/NCT01988077
SA - ClinicalTrials.gov/NCT01643278
SA - ClinicalTrials.gov/NCT01468311
SA - ClinicalTrials.gov/NCT01905657
SA - ClinicalTrials.gov/NCT01524991
SA - ClinicalTrials.gov/NCT01689974
SA - ClinicalTrials.gov/NCT01673854
SA - ClinicalTrials.gov/NCT01307618
SA - ClinicalTrials.gov/NCT01629758
SA - ClinicalTrials.gov/NCT01775631
SA - ClinicalTrials.gov/NCT01827111
SA - ClinicalTrials.gov/NCT01295827
SA - ClinicalTrials.gov/NCT01363206
SA - ClinicalTrials.gov/NCT01331525
SA - ClinicalTrials.gov/NCT01274338
SA - ClinicalTrials.gov/NCT01489059
SA - ClinicalTrials.gov/NCT01642004
SA - ClinicalTrials.gov/NCT01853618
SA - ClinicalTrials.gov/NCT00729664
SA - ClinicalTrials.gov/NCT01767454
SA - ClinicalTrials.gov/NCT01928394
SA - ClinicalTrials.gov/NCT01721772
SA - ClinicalTrials.gov/NCT01592370
SA - ClinicalTrials.gov/NCT01656642
SA - ClinicalTrials.gov/NCT01611558
SA - ClinicalTrials.gov/NCT01968109
SA - ClinicalTrials.gov/NCT01711515
SA - ClinicalTrials.gov/NCT01740297
SA - ClinicalTrials.gov/NCT01450761
SA - ClinicalTrials.gov/NCT01285609
SA - ClinicalTrials.gov/NCT01783938
SA - ClinicalTrials.gov/NCT01676649
SA - ClinicalTrials.gov/NCT01903993
SA - ClinicalTrials.gov/NCT01843374
SA - ClinicalTrials.gov/NCT01848834
SA - ClinicalTrials.gov/NCT01860430
SA - ClinicalTrials.gov/NCT01975831
SA - ClinicalTrials.gov/NCT01856023
SA - ClinicalTrials.gov/NCT01896999
SL - https://clinicaltrials.gov/search/term=NCT01454102
SL - https://clinicaltrials.gov/search/term=NCT01927419
SL - https://clinicaltrials.gov/search/term=NCT01608594
SL - https://clinicaltrials.gov/search/term=NCT01750983
SL - https://clinicaltrials.gov/search/term=NCT01844505
SL - https://clinicaltrials.gov/search/term=NCT01840579
SL - https://clinicaltrials.gov/search/term=NCT01822509
SL - https://clinicaltrials.gov/search/term=NCT01896869
SL - https://clinicaltrials.gov/search/term=NCT01633970
SL - https://clinicaltrials.gov/search/term=NCT01846416
SL - https://clinicaltrials.gov/search/term=NCT00636168
SL - https://clinicaltrials.gov/search/term=NCT01668784
SL - https://clinicaltrials.gov/search/term=NCT00836407
SL - https://clinicaltrials.gov/search/term=NCT01103635
SL - https://clinicaltrials.gov/search/term=NCT00612664
SL - https://clinicaltrials.gov/search/term=NCT01832870
SL - https://clinicaltrials.gov/search/term=NCT01866319
SL - https://clinicaltrials.gov/search/term=NCT01498978
SL - https://clinicaltrials.gov/search/term=NCT01750580
SL - https://clinicaltrials.gov/search/term=NCT01810016
SL - https://clinicaltrials.gov/search/term=NCT01565837
SL - https://clinicaltrials.gov/search/term=NCT01590082
SL - https://clinicaltrials.gov/search/term=NCT01729806
SL - https://clinicaltrials.gov/search/term=NCT01738139
SL - https://clinicaltrials.gov/search/term=NCT01024231
SL - https://clinicaltrials.gov/search/term=NCT01604889
SL - https://clinicaltrials.gov/search/term=NCT01471210
SL - https://clinicaltrials.gov/search/term=NCT01473940
SL - https://clinicaltrials.gov/search/term=NCT01988077
SL - https://clinicaltrials.gov/search/term=NCT01643278
SL - https://clinicaltrials.gov/search/term=NCT01468311
SL - https://clinicaltrials.gov/search/term=NCT01905657
SL - https://clinicaltrials.gov/search/term=NCT01524991
SL - https://clinicaltrials.gov/search/term=NCT01689974
SL - https://clinicaltrials.gov/search/term=NCT01673854
SL - https://clinicaltrials.gov/search/term=NCT01307618
SL - https://clinicaltrials.gov/search/term=NCT01629758
SL - https://clinicaltrials.gov/search/term=NCT01775631
SL - https://clinicaltrials.gov/search/term=NCT01827111
SL - https://clinicaltrials.gov/search/term=NCT01295827
SL - https://clinicaltrials.gov/search/term=NCT01363206
SL - https://clinicaltrials.gov/search/term=NCT01331525
SL - https://clinicaltrials.gov/search/term=NCT01274338
SL - https://clinicaltrials.gov/search/term=NCT01489059
SL - https://clinicaltrials.gov/search/term=NCT01642004
SL - https://clinicaltrials.gov/search/term=NCT01853618
SL - https://clinicaltrials.gov/search/term=NCT00729664
SL - https://clinicaltrials.gov/search/term=NCT01767454
SL - https://clinicaltrials.gov/search/term=NCT01928394
SL - https://clinicaltrials.gov/search/term=NCT01721772
SL - https://clinicaltrials.gov/search/term=NCT01592370
SL - https://clinicaltrials.gov/search/term=NCT01656642
SL - https://clinicaltrials.gov/search/term=NCT01611558
SL - https://clinicaltrials.gov/search/term=NCT01968109
SL - https://clinicaltrials.gov/search/term=NCT01711515
SL - https://clinicaltrials.gov/search/term=NCT01740297
SL - https://clinicaltrials.gov/search/term=NCT01450761
SL - https://clinicaltrials.gov/search/term=NCT01285609
SL - https://clinicaltrials.gov/search/term=NCT01783938
SL - https://clinicaltrials.gov/search/term=NCT01676649
SL - https://clinicaltrials.gov/search/term=NCT01903993
SL - https://clinicaltrials.gov/search/term=NCT01843374
SL - https://clinicaltrials.gov/search/term=NCT01848834
SL - https://clinicaltrials.gov/search/term=NCT01860430
SL - https://clinicaltrials.gov/search/term=NCT01975831
SL - https://clinicaltrials.gov/search/term=NCT01856023
SL - https://clinicaltrials.gov/search/term=NCT01896999
LG - English
EP - 20140303
DP - 2014 Mar 03
DC - 20140305
EZ - 2014/03/06 06:00
DA - 2014/11/02 06:00
DT - 2014/03/07 06:00
YR - 2014
ED - 20141031
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24594636
<240. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24594636
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Gelao L
AU - Criscitiello C
AU - Esposito A
AU - Goldhirsch A
AU - Curigliano G
FA - Gelao, Lucia
FA - Criscitiello, Carmen
FA - Esposito, Angela
FA - Goldhirsch, Aron
FA - Curigliano, Giuseppe
IN - Gelao, Lucia. Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. lucia.gelao@ieo.it.
IN - Criscitiello, Carmen. Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. carmen.criscitiello@ieo.it.
IN - Esposito, Angela. Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. angela.esposito@ieo.it.
IN - Goldhirsch, Aron. Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. aaron.goldhirsch@ieo.it.
IN - Curigliano, Giuseppe. Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Via Ripamonti 435, Milano 20141, Italy. giuseppe.curigliano@ieo.it.
TI - Immune checkpoint blockade in cancer treatment: a double-edged sword cross-targeting the host as an "innocent bystander". [Review]
SO - Toxins. 6(3):914-33, 2014 Mar 03
AS - Toxins (Basel). 6(3):914-33, 2014 Mar 03
NJ - Toxins
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101530765
IO - Toxins (Basel)
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3968368
SB - Index Medicus
CP - Switzerland
MH - Animals
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Humans
MH - Immune Tolerance
MH - Immunologic Factors/ae [Adverse Effects]
MH - Immunologic Factors/tu [Therapeutic Use]
MH - *Immunotherapy/ae [Adverse Effects]
MH - *Neoplasms/th [Therapy]
AB - Targeted immune checkpoint blockade augments anti-tumor immunity and induces durable responses in patients with melanoma and other solid tumors. It also induces specific "immune-related adverse events" (irAEs). IrAEs mainly include gastrointestinal, dermatological, hepatic and endocrinological toxicities. Off-target effects that arise appear to account for much of the toxicity of the immune checkpoint blockade. These unique "innocent bystander" effects are likely a direct result of breaking immune tolerance upon immune check point blockade and require specific treatment guidelines that include symptomatic therapies or systemic corticosteroids. What do we need going forward to limit immune checkpoint blockade-induced toxicity? Most importantly, we need a better understanding of the roles played by these agents in normal tissues, so that we can begin to predict potentially problematic side effects on the basis of their selectivity profile. Second, we need to focus on the predictive factors of the response and toxicity of the host rather than serially focusing on individual agents. Third, rigorous biomarker-driven clinical trials are needed to further elucidate the mechanisms of both the benefit and toxicity. We will summarize the double-edged sword effect of immunotherapeutics in cancer treatment.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Immunologic Factors)
ES - 2072-6651
IL - 2072-6651
DI - toxins6030914
DO - https://dx.doi.org/10.3390/toxins6030914
PT - Journal Article
PT - Review
ID - 24594636 [pubmed]
ID - toxins6030914 [pii]
ID - 10.3390/toxins6030914 [doi]
ID - PMC3968368 [pmc]
PP - epublish
PH - 2013/11/27 [received]
PH - 2014/01/21 [revised]
PH - 2014/02/18 [accepted]
LG - English
EP - 20140303
DP - 2014 Mar 03
DC - 20140305
EZ - 2014/03/06 06:00
DA - 2014/11/02 06:00
DT - 2014/03/07 06:00
YR - 2014
ED - 20141031
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=24594636
<241. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24556918
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Kopper F
AU - Binkowski AM
AU - Bierwirth C
AU - Dobbelstein M
FA - Kopper, Frederik
FA - Binkowski, Anna Maria
FA - Bierwirth, Cathrin
FA - Dobbelstein, Matthias
IN - Kopper, Frederik. Institute of Molecular Oncology; Gottingen Centre of Molecular Biosciences (GZMB); Faculty of Medicine; University of Gottingen; Gottingen, Germany.
IN - Binkowski, Anna Maria. Institute of Molecular Oncology; Gottingen Centre of Molecular Biosciences (GZMB); Faculty of Medicine; University of Gottingen; Gottingen, Germany.
IN - Bierwirth, Cathrin. Institute of Molecular Oncology; Gottingen Centre of Molecular Biosciences (GZMB); Faculty of Medicine; University of Gottingen; Gottingen, Germany.
IN - Dobbelstein, Matthias. Institute of Molecular Oncology; Gottingen Centre of Molecular Biosciences (GZMB); Faculty of Medicine; University of Gottingen; Gottingen, Germany.
TI - The MAPK-activated protein kinase 2 mediates gemcitabine sensitivity in pancreatic cancer cells.
SO - Cell Cycle. 13(6):884-9, 2014
AS - Cell Cycle. 13(6):884-9, 2014
NJ - Cell cycle (Georgetown, Tex.)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101137841
IO - Cell Cycle
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984311
SB - Index Medicus
CP - United States
MH - *Adenocarcinoma/me [Metabolism]
MH - Adenocarcinoma/pa [Pathology]
MH - *Antimetabolites, Antineoplastic/pd [Pharmacology]
MH - Cell Line, Tumor/de [Drug Effects]
MH - Cell Survival/de [Drug Effects]
MH - Checkpoint Kinase 1
MH - DNA Damage
MH - *Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - *Drug Resistance, Neoplasm
MH - Histones/me [Metabolism]
MH - Humans
MH - Intracellular Signaling Peptides and Proteins/ai [Antagonists & Inhibitors]
MH - *Intracellular Signaling Peptides and Proteins/me [Metabolism]
MH - *Pancreatic Neoplasms/me [Metabolism]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Phosphorylation
MH - Protein Kinases/me [Metabolism]
MH - Protein-Serine-Threonine Kinases/ai [Antagonists & Inhibitors]
MH - *Protein-Serine-Threonine Kinases/me [Metabolism]
KW - Chk1; DNA damage; MAPKAPK2; MK2; chemotherapy; gemcitabine; pancreatic carcinoma
AB - Pancreatic carcinoma is the major clinical entity where the nucleoside analog gemcitabine is used for first-line therapy. Overcoming cellular resistance toward gemcitabine remains a major challenge in this context. This raises the need to identify factors that determine gemcitabine sensitivity in pancreatic carcinoma cells. We previously found the MAPK-activated protein kinase 2 (MK2), part of the p38/MK2 stress response pathway, to be required for DNA replication fork stalling when osteosarcoma-derived cells were treated with gemcitabine. As a consequence, inhibition or depletion of MK2 protects these cells from gemcitabine-induced death (Kopper, et al. Proc Natl Acad Sci USA 2013; 110:16856-61). Here, we addressed whether MK2 also determines the sensitivity of pancreatic cancer cells toward gemcitabine. We found that MK2 inhibition reduced the intensity of the DNA damage response and enhanced survival of the pancreatic cancer cell lines BxPC-3, MIA PaCa-2, and Panc-1, which display a moderate to strong sensitivity to gemcitabine. In contrast, MK2 inhibition only weakly attenuated the DNA damage response intensity and did not enhance long-term survival in the gemcitabine-resistant cell line PaTu 8902. Importantly, in BxPC-3 and MIA PaCa-2 cells, inhibition of MK2 also rescued increased H2AX phosphorylation caused by inhibition of the checkpoint kinase Chk1 in the presence of gemcitabine. These results indicate that MK2 mediates gemcitabine efficacy in pancreatic cancer cells that respond to the drug, suggesting that the p38/MK2 pathway represents a determinant of the efficacy by that gemcitabine counteracts pancreatic cancer.
RN - 0 (Antimetabolites, Antineoplastic)
RN - 0 (Histones)
RN - 0 (Intracellular Signaling Peptides and Proteins)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7 (Protein Kinases)
RN - EC 2-7-1 (MAP-kinase-activated kinase 2)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
RN - EC 2-7-11-1 (Protein-Serine-Threonine Kinases)
RS - Pancreatic Carcinoma
ES - 1551-4005
IL - 1551-4005
DI - 28292
DO - https://dx.doi.org/10.4161/cc.28292
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 24556918 [pubmed]
ID - 28292 [pii]
ID - 10.4161/cc.28292 [doi]
ID - PMC3984311 [pmc]
PP - ppublish
LG - English
EP - 20140221
DP - 2014
DC - 20140320
EZ - 2014/02/22 06:00
DA - 2014/10/23 06:00
DT - 2014/02/22 06:00
YR - 2014
ED - 20141022
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24556918
<242. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24686174
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Mackay C
AU - Carroll E
AU - Ibrahim AF
AU - Garg A
AU - Inman GJ
AU - Hay RT
AU - Alpi AF
FA - Mackay, Craig
FA - Carroll, Eilis
FA - Ibrahim, Adel F M
FA - Garg, Amit
FA - Inman, Gareth J
FA - Hay, Ronald T
FA - Alpi, Arno F
IN - Mackay, Craig. Authors' Affiliations: MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Science; Division of Cancer Research, Medical Research Institute, Ninewells Hospital and Medical School; and Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom.
TI - E3 ubiquitin ligase HOIP attenuates apoptotic cell death induced by cisplatin.
SO - Cancer Research. 74(8):2246-57, 2014 Apr 15
AS - Cancer Res. 74(8):2246-57, 2014 Apr 15
NJ - Cancer research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cnf, 2984705r
IO - Cancer Res.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990471
OI - Source: NLM. EMS57229
SB - Index Medicus
CP - United States
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - *Apoptosis/de [Drug Effects]
MH - Apoptosis/ph [Physiology]
MH - Cell Cycle Checkpoints/ph [Physiology]
MH - Cell Death/de [Drug Effects]
MH - Cell Death/ph [Physiology]
MH - *Cisplatin/pd [Pharmacology]
MH - DNA Damage
MH - Female
MH - HCT116 Cells
MH - HEK293 Cells
MH - HeLa Cells
MH - Humans
MH - MAP Kinase Kinase 4/me [Metabolism]
MH - Ovarian Neoplasms/dt [Drug Therapy]
MH - Ovarian Neoplasms/en [Enzymology]
MH - Ovarian Neoplasms/pa [Pathology]
MH - RNA, Small Interfering/ad [Administration & Dosage]
MH - RNA, Small Interfering/ge [Genetics]
MH - Signal Transduction
MH - Ubiquitin-Protein Ligases/ge [Genetics]
MH - *Ubiquitin-Protein Ligases/me [Metabolism]
AB - The genotoxin cisplatin is commonly used in chemotherapy to treat solid tumors, yet our understanding of the mechanism underlying the drug response is limited. In a focused siRNA screen, using an siRNA library targeting genes involved in ubiquitin and ubiquitin-like signaling, we identified the E3 ubiquitin ligase HOIP as a key regulator of cisplatin-induced genotoxicity. HOIP forms, with SHARPIN and HOIL-1L, the linear ubiquitin assembly complex (LUBAC). We show that cells deficient in the HOIP ligase complex exhibit hypersensitivity to cisplatin. This is due to a dramatic increase in caspase-8/caspase-3-mediated apoptosis that is strictly dependent on ATM-, but not ATR-mediated DNA damage checkpoint activation. Moreover, basal and cisplatin-induced activity of the stress response kinase JNK is enhanced in HOIP-depleted cells and, conversely, JNK inhibition can increase cellular resistance to cisplatin and reverse the apoptotic hyperactivation in HOIP-depleted cells. Furthermore, we show that HOIP depletion sensitizes cancer cells, derived from carcinomas of various origins, through an enhanced apoptotic cell death response. We also provide evidence that ovarian cancer cells classified as cisplatin-resistant can regain sensitivity following HOIP downregulation. Cumulatively, our study identifies a HOIP-regulated antiapoptotic signaling pathway, and we envisage HOIP as a potential target for the development of combinatorial chemotherapies to potentiate the efficacy of platinum-based anticancer drugs.
AB - Copyright ©2014 AACR.
RN - 0 (Antineoplastic Agents)
RN - 0 (RNA, Small Interfering)
RN - EC 2-3-2-27 (RNF31 protein, human)
RN - EC 2-3-2-27 (Ubiquitin-Protein Ligases)
RN - EC 2-7-12-2 (MAP Kinase Kinase 4)
RN - Q20Q21Q62J (Cisplatin)
ES - 1538-7445
IL - 0008-5472
DI - 0008-5472.CAN-13-2131
DO - https://dx.doi.org/10.1158/0008-5472.CAN-13-2131
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 24686174 [pubmed]
ID - 0008-5472.CAN-13-2131 [pii]
ID - 10.1158/0008-5472.CAN-13-2131 [doi]
ID - PMC3990471 [pmc]
ID - EMS57229 [mid]
PP - ppublish
GI - No: 097945
Organization: *Wellcome Trust*
Country: United Kingdom
LG - English
EP - 20140331
DP - 2014 Apr 15
DC - 20140416
EZ - 2014/04/02 06:00
DA - 2014/07/25 06:00
DT - 2014/04/02 06:00
YR - 2014
ED - 20140724
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24686174
<243. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24122241
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Lammert A
AU - Schneider HJ
AU - Bergmann T
AU - Benck U
AU - Kramer BK
AU - Gartner R
AU - Metzner C
AU - Schofl C
AU - Berking C
FA - Lammert, A
FA - Schneider, H J
FA - Bergmann, T
FA - Benck, U
FA - Kramer, B K
FA - Gartner, R
FA - Metzner, C
FA - Schofl, C
FA - Berking, C
IN - Lammert, A. Fifth Medical Clinic, University Medical Center Mannheim, Mannheim, Germany.
TI - Hypophysitis caused by ipilimumab in cancer patients: hormone replacement or immunosuppressive therapy.
SO - Experimental & Clinical Endocrinology & Diabetes. 121(10):581-7, 2013 Nov
AS - Exp Clin Endocrinol Diabetes. 121(10):581-7, 2013 Nov
NJ - Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ccv, 9505926
IO - Exp. Clin. Endocrinol. Diabetes
SB - Index Medicus
CP - Germany
MH - Adrenal Cortex Hormones/ae [Adverse Effects]
MH - Adrenal Cortex Hormones/tu [Therapeutic Use]
MH - *Adrenal Cortex Hormones
MH - Adult
MH - Aged
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Female
MH - *Hormone Replacement Therapy/ae [Adverse Effects]
MH - Humans
MH - *Immunosuppression/ae [Adverse Effects]
MH - Melanoma/dg [Diagnostic Imaging]
MH - Melanoma/dt [Drug Therapy]
MH - *Melanoma
MH - Middle Aged
MH - Neoplasm Metastasis
MH - *Pituitary Diseases/ci [Chemically Induced]
MH - *Pituitary Diseases/dg [Diagnostic Imaging]
MH - Radiography
AB - Ipilimumab is besides the BRAF inhibitor vemurafenib the first officially approved medical treatment for metastatic melanoma, which results in improved survival. Ipilimumab leads to a release of a CTLA4-mediated inhibition of T-cell immunoreactions. Therefore, patients may also suffer from immune-related adverse events affecting different organs, which are typically treated by high-dose corticosteroids. Ipilimumab-induced hypophysitis (iH) has been reported in up to 17% of melanoma patients in clinical trials.Here we present 5 patients with metastatic melanoma and 2 patients with prostate cancer who developed hypophysitis after ipilimumab therapy. Patients were treated by high-dose corticosteroid therapy resulting in the resolution of local inflammation but not of pituitary deficiencies. Partial or complete hypopituitarism remained in all patients. Pharmacotherapy with high-dose corticosteroids caused complications in 5 patients, necessitating hospitalization in 4. 2 of the 3 patients with progressive disease died, while 3 patients had stable disease and 1 patient showed tumor regression after discontinuation of ipilimumab.In summary, with regard to safety and simplicity of hormonal substitution therapy we have to scrutinize high-dose corticosteroid therapy, though it only improves inflammation but not neuro-endocrine function and may cause further morbidity. Regression of the tumor depends on the ipilimumab-mediated immune events, in which high-dose and long-term corticosteroid therapy for iH appears to be counter-intuitive. Herein, we discuss screening and the diagnostic as well as therapeutic management of iH in metastatic cancer patients from an endocrinologic perspective.
AB - Copyright © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart . New York.
RN - 0 (Adrenal Cortex Hormones)
RN - 0 (Antibodies, Monoclonal)
RN - 6T8C155666 (ipilimumab)
ES - 1439-3646
IL - 0947-7349
DO - https://dx.doi.org/10.1055/s-0033-1355337
PT - Case Reports
PT - Journal Article
ID - 24122241 [pubmed]
ID - 10.1055/s-0033-1355337 [doi]
PP - ppublish
LG - English
EP - 20131011
DP - 2013 Nov
DC - 20131126
EZ - 2013/10/15 06:00
DA - 2014/07/08 06:00
DT - 2013/10/15 06:00
YR - 2013
ED - 20140707
RD - 20161128
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24122241
<244. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23750887
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Torino F
AU - Barnabei A
AU - Paragliola R
AU - Baldelli R
AU - Appetecchia M
AU - Corsello SM
FA - Torino, Francesco
FA - Barnabei, Agnese
FA - Paragliola, Rosamaria
FA - Baldelli, Roberto
FA - Appetecchia, Marialuisa
FA - Corsello, Salvatore Maria
IN - Torino, Francesco. 1 Department of Systems Medicine, Tor Vergata University of Rome , Rome, Italy .
TI - Thyroid dysfunction as an unintended side effect of anticancer drugs. [Review]
SO - Thyroid. 23(11):1345-66, 2013 Nov
AS - Thyroid. 23(11):1345-66, 2013 Nov
NJ - Thyroid : official journal of the American Thyroid Association
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - bjw, 9104317
IO - Thyroid
SB - Index Medicus
CP - United States
MH - Animals
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Diphtheria Toxin/ae [Adverse Effects]
MH - Humans
MH - Hypothyroidism/ci [Chemically Induced]
MH - Interferon-alpha/me [Metabolism]
MH - Interleukin-2/ae [Adverse Effects]
MH - Interleukin-2/me [Metabolism]
MH - Neoplasms/co [Complications]
MH - *Neoplasms/dt [Drug Therapy]
MH - Recombinant Fusion Proteins/ae [Adverse Effects]
MH - Tetrahydronaphthalenes/ae [Adverse Effects]
MH - Thalidomide/ae [Adverse Effects]
MH - Thalidomide/aa [Analogs & Derivatives]
MH - *Thyroid Diseases/ci [Chemically Induced]
MH - *Thyroid Gland/de [Drug Effects]
MH - Thyroid Hormones/me [Metabolism]
MH - Thyroxine/me [Metabolism]
AB - BACKGROUND: Several of the currently used anticancer drugs may variably affect thyroid function, with impairment ranging from modified total but not free concentration of thyroid hormones to overt thyroid disease.
AB - SUMMARY: Cytotoxic agents seem to alter thyroid function in a relatively small proportion of adult patients. Anticancer hormone drugs may mainly alter serum levels of thyroid hormone-binding proteins without clinically relevant thyroid dysfunction. Old immunomodulating drugs, such as interferon-alpha and interleukin-2, are known to induce variably high incidence of autoimmune thyroid dysfunction. Newer immune checkpoint inhibitors, such as anti-CTLA4 monoclonal antibodies, are responsible for a relatively low incidence of thyroiditis and may induce secondary hypothyroidism resulting from hypophysitis. Central hypothyroidism is a well-recognized side effect of bexarotene. Despite their inherent selectivity, tyrosine kinase inhibitors may cause high rates of thyroid dysfunction. Notably, thyroid toxicity seems to be restricted to tyrosine kinase inhibitors targeting key kinase-receptors in angiogenic pathways, but not other kinase-receptors (e.g., epidermal growth factor receptors family or c-KIT). In addition, a number of these agents may also increase the levothyroxine requirement in thyroidectomized patients.
AB - CONCLUSIONS: The pathophysiology of thyroid toxicity induced by many anticancer agents is not fully clarified and for others it remains speculative. Thyroid dysfunction induced by anticancer agents is generally manageable and dose reduction or discontinuation of these agents is not required. The prognostic relevance of thyroid autoimmunity, overt and subclinical hypothyroidism induced by anticancer drugs, the value of thyroid hormone replacement in individuals with abnormal thyrotropin following anticancer systemic therapy, and the correct timing of replacement therapy in cancer patients need to be defined more accurately in well-powered prospective clinical trials.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antineoplastic Agents)
RN - 0 (Diphtheria Toxin)
RN - 0 (Interferon-alpha)
RN - 0 (Interleukin-2)
RN - 0 (Recombinant Fusion Proteins)
RN - 0 (Tetrahydronaphthalenes)
RN - 0 (Thyroid Hormones)
RN - 25E79B5CTM (denileukin diftitox)
RN - 3A189DH42V (alemtuzumab)
RN - 4Z8R6ORS6L (Thalidomide)
RN - A61RXM4375 (bexarotene)
RN - F0P408N6V4 (lenalidomide)
RN - Q51BO43MG4 (Thyroxine)
ES - 1557-9077
IL - 1050-7256
DO - https://dx.doi.org/10.1089/thy.2013.0241
PT - Journal Article
PT - Review
ID - 23750887 [pubmed]
ID - 10.1089/thy.2013.0241 [doi]
PP - ppublish
LG - English
EP - 20130921
DP - 2013 Nov
DC - 20131107
EZ - 2013/06/12 06:00
DA - 2014/07/01 06:00
DT - 2013/06/12 06:00
YR - 2013
ED - 20140630
RD - 20141120
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23750887
<245. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24570590
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Della Vittoria Scarpati G
AU - Fusciello C
AU - Perri F
AU - Sabbatino F
AU - Ferrone S
AU - Carlomagno C
AU - Pepe S
FA - Della Vittoria Scarpati, Giuseppina
FA - Fusciello, Celeste
FA - Perri, Francesco
FA - Sabbatino, Francesco
FA - Ferrone, Soldano
FA - Carlomagno, Chiara
FA - Pepe, Stefano
IN - Della Vittoria Scarpati, Giuseppina. Department of Medicine, University of Salerno, Salerno, Italy ; Division of Oncology, "San Giovanni di Dio e Ruggi d'Aragona" Hospital, Salerno, Italy.
IN - Fusciello, Celeste. Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy.
IN - Perri, Francesco. Head and Neck Medical Oncology Unit, National Tumor Institute, Naples, Italy.
IN - Sabbatino, Francesco. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
IN - Ferrone, Soldano. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
IN - Carlomagno, Chiara. Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy.
IN - Pepe, Stefano. Department of Medicine, University of Salerno, Salerno, Italy ; Division of Oncology, "San Giovanni di Dio e Ruggi d'Aragona" Hospital, Salerno, Italy.
TI - Ipilimumab in the treatment of metastatic melanoma: management of adverse events. [Review]
SO - OncoTargets and therapy. 7:203-9, 2014
AS - Onco Targets Ther. 7:203-9, 2014
NJ - OncoTargets and therapy
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101514322
IO - Onco Targets Ther
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933725
CP - New Zealand
KW - CTLA-4; T-cells; adverse events; autoimmunity; melanoma
AB - Recently, "ipilimumab," an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody, has been demonstrated to improve overall survival in metastatic melanoma. "CTLA-4" is an immune-checkpoint molecule that downregulates pathways of T-cell activation. Ipilimumab, by targeting CTLA-4, is able to remove the CTLA-4 inhibitory signal, allowing the immune system to react to cancer cells. Due to its immune-based mechanism of action, ipilimumab causes the inhibition of CTLA-4-mediated immunomodulatory effects, the enhancement of antitumor specific immune response mediated by the weakening of self-tolerance mechanisms while exacerbating the development of autoimmune diseases and immune-related adverse events, including dermatitis, hepatitis, enterocolitis, hypophysitis, and uveitis.
IL - 1178-6930
DI - ott-7-203
DO - https://dx.doi.org/10.2147/OTT.S57335
PT - Journal Article
PT - Review
ID - 24570590 [pubmed]
ID - 10.2147/OTT.S57335 [doi]
ID - ott-7-203 [pii]
ID - PMC3933725 [pmc]
PP - epublish
LG - English
EP - 20140219
DP - 2014
DC - 20140226
EZ - 2014/02/27 06:00
DA - 2014/02/27 06:01
DT - 2014/02/27 06:00
YR - 2014
ED - 20140624
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=24570590
<246. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24904570
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Kong YC
AU - Flynn JC
FA - Kong, Yi-Chi M
FA - Flynn, Jeffrey C
IN - Kong, Yi-Chi M. Department of Immunology and Microbiology, Wayne State University School of Medicine , Detroit, MI , USA.
IN - Flynn, Jeffrey C. Department of Orthopaedic Surgery, Providence Hospital and Medical Centers , Southfield, MI , USA.
TI - Opportunistic Autoimmune Disorders Potentiated by Immune-Checkpoint Inhibitors Anti-CTLA-4 and Anti-PD-1. [Review]
SO - Frontiers in Immunology. 5:206, 2014
AS - Front. immunol.. 5:206, 2014
NJ - Frontiers in immunology
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101560960
IO - Front Immunol
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032988
CP - Switzerland
KW - anti-CTLA-4; anti-PD-1; autoimmune disease; immune-checkpoint inhibitor; tumor immunity
AB - To improve the efficacy of immunotherapy for cancer and autoimmune diseases, recent ongoing and completed clinical trials have focused on specific targets to redirect the immune network toward eradicating a variety of tumors and ameliorating the self-destructive process. In a previous review, both systemic immunomodulators and monoclonal antibodies (mAbs), anti-CTLA-4, and anti-CD52, were discussed regarding therapeutics and autoimmune sequelae, as well as predisposing factors known to exacerbate immune-related adverse events (irAEs). This review will focus on immune-checkpoint inhibitors, and the data from most clinical trials involve blockade with anti-CTLA-4 such as ipilimumab. However, despite the mild to severe irAEs observed with ipilimumab in ~60% of patients, overall survival (OS) averaged ~22-25% at 3-5years. To boost OS, other mAbs targeting programed death-1 and its ligand are undergoing clinical trials as monotherapy or dual therapy with anti-CTLA-4. Therapeutic combinations may generate different spectrum of opportunistic autoimmune disorders. To simulate clinical scenarios, we have applied regulatory T cell perturbation to murine models combined to examine the balance between thyroid autoimmunity and tumor-specific immunity.
IL - 1664-3224
DO - https://dx.doi.org/10.3389/fimmu.2014.00206
PT - Journal Article
PT - Review
ID - 24904570 [pubmed]
ID - 10.3389/fimmu.2014.00206 [doi]
ID - PMC4032988 [pmc]
PP - epublish
PH - 2014/02/11 [received]
PH - 2014/04/25 [accepted]
LG - English
EP - 20140516
DP - 2014
DC - 20140606
EZ - 2014/06/07 06:00
DA - 2014/06/07 06:01
DT - 2014/06/07 06:00
YR - 2014
ED - 20140624
RD - 20140624
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=24904570
<247. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24782152
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Fischli S
AU - Allelein S
AU - Zander T
AU - Henzen C
FA - Fischli, S
FA - Allelein, S
FA - Zander, T
FA - Henzen, C
IN - Fischli, S. Departement Medizin, Klinik fur Endokrinologie, Diabetologie und Klinische Ernahrung, Luzerner Kantonsspital, Luzern.
IN - Allelein, S. Departement Medizin, Klinik fur Endokrinologie, Diabetologie und Klinische Ernahrung, Luzerner Kantonsspital, Luzern.
IN - Zander, T. Departement Medizin, Klinik fur Medizinische Onkologie, Luzerner Kantonsspital, Luzern.
IN - Henzen, C. Departement Medizin, Klinik fur Endokrinologie, Diabetologie und Klinische Ernahrung, Luzerner Kantonsspital, Luzern.
TI - [Endocrinologic side effects of oncologic treatment with anti-CTLA-4-antibodies]. [German]
OT - Endokrinologische Nebenwirkungen einer onkologischen Therapie mit Anti-CTLA-4-Antikorpern.
SO - Deutsche Medizinische Wochenschrift. 139(19):996-1000, 2014 May
AS - Dtsch Med Wochenschr. 139(19):996-1000, 2014 May
NJ - Deutsche medizinische Wochenschrift (1946)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ecl, 0006723
IO - Dtsch. Med. Wochenschr.
SB - Index Medicus
CP - Germany
MH - Adrenal Gland Diseases/ci [Chemically Induced]
MH - Adrenal Gland Diseases/di [Diagnosis]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Brain Neoplasms/dt [Drug Therapy]
MH - *Brain Neoplasms/sc [Secondary]
MH - *CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - Colitis/ci [Chemically Induced]
MH - Colitis/di [Diagnosis]
MH - Follow-Up Studies
MH - Humans
MH - Hyperthyroidism/ci [Chemically Induced]
MH - Hyperthyroidism/di [Diagnosis]
MH - *Hypopituitarism/ci [Chemically Induced]
MH - Hypopituitarism/di [Diagnosis]
MH - *Liver Neoplasms/dt [Drug Therapy]
MH - *Liver Neoplasms/sc [Secondary]
MH - *Lung Neoplasms/dt [Drug Therapy]
MH - *Lung Neoplasms/sc [Secondary]
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - *Melanoma/sc [Secondary]
MH - Middle Aged
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Thyroiditis/ci [Chemically Induced]
MH - Thyroiditis/di [Diagnosis]
AB - New immune-modulating treatments like the anti-CTLA-4-antibodies-based therapies are increasingly used in medical oncology. The action of Ipilimumab, a monoclonal anti-CTLA-4-antibody used for the treatment of metastasized melanoma and other solid tumors, is well documented. Blocking the CTLA-4-receptors on lymphocytes leads to T-cell activation and hence reduction of the tumor-mediated immunotolerance. This mechanism constitutes the basis of the antiproliferative effects but is also responsible for a spectrum of specific adverse events (immune-related adverse events, IRAE). IRAE of the endocrine system comprise hypophysitis, thyroiditis and adrenalitis. Especially adrenal insufficiency can be fatal when not diagnosed and treated. Symptoms often are unspecific and early diagnosis and targeted treatment are crucial. We present a case report and summarize - based upon the current literature - the diagnosis and treatment of endocrinologic IRAEs.
AB - Copyright © Georg Thieme Verlag KG Stuttgart . New York.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
RS - Combined Pituitary Hormone Deficiency
ES - 1439-4413
IL - 0012-0472
DO - https://dx.doi.org/10.1055/s-0034-1369961
PT - Case Reports
PT - Journal Article
ID - 24782152 [pubmed]
ID - 10.1055/s-0034-1369961 [doi]
PP - ppublish
LG - German
EP - 20140429
DP - 2014 May
DC - 20140430
EZ - 2014/05/01 06:00
DA - 2014/06/17 06:00
DT - 2014/05/02 06:00
YR - 2014
ED - 20140616
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24782152
<248. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24106007
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Gupta S
AU - Jaworska-Bieniek K
AU - Lubinski J
AU - Jakubowska A
FA - Gupta, Satish
FA - Jaworska-Bieniek, Katarzyna
FA - Lubinski, Jan
FA - Jakubowska, Anna
IN - Gupta, Satish. International Hereditary Cancer Centre, Department of Genetics and Pathology, Pomeranian Medical University, Polabska 4, 70-115, Szczecin, Poland and.
TI - Can selenium be a modifier of cancer risk in CHEK2 mutation carriers?.
SO - Mutagenesis. 28(6):625-9, 2013 Nov
AS - Mutagenesis. 28(6):625-9, 2013 Nov
NJ - Mutagenesis
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - mug, 8707812
IO - Mutagenesis
SB - Index Medicus
CP - England
MH - *Checkpoint Kinase 2/ge [Genetics]
MH - Checkpoint Kinase 2/me [Metabolism]
MH - Dietary Supplements
MH - Humans
MH - Mutation
MH - *Neoplasms/en [Enzymology]
MH - Neoplasms/ge [Genetics]
MH - Neoplasms/pc [Prevention & Control]
MH - Selenium/ad [Administration & Dosage]
MH - *Selenium/ph [Physiology]
MH - Selenoproteins/me [Metabolism]
MH - Signal Transduction
AB - Selenium is an essential trace element for humans, playing an important role in various major metabolic pathways. Selenium helps to protect the body from the poisonous effects of heavy metals and other harmful substances. Medical studies have provided evidence of selenium supplementation in preventing certain cancers. Low and too high selenium (Se) status correlates with increased risk of e.g. lung, larynx, colorectal and prostate cancers. A higher level of selenium and supplementation with selenium has been shown to be associated with substantially reduced cancer mortality. Selenium exerts its biological roles through selenoproteins, which are involved in oxidoreductions, redox signalling, antioxidant defence, thyroid hormone metabolism and immune responses. Checkpoint kinase 2 (CHEK2) is an important signal transducer of cellular responses to DNA damage and acts as a tumour suppressor gene. Mutations in the CHEK2 gene have been shown to be associated with increased risks of several cancers. Four common mutations in CHEK2 gene (1100delC, IVS2+1G>A, del5395 and I157T) have been identified in the Polish population. Studies have provided evidence that CHEK2-truncating and/or missense mutations are associated with increased risk of breast, prostate, thyroid, colon and kidney cancers. The variability in penetrance and cancer expression in CHEK2 mutation carriers can probably be explained by the influence of other genetic or environmental factors. One of the possible candidates is Se, which together with genetic variations in selenoprotein genes may influence susceptibility to cancer risk.
RN - 0 (Selenoproteins)
RN - EC 2-7-1-11 (Checkpoint Kinase 2)
RN - EC 2-7-11-1 (CHEK2 protein, human)
RN - H6241UJ22B (Selenium)
ES - 1464-3804
IL - 0267-8357
DI - get050
DO - https://dx.doi.org/10.1093/mutage/get050
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 24106007 [pubmed]
ID - get050 [pii]
ID - 10.1093/mutage/get050 [doi]
PP - ppublish
LG - English
EP - 20131008
DP - 2013 Nov
DC - 20131023
EZ - 2013/10/10 06:00
DA - 2014/05/31 06:00
DT - 2013/10/10 06:00
YR - 2013
ED - 20140530
RD - 20131023
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24106007
<249. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23855452
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Duong HQ
AU - Hong YB
AU - Kim JS
AU - Lee HS
AU - Yi YW
AU - Kim YJ
AU - Wang A
AU - Zhao W
AU - Cho CH
AU - Seong YS
AU - Bae I
FA - Duong, Hong-Quan
FA - Hong, Young Bin
FA - Kim, Jung Soon
FA - Lee, Hee-Seok
FA - Yi, Yong Weon
FA - Kim, Yeon Jeong
FA - Wang, Antai
FA - Zhao, Wenjing
FA - Cho, Chi Heum
FA - Seong, Yeon-Sun
FA - Bae, Insoo
IN - Duong, Hong-Quan. Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA; WCU (World Class University) Research Center of Nanobiomedical Science, Dankook University, Cheonan, Korea.
TI - Inhibition of checkpoint kinase 2 (CHK2) enhances sensitivity of pancreatic adenocarcinoma cells to gemcitabine.
SO - Journal of Cellular & Molecular Medicine. 17(10):1261-70, 2013 Oct
AS - J Cell Mol Med. 17(10):1261-70, 2013 Oct
NJ - Journal of cellular and molecular medicine
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101083777
IO - J. Cell. Mol. Med.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159025
SB - Index Medicus
CP - England
MH - *Adenocarcinoma/dt [Drug Therapy]
MH - Adenocarcinoma/me [Metabolism]
MH - Adenocarcinoma/pa [Pathology]
MH - *Antimetabolites, Antineoplastic/tu [Therapeutic Use]
MH - Apoptosis
MH - Blotting, Western
MH - Cell Line, Tumor
MH - *Checkpoint Kinase 2/ai [Antagonists & Inhibitors]
MH - *Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/tu [Therapeutic Use]
MH - Humans
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/me [Metabolism]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Phosphorylation
MH - Reactive Oxygen Species/me [Metabolism]
KW - Checkpoint kinase 2 (CHK2) inhibitor; NSC109555; combination; gemcitabine; pancreatic adenocarcinoma; synergism
AB - Checkpoint kinase 2 (CHK2) plays pivotal function as an effector of cell cycle checkpoint arrest following DNA damage. Recently, we found that co-treatment of NSC109555 (a potent and selective CHK2 inhibitor) potentiated the cytotoxic effect of gemcitabine (GEM) in pancreatic cancer MIA PaCa-2 cells. Here, we further examined whether NSC109555 could enhance the antitumour effect of GEM in pancreatic adenocarcinoma cell lines. In this study, the combination treatment of NSC109555 plus GEM demonstrated strong synergistic antitumour effect in four pancreatic cancer cells (MIA PaCa-2, CFPAC-1, Panc-1 and BxPC-3). In addition, the GEM/NSC109555 combination significantly increased the level of intracellular reactive oxygen species (ROS), accompanied by induction of apoptotic cell death. Inhibition of ROS generation by N-acetyl cysteine (NAC) significantly reversed the effect of GEM/NSC109555 in apoptosis and cytotoxicity. Furthermore, genetic knockdown of CHK2 by siRNA enhanced GEM-induced apoptotic cell death. These findings suggest that inhibition of CHK2 would be a beneficial therapeutic approach for pancreatic cancer therapy in clinical treatment.
AB - Copyright © 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
RN - 0 (Antimetabolites, Antineoplastic)
RN - 0 (Reactive Oxygen Species)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7-1-11 (Checkpoint Kinase 2)
ES - 1582-4934
IL - 1582-1838
DO - https://dx.doi.org/10.1111/jcmm.12101
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 23855452 [pubmed]
ID - 10.1111/jcmm.12101 [doi]
ID - PMC4159025 [pmc]
PP - ppublish
PH - 2013/01/15 [received]
PH - 2013/05/26 [revised]
PH - 2013/06/03 [accepted]
GI - No: P30 CA051008
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R03 CA152530
Organization: (CA) *NCI NIH HHS*
Country: United States
No: 1R03CA152530
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30-CA051008
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20130716
DP - 2013 Oct
DC - 20131127
EZ - 2013/07/17 06:00
DA - 2014/05/28 06:00
DT - 2013/07/17 06:00
YR - 2013
ED - 20140527
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23855452
<250. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23687379
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Fredebohm J
AU - Wolf J
AU - Hoheisel JD
AU - Boettcher M
FA - Fredebohm, Johannes
FA - Wolf, Jonas
FA - Hoheisel, Jorg D
FA - Boettcher, Michael
IN - Fredebohm, Johannes. Functional Genome Analysis, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
TI - Depletion of RAD17 sensitizes pancreatic cancer cells to gemcitabine.
SO - Journal of Cell Science. 126(Pt 15):3380-9, 2013 Aug 01
AS - J Cell Sci. 126(Pt 15):3380-9, 2013 Aug 01
NJ - Journal of cell science
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - hnk, 0052457
IO - J. Cell. Sci.
SB - Index Medicus
CP - England
MH - *Antimetabolites, Antineoplastic/pd [Pharmacology]
MH - *Cell Cycle Proteins/df [Deficiency]
MH - *Cell Cycle Proteins/ge [Genetics]
MH - Cell Cycle Proteins/me [Metabolism]
MH - Cell Line, Tumor
MH - *Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Humans
MH - Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - *Pancreatic Neoplasms/me [Metabolism]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Phosphorylation
MH - RNA, Small Interfering/ge [Genetics]
MH - RNA, Small Interfering/me [Metabolism]
MH - Signal Transduction
KW - ATR/CHK1 signalling pathway; Gemcitabine; Gemcitabine-combination therapy; Pancreatic cancer; RAD17; shRNA screening
AB - Chemotherapy of advanced pancreatic cancer has mainly been gemcitabine-based for the past 15 years, with only limited effect. Recently, combination therapy that also targets checkpoint kinase 1 (CHK1) has become an attractive option. The central role of CHK1 in many DNA-damage response pathways, however, may result in undesired cytotoxicity in normal cells, causing side effects. We were searching for other target molecules of similar function that may be more specific and thus better suited for combination therapy. To this end a negative selection RNAi screen was performed in cell lines with small hairpin RNA molecules targeting over 10,000 genes. Genes that were found to be synthetically lethal with gemcitabine and whose proteins act upstream of CHK1 were characterised in more detail. In particular, the inhibition of RAD17 potentiated gemcitabine cytotoxicity in the pancreatic cancer cell lines BxPC-3 and MiaPaca-2 and in the primary cell line JoPaca-1 that closely resembles primary tumour tissue. Further analysis showed that the synergistic effect of RAD17 knockdown and gemcitabine leads to forced mitotic entry of cells arrested in S phase by gemcitabine treatment, resulting in asymmetric DNA distribution during anaphase followed by DNA fragmentation and finally cell death by mitotic catastrophe. Our data suggest RAD17 as a novel target protein for gemcitabine combination therapy supplementing or complementing inhibition of CHK1. In contrast to CHK1, RAD17 knockdown by itself does not lead to abnormal DNA segregation, suggesting a more specific action.
RN - 0 (Antimetabolites, Antineoplastic)
RN - 0 (Cell Cycle Proteins)
RN - 0 (RNA, Small Interfering)
RN - 0 (Rad17 protein, human)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
ES - 1477-9137
IL - 0021-9533
DI - jcs.124768
DO - https://dx.doi.org/10.1242/jcs.124768
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 23687379 [pubmed]
ID - jcs.124768 [pii]
ID - 10.1242/jcs.124768 [doi]
PP - ppublish
LG - English
EP - 20130517
DP - 2013 Aug 01
DC - 20130802
EZ - 2013/05/21 06:00
DA - 2014/05/23 06:00
DT - 2013/05/21 06:00
YR - 2013
ED - 20140522
RD - 20130802
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23687379
<251. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24516200
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Kim PS
AU - Jochems C
AU - Grenga I
AU - Donahue RN
AU - Tsang KY
AU - Gulley JL
AU - Schlom J
AU - Farsaci B
FA - Kim, Peter S
FA - Jochems, Caroline
FA - Grenga, Italia
FA - Donahue, Renee N
FA - Tsang, Kwong Y
FA - Gulley, James L
FA - Schlom, Jeffrey
FA - Farsaci, Benedetto
IN - Kim, Peter S. Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
TI - Pan-Bcl-2 inhibitor, GX15-070 (obatoclax), decreases human T regulatory lymphocytes while preserving effector T lymphocytes: a rationale for its use in combination immunotherapy.
SO - Journal of Immunology. 192(6):2622-33, 2014 Mar 15
AS - J Immunol. 192(6):2622-33, 2014 Mar 15
NJ - Journal of immunology (Baltimore, Md. : 1950)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ifb, 2985117r
IO - J. Immunol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122292
OI - Source: NLM. NIHMS555469
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Apoptosis/de [Drug Effects]
MH - Apoptosis/im [Immunology]
MH - CTLA-4 Antigen/im [Immunology]
MH - CTLA-4 Antigen/me [Metabolism]
MH - Cells, Cultured
MH - Combined Modality Therapy
MH - Dose-Response Relationship, Drug
MH - Down-Regulation/de [Drug Effects]
MH - Down-Regulation/im [Immunology]
MH - Female
MH - Flow Cytometry
MH - Forkhead Transcription Factors/im [Immunology]
MH - Forkhead Transcription Factors/me [Metabolism]
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Leukocytes, Mononuclear/de [Drug Effects]
MH - Leukocytes, Mononuclear/im [Immunology]
MH - Leukocytes, Mononuclear/me [Metabolism]
MH - Lymphocyte Activation/de [Drug Effects]
MH - Lymphocyte Activation/im [Immunology]
MH - Ovarian Neoplasms/bl [Blood]
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Proto-Oncogene Proteins c-bcl-2/ai [Antagonists & Inhibitors]
MH - Proto-Oncogene Proteins c-bcl-2/im [Immunology]
MH - Proto-Oncogene Proteins c-bcl-2/me [Metabolism]
MH - *Pyrroles/pd [Pharmacology]
MH - *T-Lymphocyte Subsets/de [Drug Effects]
MH - T-Lymphocyte Subsets/im [Immunology]
MH - T-Lymphocyte Subsets/me [Metabolism]
MH - *T-Lymphocytes, Regulatory/de [Drug Effects]
MH - T-Lymphocytes, Regulatory/im [Immunology]
MH - T-Lymphocytes, Regulatory/me [Metabolism]
MH - Time Factors
AB - Bcl-2 inhibitors are currently being evaluated in clinical studies for treatment of patients with solid tumors and hematopoietic malignancies. In this study we explored the potential for combining the pan-Bcl-2 inhibitor GX15-070 (GX15; obatoclax) with immunotherapeutic modalities. We evaluated the in vitro effects of GX15 on human T cell subsets obtained from PBMCs in terms of activation, memory, and suppressive function. Our results indicated that in healthy-donor PBMCs, mature-activated T cells were more resistant to GX15 than early-activated T cells, and that GX15 preserved memory but not non-memory T cell populations. Furthermore, GX15 increased the apoptosis of regulatory T cells (Tregs), profoundly downregulated FOXP3 and CTLA-4 in a dose-dependent manner, and decreased their suppressive function. Treating PBMCs obtained from ovarian cancer patients with GX15 also resulted in increased CD8(+):Treg and CD4(+):Treg ratios. These results support preclinical studies in which mice vaccinated before treatment with GX15 showed the greatest reduction in metastatic lung tumors as a result of increased apoptotic resistance of mature CD8(+) T cells and decreased Treg function brought about by GX15. Taken together, these findings suggest that when a Bcl-2 inhibitor is combined with active immunotherapy in humans, such as the use of a vaccine or immune checkpoint inhibitor, immunotherapy should precede administration of the Bcl-2 inhibitor to allow T cells to become mature, and thus resistant to the cytotoxic effects of the Bcl-2 inhibitor.
RN - 0 (CTLA-4 Antigen)
RN - 0 (FOXP3 protein, human)
RN - 0 (Forkhead Transcription Factors)
RN - 0 (Proto-Oncogene Proteins c-bcl-2)
RN - 0 (Pyrroles)
RN - 0 (obatoclax)
ES - 1550-6606
IL - 0022-1767
DI - jimmunol.1301369
DO - https://dx.doi.org/10.4049/jimmunol.1301369
PT - Journal Article
PT - Research Support, N.I.H., Intramural
ID - 24516200 [pubmed]
ID - jimmunol.1301369 [pii]
ID - 10.4049/jimmunol.1301369 [doi]
ID - PMC4122292 [pmc]
ID - NIHMS555469 [mid]
PP - ppublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00088413
SL - https://clinicaltrials.gov/search/term=NCT00088413
GI - No: ZIA BC010944-06
Organization: *Intramural NIH HHS*
Country: United States
LG - English
EP - 20140210
DP - 2014 Mar 15
DC - 20140310
EZ - 2014/02/12 06:00
DA - 2014/05/16 06:00
DT - 2014/02/12 06:00
YR - 2014
ED - 20140515
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24516200
<252. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24516200
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Kim PS
AU - Jochems C
AU - Grenga I
AU - Donahue RN
AU - Tsang KY
AU - Gulley JL
AU - Schlom J
AU - Farsaci B
FA - Kim, Peter S
FA - Jochems, Caroline
FA - Grenga, Italia
FA - Donahue, Renee N
FA - Tsang, Kwong Y
FA - Gulley, James L
FA - Schlom, Jeffrey
FA - Farsaci, Benedetto
IN - Kim, Peter S. Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
TI - Pan-Bcl-2 inhibitor, GX15-070 (obatoclax), decreases human T regulatory lymphocytes while preserving effector T lymphocytes: a rationale for its use in combination immunotherapy.
SO - Journal of Immunology. 192(6):2622-33, 2014 Mar 15
AS - J Immunol. 192(6):2622-33, 2014 Mar 15
NJ - Journal of immunology (Baltimore, Md. : 1950)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ifb, 2985117r
IO - J. Immunol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122292
OI - Source: NLM. NIHMS555469
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Apoptosis/de [Drug Effects]
MH - Apoptosis/im [Immunology]
MH - CTLA-4 Antigen/im [Immunology]
MH - CTLA-4 Antigen/me [Metabolism]
MH - Cells, Cultured
MH - Combined Modality Therapy
MH - Dose-Response Relationship, Drug
MH - Down-Regulation/de [Drug Effects]
MH - Down-Regulation/im [Immunology]
MH - Female
MH - Flow Cytometry
MH - Forkhead Transcription Factors/im [Immunology]
MH - Forkhead Transcription Factors/me [Metabolism]
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Leukocytes, Mononuclear/de [Drug Effects]
MH - Leukocytes, Mononuclear/im [Immunology]
MH - Leukocytes, Mononuclear/me [Metabolism]
MH - Lymphocyte Activation/de [Drug Effects]
MH - Lymphocyte Activation/im [Immunology]
MH - Ovarian Neoplasms/bl [Blood]
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Proto-Oncogene Proteins c-bcl-2/ai [Antagonists & Inhibitors]
MH - Proto-Oncogene Proteins c-bcl-2/im [Immunology]
MH - Proto-Oncogene Proteins c-bcl-2/me [Metabolism]
MH - *Pyrroles/pd [Pharmacology]
MH - *T-Lymphocyte Subsets/de [Drug Effects]
MH - T-Lymphocyte Subsets/im [Immunology]
MH - T-Lymphocyte Subsets/me [Metabolism]
MH - *T-Lymphocytes, Regulatory/de [Drug Effects]
MH - T-Lymphocytes, Regulatory/im [Immunology]
MH - T-Lymphocytes, Regulatory/me [Metabolism]
MH - Time Factors
AB - Bcl-2 inhibitors are currently being evaluated in clinical studies for treatment of patients with solid tumors and hematopoietic malignancies. In this study we explored the potential for combining the pan-Bcl-2 inhibitor GX15-070 (GX15; obatoclax) with immunotherapeutic modalities. We evaluated the in vitro effects of GX15 on human T cell subsets obtained from PBMCs in terms of activation, memory, and suppressive function. Our results indicated that in healthy-donor PBMCs, mature-activated T cells were more resistant to GX15 than early-activated T cells, and that GX15 preserved memory but not non-memory T cell populations. Furthermore, GX15 increased the apoptosis of regulatory T cells (Tregs), profoundly downregulated FOXP3 and CTLA-4 in a dose-dependent manner, and decreased their suppressive function. Treating PBMCs obtained from ovarian cancer patients with GX15 also resulted in increased CD8(+):Treg and CD4(+):Treg ratios. These results support preclinical studies in which mice vaccinated before treatment with GX15 showed the greatest reduction in metastatic lung tumors as a result of increased apoptotic resistance of mature CD8(+) T cells and decreased Treg function brought about by GX15. Taken together, these findings suggest that when a Bcl-2 inhibitor is combined with active immunotherapy in humans, such as the use of a vaccine or immune checkpoint inhibitor, immunotherapy should precede administration of the Bcl-2 inhibitor to allow T cells to become mature, and thus resistant to the cytotoxic effects of the Bcl-2 inhibitor.
RN - 0 (CTLA-4 Antigen)
RN - 0 (FOXP3 protein, human)
RN - 0 (Forkhead Transcription Factors)
RN - 0 (Proto-Oncogene Proteins c-bcl-2)
RN - 0 (Pyrroles)
RN - 0 (obatoclax)
ES - 1550-6606
IL - 0022-1767
DI - jimmunol.1301369
DO - https://dx.doi.org/10.4049/jimmunol.1301369
PT - Journal Article
PT - Research Support, N.I.H., Intramural
ID - 24516200 [pubmed]
ID - jimmunol.1301369 [pii]
ID - 10.4049/jimmunol.1301369 [doi]
ID - PMC4122292 [pmc]
ID - NIHMS555469 [mid]
PP - ppublish
GI - No: ZIA BC010944-06
Organization: *Intramural NIH HHS*
Country: United States
LG - English
EP - 20140210
DP - 2014 Mar 15
DC - 20140310
EZ - 2014/02/12 06:00
DA - 2014/05/16 06:00
DT - 2014/02/12 06:00
YR - 2014
ED - 20140515
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=24516200
<253. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23717490
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Gardiner D
AU - Lalezari J
AU - Lawitz E
AU - DiMicco M
AU - Ghalib R
AU - Reddy KR
AU - Chang KM
AU - Sulkowski M
AU - Marro SO
AU - Anderson J
AU - He B
AU - Kansra V
AU - McPhee F
AU - Wind-Rotolo M
AU - Grasela D
AU - Selby M
AU - Korman AJ
AU - Lowy I
FA - Gardiner, David
FA - Lalezari, Jay
FA - Lawitz, Eric
FA - DiMicco, Michael
FA - Ghalib, Rheem
FA - Reddy, K Rajender
FA - Chang, Kyong-Mi
FA - Sulkowski, Mark
FA - Marro, Steven O'
FA - Anderson, Jeffrey
FA - He, Bing
FA - Kansra, Vikram
FA - McPhee, Fiona
FA - Wind-Rotolo, Megan
FA - Grasela, Dennis
FA - Selby, Mark
FA - Korman, Alan J
FA - Lowy, Israel
IN - Gardiner, David. Bristol-Myers Squibb, Pennington, New Jersey, USA. david.gardiner@bms.com
TI - A randomized, double-blind, placebo-controlled assessment of BMS-936558, a fully human monoclonal antibody to programmed death-1 (PD-1), in patients with chronic hepatitis C virus infection.
SO - PLoS ONE [Electronic Resource]. 8(5):e63818, 2013
AS - PLoS ONE. 8(5):e63818, 2013
NJ - PloS one
PI - Journal available in: Electronic-Print
PI - Citation processed from: Internet
JC - 101285081
IO - PLoS ONE
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661719
SB - Index Medicus
CP - United States
MH - Adult
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/pk [Pharmacokinetics]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antiviral Agents/ae [Adverse Effects]
MH - *Antiviral Agents/tu [Therapeutic Use]
MH - Double-Blind Method
MH - Female
MH - Half-Life
MH - *Hepacivirus/de [Drug Effects]
MH - Hepacivirus/ge [Genetics]
MH - *Hepatitis C, Chronic/dt [Drug Therapy]
MH - Humans
MH - Interferon-alpha/tu [Therapeutic Use]
MH - Male
MH - Middle Aged
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/me [Metabolism]
MH - RNA, Viral/ge [Genetics]
MH - Viral Load/de [Drug Effects]
MH - Viral Load/ge [Genetics]
AB - UNLABELLED: Expression of the programmed death 1 (PD-1) receptor and its ligands are implicated in the T cell exhaustion phenotype which contributes to the persistence of several chronic viral infections, including human hepatitis C virus (HCV). The antiviral potential of BMS-936558 (MDX-1106) - a fully human anti-PD-1 monoclonal immunoglobulin-G4 that blocks ligand binding - was explored in a proof-of-concept, placebo-controlled single-ascending-dose study in patients (N = 54) with chronic HCV infection. Interferon-alfa treatment-experienced patients (n = 42) were randomized 5:1 to receive a single infusion of BMS-936558 (0.03, 0.1, 0.3, 1.0, 3.0 mg/kg [n = 5 each] or 10 mg/kg [n = 10]) or of placebo (n = 7). An additional 12 HCV treatment-naive patients were randomized to receive 10 mg/kg BMS-936558 (n = 10) or placebo (n = 2). Patients were followed for 85 days post-dose. Five patients who received BMS-936558 (0.1 [n = 1] or 10 mg/kg) and one placebo patient achieved the primary study endpoint of a reduction in HCV RNA >=0.5 log10 IU/mL on at least 2 consecutive visits; 3 (10 mg/kg) achieved a >4 log10 reduction. Two patients (10 mg/kg) achieved HCV RNA below the lower limit of quantitation (25 IU/mL), one of whom (a prior null-responder) remained RNA-undetectable 1 year post-study. Transient reductions in CD4(+), CD8(+) and CD19(+) cells, including both naive and memory CD4(+) and CD8(+) subsets, were observed at Day 2 without evidence of immune deficit. No clinically relevant changes in immunoglobulin subsets or treatment-related trends in circulating cytokines were noted. BMS-936558 exhibited dose-related exposure increases, with a half-life of 20-24 days. BMS-936558 was mostly well tolerated. One patient (10 mg/kg) experienced an asymptomatic grade 4 ALT elevation coincident with the onset of a 4-log viral load reduction. Six patients exhibited immune-related adverse events of mild-to-moderate intensity, including two cases of hyperthyroidism consistent with autoimmune thyroiditis. Further investigation of PD-1 pathway blockade in chronic viral disease is warranted.
AB - TRIAL REGISTRATION: ClinicalTrials.gov NCT00703469.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antiviral Agents)
RN - 0 (Interferon-alpha)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 0 (RNA, Viral)
RN - 31YO63LBSN (nivolumab)
ES - 1932-6203
IL - 1932-6203
DI - PONE-D-12-35786
DO - https://dx.doi.org/10.1371/journal.pone.0063818
PT - Clinical Trial
PT - Journal Article
PT - Randomized Controlled Trial
PT - Research Support, Non-U.S. Gov't
ID - 23717490 [pubmed]
ID - 10.1371/journal.pone.0063818 [doi]
ID - PONE-D-12-35786 [pii]
ID - PMC3661719 [pmc]
PP - epublish
PH - 2012/11/08 [received]
PH - 2013/04/04 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00703469
SA - ClinicalTrials.gov/NCT00703469
SA - ClinicalTrials.gov/NCT01642004
SA - ClinicalTrials.gov/NCT01668784
SA - ClinicalTrials.gov/NCT01673867
SL - https://clinicaltrials.gov/search/term=NCT00703469
SL - https://clinicaltrials.gov/search/term=NCT00703469
SL - https://clinicaltrials.gov/search/term=NCT01642004
SL - https://clinicaltrials.gov/search/term=NCT01668784
SL - https://clinicaltrials.gov/search/term=NCT01673867
GI - No: K24 DA034621
Organization: (DA) *NIDA NIH HHS*
Country: United States
No: R01 DA016065
Organization: (DA) *NIDA NIH HHS*
Country: United States
LG - English
EP - 20130522
DP - 2013
DC - 20130529
EZ - 2013/05/30 06:00
DA - 2014/04/18 06:00
DT - 2013/05/30 06:00
YR - 2013
ED - 20140417
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23717490
<254. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23717490
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Gardiner D
AU - Lalezari J
AU - Lawitz E
AU - DiMicco M
AU - Ghalib R
AU - Reddy KR
AU - Chang KM
AU - Sulkowski M
AU - Marro SO
AU - Anderson J
AU - He B
AU - Kansra V
AU - McPhee F
AU - Wind-Rotolo M
AU - Grasela D
AU - Selby M
AU - Korman AJ
AU - Lowy I
FA - Gardiner, David
FA - Lalezari, Jay
FA - Lawitz, Eric
FA - DiMicco, Michael
FA - Ghalib, Rheem
FA - Reddy, K Rajender
FA - Chang, Kyong-Mi
FA - Sulkowski, Mark
FA - Marro, Steven O'
FA - Anderson, Jeffrey
FA - He, Bing
FA - Kansra, Vikram
FA - McPhee, Fiona
FA - Wind-Rotolo, Megan
FA - Grasela, Dennis
FA - Selby, Mark
FA - Korman, Alan J
FA - Lowy, Israel
IN - Gardiner, David. Bristol-Myers Squibb, Pennington, New Jersey, USA. david.gardiner@bms.com
TI - A randomized, double-blind, placebo-controlled assessment of BMS-936558, a fully human monoclonal antibody to programmed death-1 (PD-1), in patients with chronic hepatitis C virus infection.
SO - PLoS ONE [Electronic Resource]. 8(5):e63818, 2013
AS - PLoS ONE. 8(5):e63818, 2013
NJ - PloS one
PI - Journal available in: Electronic-Print
PI - Citation processed from: Internet
JC - 101285081
IO - PLoS ONE
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661719
SB - Index Medicus
CP - United States
MH - Adult
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/pk [Pharmacokinetics]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antiviral Agents/ae [Adverse Effects]
MH - *Antiviral Agents/tu [Therapeutic Use]
MH - Double-Blind Method
MH - Female
MH - Half-Life
MH - *Hepacivirus/de [Drug Effects]
MH - Hepacivirus/ge [Genetics]
MH - *Hepatitis C, Chronic/dt [Drug Therapy]
MH - Humans
MH - Interferon-alpha/tu [Therapeutic Use]
MH - Male
MH - Middle Aged
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/me [Metabolism]
MH - RNA, Viral/ge [Genetics]
MH - Viral Load/de [Drug Effects]
MH - Viral Load/ge [Genetics]
AB - UNLABELLED: Expression of the programmed death 1 (PD-1) receptor and its ligands are implicated in the T cell exhaustion phenotype which contributes to the persistence of several chronic viral infections, including human hepatitis C virus (HCV). The antiviral potential of BMS-936558 (MDX-1106) - a fully human anti-PD-1 monoclonal immunoglobulin-G4 that blocks ligand binding - was explored in a proof-of-concept, placebo-controlled single-ascending-dose study in patients (N = 54) with chronic HCV infection. Interferon-alfa treatment-experienced patients (n = 42) were randomized 5:1 to receive a single infusion of BMS-936558 (0.03, 0.1, 0.3, 1.0, 3.0 mg/kg [n = 5 each] or 10 mg/kg [n = 10]) or of placebo (n = 7). An additional 12 HCV treatment-naive patients were randomized to receive 10 mg/kg BMS-936558 (n = 10) or placebo (n = 2). Patients were followed for 85 days post-dose. Five patients who received BMS-936558 (0.1 [n = 1] or 10 mg/kg) and one placebo patient achieved the primary study endpoint of a reduction in HCV RNA >=0.5 log10 IU/mL on at least 2 consecutive visits; 3 (10 mg/kg) achieved a >4 log10 reduction. Two patients (10 mg/kg) achieved HCV RNA below the lower limit of quantitation (25 IU/mL), one of whom (a prior null-responder) remained RNA-undetectable 1 year post-study. Transient reductions in CD4(+), CD8(+) and CD19(+) cells, including both naive and memory CD4(+) and CD8(+) subsets, were observed at Day 2 without evidence of immune deficit. No clinically relevant changes in immunoglobulin subsets or treatment-related trends in circulating cytokines were noted. BMS-936558 exhibited dose-related exposure increases, with a half-life of 20-24 days. BMS-936558 was mostly well tolerated. One patient (10 mg/kg) experienced an asymptomatic grade 4 ALT elevation coincident with the onset of a 4-log viral load reduction. Six patients exhibited immune-related adverse events of mild-to-moderate intensity, including two cases of hyperthyroidism consistent with autoimmune thyroiditis. Further investigation of PD-1 pathway blockade in chronic viral disease is warranted.
AB - TRIAL REGISTRATION: ClinicalTrials.gov NCT00703469.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antiviral Agents)
RN - 0 (Interferon-alpha)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 0 (RNA, Viral)
RN - 31YO63LBSN (nivolumab)
ES - 1932-6203
IL - 1932-6203
DI - PONE-D-12-35786
DO - https://dx.doi.org/10.1371/journal.pone.0063818
PT - Clinical Trial
PT - Journal Article
PT - Randomized Controlled Trial
PT - Research Support, Non-U.S. Gov't
ID - 23717490 [pubmed]
ID - 10.1371/journal.pone.0063818 [doi]
ID - PONE-D-12-35786 [pii]
ID - PMC3661719 [pmc]
PP - epublish
PH - 2012/11/08 [received]
PH - 2013/04/04 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00703469
SL - https://clinicaltrials.gov/search/term=NCT00703469
GI - No: K24 DA034621
Organization: (DA) *NIDA NIH HHS*
Country: United States
No: R01 DA016065
Organization: (DA) *NIDA NIH HHS*
Country: United States
LG - English
EP - 20130522
DP - 2013
DC - 20130529
EZ - 2013/05/30 06:00
DA - 2014/04/18 06:00
DT - 2013/05/30 06:00
YR - 2013
ED - 20140417
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=23717490
<255. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23804422
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Engelke CG
AU - Parsels LA
AU - Qian Y
AU - Zhang Q
AU - Karnak D
AU - Robertson JR
AU - Tanska DM
AU - Wei D
AU - Davis MA
AU - Parsels JD
AU - Zhao L
AU - Greenson JK
AU - Lawrence TS
AU - Maybaum J
AU - Morgan MA
FA - Engelke, Carl G
FA - Parsels, Leslie A
FA - Qian, Yushen
FA - Zhang, Qiang
FA - Karnak, David
FA - Robertson, Jordan R
FA - Tanska, Daria M
FA - Wei, Dongping
FA - Davis, Mary A
FA - Parsels, Joshua D
FA - Zhao, Lili
FA - Greenson, Joel K
FA - Lawrence, Theodore S
FA - Maybaum, Jonathan
FA - Morgan, Meredith A
IN - Engelke, Carl G. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109-5637, USA.
TI - Sensitization of pancreatic cancer to chemoradiation by the Chk1 inhibitor MK8776.
SO - Clinical Cancer Research. 19(16):4412-21, 2013 Aug 15
AS - Clin Cancer Res. 19(16):4412-21, 2013 Aug 15
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c2h, 9502500
IO - Clin. Cancer Res.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745540
OI - Source: NLM. NIHMS498288
SB - Index Medicus
CP - United States
MH - Animals
MH - Cell Line, Tumor
MH - Checkpoint Kinase 1
MH - Chemoradiotherapy
MH - Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Disease Models, Animal
MH - Drug Resistance, Neoplasm/ge [Genetics]
MH - Female
MH - Humans
MH - Inhibitory Concentration 50
MH - Mice
MH - Pancreatic Neoplasms/ge [Genetics]
MH - *Pancreatic Neoplasms/me [Metabolism]
MH - Pancreatic Neoplasms/th [Therapy]
MH - Protein Kinase Inhibitors/ad [Administration & Dosage]
MH - *Protein Kinase Inhibitors/pd [Pharmacology]
MH - *Protein Kinases/me [Metabolism]
MH - *Pyrazoles/pd [Pharmacology]
MH - *Pyrimidines/pd [Pharmacology]
MH - Radiation-Sensitizing Agents/pd [Pharmacology]
MH - Recombinational DNA Repair/de [Drug Effects]
MH - Xenograft Model Antitumor Assays
AB - PURPOSE: The combination of radiation with chemotherapy is the most effective therapy for unresectable pancreatic cancer. To improve upon this regimen, we combined the selective Checkpoint kinase 1 (Chk1) inhibitor MK8776 with gemcitabine-based chemoradiation in preclinical pancreatic cancer models.
AB - EXPERIMENTAL DESIGN: We tested the ability of MK8776 to sensitize to gemcitabine-radiation in homologous recombination repair (HRR)-proficient and -deficient pancreatic cancer cells and assessed Rad51 focus formation. In vivo, we investigated the efficacy, tumor cell selectivity, and pharmacodynamic biomarkers of sensitization by MK8776.
AB - RESULTS: We found that MK8776 significantly sensitized HRR-proficient (AsPC-1, MiaPaCa-2, BxPC-3) but not -deficient (Capan-1) pancreatic cancer cells to gemcitabine-radiation and inhibited Rad51 focus formation in HRR-proficient cells. In vivo, MiaPaCa-2 xenografts were significantly sensitized to gemcitabine-radiation by MK8776 without significant weight loss or observable toxicity in the small intestine, the dose-limiting organ for chemoradiation therapy in pancreatic cancer. We also assessed pChk1 (S345), a pharmacodynamic biomarker of DNA damage in response to Chk1 inhibition in both tumor and small intestine and found that MK8776 combined with gemcitabine or gemcitabine-radiation produced a significantly greater increase in pChk1 (S345) in tumor relative to small intestine, suggesting greater DNA damage in tumor than in normal tissue. Furthermore, we demonstrated the utility of an ex vivo platform for assessment of pharmacodynamic biomarkers of Chk1 inhibition in pancreatic cancer.
AB - CONCLUSIONS: Together, our results suggest that MK8776 selectively sensitizes HRR-proficient pancreatic cancer cells and xenografts to gemcitabine-radiation and support the clinical investigation of MK8776 in combination with gemcitabine-radiation in locally advanced pancreatic cancer.
AB - Copyright ©2013 AACR.
RN - 0 (MK-8776)
RN - 0 (Protein Kinase Inhibitors)
RN - 0 (Pyrazoles)
RN - 0 (Pyrimidines)
RN - 0 (Radiation-Sensitizing Agents)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7 (Protein Kinases)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
RN - EC 2-7-11-1 (Chek1 protein, mouse)
IS - 1078-0432
IL - 1078-0432
DI - 1078-0432.CCR-12-3748
DO - https://dx.doi.org/10.1158/1078-0432.CCR-12-3748
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 23804422 [pubmed]
ID - 1078-0432.CCR-12-3748 [pii]
ID - 10.1158/1078-0432.CCR-12-3748 [doi]
ID - PMC3745540 [pmc]
ID - NIHMS498288 [mid]
PP - ppublish
GI - No: R01CA163895
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA046592
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01CA138723
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA138723
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA130810
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA163895
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50CA130810
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20130626
DP - 2013 Aug 15
DC - 20130815
EZ - 2013/06/28 06:00
DA - 2014/04/02 06:00
DT - 2013/06/28 06:00
YR - 2013
ED - 20140401
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23804422
<256. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23716015
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Postow MA
AU - Luke JJ
AU - Bluth MJ
AU - Ramaiya N
AU - Panageas KS
AU - Lawrence DP
AU - Ibrahim N
AU - Flaherty KT
AU - Sullivan RJ
AU - Ott PA
AU - Callahan MK
AU - Harding JJ
AU - D'Angelo SP
AU - Dickson MA
AU - Schwartz GK
AU - Chapman PB
AU - Gnjatic S
AU - Wolchok JD
AU - Hodi FS
AU - Carvajal RD
FA - Postow, Michael A
FA - Luke, Jason J
FA - Bluth, Mark J
FA - Ramaiya, Nikhil
FA - Panageas, Katherine S
FA - Lawrence, Donald P
FA - Ibrahim, Nageatte
FA - Flaherty, Keith T
FA - Sullivan, Ryan J
FA - Ott, Patrick A
FA - Callahan, Margaret K
FA - Harding, James J
FA - D'Angelo, Sandra P
FA - Dickson, Mark A
FA - Schwartz, Gary K
FA - Chapman, Paul B
FA - Gnjatic, Sacha
FA - Wolchok, Jedd D
FA - Hodi, F Stephen
FA - Carvajal, Richard D
IN - Postow, Michael A. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. carvajar@mskcc.org
TI - Ipilimumab for patients with advanced mucosal melanoma.
CM - Comment in: Oncologist. 2013 Jun;18(6):658-60; PMID: 23814163
SO - Oncologist. 18(6):726-32, 2013 Jun
AS - Oncologist. 18(6):726-32, 2013 Jun
NJ - The oncologist
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dd5, 9607837
IO - Oncologist
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063400
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - *Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antigens, Neoplasm/bi [Biosynthesis]
MH - CTLA-4 Antigen/bi [Biosynthesis]
MH - Clinical Trials as Topic
MH - Female
MH - Humans
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - Mucous Membrane/de [Drug Effects]
MH - Mucous Membrane/pa [Pathology]
MH - *Neoplasm Metastasis/dt [Drug Therapy]
MH - Neoplasm Metastasis/pa [Pathology]
MH - Retrospective Studies
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/pa [Pathology]
MH - Survival Analysis
KW - CTLA-4; Cancer-testis antigens; Immunotherapy; Ipilimumab; Mucosal melanoma
AB - The outcome of patients with mucosal melanoma treated with ipilimumab is not defined. To assess the efficacy and safety of ipilimumab in this melanoma subset, we performed a multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab. The clinical characteristics, treatments, toxicities, radiographic assessment of disease burden by central radiology review at each site, and mutational profiles of the patients' tumors were recorded. Available peripheral blood samples were used to assess humoral immunity against a panel of cancer-testis antigens and other antigens. By the immune-related response criteria of the 30 patients who underwent radiographic assessment after ipilimumab at approximately week 12, there were 1 immune-related complete response, 1 immune-related partial response, 6 immune-related stable disease, and 22 immune-related progressive disease. By the modified World Health Organization criteria, there were 1 immune-related complete response, 1 immune-related partial response, 5 immune-related stable disease, and 23 immune-related progressive disease. Immune-related adverse events (as graded by Common Terminology Criteria for Adverse Events version 4.0) consisted of six patients with rash (four grade 1, two grade 2), three patients with diarrhea (one grade 1, two grade 3), one patient with grade 1 thyroiditis, one patient with grade 3 hepatitis, and 1 patient with grade 2 hypophysitis. The median overall survival from the time of the first dose of ipilimumab was 6.4 months (range: 1.8-26.7 months). Several patients demonstrated serologic responses to cancer-testis antigens and other antigens. Durable responses to ipilimumab were observed, but the overall response rate was low. Additional investigation is necessary to clarify the role of ipilimumab in patients with mucosal melanoma.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, Neoplasm)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 6T8C155666 (ipilimumab)
ES - 1549-490X
IL - 1083-7159
DI - theoncologist.2012-0464
DO - https://dx.doi.org/10.1634/theoncologist.2012-0464
PT - Journal Article
PT - Multicenter Study
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 23716015 [pubmed]
ID - theoncologist.2012-0464 [pii]
ID - 10.1634/theoncologist.2012-0464 [doi]
ID - PMC4063400 [pmc]
PP - ppublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT 01355120
SL - https://clinicaltrials.gov/search/term=NCT 01355120
GI - No: RC2CA148468
Organization: (CA) *NCI NIH HHS*
Country: United States
No: RC2 CA148468
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
No: UL1-TR000457
Organization: (TR) *NCATS NIH HHS*
Country: United States
No: UL1 TR000457
Organization: (TR) *NCATS NIH HHS*
Country: United States
LG - English
EP - 20130528
DP - 2013 Jun
DC - 20130701
EZ - 2013/05/30 06:00
DA - 2014/02/14 06:00
DT - 2013/05/30 06:00
YR - 2013
ED - 20140213
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23716015
<257. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23716015
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Postow MA
AU - Luke JJ
AU - Bluth MJ
AU - Ramaiya N
AU - Panageas KS
AU - Lawrence DP
AU - Ibrahim N
AU - Flaherty KT
AU - Sullivan RJ
AU - Ott PA
AU - Callahan MK
AU - Harding JJ
AU - D'Angelo SP
AU - Dickson MA
AU - Schwartz GK
AU - Chapman PB
AU - Gnjatic S
AU - Wolchok JD
AU - Hodi FS
AU - Carvajal RD
FA - Postow, Michael A
FA - Luke, Jason J
FA - Bluth, Mark J
FA - Ramaiya, Nikhil
FA - Panageas, Katherine S
FA - Lawrence, Donald P
FA - Ibrahim, Nageatte
FA - Flaherty, Keith T
FA - Sullivan, Ryan J
FA - Ott, Patrick A
FA - Callahan, Margaret K
FA - Harding, James J
FA - D'Angelo, Sandra P
FA - Dickson, Mark A
FA - Schwartz, Gary K
FA - Chapman, Paul B
FA - Gnjatic, Sacha
FA - Wolchok, Jedd D
FA - Hodi, F Stephen
FA - Carvajal, Richard D
IN - Postow, Michael A. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. carvajar@mskcc.org
TI - Ipilimumab for patients with advanced mucosal melanoma.
CM - Comment in: Oncologist. 2013 Jun;18(6):658-60; PMID: 23814163
SO - Oncologist. 18(6):726-32, 2013 Jun
AS - Oncologist. 18(6):726-32, 2013 Jun
NJ - The oncologist
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dd5, 9607837
IO - Oncologist
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063400
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - *Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antigens, Neoplasm/bi [Biosynthesis]
MH - CTLA-4 Antigen/bi [Biosynthesis]
MH - Clinical Trials as Topic
MH - Female
MH - Humans
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - Mucous Membrane/de [Drug Effects]
MH - Mucous Membrane/pa [Pathology]
MH - *Neoplasm Metastasis/dt [Drug Therapy]
MH - Neoplasm Metastasis/pa [Pathology]
MH - Retrospective Studies
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/pa [Pathology]
MH - Survival Analysis
KW - CTLA-4; Cancer-testis antigens; Immunotherapy; Ipilimumab; Mucosal melanoma
AB - The outcome of patients with mucosal melanoma treated with ipilimumab is not defined. To assess the efficacy and safety of ipilimumab in this melanoma subset, we performed a multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab. The clinical characteristics, treatments, toxicities, radiographic assessment of disease burden by central radiology review at each site, and mutational profiles of the patients' tumors were recorded. Available peripheral blood samples were used to assess humoral immunity against a panel of cancer-testis antigens and other antigens. By the immune-related response criteria of the 30 patients who underwent radiographic assessment after ipilimumab at approximately week 12, there were 1 immune-related complete response, 1 immune-related partial response, 6 immune-related stable disease, and 22 immune-related progressive disease. By the modified World Health Organization criteria, there were 1 immune-related complete response, 1 immune-related partial response, 5 immune-related stable disease, and 23 immune-related progressive disease. Immune-related adverse events (as graded by Common Terminology Criteria for Adverse Events version 4.0) consisted of six patients with rash (four grade 1, two grade 2), three patients with diarrhea (one grade 1, two grade 3), one patient with grade 1 thyroiditis, one patient with grade 3 hepatitis, and 1 patient with grade 2 hypophysitis. The median overall survival from the time of the first dose of ipilimumab was 6.4 months (range: 1.8-26.7 months). Several patients demonstrated serologic responses to cancer-testis antigens and other antigens. Durable responses to ipilimumab were observed, but the overall response rate was low. Additional investigation is necessary to clarify the role of ipilimumab in patients with mucosal melanoma.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, Neoplasm)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 6T8C155666 (ipilimumab)
ES - 1549-490X
IL - 1083-7159
DI - theoncologist.2012-0464
DO - https://dx.doi.org/10.1634/theoncologist.2012-0464
PT - Journal Article
PT - Multicenter Study
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 23716015 [pubmed]
ID - theoncologist.2012-0464 [pii]
ID - 10.1634/theoncologist.2012-0464 [doi]
ID - PMC4063400 [pmc]
PP - ppublish
GI - No: RC2CA148468
Organization: (CA) *NCI NIH HHS*
Country: United States
No: RC2 CA148468
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
No: UL1-TR000457
Organization: (TR) *NCATS NIH HHS*
Country: United States
No: UL1 TR000457
Organization: (TR) *NCATS NIH HHS*
Country: United States
LG - English
EP - 20130528
DP - 2013 Jun
DC - 20130701
EZ - 2013/05/30 06:00
DA - 2014/02/14 06:00
DT - 2013/05/30 06:00
YR - 2013
ED - 20140213
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=23716015
<258. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23487828
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Bot I
AU - Blank CU
AU - Boogerd W
AU - Brandsma D
FA - Bot, Ilja
FA - Blank, Christian U
FA - Boogerd, Willem
FA - Brandsma, Dieta
IN - Bot, Ilja. Department of Neurology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands. i.bot@neuro.umcn.nl
TI - Neurological immune-related adverse events of ipilimumab.
SO - Practical Neurology. 13(4):278-80, 2013 Aug
AS - Pract. neurol.. 13(4):278-80, 2013 Aug
NJ - Practical neurology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101130961
IO - Pract Neurol
SB - Index Medicus
CP - England
MH - Aged
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - CTLA-4 Antigen/im [Immunology]
MH - Humans
MH - *Immunologic Factors/tu [Therapeutic Use]
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - Middle Aged
KW - NEUROONCOLOGY; NEUROPHARMACOLOGY
AB - Ipilimumab enhances the T lymphocyte mediated immune response to both tumour cells and healthy tissue, improving survival in patients with metastatic melanoma but also leads to more immune-related adverse events (irAEs) than previously used treatments, such as dacarbazine. We present three patients with neurological irAEs from ipilimumab treatment: hypophysitis, meningitis and Guillain-Barre syndrome. Once an irAE occurs, ipilimumab should be stopped and corticosteroids started. Usually, ipilimumab-induced irAE symptoms improve within days to weeks, but can be life-threatening if unrecognised.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 0 (Immunologic Factors)
RN - 6T8C155666 (ipilimumab)
ES - 1474-7766
IL - 1474-7758
DI - practneurol-2012-000447
DO - https://dx.doi.org/10.1136/practneurol-2012-000447
PT - Case Reports
PT - Journal Article
ID - 23487828 [pubmed]
ID - practneurol-2012-000447 [pii]
ID - 10.1136/practneurol-2012-000447 [doi]
PP - ppublish
LG - English
EP - 20130313
DP - 2013 Aug
DC - 20130705
EZ - 2013/03/15 06:00
DA - 2014/02/11 06:00
DT - 2013/03/15 06:00
YR - 2013
ED - 20140210
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23487828
<259. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23588667
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Xu J
AU - Zhu W
AU - Xu W
AU - Cui X
AU - Chen L
AU - Ji S
AU - Qin Y
AU - Yao W
AU - Liu L
AU - Liu C
AU - Long J
AU - Li M
AU - Yu X
FA - Xu, Jin
FA - Zhu, Wenwei
FA - Xu, Wenyan
FA - Cui, Xiaobo
FA - Chen, Leon
FA - Ji, Shunrong
FA - Qin, Yi
FA - Yao, Wantong
FA - Liu, Liang
FA - Liu, Chen
FA - Long, Jiang
FA - Li, Min
FA - Yu, Xianjun
IN - Xu, Jin. Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
TI - Silencing of MBD1 reverses pancreatic cancer therapy resistance through inhibition of DNA damage repair.
SO - International Journal of Oncology. 42(6):2046-52, 2013 Jun
AS - Int J Oncol. 42(6):2046-52, 2013 Jun
NJ - International journal of oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cx5, 9306042
IO - Int. J. Oncol.
SB - Index Medicus
CP - Greece
MH - Cell Cycle Proteins/ge [Genetics]
MH - Cell Cycle Proteins/me [Metabolism]
MH - Cell Line, Tumor/de [Drug Effects]
MH - Cell Line, Tumor/re [Radiation Effects]
MH - Chemoradiotherapy
MH - Chromatin/me [Metabolism]
MH - Cisplatin/pd [Pharmacology]
MH - DNA Damage
MH - *DNA Repair/ge [Genetics]
MH - *DNA-Binding Proteins/ge [Genetics]
MH - DNA-Binding Proteins/me [Metabolism]
MH - *Drug Resistance, Neoplasm/ge [Genetics]
MH - Gene Knockdown Techniques
MH - Gene Silencing
MH - Humans
MH - Nuclear Proteins/ge [Genetics]
MH - Nuclear Proteins/me [Metabolism]
MH - Pancreatic Neoplasms/dt [Drug Therapy]
MH - *Pancreatic Neoplasms/ge [Genetics]
MH - *Pancreatic Neoplasms/rt [Radiotherapy]
MH - Radiation Tolerance/ge [Genetics]
MH - Trans-Activators/ge [Genetics]
MH - Trans-Activators/me [Metabolism]
MH - *Transcription Factors/ge [Genetics]
MH - Transcription Factors/me [Metabolism]
AB - High resistance to traditional chemo- and radiotherapies contributes to the poor prognosis of pancreatic cancer (PC). Methyl-CpG binding domain protein 1 (MBD1), which plays an important role in disease progression, contributes to the drug resistance of PC cells; however, the mechanism underlying the drug resistance endowed by MBD1 remains unknown. In this study, we found that MBD1 was recruited to DNA damage sites under DNA damage conditions. Silencing of MBD1 significantly impaired activation of the DNA damage checkpoint response and inhibited DNA repair capacity. MBD1 binds mediator of DNA damage checkpoint protein 1 (MDC1), which is induced by radiation and regulates NBS1 activation in the presence of DNA damage repair. Knockdown of MBD1 significantly increased the sensitivity of cells to radiation and cisplatin (diamindichloridoplatin, DDP) in vitro. Importantly, the function of MBD1 in regulating chemoradioresistance is also partially dependent on DNA damage repair. Thus, we hypothesize that MBD1 may promote PC chemoradioresistance by regulating PC cell fate in the presence of DNA damage. Collectively, these findings reveal an important function of MBD1 in DNA repair and mediation of chemoradioresistance of cancer cells. Moreover, this study suggests that MBD1 is a promising molecular target for sensitizing resistant PC tumor cells to chemoradiotherapy.
RN - 0 (Cell Cycle Proteins)
RN - 0 (Chromatin)
RN - 0 (DNA-Binding Proteins)
RN - 0 (MBD1 protein, human)
RN - 0 (MDC1 protein, human)
RN - 0 (NBN protein, human)
RN - 0 (Nuclear Proteins)
RN - 0 (Trans-Activators)
RN - 0 (Transcription Factors)
RN - Q20Q21Q62J (Cisplatin)
ES - 1791-2423
IL - 1019-6439
DO - https://dx.doi.org/10.3892/ijo.2013.1901
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 23588667 [pubmed]
ID - 10.3892/ijo.2013.1901 [doi]
PP - ppublish
PH - 2013/01/18 [received]
PH - 2013/02/22 [accepted]
LG - English
EP - 20130416
DP - 2013 Jun
DC - 20130419
EZ - 2013/04/17 06:00
DA - 2013/12/24 06:00
DT - 2013/04/17 06:00
YR - 2013
ED - 20131223
RD - 20130419
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23588667
<260. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24001893
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Torino F
AU - Barnabei A
AU - Paragliola RM
AU - Marchetti P
AU - Salvatori R
AU - Corsello SM
FA - Torino, Francesco
FA - Barnabei, Agnese
FA - Paragliola, Rosa Maria
FA - Marchetti, Paolo
FA - Salvatori, Roberto
FA - Corsello, Salvatore Maria
IN - Torino, Francesco. Department of Systems Medicine, Chair of Medical Oncology, Tor Vergata University of Rome, Rome, Italy.
TI - Endocrine side-effects of anti-cancer drugs: mAbs and pituitary dysfunction: clinical evidence and pathogenic hypotheses. [Review]
SO - European Journal of Endocrinology. 169(6):R153-64, 2013 Dec
AS - EUR. J. ENDOCRINOL.. 169(6):R153-64, 2013 Dec
NJ - European journal of endocrinology
PI - Journal available in: Electronic-Print
PI - Citation processed from: Internet
JC - bxu, 9423848
IO - Eur. J. Endocrinol.
SB - Index Medicus
CP - England
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/im [Immunology]
MH - *CTLA-4 Antigen/de [Drug Effects]
MH - CTLA-4 Antigen/me [Metabolism]
MH - Endocrine System/de [Drug Effects]
MH - Endocrine System/pp [Physiopathology]
MH - Humans
MH - *Hypopituitarism/ci [Chemically Induced]
MH - *Hypopituitarism/me [Metabolism]
MH - Hypopituitarism/pa [Pathology]
MH - Hypopituitarism/pp [Physiopathology]
MH - Inflammation/ci [Chemically Induced]
MH - Inflammation/me [Metabolism]
MH - Pituitary Diseases/ci [Chemically Induced]
MH - Pituitary Diseases/me [Metabolism]
MH - *Pituitary Gland/de [Drug Effects]
MH - *Pituitary Gland/me [Metabolism]
MH - Pituitary Gland/pa [Pathology]
MH - Pituitary Gland/pp [Physiopathology]
MH - *Programmed Cell Death 1 Receptor/de [Drug Effects]
MH - Programmed Cell Death 1 Receptor/me [Metabolism]
AB - mAbs are established targeted therapies for several diseases, including hematological and solid malignancies. These agents have shown a favorable toxicity profile, but, despite their high selectivity, new typical side-effects have emerged. In cancer patients, pituitary dysfunction may be mainly due to brain metastases or primary tumors and to related surgery and radiotherapy. Anticancer agents may induce hypopituitarism in patients cured for childhood cancers. These agents infrequently affect pituitary function in adult cancer patients. Notably, hypophysitis, a previously very rare disease, has emerged as a distinctive side-effect of ipilimumab and tremelimumab, two mAbs inhibiting the cytotoxic T-lymphocyte antigen-4 receptor, being occasionally seen with nivolumab, another immune checkpoint inhibitor. Enhanced antitumor immunity is the suggested mechanism of action of these drugs and autoimmunity the presumptive mechanism of their toxicity. Recently, ipilimumab has been licensed for the treatment of patients affected by metastatic melanoma. With the expanding use of these drugs, hypophysitis will be progressively encountered by oncologists and endocrinologists in clinical practice. The optimal management of this potentially life-threatening adverse event needs a rapid and timely diagnostic and therapeutic intervention. Hypopituitarism caused by these agents is rarely reversible, requiring prolonged or lifelong substitutive hormonal treatment. Further studies are needed to clarify several clinical and pathogenic aspects of this new form of secondary pituitary dysfunction.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 31YO63LBSN (nivolumab)
RN - 6T8C155666 (ipilimumab)
RN - QEN1X95CIX (tremelimumab)
ES - 1479-683X
IL - 0804-4643
DI - EJE-13-0434
DO - https://dx.doi.org/10.1530/EJE-13-0434
PT - Journal Article
PT - Review
ID - 24001893 [pubmed]
ID - EJE-13-0434 [pii]
ID - 10.1530/EJE-13-0434 [doi]
PP - epublish
LG - English
EP - 20131023
DP - 2013 Dec
DC - 20131024
EZ - 2013/09/05 06:00
DA - 2013/12/18 06:00
DT - 2013/09/05 06:00
YR - 2013
ED - 20131216
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24001893
<261. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23773743
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Lecouflet M
AU - Verschoore M
AU - Giard C
AU - Gohier P
AU - Le Corre Y
AU - Milea D
AU - Martin L
FA - Lecouflet, M
FA - Verschoore, M
FA - Giard, C
FA - Gohier, P
FA - Le Corre, Y
FA - Milea, D
FA - Martin, L
IN - Lecouflet, M. Service de dermatologie, universite L'UNAM, CHU d'Angers, 4, rue Larrey, 49933 Angers cedex 9, France. marie.lecouflet@gmail.com
TI - [Orbital myositis associated with ipilimumab]. [French]
OT - Myosite orbitaire associee a un traitement par ipilimumab.
SO - Annales de Dermatologie et de Venereologie. 140(6-7):448-51, 2013 Jun-Jul
AS - Ann Dermatol Venereol. 140(6-7):448-51, 2013 Jun-Jul
NJ - Annales de dermatologie et de venereologie
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 5rc, 7702013
IO - Ann Dermatol Venereol
SB - Index Medicus
CP - France
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/im [Immunology]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/im [Immunology]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - CD4-Positive T-Lymphocytes/de [Drug Effects]
MH - CTLA-4 Antigen/im [Immunology]
MH - Cavernous Sinus Thrombosis/di [Diagnosis]
MH - Cellulitis/di [Diagnosis]
MH - Combined Modality Therapy
MH - Diagnosis, Differential
MH - Diplopia/et [Etiology]
MH - Exophthalmos/et [Etiology]
MH - Female
MH - Foot Diseases/su [Surgery]
MH - Foot Diseases/th [Therapy]
MH - Humans
MH - *Immunotherapy
MH - Lymphatic Metastasis
MH - Melanoma/sc [Secondary]
MH - Melanoma/su [Surgery]
MH - Melanoma/th [Therapy]
MH - *Orbital Myositis/ci [Chemically Induced]
MH - Orbital Myositis/co [Complications]
MH - Orbital Myositis/di [Diagnosis]
MH - Orbital Myositis/dt [Drug Therapy]
MH - Skin Neoplasms/su [Surgery]
MH - Skin Neoplasms/th [Therapy]
AB - BACKGROUND: Ipilimumab is a monoclonal antibody targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) that allows increased survival and, occasionally, complete remission, in the treatment of metastatic melanoma. The most frequent adverse effects are attributed to dysimmunity. We report the case of a female patient who developed orbital myositis during treatment with ipilimumab.
AB - PATIENTS AND METHODS: A woman on ipilimumab for a heel melanoma with mediastinal metastases was referred for evaluation of painful diplopia and proptosis that began three days after the fourth infusion of ipilimumab. The clinical examination disclosed a left abductiondeficit associated with conjunctival hyperaemia and palpebral oedema. Orbital MRI disclosed enlargement of the left lateral rectus, enhancing after contrast. An extensive work-up did not find any evidence for thyroid-related eye disease, as well as other orbital inflammatory processes, orbital cellulitis or orbital metastases. Treatment with high-dose oral steroids resulted in complete clinical recovery within a few days.
AB - DISCUSSION: To our knowledge, this is the first clinical report of orbital myositis as an adverse event related to anti-CTLA-4 antibody treatment. Both timing and usual profile of adverse events support the hypothesis that orbital myositis has to be attributed there to ipilimumab. Several dysimmune toxicities were observed with ipilimumab. Ophtalmic toxicity has unusually been described. Most cases were uveitis. Whether immune-related adverse events correlate with clinical response to ipilimumab treatment remains to be determined.
AB - Copyright © 2013 Elsevier Masson SAS. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 6T8C155666 (ipilimumab)
IS - 0151-9638
IL - 0151-9638
DI - S0151-9638(13)00720-5
DO - https://dx.doi.org/10.1016/j.annder.2013.02.029
PT - Case Reports
PT - Journal Article
ID - 23773743 [pubmed]
ID - S0151-9638(13)00720-5 [pii]
ID - 10.1016/j.annder.2013.02.029 [doi]
PP - ppublish
PH - 2012/10/22 [received]
PH - 2013/01/05 [revised]
PH - 2013/02/14 [accepted]
LG - French
EP - 20130509
DP - 2013 Jun-Jul
DC - 20130618
EZ - 2013/06/19 06:00
DA - 2013/12/16 06:00
DT - 2013/06/19 06:00
YR - 2013
ED - 20131209
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23773743
<262. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24278787
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Tarhini A
FA - Tarhini, Ahmad
IN - Tarhini, Ahmad. Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh Cancer Institute, UPMC Cancer Pavilion, 5150 Centre Avenue, Room 555, Pittsburgh, PA 15232, USA.
TI - Immune-mediated adverse events associated with ipilimumab ctla-4 blockade therapy: the underlying mechanisms and clinical management. [Review]
SO - Scientifica. 2013:857519, 2013
AS - Scientifica (Cairo). 2013:857519, 2013
NJ - Scientifica
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - 101589932
IO - Scientifica (Cairo)
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3820355
CP - Egypt
AB - Immunomodulation with the anti-CTLA-4 monoclonal antibody ipilimumab has been shown to extend overall survival (OS) in previously treated and treatment-naive patients with unresectable stage III or IV melanoma. Blockade of CTLA-4 signaling with ipilimumab prolongs T-cell activation and restores T-cell proliferation, thus amplifying T-cell-mediated immunity and the patient's capacity to mount an effective antitumor immune response. While this immunostimulation has unprecedented OS benefits in the melanoma setting, it can also result in immune-mediated effects on various organ systems, leading to immune-related adverse events (irAEs). Ipilimumab-associated irAEs are common and typically low grade and manageable, but can also be serious and life threatening. The skin and gastrointestinal tract are most frequently affected, while hepatic, endocrine, and neurologic events are less common. With proper management, most irAEs resolve within a relatively short time, with a predictable resolution pattern. Prompt and appropriate management of these irAEs is essential and treatment guidelines have been developed to assist oncologists and their teams. Implementation of these irAE management algorithms will help ensure that patients are able to benefit from ipilimumab therapy with adequate control of toxicities.
IL - 2090-908X
DO - https://dx.doi.org/10.1155/2013/857519
PT - Journal Article
PT - Review
ID - 24278787 [pubmed]
ID - 10.1155/2013/857519 [doi]
ID - PMC3820355 [pmc]
PP - ppublish
PH - 2012/12/06 [received]
PH - 2013/01/10 [accepted]
LG - English
EP - 20130417
DP - 2013
DC - 20131126
EZ - 2013/11/27 06:00
DA - 2013/11/28 06:01
DT - 2013/11/28 06:00
YR - 2013
ED - 20131126
RD - 20131216
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=24278787
<263. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 24175496
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Anderson L
AU - Bhatia V
FA - Anderson, Laura
FA - Bhatia, Vishal
IN - Anderson, Laura. Sanford School of Medicine, University of South Dakota, USA.
TI - Ipilimumab immune-related adverse reactions: a case report.
SO - South Dakota Medicine: The Journal of the South Dakota State Medical Association. 66(8):315-7, 2013 Aug
AS - S D Med. 66(8):315-7, 2013 Aug
NJ - South Dakota medicine : the journal of the South Dakota State Medical Association
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 101265265
IO - S D Med
SB - Index Medicus
CP - United States
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/im [Immunology]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Autoimmune Diseases/ci [Chemically Induced]
MH - Autoimmune Diseases/im [Immunology]
MH - Female
MH - Follow-Up Studies
MH - Humans
MH - Hydrocortisone/tu [Therapeutic Use]
MH - *Hypopituitarism/ci [Chemically Induced]
MH - Hypopituitarism/dt [Drug Therapy]
MH - *Hypopituitarism/im [Immunology]
MH - Hypothyroidism/co [Complications]
MH - Hypothyroidism/dt [Drug Therapy]
MH - Hypothyroidism/im [Immunology]
MH - Immunomodulation/de [Drug Effects]
MH - Immunomodulation/im [Immunology]
MH - Liver Neoplasms/co [Complications]
MH - Liver Neoplasms/dt [Drug Therapy]
MH - Liver Neoplasms/sc [Secondary]
MH - Lung Neoplasms/co [Complications]
MH - Lung Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/sc [Secondary]
MH - *Melanoma/pa [Pathology]
MH - Middle Aged
MH - Prednisone/tu [Therapeutic Use]
MH - Thyroxine/tu [Therapeutic Use]
MH - Up-Regulation/de [Drug Effects]
MH - Up-Regulation/im [Immunology]
AB - Ipilimumab is an immunomodulating agent approved by the Food and Drug Administration (FDA) as of March 2011 for the treatment of metastatic melanoma. The medication works by inhibiting cytotoxic T-lymphocyte antigen 4, which typically works to down-regulate the T-cell response and protects self-antigens from recognition by the immune system. Since the T-cells are no longer down-regulated by this antigen, they are allowed to proliferate, thereby helping to prevent melanoma tumor evasion. As a result of the up-regulation of the immune system, numerous immune-mediated adverse effects have been reported including colitis, dermatitis, hepatitis and rarely hypophysitis. Typically, these effects are treated with high-dose steroids and most eventually resolve. We present a case of autoimmune (lymphocytic) hypophysitis following treatment with four doses of ipilimumab 3mg/kg and discuss the work-up, treatment and prognosis of the event.
RN - 0 (Antibodies, Monoclonal)
RN - 6T8C155666 (ipilimumab)
RN - Q51BO43MG4 (Thyroxine)
RN - VB0R961HZT (Prednisone)
RN - WI4X0X7BPJ (Hydrocortisone)
IS - 0038-3317
IL - 0038-3317
PT - Case Reports
PT - Journal Article
ID - 24175496 [pubmed]
PP - ppublish
LG - English
DP - 2013 Aug
DC - 20131101
EZ - 2013/11/02 06:00
DA - 2013/11/20 06:00
DT - 2013/11/02 06:00
YR - 2013
ED - 20131119
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=24175496
<264. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23835677
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Hamed SS
AU - Straubinger RM
AU - Jusko WJ
FA - Hamed, Salaheldin S
FA - Straubinger, Robert M
FA - Jusko, William J
IN - Hamed, Salaheldin S. Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY 14214, USA.
TI - Pharmacodynamic modeling of cell cycle and apoptotic effects of gemcitabine on pancreatic adenocarcinoma cells.
SO - Cancer Chemotherapy & Pharmacology. 72(3):553-63, 2013 Sep
AS - Cancer Chemother Pharmacol. 72(3):553-63, 2013 Sep
NJ - Cancer chemotherapy and pharmacology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c9s, 7806519
IO - Cancer Chemother. Pharmacol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777243
OI - Source: NLM. NIHMS503569
SB - Index Medicus
CP - Germany
MH - *Adenocarcinoma/dt [Drug Therapy]
MH - Adenocarcinoma/pa [Pathology]
MH - Antimetabolites, Antineoplastic/ad [Administration & Dosage]
MH - *Antimetabolites, Antineoplastic/pd [Pharmacology]
MH - *Apoptosis/de [Drug Effects]
MH - Cell Cycle Checkpoints/de [Drug Effects]
MH - Cell Line, Tumor
MH - Cell Proliferation
MH - Deoxycytidine/ad [Administration & Dosage]
MH - *Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Dose-Response Relationship, Drug
MH - Humans
MH - Models, Biological
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Time Factors
AB - PURPOSE: The standard of care for treating patients with pancreatic adenocarcinomas includes gemcitabine (2',2'-difluorodeoxycytidine). Gemcitabine primarily elicits its response by stalling the DNA replication forks of cells in the S phase of the cell cycle. To provide a quantitative framework for characterizing the cell cycle and apoptotic effects of gemcitabine, we developed a pharmacodynamic model in which the activation of cell cycle checkpoints or cell death is dependent on gemcitabine exposure.
AB - METHODS: Three pancreatic adenocarcinoma cell lines (AsPC-1, BxPC-3, and MiaPaca-2) were exposed to varying concentrations (0-100,000 ng/mL) of gemcitabine over a period of 96 h in order to quantify proliferation kinetics and cell distributions among the cell cycle phases. The model assumes that the drug can inhibit cycle-phase transitioning in each of the 3 phases (G1, S, and G2/M) and can cause apoptosis of cells in G1 and G2/M phases. Fitting was performed using the ADAPT5 program.
AB - RESULTS: The time course of gemcitabine effects was well described by the model, and parameters were estimated with good precision. Model predictions and experimental data show that gemcitabine induces cell cycle arrest in the S phase at low concentrations, whereas higher concentrations induce arrest in all cell cycle phases. Furthermore, apoptotic effects of gemcitabine appear to be minimal and take place at later time points.
AB - CONCLUSION: The pharmacodynamic model developed provides a quantitative, mechanistic interpretation of gemcitabine efficacy in 3 pancreatic cancer cell lines, and provides useful insights for rational selection of chemotherapeutic agents for combination therapy.
RN - 0 (Antimetabolites, Antineoplastic)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
ES - 1432-0843
IL - 0344-5704
DO - https://dx.doi.org/10.1007/s00280-013-2226-6
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 23835677 [pubmed]
ID - 10.1007/s00280-013-2226-6 [doi]
ID - PMC3777243 [pmc]
ID - NIHMS503569 [mid]
PP - ppublish
PH - 2012/12/05 [received]
PH - 2013/06/08 [accepted]
GI - No: R01 GM057980
Organization: (GM) *NIGMS NIH HHS*
Country: United States
No: GM57980
Organization: (GM) *NIGMS NIH HHS*
Country: United States
LG - English
EP - 20130709
DP - 2013 Sep
DC - 20130827
EZ - 2013/07/10 06:00
DA - 2013/10/24 06:00
DT - 2013/07/10 06:00
YR - 2013
ED - 20131023
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23835677
<265. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23924790
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Le DT
AU - Lutz E
AU - Uram JN
AU - Sugar EA
AU - Onners B
AU - Solt S
AU - Zheng L
AU - Diaz LA Jr
AU - Donehower RC
AU - Jaffee EM
AU - Laheru DA
FA - Le, Dung T
FA - Lutz, Eric
FA - Uram, Jennifer N
FA - Sugar, Elizabeth A
FA - Onners, Beth
FA - Solt, Sara
FA - Zheng, Lei
FA - Diaz, Luis A Jr
FA - Donehower, Ross C
FA - Jaffee, Elizabeth M
FA - Laheru, Daniel A
IN - Le, Dung T. The Sidney Kimmel Cancer Center, the Skip Viragh Center for Pancreatic Cancer, Research and Clinical Care, and the Sol Goldman Pancreatic Cancer Center at Johns Hopkins, Baltimore, MD, USA. dle2@jhmi.edu
TI - Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer.
CM - Comment in: J Immunother. 2013 Sep;36(7):362-4; PMID: 23924787
SO - Journal of Immunotherapy. 36(7):382-9, 2013 Sep
AS - J Immunother. 36(7):382-9, 2013 Sep
NJ - Journal of immunotherapy (Hagerstown, Md. : 1997)
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - cuq, 9706083
IO - J. Immunother.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779664
OI - Source: NLM. NIHMS505598
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - *Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antineoplastic Agents/ad [Administration & Dosage]
MH - CTLA-4 Antigen/im [Immunology]
MH - *Cancer Vaccines/ad [Administration & Dosage]
MH - Carcinoma, Pancreatic Ductal/dg [Diagnostic Imaging]
MH - Carcinoma, Pancreatic Ductal/im [Immunology]
MH - *Carcinoma, Pancreatic Ductal/th [Therapy]
MH - Combined Modality Therapy
MH - Female
MH - GPI-Linked Proteins/im [Immunology]
MH - Granulocyte-Macrophage Colony-Stimulating Factor/ge [Genetics]
MH - Humans
MH - Male
MH - Middle Aged
MH - Pancreatic Neoplasms/dg [Diagnostic Imaging]
MH - Pancreatic Neoplasms/im [Immunology]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - Radiography
MH - T-Lymphocytes/im [Immunology]
MH - Transfection
AB - Preclinical reports support the concept of synergy between cancer vaccines and immune checkpoint blockade in nonimmunogenic tumors. In particular, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibodies have been successfully combined with GM-CSF cell-based vaccines (GVAX). Ipilimumab (anti-CTLA-4) has been tested as a single agent in patients with pancreatic ductal adenocarcinoma (PDA) resulting in a delayed response at a dose of 3 mg/kg. Our study evaluated ipilimumab 10 mg/kg (arm 1) and ipilimumab 10 mg/kg + GVAX (arm 2). A total of 30 patients with previously treated advanced PDA were randomized (1:1). Induction doses were administered every 3 weeks for a total of 4 doses followed by maintenance dosing every 12 weeks. Two patients in arm 1 showed evidence of stable disease (7 and 22 wk) but none demonstrated CA19-9 biochemical responses. In contrast, 3 patients in arm 2 had evidence of prolonged disease stabilization (31, 71, and 81 wk) and 7 patients experienced CA19-9 declines. In 2 of these patients, disease stabilization occurred after an initial period of progression. The median overall survival (OS) (3.6 vs. 5.7 mo, hazards ratio: 0.51, P = 0.072) and 1 year OS (7 vs. 27%) favored arm 2. Similar to prior ipilimumab studies, 20% of patients in each arm had grade 3/4 immune-related adverse events. Among patients with OS > 4.3 months, there was an increase in the peak mesothelin-specific T cells (P = 0.014) and enhancement of the T-cell repertoire (P = 0.031). In conclusion, checkpoint blockade in combination with GVAX has the potential for clinical benefit and should be evaluated in a larger study.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (Cancer Vaccines)
RN - 0 (GPI-Linked Proteins)
RN - 0 (mesothelin)
RN - 6T8C155666 (ipilimumab)
RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
ES - 1537-4513
IL - 1524-9557
DI - 00002371-201309000-00005
DO - https://dx.doi.org/10.1097/CJI.0b013e31829fb7a2
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Randomized Controlled Trial
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 23924790 [pubmed]
ID - 10.1097/CJI.0b013e31829fb7a2 [doi]
ID - 00002371-201309000-00005 [pii]
ID - PMC3779664 [pmc]
ID - NIHMS505598 [mid]
PP - ppublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00836407
SL - https://clinicaltrials.gov/search/term=NCT00836407
GI - No: P50 CA062924
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA148964
Organization: (CA) *NCI NIH HHS*
Country: United States
No: 2P50 CA062924
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA1266058
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA126058
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA163672
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2013 Sep
DC - 20130808
EZ - 2013/08/09 06:00
DA - 2013/10/23 06:00
DT - 2013/08/09 06:00
YR - 2013
ED - 20131022
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23924790
<266. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23924790
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Le DT
AU - Lutz E
AU - Uram JN
AU - Sugar EA
AU - Onners B
AU - Solt S
AU - Zheng L
AU - Diaz LA Jr
AU - Donehower RC
AU - Jaffee EM
AU - Laheru DA
FA - Le, Dung T
FA - Lutz, Eric
FA - Uram, Jennifer N
FA - Sugar, Elizabeth A
FA - Onners, Beth
FA - Solt, Sara
FA - Zheng, Lei
FA - Diaz, Luis A Jr
FA - Donehower, Ross C
FA - Jaffee, Elizabeth M
FA - Laheru, Daniel A
IN - Le, Dung T. The Sidney Kimmel Cancer Center, the Skip Viragh Center for Pancreatic Cancer, Research and Clinical Care, and the Sol Goldman Pancreatic Cancer Center at Johns Hopkins, Baltimore, MD, USA. dle2@jhmi.edu
TI - Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer.
CM - Comment in: J Immunother. 2013 Sep;36(7):362-4; PMID: 23924787
SO - Journal of Immunotherapy. 36(7):382-9, 2013 Sep
AS - J Immunother. 36(7):382-9, 2013 Sep
NJ - Journal of immunotherapy (Hagerstown, Md. : 1997)
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - cuq, 9706083
IO - J. Immunother.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779664
OI - Source: NLM. NIHMS505598
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - *Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antineoplastic Agents/ad [Administration & Dosage]
MH - CTLA-4 Antigen/im [Immunology]
MH - *Cancer Vaccines/ad [Administration & Dosage]
MH - Carcinoma, Pancreatic Ductal/dg [Diagnostic Imaging]
MH - Carcinoma, Pancreatic Ductal/im [Immunology]
MH - *Carcinoma, Pancreatic Ductal/th [Therapy]
MH - Combined Modality Therapy
MH - Female
MH - GPI-Linked Proteins/im [Immunology]
MH - Granulocyte-Macrophage Colony-Stimulating Factor/ge [Genetics]
MH - Humans
MH - Male
MH - Middle Aged
MH - Pancreatic Neoplasms/dg [Diagnostic Imaging]
MH - Pancreatic Neoplasms/im [Immunology]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - Radiography
MH - T-Lymphocytes/im [Immunology]
MH - Transfection
AB - Preclinical reports support the concept of synergy between cancer vaccines and immune checkpoint blockade in nonimmunogenic tumors. In particular, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibodies have been successfully combined with GM-CSF cell-based vaccines (GVAX). Ipilimumab (anti-CTLA-4) has been tested as a single agent in patients with pancreatic ductal adenocarcinoma (PDA) resulting in a delayed response at a dose of 3 mg/kg. Our study evaluated ipilimumab 10 mg/kg (arm 1) and ipilimumab 10 mg/kg + GVAX (arm 2). A total of 30 patients with previously treated advanced PDA were randomized (1:1). Induction doses were administered every 3 weeks for a total of 4 doses followed by maintenance dosing every 12 weeks. Two patients in arm 1 showed evidence of stable disease (7 and 22 wk) but none demonstrated CA19-9 biochemical responses. In contrast, 3 patients in arm 2 had evidence of prolonged disease stabilization (31, 71, and 81 wk) and 7 patients experienced CA19-9 declines. In 2 of these patients, disease stabilization occurred after an initial period of progression. The median overall survival (OS) (3.6 vs. 5.7 mo, hazards ratio: 0.51, P = 0.072) and 1 year OS (7 vs. 27%) favored arm 2. Similar to prior ipilimumab studies, 20% of patients in each arm had grade 3/4 immune-related adverse events. Among patients with OS > 4.3 months, there was an increase in the peak mesothelin-specific T cells (P = 0.014) and enhancement of the T-cell repertoire (P = 0.031). In conclusion, checkpoint blockade in combination with GVAX has the potential for clinical benefit and should be evaluated in a larger study.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (Cancer Vaccines)
RN - 0 (GPI-Linked Proteins)
RN - 0 (mesothelin)
RN - 6T8C155666 (ipilimumab)
RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
ES - 1537-4513
IL - 1524-9557
DI - 00002371-201309000-00005
DO - https://dx.doi.org/10.1097/CJI.0b013e31829fb7a2
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Randomized Controlled Trial
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 10.1097/CJI.0b013e31829fb7a2 [doi]
ID - 00002371-201309000-00005 [pii]
ID - PMC3779664 [pmc]
ID - NIHMS505598 [mid]
PP - ppublish
GI - No: P50 CA062924
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA148964
Organization: (CA) *NCI NIH HHS*
Country: United States
No: 2P50 CA062924
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA1266058
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA169702
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA126058
Organization: (CA) *NCI NIH HHS*
Country: United States
No: K23 CA163672
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2013 Sep
DC - 20130808
EZ - 2013/08/09 06:00
DA - 2013/10/23 06:00
DT - 2013/08/09 06:00
YR - 2013
ED - 20131022
RD - 20170408
UP - 20170410
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=23924790
<267. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23340297
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Abiko K
AU - Mandai M
AU - Hamanishi J
AU - Yoshioka Y
AU - Matsumura N
AU - Baba T
AU - Yamaguchi K
AU - Murakami R
AU - Yamamoto A
AU - Kharma B
AU - Kosaka K
AU - Konishi I
FA - Abiko, Kaoru
FA - Mandai, Masaki
FA - Hamanishi, Junzo
FA - Yoshioka, Yumiko
FA - Matsumura, Noriomi
FA - Baba, Tsukasa
FA - Yamaguchi, Ken
FA - Murakami, Ryusuke
FA - Yamamoto, Ayaka
FA - Kharma, Budiman
FA - Kosaka, Kenzo
FA - Konishi, Ikuo
IN - Abiko, Kaoru. Department of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
TI - PD-L1 on tumor cells is induced in ascites and promotes peritoneal dissemination of ovarian cancer through CTL dysfunction.
SO - Clinical Cancer Research. 19(6):1363-74, 2013 Mar 15
AS - Clin Cancer Res. 19(6):1363-74, 2013 Mar 15
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c2h, 9502500
IO - Clin. Cancer Res.
SB - Index Medicus
CP - United States
MH - Animals
MH - *Antigens, CD274/ge [Genetics]
MH - Antigens, CD274/me [Metabolism]
MH - Ascites/ge [Genetics]
MH - Ascites/pa [Pathology]
MH - Cell Line, Tumor
MH - Female
MH - Gene Expression Regulation, Neoplastic
MH - Humans
MH - Mice
MH - Neoplasm Invasiveness/ge [Genetics]
MH - Neoplasm Invasiveness/pa [Pathology]
MH - *Ovarian Neoplasms/ge [Genetics]
MH - Ovarian Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Peritoneal Cavity/pa [Pathology]
MH - *T-Lymphocytes, Cytotoxic/me [Metabolism]
MH - T-Lymphocytes, Cytotoxic/pa [Pathology]
AB - PURPOSE: Ovarian cancer often progresses by disseminating to the peritoneal cavity, but how the tumor cells evade host immunity during this process is poorly understood. Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be expressed in cancer cells. The purpose of this study is to elucidate the function of PD-L1 in peritoneal dissemination.
AB - EXPERIMENTAL DESIGN: Ovarian cancer cases were studied by microarray and immunohistochemistry. PD-L1 expression in mouse ovarian cancer cell line in various conditions was assessed by flow cytometry. PD-L1-overexpression cell line and PD-L1-depleted cell line were generated, and cytolysis by CTLs was analyzed, and alterations in CTLs were studied by means of timelapse and microarray. These cell lines were injected intraperitoneally to syngeneic immunocompetent mice.
AB - RESULTS: Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and peritoneal positive cytology. PD-L1 expression in mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and coculture with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression inhibited gathering and degranulation of CTLs. Gene expression profile of CTLs caused by PD-L1-overexpressing ovarian cancer was associated with CTLs exhaustion. In mouse models, PD-L1 depletion resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival.
AB - CONCLUSION: PD-L1 expression in tumor cell promotes peritoneal dissemination by repressing CTL function. PD-L1-targeted therapy is a promising strategy for preventing and treating peritoneal dissemination.
RN - 0 (Antigens, CD274)
IS - 1078-0432
IL - 1078-0432
DI - 1078-0432.CCR-12-2199
DO - https://dx.doi.org/10.1158/1078-0432.CCR-12-2199
PT - Journal Article
ID - 23340297 [pubmed]
ID - 1078-0432.CCR-12-2199 [pii]
ID - 10.1158/1078-0432.CCR-12-2199 [doi]
PP - ppublish
LG - English
EP - 20130122
DP - 2013 Mar 15
DC - 20130318
EZ - 2013/01/24 06:00
DA - 2013/09/24 06:00
DT - 2013/01/24 06:00
YR - 2013
ED - 20130923
RD - 20130318
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23340297
<268. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23455528
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - van der Hiel B
AU - Blank CU
AU - Haanen JB
AU - Stokkel MP
FA - van der Hiel, Bernies
FA - Blank, Christian U
FA - Haanen, John B A G
FA - Stokkel, Marcel P M
IN - van der Hiel, Bernies. Division of Nuclear Medicine, Leiden University Medical Center, Leiden, The Netherlands.
TI - Detection of early onset of hypophysitis by (18)F-FDG PET-CT in a patient with advanced stage melanoma treated with ipilimumab.
SO - Clinical Nuclear Medicine. 38(4):e182-4, 2013 Apr
AS - Clin Nucl Med. 38(4):e182-4, 2013 Apr
NJ - Clinical nuclear medicine
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - df6, 7611109
IO - Clin Nucl Med
SB - Index Medicus
CP - United States
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Disease Progression
MH - *Fluorodeoxyglucose F18
MH - Humans
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - *Melanoma/pa [Pathology]
MH - *Multimodal Imaging
MH - Neoplasm Staging
MH - *Pituitary Diseases/ci [Chemically Induced]
MH - *Pituitary Diseases/dg [Diagnostic Imaging]
MH - *Positron-Emission Tomography
MH - *Tomography, X-Ray Computed
AB - Ipilimumab is a human monoclonal antibody directed against a receptor expressed on activated T-lymphocytes (CTLA-4). Binding to this receptor induces T-cell activation against tumor cells. A 77-year-old man with a stage IV metastatic melanoma was treated with ipilimumab. F-FDG PET-CT performed for response evaluation revealed intense uptake in the pituitary gland. Two weeks later, biochemical parameters altered confirming hypophysitis. Treatment of the hypophysitis was started, and shortly thereafter, biochemical parameters normalized. Follow-up PET-CT revealed normalization of F-FDG uptake in the pituitary gland. In this case, we present a patient with ipilimumab-induced hypophysitis initially diagnosed on F-FDG PET-CT.
RN - 0 (Antibodies, Monoclonal)
RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN - 6T8C155666 (ipilimumab)
ES - 1536-0229
IL - 0363-9762
DO - https://dx.doi.org/10.1097/RLU.0b013e3182639765
PT - Case Reports
PT - Journal Article
ID - 23455528 [pubmed]
ID - 10.1097/RLU.0b013e3182639765 [doi]
PP - ppublish
LG - English
DP - 2013 Apr
DC - 20130308
EZ - 2013/03/05 06:00
DA - 2013/09/07 06:00
DT - 2013/03/05 06:00
YR - 2013
ED - 20130906
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23455528
<269. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23262440
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Bernardo SG
AU - Moskalenko M
AU - Pan M
AU - Shah S
AU - Sidhu HK
AU - Sicular S
AU - Harcharik S
AU - Chang R
AU - Friedlander P
AU - Saenger YM
FA - Bernardo, Sebastian G
FA - Moskalenko, Marina
FA - Pan, Michael
FA - Shah, Shaily
FA - Sidhu, Harleen K
FA - Sicular, Serge
FA - Harcharik, Sara
FA - Chang, Rui
FA - Friedlander, Philip
FA - Saenger, Yvonne M
IN - Bernardo, Sebastian G. Departments of Dermatology, Mount Sinai School of Medicine, New York, New York 10029, USA.
TI - Elevated rates of transaminitis during ipilimumab therapy for metastatic melanoma.
SO - Melanoma Research. 23(1):47-54, 2013 Feb
AS - Melanoma Res. 23(1):47-54, 2013 Feb
NJ - Melanoma research
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - bjr, 9109623
IO - Melanoma Res.
SB - Index Medicus
CP - England
MH - *Alanine Transaminase/bl [Blood]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Aspartate Aminotransferases/bl [Blood]
MH - *Chemical and Drug Induced Liver Injury/bl [Blood]
MH - Chemical and Drug Induced Liver Injury/im [Immunology]
MH - Chi-Square Distribution
MH - Female
MH - Humans
MH - *Immunologic Factors/ae [Adverse Effects]
MH - Immunologic Factors/tu [Therapeutic Use]
MH - Kaplan-Meier Estimate
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/sc [Secondary]
MH - Middle Aged
MH - Retrospective Studies
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/pa [Pathology]
AB - Melanoma is the deadliest form of skin cancer. Ipilimumab, a novel immunotherapy, is the first treatment shown to improve survival in patients with metastatic melanoma in large randomized controlled studies. The most concerning side effects reported in clinical studies of ipilimumab fall into the category of immune-related adverse events, which include enterocolitis, dermatitis, thyroiditis, hepatitis, hypophysitis, uveitis, and others. During the course of routine clinical care at Mount Sinai Medical Center, frequent hepatotoxicity was noted when ipilimumab was administered at a dose of 3 mg/kg according to Food and Drug Administration (FDA) guidelines. To better characterize these adverse events, we conducted a retrospective review of the first 11 patients with metastatic melanoma treated with ipilimumab at the Mount Sinai Medical Center after FDA approval. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevation, as defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events, each occurred in six of 11 cases (>=grade 1), a notably higher frequency than could be expected on the basis of the FDA licensing study where elevations were reported in 0.8 and 1.5% of patients for AST and ALT, respectively. Grade 3 elevations in AST occurred in three of 11 patients as compared with 0% in the licensing trial. All cases of transaminitis resolved when ipilimumab was temporarily withheld without administration of immunosuppressive medication. During routine clinical care of late-stage melanoma patients with ipilimumab, physicians should monitor patients closely for hepatotoxicity and be aware that toxicity rates may differ across populations during ipilimumab therapy.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Immunologic Factors)
RN - 6T8C155666 (ipilimumab)
RN - EC 2-6-1-1 (Aspartate Aminotransferases)
RN - EC 2-6-1-2 (Alanine Transaminase)
ES - 1473-5636
IL - 0960-8931
DI - 00008390-201302000-00008
DO - https://dx.doi.org/10.1097/CMR.0b013e32835c7e68
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 23262440 [pubmed]
ID - 10.1097/CMR.0b013e32835c7e68 [doi]
ID - 00008390-201302000-00008 [pii]
PP - ppublish
LG - English
DP - 2013 Feb
DC - 20121224
EZ - 2012/12/25 06:00
DA - 2013/06/19 06:00
DT - 2012/12/25 06:00
YR - 2013
ED - 20130617
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23262440
<270. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23471977
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Corsello SM
AU - Barnabei A
AU - Marchetti P
AU - De Vecchis L
AU - Salvatori R
AU - Torino F
FA - Corsello, Salvatore Maria
FA - Barnabei, Agnese
FA - Marchetti, Paolo
FA - De Vecchis, Liana
FA - Salvatori, Roberto
FA - Torino, Francesco
IN - Corsello, Salvatore Maria. Endocrinology Unit, Universita Cattolica, Via Federico Cesi 72, I-00193 Rome, Italy. corsello.sm@mclink.it
TI - Endocrine side effects induced by immune checkpoint inhibitors. [Review]
SO - Journal of Clinical Endocrinology & Metabolism. 98(4):1361-75, 2013 Apr
AS - J Clin Endocrinol Metab. 98(4):1361-75, 2013 Apr
NJ - The Journal of clinical endocrinology and metabolism
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - hrb, 0375362
IO - J. Clin. Endocrinol. Metab.
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - *Cell Cycle Checkpoints/im [Immunology]
MH - Drug-Related Side Effects and Adverse Reactions/ci [Chemically Induced]
MH - Drug-Related Side Effects and Adverse Reactions/ep [Epidemiology]
MH - *Endocrine System/de [Drug Effects]
MH - *Endocrine System Diseases/ci [Chemically Induced]
MH - Endocrine System Diseases/ep [Epidemiology]
MH - Humans
MH - Immunotherapy/ae [Adverse Effects]
MH - Neoplasms/th [Therapy]
AB - CONTEXT: In recent years, progress has been made in cancer immunotherapy by the development of drugs acting as modulators of immune checkpoint proteins, such as the cytotoxic T-lymphocyte antigen-4 (CTLA4) and programmed death-1 (PD-1), two co-inhibitory receptors that are expressed on T cells upon activation. These molecules play crucial roles in maintaining immune homeostasis by down-regulating T-cell signaling, thereby preventing unbridled T-cell proliferation while maintaining tolerance to self-antigens, such as tumor-associated antigens. CTLA4 blockade through systemic administration of the CTLA4-blocking antibody ipilimumab was shown to confer significant survival benefit and prolonged stable disease in patients affected by advanced cutaneous melanoma. Other immune checkpoint inhibitors are under clinical evaluation. However, immune checkpoint blockade can lead to the breaking of immune self-tolerance, thereby inducing a novel syndrome of autoimmune/autoinflammatory side effects, designated as "immune-related adverse events," mainly including rash, colitis, hepatitis, and endocrinopathies.
AB - DATA ACQUISITION: We searched the medical literature using the words "hypophysitis," "hypopituitarism," "thyroid," "adrenal insufficiency," and "endocrine adverse events" in association with "immune checkpoint inhibitors," "ipilimumab," "tremelimumab," "PD-1," and "PD-1-L."
AB - EVIDENCE SYNTHESIS: The spectrum of endocrine disease experienced by patients treated with ipilimumab includes most commonly hypophysitis, more rarely thyroid disease or abnormalities in thyroid function tests, and occasionally primary adrenal insufficiency. Hypophysitis has emerged as a distinctive side effect of CTLA4-blocking antibodies, establishing a new form of autoimmune pituitary disease. This condition, if not promptly recognized, may be life-threatening (due to secondary hypoadrenalism). Hypopituitarism caused by these agents is rarely reversible, and prolonged or lifelong substitutive hormonal treatment is often required. The precise mechanism of injury to the endocrine system triggered by these drugs is yet to be fully elucidated.
AB - CONCLUSIONS: Although reports of endocrine side effects caused by cancer immune therapy are abundant, their exact prevalence and mechanism are unclear. Well-designed correlative studies oriented to finding and validating predictive factors of autoimmune toxicity are urgently needed.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
ES - 1945-7197
IL - 0021-972X
DI - jc.2012-4075
DO - https://dx.doi.org/10.1210/jc.2012-4075
PT - Evaluation Studies
PT - Journal Article
PT - Review
ID - 23471977 [pubmed]
ID - jc.2012-4075 [pii]
ID - 10.1210/jc.2012-4075 [doi]
PP - ppublish
LG - English
EP - 20130307
DP - 2013 Apr
DC - 20130408
EZ - 2013/03/09 06:00
DA - 2013/06/12 06:00
DT - 2013/03/09 06:00
YR - 2013
ED - 20130611
RD - 20131121
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23471977
<271. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23154861
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Schleder S
AU - Schreml S
AU - Heiss P
FA - Schleder, S
FA - Schreml, S
FA - Heiss, P
TI - [Ipilimumab-induced hypophysitis]. [German]
OT - Ipilimumab-induzierte Hypophysitis.
SO - Rofo: Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin. 185(3):268-9, 2013 Mar
AS - ROFO Fortschr Geb Rontgenstr Nuklearmed. 185(3):268-9, 2013 Mar
NJ - RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - rof, 7507497
IO - Rofo
SB - Index Medicus
CP - Germany
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - *Brain Neoplasms/dt [Drug Therapy]
MH - Brain Neoplasms/pa [Pathology]
MH - *Brain Neoplasms/sc [Secondary]
MH - Diagnosis, Differential
MH - Dose-Response Relationship, Drug
MH - Female
MH - Frontal Lobe/de [Drug Effects]
MH - Frontal Lobe/pa [Pathology]
MH - Humans
MH - *Image Interpretation, Computer-Assisted
MH - Infusions, Intravenous
MH - *Lung Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/pa [Pathology]
MH - *Lung Neoplasms/sc [Secondary]
MH - *Magnetic Resonance Imaging
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/pa [Pathology]
MH - *Melanoma/sc [Secondary]
MH - Middle Aged
MH - Neoplasm Staging
MH - *Pituitary Diseases/ci [Chemically Induced]
MH - Pituitary Diseases/di [Diagnosis]
MH - *Pituitary Gland/de [Drug Effects]
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/pa [Pathology]
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
ES - 1438-9010
IL - 1438-9010
DO - https://dx.doi.org/10.1055/s-0032-1325515
PT - Case Reports
PT - Journal Article
ID - 23154861 [pubmed]
ID - 10.1055/s-0032-1325515 [doi]
PP - ppublish
LG - German
EP - 20121115
DP - 2013 Mar
DC - 20130226
EZ - 2012/11/17 06:00
DA - 2013/04/24 06:00
DT - 2012/11/17 06:00
YR - 2013
ED - 20130423
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23154861
<272. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23116250
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Sharma A
AU - Shah SR
AU - Illum H
AU - Dowell J
FA - Sharma, Anant
FA - Shah, Sachin R
FA - Illum, Henrik
FA - Dowell, Jonathan
IN - Sharma, Anant. VA North Texas Health Care System, Dallas, TX 75216, USA. Anant.Sharma@va.gov
TI - Vemurafenib: targeted inhibition of mutated BRAF for treatment of advanced melanoma and its potential in other malignancies. [Review]
SO - Drugs. 72(17):2207-22, 2012 Dec 03
AS - Drugs. 72(17):2207-22, 2012 Dec 03
NJ - Drugs
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - ec2, 7600076
IO - Drugs
SB - Index Medicus
CP - New Zealand
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - Humans
MH - *Indoles/pd [Pharmacology]
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/me [Metabolism]
MH - Mitogen-Activated Protein Kinases/me [Metabolism]
MH - *Mutation
MH - *Proto-Oncogene Proteins B-raf/ai [Antagonists & Inhibitors]
MH - Proto-Oncogene Proteins B-raf/ge [Genetics]
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/me [Metabolism]
MH - *Sulfonamides/pd [Pharmacology]
MH - Treatment Outcome
AB - Vemurafenib is the first molecularly targeted therapy to be licensed in the US and Europe for treatment of advanced melanoma. Its mechanism of action involves selective inhibition of the mutated BRAF V600E kinase that leads to reduced signalling through the aberrant mitogen-activated protein kinase (MAPK) pathway. Its efficacy is restricted to melanomas carrying the BRAF V600E mutation, which is seen in approximately 50% of all melanomas. In a randomized phase III trial, it was superior to dacarbazine in first-line treatment of advanced melanoma, with an overall response rate (ORR) of 48% (95% CI 42, 45), an estimated 6-month progression-free survival (PFS) of 5.3 versus 1.6 months (hazard ratio [HR] 0.26; 95% CI 0.20, 0.33; p<0.001) and a statistically superior 12-month overall survival (OS) rate of 55% versus 43% (HR 0.62 [95% CI 0.49, 0.77]). Vemurafenib is generally well tolerated, but its use can be associated with development of cutaneous neoplasms such as squamous cell carcinoma (SCC) and keratoacanthoma (KA). These lesions can be excised safely without the need for withholding the drug or reducing its dose. Mechanisms of resistance to vemurafenib do not involve development of secondary mutations in the BRAF kinase domain, but may be related to BRAF V600E over-amplification, bypassing mechanisms via upregulation and overexpression of other components in the MAPK signalling cascade or activation of alternative pathways with potential to enhance cell growth, proliferation and survival. Clinical trials to test the efficacy of vemurafenib in combination with immunomodulatory agents, such as ipilimumab, and MAPK kinase (MEK) inhibitors, such as GDC-0973, in the treatment of advanced melanoma are currently underway. Also under investigation is the use of vemurafenib in other solid tumours with BRAF mutations, such as papillary thyroid cancer.
RN - 0 (Antineoplastic Agents)
RN - 0 (Indoles)
RN - 0 (Sulfonamides)
RN - 207SMY3FQT (vemurafenib)
RN - EC 2-7-11-1 (BRAF protein, human)
RN - EC 2-7-11-1 (Proto-Oncogene Proteins B-raf)
RN - EC 2-7-11-24 (Mitogen-Activated Protein Kinases)
ES - 1179-1950
IL - 0012-6667
DO - https://dx.doi.org/10.2165/11640870-000000000-00000
PT - Journal Article
PT - Review
ID - 23116250 [pubmed]
ID - 10.2165/11640870-000000000-00000 [doi]
PP - ppublish
LG - English
DP - 2012 Dec 03
DC - 20121122
EZ - 2012/11/03 06:00
DA - 2013/04/10 06:00
DT - 2012/11/03 06:00
YR - 2012
ED - 20130409
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=23116250
<273. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23559884
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Assi H
AU - Wilson KS
FA - Assi, H
FA - Wilson, K S
TI - Immune toxicities and long remission duration after ipilimumab therapy for metastatic melanoma: two illustrative cases.
SO - Current Oncology. 20(2):e165-9, 2013 Apr
AS - Curr. oncol.. 20(2):e165-9, 2013 Apr
NJ - Current oncology (Toronto, Ont.)
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 9502503
IO - Curr Oncol
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615868
CP - Canada
KW - Ipilimumab; immune response; melanoma; safety
AB - New antitumour immunotherapy strategies for stage iv metastatic melanoma include ipilimumab, a monoclonal antibody against ctla-4. Patterns of response with cancer immunotherapy differ from those with cytotoxic chemotherapy. We present two cases of long-duration immune-related responses with ipilimumab in a phase ii trial. A 66-year-old woman with multiple lung metastases from a scalp primary melanoma received 4 doses of ipilimumab with mixed clinical response. However, after the first maintenance dose, she developed severe ileitis and colitis that responded to steroid therapy. Four months later, she had surgery and radiotherapy for a single brain metastasis. Radiologically, stable disease continued for 36 months after the last ipilimumab dose, and partial response for 5 years after ipilimumab start. A 54-year-old man with cervical lymph node and pulmonary metastases from a scalp primary melanoma received three induction doses of ipilimumab. He developed alopecia universalis and widespread vitiligo, and he discontinued treatment because of hypophysitis. Maintenance ipilimumab was started after a 6-month drug-free interval, with no further adverse events over 15 cycles. At week 12, computed tomography imaging showed no lung metastases and partial response in a supraclavicular lymph node, which was positive on positron-emission tomography. Five years after starting ipilimumab, the supraclavicular lymph node was calcified, and the patient was off steroid therapy and asymptomatic. The foregoing patients demonstrate long responses with ipilimumab (in association with delayed severe colitis in one case, and a constellation of immune events, including alopecia universalis in another). Re-treatment with ipilimumab may be possible even after significant immune adverse events.
IS - 1198-0052
IL - 1198-0052
DI - conc-20-e165
DO - https://dx.doi.org/10.3747/co.20.1265
PT - Journal Article
ID - 23559884 [pubmed]
ID - 10.3747/co.20.1265 [doi]
ID - conc-20-e165 [pii]
ID - PMC3615868 [pmc]
PP - ppublish
LG - English
DP - 2013 Apr
DC - 20130405
EZ - 2013/04/06 06:00
DA - 2013/04/06 06:01
DT - 2013/04/06 06:00
YR - 2013
ED - 20130408
RD - 20130408
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=23559884
<274. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23306915
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Takahashi S
FA - Takahashi, Shunji
IN - Takahashi, Shunji. Dept. of Medical Oncology, Japanese Foundation for Cancer Research, Japan.
TI - [Molecular-target therapy for advanced malignant melanoma]. [Japanese]
SO - Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy]. 40(1):19-25, 2013 Jan
AS - Gan To Kagaku Ryoho. 40(1):19-25, 2013 Jan
NJ - Gan to kagaku ryoho. Cancer & chemotherapy
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 7810034, 6t8
IO - Gan To Kagaku Ryoho
SB - Index Medicus
CP - Japan
MH - Clinical Trials as Topic
MH - Humans
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/ge [Genetics]
MH - Melanoma/pa [Pathology]
MH - *Molecular Targeted Therapy
MH - Mutation
MH - Neoplasm Staging
AB - Malignant melanoma is insensitive to chemotherapy, and standard therapy for metastatic melanoma has been dacarbazine for years. Molecular abnormalities of malignant melanoma, mainly of MAP kinase signals such as BRAF mutation, have been clarified, and molecular target therapy for melanoma has been developed recently. Vemurafenib, an inhibitor for mutated BRAF, has shown its efficacy for the first time, with response rate of more than 50%, and an overall improvement in survival compared with dacarbazine in a phase III study. Skin toxicities including squamous cell carcinoma, are the most severe adverse events. Another BRAF inhibitor, dabrafenib, and a MEK inhibitor, trametinib, have shown excellent efficacy in clinical studies. Melanoma also has high immunogenicity, and cytokines or cell immunotherapy have shown some efficacy. Recently, the importance of immune checkpoints which adjust T-cell activation, such as the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), -B7 or the programmed cell death protein-1(PD1)-PD1 ligand(PDL1), have been clarified. Targeting those immune checkpoints is expected to be effective for enhancing tumor immunity. CTLA-4 antibody ipilimumab has been reported to improve overall survival in two phase III studies. Major adverse events were autoimmune response such as colitis, eruption, liver dysfunction and endocrineopathies. Antibodies to PD1 or PDL1 have shown a higher response rate than those of ipilimumab, and seem to accompany fewer autoimmune responses in phase I studies. These two types of targeting therapy are expected to be standard therapies for melanoma.
IS - 0385-0684
IL - 0385-0684
PT - English Abstract
PT - Journal Article
ID - 23306915 [pubmed]
PP - ppublish
LG - Japanese
DP - 2013 Jan
DC - 20130111
EZ - 2013/01/12 06:00
DA - 2013/03/09 06:00
DT - 2013/01/12 06:00
YR - 2013
ED - 20130308
RD - 20130111
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=23306915
<275. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23316667
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Lotem M
AU - Merims S
AU - Frank S
AU - Ospovat I
AU - Peretz T
FA - Lotem, Michal
FA - Merims, Sharon
FA - Frank, Steven
FA - Ospovat, Inna
FA - Peretz, Tamar
IN - Lotem, Michal. Sharett Institute of Oncology, Hadassah Hebrew University Hospital, Jerusalem. mlotem@hadassah.org.il
TI - [Ctla-4 blockade: a new hope for the immunotherapy of malignant melanoma]. [Review] [Hebrew]
SO - Harefuah. 151(10):585-8, 604, 2012 Oct
AS - Harefuah. 151(10):585-8, 604, 2012 Oct
NJ - Harefuah
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 0034351, fzf
IO - Harefuah
SB - Index Medicus
CP - Israel
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal
MH - Antineoplastic Agents, Alkylating/tu [Therapeutic Use]
MH - Antineoplastic Combined Chemotherapy Protocols
MH - Autoimmunity/de [Drug Effects]
MH - *CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Clinical Trials, Phase II as Topic
MH - Clinical Trials, Phase III as Topic
MH - Dacarbazine/tu [Therapeutic Use]
MH - Drug Approval
MH - Drug Monitoring
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Immunotherapy/td [Trends]
MH - *Immunotherapy
MH - Melanoma/pa [Pathology]
MH - Melanoma/th [Therapy]
MH - *Melanoma
MH - Pharmacovigilance
MH - Proportional Hazards Models
MH - Skin Neoplasms/pa [Pathology]
MH - Skin Neoplasms/th [Therapy]
MH - *Skin Neoplasms
MH - T-Lymphocytes, Cytotoxic/im [Immunology]
MH - Treatment Outcome
AB - Ipilimumab (Yervoy) is a monocLonal antibody designed to block cytotoxic T cell antigen 4 (CTLA-4), an inhibitory receptor of T lymphocytes. This drug is the first to receive US FDAs approval for advanced stage malignant melanoma in the last 13 years. So far, no survival benefit was achieved for this patient group with single drug or combination chemo- and chemo-immunotherapy. In phase II and III trials, up to 15% of patients had melanoma regressions, with a decreased hazard ratio of death of 0.72 compared to the standard chemotherapy with Dacarbazine. The development of Ipilimumab marks a success in deciphering the check-point control on the immune response. Activated T cells over-express CTLA-4 molecule on their surface and become susceptible to its inhibitory effect. CTLA-4 decreases the signaling network derived by antigen recognition of T cells. Alongside of its therapeutic effect, the CTLA-4 blockade enhances autoimmune responses. Severe diarrhea results from toxicity to the colonic mucosa which may eventuate in perforation and, in rare cases, death. Other adverse events of varying severity occur in many patients and include skin eruption, uveitis, endocrinopathies such as thyroiditis and hypophysitis and autoimmune hepatitis. Ipilimumab toxicity is reversible with systemic use of corticosteroids, but the use of TNF inhibitors is sometimes indicated in the absence of resolution. The clinical success of the CTLA-4 blockade motivated intense searches for additional check-point modifiers, such as PD-1 molecule, with encouraging preliminary results. Ipilimumab's entry into the clinic is the opening of a new chapter in the immunotherapy of melanoma in particular, and of cancer, in general.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents, Alkylating)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
RN - 7GR28W0FJI (Dacarbazine)
IS - 0017-7768
IL - 0017-7768
PT - Journal Article
PT - Review
ID - 23316667 [pubmed]
PP - ppublish
LG - Hebrew
DP - 2012 Oct
DC - 20130115
EZ - 2013/01/16 06:00
DA - 2013/02/16 06:00
DT - 2013/01/16 06:00
YR - 2012
ED - 20130215
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=23316667
<276. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22889227
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Nikolajczyk BS
AU - Jagannathan-Bogdan M
AU - Denis GV
FA - Nikolajczyk, Barbara S
FA - Jagannathan-Bogdan, Madhumita
FA - Denis, Gerald V
IN - Nikolajczyk, Barbara S. Department of Microbiology, Boston University, Boston, MA 02118, USA. bnikol@bu.edu
TI - The outliers become a stampede as immunometabolism reaches a tipping point. [Review]
SO - Immunological Reviews. 249(1):253-75, 2012 Sep
AS - Immunol Rev. 249(1):253-75, 2012 Sep
NJ - Immunological reviews
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - gg4, 7702118
IO - Immunol. Rev.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419483
OI - Source: NLM. NIHMS379470
SB - Index Medicus
CP - England
MH - Adipocytes/im [Immunology]
MH - Adipose Tissue/im [Immunology]
MH - Adipose Tissue/me [Metabolism]
MH - Animals
MH - B-Lymphocytes/im [Immunology]
MH - Cell Differentiation
MH - *Diabetes Mellitus, Type 2/im [Immunology]
MH - *Diabetes Mellitus, Type 2/me [Metabolism]
MH - *Energy Metabolism
MH - Humans
MH - Inflammation/im [Immunology]
MH - Insulin Resistance
MH - Leukocytes/im [Immunology]
MH - Mice
MH - Obesity/im [Immunology]
MH - *Obesity/me [Metabolism]
MH - T-Lymphocytes/im [Immunology]
AB - Obesity and Type 2 diabetes mellitus (T2D) are characterized by pro-inflammatory alterations in the immune system including shifts in leukocyte subset differentiation and in cytokine/chemokine balance. The chronic, low-grade inflammation resulting largely from changes in T-cell, B-cell, and myeloid compartments promotes and/or exacerbates insulin resistance (IR) that, together with pancreatic islet failure, defines T2D. Animal model studies show that interruption of immune cell-mediated inflammation by any one of several methods almost invariably results in the prevention or delay of obesity and/or IR. However, anti-inflammatory therapies have had a modest impact on established T2D in clinical trials. These seemingly contradictory results indicate that a more comprehensive understanding of human IR/T2D-associated immune cell function is needed to leverage animal studies into clinical treatments. Important outstanding analyses include identifying potential immunological checkpoints in disease etiology, detailing immune cell/adipose tissue cross-talk, and defining strengths/weaknesses of model organism studies to determine whether we can harness the promising new field of immunometabolism to curb the global obesity and T2D epidemics.
AB - Copyright © 2012 John Wiley & Sons A/S.
ES - 1600-065X
IL - 0105-2896
DO - https://dx.doi.org/10.1111/j.1600-065X.2012.01142.x
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 22889227 [pubmed]
ID - PMC3419483 [pmc]
ID - NIHMS379470 [mid]
ID - 10.1111/j.1600-065X.2012.01142.x [doi]
PP - ppublish
GI - No: DK046200
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: R21 DE021154
Organization: (DE) *NIDCR NIH HHS*
Country: United States
No: U01 CA182898
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 DK089270
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: P30 DK046200
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: R56 DK090455
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: P30 DK057521
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: R21DK089270
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: 5R21DE021154
Organization: (DE) *NIDCR NIH HHS*
Country: United States
No: T32 AI007309
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: AI007309
Organization: (AI) *NIAID NIH HHS*
Country: United States
LG - English
DP - 2012 Sep
DC - 20120814
EZ - 2012/08/15 06:00
DA - 2013/02/05 06:00
DT - 2012/08/15 06:00
YR - 2012
ED - 20130204
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22889227
<277. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23060594
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Forde PM
AU - Rock K
AU - Wilson G
AU - O'Byrne KJ
FA - Forde, Patrick M
FA - Rock, Kathy
FA - Wilson, Graham
FA - O'Byrne, Kenneth J
IN - Forde, Patrick M. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD 21231, USA. pforde1@jhmi.edu
TI - Ipilimumab-induced immune-related renal failure--a case report.
SO - Anticancer Research. 32(10):4607-8, 2012 Oct
AS - Anticancer Res. 32(10):4607-8, 2012 Oct
NJ - Anticancer research
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 59l, 8102988
IO - Anticancer Res.
SB - Index Medicus
CP - Greece
MH - *Acute Kidney Injury/ci [Chemically Induced]
MH - Acute Kidney Injury/dg [Diagnostic Imaging]
MH - Acute Kidney Injury/dt [Drug Therapy]
MH - Acute Kidney Injury/im [Immunology]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Creatinine/bl [Blood]
MH - Glucocorticoids/tu [Therapeutic Use]
MH - Humans
MH - Lymphatic Metastasis
MH - Male
MH - Melanoma/dt [Drug Therapy]
MH - Methylprednisolone/tu [Therapeutic Use]
MH - Middle Aged
MH - Radiography
MH - Skin Neoplasms/dt [Drug Therapy]
MH - Treatment Outcome
AB - Ipilimumab is a fully human monoclonal antibody targeting cytotoxic T-lymphocyte antigen-4 and has become the first immune checkpoint inhibitor to enter clinical practice, being recently approved for the treatment of metastatic melanoma. Immune toxicity due to ipilimumab causing colitis, hepatitis, dermatitis and hypophysitis is well-described. We report on a case of acute renal failure resolving rapidly with high-dose corticosteroid treatment highlighting the importance of vigilance for rarer immune-related toxicities as clinical experience with ipilimumab grows.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Glucocorticoids)
RN - 6T8C155666 (ipilimumab)
RN - AYI8EX34EU (Creatinine)
RN - X4W7ZR7023 (Methylprednisolone)
ES - 1791-7530
IL - 0250-7005
DI - 32/10/4607
PT - Case Reports
PT - Journal Article
ID - 23060594 [pubmed]
ID - 32/10/4607 [pii]
PP - ppublish
LG - English
DP - 2012 Oct
DC - 20121012
EZ - 2012/10/13 06:00
DA - 2013/01/15 06:00
DT - 2012/10/13 06:00
YR - 2012
ED - 20130114
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=23060594
<278. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22787433
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Venkatesha VA
AU - Parsels LA
AU - Parsels JD
AU - Zhao L
AU - Zabludoff SD
AU - Simeone DM
AU - Maybaum J
AU - Lawrence TS
AU - Morgan MA
FA - Venkatesha, Venkatasubbaiah A
FA - Parsels, Leslie A
FA - Parsels, Joshua D
FA - Zhao, Lili
FA - Zabludoff, Sonya D
FA - Simeone, Diane M
FA - Maybaum, Jonathan
FA - Lawrence, Theodore S
FA - Morgan, Meredith A
IN - Venkatesha, Venkatasubbaiah A. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109-5637, USA.
TI - Sensitization of pancreatic cancer stem cells to gemcitabine by Chk1 inhibition.
SO - Neoplasia (New York). 14(6):519-25, 2012 Jun
AS - Neoplasia. 14(6):519-25, 2012 Jun
NJ - Neoplasia (New York, N.Y.)
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - dru, 100886622
IO - Neoplasia
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394194
SB - Index Medicus
CP - United States
MH - Animals
MH - Antimetabolites, Antineoplastic/ad [Administration & Dosage]
MH - *Antimetabolites, Antineoplastic/pd [Pharmacology]
MH - Checkpoint Kinase 1
MH - Deoxycytidine/ad [Administration & Dosage]
MH - *Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Humans
MH - Mice
MH - Mice, Inbred NOD
MH - Mice, SCID
MH - *Neoplastic Stem Cells/de [Drug Effects]
MH - *Neoplastic Stem Cells/me [Metabolism]
MH - Pancreatic Neoplasms/dt [Drug Therapy]
MH - *Pancreatic Neoplasms/me [Metabolism]
MH - Protein Kinase Inhibitors/ad [Administration & Dosage]
MH - *Protein Kinase Inhibitors/pd [Pharmacology]
MH - *Protein Kinases/me [Metabolism]
MH - Tumor Burden/de [Drug Effects]
MH - Xenograft Model Antitumor Assays
AB - Checkpoint kinase 1 (Chk1) inhibition sensitizes pancreatic cancer cells and tumors to gemcitabine. We hypothesized that Chk1 inhibition would sensitize pancreatic cancer stem cells to gemcitabine. We tested this hypothesis by using two patient-derived xenograft models (designated J and F) and the pancreatic cancer stem cell markers CD24, CD44, and ESA. We determined the percentage of marker-positive cells and their tumor-initiating capacity (by limiting dilution assays) after treatment with gemcitabine and the Chk1 inhibitor, AZD7762. We found that marker-positive cells were significantly reduced by the combination of gemcitabine and AZD7762. In addition, secondary tumor initiation was significantly delayed in response to primary tumor treatment with gemcitabine + AZD7762 compared with control, gemcitabine, or AZD7762 alone. Furthermore, for the same number of stem cells implanted from gemcitabine- versus gemcitabine + AZD7762-treated primary tumors, secondary tumor initiation at 10 weeks was 83% versus 43%, respectively. We also found that pS345 Chk1, which is a measure of DNA damage, was induced in marker-positive cells but not in the marker-negative cells. These data demonstrate that Chk1 inhibition in combination with gemcitabine reduces both the percentage and the tumor-initiating capacity of pancreatic cancer stem cells. Furthermore, the finding that the Chk1-mediated DNA damage response was greater in stem cells than in non-stem cells suggests that Chk1 inhibition may selectively sensitize pancreatic cancer stem cells to gemcitabine, thus making Chk1 a potential therapeutic target for improving pancreatic cancer therapy.
RN - 0 (Antimetabolites, Antineoplastic)
RN - 0 (Protein Kinase Inhibitors)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7 (Protein Kinases)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
RN - EC 2-7-11-1 (Chek1 protein, mouse)
ES - 1476-5586
IL - 1476-5586
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 22787433 [pubmed]
ID - PMC3394194 [pmc]
PP - ppublish
PH - 2012/03/19 [received]
PH - 2012/04/30 [revised]
PH - 2012/05/04 [accepted]
GI - No: P30 CA046592
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01CA78554
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA138723
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA130810
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA078554
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2012 Jun
DC - 20120712
EZ - 2012/07/13 06:00
DA - 2012/11/14 06:00
DT - 2012/07/13 06:00
YR - 2012
ED - 20121113
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22787433
<279. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22477725
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Torino F
AU - Barnabei A
AU - De Vecchis L
AU - Salvatori R
AU - Corsello SM
FA - Torino, Francesco
FA - Barnabei, Agnese
FA - De Vecchis, Liana
FA - Salvatori, Roberto
FA - Corsello, Salvatore M
IN - Torino, Francesco. Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy.
TI - Hypophysitis induced by monoclonal antibodies to cytotoxic T lymphocyte antigen 4: challenges from a new cause of a rare disease. [Review]
SO - Oncologist. 17(4):525-35, 2012
AS - Oncologist. 17(4):525-35, 2012
NJ - The oncologist
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dd5, 9607837
IO - Oncologist
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336822
SB - Index Medicus
CP - United States
MH - Adrenal Cortex Hormones/tu [Therapeutic Use]
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Autoimmune Diseases/ci [Chemically Induced]
MH - Autoimmune Diseases/di [Diagnosis]
MH - Autoimmune Diseases/dt [Drug Therapy]
MH - Autoimmune Diseases/im [Immunology]
MH - *CTLA-4 Antigen/im [Immunology]
MH - Clinical Trials, Phase III as Topic
MH - Humans
MH - *Inflammation/ci [Chemically Induced]
MH - *Inflammation/di [Diagnosis]
MH - Inflammation/dt [Drug Therapy]
MH - Inflammation/im [Immunology]
MH - Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - *Pituitary Diseases/ci [Chemically Induced]
MH - *Pituitary Diseases/di [Diagnosis]
MH - Pituitary Diseases/im [Immunology]
MH - Randomized Controlled Trials as Topic
MH - *Rare Diseases/ci [Chemically Induced]
MH - *Rare Diseases/di [Diagnosis]
MH - Rare Diseases/dt [Drug Therapy]
MH - Rare Diseases/im [Immunology]
MH - Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/im [Immunology]
AB - Specific human monoclonal antibodies antagonize cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4 mAbs), a negative regulator of the immune system, inducing unrestrained T-cell activation. In patients with advanced or metastatic melanoma, one of these agents, ipilimumab, produced considerable disease control rates and, for the first time, a clear improvement in overall survival outcomes. However, accumulating clinical experience with anti-CTLA-4 mAbs identified a novel syndrome of autoimmune and autoinflammatory side effects, designated as "immune-related adverse events," including mainly rash, colitis, and hepatitis. Autoimmune hypophysitis has emerged as a distinctive side effect induced by anti-CTLA-4 mAbs. This condition may be life threatening because of adrenal insufficiency if not promptly recognized, but it may easily be diagnosed and treated if clinically suspected. Hypopituitarism caused by these agents is rarely reversible and prolonged or life-long substitutive hormonal treatment is often required. The precise mechanism of injury to the pituitary triggered by anti-CTLA-4 mAbs is yet to be fully elucidated.
RN - 0 (Adrenal Cortex Hormones)
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 6T8C155666 (ipilimumab)
ES - 1549-490X
IL - 1083-7159
DI - theoncologist.2011-0404
DO - https://dx.doi.org/10.1634/theoncologist.2011-0404
PT - Journal Article
PT - Review
ID - 22477725 [pubmed]
ID - theoncologist.2011-0404 [pii]
ID - 10.1634/theoncologist.2011-0404 [doi]
ID - PMC3336822 [pmc]
PP - ppublish
LG - English
EP - 20120403
DP - 2012
DC - 20120425
EZ - 2012/04/06 06:00
DA - 2012/10/24 06:00
DT - 2012/04/06 06:00
YR - 2012
ED - 20121023
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22477725
<280. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 23049279
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Andrews S
AU - Holden R
FA - Andrews, Stephanie
FA - Holden, Rita
IN - Andrews, Stephanie. H Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
TI - Characteristics and management of immunerelated adverse effects associated with ipilimumab, a new immunotherapy for metastatic melanoma.
SO - Cancer management and research. 4:299-307, 2012
AS - Cancer Manag Res. 4:299-307, 2012
NJ - Cancer management and research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101512700
IO - Cancer Manag Res
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459593
CP - New Zealand
KW - case studies; immunotherapy; ipilimumab; melanoma
AB - When diagnosed in its early stages, melanoma is highly treatable and associated with good long-term outcomes; however, the prognosis is much poorer for patients diagnosed with advanced or metastatic melanoma. For decades, available treatments were effective in only a few patients and associated with significant safety concerns. Ipilimumab is a novel immunotherapy which has proved to be an exciting breakthrough in the treatment of melanoma. It is the first drug approved for the treatment of melanoma by the Food and Drug Administration (FDA) which has shown a survival benefit in a randomized Phase III clinical trial. The objective of this review is to provide information on the administration, treatment responses, and expected outcomes of treatment of metastatic melanoma with the new immunotherapeutic agent, ipilimumab, a drug with a unique mechanism of action that differentiates it from current treatments. Guidelines for the management of immune-related adverse events associated with ipilimumab therapy are also presented. These stress vigilance, prompt intervention, and the use of corticosteroids as appropriate. Various ipilimumab-associated immune-related adverse events, both common (enterocolitis, dermatitis) and less frequent (hepatitis, hypophysitis), are illustrated in case studies. Nurses are uniquely positioned to provide patient and caregiver education on how this new therapy differs from traditional cytotoxic agents, to recognize the signs and symptoms of immune-related adverse events, and to report them immediately, and finally, to be aware of the patterns of response that are commonly observed in patients receiving ipilimumab therapy.
ES - 1179-1322
IL - 1179-1322
DI - cmar-4-299
DO - https://dx.doi.org/10.2147/CMAR.S31873
PT - Journal Article
ID - 23049279 [pubmed]
ID - 10.2147/CMAR.S31873 [doi]
ID - cmar-4-299 [pii]
ID - PMC3459593 [pmc]
PP - ppublish
LG - English
EP - 20120912
DP - 2012
DC - 20121010
EZ - 2012/10/11 06:00
DA - 2012/10/11 06:01
DT - 2012/10/11 06:00
YR - 2012
ED - 20121011
RD - 20130530
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=23049279
<281. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22698916
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Henry RA
AU - Kendall PL
AU - Thomas JW
FA - Henry, Rachel A
FA - Kendall, Peggy L
FA - Thomas, James W
IN - Henry, Rachel A. Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt University, Nashville, Tennessee, USA.
TI - Autoantigen-specific B-cell depletion overcomes failed immune tolerance in type 1 diabetes.
SO - Diabetes. 61(8):2037-44, 2012 Aug
AS - Diabetes. 61(8):2037-44, 2012 Aug
NJ - Diabetes
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - e8x, 0372763
IO - Diabetes
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402296
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Animals
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antigens, CD86/bi [Biosynthesis]
MH - *Autoantigens/im [Immunology]
MH - *B-Lymphocytes/im [Immunology]
MH - *Diabetes Mellitus, Type 1/im [Immunology]
MH - Humans
MH - *Immune Tolerance/im [Immunology]
MH - Insulin/im [Immunology]
MH - Mice
MH - Mice, Inbred NOD
MH - Mice, Transgenic
MH - *Receptors, Antigen, B-Cell/im [Immunology]
AB - Eliminating autoantigen-specific B cells is an attractive alternative to global B-cell depletion for autoimmune disease treatment. To identify the potential for targeting a key autoimmune B-cell specificity in type 1 diabetes, insulin-binding B cells were tracked within a polyclonal repertoire using heavy chain B-cell receptor (BCR) transgenic (VH125Tg) mice. Insulin-specific B cells are rare in the periphery of nonautoimmune VH125Tg/C57BL/6 mice and WT/NOD autoimmune mice, whereas they clearly populate 1% of mature B-cell subsets in VH125Tg/NOD mice. Autoantigen upregulates CD86 in anti-insulin B cells, suggesting they are competent to interact with T cells. Endogenous insulin occupies anti-insulin BCR beginning with antigen commitment in bone marrow parenchyma, as identified by a second anti-insulin monoclonal antibody. Administration of this monoclonal antibody selectively eliminates insulin-reactive B cells in vivo and prevents disease in WT/NOD mice. Unexpectedly, developing B cells are less amenable to depletion, despite increased BCR sensitivity. These findings exemplify how a critical type 1 diabetes B-cell specificity escapes immune tolerance checkpoints. Disease liability is corrected by eliminating this B-cell specificity, providing proof of concept for a novel therapeutic approach for autoimmune disease.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD86)
RN - 0 (Autoantigens)
RN - 0 (Cd86 protein, mouse)
RN - 0 (Insulin)
RN - 0 (Receptors, Antigen, B-Cell)
ES - 1939-327X
IL - 0012-1797
DI - db11-1746
DO - https://dx.doi.org/10.2337/db11-1746
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 22698916 [pubmed]
ID - db11-1746 [pii]
ID - 10.2337/db11-1746 [doi]
ID - PMC3402296 [pmc]
PP - ppublish
GI - No: R01 DK084246
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: 5T32-AR-059039
Organization: (AR) *NIAMS NIH HHS*
Country: United States
No: R01-DK-08246
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: P30 CA68485
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 DK058404
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: R01 AI051448
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: T32 AR059039
Organization: (AR) *NIAMS NIH HHS*
Country: United States
No: T32 HL069765
Organization: (HL) *NHLBI NIH HHS*
Country: United States
No: P30 CA068485
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01-AI-051448
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: DK058404
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: 5T32-HL-069765
Organization: (HL) *NHLBI NIH HHS*
Country: United States
LG - English
EP - 20120614
DP - 2012 Aug
DC - 20120724
EZ - 2012/06/16 06:00
DA - 2012/10/09 06:00
DT - 2012/06/16 06:00
YR - 2012
ED - 20121008
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22698916
<282. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22614989
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Weber JS
AU - Kahler KC
AU - Hauschild A
FA - Weber, Jeffrey S
FA - Kahler, Katharina C
FA - Hauschild, Axel
IN - Weber, Jeffrey S. H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. jeffrey.weber@moffitt.org
TI - Management of immune-related adverse events and kinetics of response with ipilimumab. [Review]
SO - Journal of Clinical Oncology. 30(21):2691-7, 2012 Jul 20
AS - J Clin Oncol. 30(21):2691-7, 2012 Jul 20
NJ - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - jco, 8309333
IO - J. Clin. Oncol.
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/im [Immunology]
MH - Antibodies, Monoclonal/pk [Pharmacokinetics]
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/im [Immunology]
MH - *CTLA-4 Antigen/de [Drug Effects]
MH - *CTLA-4 Antigen/im [Immunology]
MH - Chemical and Drug Induced Liver Injury/im [Immunology]
MH - Colitis/im [Immunology]
MH - Diarrhea/im [Immunology]
MH - Drug Eruptions/im [Immunology]
MH - Humans
MH - Liver/de [Drug Effects]
MH - Liver/im [Immunology]
MH - Lymphatic Diseases/ci [Chemically Induced]
MH - Lymphatic Diseases/im [Immunology]
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - Melanoma/me [Metabolism]
MH - Melanoma/sc [Secondary]
MH - Mucous Membrane/de [Drug Effects]
MH - Mucous Membrane/im [Immunology]
MH - Pancreatitis/ci [Chemically Induced]
MH - Pancreatitis/im [Immunology]
MH - Peripheral Nervous System Diseases/ci [Chemically Induced]
MH - Peripheral Nervous System Diseases/im [Immunology]
MH - Pituitary Gland/de [Drug Effects]
MH - Pituitary Gland/im [Immunology]
MH - Scleritis/ci [Chemically Induced]
MH - Scleritis/im [Immunology]
MH - Skin/de [Drug Effects]
MH - Skin/im [Immunology]
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/im [Immunology]
MH - Skin Neoplasms/me [Metabolism]
MH - Skin Neoplasms/pa [Pathology]
MH - Stevens-Johnson Syndrome/im [Immunology]
MH - Uveitis/ci [Chemically Induced]
MH - Uveitis/im [Immunology]
AB - Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152)-ipilimumab and tremelimumab-have been investigated in metastatic melanoma and other cancers and have shown promising results. Recently, ipilimumab was approved by the US Food and Drug Administration for the treatment of metastatic melanoma. We review the literature on managing the adverse effects and kinetics of tumor regression with ipilimumab and provide guidelines on their management. During treatment with these antibodies, a unique set of adverse effects may occur, called immune-related adverse events (irAEs). These include rashes, which may rarely progress to life-threatening toxic epidermal necrolysis, and colitis, characterized by a mild to moderate, but occasionally also severe and persistent diarrhea. Hypophysitis, hepatitis, pancreatitis, iridocyclitis, lymphadenopathy, neuropathies, and nephritis have also been reported with ipilimumab. Early recognition of irAEs and initiation of treatment are critical to reduce the risk of sequelae. Interestingly, irAEs correlated with treatment response in some studies. Unique kinetics of response have been observed with CTLA-4 blockade with at least four patterns: (1) response in baseline lesions by week 12, with no new lesions seen; (2) stable disease, followed by a slow, steady decline in total tumor burden; (3) regression of tumor after initial increase in total tumor burden; and (4) reduction in total tumor burden during or after the appearance of new lesion(s) after week 12. We provide a detailed description of irAEs and recommendations for practicing oncologists who are managing them, along with the unusual kinetics of response associated with ipilimumab therapy.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
RN - QEN1X95CIX (tremelimumab)
ES - 1527-7755
IL - 0732-183X
DI - JCO.2012.41.6750
DO - https://dx.doi.org/10.1200/JCO.2012.41.6750
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 22614989 [pubmed]
ID - JCO.2012.41.6750 [pii]
ID - 10.1200/JCO.2012.41.6750 [doi]
PP - ppublish
LG - English
EP - 20120521
DP - 2012 Jul 20
DC - 20120720
EZ - 2012/05/23 06:00
DA - 2012/09/25 06:00
DT - 2012/05/23 06:00
YR - 2012
ED - 20120924
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22614989
<283. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22495490
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Juszczak A
AU - Gupta A
AU - Karavitaki N
AU - Middleton MR
AU - Grossman AB
FA - Juszczak, Agata
FA - Gupta, Avinash
FA - Karavitaki, Niki
FA - Middleton, Mark R
FA - Grossman, Ashley B
IN - Juszczak, Agata. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LE, UK.
TI - Ipilimumab: a novel immunomodulating therapy causing autoimmune hypophysitis: a case report and review. [Review]
SO - European Journal of Endocrinology. 167(1):1-5, 2012 Jul
AS - EUR. J. ENDOCRINOL.. 167(1):1-5, 2012 Jul
NJ - European journal of endocrinology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - bxu, 9423848
IO - Eur. J. Endocrinol.
SB - Index Medicus
CP - England
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Autoimmune Diseases/ci [Chemically Induced]
MH - Autoimmune Diseases/im [Immunology]
MH - *CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Humans
MH - *Hypopituitarism/ci [Chemically Induced]
MH - Hypopituitarism/im [Immunology]
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - Middle Aged
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/im [Immunology]
MH - T-Lymphocytes, Cytotoxic/im [Immunology]
AB - Ipilimumab (Yervoy; Medarex and Bristol-Myers Squibb) is a human MAB against cytotoxic T-lymphocyte antigen 4, which enhances co-stimulation of cytotoxic T-lymphocytes, resulting in their proliferation and an anti-tumour response. It is licensed for the treatment of unresectable or metastatic malignant melanoma, while multiple clinical trials using this medication in the treatment of other malignancies are ongoing. As a clinical response to ipilimumab results from immunostimulation, predictably it generates autoimmunity as well, causing immune-related adverse events in the majority of patients. Of those, endocrinopathies are frequently seen, and in particular, autoimmune lymphocytic hypophysitis with anterior panhypopituitarism has been reported a number of times in North America. We present a case of a male referred to our department with manifestations of anterior panhypopituitarism after his third dose of ipilimumab for metastatic malignant melanoma, and we discuss the management of his case in the light of previous reports. We also review the published literature on the presenting symptoms, time to presentation, investigations, imaging, treatment and follow-up of ipilimumab-induced autoimmune lymphocytic hypophysitis.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
ES - 1479-683X
IL - 0804-4643
DI - EJE-12-0167
DO - https://dx.doi.org/10.1530/EJE-12-0167
PT - Case Reports
PT - Journal Article
PT - Review
ID - 22495490 [pubmed]
ID - EJE-12-0167 [pii]
ID - 10.1530/EJE-12-0167 [doi]
PP - ppublish
LG - English
EP - 20120410
DP - 2012 Jul
DC - 20120625
EZ - 2012/04/13 06:00
DA - 2012/09/15 06:00
DT - 2012/04/13 06:00
YR - 2012
ED - 20120914
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22495490
<284. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22138079
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Min L
AU - Vaidya A
AU - Becker C
FA - Min, Le
FA - Vaidya, Anand
FA - Becker, Carolyn
IN - Min, Le. Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
TI - Association of ipilimumab therapy for advanced melanoma with secondary adrenal insufficiency: a case series.
SO - Endocrine Practice. 18(3):351-5, 2012 May-Jun
AS - Endocr Pract. 18(3):351-5, 2012 May-Jun
NJ - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 9607439, dy1
IO - Endocr Pract
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997164
OI - Source: NLM. NIHMS498257
SB - Index Medicus
CP - United States
MH - *Adrenal Insufficiency/ci [Chemically Induced]
MH - Adrenal Insufficiency/pp [Physiopathology]
MH - Adult
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - Drug Monitoring
MH - Female
MH - Humans
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/sc [Secondary]
MH - Middle Aged
MH - Severity of Illness Index
AB - OBJECTIVE: To present a case series of ipilimumab-related secondary adrenal insufficiency.
AB - METHODS: In this cases series, we review the presentation, evaluation, diagnosis, and management of patients with advanced melanoma who received ipilimumab and were referred to our endocrinology clinic for evaluation of hormonal abnormalities.
AB - RESULTS: Seven patients presented with symptoms, signs, or biochemical evidence of adrenal insufficiency 6 to 12 weeks after starting ipilimumab therapy. Ipilimumab is a cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody that is approved for the treatment of metastatic melanoma and has widespread use for this disease. All 7 patients had biochemical evidence of profound secondary adrenal insufficiency. Thyroid function abnormalities, central hypogonadism, and low insulinlike growth factor 1 levels were seen in a subset of patients. Only 2 patients had abnormal findings on pituitary magnetic resonance imaging. Posterior pituitary function remained normal.
AB - CONCLUSIONS: Our findings suggest that the enhanced immune response associated with ipilimumab therapy may have a predilection for corticotroph and possibly thyrotroph cells. We recommend periodic hypothalamic-pituitary-adrenal axis monitoring for patients on this therapy.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
ES - 1934-2403
IL - 1530-891X
DI - 48L3427473P81522
DO - https://dx.doi.org/10.4158/EP11273.OR
PT - Case Reports
PT - Journal Article
ID - 22138079 [pubmed]
ID - 48L3427473P81522 [pii]
ID - 10.4158/EP11273.OR [doi]
ID - PMC3997164 [pmc]
ID - NIHMS498257 [mid]
PP - ppublish
GI - No: F32 HL104776
Organization: (HL) *NHLBI NIH HHS*
Country: United States
No: F32 HL104776-02
Organization: (HL) *NHLBI NIH HHS*
Country: United States
No: K08 HD070957
Organization: (HD) *NICHD NIH HHS*
Country: United States
No: T32 DK007529
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG - English
DP - 2012 May-Jun
DC - 20120517
EZ - 2011/12/06 06:00
DA - 2012/09/15 06:00
DT - 2011/12/06 06:00
YR - 2012
ED - 20120914
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22138079
<285. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22735122
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Thomsen HH
FA - Thomsen, Henrik Holm
IN - Thomsen, Henrik Holm. Medicinsk Endokrinologisk Afdeling, Aarhus Universitetshospital, Norrebrogade 44, 8000 Aarhus C, Denmark. hehoth@gmail.com
TI - [Lymphocytic hypophysitis due to ipilimumap therapy]. [Danish]
OT - Lymfocytaer hypofysitis pa baggrund af behandling med ipilimumab.
SO - Ugeskrift for Laeger. 174(26):1829-30, 2012 Jun 25
AS - Ugeskr Laeger. 174(26):1829-30, 2012 Jun 25
NJ - Ugeskrift for laeger
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 0141730, wm8
IO - Ugeskr. Laeg.
SB - Index Medicus
CP - Denmark
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/pk [Pharmacokinetics]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/pk [Pharmacokinetics]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Fatal Outcome
MH - Humans
MH - Immune System Diseases/ci [Chemically Induced]
MH - Immunologic Factors/ae [Adverse Effects]
MH - Immunologic Factors/pk [Pharmacokinetics]
MH - Immunologic Factors/tu [Therapeutic Use]
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/pa [Pathology]
MH - *Neoplasm Metastasis/dt [Drug Therapy]
MH - Neoplasm Recurrence, Local/dt [Drug Therapy]
MH - *Pituitary Diseases/ci [Chemically Induced]
AB - Ipilimumab is a newer drug that has shown considerable improvement of survival rates in malignant melanoma. It works by stimulating the immune system. Frequently harmless side effects can be seen, but serious reactions also occur. We report a case of hypophysitis and a case with severe diarrhoea on tapering off from glucocorticoid therapy for hypophysitis. Attentiveness of these adverse reactions is important, since they can be rapidly fatal if they are left untreated. The relevant specialties are required to ensure diagnosis, treatment and follow-up at an early stage.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (Immunologic Factors)
RN - 6T8C155666 (ipilimumab)
ES - 1603-6824
IL - 0041-5782
DI - VP10110481
PT - Case Reports
PT - Journal Article
ID - 22735122 [pubmed]
ID - VP10110481 [pii]
PP - ppublish
LG - Danish
DP - 2012 Jun 25
DC - 20120627
EZ - 2012/06/28 06:00
DA - 2012/09/08 06:00
DT - 2012/06/28 06:00
YR - 2012
ED - 20120907
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22735122
<286. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22134241
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Vance S
AU - Liu E
AU - Zhao L
AU - Parsels JD
AU - Parsels LA
AU - Brown JL
AU - Maybaum J
AU - Lawrence TS
AU - Morgan MA
FA - Vance, Sean
FA - Liu, Erqi
FA - Zhao, Lili
FA - Parsels, Joshua D
FA - Parsels, Leslie A
FA - Brown, Jeffery L
FA - Maybaum, Jonathan
FA - Lawrence, Theodore S
FA - Morgan, Meredith A
IN - Vance, Sean. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA.
TI - Selective radiosensitization of p53 mutant pancreatic cancer cells by combined inhibition of Chk1 and PARP1.
SO - Cell Cycle. 10(24):4321-9, 2011 Dec 15
AS - Cell Cycle. 10(24):4321-9, 2011 Dec 15
NJ - Cell cycle (Georgetown, Tex.)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101137841
IO - Cell Cycle
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272262
SB - Index Medicus
CP - United States
MH - Analysis of Variance
MH - Cell Cycle Checkpoints/de [Drug Effects]
MH - Checkpoint Kinase 1
MH - DNA Repair/de [Drug Effects]
MH - *DNA Repair/ph [Physiology]
MH - Drug Combinations
MH - Flow Cytometry
MH - Histones/me [Metabolism]
MH - Humans
MH - Immunoblotting
MH - Intestinal Mucosa/cy [Cytology]
MH - Intestinal Mucosa/me [Metabolism]
MH - Mutation/ge [Genetics]
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/rt [Radiotherapy]
MH - Phthalazines/pd [Pharmacology]
MH - Piperazines/pd [Pharmacology]
MH - Poly (ADP-Ribose) Polymerase-1
MH - *Poly(ADP-ribose) Polymerase Inhibitors
MH - *Protein Kinases/me [Metabolism]
MH - *Radiation Tolerance/de [Drug Effects]
MH - *Radiation-Sensitizing Agents/pd [Pharmacology]
MH - Thiophenes/pd [Pharmacology]
MH - *Tumor Suppressor Protein p53/ge [Genetics]
MH - Urea/aa [Analogs & Derivatives]
MH - Urea/pd [Pharmacology]
AB - We have recently shown that inhibition of HRR (homologous recombination repair) by Chk1 (checkpoint kinase 1) inhibition radiosensitizes pancreatic cancer cells and others have demonstrated that Chk1 inhibition selectively sensitizes p53 mutant tumor cells. Furthermore, PARP1 [poly (ADP-ribose) polymerase-1] inhibitors dramatically radiosensitize cells with DNA double strand break repair defects. Thus, we hypothesized that inhibition of HRR (mediated by Chk1 via AZD7762) and PARP1 [via olaparib (AZD2281)] would selectively sensitize p53 mutant pancreatic cancer cells to radiation. We also used 2 isogenic p53 cell models to assess the role of p53 status in cancer cells and intestinal epithelial cells to assess overall cancer specificity. DNA damage response and repair were assessed by flow cytometry, gammaH2AX, and an HRR reporter assay. We found that the combination of AZD7762 and olaparib produced significant radiosensitization in p53 mutant pancreatic cancer cells and in all of the isogenic cancer cell lines. The magnitude of radiosensitization by AZD7762 and olaparib was greater in p53 mutant cells compared with p53 wild type cells. Importantly, normal intestinal epithelial cells were not radiosensitized. The combination of AZD7762 and olaparib caused G 2 checkpoint abrogation, inhibition of HRR, and persistent DNA damage responses. These findings demonstrate that the combination of Chk1 and PARP1 inhibition selectively radiosensitizes p53 mutant pancreatic cancer cells. Furthermore, these studies suggest that inhibition of HRR by Chk1 inhibitors may be a useful strategy for selectively inducing a BRCA1/2 'deficient-like' phenotype in p53 mutant tumor cells, while sparing normal tissue.
RN - 0 (3-(carbamoylamino)-5-(3-fluorophenyl)-N-(3-piperidyl)thiophene-2-carboxamide)
RN - 0 (Drug Combinations)
RN - 0 (H2AFX protein, human)
RN - 0 (Histones)
RN - 0 (Phthalazines)
RN - 0 (Piperazines)
RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN - 0 (Radiation-Sensitizing Agents)
RN - 0 (Thiophenes)
RN - 0 (Tumor Suppressor Protein p53)
RN - 8W8T17847W (Urea)
RN - EC 2-4-2-30 (PARP1 protein, human)
RN - EC 2-4-2-30 (Poly (ADP-Ribose) Polymerase-1)
RN - EC 2-7 (Protein Kinases)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
RN - WOH1JD9AR8 (olaparib)
ES - 1551-4005
IL - 1551-4005
DI - 18661
DO - https://dx.doi.org/10.4161/cc.10.24.18661
PT - Journal Article
PT - Research Support, N.I.H., Extramural
ID - 22134241 [pubmed]
ID - 18661 [pii]
ID - 10.4161/cc.10.24.18661 [doi]
ID - PMC3272262 [pmc]
PP - ppublish
GI - No: R01CA78554 10S1
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA046592
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01CA78554
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01CA138723
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA138723
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA130810
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50CA130810
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA078554
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20111215
DP - 2011 Dec 15
DC - 20120117
EZ - 2011/12/03 06:00
DA - 2012/08/30 06:00
DT - 2011/12/03 06:00
YR - 2011
ED - 20120829
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22134241
<287. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22271879
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Prieto PA
AU - Yang JC
AU - Sherry RM
AU - Hughes MS
AU - Kammula US
AU - White DE
AU - Levy CL
AU - Rosenberg SA
AU - Phan GQ
FA - Prieto, Peter A
FA - Yang, James C
FA - Sherry, Richard M
FA - Hughes, Marybeth S
FA - Kammula, Udai S
FA - White, Donald E
FA - Levy, Catherine L
FA - Rosenberg, Steven A
FA - Phan, Giao Q
IN - Prieto, Peter A. Surgery Branch, National Cancer Institute, NIH, Bldg 10-CRC, Room 3-5760, 10 Center Drive, Bethesda, MD 20892, USA.
TI - CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma.
CM - Comment in: Clin Cancer Res. 2012 Apr 1;18(7):1821-3; PMID: 22338019
SO - Clinical Cancer Research. 18(7):2039-47, 2012 Apr 01
AS - Clin Cancer Res. 18(7):2039-47, 2012 Apr 01
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c2h, 9502500
IO - Clin. Cancer Res.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319861
OI - Source: NLM. NIHMS352309
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
MH - *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - *CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH - CTLA-4 Antigen/im [Immunology]
MH - Cancer Vaccines/ad [Administration & Dosage]
MH - Cancer Vaccines/ae [Adverse Effects]
MH - Clinical Trials as Topic
MH - Dermatitis/et [Etiology]
MH - Female
MH - Follow-Up Studies
MH - Humans
MH - Interleukin-2/ad [Administration & Dosage]
MH - Interleukin-2/ae [Adverse Effects]
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - Neoplasm Metastasis
MH - Pituitary Diseases/ci [Chemically Induced]
MH - Survival Analysis
MH - Treatment Outcome
MH - Young Adult
AB - PURPOSE: Treatment with ipilimumab can cause objective tumor responses in patients with metastatic melanoma. We have treated 177 evaluable patients in three clinical trials and have long-term follow-up to evaluate the durability of responses.
AB - EXPERIMENTAL DESIGN: Patients with metastatic melanoma were treated in three trials from 2002 to 2005. In protocol 1, 56 patients received ipilimumab with gp100 peptides. In protocol 2, 36 patients received ipilimumab with interleukin-2. In protocol 3, 85 patients received ipilimumab with intrapatient dose-escalation and were randomized to receive gp100 peptides. We have analyzed their long-term follow-up and survival data.
AB - RESULTS: With median follow-up for protocols 1, 2, and 3 being 92, 84, and 71 months, median survival was 14, 16, and 13 months with 5-year survival rates being 13%, 25%, and 23%, respectively. Patients in protocol 2 had a 17% complete response (CR) rate, compared with 7% in protocol 1 and 6% in protocol 3. These CR rates are higher than previously reported for the same trials because some patients who eventually became complete responders had continual tumor regression months to years after therapy. All but one of the 15 complete responders are ongoing at 54+ to 99+ months.
AB - CONCLUSIONS: This report provides the longest follow-up of patients with melanoma treated with ipilimumab and shows that ipilimumab can induce durable, potentially curative tumor regression in a small percentage of patients with metastatic melanoma. The combination of ipilimumab and interleukin-2 seems to have an increased CR rate, but this needs to be tested in a randomized trial.
AB - Copyright ©2012 AACR.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (CTLA-4 Antigen)
RN - 0 (Cancer Vaccines)
RN - 0 (Interleukin-2)
RN - 0 (gp100(209-2M) vaccine)
RN - 6T8C155666 (ipilimumab)
IS - 1078-0432
IL - 1078-0432
DI - 1078-0432.CCR-11-1823
DO - https://dx.doi.org/10.1158/1078-0432.CCR-11-1823
PT - Journal Article
PT - Research Support, N.I.H., Extramural
ID - 22271879 [pubmed]
ID - 1078-0432.CCR-11-1823 [pii]
ID - 10.1158/1078-0432.CCR-11-1823 [doi]
ID - PMC3319861 [pmc]
ID - NIHMS352309 [mid]
PP - ppublish
GI - No: Z99 CA999999
Organization: *Intramural NIH HHS*
Country: United States
LG - English
EP - 20120123
DP - 2012 Apr 01
DC - 20120404
EZ - 2012/01/25 06:00
DA - 2012/08/24 06:00
DT - 2012/01/25 06:00
YR - 2012
ED - 20120823
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22271879
<288. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 21264545
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Barnard ZR
AU - Walcott BP
AU - Kahle KT
AU - Nahed BV
AU - Coumans JV
FA - Barnard, Zachary R
FA - Walcott, Brian P
FA - Kahle, Kristopher T
FA - Nahed, Brian V
FA - Coumans, Jean Valery
IN - Barnard, Zachary R. Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, White Building Room 502, Boston, MA 02114, USA.
TI - Hyponatremia associated with Ipilimumab-induced hypophysitis.
SO - Medical Oncology. 29(1):374-7, 2012 Mar
AS - Med Oncol. 29(1):374-7, 2012 Mar
NJ - Medical oncology (Northwood, London, England)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - b3a, 9435512
IO - Med. Oncol.
SB - Index Medicus
CP - United States
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Female
MH - Humans
MH - *Hyponatremia/et [Etiology]
MH - Hyponatremia/pp [Physiopathology]
MH - Inappropriate ADH Syndrome/et [Etiology]
MH - Inappropriate ADH Syndrome/pp [Physiopathology]
MH - Melanoma/dt [Drug Therapy]
MH - *Pituitary Diseases/ci [Chemically Induced]
MH - *Pituitary Diseases/co [Complications]
MH - Pituitary Diseases/pp [Physiopathology]
AB - A 75-year-old woman with a history of stage IV metastatic melanoma underwent treatment with the CTLA-4 blocking agent Ipilimumab. She presented 2 months after initiating treatment with a severe headache. Laboratories were consistent with severe hyponatremia. MRI of the brain revealed enlargement of the pituitary gland, enhancement of the infundibulum, and an enhancing, centrally necrotic foci in the anterior pituitary. Based on the clinical and radiographic findings, she was diagnosed with treatment-related syndrome of inappropriate antidiuretic hormone secretion (SIADH). Effective treatment consisted of fluid restriction, hyperosmolar therapy, and steroids.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
ES - 1559-131X
IL - 1357-0560
DO - https://dx.doi.org/10.1007/s12032-010-9794-7
PT - Case Reports
PT - Journal Article
ID - 21264545 [pubmed]
ID - 10.1007/s12032-010-9794-7 [doi]
PP - ppublish
PH - 2010/10/02 [received]
PH - 2010/12/20 [accepted]
LG - English
EP - 20110125
DP - 2012 Mar
DC - 20120209
EZ - 2011/01/26 06:00
DA - 2012/08/24 06:00
DT - 2011/01/26 06:00
YR - 2012
ED - 20120823
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=21264545
<289. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22423263
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Tomasini P
AU - Khobta N
AU - Greillier L
AU - Barlesi F
FA - Tomasini, Pascale
FA - Khobta, Nataliya
FA - Greillier, Laurent
FA - Barlesi, Fabrice
IN - Tomasini, Pascale. Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University - Assistance Publique Hopitaux de Marseille; Aix Marseille University - Inserm U911, Marseille, France.
TI - Ipilimumab: its potential in non-small cell lung cancer.
SO - Therapeutic Advances in Medical Oncology. 4(2):43-50, 2012 Mar
AS - Ther Adv Med Oncol. 4(2):43-50, 2012 Mar
NJ - Therapeutic advances in medical oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101510808
IO - Ther Adv Med Oncol
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296082
CP - England
KW - biomarkers; immunotherapy; ipilimumab; lung cancer; targeted therapy
AB - Ipilimumab is a fully human monoclonal antibody that enhances antitumor immunity by way of cytotoxic T-lymphocyte antigen 4 blockade. It has already been approved by the US Food and Drug Administration for the treatment of metastatic melanoma and is being investigated for treating other solid tumors such as renal cell, prostate and lung cancers. This review details the potential of ipilimumab in the management of non-small cell lung cancer (NSCLC). In particular, ipilimumab showed promising results in a first-line NSCLC phase II study combining carboplatin/paclitaxel chemotherapy with concurrent or phased ipilimumab. The median immune-related progression-free survival was 5.68 months for the phased ipilimumab arm versus 4.63 months for chemotherapy alone (hazard ratio [HR] = 0.68, p = 0.026) and 5.52 months for the concurrent ipilimumab arm versus 4.63 months for chemotherapy alone (HR = 0.77, p = 0.094). The main adverse events were immune related, such as hypophysitis, enterocolitis, and hyperthyroidism. These adverse events may be improved with high-dose glucocorticoids and may be correlated with tumor response. Phase III studies are ongoing. Future studies may investigate ipilimumab in the management of early stage lung cancer. Strategies for potential translational research studies are also discussed to identify prognostic and predictive biomarkers for the use of ipilimumab in the treatment of patients with NSCLC.
ES - 1758-8359
IL - 1758-8340
DI - 10.1177_1758834011431718
DO - https://dx.doi.org/10.1177/1758834011431718
PT - Journal Article
ID - 22423263 [pubmed]
ID - 10.1177/1758834011431718 [doi]
ID - 10.1177_1758834011431718 [pii]
ID - PMC3296082 [pmc]
PP - ppublish
LG - English
DP - 2012 Mar
DC - 20120316
EZ - 2012/03/17 06:00
DA - 2012/03/17 06:01
DT - 2012/03/17 06:00
YR - 2012
ED - 20120823
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=22423263
<290. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22822590
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Anonymous
TI - Ipilimumab. Immunostimulant; more assessment needed.
CM - Comment in: Prescrire Int. 2012 Jun;21(128):144; PMID: 22822589
SO - Prescrire International. 21(128):145-7, 2012 Jun
AS - Prescrire Int. 21(128):145-7, 2012 Jun
NJ - Prescrire international
PI - Journal available in: Print
PI - Citation processed from: Print
JC - c9k, 9439295
IO - Prescrire Int
SB - Health Technology Assessment Journals
CP - France
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - CTLA-4 Antigen/ph [Physiology]
MH - Clinical Trials as Topic
MH - Humans
MH - *Lymphocyte Activation/de [Drug Effects]
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - Melanoma/mo [Mortality]
MH - gp100 Melanoma Antigen/an [Analysis]
AB - In patients with inoperable or metastatic melanoma, first-line cytotoxic drugs have no proven impact on survival, which is generally limited to only a few months. There is no standard second-line treatment. Ipilimumab, a monoclonal antibody, stimulates T lymphocyte proliferation and activation. It has been authorised in the European Union for melanoma patients in whom one or more lines of chemotherapy have failed. Clinical evaluation is based on a double-blind randomised trial in 676 patients comparing ipilimumab + gp 100, ipilimumab + placebo, and 100 gp + placebo. Gp 100 is an experimental mixture of proteins being tested in melanoma. The median overall survival time was significantly longer among patients treated with ipilimumab, with or without gp 100 (about 10 months), than among those receiving gp 100 + placebo (about 6 months). In another trial, involving previously untreated melanoma patients, adding ipilimumab (at a dose 3 times higher than in the previous trial) to dacarbazine prolonged median overall survival by 2 months. The main adverse effects of ipilimumab are immune-related adverse reactions, and include gastrointestinal, cutaneous and endocrine disorders (enterocolitis with or without perforation, dermatitis, hypopituitarism and hepatitis). In practice, in patients with metastatic melanoma in whom one or more treatments have failed, the use of ipilimumab should be restricted to well-designed clinical trials designed to better assess the survival benefit, serious adverse effects, and the optimal dosage.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (gp100 Melanoma Antigen)
RN - 6T8C155666 (ipilimumab)
IS - 1167-7422
IL - 1167-7422
PT - Journal Article
ID - 22822590 [pubmed]
PP - ppublish
LG - English
DP - 2012 Jun
DC - 20120724
EZ - 2012/07/25 06:00
DA - 2012/08/08 06:00
DT - 2012/07/25 06:00
YR - 2012
ED - 20120807
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22822590
<291. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22406592
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Strimpakos AS
AU - Syrigos KN
AU - Saif MW
FA - Strimpakos, Alexios S
FA - Syrigos, Kostas N
FA - Saif, Muhammad Wasif
IN - Strimpakos, Alexios S. Oncology Unit, Third Department of Medicine, University of Athens, Sotiria General Hospital, Athens, Greece.
TI - Novel agents in early phase clinical studies on refractory pancreatic cancer. [Review]
SO - Jop: Journal of the Pancreas [Electronic Resource]. 13(2):166-8, 2012 Mar 10
AS - JOP. 13(2):166-8, 2012 Mar 10
NJ - JOP : Journal of the pancreas
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101091810
IO - JOP
SB - Index Medicus
CP - Italy
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antimetabolites, Antineoplastic/tu [Therapeutic Use]
MH - Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/tu [Therapeutic Use]
MH - Erlotinib Hydrochloride
MH - Humans
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/mo [Mortality]
MH - Protein Kinase Inhibitors/tu [Therapeutic Use]
MH - *Quinazolines/tu [Therapeutic Use]
MH - Radiation-Sensitizing Agents/tu [Therapeutic Use]
AB - The standard current treatment options in advanced pancreatic cancer have demonstrated minimal or modest only efficacy for the majority of patients. Unfortunately, the mortality and morbidity remain high crying out for better treatments and results. With the exception of erlotinib, which received approval by the Food and Drug Administration of the United States in 2005, no other novel agents have since been added in our treatment quiver. Therefore, the search for novel approaches continuous at the laboratory and clinical level. At the 2012 American Society of Clinical Oncology Gastrointestinal Symposium, results of some interesting early phases clinical studies were presented. First, in Abstract #198, toxicity and efficacy results from the phase I/II study of cixutumumab, an insulin growth factor-1 receptor (IGF-1R) antibody combined with the standard gemcitabine and erlotinib treatment were presented, but the outcomes suggest no real clinical benefit. Second, the early safety and clinical data from the novel monoclonal antibody (ensituximab) against the mucin epitope NPC-1C in pancreatic and colon cancer patients were presented (Abstract #233) and again no particular efficacy was observed. Finally, interesting results which definitely deserve further exploration were presented in Abstract #211, which tested the combination of ipilimumab, an antibody against the cytotoxic T-lymphocyte antigen 4 (CTLA-4), with a cell-based vaccine transfected with the granulocyte macrophage colony-stimulating factor (GM-CSF) gene in advanced refractory pancreatic cancer. Though, it seems we have not yet found the culprit and the solution of this devastating disease, a small step forward might have been achieved.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antimetabolites, Antineoplastic)
RN - 0 (Protein Kinase Inhibitors)
RN - 0 (Quinazolines)
RN - 0 (Radiation-Sensitizing Agents)
RN - 0 (anti-IGF-1R antibody A12)
RN - 0W860991D6 (Deoxycytidine)
RN - 6T8C155666 (ipilimumab)
RN - B76N6SBZ8R (gemcitabine)
RN - DA87705X9K (Erlotinib Hydrochloride)
ES - 1590-8577
IL - 1590-8577
PT - Journal Article
PT - Review
ID - 22406592 [pubmed]
PP - epublish
LG - English
EP - 20120310
DP - 2012 Mar 10
DC - 20120312
EZ - 2012/03/13 06:00
DA - 2012/07/14 06:00
DT - 2012/03/13 06:00
YR - 2012
ED - 20120713
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22406592
<292. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22658128
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Brahmer JR
AU - Tykodi SS
AU - Chow LQ
AU - Hwu WJ
AU - Topalian SL
AU - Hwu P
AU - Drake CG
AU - Camacho LH
AU - Kauh J
AU - Odunsi K
AU - Pitot HC
AU - Hamid O
AU - Bhatia S
AU - Martins R
AU - Eaton K
AU - Chen S
AU - Salay TM
AU - Alaparthy S
AU - Grosso JF
AU - Korman AJ
AU - Parker SM
AU - Agrawal S
AU - Goldberg SM
AU - Pardoll DM
AU - Gupta A
AU - Wigginton JM
FA - Brahmer, Julie R
FA - Tykodi, Scott S
FA - Chow, Laura Q M
FA - Hwu, Wen-Jen
FA - Topalian, Suzanne L
FA - Hwu, Patrick
FA - Drake, Charles G
FA - Camacho, Luis H
FA - Kauh, John
FA - Odunsi, Kunle
FA - Pitot, Henry C
FA - Hamid, Omid
FA - Bhatia, Shailender
FA - Martins, Renato
FA - Eaton, Keith
FA - Chen, Shuming
FA - Salay, Theresa M
FA - Alaparthy, Suresh
FA - Grosso, Joseph F
FA - Korman, Alan J
FA - Parker, Susan M
FA - Agrawal, Shruti
FA - Goldberg, Stacie M
FA - Pardoll, Drew M
FA - Gupta, Ashok
FA - Wigginton, Jon M
IN - Brahmer, Julie R. Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA.
TI - Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
CM - Comment in: Nat Rev Clin Oncol. 2012 Aug;9(8):427; PMID: 22710340
CM - Comment in: N Engl J Med. 2012 Jun 28;366(26):2517-9; PMID: 22658126
CM - Comment in: Cancer Cell. 2012 Jul 10;22(1):7-8; PMID: 22789534
CM - Comment in: J Urol. 2012 Dec;188(6):2148-9; PMID: 23141220
SO - New England Journal of Medicine. 366(26):2455-65, 2012 Jun 28
AS - N Engl J Med. 366(26):2455-65, 2012 Jun 28
NJ - The New England journal of medicine
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 0255562, now
IO - N. Engl. J. Med.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563263
OI - Source: NLM. NIHMS396200
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Adult
MH - *Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ad [Administration & Dosage]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Breast Neoplasms/dt [Drug Therapy]
MH - Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Carcinoma, Renal Cell/dt [Drug Therapy]
MH - Colorectal Neoplasms/dt [Drug Therapy]
MH - Dose-Response Relationship, Drug
MH - Female
MH - Humans
MH - Male
MH - Melanoma/dt [Drug Therapy]
MH - *Neoplasms/dt [Drug Therapy]
MH - Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/dt [Drug Therapy]
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - Programmed Cell Death 1 Receptor/me [Metabolism]
MH - Stomach Neoplasms/dt [Drug Therapy]
AB - BACKGROUND: Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models.
AB - METHODS: In this multicenter phase 1 trial, we administered intravenous anti-PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression.
AB - RESULTS: As of February 24, 2012, a total of 207 patients--75 with non-small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer--had received anti-PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non-small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up.
AB - CONCLUSIONS: Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.).
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 31YO63LBSN (nivolumab)
ES - 1533-4406
IL - 0028-4793
DO - https://dx.doi.org/10.1056/NEJMoa1200694
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Multicenter Study
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 22658128 [pubmed]
ID - 10.1056/NEJMoa1200694 [doi]
ID - PMC3563263 [pmc]
ID - NIHMS396200 [mid]
PP - ppublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00729664
SL - https://clinicaltrials.gov/search/term=NCT00729664
GI - No: P30 CA015704
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA006973
Organization: (CA) *NCI NIH HHS*
Country: United States
No: 5R01 CA142779
Organization: (CA) *NCI NIH HHS*
Country: United States
No: UL1 TR000454
Organization: (TR) *NCATS NIH HHS*
Country: United States
No: UL1 RR024148
Organization: (RR) *NCRR NIH HHS*
Country: United States
No: R01 CA142779
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20120602
DP - 2012 Jun 28
DC - 20120628
EZ - 2012/06/05 06:00
DA - 2012/07/12 06:00
DT - 2012/06/05 06:00
YR - 2012
ED - 20120711
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=22658128
<293. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22658128
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Brahmer JR
AU - Tykodi SS
AU - Chow LQ
AU - Hwu WJ
AU - Topalian SL
AU - Hwu P
AU - Drake CG
AU - Camacho LH
AU - Kauh J
AU - Odunsi K
AU - Pitot HC
AU - Hamid O
AU - Bhatia S
AU - Martins R
AU - Eaton K
AU - Chen S
AU - Salay TM
AU - Alaparthy S
AU - Grosso JF
AU - Korman AJ
AU - Parker SM
AU - Agrawal S
AU - Goldberg SM
AU - Pardoll DM
AU - Gupta A
AU - Wigginton JM
FA - Brahmer, Julie R
FA - Tykodi, Scott S
FA - Chow, Laura Q M
FA - Hwu, Wen-Jen
FA - Topalian, Suzanne L
FA - Hwu, Patrick
FA - Drake, Charles G
FA - Camacho, Luis H
FA - Kauh, John
FA - Odunsi, Kunle
FA - Pitot, Henry C
FA - Hamid, Omid
FA - Bhatia, Shailender
FA - Martins, Renato
FA - Eaton, Keith
FA - Chen, Shuming
FA - Salay, Theresa M
FA - Alaparthy, Suresh
FA - Grosso, Joseph F
FA - Korman, Alan J
FA - Parker, Susan M
FA - Agrawal, Shruti
FA - Goldberg, Stacie M
FA - Pardoll, Drew M
FA - Gupta, Ashok
FA - Wigginton, Jon M
IN - Brahmer, Julie R. Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA.
TI - Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
CM - Comment in: Nat Rev Clin Oncol. 2012 Aug;9(8):427; PMID: 22710340
CM - Comment in: N Engl J Med. 2012 Jun 28;366(26):2517-9; PMID: 22658126
CM - Comment in: Cancer Cell. 2012 Jul 10;22(1):7-8; PMID: 22789534
CM - Comment in: J Urol. 2012 Dec;188(6):2148-9; PMID: 23141220
SO - New England Journal of Medicine. 366(26):2455-65, 2012 Jun 28
AS - N Engl J Med. 366(26):2455-65, 2012 Jun 28
NJ - The New England journal of medicine
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 0255562, now
IO - N. Engl. J. Med.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563263
OI - Source: NLM. NIHMS396200
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Adult
MH - *Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/ad [Administration & Dosage]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Breast Neoplasms/dt [Drug Therapy]
MH - Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Carcinoma, Renal Cell/dt [Drug Therapy]
MH - Colorectal Neoplasms/dt [Drug Therapy]
MH - Dose-Response Relationship, Drug
MH - Female
MH - Humans
MH - Male
MH - Melanoma/dt [Drug Therapy]
MH - *Neoplasms/dt [Drug Therapy]
MH - Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/dt [Drug Therapy]
MH - *Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors]
MH - Programmed Cell Death 1 Receptor/im [Immunology]
MH - Programmed Cell Death 1 Receptor/me [Metabolism]
MH - Stomach Neoplasms/dt [Drug Therapy]
AB - BACKGROUND: Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models.
AB - METHODS: In this multicenter phase 1 trial, we administered intravenous anti-PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression.
AB - RESULTS: As of February 24, 2012, a total of 207 patients--75 with non-small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer--had received anti-PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non-small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up.
AB - CONCLUSIONS: Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.).
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
RN - 31YO63LBSN (nivolumab)
ES - 1533-4406
IL - 0028-4793
DO - https://dx.doi.org/10.1056/NEJMoa1200694
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Multicenter Study
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 22658128 [pubmed]
ID - 10.1056/NEJMoa1200694 [doi]
ID - PMC3563263 [pmc]
ID - NIHMS396200 [mid]
PP - ppublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00729664
SA - ClinicalTrials.gov/NCT00729664
SL - https://clinicaltrials.gov/search/term=NCT00729664
SL - https://clinicaltrials.gov/search/term=NCT00729664
GI - No: P30 CA015704
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA006973
Organization: (CA) *NCI NIH HHS*
Country: United States
No: 5R01 CA142779
Organization: (CA) *NCI NIH HHS*
Country: United States
No: UL1 TR000454
Organization: (TR) *NCATS NIH HHS*
Country: United States
No: UL1 RR024148
Organization: (RR) *NCRR NIH HHS*
Country: United States
No: R01 CA142779
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20120602
DP - 2012 Jun 28
DC - 20120628
EZ - 2012/06/05 06:00
DA - 2012/07/12 06:00
DT - 2012/06/05 06:00
YR - 2012
ED - 20120711
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22658128
<294. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22326924
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Madan RA
AU - Mohebtash M
AU - Arlen PM
AU - Vergati M
AU - Rauckhorst M
AU - Steinberg SM
AU - Tsang KY
AU - Poole DJ
AU - Parnes HL
AU - Wright JJ
AU - Dahut WL
AU - Schlom J
AU - Gulley JL
FA - Madan, Ravi A
FA - Mohebtash, Mahsa
FA - Arlen, Philip M
FA - Vergati, Matteo
FA - Rauckhorst, Myrna
FA - Steinberg, Seth M
FA - Tsang, Kwong Y
FA - Poole, Diane J
FA - Parnes, Howard L
FA - Wright, John J
FA - Dahut, William L
FA - Schlom, Jeffrey
FA - Gulley, James L
IN - Madan, Ravi A. Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
TI - Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial.
CM - Comment in: Lancet Oncol. 2012 May;13(5):440-2; PMID: 22326921
SO - Lancet Oncology. 13(5):501-8, 2012 May
AS - Lancet Oncol. 13(5):501-8, 2012 May
NJ - The Lancet. Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 100957246
IO - Lancet Oncol.
SB - Index Medicus
CP - England
MH - Aged
MH - Aged, 80 and over
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antigens, CD/im [Immunology]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Cancer Vaccines/im [Immunology]
MH - *Cancer Vaccines/tu [Therapeutic Use]
MH - Dose-Response Relationship, Drug
MH - Humans
MH - Immunotherapy, Active
MH - Male
MH - Middle Aged
MH - Orchiectomy
MH - Poxviridae/im [Immunology]
MH - *Poxviridae
MH - *Prostate-Specific Antigen/im [Immunology]
MH - Prostatic Neoplasms/im [Immunology]
MH - Prostatic Neoplasms/sc [Secondary]
MH - *Prostatic Neoplasms/th [Therapy]
MH - Viral Vaccines/im [Immunology]
MH - *Viral Vaccines/tu [Therapeutic Use]
AB - BACKGROUND: Therapeutic cancer vaccines have shown activity in metastatic castration-resistant prostate cancer (mCRPC), and methods are being assessed to enhance their efficacy. Ipilimumab is an antagonistic monoclonal antibody that binds cytotoxic T-lymphocyte-associated protein 4, an immunomodulatory molecule expressed by activated T cells, and to CD80 on antigen-presenting cells. We aimed to assess the safety and tolerability of ipilimumab in combination with a poxviral-based vaccine targeting prostate-specific antigen (PSA) and containing transgenes for T-cell co-stimulatory molecule expression, including CD80.
AB - METHODS: We did a phase 1 dose-escalation trial, with a subsequent expansion phase, to assess the safety and tolerability of escalating doses of ipilimumab in combination with a fixed dose of the PSA-Tricom vaccine. Patients with mCRPC received 2x10(8) plaque-forming units of recombinant vaccinia PSA-Tricom subcutaneously on day 1 of cycle 1, with subsequent monthly boosts of 1x10(9) plaque-forming units, starting on day 15. Intravenous ipilimumab was given monthly starting at day 15, in doses of 1, 3, 5, and 10 mg/kg. Our primary goal was to assess the safety of the combination. This study is registered with ClinicalTrials.gov, number NCT00113984.
AB - FINDINGS: We completed enrolment with 30 patients (24 of whom had not been previously treated with chemotherapy) and we did not identify any dose-limiting toxic effects. Grade 1 and 2 vaccination-site reactions were the most common toxic effects: three of 30 patients had grade 1 reactions and 26 had grade 2 reactions. 21 patients had grade 2 or greater immune-related adverse events. Grade 3 or 4 immune-related adverse events included diarrhoea or colitis in four patients and grade 3 rash (two patients), grade 3 raised aminotransferases (two patients), grade 3 endocrine immune-related adverse events (two patients), and grade 4 neutropenia (one patient). Only one of the six patients previously treated with chemotherapy had a PSA decline from baseline. Of the 24 patients who were chemotherapy-naive, 14 (58%) had PSA declines from baseline, of which six were greater than 50%.
AB - INTERPRETATION: The use of a vaccine targeting PSA that also enhances co-stimulation of the immune system did not seem to exacerbate the immune-related adverse events associated with ipilimumab. Randomised trials are needed to further assess clinical outcomes of the combination of ipilimumab and vaccine in mCRPC.
AB - FUNDING: US National Institutes of Health.
AB - Copyright © 2012 Elsevier Ltd. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (Antineoplastic Agents)
RN - 0 (Cancer Vaccines)
RN - 0 (Viral Vaccines)
RN - 6T8C155666 (ipilimumab)
RN - EC 3-4-21-77 (Prostate-Specific Antigen)
ES - 1474-5488
IL - 1470-2045
DI - S1470-2045(12)70006-2
DO - https://dx.doi.org/10.1016/S1470-2045(12)70006-2
PT - Clinical Trial, Phase I
PT - Journal Article
PT - Research Support, N.I.H., Intramural
ID - 22326924 [pubmed]
ID - S1470-2045(12)70006-2 [pii]
ID - 10.1016/S1470-2045(12)70006-2 [doi]
PP - ppublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00113984
SL - https://clinicaltrials.gov/search/term=NCT00113984
GI - Organization: *Intramural NIH HHS*
Country: United States
LG - English
EP - 20120210
DP - 2012 May
DC - 20120504
EZ - 2012/02/14 06:00
DA - 2012/06/27 06:00
DT - 2012/02/14 06:00
YR - 2012
ED - 20120626
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22326924
<295. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22326922
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - van den Eertwegh AJ
AU - Versluis J
AU - van den Berg HP
AU - Santegoets SJ
AU - van Moorselaar RJ
AU - van der Sluis TM
AU - Gall HE
AU - Harding TC
AU - Jooss K
AU - Lowy I
AU - Pinedo HM
AU - Scheper RJ
AU - Stam AG
AU - von Blomberg BM
AU - de Gruijl TD
AU - Hege K
AU - Sacks N
AU - Gerritsen WR
FA - van den Eertwegh, Alfons J M
FA - Versluis, Jurjen
FA - van den Berg, H Pieter
FA - Santegoets, Saskia J A M
FA - van Moorselaar, R Jeroen A
FA - van der Sluis, Tim M
FA - Gall, Helen E
FA - Harding, Thomas C
FA - Jooss, Karin
FA - Lowy, Israel
FA - Pinedo, Herbert M
FA - Scheper, Rik J
FA - Stam, Anita G M
FA - von Blomberg, B Mary E
FA - de Gruijl, Tanja D
FA - Hege, Kristen
FA - Sacks, Natalie
FA - Gerritsen, Winald R
IN - van den Eertwegh, Alfons J M. Department of Medical Oncology, VU University Medical Centre, Amsterdam, Netherlands.
TI - Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial.
CM - Comment in: Immunotherapy. 2012 Jun;4(6):577-80; PMID: 22788125
CM - Comment in: Lancet Oncol. 2012 May;13(5):440-2; PMID: 22326921
SO - Lancet Oncology. 13(5):509-17, 2012 May
AS - Lancet Oncol. 13(5):509-17, 2012 May
NJ - The Lancet. Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 100957246
IO - Lancet Oncol.
SB - Index Medicus
CP - England
MH - Adult
MH - Aged
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Cancer Vaccines/tu [Therapeutic Use]
MH - Combined Modality Therapy
MH - Granulocyte-Macrophage Colony-Stimulating Factor/im [Immunology]
MH - *Granulocyte-Macrophage Colony-Stimulating Factor/tu [Therapeutic Use]
MH - Humans
MH - Immunotherapy
MH - Male
MH - Middle Aged
MH - Orchiectomy
MH - Prostatic Neoplasms/im [Immunology]
MH - Prostatic Neoplasms/sc [Secondary]
MH - *Prostatic Neoplasms/th [Therapy]
MH - Transplantation, Homologous
MH - Tumor Cells, Cultured
AB - BACKGROUND: The granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells vaccine (GVAX) has antitumour activity against prostate cancer; preclinical studies have shown potent synergy when combined with ipilimumab, an antibody that blocks cytotoxic T-lymphocyte antigen 4. We aimed to assess the safety of combined treatment with GVAX and ipilimumab in patients with metastatic castration-resistant prostate cancer (mCRPC).
AB - METHODS: We did an open-labelled, single-centre, dose-escalation study of ipilimumab concurrent with a fixed dose of GVAX, with a subsequent expansion phase, both at the VU University Medical Centre (Amsterdam, Netherlands). Eligible patients had documented mCRPC and had not been previously treated with chemotherapy. All patients received a 5x10(8) cell priming dose of GVAX intradermally on day 1 with subsequent intradermal injections of 3x10(8) cells every 2 weeks for 24 weeks. The vaccinations were combined with intravenous ipilimumab every 4 weeks. We enrolled patients in cohorts of three; each cohort received an escalating dose of ipilimumab at 0.3, 1.0, 3.0, or 5.0 mg/kg. Our primary endpoint was safety. This study is registered with ClinicalTrials.gov, number NCT01510288.
AB - FINDINGS: We enrolled 12 patients into our dose-escalation cohort. We did not record any severe immune-related adverse events at the first two dose levels. At the 3.0 mg/kg dose level, one patient had grade 2 and two patients grade 3 hypophysitis; at the 5.0 mg/kg dose level, two patients had grade 3 hypophysitis and one patient developed grade 4 sarcoid alveolitis (a dose-limiting toxic effect). Due to observed clinical activity and toxic events, we decided to expand the 3.0 mg/kg dose level, rather than enrol a further three patients at the 5.0 mg/kg level. 16 patients were enrolled in the expansion cohort, two of whom developed grade 2 hypophysitis, three colitis (one grade 1 and two grade 2), and one grade 3 hepatitis--all immune-related adverse events. The most common adverse events noted in all 28 patients were injection-site reactions (grade 1-2 events seen in all patients), fatigue (grade 1-2 in 20 patients, grade 3 in two), and pyrexia (grade 1-2 in 15 patients, grade 3 in one). 50% or greater declines in prostate-specific antigen from baseline was recorded in seven patients (25%); all had received 3.0 mg/kg or 5.0 mg/kg ipilimumab.
AB - INTERPRETATION: GVAX combined with 3.0 mg/kg ipilimumab is tolerable and safe for patients with mCRPC. Further research on the combined treatment of patients with mCRPC with vaccination and ipilimumab is warranted.
AB - FUNDING: Cell Genesys Inc, Prostate Cancer Foundation, Dutch Cancer Society (KWF-VU 2006-3697), and Foundation Stichting VUmc Cancer Center Amsterdam.
AB - Copyright © 2012 Elsevier Ltd. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 0 (Cancer Vaccines)
RN - 6T8C155666 (ipilimumab)
RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
ES - 1474-5488
IL - 1470-2045
DI - S1470-2045(12)70007-4
DO - https://dx.doi.org/10.1016/S1470-2045(12)70007-4
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 22326922 [pubmed]
ID - S1470-2045(12)70007-4 [pii]
ID - 10.1016/S1470-2045(12)70007-4 [doi]
PP - ppublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT01510288
SL - https://clinicaltrials.gov/search/term=NCT01510288
LG - English
EP - 20120210
DP - 2012 May
DC - 20120504
EZ - 2012/02/14 06:00
DA - 2012/06/27 06:00
DT - 2012/02/14 06:00
YR - 2012
ED - 20120626
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22326922
<296. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22272332
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wei N
AU - Liu SS
AU - Chan KK
AU - Ngan HY
FA - Wei, Na
FA - Liu, Stephanie S
FA - Chan, Karen K L
FA - Ngan, Hextan Y S
IN - Wei, Na. Department of Obstetrics & Gynaecology, Queen Mary Hospital, the University of Hong Kong, Hong Kong, Hong Kong.
TI - Tumour suppressive function and modulation of programmed cell death 4 (PDCD4) in ovarian cancer.
SO - PLoS ONE [Electronic Resource]. 7(1):e30311, 2012
AS - PLoS ONE. 7(1):e30311, 2012
NJ - PloS one
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101285081
IO - PLoS ONE
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260274
SB - Index Medicus
CP - United States
MH - Apoptosis Regulatory Proteins/ge [Genetics]
MH - Apoptosis Regulatory Proteins/me [Metabolism]
MH - *Apoptosis Regulatory Proteins/ph [Physiology]
MH - Blotting, Western
MH - *Cell Cycle/ph [Physiology]
MH - Cell Line, Tumor
MH - Cell Movement/ph [Physiology]
MH - *Cell Proliferation
MH - Culture Media, Serum-Free/pd [Pharmacology]
MH - Cyclin-Dependent Kinase Inhibitor p21/me [Metabolism]
MH - Cyclin-Dependent Kinase Inhibitor p27/me [Metabolism]
MH - Down-Regulation/de [Drug Effects]
MH - Extracellular Signal-Regulated MAP Kinases/me [Metabolism]
MH - Female
MH - Humans
MH - Neoplasm Invasiveness
MH - Ovarian Neoplasms/ge [Genetics]
MH - Ovarian Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/pa [Pathology]
MH - PTEN Phosphohydrolase/me [Metabolism]
MH - Phosphatidylinositol 3-Kinases/me [Metabolism]
MH - Protein Transport/de [Drug Effects]
MH - Proto-Oncogene Proteins c-akt/me [Metabolism]
MH - RNA-Binding Proteins/ge [Genetics]
MH - RNA-Binding Proteins/me [Metabolism]
MH - *RNA-Binding Proteins/ph [Physiology]
MH - Transfection
MH - Tumor Suppressor Proteins/ge [Genetics]
MH - Tumor Suppressor Proteins/me [Metabolism]
MH - *Tumor Suppressor Proteins/ph [Physiology]
AB - BACKGROUND: Programmed cell death 4 (PDCD4), originally identified as the neoplastic transformation inhibitor, was attenuated in various cancer types. Our previous study demonstrated a continuous down-regulation of PDCD4 expression in the sequence of normal-borderline-malignant ovarian tissue samples and a significant correlation of PDCD4 expression with disease-free survival. The objective of the current study was to further investigate the function and modulation of PDCD4 in ovarian cancer cells.
AB - PRINCIPAL FINDINGS: We demonstrated that ectopic PDCD4 expression significantly inhibited cell proliferation by inducing cell cycle arrest at G(1) stage and up-regulation of cell cycle inhibitors of p27 and p21. Cell migration and invasion were also inhibited by PDCD4. PDCD4 over-expressing cells exhibited elevated phosphatase and tensin homolog (PTEN) and inhibited protein kinase B (p-Akt). In addition, the expression of PDCD4 was up-regulated and it was exported to the cytoplasm upon serum withdrawal treatment, but it was rapidly depleted via proteasomal degradation upon serum re-administration. Treatment of a phosphoinositide 3-kinase (PI3K) inhibitor prevented the degradation of PDCD4, indicating the involvement of PI3K-Akt pathway in the modulation of PDCD4.
AB - CONCLUSION: PDCD4 may play a critical function in arresting cell cycle progression at key checkpoint, thus inhibiting cell proliferation, as well as suppressing tumour metastasis. The PI3K-Akt pathway was implied to be involved in the regulation of PDCD4 degradation in ovarian cancer cells. In response to the stress condition, endogenous PDCD4 was able to shuttle between cell compartments to perform its diverted functions.
RN - 0 (Apoptosis Regulatory Proteins)
RN - 0 (Culture Media, Serum-Free)
RN - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN - 0 (PDCD4 protein, human)
RN - 0 (RNA-Binding Proteins)
RN - 0 (Tumor Suppressor Proteins)
RN - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN - EC 2-7-1 (Phosphatidylinositol 3-Kinases)
RN - EC 2-7-11-1 (Proto-Oncogene Proteins c-akt)
RN - EC 2-7-11-24 (Extracellular Signal-Regulated MAP Kinases)
RN - EC 3-1-3-67 (PTEN Phosphohydrolase)
ES - 1932-6203
IL - 1932-6203
DI - PONE-D-11-08426
DO - https://dx.doi.org/10.1371/journal.pone.0030311
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 22272332 [pubmed]
ID - 10.1371/journal.pone.0030311 [doi]
ID - PONE-D-11-08426 [pii]
ID - PMC3260274 [pmc]
PP - ppublish
PH - 2011/05/12 [received]
PH - 2011/12/13 [accepted]
LG - English
EP - 20120117
DP - 2012
DC - 20120124
EZ - 2012/01/25 06:00
DA - 2012/06/12 06:00
DT - 2012/01/25 06:00
YR - 2012
ED - 20120611
RD - 20150128
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22272332
<297. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22340593
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Katayama H
AU - Wang J
AU - Treekitkarnmongkol W
AU - Kawai H
AU - Sasai K
AU - Zhang H
AU - Wang H
AU - Adams HP
AU - Jiang S
AU - Chakraborty SN
AU - Suzuki F
AU - Arlinghaus RB
AU - Liu J
AU - Mobley JA
AU - Grizzle WE
AU - Wang H
AU - Sen S
FA - Katayama, Hiroshi
FA - Wang, Jin
FA - Treekitkarnmongkol, Warapen
FA - Kawai, Hidehiko
FA - Sasai, Kaori
FA - Zhang, Hui
FA - Wang, Hua
FA - Adams, Henry P
FA - Jiang, Shoulei
FA - Chakraborty, Sandip N
FA - Suzuki, Fumio
FA - Arlinghaus, Ralph B
FA - Liu, Jinsong
FA - Mobley, James A
FA - Grizzle, William E
FA - Wang, Huamin
FA - Sen, Subrata
IN - Katayama, Hiroshi. Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USA.
TI - Aurora kinase-A inactivates DNA damage-induced apoptosis and spindle assembly checkpoint response functions of p73.
SO - Cancer Cell. 21(2):196-211, 2012 Feb 14
AS - Cancer Cell. 21(2):196-211, 2012 Feb 14
NJ - Cancer cell
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101130617
IO - Cancer Cell
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760020
OI - Source: NLM. NIHMS354870
SB - Index Medicus
CP - United States
MH - *Apoptosis
MH - Aurora Kinase A
MH - Aurora Kinases
MH - *DNA Damage
MH - DNA-Binding Proteins/me [Metabolism]
MH - *DNA-Binding Proteins/ph [Physiology]
MH - HSP70 Heat-Shock Proteins/me [Metabolism]
MH - Humans
MH - *M Phase Cell Cycle Checkpoints
MH - Nuclear Proteins/me [Metabolism]
MH - *Nuclear Proteins/ph [Physiology]
MH - Pancreatic Neoplasms/me [Metabolism]
MH - Phosphorylation
MH - Protein-Serine-Threonine Kinases/ge [Genetics]
MH - Protein-Serine-Threonine Kinases/me [Metabolism]
MH - *Protein-Serine-Threonine Kinases/ph [Physiology]
MH - Tumor Cells, Cultured
MH - Tumor Protein p73
MH - Tumor Suppressor Proteins/me [Metabolism]
MH - *Tumor Suppressor Proteins/ph [Physiology]
AB - Elevated Aurora kinase-A expression is correlated with abrogation of DNA damage-induced apoptotic response and mitotic spindle assembly checkpoint (SAC) override in human tumor cells. We report that Aurora-A phosphorylation of p73 at serine235 abrogates its transactivation function and causes cytoplasmic sequestration in a complex with the chaperon protein mortalin. Aurora-A phosphorylated p73 also facilitates inactivation of SAC through dissociation of the MAD2-CDC20 complex in cells undergoing mitosis. Cells expressing phosphor-mimetic mutant (S235D) of p73 manifest altered growth properties, resistance to cisplatin- induced apoptosis, as well as premature dissociation of the MAD2-CDC20 complex, and accelerated mitotic exit with SAC override in the presence of spindle damage. Elevated cytoplasmic p73 in Aurora-A overexpressing primary human tumors corroborates the experimental findings.
AB - Copyright A© 2012 Elsevier Inc. All rights reserved.
RN - 0 (DNA-Binding Proteins)
RN - 0 (HSP70 Heat-Shock Proteins)
RN - 0 (Nuclear Proteins)
RN - 0 (Tumor Protein p73)
RN - 0 (Tumor Suppressor Proteins)
RN - 0 (mortalin)
RN - 0 (p73 protein, human)
RN - EC 2-7-11-1 (AURKA protein, human)
RN - EC 2-7-11-1 (Aurora Kinase A)
RN - EC 2-7-11-1 (Aurora Kinases)
RN - EC 2-7-11-1 (Protein-Serine-Threonine Kinases)
ES - 1878-3686
IL - 1535-6108
DI - S1535-6108(12)00004-9
DO - https://dx.doi.org/10.1016/j.ccr.2011.12.025
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 22340593 [pubmed]
ID - S1535-6108(12)00004-9 [pii]
ID - 10.1016/j.ccr.2011.12.025 [doi]
ID - PMC3760020 [pmc]
ID - NIHMS354870 [mid]
PP - ppublish
PH - 2010/03/11 [received]
PH - 2011/09/21 [revised]
PH - 2011/12/23 [accepted]
GI - No: 5P30CA0101955
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA016672
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P20 CA101955
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA089716-06
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA101955
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01CA089716
Organization: (CA) *NCI NIH HHS*
Country: United States
No: U01 CA111302
Organization: (CA) *NCI NIH HHS*
Country: United States
No: U01CA111302
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA089716
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA16872
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA089716-08
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA089716-07
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2012 Feb 14
DC - 20120220
EZ - 2012/02/21 06:00
DA - 2012/05/05 06:00
DT - 2012/02/22 06:00
YR - 2012
ED - 20120504
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22340593
<298. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 21878655
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Ewton DZ
AU - Hu J
AU - Vilenchik M
AU - Deng X
AU - Luk KC
AU - Polonskaia A
AU - Hoffman AF
AU - Zipf K
AU - Boylan JF
AU - Friedman EA
FA - Ewton, Daina Z
FA - Hu, Jing
FA - Vilenchik, Maria
FA - Deng, Xiaobing
FA - Luk, Kin-Chun
FA - Polonskaia, Ann
FA - Hoffman, Ann F
FA - Zipf, Karen
FA - Boylan, John F
FA - Friedman, Eileen A
IN - Ewton, Daina Z. SUNY Upstate Medical University, Department of Pathology, Syracuse, New York 13210, USA.
TI - Inactivation of mirk/dyrk1b kinase targets quiescent pancreatic cancer cells.
SO - Molecular Cancer Therapeutics. 10(11):2104-14, 2011 Nov
AS - Mol Cancer Ther. 10(11):2104-14, 2011 Nov
NJ - Molecular cancer therapeutics
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101132535
IO - Mol. Cancer Ther.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213302
OI - Source: NLM. NIHMS321716
SB - Index Medicus
CP - United States
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - Apoptosis
MH - Cell Aging
MH - Cell Cycle/de [Drug Effects]
MH - Cell Line, Tumor
MH - Cisplatin/pd [Pharmacology]
MH - DNA Damage/de [Drug Effects]
MH - Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Drug Synergism
MH - Exons
MH - Humans
MH - *Pancreatic Neoplasms/en [Enzymology]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - *Protein Kinase Inhibitors/pd [Pharmacology]
MH - *Protein-Serine-Threonine Kinases/ai [Antagonists & Inhibitors]
MH - Protein-Serine-Threonine Kinases/ge [Genetics]
MH - Protein-Serine-Threonine Kinases/me [Metabolism]
MH - *Protein-Tyrosine Kinases/ai [Antagonists & Inhibitors]
MH - Protein-Tyrosine Kinases/ge [Genetics]
MH - Protein-Tyrosine Kinases/me [Metabolism]
MH - *Resting Phase, Cell Cycle/de [Drug Effects]
AB - A major problem in the treatment of cancer arises from quiescent cancer cells that are relatively insensitive to most chemotherapeutic drugs and radiation. Such residual cancer cells can cause tumor regrowth or recurrence when they reenter the cell cycle. Earlier studies showed that levels of the serine/theronine kinase Mirk/dyrk1B are elevated up to 10-fold in quiescent G(0) tumor cells. Mirk uses several mechanisms to block cell cycling, and Mirk increases expression of antioxidant genes that decrease reactive oxygen species (ROS) levels and increase quiescent cell viability. We now show that a novel small molecule Mirk kinase inhibitor blocked tumor cells from undergoing reversible arrest in a quiescent G(0) state and enabled some cells to exit quiescence. The inhibitor increased cycling in Panc1, AsPc1, and SW620 cells that expressed Mirk, but not in HCT116 cells that did not. Mirk kinase inhibition elevated ROS levels and DNA damage detected by increased phosphorylation of the histone protein H2AX and by S-phase checkpoints. The Mirk kinase inhibitor increased cleavage of the apoptotic proteins PARP and caspase 3, and increased tumor cell kill several-fold by gemcitabine and cisplatin. A phenocopy of these effects occurred following Mirk depletion, showing drug specificity. In previous studies Mirk knockout or depletion had no detectable effect on normal tissue, suggesting that the Mirk kinase inhibitor could have a selective effect on cancer cells expressing elevated levels of Mirk kinase.
RN - 0 (Antineoplastic Agents)
RN - 0 (Protein Kinase Inhibitors)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7-1 (Dyrk kinase)
RN - EC 2-7-10-1 (Protein-Tyrosine Kinases)
RN - EC 2-7-11-1 (Protein-Serine-Threonine Kinases)
RN - Q20Q21Q62J (Cisplatin)
ES - 1538-8514
IL - 1535-7163
DI - 1535-7163.MCT-11-0498
DO - https://dx.doi.org/10.1158/1535-7163.MCT-11-0498
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 21878655 [pubmed]
ID - 1535-7163.MCT-11-0498 [pii]
ID - 10.1158/1535-7163.MCT-11-0498 [doi]
ID - PMC3213302 [pmc]
ID - NIHMS321716 [mid]
PP - ppublish
GI - No: R01 CA067405
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA135164
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R21 CA135164-02
Organization: (CA) *NCI NIH HHS*
Country: United States
No: 5R21CA135164
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20110830
DP - 2011 Nov
DC - 20111110
EZ - 2011/09/01 06:00
DA - 2012/03/16 06:00
DT - 2011/09/01 06:00
YR - 2011
ED - 20120315
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=21878655
<299. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22335028
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Huo X
AU - Ren L
AU - Shang L
AU - Wang X
AU - Wang J
FA - Huo, X
FA - Ren, L
FA - Shang, L
FA - Wang, X
FA - Wang, J
IN - Huo, X. Department of Obstetrics and Gynecology, Beijing General Hospital of Beijing Military Command, Beijing China.
TI - Effect of WT1 antisense mRNA on the induction of apoptosis in ovarian carcinoma SKOV3 cells.
SO - European Journal of Gynaecological Oncology. 32(6):651-6, 2011
AS - Eur J Gynaecol Oncol. 32(6):651-6, 2011
NJ - European journal of gynaecological oncology
PI - Journal available in: Print
PI - Citation processed from: Print
JC - ena, 8100357
IO - Eur. J. Gynaecol. Oncol.
SB - Index Medicus
CP - Italy
MH - *Apoptosis
MH - Cell Cycle
MH - Cell Line, Tumor
MH - Cell Proliferation
MH - Female
MH - Humans
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Ovarian Neoplasms/th [Therapy]
MH - *RNA, Antisense/tu [Therapeutic Use]
MH - *RNA, Messenger/an [Analysis]
MH - Transfection
MH - *WT1 Proteins/ai [Antagonists & Inhibitors]
MH - WT1 Proteins/ge [Genetics]
AB - PURPOSE: To study the effect of WT1 antisense oligodeoxynucleotide (ASODN) transfection on the proliferation and apoptosis of SKOV3 cells.
AB - METHODS: There were four groups in our study: normal control group, WT1 ASODN group, WT1 SODN group and lipofectamine group. Cell apoptosis was observed by flow cytometry. The effect of WT1 ASODN on cell proliferation was assayed by the MTT method. RT-PCR and Western blot were used to detect the expression level of WT1 mRNA and protein.
AB - RESULTS: The growth of the ovarian cancer cell line SKOV3 became significantly slower and its activity was reduced after being transfected by WT1 ASODN, with the inhibition rate of 49.48%. WT1 antisense phosphorothioate oligonucleotides did not only inhibit cell proliferation, arrest cell cycle at G0-G1 checkpoint and induce apoptosis in SKOV3 ovarian carcinoma cells, but also downregulated WT1 mRNA and protein expression, which contributed to the apoptosis (p < 0.05).
AB - CONCLUSION: WT1 antisense phosphorothioate oligonucleotides could both inhibit the proliferation and induce the apoptosis in SKOV3 ovarin carcinoma cell lines. Antisense oligonucleotides of WT1 may potentially help with the gene therapy of ovarian carcinoma.
RN - 0 (RNA, Antisense)
RN - 0 (RNA, Messenger)
RN - 0 (WT1 Proteins)
IS - 0392-2936
IL - 0392-2936
PT - Journal Article
ID - 22335028 [pubmed]
PP - ppublish
LG - English
DP - 2011
DC - 20120216
EZ - 2012/02/17 06:00
DA - 2012/03/14 06:00
DT - 2012/02/18 06:00
YR - 2011
ED - 20120313
RD - 20120216
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22335028
<300. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22109345
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Bronstein Y
AU - Ng CS
AU - Hwu P
AU - Hwu WJ
FA - Bronstein, Yulia
FA - Ng, Chaan S
FA - Hwu, Patrick
FA - Hwu, Wen-Jen
IN - Bronstein, Yulia. Department of Diagnostic Radiology, M. D. Anderson Cancer Center, T. Boone Pickens Academic Tower, Houston, TX 77030, USA. yulia.bronstein@mdanderson.org
TI - Radiologic manifestations of immune-related adverse events in patients with metastatic melanoma undergoing anti-CTLA-4 antibody therapy.
SO - AJR. American Journal of Roentgenology. 197(6):W992-W1000, 2011 Dec
AS - AJR Am J Roentgenol. 197(6):W992-W1000, 2011 Dec
NJ - AJR. American journal of roentgenology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 3ae, 7708173
IO - AJR Am J Roentgenol
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/im [Immunology]
MH - Antigens, Neoplasm/im [Immunology]
MH - *CTLA-4 Antigen/im [Immunology]
MH - Female
MH - Humans
MH - *Immunotherapy/ae [Adverse Effects]
MH - Magnetic Resonance Imaging
MH - Male
MH - *Melanoma/dt [Drug Therapy]
MH - *Melanoma/im [Immunology]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - Positron-Emission Tomography
MH - Retrospective Studies
MH - Statistics, Nonparametric
MH - Tomography, X-Ray Computed
MH - Treatment Outcome
AB - OBJECTIVE: Monoclonal antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4) used for treatment of metastatic melanoma produce inflammatory immune-related adverse events. The purpose of the current study was to retrospectively identify and characterize the radiologic manifestations of immune-related adverse events and to evaluate the possible association between these events and clinical responses to anti-CTLA-4 therapy.
AB - MATERIALS AND METHODS: We retrospectively reviewed the images and medical records of 119 patients with metastatic melanoma treated with anti-CTLA-4 at our institution and assessed the presence of radiologic manifestations of immune-related adverse events and the clinical responses to therapy. The responses were categorized as progressive or controlled disease. The controlled disease category included stable disease, partial response, and complete response according to the Response Evaluation Criteria in Solid Tumors, version 1.1.
AB - RESULTS: Radiologic manifestations of immune-related adverse events were found in 20 patients (16.8%). Clinically evident manifestations included colitis, hypophysitis, thyroiditis, and arthritis. Clinically silent manifestations were benign lymphadenopathy and inflammatory changes in the soft tissues, such as myositis, fasciitis, and retroperitoneal fat haziness. There was a significant association between the incidence of radiologic manifestations of immune-related adverse events and clinical responses to anti-CTLA-4 therapy. The disease control rates were 18% for the entire group, 55% for the group with, and 10% for the group without radiologic manifestations of immune-related adverse events. In three patients (2.5%), lymphadenopathy related to radiologic manifestations of immune-related adverse events was interpreted as suspected metastasis but was proved benign at biopsy.
AB - CONCLUSION: Radiologic manifestations of immune-related adverse events are associated with significant clinical benefit of anti-CTLA-4 therapy. In the era of developing immune checkpoint-targeted therapy for metastatic melanoma, radiologists should be alert to the possibility of these manifestations, which can mimic radiologic disease progression.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, Neoplasm)
RN - 0 (CTLA-4 Antigen)
RN - 6T8C155666 (ipilimumab)
RN - QEN1X95CIX (tremelimumab)
ES - 1546-3141
IL - 0361-803X
DI - 197/6/W992
DO - https://dx.doi.org/10.2214/AJR.10.6198
PT - Journal Article
PT - Research Support, N.I.H., Extramural
ID - 22109345 [pubmed]
ID - 197/6/W992 [pii]
ID - 10.2214/AJR.10.6198 [doi]
PP - ppublish
GI - No: CA016672
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2011 Dec
DC - 20111123
EZ - 2011/11/24 06:00
DA - 2012/01/27 06:00
DT - 2011/11/24 06:00
YR - 2011
ED - 20120126
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22109345
<301. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 21976060
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Man J
AU - Zhang X
FA - Man, Jianghong
FA - Zhang, Xuemin
IN - Man, Jianghong. Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing 100850, China.
TI - CUEDC2: an emerging key player in inflammation and tumorigenesis. [Review]
SO - Protein & Cell. 2(9):699-703, 2011 Sep
AS - Protein Cell. 2(9):699-703, 2011 Sep
NJ - Protein & cell
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101532368
IO - Protein Cell
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4875262
SB - Index Medicus
CP - Germany
MH - Anaphase-Promoting Complex-Cyclosome
MH - Breast Neoplasms/pa [Pathology]
MH - *Carrier Proteins/me [Metabolism]
MH - Cell Cycle Proteins/me [Metabolism]
MH - *Cell Transformation, Neoplastic/pa [Pathology]
MH - Estrogen Receptor alpha/me [Metabolism]
MH - Female
MH - Humans
MH - I-kappa B Kinase/me [Metabolism]
MH - Inflammation/pa [Pathology]
MH - *M Phase Cell Cycle Checkpoints
MH - *Membrane Proteins/me [Metabolism]
MH - Mitosis
MH - NF-kappa B p50 Subunit/me [Metabolism]
MH - Receptor-Interacting Protein Serine-Threonine Kinases/me [Metabolism]
MH - Signal Transduction
MH - Ubiquitin-Protein Ligase Complexes/me [Metabolism]
MH - Ubiquitination
AB - CUE domain-containing 2 (CUEDC2) is a protein involved in the regulation of the cell cycle, inflammation, and tumorigenesis and is highly expressed in many types of tumors. CUEDC2 is phosphorylated by Cdk1 during mitosis and promotes the release of anaphase-promoting complex or cyclosome (APC/C) from checkpoint inhibition. CUEDC2 is also known to interact with IkB kinase alpha (IKKalpha) and IKKbeta and has an inhibitory role in the activation of transcription factor nuclear factor-kappaB. Moreover, CUEDC2 plays an important role in downregulating the expression of hormone receptors estrogen receptor-alpha and progesterone receptor, thereby impairing the responsiveness of breast cancer to endocrine therapies. In this review, current knowledge on the multi-functions of CUEDC2 in normal processes and tumorigenesis are discussed and summarized.
RN - 0 (CUEDC2 protein, human)
RN - 0 (Carrier Proteins)
RN - 0 (Cell Cycle Proteins)
RN - 0 (Estrogen Receptor alpha)
RN - 0 (Membrane Proteins)
RN - 0 (NF-kappa B p50 Subunit)
RN - 0 (NFKB1 protein, human)
RN - 0 (estrogen receptor alpha, human)
RN - EC 2-3-2-23 (Ubiquitin-Protein Ligase Complexes)
RN - EC 2-3-2-27 (Anaphase-Promoting Complex-Cyclosome)
RN - EC 2-7-11-1 (Receptor-Interacting Protein Serine-Threonine Kinases)
RN - EC 2-7-11-10 (I-kappa B Kinase)
ES - 1674-8018
IL - 1674-800X
DO - https://dx.doi.org/10.1007/s13238-011-1089-z
PT - Journal Article
PT - Review
ID - 21976060 [pubmed]
ID - 10.1007/s13238-011-1089-z [doi]
ID - PMC4875262 [pmc]
PP - ppublish
PH - 2011/08/02 [received]
PH - 2011/08/14 [accepted]
LG - English
EP - 20111006
DP - 2011 Sep
DC - 20111006
EZ - 2011/10/07 06:00
DA - 2012/01/27 06:00
DT - 2011/10/07 06:00
YR - 2011
ED - 20120126
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=21976060
<302. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22003106
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Tu Z
AU - Li Y
AU - Smith DS
AU - Sheibani N
AU - Huang S
AU - Kern T
AU - Lin F
FA - Tu, Zhidan
FA - Li, Yan
FA - Smith, Dawn S
FA - Sheibani, Nader
FA - Huang, Suber
FA - Kern, Timothy
FA - Lin, Feng
IN - Tu, Zhidan. Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
TI - Retinal pericytes inhibit activated T cell proliferation.
SO - Investigative Ophthalmology & Visual Science. 52(12):9005-10, 2011 Nov 21
AS - Invest Ophthalmol Vis Sci. 52(12):9005-10, 2011 Nov 21
NJ - Investigative ophthalmology & visual science
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - gwi, 7703701
IO - Invest. Ophthalmol. Vis. Sci.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3231798
SB - Index Medicus
CP - United States
MH - Animals
MH - Apoptosis/im [Immunology]
MH - *Cell Communication/im [Immunology]
MH - Cell Division/im [Immunology]
MH - Cell Line, Transformed
MH - Diabetic Retinopathy/im [Immunology]
MH - Diabetic Retinopathy/pa [Pathology]
MH - *Endothelial Cells/cy [Cytology]
MH - Endothelial Cells/im [Immunology]
MH - Humans
MH - Hyperglycemia/im [Immunology]
MH - Hyperglycemia/pa [Pathology]
MH - Membrane Proteins/im [Immunology]
MH - Mice
MH - Mice, Transgenic
MH - *Pericytes/cy [Cytology]
MH - Pericytes/im [Immunology]
MH - *Retina/cy [Cytology]
MH - Retina/im [Immunology]
MH - *Retinitis/im [Immunology]
MH - Retinitis/pa [Pathology]
MH - *T-Lymphocytes/cy [Cytology]
AB - PURPOSE: To test the hypothesis that retinal pericytes (RPCs) are immunosuppressive; therefore, their loss of function under hyperglycemic conditions favors retinal inflammation and contributes to the pathogenesis of diabetic retinopathy (DR).
AB - METHODS: Isolated mouse and human RPCs were tested in T cell function assays to evaluate their capability of inhibiting T cell responses. To elucidate the underlying mechanisms, transwell systems, blocking mAbs against PD-L1 and IL-10 were used. The efficacy of RPCs in protecting retinal endothelial cells (RECs) from inflammation-induced apoptosis was assessed by apoptosis detection staining. Finally, to test whether hyperglycemic conditions impair the immunomodulatory activity of RPCs, RPCs pre-incubated in high glucose or methylglyoxal (MGO) were evaluated using the T cell proliferation assays.
AB - RESULTS: RPCs profoundly inhibited activated T cell proliferation and inflammatory cytokine production. The T cell inhibitory activity of RPCs was decreased, but was not abolished, in transwell experiments. RPCs express PD-L1, and blocking PD-L1 reduced RPCs' efficacy of T cell inhibition. RPCs also produce IL-10, and neutralization of IL-10 reduced their immunosuppressive activity. There were significantly reduced numbers of inflammation-induced apoptosis-detected RECs in the presence of RPCs. Incubation of RPCs with either high glucose or MGO reduced the activity of RPCs to inhibit activated T cell proliferation.
AB - CONCLUSIONS: RPCs are highly immunosuppressive and they protected RECs from inflammation-mediated apoptosis. Hyperglycemic conditions impaired the T cell inhibitory activity of RPCs. These results reveal a new function of RPCs, and its regulation under hyperglycemic conditions. This may represent a novel mechanism by which RPCs contribute to preservation of retinal integrity in diseases, including DR.
RN - 0 (Membrane Proteins)
ES - 1552-5783
IL - 0146-0404
DI - iovs.11-8008
DO - https://dx.doi.org/10.1167/iovs.11-8008
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 22003106 [pubmed]
ID - iovs.11-8008 [pii]
ID - 10.1167/iovs.11-8008 [doi]
ID - PMC3231798 [pmc]
PP - epublish
GI - No: RC4 EY021357
Organization: (EY) *NEI NIH HHS*
Country: United States
No: R01 EY000300
Organization: (EY) *NEI NIH HHS*
Country: United States
No: NS052471
Organization: (NS) *NINDS NIH HHS*
Country: United States
No: R01 NS052471
Organization: (NS) *NINDS NIH HHS*
Country: United States
No: EY020956
Organization: (EY) *NEI NIH HHS*
Country: United States
No: EY21357
Organization: (EY) *NEI NIH HHS*
Country: United States
No: R21 EY020956
Organization: (EY) *NEI NIH HHS*
Country: United States
LG - English
EP - 20111121
DP - 2011 Nov 21
DC - 20111122
EZ - 2011/10/18 06:00
DA - 2012/01/17 06:00
DT - 2011/10/18 06:00
YR - 2011
ED - 20120116
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22003106
<303. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 22010182
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Hamnvik OP
AU - Larsen PR
AU - Marqusee E
FA - Hamnvik, Ole-Petter Riksfjord
FA - Larsen, P Reed
FA - Marqusee, Ellen
IN - Hamnvik, Ole-Petter Riksfjord. Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ohamnvik@partners.org
TI - Thyroid dysfunction from antineoplastic agents. [Review]
CM - Comment in: J Natl Cancer Inst. 2012 Mar 7;104(5):422-3; author reply 423; PMID: 22291212
SO - Journal of the National Cancer Institute. 103(21):1572-87, 2011 Nov 02
AS - J Natl Cancer Inst. 103(21):1572-87, 2011 Nov 02
NJ - Journal of the National Cancer Institute
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - j9j, 7503089
IO - J. Natl. Cancer Inst.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206040
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal, Humanized/ae [Adverse Effects]
MH - Antibodies, Neoplasm/ae [Adverse Effects]
MH - Anticarcinogenic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Diphtheria Toxin/ae [Adverse Effects]
MH - Humans
MH - Hyperthyroidism/bl [Blood]
MH - *Hyperthyroidism/ci [Chemically Induced]
MH - Hyperthyroidism/di [Diagnosis]
MH - Hypopituitarism/co [Complications]
MH - Hypopituitarism/et [Etiology]
MH - Hypothyroidism/bl [Blood]
MH - *Hypothyroidism/ci [Chemically Induced]
MH - Hypothyroidism/di [Diagnosis]
MH - Hypothyroidism/dt [Drug Therapy]
MH - Hypothyroidism/et [Etiology]
MH - Interferon-alpha/ae [Adverse Effects]
MH - Interleukin-2/ae [Adverse Effects]
MH - Interleukin-2/aa [Analogs & Derivatives]
MH - Iodine Radioisotopes/ad [Administration & Dosage]
MH - Molecular Targeted Therapy/mt [Methods]
MH - *Neoplasms/dt [Drug Therapy]
MH - Neoplasms/im [Immunology]
MH - Protein-Tyrosine Kinases/ai [Antagonists & Inhibitors]
MH - Quality of Life
MH - Radioimmunotherapy
MH - Recombinant Fusion Proteins/ae [Adverse Effects]
MH - Recombinant Proteins/ae [Adverse Effects]
MH - Tetrahydronaphthalenes/ae [Adverse Effects]
MH - Thalidomide/ae [Adverse Effects]
MH - Thalidomide/aa [Analogs & Derivatives]
MH - Thyroid Function Tests
MH - *Thyroid Gland/de [Drug Effects]
MH - Thyroid Gland/me [Metabolism]
MH - *Thyroid Hormones/bl [Blood]
MH - Thyroiditis, Autoimmune/ci [Chemically Induced]
AB - Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-alpha, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%-50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient's quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antibodies, Monoclonal, Humanized)
RN - 0 (Antibodies, Neoplasm)
RN - 0 (Anticarcinogenic Agents)
RN - 0 (Antineoplastic Agents)
RN - 0 (Diphtheria Toxin)
RN - 0 (Interferon-alpha)
RN - 0 (Interleukin-2)
RN - 0 (Iodine Radioisotopes)
RN - 0 (Recombinant Fusion Proteins)
RN - 0 (Recombinant Proteins)
RN - 0 (Tetrahydronaphthalenes)
RN - 0 (Thyroid Hormones)
RN - 25E79B5CTM (denileukin diftitox)
RN - 3A189DH42V (alemtuzumab)
RN - 4Z8R6ORS6L (Thalidomide)
RN - 6T8C155666 (ipilimumab)
RN - A61RXM4375 (bexarotene)
RN - EC 2-7-10-1 (Protein-Tyrosine Kinases)
RN - F0P408N6V4 (lenalidomide)
RN - M89N0Q7EQR (aldesleukin)
RN - QEN1X95CIX (tremelimumab)
ES - 1460-2105
IL - 0027-8874
DI - djr373
DO - https://dx.doi.org/10.1093/jnci/djr373
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Review
ID - 22010182 [pubmed]
ID - djr373 [pii]
ID - 10.1093/jnci/djr373 [doi]
ID - PMC3206040 [pmc]
PP - ppublish
GI - No: R01 DK044128
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: DK36256
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: DK44128
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG - English
EP - 20111018
DP - 2011 Nov 02
DC - 20111102
EZ - 2011/10/20 06:00
DA - 2011/12/21 06:00
DT - 2011/10/20 06:00
YR - 2011
ED - 20111220
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22010182
<304. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 21737890
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Cheng H
AU - Merika E
AU - Syrigos KN
AU - Saif MW
FA - Cheng, Haiying
FA - Merika, Eirini
FA - Syrigos, Kostas N
FA - Saif, Muhammad Wasif
IN - Cheng, Haiying. Columbia University College of Physicians and Surgeons, New York, NY, USA.
TI - Novel agents for the treatment of pancreatic adenocarcinoma. Highlights from the "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011. [Review]
SO - Jop: Journal of the Pancreas [Electronic Resource]. 12(4):334-8, 2011 Jul 08
AS - JOP. 12(4):334-8, 2011 Jul 08
NJ - JOP : Journal of the pancreas
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101091810
IO - JOP
SB - Index Medicus
CP - Italy
MH - *Adenocarcinoma/dt [Drug Therapy]
MH - Adenocarcinoma/me [Metabolism]
MH - Animals
MH - *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - Chicago
MH - Congresses as Topic
MH - Drugs, Investigational/ad [Administration & Dosage]
MH - *Drugs, Investigational/tu [Therapeutic Use]
MH - Humans
MH - Medical Oncology
MH - Models, Biological
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/me [Metabolism]
MH - Signal Transduction/ge [Genetics]
MH - Signal Transduction/ph [Physiology]
MH - Societies, Medical
MH - United States
AB - There are urgent needs to develop novel and more effective regimens to improve outcomes of pancreatic cancer given its dismal prognosis and limited treatment options. Several phase I clinical trials involving novel agents were recently presented at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting. It appears that hedgehog inhibition with IPI-926 was well-tolerated and might be effective in treating pancreatic cancer when combined with gemcitabine. The survival benefits will be tested in the following randomized phase II trial. The new combination of gemcitabine and blockade of checkpoint kinases with AZD7762 showed an acceptable safety profile. Furthermore, inhibition of PI3K by BAY80-6946 was well tolerated with PET-CT suggesting reduction in FDG uptake in some pancreatic cancer. The benefits of above novel agents/regimens need to be further tested in phase II trials.
RN - 0 (Drugs, Investigational)
ES - 1590-8577
IL - 1590-8577
DI - v12i04a05
PT - Journal Article
PT - Review
ID - 21737890 [pubmed]
ID - v12i04a05 [pii]
PP - epublish
LG - English
EP - 20110708
DP - 2011 Jul 08
DC - 20110708
EZ - 2011/07/09 06:00
DA - 2011/12/16 06:00
DT - 2011/07/09 06:00
YR - 2011
ED - 20111215
RD - 20110708
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=21737890
<305. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 21815696
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Lowery MA
AU - O'Reilly EM
FA - Lowery, Maeve A
FA - O'Reilly, Eileen M
IN - Lowery, Maeve A. Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, USA.
TI - New approaches to the treatment of pancreatic cancer: from tumor-directed therapy to immunotherapy.
SO - Biodrugs. 25(4):207-16, 2011 Aug 01
AS - BioDrugs. 25(4):207-16, 2011 Aug 01
NJ - BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - d3a, 9705305
IO - BioDrugs
SB - Index Medicus
CP - New Zealand
MH - Adenocarcinoma/dt [Drug Therapy]
MH - Adenocarcinoma/ge [Genetics]
MH - Adenocarcinoma/im [Immunology]
MH - *Adenocarcinoma/th [Therapy]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - Camptothecin/aa [Analogs & Derivatives]
MH - Camptothecin/tu [Therapeutic Use]
MH - Cancer Vaccines/tu [Therapeutic Use]
MH - Combined Modality Therapy/mt [Methods]
MH - Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/tu [Therapeutic Use]
MH - Fluorouracil/tu [Therapeutic Use]
MH - Humans
MH - Immunotherapy/mt [Methods]
MH - Leucovorin/tu [Therapeutic Use]
MH - Organoplatinum Compounds/tu [Therapeutic Use]
MH - Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - Pancreatic Neoplasms/im [Immunology]
MH - *Pancreatic Neoplasms/th [Therapy]
AB - The development of novel therapeutic strategies for pancreatic adenocarcinoma (PAC) has traditionally been considered particularly challenging for clinical and laboratory investigators due to its aggressive underlying biology and inherent resistance to currently available therapies. More recently, however, advances have been made in the identification of promising therapeutic targets for intervention, along with several key insights into the complex sequence of genetic alterations involved in the evolution of PAC from premalignant precursor lesion to malignant cells with metastatic potential. FOLFIRINOX (5-fluorouracil/leucovorin/irinotecan/oxaliplatin) has recently been identified as a combination cytotoxic therapy associated with a significant survival benefit over single-agent gemcitabine in good performance status patients with advanced disease; it is hoped that a similar benefit will be seen in planned trials of FOLFIRINOX as perioperative therapy. The success of immune therapy with the anti-cytotoxic T-lymphocyte antigen-4 antibody ipilimumab in advanced melanoma has spurred interest in the development of vaccines and immune therapies for other solid tumors. Certainly, the concept of harnessing the power of the immune system for cancer treatment is an attractive concept to patients and clinicians alike. Herein we discuss recent advances in the development of novel therapeutic approaches to PAC, focusing in particular on recent developments in immune and vaccine therapy.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Cancer Vaccines)
RN - 0 (Organoplatinum Compounds)
RN - 04ZR38536J (oxaliplatin)
RN - 0W860991D6 (Deoxycytidine)
RN - 6T8C155666 (ipilimumab)
RN - B76N6SBZ8R (gemcitabine)
RN - Q573I9DVLP (Leucovorin)
RN - U3P01618RT (Fluorouracil)
RN - XT3Z54Z28A (Camptothecin)
PS - IFL protocol
ES - 1179-190X
IL - 1173-8804
DI - 1
DO - https://dx.doi.org/10.2165/11592470-000000000-00000
PT - Journal Article
ID - 21815696 [pubmed]
ID - 1 [pii]
ID - 10.2165/11592470-000000000-00000 [doi]
PP - ppublish
LG - English
DP - 2011 Aug 01
DC - 20110805
EZ - 2011/08/06 06:00
DA - 2011/12/13 00:00
DT - 2011/08/06 06:00
YR - 2011
ED - 20111207
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=21815696
<306. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 21242854
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Borodic G
AU - Hinkle DM
AU - Cia Y
FA - Borodic, Gary
FA - Hinkle, David M
FA - Cia, Yihong
IN - Borodic, Gary. Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02142, USA. borodic@aol.com
TI - Drug-induced graves disease from CTLA-4 receptor suppression.
CM - Comment in: Ophthal Plast Reconstr Surg. 2013 May-Jun;29(3):239-40; PMID: 23652294
CM - Comment in: Ophthal Plast Reconstr Surg. 2013 May-Jun;29(3):241; PMID: 23652295
SO - Ophthalmic Plastic & Reconstructive Surgery. 27(4):e87-8, 2011 Jul-Aug
AS - Ophthal Plast Reconstr Surg. 27(4):e87-8, 2011 Jul-Aug
NJ - Ophthalmic plastic and reconstructive surgery
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - ay2, 8508431
IO - Ophthal Plast Reconstr Surg
SB - Index Medicus
CP - United States
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antigens, CD/de [Drug Effects]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - CTLA-4 Antigen
MH - Diplopia/ci [Chemically Induced]
MH - Exophthalmos/ci [Chemically Induced]
MH - Female
MH - *Graves Ophthalmopathy/ci [Chemically Induced]
MH - Humans
MH - Lung Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/sc [Secondary]
MH - Magnetic Resonance Imaging
MH - Melanoma/dt [Drug Therapy]
MH - Melanoma/sc [Secondary]
MH - Middle Aged
MH - Neoplasms, Unknown Primary/dt [Drug Therapy]
MH - Neoplasms, Unknown Primary/pa [Pathology]
MH - Oculomotor Muscles/de [Drug Effects]
AB - Monoclonal antibody, ipilimumab, useful for treatment of metastatic melanoma, blocks CTLA-4 mediated T-cell suppression and can also cause a Graves ophthalmopathy like syndrome. Epidemiologic study has linked variant polymorphisms of CTLA-4 receptor gene to the presence of thyroid eye disease. The combination of these observations suggests CTLA-4 mediated T-cell functions are important to the pathogenesis of thyroid-associated eye disease.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 6T8C155666 (ipilimumab)
ES - 1537-2677
IL - 0740-9303
DO - https://dx.doi.org/10.1097/IOP.0b013e3181ef72a1
PT - Case Reports
PT - Journal Article
ID - 21242854 [pubmed]
ID - 10.1097/IOP.0b013e3181ef72a1 [doi]
PP - ppublish
LG - English
DP - 2011 Jul-Aug
DC - 20110712
EZ - 2011/01/19 06:00
DA - 2011/09/22 06:00
DT - 2011/01/19 06:00
YR - 2011
ED - 20110921
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=21242854
<307. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 21083648
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Kahler KC
AU - Hauschild A
FA - Kahler, Katharina C
FA - Hauschild, Axel
IN - Kahler, Katharina C. Department of Dermatology, Venerology and Allergology, University of Schleswig-Holstein Hospital, Campus Kiel, Germany.
TI - Treatment and side effect management of CTLA-4 antibody therapy in metastatic melanoma. [Review]
SO - Journal der Deutschen Dermatologischen Gesellschaft. 9(4):277-86, 2011 Apr
AS - J.Deutschen Dermatologischen Gesellschaft. 9(4):277-86, 2011 Apr
NJ - Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101164708
IO - J Dtsch Dermatol Ges
SB - Index Medicus
CP - Germany
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/im [Immunology]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antigens, CD/de [Drug Effects]
MH - Antigens, CD/im [Immunology]
MH - CTLA-4 Antigen
MH - Humans
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - *Melanoma/sc [Secondary]
MH - Models, Immunological
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/im [Immunology]
MH - Treatment Outcome
AB - Immune-modifying monoclonal antibodies may induce or enhance the natural immune response against tumor cells. The complex interaction between antigen-presenting cells and T lymphocytes as an immune response is strongly affected by anti-CD152 (CTLA-4)-antibodies. The cytotoxic T-lymphocyte (CTLA-4) receptor binds molecules of the B7-family which leads to a suppression of T cells. Specific CTLA-4 antibodies induce an unrestrained T-cell activation. Treatment with the CTLA-4 antibodies ipilimumab and tremelimumab has been investigated in metastatic melanoma only within clinical trials. Currently, the critical phase III trial on ipilimumab is in the final analysis process and expected to lead to approval. CTLA-4 antibodies belong to the most promising new molecules for the treatment of advanced melanoma. During treatment with CTLA-4 antibodies, distinct adverse events may occur. Treating physicians must be familiar with their appropriate treatment and prophylaxis. The most frequently observed side effects are diseases such as an autoimmune colitis which is typically characterized by a mild to moderate, but occasionally also severe and persistent diarrhea. Other autoimmune-mediated side effects like hypophysitis, hepatitis, iridocyclitis or an exacerbation of lupus nephritis have been reported in the literature. Their early recognition and treatment are mandatory to reduce the risk of sequelae for CTLA-4-antibod-treated patients. Autoimmune-mediated side effects are reported to correlate positively with treatment response. We review the mechanisms of action, provide an update on clinical trials with the two CTLA-4-antibodies for metastatic melanoma, and present detailed recommendations for managing the side effects of these new agents.
AB - Copyright © The Authors * Journal compilation © Blackwell Verlag GmbH, Berlin.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
ES - 1610-0387
IL - 1610-0379
DO - https://dx.doi.org/10.1111/j.1610-0387.2010.07568.x
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 21083648 [pubmed]
ID - 10.1111/j.1610-0387.2010.07568.x [doi]
PP - ppublish
LG - English
LG - German
EP - 20101117
DP - 2011 Apr
DC - 20110328
EZ - 2010/11/19 06:00
DA - 2011/08/24 06:00
DT - 2010/11/19 06:00
YR - 2011
ED - 20110823
RD - 20111117
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=21083648
<308. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 21249150
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Lee SJ
AU - Lee MH
AU - Kim DW
AU - Lee S
AU - Huang S
AU - Ryu MJ
AU - Kim YK
AU - Kim SJ
AU - Kim SJ
AU - Hwang JH
AU - Oh S
AU - Cho H
AU - Kim JM
AU - Lim DS
AU - Jo YS
AU - Shong M
FA - Lee, Seong Jin
FA - Lee, Min Hee
FA - Kim, Dong Wook
FA - Lee, Seongeun
FA - Huang, Songmei
FA - Ryu, Min Jeong
FA - Kim, Yong Kyung
FA - Kim, Sung Jin
FA - Kim, Soung Jung
FA - Hwang, Jung Hwan
FA - Oh, Sangphil
FA - Cho, Heeyeong
FA - Kim, Jin Man
FA - Lim, Dae-Sik
FA - Jo, Young Suk
FA - Shong, Minho
IN - Lee, Seong Jin. Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
TI - Cross-regulation between oncogenic BRAF(V600E) kinase and the MST1 pathway in papillary thyroid carcinoma.
SO - PLoS ONE [Electronic Resource]. 6(1):e16180, 2011 Jan 13
AS - PLoS ONE. 6(1):e16180, 2011 Jan 13
NJ - PloS one
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101285081
IO - PLoS ONE
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020965
SB - Index Medicus
CP - United States
MH - Animals
MH - Apoptosis
MH - Carcinoma
MH - Cell Cycle Proteins
MH - Forkhead Box Protein O3
MH - Forkhead Transcription Factors/me [Metabolism]
MH - Gene Expression Regulation, Neoplastic
MH - Humans
MH - Mice
MH - Mutation, Missense
MH - Neoplasms, Experimental
MH - Phenotype
MH - Protein-Serine-Threonine Kinases/ai [Antagonists & Inhibitors]
MH - *Protein-Serine-Threonine Kinases/me [Metabolism]
MH - Proto-Oncogene Proteins B-raf/ge [Genetics]
MH - *Proto-Oncogene Proteins B-raf/me [Metabolism]
MH - *Receptor Cross-Talk/ph [Physiology]
MH - Thyroid Neoplasms/me [Metabolism]
MH - Thyroid Neoplasms/pa [Pathology]
MH - Tumor Suppressor Proteins/ai [Antagonists & Inhibitors]
MH - Tumor Suppressor Proteins/me [Metabolism]
AB - BACKGROUND: The BRAF(V600E) mutation leading to constitutive signaling of MEK-ERK pathways causes papillary thyroid cancer (PTC). Ras association domain family 1A (RASSF1A), which is an important regulator of MST1 tumor suppressor pathways, is inactivated by hypermethylation of its promoter region in 20 to 32% of PTC. However, in PTC without RASSF1A methylation, the regulatory mechanisms of RASSF1A-MST1 pathways remain to be elucidated, and the functional cooperation or cross regulation between BRAF(V600E) and MST1,which activates Foxo3,has not been investigated.
AB - METHODOLOGY/PRINCIPAL FINDINGS: The negative regulators of the cell cycle, p21 and p27, are strongly induced by transcriptional activation of FoxO3 in BRAF(V600E) positive thyroid cancer cells. The FoxO3 transactivation is augmented by RASSF1A and the MST1 signaling pathway. Interestingly, introduction of BRAF(V600E)markedly abolished FoxO3 transactivation and resulted in the suppression of p21 and p27 expression. The suppression of FoxO3 transactivation by BRAF(V600E)is strongly increased by coexpression of MST1 but it is not observed in the cells in which MST1, but not MST2,is silenced. Mechanistically, BRAF(V600E)was able to bind to the C-terminal region of MST1 and resulted in the suppression of MST1 kinase activities. The induction of the G1-checkpoint CDK inhibitors, p21 and p27,by the RASSF1A-MST1-FoxO3 pathway facilitates cellular apoptosis, whereas addition of BRAF(V600E) inhibits the apoptotic processes through the inactivation of MST1. Transgenic induction of BRAF(V600E)in the thyroid gland results in cancers resembling human papillary thyroid cancers. The development of BRAF(V600E)transgenic mice with the MST1 knockout background showed that these mice had abundant foci of poorly differentiated carcinomas and large areas without follicular architecture or colloid formation.
AB - CONCLUSIONS/SIGNIFICANCE: The results of this study revealed that the oncogenic effect of BRAF(V600E) is associated with the inhibition of MST1 tumor suppressor pathways, and that the activity of RASSF1A-MST1-FoxO3 pathways determines the phenotypes of BRAF(V600E) tumors.
RN - 0 (Cell Cycle Proteins)
RN - 0 (FOXO3 protein, human)
RN - 0 (Forkhead Box Protein O3)
RN - 0 (Forkhead Transcription Factors)
RN - 0 (RASSF1 protein, human)
RN - 0 (Tumor Suppressor Proteins)
RN - EC 2-7-1 (STK4 protein, human)
RN - EC 2-7-11-1 (BRAF protein, human)
RN - EC 2-7-11-1 (Protein-Serine-Threonine Kinases)
RN - EC 2-7-11-1 (Proto-Oncogene Proteins B-raf)
RS - Thyroid cancer, papillary
ES - 1932-6203
IL - 1932-6203
DO - https://dx.doi.org/10.1371/journal.pone.0016180
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 21249150 [pubmed]
ID - 10.1371/journal.pone.0016180 [doi]
ID - PMC3020965 [pmc]
PP - epublish
PH - 2010/09/08 [received]
PH - 2010/12/07 [accepted]
LG - English
EP - 20110113
DP - 2011 Jan 13
DC - 20110120
EZ - 2011/01/21 06:00
DA - 2011/08/04 06:00
DT - 2011/01/21 06:00
YR - 2011
ED - 20110802
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=21249150
<309. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 20842054
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Royal RE
AU - Levy C
AU - Turner K
AU - Mathur A
AU - Hughes M
AU - Kammula US
AU - Sherry RM
AU - Topalian SL
AU - Yang JC
AU - Lowy I
AU - Rosenberg SA
FA - Royal, Richard E
FA - Levy, Catherine
FA - Turner, Keli
FA - Mathur, Aarti
FA - Hughes, Marybeth
FA - Kammula, Udai S
FA - Sherry, Richard M
FA - Topalian, Suzanne L
FA - Yang, James C
FA - Lowy, Israel
FA - Rosenberg, Steven A
IN - Royal, Richard E. Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. rroyal@mdanderson.org
TI - Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma.
SO - Journal of Immunotherapy. 33(8):828-33, 2010 Oct
AS - J Immunother. 33(8):828-33, 2010 Oct
NJ - Journal of immunotherapy (Hagerstown, Md. : 1997)
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - cuq, 9706083
IO - J. Immunother.
SB - Index Medicus
CP - United States
MH - Adenocarcinoma/im [Immunology]
MH - Adenocarcinoma/pa [Pathology]
MH - Adenocarcinoma/pp [Physiopathology]
MH - *Adenocarcinoma/th [Therapy]
MH - Adult
MH - Aged
MH - *Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antigens, CD/im [Immunology]
MH - CTLA-4 Antigen
MH - Colitis/et [Etiology]
MH - Colitis/im [Immunology]
MH - Disease Progression
MH - Female
MH - Humans
MH - *Immunotherapy
MH - Injections, Intravenous
MH - Male
MH - Middle Aged
MH - Neoplasm Metastasis
MH - Pancreatic Neoplasms/im [Immunology]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Pancreatic Neoplasms/pp [Physiopathology]
MH - *Pancreatic Neoplasms/th [Therapy]
MH - Treatment Failure
AB - New, effective therapies are needed for pancreatic ductal adenocarcinoma. Ipilimumab can mediate an immunologic tumor regression in other histologies. This phase II trial evaluated the efficacy of Ipilimumab for advanced pancreatic cancer. Subjects were adults with locally advanced or metastatic pancreas adenocarcinoma with measurable disease, good performance status, and minimal comorbidities. Ipilimumab was administered intravenously (3.0 mg/kg every 3 wk; 4 doses/course) for a maximum of 2 courses. Response rate by response evaluation criteria in solid tumors criteria and toxicity were measured. Twenty-seven subjects were enrolled (metastatic disease: 20 and locally advanced: 7) with median age of 55 years (27 to 68 y) and good performance status (26 with Eastern Cooperative Oncology Group performance status =0 to 1). Three subjects experienced >= grade 3 immune-mediated adverse events (colitis:1, encephalitis:1, hypohysitis:1). There were no responders by response evaluation criteria in solid tumors criteria but a subject experienced a delayed response after initial progressive disease. In this subject, new metastases after 2 doses of Ipilimumab established progressive disease. But continued administration of the agent per protocol resulted in significant delayed regression of the primary lesion and 20 hepatic metastases. This was reflected in tumor markers normalization, and clinically significant improvement of performance status. Single agent Ipilimumab at 3.0 mg/kg/dose is ineffective for the treatment of advanced pancreas cancer. However, a significant delayed response in one subject of this trial suggests that immunotherapeutic approaches to pancreas cancer deserve further exploration.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 6T8C155666 (ipilimumab)
ES - 1537-4513
IL - 1524-9557
DO - https://dx.doi.org/10.1097/CJI.0b013e3181eec14c
PT - Clinical Trial, Phase II
PT - Journal Article
PT - Research Support, N.I.H., Intramural
ID - 20842054 [pubmed]
ID - 10.1097/CJI.0b013e3181eec14c [doi]
PP - ppublish
GI - Organization: *Intramural NIH HHS*
Country: United States
LG - English
DP - 2010 Oct
DC - 20100924
EZ - 2010/09/16 06:00
DA - 2011/05/18 06:00
DT - 2010/09/16 06:00
YR - 2010
ED - 20110517
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=20842054
<310. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 20871480
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Xia QS
AU - Ishigaki Y
AU - Zhao X
AU - Shimasaki T
AU - Nakajima H
AU - Nakagawa H
AU - Takegami T
AU - Chen ZH
AU - Motoo Y
FA - Xia, Qi-sheng
FA - Ishigaki, Yasuhito
FA - Zhao, Xia
FA - Shimasaki, Takeo
FA - Nakajima, Hideo
FA - Nakagawa, Hideaki
FA - Takegami, Tsutomu
FA - Chen, Zhi-hua
FA - Motoo, Yoshiharu
IN - Xia, Qi-sheng. Department of Medical Oncology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
TI - Human SMG-1 is involved in gemcitabine-induced primary microRNA-155/BIC up-regulation in human pancreatic cancer PANC-1 cells.
SO - Pancreas. 40(1):55-60, 2011 Jan
AS - Pancreas. 40(1):55-60, 2011 Jan
NJ - Pancreas
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - prs, 8608542
IO - Pancreas
SB - Index Medicus
CP - United States
MH - Androstadienes/pd [Pharmacology]
MH - *Antimetabolites, Antineoplastic/pd [Pharmacology]
MH - Ataxia Telangiectasia Mutated Proteins
MH - Cell Cycle Proteins/ph [Physiology]
MH - Cell Line, Tumor
MH - DNA-Binding Proteins/ph [Physiology]
MH - *Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Extracellular Signal-Regulated MAP Kinases/ph [Physiology]
MH - Gene Expression Regulation, Neoplastic
MH - Humans
MH - JNK Mitogen-Activated Protein Kinases/ph [Physiology]
MH - *MicroRNAs/ge [Genetics]
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - *Phosphatidylinositol 3-Kinases/ph [Physiology]
MH - Protein-Serine-Threonine Kinases/ph [Physiology]
MH - Tumor Suppressor Proteins/ph [Physiology]
MH - Up-Regulation
AB - OBJECTIVES: Human primary microRNA-155/B-cell integration cluster (BIC) transcript is the precursor of microRNA-155. The overexpression of them has been widely observed in the progression of various types of tumors. Our objective was to investigate the effect of anticancer agents on the expression of BIC and possible signal pathways that involved in.
AB - METHODS: Quantitative real-time reverse transcriptase polymerase chain reaction was used to measure the expression of BIC. Chemical inhibitors against c-Jun N-terminal kinase 1, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2, protein kinase C, checkpoint kinase 1, and phosphatidylinositol 3 kinase (PI3K) were used for the evaluation of involved signal pathways. RNA interference was used to knock down the expression of ataxia-telangiectasia mutated, ataxia-telangiectasia and Rad3 related, and suppressor of morphogenesis in genitalia-1 (SMG-1), and Western blot was carried out to evaluate the knockdown effect.
AB - RESULTS: B-cell integration cluster expression was induced by a representative anti-pancreatic cancer drug, gemcitabine, in human pancreatic cancer PANC-1 cells. The mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 and c-Jun N-terminal kinase inhibitors, but not the checkpoint kinase 1 and protein kinase C inhibitors, suppressed the up-regulation of BIC. B-cell integration cluster up-regulation was also significantly inhibited by the PI3K inhibitor wortmannin. RNA interference studies showed that wortmannin-sensitive SMG-1 but not ataxia-telangiectasia mutated or ataxia-telangiectasia and Rad3 related was involved in the up-regulation.
AB - CONCLUSIONS: Our results show that multiple pathways can be involved in the up-regulation of BIC. Furthermore, we demonstrate for the first time that PI3K SMG-1 is required for gemcitabine-induced up-regulation of BIC transcript.
RN - 0 (Androstadienes)
RN - 0 (Antimetabolites, Antineoplastic)
RN - 0 (Cell Cycle Proteins)
RN - 0 (DNA-Binding Proteins)
RN - 0 (MIRN155 microRNA, human)
RN - 0 (MicroRNAs)
RN - 0 (Tumor Suppressor Proteins)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7-1 (Phosphatidylinositol 3-Kinases)
RN - EC 2-7-1-137 (SMG1 protein, human)
RN - EC 2-7-11-1 (ATM protein, human)
RN - EC 2-7-11-1 (ATR protein, human)
RN - EC 2-7-11-1 (Ataxia Telangiectasia Mutated Proteins)
RN - EC 2-7-11-1 (Protein-Serine-Threonine Kinases)
RN - EC 2-7-11-24 (Extracellular Signal-Regulated MAP Kinases)
RN - EC 2-7-11-24 (JNK Mitogen-Activated Protein Kinases)
RN - XVA4O219QW (wortmannin)
ES - 1536-4828
IL - 0885-3177
DO - https://dx.doi.org/10.1097/MPA.0b013e3181e89f74
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 20871480 [pubmed]
ID - 10.1097/MPA.0b013e3181e89f74 [doi]
PP - ppublish
LG - English
DP - 2011 Jan
DC - 20101216
EZ - 2010/09/28 06:00
DA - 2011/04/19 06:00
DT - 2010/09/28 06:00
YR - 2011
ED - 20110418
RD - 20151119
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=20871480
<311. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 21150603
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Bouwhuis MG
AU - Ten Hagen TL
AU - Suciu S
AU - Eggermont AM
FA - Bouwhuis, Marna G
FA - Ten Hagen, Timo L M
FA - Suciu, Stefan
FA - Eggermont, Alexander Mm
IN - Bouwhuis, Marna G. Department of Surgery, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
TI - Autoimmunity and treatment outcome in melanoma. [Review]
SO - Current Opinion in Oncology. 23(2):170-6, 2011 Mar
AS - Curr Opin Oncol. 23(2):170-6, 2011 Mar
NJ - Current opinion in oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - a1v, 9007265
IO - Curr Opin Oncol
SB - Index Medicus
CP - United States
MH - Autoimmunity/im [Immunology]
MH - Humans
MH - *Immunotherapy/mt [Methods]
MH - *Melanoma/im [Immunology]
MH - *Melanoma/th [Therapy]
MH - Treatment Outcome
AB - PURPOSE OF REVIEW: Only a subset of melanoma patients with advanced disease seems to benefit from immunotherapy. Predictive markers identifying these patients are unfortunately not available. Whether immune-related side effects could serve as predictors for treatment response or just resemble unwanted side effects from immunotherapy will be outlined in this review.
AB - RECENT FINDINGS: Early studies suggested an association of immune-related side effects such as vitiligo and autoimmune thyroiditis with response in patients receiving IL-2 or IFNalpha. However, conflicting data have been reported as well, mentioning the effect of a higher rate of immune-related toxicities during prolonged administration of the drug in responders/survivors. This type of bias is also known as guarantee-time bias. Recently, a clearly significant and clinically relevant prolongation of survival was demonstrated in patients with metastatic melanoma treated with ipilimumab. Immune-related adverse events were associated with response to ipilimumab, however, at the cost of considerable toxicity.
AB - SUMMARY: Evidence for an association of immune-related toxicities and response in patients receiving IL-2 or IFNalpha is weak, considering guarantee-time bias. On the contrary, this association for patients receiving anti-cytotoxic T-lymphocyte antigen-4 therapy (ipilimumab) appears much stronger. Importantly, can we uncouple tumor immunity from autoimmunity in order to optimize immunotherapy in melanoma?
ES - 1531-703X
IL - 1040-8746
DO - https://dx.doi.org/10.1097/CCO.0b013e328341edff
PT - Journal Article
PT - Review
ID - 21150603 [pubmed]
ID - 10.1097/CCO.0b013e328341edff [doi]
PP - ppublish
LG - English
DP - 2011 Mar
DC - 20110210
EZ - 2010/12/15 06:00
DA - 2011/04/09 06:00
DT - 2010/12/15 06:00
YR - 2011
ED - 20110408
RD - 20110210
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=21150603
<312. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 21088057
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Min L
AU - Vaidya A
AU - Becker C
FA - Min, Le
FA - Vaidya, Anand
FA - Becker, Carolyn
IN - Min, Le. Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
TI - Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy.
SO - European Journal of Endocrinology. 164(2):303-7, 2011 Feb
AS - EUR. J. ENDOCRINOL.. 164(2):303-7, 2011 Feb
NJ - European journal of endocrinology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - bxu, 9423848
IO - Eur. J. Endocrinol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080629
OI - Source: NLM. NIHMS367388
SB - Index Medicus
CP - England
MH - Adult
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/im [Immunology]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Female
MH - *Graves Ophthalmopathy/ci [Chemically Induced]
MH - Graves Ophthalmopathy/di [Diagnosis]
MH - Graves Ophthalmopathy/im [Immunology]
MH - Humans
MH - Male
MH - Melanoma/im [Immunology]
MH - *Melanoma/th [Therapy]
MH - Middle Aged
MH - Skin Neoplasms/im [Immunology]
MH - *Skin Neoplasms/th [Therapy]
MH - *Thyroiditis, Autoimmune/ci [Chemically Induced]
MH - Thyroiditis, Autoimmune/di [Diagnosis]
MH - Thyroiditis, Autoimmune/im [Immunology]
AB - OBJECTIVE: Ipilimumab is a fully human MAB against cytotoxic T-lymphocyte antigen 4 (CTLA4). CTLA4 negatively regulates immune cell activation. In patients with metastatic melanoma, ipilimumab increases survival time and induces complete remission in some patients. However, immune-related adverse events including endocrinopathies have been reported. Bevacizumab, an angiogenesis inhibitor, has been used in combination with ipilimumab in patients with advanced melanoma.
AB - PATIENTS AND METHODS: In this study, we report three patients who received ipilimumab alone or combined with bevacizumab therapy and developed thyroiditis, and the first report of euthyroid Graves' ophthalmopathy.
AB - RESULTS: Case 1 is a 51-year-old female who presented with severe eye pain, proptosis, and periorbital edema. Laboratory results revealed normal TSH, elevated thyroid antibodies but low titer of anti-TSH receptor antibody. Imaging was consistent with Graves' ophthalmopathy. Cases 2 and 3 were referred for hyperthyroidism, and workup revealed thyroiditis. These three cases suggest that patients with advanced melanoma treated with ipilimumab +/- bevacizumab may be susceptible to a variety of thyroid disorders.
AB - CONCLUSIONS: Anti-CTLA4 therapy has shown promising results in treating advanced malignancy such as melanoma and renal carcinoma. A number of endocrinopathies, including thyroid disorders, may develop during ipilimumab therapy. The association of bevacizumab with endocrinopathies is not clear, although a few reports suggest a link to hypothyroidism. All patients on ipilimumab and/or bevacizumab therapy should be monitored for signs or symptoms of thyroiditis.
RN - 0 (Antibodies, Monoclonal)
RN - 6T8C155666 (ipilimumab)
ES - 1479-683X
IL - 0804-4643
DI - EJE-10-0833
DO - https://dx.doi.org/10.1530/EJE-10-0833
PT - Case Reports
PT - Journal Article
ID - 21088057 [pubmed]
ID - EJE-10-0833 [pii]
ID - 10.1530/EJE-10-0833 [doi]
ID - PMC4080629 [pmc]
ID - NIHMS367388 [mid]
PP - ppublish
GI - No: F32 HL104776
Organization: (HL) *NHLBI NIH HHS*
Country: United States
No: F32 HL104776-01
Organization: (HL) *NHLBI NIH HHS*
Country: United States
No: K08 HD070957
Organization: (HD) *NICHD NIH HHS*
Country: United States
No: T32 DK007529
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG - English
EP - 20101118
DP - 2011 Feb
DC - 20110119
EZ - 2010/11/20 06:00
DA - 2011/02/22 06:00
DT - 2010/11/20 06:00
YR - 2011
ED - 20110218
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=21088057
<313. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 21220230
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Andre T
AU - Wislez M
AU - Goncalves A
AU - de La Motte Rouge T
AU - Blay JY
AU - Massard C
AU - Bay JO
AU - comite de redaction du Bulletin du Cancer
FA - Andre, T
FA - Wislez, M
FA - Goncalves, A
FA - de La Motte Rouge, T
FA - Blay, J-Y
FA - Massard, C
FA - Bay, J-O
FA - comite de redaction du Bulletin du Cancer
IN - Andre, T. Service d'hepatogastroenterologie, hopital Pitie-Salpetriere, 47-83, boulevard de l'Hopital, 75651 Paris cedex 13, France. thierry.andre@psl.aphp.fr
TI - [Following communications made at American Society of Clinical Oncology 2010, what will change our practice? The point of view of the editorial board of Bulletin du Cancer]. [French]
OT - Suite aux communications faites au congres de l'American Society of Clinical Oncology 2010, qu'est ce qui va changer nos pratiques ? Le point de vue du comite de redaction du Bulletin du cancer.
SO - Bulletin du Cancer. 97(12):1551-62, 2010 Dec
AS - Bull Cancer. 97(12):1551-62, 2010 Dec
NJ - Bulletin du cancer
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 0072416
IO - Bull Cancer
SB - Index Medicus
CP - France
MH - Breast Neoplasms/th [Therapy]
MH - Digestive System Neoplasms/th [Therapy]
MH - Female
MH - Gastrointestinal Stromal Tumors/dt [Drug Therapy]
MH - Genital Neoplasms, Female/dt [Drug Therapy]
MH - Hematologic Neoplasms/th [Therapy]
MH - Humans
MH - Lung Neoplasms/dt [Drug Therapy]
MH - Male
MH - *Medical Oncology/st [Standards]
MH - Melanoma/dt [Drug Therapy]
MH - *Neoplasms/th [Therapy]
MH - *Practice Patterns, Physicians'/st [Standards]
MH - Prostatic Neoplasms/dt [Drug Therapy]
MH - Sarcoma/dt [Drug Therapy]
MH - *Societies, Medical/st [Standards]
MH - Testicular Neoplasms/dt [Drug Therapy]
MH - Thyroid Neoplasms/dt [Drug Therapy]
MH - United States
AB - The congress of Asco made the object of numerous summaries of congress made in the heat of the moment and the Bulletin du Cancer decided to ask to his editorial board, a digested summary, at distance of the congress, to try to sum up the data of the congress which are going to change practice. Of the considerable number of communications, editorial board chose 40 communications which appeared to answer these rules. Best understanding of biological mechanisms and new molecules to inhibit targets allow in certain case, to use therapeutic targeting in the true sense. The identification of the gene of fusion EML4-ALK in lung adenocarcinoma, and its inhibition by the crizotinib, constitute a considerable progress for 5% of patients with this disease. Molecular biology with the mutations of the exon 11 in GIST, allow to better define the population which is going to benefit from adjuvant imatinib. In Advanced non-small cell lung cancer, myeloma and advanced lymphoma, maintenance therapy by monoclonal anti-body or inhibitors of tyrosines kinases showed the proof of their effectiveness. In advanced melanoma, ipilimumab is a light of hope in a pathology in always prognostic is so dark. In metastatic adenocarcinoma of the pancreas, there is finally an alternative to gemcitabine with the Folfirinox regimen, with an improvement of overall survival. Biological personalization of cancer treatments is on the road run but the road is still long.
ES - 1769-6917
IL - 0007-4551
DI - S0007-4551(15)30739-6
DO - https://dx.doi.org/10.1684/bdc.2010.1221
PT - English Abstract
PT - Journal Article
ID - 21220230 [pubmed]
ID - S0007-4551(15)30739-6 [pii]
ID - 10.1684/bdc.2010.1221 [doi]
PP - ppublish
LG - French
DP - 2010 Dec
DC - 20110111
EZ - 2011/01/12 06:00
DA - 2011/02/04 06:00
DT - 2011/01/12 06:00
YR - 2010
ED - 20110203
RD - 20151119
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=21220230
<314. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 21074064
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Kaehler KC
AU - Piel S
AU - Livingstone E
AU - Schilling B
AU - Hauschild A
AU - Schadendorf D
FA - Kaehler, Katharina C
FA - Piel, Sarah
FA - Livingstone, Elisabeth
FA - Schilling, Bastian
FA - Hauschild, Axel
FA - Schadendorf, Dirk
IN - Kaehler, Katharina C. Department of Dermatology and Skin Cancer Center, University Hospital Schleswig-Holtstein, Campus Kiel, Germany.
TI - Update on immunologic therapy with anti-CTLA-4 antibodies in melanoma: identification of clinical and biological response patterns, immune-related adverse events, and their management. [Review][Erratum appears in Semin Oncol. 2012 Oct;39(5):625]
SO - Seminars in Oncology. 37(5):485-98, 2010 Oct
AS - Semin Oncol. 37(5):485-98, 2010 Oct
NJ - Seminars in oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - un5, 0420432
IO - Semin. Oncol.
SB - Index Medicus
CP - United States
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/im [Immunology]
MH - *Antigens, CD/im [Immunology]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/im [Immunology]
MH - Biomarkers/bl [Blood]
MH - C-Reactive Protein/me [Metabolism]
MH - CTLA-4 Antigen
MH - Chemical and Drug Induced Liver Injury/im [Immunology]
MH - Chemical and Drug Induced Liver Injury/th [Therapy]
MH - Digestive System Diseases/ci [Chemically Induced]
MH - Digestive System Diseases/im [Immunology]
MH - Digestive System Diseases/th [Therapy]
MH - Endocrine System Diseases/ci [Chemically Induced]
MH - Endocrine System Diseases/im [Immunology]
MH - Endocrine System Diseases/th [Therapy]
MH - Humans
MH - *Immune System Diseases/ci [Chemically Induced]
MH - Immune System Diseases/th [Therapy]
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - Skin Diseases/ci [Chemically Induced]
MH - Skin Diseases/im [Immunology]
MH - Skin Diseases/th [Therapy]
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/im [Immunology]
AB - Immune-modifying monoclonal antibodies may induce or enhance the natural immune response against tumor cells. The complex interaction between antigen-presenting cells and T lymphocytes as an immune response is strongly affected by anti-CD152 (cytotoxic T-lymphocyte antigen-4, CTLA-4)-antibodies. However, specific CTLA-4 antibodies can block the CTLA-4 receptor and thus induce an unrestrained T-cell activation. To this stage, treatment of patients with metastatic melanoma with the CTLA-4 antibodies ipilimumab and tremelimumab has only been investigated within clinical trials. The results of a phase III trial in patients with advanced disease treated with ipilimumab alone or in combination with a peptide vaccination (gp100) recently presented at the 2010 annual meeting of the Ameircan Society of Clinical Oncology (ASCO) made groundbreaking news as ipilimumab was demonstrated to be the first drug in melanoma treatment to show a significant prolongation of survival time. Patients undergoing treatment with CTLA-4 antibodies may experience immune-related phenomena and adverse events (irAEs) that differ greatly from the well-known adverse events of cytotoxic drugs and which are due to the CTLA-4 antibodies' specific mode of action. This review gives a condensed overview on the mechanisms of action, an update on clinical data of the two CTLA-4 antibodies, ipilimumab and tremelimumab, and detailed recommendations for adverse event management strategies.
AB - Copyright © 2010 Elsevier Inc. All rights reserved.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (Antineoplastic Agents)
RN - 0 (Biomarkers)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 6T8C155666 (ipilimumab)
RN - 9007-41-4 (C-Reactive Protein)
RN - QEN1X95CIX (tremelimumab)
ES - 1532-8708
IL - 0093-7754
DI - S0093-7754(10)00157-0
DO - https://dx.doi.org/10.1053/j.seminoncol.2010.09.003
PT - Journal Article
PT - Review
ID - 21074064 [pubmed]
ID - S0093-7754(10)00157-0 [pii]
ID - 10.1053/j.seminoncol.2010.09.003 [doi]
PP - ppublish
LG - English
DP - 2010 Oct
DC - 20101115
EZ - 2010/11/16 06:00
DA - 2010/12/16 06:00
DT - 2010/11/16 06:00
YR - 2010
ED - 20101214
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=21074064
<315. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 21074058
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Boasberg P
AU - Hamid O
AU - O'Day S
FA - Boasberg, Peter
FA - Hamid, Omid
FA - O'Day, Steven
IN - Boasberg, Peter. The Angeles Clinic & Research Institute, 2001 Santa Monica Blvd, Suite 560W, Santa Monica, CA 90404, USA. pboasberg@theangelesclinic.org
TI - Ipilimumab: unleashing the power of the immune system through CTLA-4 blockade. [Review]
SO - Seminars in Oncology. 37(5):440-9, 2010 Oct
AS - Semin Oncol. 37(5):440-9, 2010 Oct
NJ - Seminars in oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - un5, 0420432
IO - Semin. Oncol.
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antigens, CD/im [Immunology]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - CTLA-4 Antigen
MH - Dacarbazine/ad [Administration & Dosage]
MH - Drug-Related Side Effects and Adverse Reactions
MH - Humans
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/im [Immunology]
AB - Malignant melanoma is rising faster in incidence than any other malignancy. Long-term remission or "cure" is rare and is almost exclusively limited to therapies that stimulate an immune antitumor response. Ipilimumab is a novel targeted human immunostimulatory monoclonal antibody that blocks cytotoxic T-lymphocyte antigen4 (CTLA-4), an immune-inhibitory site expressed on activated T cells. Ipilimumab is well tolerated as an outpatient infusion therapy. Multiple studies have confirmed significant antimelanoma activity. A randomized trial has documented a survival benefit when ipilimumab was compared to a gp-100 vaccine only arm. The unique mechanism of action of ipilimumab makes assessment of response by conventional criteria difficult. Benefit from ipilimumab can occur after what would be considered progression with World Health Oganization (WHO) or Response Evaluation Criteria in Solid Tumors (RECIST) criteria. New immune response criteria have been proposed. Therapeutic responses peak between 12 and 24 weeks, with slow responses continuing up to and beyond 12 months. The major drug- related adverse side effects (10%-15% grade 3 or above) are immune-related and consist most commonly of rash, colitis, hypophysitis, thyroiditis, and hepatitis. Colonic perforation can occur and patients with diarrhea have to be monitored carefully with strict adherence to treatment algorithms. Algorithms for the treatment of other adverse side effects have been developed. The treatment of immune-related side effects with immunosuppressive agents, such as corticosteroids, does not appear to impair antitumor response. With proper monitoring and management of side effects, ipilimumab is an extremely safe drug to administer. The benefits of ipilimumab will most certainly extend to other malignancies in the near future.
AB - Copyright © 2010. Published by Elsevier Inc.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 6T8C155666 (ipilimumab)
RN - 7GR28W0FJI (Dacarbazine)
ES - 1532-8708
IL - 0093-7754
DI - S0093-7754(10)00158-2
DO - https://dx.doi.org/10.1053/j.seminoncol.2010.09.004
PT - Journal Article
PT - Review
ID - 21074058 [pubmed]
ID - S0093-7754(10)00158-2 [pii]
ID - 10.1053/j.seminoncol.2010.09.004 [doi]
PP - ppublish
LG - English
DP - 2010 Oct
DC - 20101115
EZ - 2010/11/16 06:00
DA - 2010/12/16 06:00
DT - 2010/11/16 06:00
YR - 2010
ED - 20101214
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=21074058
<316. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 20455200
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Pinto-Garcia L
AU - Efferth T
AU - Torres A
AU - Hoheisel JD
AU - Youns M
FA - Pinto-Garcia, Lina
FA - Efferth, Thomas
FA - Torres, Amada
FA - Hoheisel, Jorg D
FA - Youns, Mahmoud
IN - Pinto-Garcia, Lina. Department of Functional Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany.
TI - Berberine inhibits cell growth and mediates caspase-independent cell death in human pancreatic cancer cells.
SO - Planta Medica. 76(11):1155-61, 2010 Aug
AS - Planta Med. 76(11):1155-61, 2010 Aug
NJ - Planta medica
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 0066751, p9f
IO - Planta Med.
SB - Index Medicus
CP - Germany
MH - Antineoplastic Agents, Phytogenic/an [Analysis]
MH - *Antineoplastic Agents, Phytogenic/pd [Pharmacology]
MH - Antineoplastic Agents, Phytogenic/tu [Therapeutic Use]
MH - *Apoptosis/de [Drug Effects]
MH - Berberine/an [Analysis]
MH - *Berberine/pd [Pharmacology]
MH - Berberine/tu [Therapeutic Use]
MH - Caspase Inhibitors
MH - Caspases/me [Metabolism]
MH - *Caspases/ph [Physiology]
MH - Cell Line, Tumor
MH - Cell Proliferation/de [Drug Effects]
MH - Enzyme Activation
MH - Gene Expression Profiling
MH - Humans
MH - Immunohistochemistry
MH - Oligonucleotide Array Sequence Analysis
MH - Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - *Pancreatic Neoplasms/pa [Pathology]
MH - RNA, Messenger/me [Metabolism]
MH - Signal Transduction/de [Drug Effects]
AB - Pancreatic cancer is one of the most aggressive human malignancies with an increasing incidence worldwide. In addition to the poor survival rates, combinations using gemcitabine as a backbone have failed to show any benefit beyond monotherapy. These facts underscore an urgent need for novel therapeutic options and motivated us to study the effect of berberine on pancreatic cancer cells. Here, we undertook an mRNA-based gene expression profiling study in order to get deeper insight into the molecular targets mediating the growth inhibitory effects of berberine on pancreatic cancer cells compared to normal ones. Twenty-four hours after treatment, berberine showed preferential selectivity toward pancreatic cancer cells compared to normal ones. Moreover, expression profiling and Ingenuity pathway analysis results showed that the cytotoxicity of berberine was accompanied with an activation of BRCA1-mediated DNA damage response, G1/S and G2/M cell cycle checkpoint regulation, and P53 signalling pathways. The activation of these signalling pathways might be explained by the fact that berberine intercalates DNA and induces DNA strand break through inhibition of topoisomerases and induction of DNA lesions.
AB - Copyright Georg Thieme Verlag KG Stuttgart-New York.
RN - 0 (Antineoplastic Agents, Phytogenic)
RN - 0 (Caspase Inhibitors)
RN - 0 (RNA, Messenger)
RN - 0I8Y3P32UF (Berberine)
RN - EC 3-4-22 (Caspases)
ES - 1439-0221
IL - 0032-0943
DO - https://dx.doi.org/10.1055/s-0030-1249931
PT - Journal Article
ID - 20455200 [pubmed]
ID - 10.1055/s-0030-1249931 [doi]
PP - ppublish
LG - English
EP - 20100507
DP - 2010 Aug
DC - 20100728
EZ - 2010/05/11 06:00
DA - 2010/12/14 06:00
DT - 2010/05/11 06:00
YR - 2010
ED - 20101202
RD - 20131121
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=20455200
<317. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 20734041
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Frankel TL
AU - Burns W
AU - Riley J
AU - Morgan RA
AU - Davis JL
AU - Hanada K
AU - Quezado M
AU - Rosenberg SA
AU - Royal RE
FA - Frankel, Timothy L
FA - Burns, William
FA - Riley, John
FA - Morgan, Richard A
FA - Davis, Jeremy L
FA - Hanada, Kenichi
FA - Quezado, Martha
FA - Rosenberg, Steven A
FA - Royal, Richard E
IN - Frankel, Timothy L. Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
TI - Identification and characterization of a tumor infiltrating CD56(+)/CD16 (-) NK cell subset with specificity for pancreatic and prostate cancer cell lines.
SO - Cancer Immunology, Immunotherapy. 59(12):1757-69, 2010 Dec
AS - Cancer Immunol Immunother. 59(12):1757-69, 2010 Dec
NJ - Cancer immunology, immunotherapy : CII
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cn3, 8605732
IO - Cancer Immunol. Immunother.
SB - Index Medicus
CP - Germany
MH - *Antigens, CD56/an [Analysis]
MH - Cell Line, Tumor
MH - Female
MH - GPI-Linked Proteins
MH - HLA-A2 Antigen/im [Immunology]
MH - Humans
MH - Immunophenotyping
MH - Immunotherapy
MH - Interferon-gamma/bi [Biosynthesis]
MH - *Killer Cells, Natural/im [Immunology]
MH - *Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Male
MH - *Pancreatic Neoplasms/im [Immunology]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Pancreatic Neoplasms/th [Therapy]
MH - *Prostatic Neoplasms/im [Immunology]
MH - Prostatic Neoplasms/pa [Pathology]
MH - Prostatic Neoplasms/th [Therapy]
MH - *Receptors, IgG/an [Analysis]
MH - TNF-Related Apoptosis-Inducing Ligand/ph [Physiology]
AB - In a recent clinical trial, a patient exhibited regression of several pancreatic cancer metastases following the administration of the immune modulator Ipilimumab (anti-CTLA-4 antibody). We sought to characterize the immune cells responsible for this regression. Tumor infiltrating lymphocytes (TIL-2742) and an autologous tumor line (TC-2742) were expanded from a regressing metastatic lesion excised from this patient. Natural killer (NK) cells predominated in the TIL (92% CD56(+)) with few T cells (12% CD3(+)). A majority (88%) of the NK cells were CD56(bright)CD16(-). TIL-2742 secreted IFN-gamma and GM-CSF following co-culture with TC-2742 and major histocompatibility complex mismatched pancreatic tumor lines. After sorting TIL-2742, the purified CD56(+)CD16(-)CD3(-) subset showed reactivity similar to TIL-2742 while the CD56(-)CD16(-)CD3(+) cells exhibited no tumor recognition. In co-culture assays, TIL-2742 and the NK subset expressed high reactivity to several pancreatic and prostate cancer cell lines and could lyse the autologous tumor as well as pancreas and prostate cancer lines. Reactivity was partially abrogated by blockade of TRAIL. We thus identified a unique subset of NK cells (CD56(bright)CD16(dim)) isolated from a regressing metastatic pancreatic cancer in a patient responding to Ipilimumab. This represents the first report of CD56(+)CD16(-) NK cells with apparent specificity for pancreatic and prostate cancer cell lines and associated with tumor regression following the treatment with an immune modulating agent.
RN - 0 (Antigens, CD56)
RN - 0 (FCGR3B protein, human)
RN - 0 (GPI-Linked Proteins)
RN - 0 (HLA-A2 Antigen)
RN - 0 (Receptors, IgG)
RN - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN - 0 (TNFSF10 protein, human)
RN - 82115-62-6 (Interferon-gamma)
ES - 1432-0851
IL - 0340-7004
DO - https://dx.doi.org/10.1007/s00262-010-0897-y
PT - Journal Article
ID - 20734041 [pubmed]
ID - 10.1007/s00262-010-0897-y [doi]
PP - ppublish
PH - 2010/04/13 [received]
PH - 2010/07/22 [accepted]
LG - English
EP - 20100824
DP - 2010 Dec
DC - 20100927
EZ - 2010/08/25 06:00
DA - 2010/10/22 06:00
DT - 2010/08/25 06:00
YR - 2010
ED - 20101021
RD - 20101118
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=20734041
<318. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 20004555
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Van Belle TL
AU - Juntti T
AU - Liao J
AU - von Herrath MG
FA - Van Belle, Tom L
FA - Juntti, Therese
FA - Liao, Jeanette
FA - von Herrath, Matthias G
IN - Van Belle, Tom L. Diabetes Center at San Diego, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
TI - Pre-existing autoimmunity determines type 1 diabetes outcome after Flt3-ligand treatment.
SO - Journal of Autoimmunity. 34(4):445-52, 2010 Jun
AS - J Autoimmun. 34(4):445-52, 2010 Jun
NJ - Journal of autoimmunity
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - adl, 8812164
IO - J. Autoimmun.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860005
OI - Source: NLM. NIHMS160979
SB - Index Medicus
CP - England
MH - Animals
MH - *Autoimmunity
MH - CD8-Positive T-Lymphocytes/cy [Cytology]
MH - CD8-Positive T-Lymphocytes/im [Immunology]
MH - Cell Proliferation
MH - Dendritic Cells/cy [Cytology]
MH - *Diabetes Mellitus, Type 1/dt [Drug Therapy]
MH - Humans
MH - Islets of Langerhans/im [Immunology]
MH - *Membrane Proteins/tu [Therapeutic Use]
MH - Mice
MH - Mice, Inbred NOD
MH - T-Lymphocytes, Regulatory/cy [Cytology]
MH - Treatment Outcome
AB - Redirection of immune responses by manipulation of antigen-presenting cells is an emerging strategy for immunosuppressive treatment of autoimmune diseases. In vivo expansion of dendritic cells (DC) by Fms-like tyrosine kinase-3 (Flt3)-Ligand (FL) treatment was shown to delay diabetes onset in the NOD model of autoimmune diabetes. However, we show here that Flt3 stimulation actually accelerates autoimmunity when autoreactive CD8 T cells are detectable in blood prior to treatment. With autoreactive CD8 cells present, the capacity of FL to expand DCs and induce Treg remained intact, but both numbers and the functional response of islet-specific CD8s were boosted. Also, the inhibitory receptor PD-1 on (autoreactive) CD8 T cells and its ligand PD-L1 on Treg were no longer upregulated. These data highlight the need to pre-screen for T cell autoreactivity prior to generalized DC expansion and illustrate how accelerated disease can occur when the intended initiation of regulatory mechanisms is impaired later in diabetogenesis.
RN - 0 (Membrane Proteins)
RN - 0 (flt3 ligand protein)
ES - 1095-9157
IL - 0896-8411
DI - S0896-8411(09)00150-4
DO - https://dx.doi.org/10.1016/j.jaut.2009.11.010
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 20004555 [pubmed]
ID - S0896-8411(09)00150-4 [pii]
ID - 10.1016/j.jaut.2009.11.010 [doi]
ID - PMC2860005 [pmc]
ID - NIHMS160979 [mid]
PP - ppublish
PH - 2009/10/26 [received]
PH - 2009/11/13 [revised]
PH - 2009/11/16 [accepted]
GI - No: R01 AI044451-08
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: R01 AI044451
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: R01 DK066346-05S1
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: R01 DK066346
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: P01 AI058105
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: P01 AI058105-05
Organization: (AI) *NIAID NIH HHS*
Country: United States
LG - English
EP - 20091209
DP - 2010 Jun
DC - 20100426
EZ - 2009/12/17 06:00
DA - 2010/08/14 06:00
DT - 2009/12/17 06:00
YR - 2010
ED - 20100813
RD - 20161215
UP - 20161221
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=20004555
<319. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 20004555
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Van Belle TL
AU - Juntti T
AU - Liao J
AU - von Herrath MG
FA - Van Belle, Tom L
FA - Juntti, Therese
FA - Liao, Jeanette
FA - von Herrath, Matthias G
IN - Van Belle, Tom L. Diabetes Center at San Diego, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
TI - Pre-existing autoimmunity determines type 1 diabetes outcome after Flt3-ligand treatment.
SO - Journal of Autoimmunity. 34(4):445-52, 2010 Jun
AS - J Autoimmun. 34(4):445-52, 2010 Jun
NJ - Journal of autoimmunity
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - adl, 8812164
IO - J. Autoimmun.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860005
OI - Source: NLM. NIHMS160979
SB - Index Medicus
CP - England
MH - Animals
MH - *Autoimmunity
MH - CD8-Positive T-Lymphocytes/cy [Cytology]
MH - CD8-Positive T-Lymphocytes/im [Immunology]
MH - Cell Proliferation
MH - Dendritic Cells/cy [Cytology]
MH - *Diabetes Mellitus, Type 1/dt [Drug Therapy]
MH - Humans
MH - Islets of Langerhans/im [Immunology]
MH - *Membrane Proteins/tu [Therapeutic Use]
MH - Mice
MH - Mice, Inbred NOD
MH - T-Lymphocytes, Regulatory/cy [Cytology]
MH - Treatment Outcome
AB - Redirection of immune responses by manipulation of antigen-presenting cells is an emerging strategy for immunosuppressive treatment of autoimmune diseases. In vivo expansion of dendritic cells (DC) by Fms-like tyrosine kinase-3 (Flt3)-Ligand (FL) treatment was shown to delay diabetes onset in the NOD model of autoimmune diabetes. However, we show here that Flt3 stimulation actually accelerates autoimmunity when autoreactive CD8 T cells are detectable in blood prior to treatment. With autoreactive CD8 cells present, the capacity of FL to expand DCs and induce Treg remained intact, but both numbers and the functional response of islet-specific CD8s were boosted. Also, the inhibitory receptor PD-1 on (autoreactive) CD8 T cells and its ligand PD-L1 on Treg were no longer upregulated. These data highlight the need to pre-screen for T cell autoreactivity prior to generalized DC expansion and illustrate how accelerated disease can occur when the intended initiation of regulatory mechanisms is impaired later in diabetogenesis.
RN - 0 (Membrane Proteins)
RN - 0 (flt3 ligand protein)
ES - 1095-9157
IL - 0896-8411
DI - S0896-8411(09)00150-4
DO - https://dx.doi.org/10.1016/j.jaut.2009.11.010
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 20004555 [pubmed]
ID - S0896-8411(09)00150-4 [pii]
ID - 10.1016/j.jaut.2009.11.010 [doi]
ID - PMC2860005 [pmc]
ID - NIHMS160979 [mid]
PP - ppublish
PH - 2009/10/26 [received]
PH - 2009/11/13 [revised]
PH - 2009/11/16 [accepted]
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00445913
SL - https://clinicaltrials.gov/search/term=NCT00445913
GI - No: R01 AI044451-08
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: R01 AI044451
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: R01 DK066346-05S1
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: R01 DK066346
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: P01 AI058105
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: P01 AI058105-05
Organization: (AI) *NIAID NIH HHS*
Country: United States
LG - English
EP - 20091209
DP - 2010 Jun
DC - 20100426
EZ - 2009/12/17 06:00
DA - 2010/08/14 06:00
DT - 2009/12/17 06:00
YR - 2010
ED - 20100813
RD - 20161206
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=20004555
<320. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 20501833
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Morgan MA
AU - Parsels LA
AU - Zhao L
AU - Parsels JD
AU - Davis MA
AU - Hassan MC
AU - Arumugarajah S
AU - Hylander-Gans L
AU - Morosini D
AU - Simeone DM
AU - Canman CE
AU - Normolle DP
AU - Zabludoff SD
AU - Maybaum J
AU - Lawrence TS
FA - Morgan, Meredith A
FA - Parsels, Leslie A
FA - Zhao, Lili
FA - Parsels, Joshua D
FA - Davis, Mary A
FA - Hassan, Maria C
FA - Arumugarajah, Sankari
FA - Hylander-Gans, Linda
FA - Morosini, Deborah
FA - Simeone, Diane M
FA - Canman, Christine E
FA - Normolle, Daniel P
FA - Zabludoff, Sonya D
FA - Maybaum, Jonathan
FA - Lawrence, Theodore S
IN - Morgan, Meredith A. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109-5637, USA. mmccrack@med.umich.edu
TI - Mechanism of radiosensitization by the Chk1/2 inhibitor AZD7762 involves abrogation of the G2 checkpoint and inhibition of homologous recombinational DNA repair.
SO - Cancer Research. 70(12):4972-81, 2010 Jun 15
AS - Cancer Res. 70(12):4972-81, 2010 Jun 15
NJ - Cancer research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cnf, 2984705r
IO - Cancer Res.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889008
OI - Source: NLM. NIHMS201260
SB - Index Medicus
CP - United States
MH - Adenocarcinoma/dt [Drug Therapy]
MH - Adenocarcinoma/me [Metabolism]
MH - Adenocarcinoma/pa [Pathology]
MH - Animals
MH - Blotting, Western
MH - Cell Line, Tumor
MH - Checkpoint Kinase 1
MH - Checkpoint Kinase 2
MH - DNA Damage/de [Drug Effects]
MH - DNA Damage/re [Radiation Effects]
MH - *DNA Repair/de [Drug Effects]
MH - DNA Repair/re [Radiation Effects]
MH - Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Drug Therapy, Combination
MH - Flow Cytometry
MH - Fluorescent Antibody Technique
MH - *G2 Phase/de [Drug Effects]
MH - G2 Phase/re [Radiation Effects]
MH - Gamma Rays
MH - Humans
MH - Immunoblotting
MH - Immunoenzyme Techniques
MH - Mice
MH - Mice, Inbred NOD
MH - Mice, SCID
MH - Pancreatic Neoplasms/me [Metabolism]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - *Pancreatic Neoplasms/rt [Radiotherapy]
MH - *Protein Kinase Inhibitors/pd [Pharmacology]
MH - Protein Kinases/ch [Chemistry]
MH - Protein Kinases/me [Metabolism]
MH - *Protein-Serine-Threonine Kinases/ai [Antagonists & Inhibitors]
MH - RNA, Messenger/ge [Genetics]
MH - RNA, Messenger/me [Metabolism]
MH - Rad51 Recombinase/me [Metabolism]
MH - *Radiation-Sensitizing Agents/pd [Pharmacology]
MH - Recombination, Genetic/de [Drug Effects]
MH - Recombination, Genetic/re [Radiation Effects]
MH - Reverse Transcriptase Polymerase Chain Reaction
MH - *Thiophenes/pd [Pharmacology]
MH - *Urea/aa [Analogs & Derivatives]
MH - Urea/pd [Pharmacology]
MH - Xenograft Model Antitumor Assays
AB - The median survival for patients with locally advanced pancreatic cancer treated with gemcitabine and radiation is approximately 1 year. To develop improved treatment, we have combined a Chk1/2-targeted agent, AZD7762, currently in phase I clinical trials, with gemcitabine and ionizing radiation in preclinical pancreatic tumor models. We found that in vitro AZD7762 alone or in combination with gemcitabine significantly sensitized MiaPaCa-2 cells to radiation. AZD7762 inhibited Chk1 autophosphorylation (S296 Chk1), stabilized Cdc25A, and increased ATR/ATM-mediated Chk1 phosphorylation (S345 Chk1). Radiosensitization by AZD7762 was associated with abrogation of the G(2) checkpoint as well as with inhibition of Rad51 focus formation, inhibition of homologous recombination repair, and persistent gamma-H2AX expression. AZD7762 was also a radiation sensitizer in multiple tumor xenograft models. In both MiaPaCa-2- and patient-derived xenografts, AZD7762 significantly prolonged the median time required for tumor volume doubling in response to gemcitabine and radiation. Together, our findings suggest that G(2) checkpoint abrogation and homologous recombination repair inhibition both contribute to sensitization by Chk1 inhibition. Furthermore, they support the clinical use of AZD7762 in combination with gemcitabine and radiation for patients with locally advanced pancreatic cancer.
RN - 0 (3-(carbamoylamino)-5-(3-fluorophenyl)-N-(3-piperidyl)thiophene-2-carboxamide)
RN - 0 (Protein Kinase Inhibitors)
RN - 0 (RNA, Messenger)
RN - 0 (Radiation-Sensitizing Agents)
RN - 0 (Thiophenes)
RN - 0W860991D6 (Deoxycytidine)
RN - 8W8T17847W (Urea)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7 (Protein Kinases)
RN - EC 2-7-1-11 (Checkpoint Kinase 2)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (CHEK2 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
RN - EC 2-7-11-1 (Chek1 protein, mouse)
RN - EC 2-7-11-1 (Chek2 protein, mouse)
RN - EC 2-7-11-1 (Protein-Serine-Threonine Kinases)
RN - EC 2-7-7 (Rad51 Recombinase)
ES - 1538-7445
IL - 0008-5472
DI - 0008-5472.CAN-09-3573
DO - https://dx.doi.org/10.1158/0008-5472.CAN-09-3573
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 20501833 [pubmed]
ID - 0008-5472.CAN-09-3573 [pii]
ID - 10.1158/0008-5472.CAN-09-3573 [doi]
ID - PMC2889008 [pmc]
ID - NIHMS201260 [mid]
PP - ppublish
GI - No: P30 CA046592
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01CA78554
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA138723
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA078554-11
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA078554
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA046592-22S39027
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20100525
DP - 2010 Jun 15
DC - 20100616
EZ - 2010/05/27 06:00
DA - 2010/07/23 06:00
DT - 2010/05/27 06:00
YR - 2010
ED - 20100722
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=20501833
<321. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 18577252
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Selvakumar E
AU - Hsieh TC
FA - Selvakumar, Elangovan
FA - Hsieh, Tze-Chen
IN - Selvakumar, Elangovan. Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, USA. eselva@gmail.com
TI - Regulation of cell cycle transition and induction of apoptosis in HL-60 leukemia cells by lipoic acid: role in cancer prevention and therapy.
SO - Journal of hematology & oncology. 1:4, 2008 May 30
AS - J Hematol Oncol. 1:4, 2008 May 30
NJ - Journal of hematology & oncology
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101468937
IO - J Hematol Oncol
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2438439
SB - Index Medicus
CP - England
MH - *Anticarcinogenic Agents/pd [Pharmacology]
MH - Anticarcinogenic Agents/tu [Therapeutic Use]
MH - *Apoptosis/de [Drug Effects]
MH - Apoptosis Inducing Factor/me [Metabolism]
MH - *Cell Cycle/de [Drug Effects]
MH - Cytochromes c/me [Metabolism]
MH - HL-60 Cells
MH - Humans
MH - *Leukemia/pc [Prevention & Control]
MH - Poly(ADP-ribose) Polymerases/me [Metabolism]
MH - Protein Transport/de [Drug Effects]
MH - Proto-Oncogene Proteins c-bcl-2/me [Metabolism]
MH - *Thioctic Acid/pd [Pharmacology]
MH - Thioctic Acid/tu [Therapeutic Use]
MH - bcl-2-Associated X Protein/me [Metabolism]
AB - BACKGROUND: Lipoic acid (LA), a potent antioxidant, has been used as a dietary supplement to prevent and treat many diseases, including stroke, diabetes, neurodegenerative and hepatic disorders. Recently, potent anti-tumorigenic effects induced by LA were also reported and evident as assayed by suppression of cell proliferation and induction of apoptosis in malignant cells. However, the mechanism by which LA elicits its chemopreventive effects remains unclear.
AB - METHODS AND RESULTS: Herein, we investigated whether LA elicits its anti-tumor effects by inducing cell cycle arrest and cell death in human promyelocytic HL-60 cells. The results showed that LA inhibits both cell growth and viability in a time- and dose-dependent manner. Disruption of the G1/S and G2/M phases of cell cycle progression accompanied by the induction of apoptosis was also observed following LA treatment. Cell cycle arrest by LA was correlated with dose-dependent down regulation of Rb phosphorylation, likely via suppression of E2F-dependent cell cycle progression with an accompanying inhibition of cyclin E/cdk2 and cyclin B1/cdk1 levels. Evidence supporting the induction of apoptosis by LA was based on the appearance of sub-G1 peak in flow cytometry analysis and the cleavage of poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the 89-kDa truncated product in immunoblot assays. Apoptosis elicited by LA was preceded by diminution in the expression of anti-apoptotic protein bcl-2 and increased expression of apoptogenic protein bax, and also the release and translocation of apoptosis inducing factor AIF and cytochrome c from the mitochondria to the nucleus, without altering the subcellular distribution of the caspases.
AB - CONCLUSION: This study provides evidence that LA induces multiple cell cycle checkpoint arrest and caspase-independent cell death in HL-60 cells, in support of its efficacious potential as a chemopreventive agent.
RN - 0 (Anticarcinogenic Agents)
RN - 0 (Apoptosis Inducing Factor)
RN - 0 (Proto-Oncogene Proteins c-bcl-2)
RN - 0 (bcl-2-Associated X Protein)
RN - 73Y7P0K73Y (Thioctic Acid)
RN - 9007-43-6 (Cytochromes c)
RN - EC 2-4-2-30 (Poly(ADP-ribose) Polymerases)
ES - 1756-8722
IL - 1756-8722
DI - 1756-8722-1-4
DO - https://dx.doi.org/10.1186/1756-8722-1-4
PT - Journal Article
ID - 18577252 [pubmed]
ID - 1756-8722-1-4 [pii]
ID - 10.1186/1756-8722-1-4 [doi]
ID - PMC2438439 [pmc]
PP - epublish
PH - 2008/04/30 [received]
PH - 2008/05/30 [accepted]
LG - English
EP - 20080530
DP - 2008 May 30
DC - 20080625
EZ - 2008/06/26 09:00
DA - 2010/06/04 06:00
DT - 2008/06/26 09:00
YR - 2008
ED - 20100603
RD - 20140903
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=18577252
<322. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 20385810
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Matsuzaki J
AU - Gnjatic S
AU - Mhawech-Fauceglia P
AU - Beck A
AU - Miller A
AU - Tsuji T
AU - Eppolito C
AU - Qian F
AU - Lele S
AU - Shrikant P
AU - Old LJ
AU - Odunsi K
FA - Matsuzaki, Junko
FA - Gnjatic, Sacha
FA - Mhawech-Fauceglia, Paulette
FA - Beck, Amy
FA - Miller, Austin
FA - Tsuji, Takemasa
FA - Eppolito, Cheryl
FA - Qian, Feng
FA - Lele, Shashikant
FA - Shrikant, Protul
FA - Old, Lloyd J
FA - Odunsi, Kunle
IN - Matsuzaki, Junko. Departments of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
TI - Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer.
SO - Proceedings of the National Academy of Sciences of the United States of America. 107(17):7875-80, 2010 Apr 27
AS - Proc Natl Acad Sci U S A. 107(17):7875-80, 2010 Apr 27
NJ - Proceedings of the National Academy of Sciences of the United States of America
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - pv3, 7505876
IO - Proc. Natl. Acad. Sci. U.S.A.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867907
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/pd [Pharmacology]
MH - *Antigens, CD/me [Metabolism]
MH - Antigens, Neoplasm/im [Immunology]
MH - *Antigens, Neoplasm/me [Metabolism]
MH - *Apoptosis Regulatory Proteins/me [Metabolism]
MH - CD8-Positive T-Lymphocytes/im [Immunology]
MH - *CD8-Positive T-Lymphocytes/me [Metabolism]
MH - Cytokines/me [Metabolism]
MH - Enzyme-Linked Immunosorbent Assay
MH - Female
MH - *Gene Expression Regulation, Neoplastic/im [Immunology]
MH - Humans
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - *Lymphocytes, Tumor-Infiltrating/me [Metabolism]
MH - Membrane Proteins/im [Immunology]
MH - *Membrane Proteins/me [Metabolism]
MH - *Ovarian Neoplasms/im [Immunology]
MH - Programmed Cell Death 1 Receptor
MH - Signal Transduction/de [Drug Effects]
MH - Signal Transduction/im [Immunology]
AB - NY-ESO-1 is a "cancer-testis" antigen frequently expressed in epithelial ovarian cancer (EOC) and is among the most immunogenic tumor antigens defined to date. In an effort to understand in vivo tolerance mechanisms, we assessed the phenotype and function of NY-ESO-1-specific CD8(+) T cells derived from peripheral blood lymphocytes (PBLs), tumor-infiltrating lymphocytes (TILs), and tumor-associated lymphocytes (TALs) of EOC patients with NY-ESO-1-expressing tumors, with or without humoral immunity to NY-ESO-1. Whereas NY-ESO-1-specific CD8(+) T cells were readily detectable ex vivo with tetramers in TILs and TALs of seropositive patients, they were only detectable in PBLs following in vitro stimulation. Compared with PBLs, tumor-derived NY-ESO-1-specific CD8(+) T cells demonstrated impaired effector function, preferential usage of dominant T-cell receptor, and enriched coexpression of inhibitory molecules LAG-3 and PD-1. Expression of LAG-3 and PD-1 on CD8(+) T cells was up-regulated by IL-10, IL-6 (cytokines found in tumor ascites), and tumor-derived antigen-presenting cells. Functionally, CD8(+)LAG-3(+)PD-1(+) T cells were more impaired in IFN-gamma/TNF-alpha production compared with LAG-3(+)PD-1(-) or LAG-3(-)PD-1(-) subsets. Dual blockade of LAG-3 and PD-1 during T-cell priming efficiently augmented proliferation and cytokine production by NY-ESO-1-specific CD8(+) T cells, indicating that antitumor function of NY-ESO-1-specific CD8(+) T cells could potentially be improved by therapeutic targeting of these inhibitory receptors.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (Antigens, Neoplasm)
RN - 0 (Apoptosis Regulatory Proteins)
RN - 0 (CD223 antigen)
RN - 0 (CTAG1B protein, human)
RN - 0 (Cytokines)
RN - 0 (Membrane Proteins)
RN - 0 (PDCD1 protein, human)
RN - 0 (Programmed Cell Death 1 Receptor)
ES - 1091-6490
IL - 0027-8424
DI - 1003345107
DO - https://dx.doi.org/10.1073/pnas.1003345107
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 20385810 [pubmed]
ID - 1003345107 [pii]
ID - 10.1073/pnas.1003345107 [doi]
ID - PMC2867907 [pmc]
PP - ppublish
LG - English
EP - 20100412
DP - 2010 Apr 27
DC - 20100428
EZ - 2010/04/14 06:00
DA - 2010/06/03 06:00
DT - 2010/04/14 06:00
YR - 2010
ED - 20100602
RD - 20141203
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=20385810
<323. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 19162512
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Schmelz HU
AU - Port M
AU - Stockinger M
AU - Ruf C
AU - Martinscheck A
AU - Sparwasser C
AU - Weidner W
AU - Abend M
FA - Schmelz, Hans U
FA - Port, Matthias
FA - Stockinger, Markus
FA - Ruf, Christian
FA - Martinscheck, Andreas
FA - Sparwasser, Christoph
FA - Weidner, Wolfgang
FA - Abend, Michael
IN - Schmelz, Hans U. Department of Urology, Federal Armed Forces Hospital, Koblenz, Germany. Hans.U.Schmelz@web.de
TI - Testis cancer cells have a genetic determination for a high sensitivity to apoptosis inducing stimuli.
SO - Urologic Oncology. 28(1):49-58, 2010 Jan-Feb
AS - UROL. ONCOL.. 28(1):49-58, 2010 Jan-Feb
NJ - Urologic oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9805460
IO - Urol. Oncol.
SB - Index Medicus
CP - United States
MH - Adult
MH - *Apoptosis/ge [Genetics]
MH - Biopsy
MH - Gene Expression Regulation
MH - Humans
MH - Male
MH - *Testicular Neoplasms/ge [Genetics]
MH - *Testicular Neoplasms/pa [Pathology]
MH - Young Adult
AB - OBJECTIVE: The effect of cytotoxic therapy in testicular tumors (TGCT) has been shown to be mediated mainly by the induction of apoptosis. So far, it is not known which genes play a role for this inherent sensitivity to apoptosis inducing drugs. The aim of this study was to investigate the differential gene expression of apoptosis regulating genes in testicular tumors and in normal testis tissue using a quantitative method. As a premature S-phase entry was shown to induce apoptosis, genes controlling the G1/S-phase checkpoint were also investigated.
AB - MATERIAL AND METHODS: Gene expression levels of a representative subset of 19 genes involved in apoptosis and cell cycle control were investigated in vivo in 19 TGCTs using real-time quantitative PCR. Measurements were performed in tumor tissues of both tumor entities, seminomatous and non-seminomatous tumors (SGCT and NSGCT), and in corresponding biopsies from the unaffected site of the resected testis.
AB - RESULTS: There was an up-regulation of genes that play a role in facilitating apoptosis, such as FasL, TRAIL, and Bax in both tumor entities. Genes inhibiting apoptosis, such as Bcl-2 were predominantly down-regulated. Regarding cell cycle regulators, a gene expression profile was found that corresponds to a premature S phase entry and subsequent apoptosis induction.
AB - CONCLUSION: This study for the first time identified in vivo a panel of genes that give TGCT an inherent sensitivity to apoptotic stimuli after exposure to DNA damaging agents. Studies on these genes in therapy-refractory cancers should provide further insight into the mechanisms of chemotherapy resistance. Furthermore, these genes are promising targets for a future targeted therapy of testis cancer.
AB - Copyright 2010 Elsevier Inc. All rights reserved.
ES - 1873-2496
IL - 1078-1439
DI - S1078-1439(08)00328-1
DO - https://dx.doi.org/10.1016/j.urolonc.2008.11.003
PT - Journal Article
ID - 19162512 [pubmed]
ID - S1078-1439(08)00328-1 [pii]
ID - 10.1016/j.urolonc.2008.11.003 [doi]
PP - ppublish
PH - 2008/05/06 [received]
PH - 2008/11/05 [revised]
PH - 2008/11/08 [accepted]
LG - English
EP - 20090122
DP - 2010 Jan-Feb
DC - 20100203
EZ - 2009/01/24 09:00
DA - 2010/05/26 06:00
DT - 2009/01/24 09:00
YR - 2010
ED - 20100525
RD - 20100203
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=19162512
<324. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 19639414
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Dillard T
AU - Yedinak CG
AU - Alumkal J
AU - Fleseriu M
FA - Dillard, Troy
FA - Yedinak, Chris G
FA - Alumkal, Joshi
FA - Fleseriu, Maria
IN - Dillard, Troy. Department of Medicine, Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health & Science University, Portland, OR, USA.
TI - Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes. [Review] [41 refs]
SO - Pituitary. 13(1):29-38, 2010
AS - Pituitary. 13(1):29-38, 2010
NJ - Pituitary
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dsi, 9814578
IO - Pituitary
SB - Index Medicus
CP - United States
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antigens, CD/im [Immunology]
MH - Autoimmune Diseases/di [Diagnosis]
MH - Autoimmune Diseases/et [Etiology]
MH - Autoimmune Diseases/th [Therapy]
MH - CTLA-4 Antigen
MH - Carcinoma, Renal Cell/co [Complications]
MH - Carcinoma, Renal Cell/dt [Drug Therapy]
MH - Humans
MH - Male
MH - Melanoma/co [Complications]
MH - Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - Pituitary Diseases/ci [Chemically Induced]
MH - Pituitary Diseases/di [Diagnosis]
MH - *Pituitary Diseases/im [Immunology]
MH - Pituitary Diseases/th [Therapy]
MH - Prostatic Neoplasms/co [Complications]
MH - Prostatic Neoplasms/dt [Drug Therapy]
AB - Anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) therapies represent a novel approach to cancer treatment via disruption of immune tolerance to antigens located on tumor cells. Disruption of immune tolerance, however, may occur at a cost. A host of immune related adverse events (IRAEs) are associated with anti-CTLA-4 therapy. Autoimmune hypophysitis has been reported in up to 17% of patients with melanoma and renal cell carcinoma treated with this therapy. Familiarity with the spectrum of IRAEs connected to these therapies is paramount for endocrinologists, oncologists and those involved in the care of these subjects. We review here key aspects of diagnosis and treatment of anti-CTLA-4 antibody therapy resultant IRAEs. We describe the first two cases of hypopituitarism in prostate cancer subjects undergoing experimental therapy with ipilimumab. The clinical evidence strongly suggests that the prostate cancer subjects developed autoimmune hypophysitis as a consequence of anti-CTLA-4 treatment. High dose glucocorticoid treatment resulted in markedly improved symptoms, and resolution of focal symptoms and diabetes insipidus. One subject recovered pituitary-thyroid axis function after 9 months; however, both continue to require GC replacement. These cases highlight the importance of early screening and treatment for hypopituitarism in all subjects undergoing treatment with anti-CTLA-4 therapy to prevent a potentially fatal outcome from secondary adrenal insufficiency, a readily treatable disease. We recommend mandatory long term follow-up to monitor the development of other hormonal deficits. [References: 41]
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 6T8C155666 (ipilimumab)
ES - 1573-7403
IL - 1386-341X
DO - https://dx.doi.org/10.1007/s11102-009-0193-z
PT - Case Reports
PT - Journal Article
PT - Review
ID - 19639414 [pubmed]
ID - 10.1007/s11102-009-0193-z [doi]
PP - ppublish
PH - 2009/06/12 [received]
PH - 2009/07/19 [accepted]
LG - English
EP - 20090729
DP - 2010
DC - 20100118
EZ - 2009/07/30 09:00
DA - 2010/05/14 06:00
DT - 2009/07/30 09:00
YR - 2010
ED - 20100513
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=19639414
<325. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 20412757
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Ziegler AG
AU - Nepom GT
FA - Ziegler, Anette-G
FA - Nepom, Gerald T
IN - Ziegler, Anette-G. Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universitat Munchen, Kolner Platz 1, 80804 Munchen, Germany. anziegler@lrz.uni-muenchen.de
TI - Prediction and pathogenesis in type 1 diabetes. [Review] [98 refs]
SO - Immunity. 32(4):468-78, 2010 Apr 23
AS - Immunity. 32(4):468-78, 2010 Apr 23
NJ - Immunity
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - ccf, 9432918
IO - Immunity
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861716
OI - Source: NLM. NIHMS195204
SB - Index Medicus
CP - United States
MH - Animals
MH - Biomarkers
MH - *Diabetes Mellitus, Type 1/et [Etiology]
MH - *Diabetes Mellitus, Type 1/ge [Genetics]
MH - Diabetes Mellitus, Type 1/im [Immunology]
MH - *Genetic Predisposition to Disease
MH - Genetic Variation
MH - Humans
MH - Risk Factors
AB - A combination of genetic and immunological features is useful for prediction of autoimmune diabetes. Patterns of immune response correspond to the progression from a preclinical phase of disease to end-stage islet damage, with biomarkers indicating transition from susceptibility to active autoimmunity, and to a final loss of immune regulation. Here, we review the markers that provide evidence for immunological checkpoint failure and that also provide tools for assessment of individualized disease risk. When viewed in the context of genetic variation that influences immune response thresholds, progression from susceptibility to overt disease displays predictable modalities of clinical presentation resulting from a sequential series of failed homeostatic checkpoints for selection and activation of immunity.
AB - Copyright 2010 Elsevier Inc. All rights reserved. [References: 98]
RN - 0 (Biomarkers)
ES - 1097-4180
IL - 1074-7613
DI - S1074-7613(10)00125-1
DO - https://dx.doi.org/10.1016/j.immuni.2010.03.018
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Review
ID - 20412757 [pubmed]
ID - S1074-7613(10)00125-1 [pii]
ID - 10.1016/j.immuni.2010.03.018 [doi]
ID - PMC2861716 [pmc]
ID - NIHMS195204 [mid]
PP - ppublish
PH - 2010/03/15 [received]
PH - 2010/03/15 [revised]
PH - 2010/03/30 [accepted]
GI - No: U19 AI050864
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: U19 AI050864-090001
Organization: (AI) *NIAID NIH HHS*
Country: United States
LG - English
DP - 2010 Apr 23
DC - 20100423
EZ - 2010/04/24 06:00
DA - 2010/05/07 06:00
DT - 2010/04/24 06:00
YR - 2010
ED - 20100506
RD - 20161122
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=20412757
<326. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 20042274
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Zuco V
AU - Benedetti V
AU - Zunino F
FA - Zuco, Valentina
FA - Benedetti, Valentina
FA - Zunino, Franco
IN - Zuco, Valentina. Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, 20133 Milan, Italy.
TI - ATM- and ATR-mediated response to DNA damage induced by a novel camptothecin, ST1968.
SO - Cancer Letters. 292(2):186-96, 2010 Jun 28
AS - Cancer Lett. 292(2):186-96, 2010 Jun 28
NJ - Cancer letters
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 7600053, cmx
IO - Cancer Lett.
SB - Index Medicus
CP - Ireland
MH - Ataxia Telangiectasia Mutated Proteins
MH - *Camptothecin/aa [Analogs & Derivatives]
MH - Camptothecin/pd [Pharmacology]
MH - Carcinoma, Squamous Cell/pa [Pathology]
MH - Cell Cycle
MH - *Cell Cycle Proteins/ph [Physiology]
MH - Cell Line, Tumor
MH - *DNA Damage
MH - *DNA-Binding Proteins/ph [Physiology]
MH - Female
MH - Humans
MH - Infrared Rays
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Protein-Serine-Threonine Kinases/ph [Physiology]
MH - *Tumor Suppressor Proteins/ph [Physiology]
MH - Ultraviolet Rays
AB - DNA damage response and checkpoint activation are expected to influence the sensitivity to DNA-damaging agents. This study was designed to investigate the DNA damage response to the novel camptothecin, ST1968, in two tumor cell lines with a different biological background (A2780 and KB), which underwent distinct cell cycle perturbations and cell death modalities. Following treatment with the camptothecin or ionizing radiation, both inducing double-strand DNA breaks, the ovarian carcinoma A2780 cells exhibited activation of the ATM-Chk2 pathway and early induction of apoptosis. In contrast, the squamous carcinoma KB cells exhibited activation of ATR-Chk1 pathway, a persistent G(2)/M-phase arrest, cellular senescence, mitotic catastrophe and delayed apoptosis, suggesting a defective ATM pathway. The cellular response to UV-induced DNA damage, which activates ATR-Chk1 pathway, was similar in the two cell lines exhibiting early apoptosis induction. Inhibition of ATM in A2780 cells, resulting in reduced phosphorylation of Chk2, enhanced ST1968-induced apoptosis, but had no effect in KB cells. The susceptibility to camptothecin-induced apoptosis of A2780 cells was likely p53-dependent but not related to the activation of the ATM pathway. In contrast, the inhibition of Chk1 enhanced apoptosis response in KB cell but not in A2780. Thus, depending on the biological context, the camptothecin activated ATM-Chk2 or ATR-Chk1 pathways, both having a protective role. In conclusion, our results are consistent with the interpretation that the modality of cell death response is not the critical determinant of sensitivity to camptothecins, and support the interest of inhibition of checkpoint kinases to improve the efficacy of camptothecins.
AB - Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
RN - 0 (Cell Cycle Proteins)
RN - 0 (DNA-Binding Proteins)
RN - 0 (Tumor Suppressor Proteins)
RN - 0 (namitecan)
RN - EC 2-7-11-1 (ATM protein, human)
RN - EC 2-7-11-1 (ATR protein, human)
RN - EC 2-7-11-1 (Ataxia Telangiectasia Mutated Proteins)
RN - EC 2-7-11-1 (Protein-Serine-Threonine Kinases)
RN - XT3Z54Z28A (Camptothecin)
ES - 1872-7980
IL - 0304-3835
DI - S0304-3835(09)00694-6
DO - https://dx.doi.org/10.1016/j.canlet.2009.12.001
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 20042274 [pubmed]
ID - S0304-3835(09)00694-6 [pii]
ID - 10.1016/j.canlet.2009.12.001 [doi]
PP - ppublish
PH - 2009/10/15 [received]
PH - 2009/11/30 [revised]
PH - 2009/12/01 [accepted]
LG - English
EP - 20091229
DP - 2010 Jun 28
DC - 20100420
EZ - 2010/01/01 06:00
DA - 2010/05/05 06:00
DT - 2010/01/01 06:00
YR - 2010
ED - 20100504
RD - 20131121
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=20042274
<327. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 19676051
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Zuco V
AU - Benedetti V
AU - De Cesare M
AU - Zunino F
FA - Zuco, Valentina
FA - Benedetti, Valentina
FA - De Cesare, Michelandrea
FA - Zunino, Franco
IN - Zuco, Valentina. Preclinical Chemotherapy and Pharmacology Unit, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
TI - Sensitization of ovarian carcinoma cells to the atypical retinoid ST1926 by the histone deacetylase inhibitor, RC307: enhanced DNA damage response.
SO - International Journal of Cancer. 126(5):1246-55, 2010 Mar 01
AS - Int J Cancer. 126(5):1246-55, 2010 Mar 01
NJ - International journal of cancer
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - gqu, 0042124
IO - Int. J. Cancer
SB - Index Medicus
CP - United States
MH - Adamantane/ad [Administration & Dosage]
MH - Adamantane/aa [Analogs & Derivatives]
MH - Animals
MH - *Antineoplastic Combined Chemotherapy Protocols/pd [Pharmacology]
MH - *Apoptosis/de [Drug Effects]
MH - Blotting, Western
MH - Cell Line, Tumor
MH - Cell Proliferation/de [Drug Effects]
MH - Cinnamates/ad [Administration & Dosage]
MH - *DNA Damage/de [Drug Effects]
MH - Enzyme Inhibitors/ad [Administration & Dosage]
MH - Female
MH - Histone Deacetylases/de [Drug Effects]
MH - Humans
MH - In Situ Nick-End Labeling
MH - Mice
MH - Mice, Nude
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - Retinoids/ad [Administration & Dosage]
MH - Xenograft Model Antitumor Assays
AB - The synthetic atypical retinoids containing an adamantyl group exhibit antiproliferative or proapoptotic activities. Apoptosis induction is a dose-dependent effect independent of retinoid receptors. We have reported that induction of apoptosis by the atypical retinoid, ST1926, is associated with early manifestations of genotoxic stress. Indeed, in this study performed in ovarian carcinoma cells, we show that exposure to ST1926 resulted in an increase of early markers of DNA damage, including ATM and H2AX phosphorylation. In addition, we found that a novel histone deacetylase (HDAC) inhibitor (RC307) was able to enhance sensitivity of ovarian carcinoma cells to ST1926. Under conditions where single-agent treatment caused only antiproliferative effects, the combination of the atypical retinoid and HDAC inhibitor resulted in marked apoptotic cell death with a more rapid onset in wild-type p53 ovarian carcinoma cells. The sensitization to ST1926-induced apoptosis was associated with an enhanced DNA damage response, because a prolonged expression of DNA damage markers (e.g., H2AX, p53 and RPA-2 phosphorylation) and a marked activation of DNA damage checkpoint kinases (in particular, phosphorylation of Chk1) were observed indicating an accumulation of DNA damage by the ST1926/HDAC inhibitor combination. The study provides additional support to the role of DNA damage as a primary event leading to the activation of apoptosis in ovarian carcinoma cells by adamantyl retinoids and documents the potential therapeutic efficacy of the combination of ST1926 and HDAC inhibitors of the novel series.
RN - 0 (3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid)
RN - 0 (Cinnamates)
RN - 0 (Enzyme Inhibitors)
RN - 0 (Retinoids)
RN - EC 3-5-1-98 (Histone Deacetylases)
RN - PJY633525U (Adamantane)
ES - 1097-0215
IL - 0020-7136
DO - https://dx.doi.org/10.1002/ijc.24819
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 19676051 [pubmed]
ID - 10.1002/ijc.24819 [doi]
PP - ppublish
LG - English
DP - 2010 Mar 01
DC - 20100104
EZ - 2009/08/14 09:00
DA - 2010/01/23 06:00
DT - 2009/08/14 09:00
YR - 2010
ED - 20100122
RD - 20160303
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=19676051
<328. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 19732843
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Ouyang G
AU - Yao L
AU - Ruan K
AU - Song G
AU - Mao Y
AU - Bao S
FA - Ouyang, Gaoliang
FA - Yao, Luming
FA - Ruan, Kai
FA - Song, Gang
FA - Mao, Yubin
FA - Bao, Shideng
IN - Ouyang, Gaoliang. Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005, China. oygldz@yahoo.com.cn
TI - Genistein induces G2/M cell cycle arrest and apoptosis of human ovarian cancer cells via activation of DNA damage checkpoint pathways.
SO - Cell Biology International. 33(12):1237-44, 2009 Dec
AS - Cell Biol Int. 33(12):1237-44, 2009 Dec
NJ - Cell biology international
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - bpn, 9307129
IO - Cell Biol. Int.
SB - Index Medicus
CP - England
MH - *Anticarcinogenic Agents/pd [Pharmacology]
MH - *Apoptosis/de [Drug Effects]
MH - Apoptosis/ge [Genetics]
MH - Ataxia Telangiectasia Mutated Proteins
MH - BRCA1 Protein/me [Metabolism]
MH - *Cell Cycle/de [Drug Effects]
MH - Cell Cycle/ge [Genetics]
MH - Cell Cycle Proteins/me [Metabolism]
MH - Cell Line, Tumor
MH - Cell Proliferation/de [Drug Effects]
MH - Checkpoint Kinase 1
MH - Checkpoint Kinase 2
MH - Cyclin B/me [Metabolism]
MH - Cyclin-Dependent Kinases
MH - *DNA Damage/de [Drug Effects]
MH - DNA-Binding Proteins/me [Metabolism]
MH - Female
MH - *Genistein/pd [Pharmacology]
MH - Humans
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - *Ovarian Neoplasms/ge [Genetics]
MH - Ovarian Neoplasms/me [Metabolism]
MH - *Ovarian Neoplasms/pa [Pathology]
MH - Phosphorylation
MH - Protein Kinases/me [Metabolism]
MH - Protein-Serine-Threonine Kinases/me [Metabolism]
MH - *Signal Transduction/de [Drug Effects]
MH - Signal Transduction/ge [Genetics]
MH - Tumor Suppressor Proteins/me [Metabolism]
MH - bcl-2-Associated X Protein/me [Metabolism]
MH - bcl-X Protein/me [Metabolism]
MH - cdc25 Phosphatases/me [Metabolism]
AB - Genistein is a major isoflavonoid in dietary soybean, commonly consumed in Asia. Genistein exerts inhibitory effects on the proliferation of various cancer cells and plays an important role in cancer prevention. However, the molecular and cellular mechanisms of genistein on human ovarian cancer cells are still little known. We show that exposure of human ovarian cancer HO-8910 cells to genistein induces DNA damage, and triggers G2/M phase arrest and apoptosis. Furthermore, we also found that checkpoint proteins ATM and ATR are phosphorylated and activated in the cells treated with genistein. It is also shown that genistein increases the phosphorylation and activation of Chk1 and Chk2, which results in the phosphorylation and inactivation of phosphatases Cdc25C and Cdc25A, and thereby the phosphorylation and inactivation of Cdc2 which arrests cells in G2/M phase. Moreover, genistein enhances the phosphorylation and activation of p53, while decreases the ratio of Bcl-2/Bax and Bcl-xL/Bax and the level of phosphorylated Akt, which result in cells undergoing apoptosis. These results demonstrate that genistein-activated ATM-Chk2-Cdc25 and ATR-Chk1-Cdc25 DNA damage checkpoint pathways can arrest ovarian cancer cells in G2/M phase, and induce apoptosis while the cellular DNA damage is too serious to be repaired. Thus, the antiproliferative, DNA damage-inducing and pro-apoptotic activities of genistein are probably responsible for its genotoxic effects on human ovarian cancer HO-8910 cells.
RN - 0 (Anticarcinogenic Agents)
RN - 0 (BRCA1 Protein)
RN - 0 (Cell Cycle Proteins)
RN - 0 (Cyclin B)
RN - 0 (DNA-Binding Proteins)
RN - 0 (Rad17 protein, human)
RN - 0 (Tumor Suppressor Proteins)
RN - 0 (bcl-2-Associated X Protein)
RN - 0 (bcl-X Protein)
RN - DH2M523P0H (Genistein)
RN - EC 2-7 (Protein Kinases)
RN - EC 2-7-1-11 (Checkpoint Kinase 2)
RN - EC 2-7-11-1 (ATM protein, human)
RN - EC 2-7-11-1 (ATR protein, human)
RN - EC 2-7-11-1 (Ataxia Telangiectasia Mutated Proteins)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (CHEK2 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
RN - EC 2-7-11-1 (Protein-Serine-Threonine Kinases)
RN - EC 2-7-11-22 (CDK1 protein, human)
RN - EC 2-7-11-22 (Cyclin-Dependent Kinases)
RN - EC 3-1-3-48 (CDC25A protein, human)
RN - EC 3-1-3-48 (CDC25C protein, human)
RN - EC 3-1-3-48 (cdc25 Phosphatases)
ES - 1095-8355
IL - 1065-6995
DI - S1065-6995(09)00223-6
DO - https://dx.doi.org/10.1016/j.cellbi.2009.08.011
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 19732843 [pubmed]
ID - S1065-6995(09)00223-6 [pii]
ID - 10.1016/j.cellbi.2009.08.011 [doi]
PP - ppublish
PH - 2009/01/19 [received]
PH - 2009/06/09 [revised]
PH - 2009/08/25 [accepted]
LG - English
EP - 20090902
DP - 2009 Dec
DC - 20091120
EZ - 2009/09/08 06:00
DA - 2010/01/20 06:00
DT - 2009/09/08 06:00
YR - 2009
ED - 20100119
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=19732843
<329. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 19850680
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Mitchell AL
AU - Cordell HJ
AU - Soemedi R
AU - Owen K
AU - Skinningsrud B
AU - Wolff AB
AU - Ericksen M
AU - Undlien D
AU - Husebye E
AU - Pearce SH
FA - Mitchell, Anna L
FA - Cordell, Heather J
FA - Soemedi, Rachel
FA - Owen, Kate
FA - Skinningsrud, Beate
FA - Wolff, Anette Boe
FA - Ericksen, Martina
FA - Undlien, Dag
FA - Husebye, Eystein
FA - Pearce, Simon H S
IN - Mitchell, Anna L. Institute of Human Genetics, Newcastle University, Newcastle upon Tyne NE1 3BZ, United Kingdom.
TI - Programmed death ligand 1 (PD-L1) gene variants contribute to autoimmune Addison's disease and Graves' disease susceptibility.
SO - Journal of Clinical Endocrinology & Metabolism. 94(12):5139-45, 2009 Dec
AS - J Clin Endocrinol Metab. 94(12):5139-45, 2009 Dec
NJ - The Journal of clinical endocrinology and metabolism
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - hrb, 0375362
IO - J. Clin. Endocrinol. Metab.
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Addison Disease/ep [Epidemiology]
MH - *Addison Disease/ge [Genetics]
MH - Addison Disease/pa [Pathology]
MH - Adolescent
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - Alleles
MH - *Antigens, CD/ge [Genetics]
MH - Antigens, CD274
MH - Autoimmune Diseases/ep [Epidemiology]
MH - *Autoimmune Diseases/ge [Genetics]
MH - Autoimmune Diseases/pa [Pathology]
MH - Cohort Studies
MH - Female
MH - Genetic Markers
MH - Genetic Predisposition to Disease
MH - Genetic Variation
MH - Genotype
MH - *Graves Disease/ge [Genetics]
MH - Graves Disease/pa [Pathology]
MH - Haplotypes
MH - Humans
MH - Male
MH - Middle Aged
MH - Norway/ep [Epidemiology]
MH - Polymorphism, Single Nucleotide
MH - United Kingdom/ep [Epidemiology]
MH - Young Adult
AB - CONTEXT: Despite much investigation, a substantial amount of the genetic susceptibility to autoimmune diseases remains unaccounted for. Recently, a single-nucleotide polymorphism (SNP) in the programmed death ligand 1 (PD-L1) gene has been associated with Graves' disease (GD) in a Japanese patient cohort. Our aim was to determine whether variants in PD-L1 are also associated with autoimmune Addison's disease (AAD) and to replicate the previous association in patients with GD from the United Kingdom.
AB - DESIGN AND PATIENTS: We analyzed eight SNPs within PD-L1 in a United Kingdom cohort of 315 AAD subjects and 316 healthy controls. We then replicated our experiment in a cohort of 342 Norwegian AAD cases and 379 controls and in 496 United Kingdom GD subjects.
AB - RESULTS: Three of the eight SNPs studied, part of a haplotype block in the PD-L1 gene, showed modest association with both AAD and GD in the United Kingdom cohort, with maximum evidence at the marker RS1411262 [United Kingdom AAD odds ratio 1.33 (5-95% confidence interval 1.02-1.73), P(genotype) = 0.028; GD odds ratio 1.36 (5-95% confidence interval 1.07-1.72), P(genotype) = 0.033]. Association with genotypes at the same three markers was confirmed in the Norwegian AAD cohort [P(genotype) = 0.011-0.020]. A recessive effect at the most associated alleles was observed in both the AAD and GD cohorts.
AB - CONCLUSIONS: We confirm the role of PD-L1 variants in GD susceptibility and extend these findings to demonstrate association in two Northern European patient cohorts with AAD. PD-L1 joins the growing number of known susceptibility loci exerting modest effects in these autoimmune disorders.
RN - 0 (Antigens, CD)
RN - 0 (Antigens, CD274)
RN - 0 (CD274 protein, human)
RN - 0 (Genetic Markers)
ES - 1945-7197
IL - 0021-972X
DI - jc.2009-1404
DO - https://dx.doi.org/10.1210/jc.2009-1404
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 19850680 [pubmed]
ID - jc.2009-1404 [pii]
ID - 10.1210/jc.2009-1404 [doi]
PP - ppublish
GI - No: G84/5959
Organization: *Medical Research Council*
Country: United Kingdom
LG - English
EP - 20091022
DP - 2009 Dec
DC - 20091204
EZ - 2009/10/24 06:00
DA - 2010/01/06 06:00
DT - 2009/10/24 06:00
YR - 2009
ED - 20100105
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=19850680
<330. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 19474123
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Carpenter KJ
AU - Murtagh RD
AU - Lilienfeld H
AU - Weber J
AU - Murtagh FR
FA - Carpenter, K J
FA - Murtagh, R D
FA - Lilienfeld, H
FA - Weber, J
FA - Murtagh, F R
IN - Carpenter, K J. Department of Radiology, University of South Florida, Tampa, FL 33629, USA.
TI - Ipilimumab-induced hypophysitis: MR imaging findings.
SO - Ajnr: American Journal of Neuroradiology. 30(9):1751-3, 2009 Oct
AS - AJNR Am J Neuroradiol. 30(9):1751-3, 2009 Oct
NJ - AJNR. American journal of neuroradiology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 3ag, 8003708
IO - AJNR Am J Neuroradiol
SB - Index Medicus
CP - United States
MH - Aged
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - *Brain/de [Drug Effects]
MH - *Brain/pa [Pathology]
MH - Female
MH - Humans
MH - *Magnetic Resonance Imaging/mt [Methods]
MH - Male
MH - Middle Aged
MH - *Pituitary Diseases/ci [Chemically Induced]
MH - *Pituitary Diseases/pa [Pathology]
AB - Ipilimumab is a promising new immunotherapeutic antineoplastic agent with clinical activity in the treatment of metastatic melanoma and renal cell carcinoma. With advances in immunotherapy, however, a host of new side effects related to the mechanism of action of these drugs has appeared. At our institution, 3 patients presented with hypophysitis, which was attributed to an autoimmune process based on the documented relationship of the drug to other autoimmune phenomena and significant and rapid improvement with discontinuation of the drug and addition of steroids. We present the imaging findings in 3 patients with presumed ipilimumab-induced hypophysitis.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
ES - 1936-959X
IL - 0195-6108
DI - ajnr.A1623
DO - https://dx.doi.org/10.3174/ajnr.A1623
PT - Case Reports
PT - Journal Article
ID - 19474123 [pubmed]
ID - ajnr.A1623 [pii]
ID - 10.3174/ajnr.A1623 [doi]
PP - ppublish
LG - English
EP - 20090527
DP - 2009 Oct
DC - 20091009
EZ - 2009/05/29 09:00
DA - 2010/01/05 06:00
DT - 2009/05/29 09:00
YR - 2009
ED - 20100104
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=19474123
<331. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 19318477
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Klein O
AU - Ebert LM
AU - Nicholaou T
AU - Browning J
AU - Russell SE
AU - Zuber M
AU - Jackson HM
AU - Dimopoulos N
AU - Tan BS
AU - Hoos A
AU - Luescher IF
AU - Davis ID
AU - Chen W
AU - Cebon J
FA - Klein, Oliver
FA - Ebert, Lisa M
FA - Nicholaou, Theo
FA - Browning, Judy
FA - Russell, Sarah E
FA - Zuber, Marina
FA - Jackson, Heather M
FA - Dimopoulos, Nektaria
FA - Tan, Bee Shin
FA - Hoos, Axel
FA - Luescher, Immanuel F
FA - Davis, Ian D
FA - Chen, Weisan
FA - Cebon, Jonathan
IN - Klein, Oliver. Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, Heidelberg, Victoria, Australia.
TI - Melan-A-specific cytotoxic T cells are associated with tumor regression and autoimmunity following treatment with anti-CTLA-4.
SO - Clinical Cancer Research. 15(7):2507-13, 2009 Apr 01
AS - Clin Cancer Res. 15(7):2507-13, 2009 Apr 01
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - c2h, 9502500
IO - Clin. Cancer Res.
SB - Index Medicus
CP - United States
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antigens, Neoplasm/im [Immunology]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Autoimmunity
MH - Cytotoxicity, Immunologic
MH - Double-Blind Method
MH - Exanthema/ci [Chemically Induced]
MH - Exanthema/im [Immunology]
MH - Humans
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - MART-1 Antigen
MH - Melanoma/dg [Diagnostic Imaging]
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - *Neoplasm Proteins/im [Immunology]
MH - Skin Neoplasms/dg [Diagnostic Imaging]
MH - *Skin Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/im [Immunology]
MH - *T-Lymphocytes, Cytotoxic/im [Immunology]
MH - Tomography, X-Ray Computed
AB - PURPOSE: Ipilimumab is a monoclonal antibody that blocks the immune-inhibitory interaction between CTL antigen 4 (CTLA-4) and its ligands on T cells. Clinical trials in cancer patients with ipilimumab have shown promising antitumor activity, particularly in patients with advanced melanoma. Often, tumor regressions in these patients are correlated with immune-related side effects such as dermatitis, enterocolitis, and hypophysitis. Although these reactions are believed to be immune-mediated, the antigenic targets for the cellular or humoral immune response are not known.
AB - EXPERIMENTAL DESIGN: We enrolled patients with advanced melanoma in a phase II study with ipilimumab. One of these patients experienced a complete remission of his tumor. The specificity and functional properties of CD8-positive T cells in his peripheral blood, in regressing tumor tissue, and at the site of an immune-mediated skin rash were investigated.
AB - RESULTS: Regressing tumor tissue was infiltrated with CD8-positive T cells, a high proportion of which were specific for Melan-A. The skin rash was similarly infiltrated with Melan-A-specific CD8-positive T cells, and a dramatic (>30-fold) increase in Melan-A-specific CD8-positive T cells was apparent in peripheral blood. These cells had an effector phenotype and lysed Melan-A-expressing tumor cells.
AB - CONCLUSIONS: Our results show that Melan-A may be a major target for both the autoimmune and antitumor reactions in patients treated with anti-CTLA-4, and describe for the first time the antigen specificity of CD8-positive T cells that mediate tumor rejection in a patient undergoing treatment with an anti-CTLA-4 antibody. These findings may allow a better integration of ipilimumab into other forms of immunotherapy.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, Neoplasm)
RN - 0 (Antineoplastic Agents)
RN - 0 (MART-1 Antigen)
RN - 0 (MLANA protein, human)
RN - 0 (Neoplasm Proteins)
RN - 6T8C155666 (ipilimumab)
IS - 1078-0432
IL - 1078-0432
DI - 1078-0432.CCR-08-2424
DO - https://dx.doi.org/10.1158/1078-0432.CCR-08-2424
PT - Clinical Trial, Phase II
PT - Journal Article
PT - Randomized Controlled Trial
PT - Research Support, Non-U.S. Gov't
ID - 19318477 [pubmed]
ID - 1078-0432.CCR-08-2424 [pii]
ID - 10.1158/1078-0432.CCR-08-2424 [doi]
PP - ppublish
LG - English
EP - 20090324
DP - 2009 Apr 01
DC - 20090402
EZ - 2009/03/26 09:00
DA - 2009/10/23 06:00
DT - 2009/03/26 09:00
YR - 2009
ED - 20091022
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=19318477
<332. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 19136343
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Ledezma B
FA - Ledezma, Blanca
IN - Ledezma, Blanca. Angeles Clinic and Research Institute, Santa Monica, CA, USA. bledezma@theangelesclinic.org
TI - Ipilimumab for advanced melanoma: a nursing perspective. [Review] [28 refs]
SO - Oncology Nursing Forum. 36(1):97-104, 2009 Jan
AS - Oncol Nurs Forum. 36(1):97-104, 2009 Jan
NJ - Oncology nursing forum
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 7809033, 7809033
IO - Oncol Nurs Forum
SB - Index Medicus
SB - Nursing Journal
CP - United States
MH - Aged
MH - Anti-Inflammatory Agents/tu [Therapeutic Use]
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antigens, CD/im [Immunology]
MH - CTLA-4 Antigen
MH - Chemical and Drug Induced Liver Injury/dt [Drug Therapy]
MH - Chemical and Drug Induced Liver Injury/et [Etiology]
MH - Clinical Trials as Topic
MH - Diarrhea/ci [Chemically Induced]
MH - Diarrhea/dh [Diet Therapy]
MH - Diarrhea/dt [Drug Therapy]
MH - Drug Eruptions/et [Etiology]
MH - Female
MH - Humans
MH - Immunity, Cellular
MH - Immunologic Factors/ad [Administration & Dosage]
MH - Immunologic Factors/ae [Adverse Effects]
MH - *Immunologic Factors/tu [Therapeutic Use]
MH - Immunosuppressive Agents/tu [Therapeutic Use]
MH - Interleukin-2/ad [Administration & Dosage]
MH - Interleukin-2/tu [Therapeutic Use]
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/im [Immunology]
MH - Melanoma/nu [Nursing]
MH - Melanoma/pa [Pathology]
MH - Middle Aged
MH - Nurse's Role
MH - Patient Education as Topic
MH - Pituitary Diseases/ci [Chemically Induced]
MH - Pruritus/ci [Chemically Induced]
MH - *Salvage Therapy
MH - T-Lymphocytes, Cytotoxic/de [Drug Effects]
MH - T-Lymphocytes, Cytotoxic/im [Immunology]
AB - PURPOSE/OBJECTIVES: To discuss the response patterns and side effects related to ipilimumab, a new immunotherapeutic agent under investigation in the treatment of advanced melanoma and other malignancies.
AB - DATA SOURCES: Published articles, abstracts, research data, and clinical experience.
AB - DATA SYNTHESIS: Ipilimumab is a fully human monoclonal antibody that inhibits the activity of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a naturally immunosuppressive molecule. The most common side effects are immune mediated (e.g., inflammatory diarrhea, pruritus) and appear to occur as a direct result of CTLA-4 inhibition and enhanced immune system activation. Side effects generally are grade I or II and resolve with standard treatments. Most grade III or IV events are managed successfully after swift diagnosis and treatment with corticosteroids; steroid-refractory events resolve after treatment with infliximab or mycophenolate.
AB - CONCLUSIONS: The response patterns and side effects associated with ipilimumab therapy greatly differ from those common to other advanced melanoma therapies (e.g., chemotherapy, cytokines, vaccines).
AB - IMPLICATIONS FOR NURSING: Nurses have an important role in educating patients about the differences between anti-CTLA-4 therapy and chemotherapy. In addition, teaching patients to recognize ipilimumab's side effects and report them early can result in fast treatment to prevent symptom progression from grade I or II to III or IV. Communication between nurses and patients throughout the treatment process will help patients benefit maximally from the new therapeutic strategy. [References: 28]
RN - 0 (Anti-Inflammatory Agents)
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (Immunologic Factors)
RN - 0 (Immunosuppressive Agents)
RN - 0 (Interleukin-2)
RN - 6T8C155666 (ipilimumab)
ES - 1538-0688
IL - 0190-535X
DI - 42U6741253M0P145
DO - https://dx.doi.org/10.1188/09.ONF.97-104
PT - Case Reports
PT - Journal Article
PT - Review
ID - 19136343 [pubmed]
ID - 42U6741253M0P145 [pii]
ID - 10.1188/09.ONF.97-104 [doi]
PP - ppublish
LG - English
DP - 2009 Jan
DC - 20090112
EZ - 2009/01/13 09:00
DA - 2009/05/09 09:00
DT - 2009/01/13 09:00
YR - 2009
ED - 20090508
RD - 20161124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=19136343
<333. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 19236381
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Montopoli M
AU - Ragazzi E
AU - Froldi G
AU - Caparrotta L
FA - Montopoli, M
FA - Ragazzi, E
FA - Froldi, G
FA - Caparrotta, L
IN - Montopoli, M. Department of Pharmacology and Anaesthesiology, University of Padova, Padova, Italy.
TI - Cell-cycle inhibition and apoptosis induced by curcumin and cisplatin or oxaliplatin in human ovarian carcinoma cells.
SO - Cell Proliferation. 42(2):195-206, 2009 Apr
AS - Cell Prolif. 42(2):195-206, 2009 Apr
NJ - Cell proliferation
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - a3a, 9105195
IO - Cell Prolif.
SB - Index Medicus
CP - England
MH - Antineoplastic Agents/pd [Pharmacology]
MH - *Apoptosis/de [Drug Effects]
MH - *Cell Cycle/de [Drug Effects]
MH - Cell Line, Tumor
MH - Cell Survival/de [Drug Effects]
MH - *Cisplatin/pd [Pharmacology]
MH - *Curcumin/pd [Pharmacology]
MH - Dose-Response Relationship, Drug
MH - Drug Resistance, Neoplasm
MH - Female
MH - Glutathione/me [Metabolism]
MH - Humans
MH - *Organoplatinum Compounds/pd [Pharmacology]
MH - Ovarian Neoplasms/me [Metabolism]
MH - *Ovarian Neoplasms/pa [Pathology]
MH - Reactive Oxygen Species/me [Metabolism]
AB - UNLABELLED: Alteration of appropriate cell-cycle progression and of closely related apoptotic process is a basic feature of tumour cells, and development of new tumour-targeted agents focus on apoptosis, either during cell-cycle arrest or following premature cell-cycle checkpoint exit. Increasingly, epidemiological and experimental studies suggest that curcumin protects against cancer, not only because of its well-known antioxidant properties, but also because it modulates intracellular signalling, which is related to cell proliferation and apoptosis. Cisplatin and oxaliplatin are first-line drugs in treatment of many types of epithelial cancer and their combination with other cytostatics are under investigation to limit their side effects and resistance to them.
AB - OBJECTIVES: The aim of this study was to evaluate effects of a combined treatment using curcumin with cisplatin or with oxaliplatin, in a human ovarian cancer cell line (2008) and in its cisplatin-resistant variant (C13).
AB - RESULTS: Curcumin per se caused concentration-dependent (0.1-100 microm) and time-persistent (24-72 h) reduction in cell proliferation, as well as altered cell cycle parameters and induced apoptosis, in both cell lines. When carcinoma cells were simultaneously exposed to curcumin and to cisplatin or oxaliplatin (at concentrations lower than IC(50)) cell viability was reduced more than with single-drug treatment. Moreover, dose and time related effects of curcumin, when combined with platinum drugs, were linked to consistent reduction in cell cycling and increased apoptosis, in comparison with single-drug treatment. These effects were significant both in wild type and in cisplatin-resistant cells, indicating that curcumin was also able to increase sensitivity of resistant ovarian cancer cells to cisplatin.
AB - CONCLUSIONS: The data suggests that curcumin is an interesting natural compound capable of limiting cell proliferation and possibly increasing clinical impact of platinum drugs, in ovarian cancer patients.
RN - 0 (Antineoplastic Agents)
RN - 0 (Organoplatinum Compounds)
RN - 0 (Reactive Oxygen Species)
RN - 04ZR38536J (oxaliplatin)
RN - GAN16C9B8O (Glutathione)
RN - IT942ZTH98 (Curcumin)
RN - Q20Q21Q62J (Cisplatin)
ES - 1365-2184
IL - 0960-7722
DI - CPR585
DO - https://dx.doi.org/10.1111/j.1365-2184.2009.00585.x
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 19236381 [pubmed]
ID - CPR585 [pii]
ID - 10.1111/j.1365-2184.2009.00585.x [doi]
PP - ppublish
LG - English
EP - 20090218
DP - 2009 Apr
DC - 20090325
EZ - 2009/02/25 09:00
DA - 2009/04/17 09:00
DT - 2009/02/25 09:00
YR - 2009
ED - 20090416
RD - 20141120
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=19236381
<334. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 19198837
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Weber J
FA - Weber, Jeffrey
IN - Weber, Jeffrey. H. Lee Moffitt Cancer Center and Research Institute, Donald A. Adam Comprehensive Melanoma Research Center, Department of Oncologic Sciences, University of South Florida, 12902 Magnolia Drive, Tampa, FL 33612, USA. Jeffrey.Weber@moffitt.org
TI - Ipilimumab: controversies in its development, utility and autoimmune adverse events. [Review] [35 refs]
SO - Cancer Immunology, Immunotherapy. 58(5):823-30, 2009 May
AS - Cancer Immunol Immunother. 58(5):823-30, 2009 May
NJ - Cancer immunology, immunotherapy : CII
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cn3, 8605732
IO - Cancer Immunol. Immunother.
SB - Index Medicus
CP - Germany
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/im [Immunology]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antigen Presentation
MH - *Antigens, CD/im [Immunology]
MH - Antigens, CD28/im [Immunology]
MH - Antigens, Neoplasm/im [Immunology]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/im [Immunology]
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - Autoimmune Diseases/et [Etiology]
MH - CTLA-4 Antigen
MH - Clinical Trials as Topic/sn [Statistics & Numerical Data]
MH - Clonal Anergy
MH - Digestive System Diseases/di [Diagnosis]
MH - Digestive System Diseases/dt [Drug Therapy]
MH - Digestive System Diseases/et [Etiology]
MH - Digestive System Diseases/im [Immunology]
MH - Humans
MH - Hypopituitarism/et [Etiology]
MH - Hypopituitarism/im [Immunology]
MH - Lymphocyte Activation
MH - Melanoma/im [Immunology]
MH - Melanoma/sc [Secondary]
MH - *Melanoma/th [Therapy]
MH - Models, Immunological
MH - *T-Lymphocytes, Cytotoxic/im [Immunology]
MH - Tumor Escape/im [Immunology]
AB - A promising new class of anti-cancer drugs includes antibodies that mediate immune regulatory effects. It has become very clear over the last decade that different types of immune cells and different pathways serve to suppress anti-cancer immunity, particularly in the microenvironment of the tumor. The first examples of immune modulating antibodies are those directed against cytotoxic T lymphocyte antigen-4 (CTLA-4), a molecule present on activated T cells. Human antibodies that abrogate the function of CTLA-4 have been tested in the clinic and found to have clinical activity against melanoma. In this review, we discuss some of the controversies surrounding the potential clinical utility of one of those antibodies, ipilimumab, formerly MDX-010, from Medarex and Bristol Myers Squibb. The optimal dose and schedule of ipilimumab was derived in multiple clinical trials whose latest results are described below. Favorable survival in patients with stage IV melanoma were observed that appear to be associated with unique side effects of the drug called "immune-related adverse events". The management of these side effects is described, and the unusual kinetics of anti-tumor response with ipilimumab as well as a newly proposed schema for assessing anti-tumor responses in patients receiving biologic compounds like ipilimumab, which may supercede RECIST or WHO criteria, are addressed. [References: 35]
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (Antigens, CD28)
RN - 0 (Antigens, Neoplasm)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 6T8C155666 (ipilimumab)
ES - 1432-0851
IL - 0340-7004
DO - https://dx.doi.org/10.1007/s00262-008-0653-8
PT - Journal Article
PT - Review
ID - 19198837 [pubmed]
ID - 10.1007/s00262-008-0653-8 [doi]
PP - ppublish
PH - 2008/12/02 [received]
PH - 2008/12/30 [accepted]
PH - 2008/12/23 [revised]
LG - English
EP - 20090206
DP - 2009 May
DC - 20090224
EZ - 2009/02/10 09:00
DA - 2009/04/02 09:00
DT - 2009/02/10 09:00
YR - 2009
ED - 20090401
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=19198837
<335. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 18974373
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Bashey A
AU - Medina B
AU - Corringham S
AU - Pasek M
AU - Carrier E
AU - Vrooman L
AU - Lowy I
AU - Solomon SR
AU - Morris LE
AU - Holland HK
AU - Mason JR
AU - Alyea EP
AU - Soiffer RJ
AU - Ball ED
FA - Bashey, Asad
FA - Medina, Bridget
FA - Corringham, Sue
FA - Pasek, Mildred
FA - Carrier, Ewa
FA - Vrooman, Linda
FA - Lowy, Israel
FA - Solomon, Scott R
FA - Morris, Lawrence E
FA - Holland, H Kent
FA - Mason, James R
FA - Alyea, Edwin P
FA - Soiffer, Robert J
FA - Ball, Edward D
IN - Bashey, Asad. Division of Blood and Marrow Transplantation, University of California, San Diego Moores Cancer Center, La Jolla, CA, USA. abashey@bmtga.com
TI - CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation.
SO - Blood. 113(7):1581-8, 2009 Feb 12
AS - Blood. 113(7):1581-8, 2009 Feb 12
NJ - Blood
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - a8g, 7603509
IO - Blood
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2644086
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - *Adoptive Transfer
MH - Adult
MH - Aged
MH - *Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/pk [Pharmacokinetics]
MH - Antigens, CD/im [Immunology]
MH - *Antigens, CD/me [Metabolism]
MH - Arthritis, Rheumatoid/ci [Chemically Induced]
MH - CTLA-4 Antigen
MH - Female
MH - Graft vs Host Disease/et [Etiology]
MH - *Graft vs Leukemia Effect/de [Drug Effects]
MH - Humans
MH - Kaplan-Meier Estimate
MH - Leukemia/mo [Mortality]
MH - *Leukemia/th [Therapy]
MH - Lymphoma/mo [Mortality]
MH - Lymphoma/th [Therapy]
MH - Male
MH - Middle Aged
MH - Neoplasm Recurrence, Local/mo [Mortality]
MH - *Neoplasm Recurrence, Local/pc [Prevention & Control]
MH - Pneumonia/ci [Chemically Induced]
MH - Transplantation, Homologous
AB - Relapse of malignancy after allogeneic hematopoietic cell transplantation (allo-HCT) remains a therapeutic challenge. Blockade of the CTLA4 molecule can effectively augment antitumor immunity mediated by autologous effector T cells. We have assessed the safety and preliminary efficacy of a neutralizing, human anti-CTLA4 monoclonal antibody, ipilimumab, in stimulating the graft-versus-malignancy (GVM) effect after allo-HCT. Twenty-nine patients with malignancies that were recurrent or progressive after allo-HCT, received ipilimumab as a single infusion at dose cohorts between 0.1 and 3.0 mg/kg. Dose-limiting toxicity was not encountered, and ipilimumab did not induce graft-versus-host disease (GVHD) or graft rejection. Organ-specific immune adverse events (IAE) were seen in 4 patients (grade 3 arthritis, grade 2 hyperthyroidism, recurrent grade 4 pneumonitis). Three patients with lymphoid malignancy developed objective disease responses following ipilimumab: complete remission (CR) in 2 patients with Hodgkin disease and partial remission (PR) in a patient with refractory mantle cell lymphoma. At the 3.0 mg/kg dose, active serum concentrations of ipilimumab were maintained for more than 30 days after a single infusion. Ipilimumab, as administered in this clinical trial, does not induce or exacerbate clinical GVHD, but may cause organ-specific IAE and regression of malignancy. This study is registered at (http://clinicaltrials.gov) under NCI protocol ID P6082.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 6T8C155666 (ipilimumab)
ES - 1528-0020
IL - 0006-4971
DI - blood-2008-07-168468
DO - https://dx.doi.org/10.1182/blood-2008-07-168468
PT - Clinical Trial
PT - Journal Article
PT - Multicenter Study
PT - Research Support, N.I.H., Extramural
ID - 18974373 [pubmed]
ID - blood-2008-07-168468 [pii]
ID - 10.1182/blood-2008-07-168468 [doi]
ID - PMC2644086 [pmc]
PP - ppublish
SI - ClinicalTrials.gov
SA - ClinicalTrials.gov/NCT00060372
SL - https://clinicaltrials.gov/search/term=NCT00060372
GI - No: R01 CA 9389-01A1
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20081030
DP - 2009 Feb 12
DC - 20090217
EZ - 2008/11/01 09:00
DA - 2009/03/25 09:00
DT - 2008/11/01 09:00
YR - 2009
ED - 20090324
RD - 20161125
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=18974373
<336. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 19139112
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Parsels LA
AU - Morgan MA
AU - Tanska DM
AU - Parsels JD
AU - Palmer BD
AU - Booth RJ
AU - Denny WA
AU - Canman CE
AU - Kraker AJ
AU - Lawrence TS
AU - Maybaum J
FA - Parsels, Leslie A
FA - Morgan, Meredith A
FA - Tanska, Daria M
FA - Parsels, Joshua D
FA - Palmer, Brian D
FA - Booth, R John
FA - Denny, William A
FA - Canman, Christine E
FA - Kraker, Alan J
FA - Lawrence, Theodore S
FA - Maybaum, Jonathan
IN - Parsels, Leslie A. Department of Pharmacology, University of Michigan Medical School, Upjohn Center for Clinical Pharmacology, 4742E Medical Science II, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5633, USA.
TI - Gemcitabine sensitization by checkpoint kinase 1 inhibition correlates with inhibition of a Rad51 DNA damage response in pancreatic cancer cells.
SO - Molecular Cancer Therapeutics. 8(1):45-54, 2009 Jan
AS - Mol Cancer Ther. 8(1):45-54, 2009 Jan
NJ - Molecular cancer therapeutics
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 101132535
IO - Mol. Cancer Ther.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730564
OI - Source: NLM. NIHMS117821
SB - Index Medicus
CP - United States
MH - Biocatalysis
MH - Carbazoles/pd [Pharmacology]
MH - Cell Line, Tumor
MH - Cell Survival/de [Drug Effects]
MH - Checkpoint Kinase 1
MH - DNA Damage
MH - *Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Humans
MH - *Pancreatic Neoplasms/en [Enzymology]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - *Pancreatic Neoplasms/pa [Pathology]
MH - Phosphorylation/de [Drug Effects]
MH - *Protein Kinase Inhibitors/pd [Pharmacology]
MH - *Protein Kinases/me [Metabolism]
MH - *Rad51 Recombinase/ge [Genetics]
MH - *Rad51 Recombinase/me [Metabolism]
AB - The protein kinase checkpoint kinase 1 (Chk1) has been implicated as a key regulator of cell cycle progression and DNA repair, and inhibitors of Chk1 (e.g., UCN-01 and EXEL-9844) potentiate the cytotoxic actions of chemotherapeutic drugs in tumor cells. We have examined the ability of PD-321852, a small-molecule Chk1 inhibitor, to potentiate gemcitabine-induced clonogenic death in a panel of pancreatic cancer cell lines and evaluated the relationship between endpoints associated with Chk1 inhibition and chemosensitization. Gemcitabine chemosensitization by minimally toxic concentrations of PD-321852 ranged from minimal (<3-fold change in survival) in Panc1 cells to >30-fold in MiaPaCa2 cells. PD-321852 inhibited Chk1 in all cell lines as evidenced by stabilization of Cdc25A; in combination with gemcitabine, a synergistic loss of Chk1 protein was observed in the more sensitized cell lines. Gemcitabine chemosensitization, however, did not correlate with abrogation of the S-M or G2-M checkpoint; PD-321852 did not induce premature mitotic entry in gemcitabine-treated BxPC3 or M-Panc96 cells, which were sensitized to gemcitabine 6.2- and 4.6-fold, respectively. In the more sensitized cells lines, PD-321852 not only inhibited gemcitabine-induced Rad51 focus formation and the recovery from gemcitabine-induced replication stress, as evidenced by persistence of gamma-H2AX, but also depleted these cells of Rad51 protein. Our data suggest the inhibition of this Chk1-mediated Rad51 response to gemcitabine-induced replication stress is an important factor in determining gemcitabine chemosensitization by Chk1 inhibition in pancreatic cancer cells.
RN - 0 (4-(2,6-dichlorophenyl)-9-hydroxy-6-(3-methylaminopropyl)-6H-pyrrolo(3,4-c)carbazole-1,3-dione)
RN - 0 (Carbazoles)
RN - 0 (Protein Kinase Inhibitors)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
RN - EC 2-7 (Protein Kinases)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
RN - EC 2-7-7 (Rad51 Recombinase)
IS - 1535-7163
IL - 1535-7163
DI - 8/1/45
DO - https://dx.doi.org/10.1158/1535-7163.MCT-08-0662
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 19139112 [pubmed]
ID - 8/1/45 [pii]
ID - 10.1158/1535-7163.MCT-08-0662 [doi]
ID - PMC2730564 [pmc]
ID - NIHMS117821 [mid]
PP - ppublish
GI - No: R01 CA078554
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA078554-09
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01-CA078554
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2009 Jan
DC - 20090113
EZ - 2009/01/14 09:00
DA - 2009/02/20 09:00
DT - 2009/01/14 09:00
YR - 2009
ED - 20090219
RD - 20161124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=19139112
<337. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 18716842
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Phan GQ
AU - Weber JS
AU - Sondak VK
FA - Phan, Giao Q
FA - Weber, Jeffrey S
FA - Sondak, Vernon K
IN - Phan, Giao Q. Division of Cutaneous Oncology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
TI - CTLA-4 blockade with monoclonal antibodies in patients with metastatic cancer: surgical issues. [Review] [37 refs]
SO - Annals of Surgical Oncology. 15(11):3014-21, 2008 Nov
AS - Ann Surg Oncol. 15(11):3014-21, 2008 Nov
NJ - Annals of surgical oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - b9r, 9420840
IO - Ann. Surg. Oncol.
SB - Index Medicus
CP - United States
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - *Antigens, CD/im [Immunology]
MH - CTLA-4 Antigen
MH - Clinical Trials as Topic
MH - Enterocolitis/ci [Chemically Induced]
MH - Enterocolitis/dt [Drug Therapy]
MH - Guidelines as Topic
MH - Humans
MH - Immunotherapy
MH - *Melanoma/dt [Drug Therapy]
MH - Melanoma/pa [Pathology]
MH - Neoplasm Metastasis
AB - BACKGROUND: CTLA-4 (cytotoxic T lymphocyte-associated antigen 4) is a modulatory receptor on T cells involved in downregulating T cell activation. In animal models, CTLA-4 blockade abrogates tolerance to "self" antigens, resulting in the augmentation of antitumor immunity and induction of autoimmunity. CTLA-4 blockade by means of monoclonal antibodies (ipilimumab and tremelimumab) has been evaluated in multiple clinical trials in patients with metastatic cancer, mainly those with melanoma and renal cell cancer.
AB - METHODS: We examine available literature and ongoing clinical trials with ipilimumab and tremelimumab and review our own experience with patients treated with CTLA-4 blockade, with an emphasis on issues of direct relevance to surgical oncologists.
AB - RESULTS: CTLA-4 blockade can cause durable tumor regression in patients with metastatic melanoma and other solid tumors. Grade III/IV autoimmune toxicity has been frequently encountered in clinical trials and includes enterocolitis, dermatitis, hypophysitis, uveitis, and hepatitis. Enterocolitis is the most common immune-related adverse event and may cause severe diarrhea requiring intravenous hydration, high-dose corticosteroids, and blockade of tumor necrosis factor alpha with infliximab. Most patients respond to medical treatment, but up to 12% with grade III/IV enterocolitis develop perforation or bleeding that requires colectomy.
AB - CONCLUSIONS: As more patients are enrolled onto clinical trials involving ipilimumab and tremelimumab, an increasing number of surgeons may be involved in the care of these patients who develop treatment-related complications. In this report, we review the rationale for CTLA-4 blockade and review selected clinical studies published so far with ipilimumab and tremelimumab. We offer guidelines on the management of patients who develop enterocolitis. [References: 37]
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 6T8C155666 (ipilimumab)
RN - QEN1X95CIX (tremelimumab)
ES - 1534-4681
IL - 1068-9265
DO - https://dx.doi.org/10.1245/s10434-008-0104-y
PT - Journal Article
PT - Review
ID - 18716842 [pubmed]
ID - 10.1245/s10434-008-0104-y [doi]
PP - ppublish
PH - 2008/03/27 [received]
PH - 2008/07/15 [accepted]
PH - 2008/07/14 [revised]
LG - English
EP - 20080821
DP - 2008 Nov
DC - 20081029
EZ - 2008/08/22 09:00
DA - 2009/01/30 09:00
DT - 2008/08/22 09:00
YR - 2008
ED - 20090129
RD - 20161124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=18716842
<338. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 18433847
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Durrant D
AU - Richards JE
AU - Walker WT
AU - Baker KA
AU - Simoni D
AU - Lee RM
FA - Durrant, David
FA - Richards, Joanna E
FA - Walker, Winston T
FA - Baker, Kristen A
FA - Simoni, Daniele
FA - Lee, Ray M
IN - Durrant, David. Massey Cancer Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
TI - Mechanism of cell death induced by cis-3, 4', 5-trimethoxy-3'-aminostilbene in ovarian cancer.
SO - Gynecologic Oncology. 110(1):110-7, 2008 Jul
AS - Gynecol Oncol. 110(1):110-7, 2008 Jul
NJ - Gynecologic oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - fxc, 0365304
IO - Gynecol. Oncol.
SB - Index Medicus
CP - United States
MH - *Apoptosis/de [Drug Effects]
MH - *Cell Cycle/de [Drug Effects]
MH - *Cell Death/de [Drug Effects]
MH - Cell Line, Tumor
MH - Female
MH - Humans
MH - Membrane Potentials/de [Drug Effects]
MH - Membrane Potentials/ph [Physiology]
MH - Mitochondria/de [Drug Effects]
MH - Mitochondria/ph [Physiology]
MH - *Ovarian Neoplasms/pa [Pathology]
MH - Reactive Oxygen Species/me [Metabolism]
MH - *Stilbenes/pd [Pharmacology]
AB - OBJECTIVE: Stilbene derivative, cis-3, 4', 5-trimethoxy-3'-aminostilbene (stilbene 5c), is highly potent to induce cell death in ovarian cancer cells. This study is to investigate its mechanism to induce cell death.
AB - METHODS: UCI101 ovarian cancer cells were used for this study. Cell death was analyzed by Alamar blue staining. Cell cycle was analyzed by flow cytometry after PI staining. Mitochondrial potential and reactive oxygen species were determined by MitoTracker green and DCF-DA, respectively. Immunofluorescent staining was done with tubulin antibody following by confocal microscope examination. Cell lysates were collected after treatment with stilbene 5c for Western blotting analysis of various cell cycle regulators and signal transduction mediators.
AB - RESULTS: Stilbene-treated cells die in both cell cycle-dependent and -independent pathways. Low concentration (30 nM) induces cell death without cell cycle arrest. This process involves disruption of mitochondrial potential and production of ROS by a Bcl-2-independent pathway. Higher concentration of stilbene 5c arrests cell cycle in G(2)/M phase, which is supported by dephosphorylation of Cdc2 and Cdc25C, and transiently elevation of spindle checkpoint BubR1. Although phosphorylation of Chk1 and Chk2 both increases after treatment, loss of Chk1 suppresses, whereas loss of Chk2 enhances, stilbene 5c-induced cell death. Phosphorylation of Akt and Stat3, but not MAPK, is suppressed after stilbene 5c treatment.
AB - CONCLUSION: These studies provide a mechanistic insight in using stilbenes in ovarian cancer. Stilbenes could be potentially useful agents for ovarian cancer therapy and induce cell death through mitochondrial damage and cell cycle arrest.
RN - 0 (3,4',5-trimethoxy-3'-aminostilbene)
RN - 0 (Reactive Oxygen Species)
RN - 0 (Stilbenes)
ES - 1095-6859
IL - 0090-8258
DI - S0090-8258(08)00182-0
DO - https://dx.doi.org/10.1016/j.ygyno.2008.02.031
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 18433847 [pubmed]
ID - S0090-8258(08)00182-0 [pii]
ID - 10.1016/j.ygyno.2008.02.031 [doi]
PP - ppublish
PH - 2007/12/17 [received]
PH - 2008/02/22 [revised]
PH - 2008/02/28 [accepted]
GI - No: P30 CA16059
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20080422
DP - 2008 Jul
DC - 20080630
EZ - 2008/04/25 09:00
DA - 2008/08/02 09:00
DT - 2008/04/25 09:00
YR - 2008
ED - 20080801
RD - 20080630
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=18433847
<339. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 18539263
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Liu M
AU - Yu H
AU - Huo L
AU - Liu J
AU - Li M
AU - Zhou J
FA - Liu, Min
FA - Yu, Haiyang
FA - Huo, Lihong
FA - Liu, Jianchao
FA - Li, Minggang
FA - Zhou, Jun
IN - Liu, Min. Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.
TI - Validating the mitotic kinesin Eg5 as a therapeutic target in pancreatic cancer cells and tumor xenografts using a specific inhibitor.
SO - Biochemical Pharmacology. 76(2):169-78, 2008 Jul 15
AS - Biochem Pharmacol. 76(2):169-78, 2008 Jul 15
NJ - Biochemical pharmacology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9z4, 0101032
IO - Biochem. Pharmacol.
SB - Index Medicus
CP - England
MH - Animals
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Apoptosis
MH - Caspase 3/me [Metabolism]
MH - Cell Line, Tumor
MH - Cell Proliferation/de [Drug Effects]
MH - Female
MH - Humans
MH - *Kinesin/ai [Antagonists & Inhibitors]
MH - Mice
MH - Mice, Nude
MH - *Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/me [Metabolism]
MH - *Quinazolines/pd [Pharmacology]
MH - Quinazolines/tu [Therapeutic Use]
MH - *Thiones/pd [Pharmacology]
MH - Thiones/tu [Therapeutic Use]
MH - Xenograft Model Antitumor Assays
AB - Pancreatic cancer is a devastating disease with a high mortality rate. Treatment of this malignancy remains a big challenge in oncology, and none of the currently available chemotherapeutic agents has a remarkable impact on improving patient survival. Consequently, it is important to explore new targets and find effective drugs for the management of this disease. Here we report that inhibition of the mitotic kinesin Eg5 by a pharmacological compound effectively prevents the proliferation of pancreatic cancer cells by halting mitotic progression, resulting in robust apoptosis. The mitotic arrest induced by this agent is attributed to its interference with spindle formation and activation of the spindle checkpoint. Impairment of the spindle checkpoint significantly compromises both mitotic arrest and apoptosis induced by the Eg5 inhibitor, suggesting the importance of the spindle checkpoint in monitoring Eg5 inhibitor sensitivity. Furthermore, treatment of nude mice bearing tumor xenografts of human pancreatic cancer results in pronounced tumor regression by triggering apoptosis. These data thus indicate Eg5 as a potential target for pancreatic cancer treatment.
RN - 0 (Antineoplastic Agents)
RN - 0 (KIF11 protein, human)
RN - 0 (Quinazolines)
RN - 0 (Thiones)
RN - 0 (dimethylenastron)
RN - EC 3-4-22 (Caspase 3)
RN - EC 3-6-4-4 (Kinesin)
ES - 1873-2968
IL - 0006-2952
DI - S0006-2952(08)00258-X
DO - https://dx.doi.org/10.1016/j.bcp.2008.04.018
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 18539263 [pubmed]
ID - S0006-2952(08)00258-X [pii]
ID - 10.1016/j.bcp.2008.04.018 [doi]
PP - ppublish
PH - 2008/03/10 [received]
PH - 2008/04/13 [revised]
PH - 2008/04/15 [accepted]
LG - English
EP - 20080504
DP - 2008 Jul 15
DC - 20080630
EZ - 2008/06/10 09:00
DA - 2008/08/01 09:00
DT - 2008/06/10 09:00
YR - 2008
ED - 20080731
RD - 20161124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=18539263
<340. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 18261847
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Righetti SC
AU - Perego P
AU - Carenini N
AU - Zunino F
FA - Righetti, Sabina Carla
FA - Perego, Paola
FA - Carenini, Nives
FA - Zunino, Franco
IN - Righetti, Sabina Carla. Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
TI - Cooperation between p53 and p73 in cisplatin-induced apoptosis in ovarian carcinoma cells.
SO - Cancer Letters. 263(1):140-4, 2008 May 08
AS - Cancer Lett. 263(1):140-4, 2008 May 08
NJ - Cancer letters
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - 7600053, cmx
IO - Cancer Lett.
SB - Index Medicus
CP - Ireland
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - *Apoptosis/de [Drug Effects]
MH - *Cisplatin/pd [Pharmacology]
MH - *DNA-Binding Proteins/me [Metabolism]
MH - Female
MH - Humans
MH - *Nuclear Proteins/me [Metabolism]
MH - *Ovarian Neoplasms/pa [Pathology]
MH - Protein Binding
MH - Tumor Protein p73
MH - *Tumor Suppressor Protein p53/me [Metabolism]
MH - *Tumor Suppressor Proteins/me [Metabolism]
AB - The present study was designed to explore the role of p73 in response to cisplatin. In contrast to cisplatin-resistant ovarian carcinoma cells, pharmacological drug concentrations, which caused induction of p53, induced a marginal increase of p73 in sensitive cells. The effect was more marked at high concentrations, with no evidence of p21(WAF1) induction. This behaviour, associated with substantial apoptosis, suggests cell inability to activate DNA damage checkpoint following extensive stress. Although p73 appears to be implicated mainly in response to high stress conditions, the available results support a cooperation between p53 and p73 in cisplatin-induced apoptosis in sensitive cells.
RN - 0 (Antineoplastic Agents)
RN - 0 (DNA-Binding Proteins)
RN - 0 (Nuclear Proteins)
RN - 0 (Tumor Protein p73)
RN - 0 (Tumor Suppressor Protein p53)
RN - 0 (Tumor Suppressor Proteins)
RN - 0 (p73 protein, human)
RN - Q20Q21Q62J (Cisplatin)
IS - 0304-3835
IL - 0304-3835
DI - S0304-3835(07)00638-6
DO - https://dx.doi.org/10.1016/j.canlet.2007.12.024
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 18261847 [pubmed]
ID - S0304-3835(07)00638-6 [pii]
ID - 10.1016/j.canlet.2007.12.024 [doi]
PP - ppublish
PH - 2007/10/17 [received]
PH - 2007/12/19 [revised]
PH - 2007/12/19 [accepted]
LG - English
EP - 20080207
DP - 2008 May 08
DC - 20080331
EZ - 2008/02/12 09:00
DA - 2008/06/06 09:00
DT - 2008/02/12 09:00
YR - 2008
ED - 20080605
RD - 20161124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=18261847
<341. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 18094405
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Danial NN
FA - Danial, Nika N
IN - Danial, Nika N. Department of Pathology, Harvard Medical School and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. nika_danial@dfci.harvard.edu
TI - BCL-2 family proteins: critical checkpoints of apoptotic cell death. [Review] [128 refs]
SO - Clinical Cancer Research. 13(24):7254-63, 2007 Dec 15
AS - Clin Cancer Res. 13(24):7254-63, 2007 Dec 15
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print
PI - Citation processed from: Print
JC - c2h, 9502500
IO - Clin. Cancer Res.
SB - Index Medicus
CP - United States
MH - Animals
MH - *Apoptosis/ph [Physiology]
MH - Humans
MH - Multiprotein Complexes/ph [Physiology]
MH - *Proto-Oncogene Proteins c-bcl-2/ph [Physiology]
AB - Apoptosis is a morphologically distinct form of programmed cell death essential for normal development and tissue homeostasis. Aberrant regulation of this pathway is linked to multiple human diseases, including cancer, autoimmunity, neurodegenerative disorders, and diabetes. The BCL-2 family of proteins constitutes a critical control point in apoptosis residing immediately upstream of irreversible cellular damage, where family members control the release of apoptogenic factors from mitochondria. The cardinal member of this family, BCL-2, was originally discovered as the defining oncogene in follicular lymphomas, located at one reciprocal breakpoint of the t(14;18) (q32;q21) chromosomal translocation. Since this original discovery, remarkable efforts marshaled by many investigators around the world have advanced our knowledge of the basic biology, molecular mechanisms, and therapeutic targets in the apoptotic pathway. This review highlights findings from many laboratories that have helped uncover some of the critical control points in apoptosis. The emerging picture is that of an intricate cellular machinery orchestrated by tightly regulated molecular interactions and conformational changes within BCL-2 family proteins that ultimately govern the cellular commitment to apoptotic death. [References: 128]
RN - 0 (Multiprotein Complexes)
RN - 0 (Proto-Oncogene Proteins c-bcl-2)
IS - 1078-0432
IL - 1078-0432
DI - 13/24/7254
DO - https://dx.doi.org/10.1158/1078-0432.CCR-07-1598
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 18094405 [pubmed]
ID - 13/24/7254 [pii]
ID - 10.1158/1078-0432.CCR-07-1598 [doi]
PP - ppublish
GI - No: K01CA10659
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2007 Dec 15
DC - 20071220
EZ - 2007/12/21 09:00
DA - 2008/03/05 09:00
DT - 2007/12/21 09:00
YR - 2007
ED - 20080304
RD - 20071220
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=18094405
<342. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 18049334
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Yang JC
AU - Hughes M
AU - Kammula U
AU - Royal R
AU - Sherry RM
AU - Topalian SL
AU - Suri KB
AU - Levy C
AU - Allen T
AU - Mavroukakis S
AU - Lowy I
AU - White DE
AU - Rosenberg SA
FA - Yang, James C
FA - Hughes, Marybeth
FA - Kammula, Udai
FA - Royal, Richard
FA - Sherry, Richard M
FA - Topalian, Suzanne L
FA - Suri, Kimberly B
FA - Levy, Catherine
FA - Allen, Tamika
FA - Mavroukakis, Sharon
FA - Lowy, Israel
FA - White, Donald E
FA - Rosenberg, Steven A
IN - Yang, James C. Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. JamesYang@mail.nih.gov
TI - Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis.
SO - Journal of Immunotherapy. 30(8):825-30, 2007 Nov-Dec
AS - J Immunother. 30(8):825-30, 2007 Nov-Dec
NJ - Journal of immunotherapy (Hagerstown, Md. : 1997)
PI - Journal available in: Print
PI - Citation processed from: Print
JC - cuq, 9706083
IO - J. Immunother.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2134980
OI - Source: NLM. NIHMS35214
SB - Index Medicus
CP - United States
MH - Adrenal Insufficiency/ci [Chemically Induced]
MH - Adult
MH - Aged
MH - Antibodies, Monoclonal/ad [Administration & Dosage]
MH - Antibodies, Monoclonal/ae [Adverse Effects]
MH - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antineoplastic Agents/ad [Administration & Dosage]
MH - Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - Bone Neoplasms/dt [Drug Therapy]
MH - Bone Neoplasms/im [Immunology]
MH - Bone Neoplasms/sc [Secondary]
MH - *Carcinoma, Renal Cell/dt [Drug Therapy]
MH - Carcinoma, Renal Cell/im [Immunology]
MH - Carcinoma, Renal Cell/pa [Pathology]
MH - Colitis/ci [Chemically Induced]
MH - Duodenitis/ci [Chemically Induced]
MH - *Enteritis/ci [Chemically Induced]
MH - Female
MH - Humans
MH - Hypopituitarism/ci [Chemically Induced]
MH - *Kidney Neoplasms/dt [Drug Therapy]
MH - Kidney Neoplasms/im [Immunology]
MH - Kidney Neoplasms/pa [Pathology]
MH - Liver Neoplasms/dt [Drug Therapy]
MH - Liver Neoplasms/im [Immunology]
MH - Liver Neoplasms/sc [Secondary]
MH - Lung Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/im [Immunology]
MH - Lung Neoplasms/sc [Secondary]
MH - Male
MH - Meningitis, Aseptic/ci [Chemically Induced]
MH - Middle Aged
MH - *Pituitary Diseases/ci [Chemically Induced]
MH - Treatment Outcome
AB - The inhibitory receptor CTLA4 has a key role in peripheral tolerance of T cells for both normal and tumor-associated antigens. Murine experiments suggested that blockade of CTLA4 might have antitumor activity and a clinical experience with the blocking antibody ipilimumab in patients with metastatic melanoma did show durable tumor regressions in some patients. Therefore, a phase II study of ipilimumab was conducted in patients with metastatic renal cell cancer with a primary end point of response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Two sequential cohorts received either 3 mg/kg followed by 1 mg/kg or all doses at 3 mg/kg every 3 weeks (with no intention of comparing cohort response rates). Major toxicities were enteritis and endocrine deficiencies of presumed autoimmune origin. One of 21 patients receiving the lower dose had a partial response. Five of 40 patients at the higher dose had partial responses (95% confidence interval for cohort response rate 4% to 27%) and responses were seen in patients who had previously not responded to IL-2. Thirty-three percent of patients experienced a grade III or IV immune-mediated toxicity. There was a highly significant association between autoimmune events (AEs) and tumor regression (response rate=30% with AE, 0% without AE). CTLA4 blockade with ipilimumab induces cancer regression in some patients with metastatic clear cell renal cancer, even if they have not responded to other immunotherapies. These regressions are highly associated with other immune-mediated events of presumed autoimmune origin by mechanisms as yet undefined.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antineoplastic Agents)
RN - 6T8C155666 (ipilimumab)
IS - 1524-9557
IL - 1524-9557
DI - 00002371-200711000-00005
DO - https://dx.doi.org/10.1097/CJI.0b013e318156e47e
PT - Clinical Trial, Phase II
PT - Journal Article
ID - 18049334 [pubmed]
ID - 10.1097/CJI.0b013e318156e47e [doi]
ID - 00002371-200711000-00005 [pii]
ID - PMC2134980 [pmc]
ID - NIHMS35214 [mid]
PP - ppublish
GI - No: Z01 SC003811-32
Organization: *Intramural NIH HHS*
Country: United States
LG - English
DP - 2007 Nov-Dec
DC - 20071130
EZ - 2007/12/01 09:00
DA - 2008/01/25 09:00
DT - 2007/12/01 09:00
YR - 2007
ED - 20080124
RD - 20161124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=18049334
<343. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 17729038
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Gatzka M
AU - Walsh CM
FA - Gatzka, Martina
FA - Walsh, Craig M
IN - Gatzka, Martina. Department of Molecular Biology and Biochemistry, Center for Immunology, University of California, Irvine, CA, USA. mgatzka@uci.edu
TI - Apoptotic signal transduction and T cell tolerance. [Review] [125 refs]
SO - Autoimmunity. 40(6):442-52, 2007 Sep
AS - Autoimmunity. 40(6):442-52, 2007 Sep
NJ - Autoimmunity
PI - Journal available in: Print
PI - Citation processed from: Print
JC - a5h, 8900070
IO - Autoimmunity
SB - Index Medicus
CP - England
MH - Animals
MH - *Apoptosis
MH - Autoimmunity
MH - Clonal Deletion
MH - Humans
MH - Lymphocyte Activation
MH - Receptors, Antigen, T-Cell/ge [Genetics]
MH - *Receptors, Antigen, T-Cell/im [Immunology]
MH - Receptors, Antigen, T-Cell/me [Metabolism]
MH - Self Tolerance/ge [Genetics]
MH - *Self Tolerance
MH - *Signal Transduction
MH - T-Lymphocyte Subsets/im [Immunology]
MH - T-Lymphocyte Subsets/me [Metabolism]
MH - T-Lymphocytes/cy [Cytology]
MH - *T-Lymphocytes/im [Immunology]
MH - T-Lymphocytes/me [Metabolism]
MH - Thymus Gland/im [Immunology]
AB - The healthy immune system makes use of a variety of surveillance mechanisms at different stages of lymphoid development to prevent the occurrence and expansion of potentially harmful autoreactive T cell clones. Disruption of these mechanisms may lead to inappropriate activation of T cells and the development of autoimmune and lymphoproliferative diseases [such as multiple sclerosis, rheumatoid arthritis, lupus erythematosus, diabetes and autoimmune lymphoproliferative syndrome (ALPS)]. Clonal deletion of T cells with high affinities for self-peptide-MHC via programmed cell death (apoptosis) is an essential mechanism leading to self-tolerance. Referred to as negative selection, central tolerance in the thymus serves as the first checkpoint for the developing T cell repertoire and involves the apoptotic elimination of potentially autoreactive T cells clones bearing high affinity T cell receptors (TCR) that recognize autoantigens presented by thymic epithelial cells. Autoreactive T cells that escape negative selection are held in check in the periphery by either functional inactivation ("anergy") or extrathymic clonal deletion, both of which are dependent on the strength and frequency of the TCR signal and the costimulatory context, or by regulatory T cells. This review provides an overview of the different molecular executioners of cell death programs that are vital to intrathymic or extrathymic clonal deletion of T cells. Further, the potential involvement of various apoptotic signaling paradigms are discussed with respect to the genesis and pathophysiology of autoimmune disease. [References: 125]
RN - 0 (Receptors, Antigen, T-Cell)
IS - 0891-6934
IL - 0891-6934
DI - 781631027
DO - https://dx.doi.org/10.1080/08916930701464962
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 17729038 [pubmed]
ID - 781631027 [pii]
ID - 10.1080/08916930701464962 [doi]
PP - ppublish
GI - No: R01AI0506
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: R01AI63419
Organization: (AI) *NIAID NIH HHS*
Country: United States
LG - English
DP - 2007 Sep
DC - 20070830
EZ - 2007/08/31 09:00
DA - 2007/12/14 09:00
DT - 2007/08/31 09:00
YR - 2007
ED - 20071213
RD - 20070830
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=17729038
<344. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 17684018
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Selvendiran K
AU - Tong L
AU - Vishwanath S
AU - Bratasz A
AU - Trigg NJ
AU - Kutala VK
AU - Hideg K
AU - Kuppusamy P
FA - Selvendiran, Karuppaiyah
FA - Tong, Liyue
FA - Vishwanath, Shilpa
FA - Bratasz, Anna
FA - Trigg, Nancy J
FA - Kutala, Vijay K
FA - Hideg, Kalman
FA - Kuppusamy, Periannan
IN - Selvendiran, Karuppaiyah. Department of Internal Medicine, Davis Heart and Lung Research Institute and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
TI - EF24 induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by increasing PTEN expression.
SO - Journal of Biological Chemistry. 282(39):28609-18, 2007 Sep 28
AS - J Biol Chem. 282(39):28609-18, 2007 Sep 28
NJ - The Journal of biological chemistry
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - hiv, 2985121r
IO - J. Biol. Chem.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610350
OI - Source: NLM. NIHMS46456
SB - Index Medicus
CP - United States
MH - Animals
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - *Apoptosis/de [Drug Effects]
MH - *Benzylidene Compounds/pd [Pharmacology]
MH - Benzylidene Compounds/tu [Therapeutic Use]
MH - Caspase Inhibitors
MH - Caspases/me [Metabolism]
MH - *Cell Division/de [Drug Effects]
MH - Cell Survival
MH - Cisplatin
MH - Cysteine Proteinase Inhibitors/pd [Pharmacology]
MH - Drug Resistance, Neoplasm/de [Drug Effects]
MH - Fas Ligand Protein/bi [Biosynthesis]
MH - Female
MH - *G2 Phase/de [Drug Effects]
MH - *Gene Expression Regulation, Neoplastic/de [Drug Effects]
MH - Humans
MH - Mice
MH - Mice, Nude
MH - Ovarian Neoplasms/dt [Drug Therapy]
MH - *Ovarian Neoplasms/me [Metabolism]
MH - PTEN Phosphohydrolase/ai [Antagonists & Inhibitors]
MH - *PTEN Phosphohydrolase/bi [Biosynthesis]
MH - Phosphorylation/de [Drug Effects]
MH - *Piperidones/pd [Pharmacology]
MH - Piperidones/tu [Therapeutic Use]
MH - Proto-Oncogene Proteins c-akt/me [Metabolism]
MH - Proto-Oncogene Proteins c-mdm2/me [Metabolism]
MH - RNA, Small Interfering/pd [Pharmacology]
MH - Time Factors
MH - Tumor Suppressor Protein p53/me [Metabolism]
MH - Ubiquitin/me [Metabolism]
MH - Up-Regulation/de [Drug Effects]
MH - Xenograft Model Antitumor Assays
AB - We report that EF24, a synthetic compound 3,5-bis(2-flurobenzylidene)piperidin-4-one, greatly inhibits cisplatin-resistant (CR) human ovarian cancer cell proliferation. The inhibitory effect of EF24 on cell proliferation is associated with G(2)/M phase cell cycle arrest and increased G(2)/M checkpoint protein (pp53, p53, and p21) levels. Within 24 h following treatment, EF24 induced apoptosis in CR cells. The apoptosis was partially blocked by the general caspase inhibitor z-VAD. Within 12 h, EF24 induced a membranous FasL expression, consistent with a substantial decrease in the Ser(473) and Thr(308) phosphorylation of Akt, a known negative regulator of FasL transcription. Also, EF24 activated the phosphorylated PTEN and marginally up-regulated total PTEN expression through the inhibition of ubiquitin-mediated PTEN degradation. Suppression of PTEN expression with siRNA significantly reduced the p53 and p21 levels and activated Akt phosphorylation at Ser(473) and Thr(308), resulting in decreased apoptosis and increased cell survival. On the other hand, overexpression of PTEN markedly induced apoptosis. Our results clearly suggested that EF24 induced significant increase in PTEN expression. The up-regulation of PTEN inhibited Akt and MDM2, which enhanced the level of p53, thereby inducing G(2)/M arrest and apoptosis. Therefore, EF24 appears to have a potential therapeutic role in human ovarian cancer through the activation of PTEN.
RN - 0 (3,5-bis(2-fluorobenzylidene)piperidin-4-one)
RN - 0 (Antineoplastic Agents)
RN - 0 (Benzylidene Compounds)
RN - 0 (Caspase Inhibitors)
RN - 0 (Cysteine Proteinase Inhibitors)
RN - 0 (FASLG protein, human)
RN - 0 (Fas Ligand Protein)
RN - 0 (Piperidones)
RN - 0 (RNA, Small Interfering)
RN - 0 (Tumor Suppressor Protein p53)
RN - 0 (Ubiquitin)
RN - EC 2-3-2-27 (MDM2 protein, human)
RN - EC 2-3-2-27 (Proto-Oncogene Proteins c-mdm2)
RN - EC 2-7-11-1 (Proto-Oncogene Proteins c-akt)
RN - EC 3-1-3-67 (PTEN Phosphohydrolase)
RN - EC 3-1-3-67 (PTEN protein, human)
RN - EC 3-4-22 (Caspases)
RN - Q20Q21Q62J (Cisplatin)
IS - 0021-9258
IL - 0021-9258
DI - M703796200
DO - https://dx.doi.org/10.1074/jbc.M703796200
PT - Journal Article
PT - Research Support, N.I.H., Extramural
PT - Research Support, Non-U.S. Gov't
ID - 17684018 [pubmed]
ID - M703796200 [pii]
ID - 10.1074/jbc.M703796200 [doi]
ID - PMC4610350 [pmc]
ID - NIHMS46456 [mid]
PP - ppublish
GI - No: R01 CA102264
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA102264-04
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA102264
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20070807
DP - 2007 Sep 28
DC - 20070924
EZ - 2007/08/09 09:00
DA - 2007/11/09 09:00
DT - 2007/08/09 09:00
YR - 2007
ED - 20071108
RD - 20161124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=17684018
<345. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 17671210
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Jacquemont C
AU - Taniguchi T
FA - Jacquemont, Celine
FA - Taniguchi, Toshiyasu
IN - Jacquemont, Celine. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
TI - Proteasome function is required for DNA damage response and fanconi anemia pathway activation.
SO - Cancer Research. 67(15):7395-405, 2007 Aug 01
AS - Cancer Res. 67(15):7395-405, 2007 Aug 01
NJ - Cancer research
PI - Journal available in: Print
PI - Citation processed from: Print
JC - cnf, 2984705r
IO - Cancer Res.
SB - Index Medicus
CP - United States
MH - Ataxia Telangiectasia Mutated Proteins
MH - BRCA1 Protein/ai [Antagonists & Inhibitors]
MH - BRCA1 Protein/ge [Genetics]
MH - BRCA1 Protein/me [Metabolism]
MH - Blotting, Western
MH - Boronic Acids/pd [Pharmacology]
MH - Bortezomib
MH - Cell Cycle Proteins/ai [Antagonists & Inhibitors]
MH - Cell Cycle Proteins/ge [Genetics]
MH - Cell Cycle Proteins/me [Metabolism]
MH - Cells, Cultured
MH - *DNA Damage/re [Radiation Effects]
MH - DNA Repair
MH - DNA-Binding Proteins/ai [Antagonists & Inhibitors]
MH - DNA-Binding Proteins/ge [Genetics]
MH - DNA-Binding Proteins/me [Metabolism]
MH - *Fanconi Anemia
MH - Fanconi Anemia Complementation Group D2 Protein/ai [Antagonists & Inhibitors]
MH - Fanconi Anemia Complementation Group D2 Protein/ge [Genetics]
MH - *Fanconi Anemia Complementation Group D2 Protein/me [Metabolism]
MH - Female
MH - Flow Cytometry
MH - Gamma Rays
MH - HeLa Cells
MH - Humans
MH - Leupeptins/pd [Pharmacology]
MH - Microscopy, Fluorescence
MH - Nuclear Proteins/ai [Antagonists & Inhibitors]
MH - Nuclear Proteins/ge [Genetics]
MH - Nuclear Proteins/me [Metabolism]
MH - Ovarian Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/pa [Pathology]
MH - Phosphorylation/de [Drug Effects]
MH - Phosphorylation/re [Radiation Effects]
MH - Proteasome Endopeptidase Complex/ge [Genetics]
MH - *Proteasome Endopeptidase Complex/me [Metabolism]
MH - Proteasome Endopeptidase Complex/re [Radiation Effects]
MH - Proteasome Inhibitors
MH - Protein-Serine-Threonine Kinases/ai [Antagonists & Inhibitors]
MH - Protein-Serine-Threonine Kinases/ge [Genetics]
MH - Protein-Serine-Threonine Kinases/me [Metabolism]
MH - Pyrazines/pd [Pharmacology]
MH - RNA, Small Interfering/pd [Pharmacology]
MH - Rad51 Recombinase/ai [Antagonists & Inhibitors]
MH - Rad51 Recombinase/ge [Genetics]
MH - Rad51 Recombinase/me [Metabolism]
MH - *Signal Transduction
MH - Tumor Suppressor Proteins/ai [Antagonists & Inhibitors]
MH - Tumor Suppressor Proteins/ge [Genetics]
MH - Tumor Suppressor Proteins/me [Metabolism]
MH - *Ubiquitin/me [Metabolism]
AB - Proteasome inhibitors sensitize tumor cells to DNA-damaging agents, including ionizing radiation (IR), and DNA cross-linking agents (melphalan and cisplatin) through unknown mechanisms. The Fanconi anemia pathway is a DNA damage-activated signaling pathway, which regulates cellular resistance to DNA cross-linking agents. Monoubiquitination and nuclear foci formation of FANCD2 are critical steps of the Fanconi anemia pathway. Here, we show that proteasome function is required for the activation of the Fanconi anemia pathway and for DNA damage signaling. Proteasome inhibitors (bortezomib and MG132) and depletion of 19S and 20S proteasome subunits (PSMD4, PSMD14, and PSMB3) inhibited monoubiquitination and/or nuclear foci formation of FANCD2, whereas depletion of DSS1/SHFM1, a subunit of the 19S proteasome that also directly binds to BRCA2, did not inhibit FANCD2 monoubiquitination or foci formation. On the other hand, DNA damage-signaling processes, such as IR-induced foci formation of phosphorylated ATM (phospho-ATM), 53BP1, NBS1, BRCA1, FANCD2, and RAD51, were delayed in the presence of proteasome inhibitors, whereas ATM autophosphorylation and nuclear foci formation of gammaH2AX, MDC1, and RPA were not inhibited. Furthermore, persistence of DNA damage and abrogation of the IR-induced G(1)-S checkpoint resulted from proteasome inhibition. In summary, we showed that the proteasome function is required for monoubiquitination of FANCD2, foci formation of 53BP1, phospho-ATM, NBS1, BRCA1, FANCD2, and RAD51. The dependence of specific DNA damage-signaling steps on the proteasome may explain the sensitization of tumor cells to DNA-damaging chemotherapeutic agents by proteasome inhibitors.
RN - 0 (BRCA1 Protein)
RN - 0 (Boronic Acids)
RN - 0 (Cell Cycle Proteins)
RN - 0 (DNA-Binding Proteins)
RN - 0 (FANCD2 protein, human)
RN - 0 (Fanconi Anemia Complementation Group D2 Protein)
RN - 0 (Leupeptins)
RN - 0 (NBN protein, human)
RN - 0 (Nuclear Proteins)
RN - 0 (PSMD4 protein, human)
RN - 0 (Proteasome Inhibitors)
RN - 0 (Pyrazines)
RN - 0 (RNA, Small Interfering)
RN - 0 (Tumor Suppressor Proteins)
RN - 0 (Ubiquitin)
RN - 69G8BD63PP (Bortezomib)
RN - EC 2-7-11-1 (ATM protein, human)
RN - EC 2-7-11-1 (Ataxia Telangiectasia Mutated Proteins)
RN - EC 2-7-11-1 (Protein-Serine-Threonine Kinases)
RN - EC 2-7-7 (Rad51 Recombinase)
RN - EC 3-4-25-1 (Proteasome Endopeptidase Complex)
RN - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
IS - 0008-5472
IL - 0008-5472
DI - 67/15/7395
DO - https://dx.doi.org/10.1158/0008-5472.CAN-07-1015
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 17671210 [pubmed]
ID - 67/15/7395 [pii]
ID - 10.1158/0008-5472.CAN-07-1015 [doi]
PP - ppublish
LG - English
DP - 2007 Aug 01
DC - 20070802
EZ - 2007/08/03 09:00
DA - 2007/09/12 09:00
DT - 2007/08/03 09:00
YR - 2007
ED - 20070911
RD - 20161124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=17671210
<346. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 17537491
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Welch S
AU - Hirte HW
AU - Carey MS
AU - Hotte SJ
AU - Tsao MS
AU - Brown S
AU - Pond GR
AU - Dancey JE
AU - Oza AM
FA - Welch, Stephen
FA - Hirte, Hal W
FA - Carey, Mark S
FA - Hotte, Sebastian J
FA - Tsao, Ming-Sound
FA - Brown, Shirley
FA - Pond, Gregory R
FA - Dancey, Janet E
FA - Oza, Amit M
IN - Welch, Stephen. Princess Margaret Hospital, Toronto, Ontario, Canada M56 2M9.
TI - UCN-01 in combination with topotecan in patients with advanced recurrent ovarian cancer: a study of the Princess Margaret Hospital Phase II consortium.
SO - Gynecologic Oncology. 106(2):305-10, 2007 Aug
AS - Gynecol Oncol. 106(2):305-10, 2007 Aug
NJ - Gynecologic oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - fxc, 0365304
IO - Gynecol. Oncol.
SB - Index Medicus
CP - United States
MH - Adult
MH - Aged
MH - Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
MH - *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH - Female
MH - Humans
MH - Middle Aged
MH - *Neoplasm Recurrence, Local/dt [Drug Therapy]
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - Staurosporine/ad [Administration & Dosage]
MH - Staurosporine/ae [Adverse Effects]
MH - Staurosporine/aa [Analogs & Derivatives]
MH - Topotecan/ad [Administration & Dosage]
MH - Topotecan/ae [Adverse Effects]
AB - BACKGROUND AND OBJECTIVE: UCN-01 is a staurosporine analogue shown to abrogate the G2 checkpoint through inhibition of cyclin-dependent kinases. Preclinical evidence suggests synergy between UCN-01 and cytotoxic chemotherapy. Topotecan is an active agent in ovarian cancer. This phase II study was conducted to investigate the safety and efficacy of topotecan and UCN-01 in patients with advanced ovarian cancer.
AB - METHODS: A two-stage phase II trial was designed for patients with advanced ovarian cancer with progressive disease despite prior treatment with platinum and paclitaxel. Patients with advanced ovarian cancer were treated with topotecan, 1 mg/m(2) IV, days 1 to 5, and UCN-01 70 mg/m(2) on day 1 of the first cycle, and 35 mg/m(2) on day 1 of all subsequent cycles. Treatment was repeated on a 3-week cycle. The primary objective of this study was objective response rate while secondary objectives included rates of stable disease, duration of response, progression-free and overall survival, as well as toxicity. Tumor biopsy specimens were also collected where possible for molecular correlative studies.
AB - RESULTS: Twenty-nine patients are evaluable for toxicity and efficacy. Three patients (10%) achieved a partial response. The median time to progression was 3.3 months (95% CI 1.5-NA), and the median overall survival was 9.7 months (95% CI: 7.5-15.3). The most common grade 3-4 toxicities were neutropenia (79%), anemia (41%), thrombocytopenia (14%), hyperglycemia (10%), and pain (10%).
AB - CONCLUSION: The combination of UCN-01 and topotecan is generally well tolerated, however, this combination is not considered to have significant antitumor activity against advanced ovarian cancer.
RN - 7BU5H4V94A (7-hydroxystaurosporine)
RN - 7M7YKX2N15 (Topotecan)
RN - H88EPA0A3N (Staurosporine)
IS - 0090-8258
IL - 0090-8258
DI - S0090-8258(07)00146-1
DO - https://dx.doi.org/10.1016/j.ygyno.2007.02.018
PT - Clinical Trial, Phase I
PT - Clinical Trial, Phase II
PT - Journal Article
PT - Research Support, N.I.H., Extramural
ID - 17537491 [pubmed]
ID - S0090-8258(07)00146-1 [pii]
ID - 10.1016/j.ygyno.2007.02.018 [doi]
PP - ppublish
PH - 2006/10/31 [received]
PH - 2007/01/13 [revised]
PH - 2007/02/20 [accepted]
GI - No: #N01-CM-1701
Organization: (CM) *NCI NIH HHS*
Country: United States
LG - English
EP - 20070529
DP - 2007 Aug
DC - 20070730
EZ - 2007/06/01 09:00
DA - 2007/09/07 09:00
DT - 2007/06/01 09:00
YR - 2007
ED - 20070906
RD - 20131121
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=17537491
<347. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 17404099
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Nomi T
AU - Sho M
AU - Akahori T
AU - Hamada K
AU - Kubo A
AU - Kanehiro H
AU - Nakamura S
AU - Enomoto K
AU - Yagita H
AU - Azuma M
AU - Nakajima Y
FA - Nomi, Takeo
FA - Sho, Masayuki
FA - Akahori, Takahiro
FA - Hamada, Kaoru
FA - Kubo, Atsushi
FA - Kanehiro, Hiromichi
FA - Nakamura, Shinji
FA - Enomoto, Koji
FA - Yagita, Hideo
FA - Azuma, Miyuki
FA - Nakajima, Yoshiyuki
IN - Nomi, Takeo. Department of Surgery, Second Department of Internal Medicine, First Department of Internal Medicine, Nara Medical University, Nara, Japan.
TI - Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer.
SO - Clinical Cancer Research. 13(7):2151-7, 2007 Apr 01
AS - Clin Cancer Res. 13(7):2151-7, 2007 Apr 01
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print
PI - Citation processed from: Print
JC - c2h, 9502500
IO - Clin. Cancer Res.
SB - Index Medicus
CP - United States
MH - Adenocarcinoma/im [Immunology]
MH - *Adenocarcinoma/me [Metabolism]
MH - Adenocarcinoma/pa [Pathology]
MH - Aged
MH - Animals
MH - Antibodies, Monoclonal/pd [Pharmacology]
MH - Antigens, CD/de [Drug Effects]
MH - *Antigens, CD/me [Metabolism]
MH - Antigens, CD274
MH - Antineoplastic Combined Chemotherapy Protocols/pd [Pharmacology]
MH - *Biomarkers, Tumor/an [Analysis]
MH - CD8-Positive T-Lymphocytes/de [Drug Effects]
MH - CD8-Positive T-Lymphocytes/im [Immunology]
MH - Deoxycytidine/aa [Analogs & Derivatives]
MH - Deoxycytidine/pd [Pharmacology]
MH - Female
MH - Humans
MH - Immunohistochemistry
MH - Lymphocytes, Tumor-Infiltrating/de [Drug Effects]
MH - Lymphocytes, Tumor-Infiltrating/im [Immunology]
MH - Male
MH - Mice
MH - Mice, Inbred C57BL
MH - Middle Aged
MH - Pancreatic Neoplasms/im [Immunology]
MH - *Pancreatic Neoplasms/me [Metabolism]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Peptides/me [Metabolism]
MH - Prognosis
MH - Programmed Cell Death 1 Ligand 2 Protein
MH - Reverse Transcriptase Polymerase Chain Reaction
AB - PURPOSE: The programmed death-1 ligand/programmed death-1 (PD-L/PD-1) pathway has been recently suggested to play a pivotal role in the immune evasion of tumors from host immune system. In this study, we tried to reveal the clinical importance and therapeutic potential of the PD-L/PD-1 pathway in pancreatic cancer, which is one of the most aggressive and intractable malignant tumors.
AB - EXPERIMENTAL DESIGN: We used immunohistochemistry to investigate PD-L expression in 51 patients with pancreatic cancer who underwent surgery and explored the therapeutic efficacy of blocking the PD-L1/PD-1 pathway in murine pancreatic cancer in vivo.
AB - RESULTS: PD-L1-positive patients had a significantly poorer prognosis than the PD-L1-negative patients, whereas there was no significant correlation of tumor PD-L2 expression with patient survival. PD-L1 expression was inversely correlated with tumor-infiltrating T lymphocytes, particularly CD8(+) T cells. These clinical data have suggested that the PD-L1/PD-1 pathway may be a critical regulator in human pancreatic cancer. Monoclonal antibodies against PD-L1 or PD-1 induced a substantial antitumor effect on murine pancreatic cancer in vivo. PD-L1 blockade promoted CD8(+) T-cell infiltration into the tumor and induced local immune activation. Furthermore, the combination of anti-PD-L1 monoclonal antibody and gemcitabine exhibited a significant synergistic effect on murine pancreatic cancer and resulted in complete response without overt toxicity.
AB - CONCLUSION: Our data suggest for the first time that PD-L1 status may be a new predictor of prognosis for patients with pancreatic cancer and provide the rationale for developing a novel therapy of targeting the PD-L/PD-1 pathway against this fatal disease.
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (Antigens, CD274)
RN - 0 (Biomarkers, Tumor)
RN - 0 (CD274 protein, human)
RN - 0 (PDCD1LG2 protein, human)
RN - 0 (Pdcd1lg2 protein, mouse)
RN - 0 (Peptides)
RN - 0 (Programmed Cell Death 1 Ligand 2 Protein)
RN - 0W860991D6 (Deoxycytidine)
RN - B76N6SBZ8R (gemcitabine)
IS - 1078-0432
IL - 1078-0432
DI - 13/7/2151
DO - https://dx.doi.org/10.1158/1078-0432.CCR-06-2746
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 17404099 [pubmed]
ID - 13/7/2151 [pii]
ID - 10.1158/1078-0432.CCR-06-2746 [doi]
PP - ppublish
LG - English
DP - 2007 Apr 01
DC - 20070403
EZ - 2007/04/04 09:00
DA - 2007/06/22 09:00
DT - 2007/04/04 09:00
YR - 2007
ED - 20070621
RD - 20151119
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=17404099
<348. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 16968694
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Fikaris AJ
AU - Lewis AE
AU - Abulaiti A
AU - Tsygankova OM
AU - Meinkoth JL
FA - Fikaris, Aphrothiti J
FA - Lewis, Aurelia E
FA - Abulaiti, Adili
FA - Tsygankova, Oxana M
FA - Meinkoth, Judy L
IN - Fikaris, Aphrothiti J. Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
TI - Ras triggers ataxia-telangiectasia-mutated and Rad-3-related activation and apoptosis through sustained mitogenic signaling.
SO - Journal of Biological Chemistry. 281(46):34759-67, 2006 Nov 17
AS - J Biol Chem. 281(46):34759-67, 2006 Nov 17
NJ - The Journal of biological chemistry
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - hiv, 2985121r
IO - J. Biol. Chem.
SB - Index Medicus
CP - United States
MH - Animals
MH - *Apoptosis/ph [Physiology]
MH - Ataxia Telangiectasia Mutated Proteins
MH - Cell Cycle
MH - Cell Cycle Proteins/ge [Genetics]
MH - *Cell Cycle Proteins/me [Metabolism]
MH - Cells, Cultured
MH - Checkpoint Kinase 1
MH - Cyclin-Dependent Kinase 2/me [Metabolism]
MH - Gene Expression Regulation
MH - Humans
MH - *Mitogens/me [Metabolism]
MH - Protein Kinases/me [Metabolism]
MH - Protein-Serine-Threonine Kinases/ge [Genetics]
MH - *Protein-Serine-Threonine Kinases/me [Metabolism]
MH - Rats
MH - Rats, Wistar
MH - *Signal Transduction
MH - Thyroid Gland/cy [Cytology]
MH - *Thyroid Gland/me [Metabolism]
MH - Up-Regulation
MH - ras Proteins/ge [Genetics]
MH - *ras Proteins/me [Metabolism]
AB - Genetic evidence indicates that Ras plays a critical role in the initiation and progression of human thyroid tumors. Paradoxically, acute expression of activated Ras in normal rat thyroid cells induced deregulated cell cycle progression and apoptosis. We investigated whether cell cycle progression was required for Ras-stimulated apoptosis. Ras increased CDK-2 activity following its introduction into quiescent cells. Apoptotic cells exhibited a sustained increase in CDK-2 activity, accompanied by the loss of CDK-2-associated p27. Blockade of Ras-induced CDK-2 activity and S phase entry via overexpression of p27 inhibited apoptosis. Inactivation of the retinoblastoma protein in quiescent cells through expression of HPV-E7 stimulated cell cycle progression and apoptosis, indicating that deregulated cell cycle progression is sufficient to induce apoptosis. Ras failed to induce G1 phase growth arrest in normal rat thyroid cells. Rather, Ras-expressing thyroid cells progressed into S and G2 phases and evoked a checkpoint response characterized by the activation of ATR. Ras-stimulated ATR activity, as evidenced by Chk1 and p53 phosphorylation, was blocked by p27, suggesting that cell cycle progression triggers checkpoint activation, likely as a consequence of replication stress. These data reveal that Ras is capable of inducing a DNA damage response with characteristics similar to those reported in precancerous lesions. Our findings also suggest that the frequent mutational activation of Ras in thyroid tumors reflects the ability of Ras-expressing cells to bypass checkpoints and evade apoptosis rather than to simply increase proliferative potential.
RN - 0 (Cell Cycle Proteins)
RN - 0 (Mitogens)
RN - EC 2-7 (Protein Kinases)
RN - EC 2-7-11-1 (ATR protein, human)
RN - EC 2-7-11-1 (Ataxia Telangiectasia Mutated Proteins)
RN - EC 2-7-11-1 (CHEK1 protein, human)
RN - EC 2-7-11-1 (Checkpoint Kinase 1)
RN - EC 2-7-11-1 (Chek1 protein, rat)
RN - EC 2-7-11-1 (Protein-Serine-Threonine Kinases)
RN - EC 2-7-11-22 (Cyclin-Dependent Kinase 2)
RN - EC 3-6-5-2 (ras Proteins)
IS - 0021-9258
IL - 0021-9258
DI - M606737200
DO - https://dx.doi.org/10.1074/jbc.M606737200
PT - Journal Article
PT - Research Support, N.I.H., Extramural
ID - 16968694 [pubmed]
ID - M606737200 [pii]
ID - 10.1074/jbc.M606737200 [doi]
PP - ppublish
GI - No: DK55757
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG - English
EP - 20060912
DP - 2006 Nov 17
DC - 20061113
EZ - 2006/09/14 09:00
DA - 2007/01/19 09:00
DT - 2006/09/14 09:00
YR - 2006
ED - 20070118
RD - 20161124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=16968694
<349. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 16801985
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Bayes M
AU - Rabasseda X
AU - Prous JR
FA - Bayes, M
FA - Rabasseda, X
FA - Prous, J R
IN - Bayes, M. Prous Science, Barcelona, Spain. mbayes@prous.com
TI - Gateways to clinical trials.
SO - Methods & Findings in Experimental & Clinical Pharmacology. 28(4):233-77, 2006 May
AS - Methods Find Exp Clin Pharmacol. 28(4):233-77, 2006 May
NJ - Methods and findings in experimental and clinical pharmacology
PI - Journal available in: Print
PI - Citation processed from: Print
JC - lzn, 7909595
IO - Methods Find Exp Clin Pharmacol
SB - Index Medicus
CP - Spain
MH - *Clinical Trials as Topic
MH - Humans
AB - Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com/. This issue focuses on the following selection of drugs: Adalimumab, adenosine triphosphate, alemtuzumab, alendronate sodium/cholecalciferol, aliskiren fumarate, AMGN-0007, aminolevulinic acid methyl ester, anakinra, anidulafungin, aripiprazole, atomoxetine hydrochloride; Bevacizumab, bosentan; Calcipotriol/beta methasone dipropionate, caldaret hydrate, caspofungin acetate, cetuximab, cinacalcet hydrochloride, clopidogrel, cocaine-BSA conjugate, conivaptan hydrochloride, Cypher; Darbepoetin alfa, delmitide, desloratadine, desmoteplase, desoxyepothilone B, disufenton sodium, DU-176b, duloxetine hydrochloride, dutasteride; EBV-specific CTLs, ecogramostim, edodekin alfa, efalizumab, eletriptan, emtricitabine, entecavir, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, etoricoxib, everolimus, ezetimibe; Fanapanel, fondaparinux sodium; Gefitinib, GTI-2040, GW-501516; Her2 E75-peptide vaccine, human insulin; Ibogaine, icatibant acetate, Id-KLH vaccine, imatinib mesylate, immune globulin subcutaneous [human], indacaterol, inolimomab, ipilimumab, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, lanthanum carbonate, lenalidomide, levocetirizine, levodopa methyl ester hydrochloride/carbidopa, levodopa/carbidopa/entacapone, lidocaine/prilocaine; Maraviroc, mecasermin, melevodopa hydrochloride, mepolizumab, mitumomab; Nesiritide; Omalizumab, oral insulin; Parathyroid hormone (human recombinant), patupilone, pegaptanib sodium, PEG-filgrastim, pemetrexed disodium, photochlor, pimecrolimus, posaconazole, prasterone, prasugrel, pregabalin, prilocaine, PRX-00023; QS-21; Ranibizumab, ranirestat, rhodamine 123, rotigaptide; Sarcosine, sirolimus-eluting stent, sitaxsentan sodium, solifenacin succinate, Staphylococcus aureus vaccine; Tadalafil, talactoferrin alfa, talaporfin sodium, Taxus, tecadenoson, tegaserod maleate, telithromycin, temsirolimus, tenofovir disoproxil fumarate, teriparatide, terutroban sodium, tesaglitazar, tesmilifene hydrochloride, TG-100115, tigecycline, torcetrapib; Ularitide; Valproic acid, sodium, voriconazole; Zotarolimus, zotarolimus-eluting stent.
IS - 0379-0355
IL - 0379-0355
DI - 3155
PT - Bibliography
ID - 16801985 [pubmed]
ID - 3155 [pii]
PP - ppublish
LG - English
DP - 2006 May
DC - 20060627
EZ - 2006/06/28 09:00
DA - 2006/12/09 09:00
DT - 2006/06/28 09:00
YR - 2006
ED - 20061204
RD - 20071115
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=16801985
<350. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 16710025
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Beck KE
AU - Blansfield JA
AU - Tran KQ
AU - Feldman AL
AU - Hughes MS
AU - Royal RE
AU - Kammula US
AU - Topalian SL
AU - Sherry RM
AU - Kleiner D
AU - Quezado M
AU - Lowy I
AU - Yellin M
AU - Rosenberg SA
AU - Yang JC
FA - Beck, Kimberly E
FA - Blansfield, Joseph A
FA - Tran, Khoi Q
FA - Feldman, Andrew L
FA - Hughes, Marybeth S
FA - Royal, Richard E
FA - Kammula, Udai S
FA - Topalian, Suzanne L
FA - Sherry, Richard M
FA - Kleiner, David
FA - Quezado, Martha
FA - Lowy, Israel
FA - Yellin, Michael
FA - Rosenberg, Steven A
FA - Yang, James C
IN - Beck, Kimberly E. Surgery Branch and Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1201, USA.
TI - Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4.
CM - Comment in: J Clin Oncol. 2006 Dec 1;24(34):5469-70; author reply 5470-1; PMID: 17135653
CM - Comment in: J Clin Oncol. 2006 May 20;24(15):2230-2; PMID: 16710020
SO - Journal of Clinical Oncology. 24(15):2283-9, 2006 May 20
AS - J Clin Oncol. 24(15):2283-9, 2006 May 20
NJ - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - jco, 8309333
IO - J. Clin. Oncol.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2140223
OI - Source: NLM. NIHMS35289
SB - Index Medicus
CP - United States
MH - Adrenal Cortex Hormones/tu [Therapeutic Use]
MH - *Antibodies, Monoclonal/ae [Adverse Effects]
MH - Antibodies, Monoclonal/tu [Therapeutic Use]
MH - Antigens, CD
MH - *Antigens, Differentiation/im [Immunology]
MH - *Antineoplastic Agents/ae [Adverse Effects]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - CTLA-4 Antigen
MH - Cancer Vaccines
MH - Carcinoma, Renal Cell/dt [Drug Therapy]
MH - *Enterocolitis/ci [Chemically Induced]
MH - Enterocolitis/dt [Drug Therapy]
MH - Female
MH - Gastrointestinal Agents/tu [Therapeutic Use]
MH - Humans
MH - Infliximab
MH - Kidney Neoplasms/dt [Drug Therapy]
MH - Male
MH - Melanoma/dt [Drug Therapy]
MH - Middle Aged
MH - *Neoplasms/dt [Drug Therapy]
MH - Skin Neoplasms/dt [Drug Therapy]
AB - PURPOSE: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is an inhibitory receptor on T cells. Knocking out CTLA4 in mice causes lethal lymphoproliferation, and polymorphisms in human CTLA4 are associated with autoimmune disease. Trials of the anti-CTLA4 antibody ipilimumab (MDX-010) have resulted in durable cancer regression and immune-mediated toxicities. A report on the diagnosis, pathology, treatment, clinical outcome, and significance of the immune-mediated enterocolitis seen with ipilimumab is presented.
AB - PATIENTS AND METHODS: We treated 198 patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) with ipilimumab.
AB - RESULTS: The overall objective tumor response rate was 14%. We observed several immune mediated toxicities including dermatitis, enterocolitis, hypophysitis, uveitis, hepatitis, and nephritis. Enterocolitis, defined by grade 3/4 clinical presentation and/or biopsy documentation, was the most common major toxicity (21% of patients). It presented with diarrhea, and biopsies showed both neutrophilic and lymphocytic inflammation. Most patients who developed enterocolitis responded to high-dose systemic corticosteroids. There was no evidence that steroid administration affected tumor responses. Five patients developed perforation or required colectomy. Four other patients with steroid-refractory enterocolitis appeared to respond promptly to tumor necrosis factor alpha blockade with infliximab. Objective tumor response rates in patients with enterocolitis were 36% for MM and 35% for RCC, compared with 11% and 2% in patients without enterocolitis, respectively (P = .0065 for MM and P = .0016 for RCC).
AB - CONCLUSION: CTLA4 seems to be a significant component of tolerance to tumor and in protection against immune mediated enterocolitis and these phenomena are significantly associated in cancer patients.
RN - 0 (Adrenal Cortex Hormones)
RN - 0 (Antibodies, Monoclonal)
RN - 0 (Antigens, CD)
RN - 0 (Antigens, Differentiation)
RN - 0 (Antineoplastic Agents)
RN - 0 (CTLA-4 Antigen)
RN - 0 (CTLA4 protein, human)
RN - 0 (Cancer Vaccines)
RN - 0 (Ctla4 protein, mouse)
RN - 0 (Gastrointestinal Agents)
RN - 6T8C155666 (ipilimumab)
RN - B72HH48FLU (Infliximab)
ES - 1527-7755
IL - 0732-183X
DI - 24/15/2283
DO - https://dx.doi.org/10.1200/JCO.2005.04.5716
PT - Journal Article
PT - Research Support, N.I.H., Intramural
ID - 16710025 [pubmed]
ID - 24/15/2283 [pii]
ID - 10.1200/JCO.2005.04.5716 [doi]
ID - PMC2140223 [pmc]
ID - NIHMS35289 [mid]
PP - ppublish
GI - No: Z01 SC003811-32
Organization: *Intramural NIH HHS*
Country: United States
LG - English
DP - 2006 May 20
DC - 20060519
EZ - 2006/05/20 09:00
DA - 2006/06/08 09:00
DT - 2006/05/20 09:00
YR - 2006
ED - 20060607
RD - 20161128
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=16710025
<351. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 16419058
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Sbrana I
AU - Veroni F
AU - Nieri M
AU - Puliti A
AU - Barale R
FA - Sbrana, Isabella
FA - Veroni, Franca
FA - Nieri, Maria
FA - Puliti, Aldamaria
FA - Barale, Roberto
IN - Sbrana, Isabella. Department of Human and Environmental Sciences, University of Pisa, Pisa, Italy. i.sbrana@geog.unipi.it
TI - Chromosomal fragile sites FRA3B and FRA16D show correlated expression and association with failure of apoptosis in lymphocytes from patients with thyroid cancer.
SO - Genes, Chromosomes & Cancer. 45(5):429-36, 2006 May
AS - Genes Chromosomes Cancer. 45(5):429-36, 2006 May
NJ - Genes, chromosomes & cancer
PI - Journal available in: Print
PI - Citation processed from: Print
JC - ayv, 9007329
IO - Genes Chromosomes Cancer
SB - Index Medicus
CP - United States
MH - Adolescent
MH - Adult
MH - *Apoptosis/ge [Genetics]
MH - *Chromosome Fragile Sites
MH - Chromosome Mapping
MH - Female
MH - Humans
MH - Loss of Heterozygosity
MH - *Lymphocytes/ul [Ultrastructure]
MH - Male
MH - Radioactive Pollutants
MH - *Thyroid Neoplasms/ge [Genetics]
AB - It has been suggested that common fragile sites (cFSs) are related to cancer development. This appears to be the case for FRA3B and FRA16D, localized in two tumor-suppressor genes (FHIT and WWOX, respectively) that are altered by deletions or loss of heterozygosity (LOH) in many cancers. The features responsible for fragility have not yet been identified. Furthermore, it is still unclear whether instability at these regions causes chance deletions and loss of function of the associated genes, or whether the gene function itself is related to the appearance of fragility. In this study, we analyzed cFS expression in lymphocytes from 20 healthy or thyroid cancer-affected subjects exposed to radiation after the Chernobyl accident. The same cells were examined for apoptosis, a principal function of both the FHIT and WWOX genes. Exceptionally elevated chromosome fragility was observed, particularly in cancer patients, affecting FRA3B, FRA16D, and a cluster of less highly expressed cFSs; levels of chromosome fragility were found to be correlated among these cFSs. Interestingly, most expressed cFSs were sites of LOH reported for thyroid tumors; moreover, cells with the highest fragility also had a reduced ability to undergo apoptosis. These findings reveal previously unknown genetic interactions affecting fragile loci, suggestive of a shared function inside mitotic cells. Attenuation of checkpoint control and apoptosis resistance seem to be the cell phenotypes associated with unusual chromosome fragility. We propose that breakage at specific cFS could derive from early epigenetic events at loci involved in radiation carcinogenesis. This article contains supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.
AB - Copyright 2006 Wiley-Liss, Inc
RN - 0 (Radioactive Pollutants)
IS - 1045-2257
IL - 1045-2257
DO - https://dx.doi.org/10.1002/gcc.20305
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 16419058 [pubmed]
ID - 10.1002/gcc.20305 [doi]
PP - ppublish
LG - English
DP - 2006 May
DC - 20060306
EZ - 2006/01/19 09:00
DA - 2006/05/31 09:00
DT - 2006/01/19 09:00
YR - 2006
ED - 20060530
RD - 20061115
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=16419058
<352. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 16585202
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Bazzaro M
AU - Lee MK
AU - Zoso A
AU - Stirling WL
AU - Santillan A
AU - Shih IeM
AU - Roden RB
FA - Bazzaro, Martina
FA - Lee, Michael K
FA - Zoso, Alessia
FA - Stirling, Wanda L H
FA - Santillan, Antonio
FA - Shih, Ie-Ming
FA - Roden, Richard B S
IN - Bazzaro, Martina. Department of Pathology, The Johns Hopkins School of Medicine, Cancer Research Building 2, 1550 Orleans Street, Baltimore, MD 21231, USA.
TI - Ubiquitin-proteasome system stress sensitizes ovarian cancer to proteasome inhibitor-induced apoptosis.
SO - Cancer Research. 66(7):3754-63, 2006 Apr 01
AS - Cancer Res. 66(7):3754-63, 2006 Apr 01
NJ - Cancer research
PI - Journal available in: Print
PI - Citation processed from: Print
JC - cnf, 2984705r
IO - Cancer Res.
SB - Index Medicus
CP - United States
MH - Animals
MH - *Apoptosis/de [Drug Effects]
MH - Apoptosis/ph [Physiology]
MH - Boronic Acids/pd [Pharmacology]
MH - Bortezomib
MH - Caspases/me [Metabolism]
MH - Cell Division/de [Drug Effects]
MH - Cell Line, Tumor
MH - Female
MH - G2 Phase/de [Drug Effects]
MH - Humans
MH - Leupeptins/pd [Pharmacology]
MH - Mice
MH - Mice, Nude
MH - Oligopeptides/pd [Pharmacology]
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - Ovarian Neoplasms/en [Enzymology]
MH - *Ovarian Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/pa [Pathology]
MH - *Protease Inhibitors/pd [Pharmacology]
MH - Proteasome Endopeptidase Complex/bi [Biosynthesis]
MH - *Proteasome Endopeptidase Complex/me [Metabolism]
MH - *Proteasome Inhibitors
MH - Pyrazines/pd [Pharmacology]
MH - *Ubiquitin/me [Metabolism]
MH - Xenograft Model Antitumor Assays
AB - The ubiquitin-proteasome system (UPS) mediates targeted protein degradation. Notably, the UPS determines levels of key checkpoint proteins controlling apoptosis and proliferation by controlling protein half-life. Herein, we show that ovarian carcinoma manifests an overstressed UPS by comparison with normal tissues by accumulation of ubiquitinated proteins despite elevated proteasome levels. Elevated levels of total ubiquitinated proteins and 19S and 20S proteasome subunits are evident in both low-grade and high-grade ovarian carcinoma tissues relative to benign ovarian tumors and in ovarian carcinoma cell lines relative to immortalized surface epithelium. We find that ovarian carcinoma cell lines exhibit greater sensitivity to apoptosis in response to proteasome inhibitors than immortalized ovarian surface epithelial cells. This sensitivity correlates with increased cellular proliferation rate and UPS stress rather than absolute proteasome levels. Proteasomal inhibition in vitro induces cell cycle arrest and the accumulation of p21 and p27 and triggers apoptosis via activation of caspase-3. Furthermore, treatment with the licensed proteasome inhibitor PS-341 slows the growth of ES-2 ovarian carcinoma xenograft in immunodeficient mice. In sum, elevated proliferation and metabolic rate resulting from malignant transformation of the epithelium stresses the UPS and renders ovarian carcinoma more sensitive to apoptosis in response to proteasomal inhibition.
RN - 0 (Boronic Acids)
RN - 0 (Leupeptins)
RN - 0 (Oligopeptides)
RN - 0 (Protease Inhibitors)
RN - 0 (Proteasome Inhibitors)
RN - 0 (Pyrazines)
RN - 0 (Ubiquitin)
RN - 69G8BD63PP (Bortezomib)
RN - EC 3-4-22 (Caspases)
RN - EC 3-4-25-1 (Proteasome Endopeptidase Complex)
RN - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
RN - Y0900I3U8U (epoxomicin)
IS - 0008-5472
IL - 0008-5472
DI - 66/7/3754
DO - https://dx.doi.org/10.1158/0008-5472.CAN-05-2321
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Research Support, U.S. Gov't, Non-P.H.S.
ID - 16585202 [pubmed]
ID - 66/7/3754 [pii]
ID - 10.1158/0008-5472.CAN-05-2321 [doi]
PP - ppublish
LG - English
DP - 2006 Apr 01
DC - 20060404
EZ - 2006/04/06 09:00
DA - 2006/05/23 09:00
DT - 2006/04/06 09:00
YR - 2006
ED - 20060522
RD - 20161128
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=16585202
<353. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 16099193
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - di Pietro A
AU - Vries EG
AU - Gietema JA
AU - Spierings DC
AU - de Jong S
FA - di Pietro, Alessandra
FA - Vries, Elisabeth G E de
FA - Gietema, Jourik A
FA - Spierings, Diana C J
FA - de Jong, Steven
IN - di Pietro, Alessandra. Department of Medical Oncology, Internal Medicine, University of Groningen and University Medical Center Groningen, 9713 GZ Hanzeplein 1, Groningen, The Netherlands.
TI - Testicular germ cell tumours: the paradigm of chemo-sensitive solid tumours. [Review] [202 refs]
SO - International Journal of Biochemistry & Cell Biology. 37(12):2437-56, 2005 Dec
AS - Int J Biochem Cell Biol. 37(12):2437-56, 2005 Dec
NJ - The international journal of biochemistry & cell biology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - cdk, 9508482
IO - Int. J. Biochem. Cell Biol.
SB - Index Medicus
CP - Netherlands
MH - Adult
MH - Animals
MH - Apoptosis
MH - Carcinoma in Situ/pp [Physiopathology]
MH - Cell Cycle/ph [Physiology]
MH - Cell Line, Tumor
MH - *Cisplatin/tu [Therapeutic Use]
MH - DNA-Binding Proteins/ph [Physiology]
MH - Genes, Neoplasm
MH - Genes, Tumor Suppressor/ph [Physiology]
MH - *Germinoma/dt [Drug Therapy]
MH - Germinoma/ge [Genetics]
MH - Germinoma/sc [Secondary]
MH - Humans
MH - Male
MH - Membrane Proteins/ph [Physiology]
MH - Mice
MH - Nuclear Proteins/ph [Physiology]
MH - *Testicular Neoplasms/dt [Drug Therapy]
MH - Testicular Neoplasms/ge [Genetics]
MH - Testicular Neoplasms/pa [Pathology]
MH - Testis/cy [Cytology]
MH - Tumor Protein p73
MH - Tumor Suppressor Protein p53/ge [Genetics]
MH - Tumor Suppressor Protein p53/me [Metabolism]
MH - Tumor Suppressor Proteins
AB - Testicular germ cell tumours (TGCTs) are the most frequent solid malignant tumour in men 20-40 years of age and the most frequent cause of death from solid tumours in this age group. Up to 50% of the patients suffer from metastatic disease at diagnosis. The majority of metastatic testicular cancer patients, in contrast to most other metastatic solid tumours, can be cured with highly effective cisplatin-based chemotherapy. From a genetic point of view, almost all TGCTs in contrast to solid tumours are characterised by the presence of wild type p53. High p53 expression levels are associated with elevated Mdm2 levels and a loss of p21(Waf1/Cip1) expression suggesting a changed functionality of p53. Expression levels of other proteins involved in the regulation of cell cycle progression indicate a deregulated G1-S phase checkpoint in TGCTs. After cisplatin-induced DNA damage, the increasing levels of p53 lead to the trans-activation of a number of genes but not of p21(Waf1/Cip1), preferentially directing TGCT cells into apoptosis or programmed cell death, both via the mitochondrial and the death receptor apoptosis pathways. The sensitivity of TGCTs to chemotherapeutic drugs may lay in the susceptibility of germ cells to apoptosis. Taken together, this provides TGCT as a tumour type model to investigate and understand the molecular determinants of chemotherapy sensitivity of solid tumours. This review aims to summarise the current knowledge on the biological basis of cisplatin-induced apoptosis and response to chemotherapy in TGCTs. [References: 202]
RN - 0 (CKAP4 protein, human)
RN - 0 (DNA-Binding Proteins)
RN - 0 (Membrane Proteins)
RN - 0 (Nuclear Proteins)
RN - 0 (Trp73 protein, mouse)
RN - 0 (Tumor Protein p73)
RN - 0 (Tumor Suppressor Protein p53)
RN - 0 (Tumor Suppressor Proteins)
RN - Q20Q21Q62J (Cisplatin)
IS - 1357-2725
IL - 1357-2725
DI - S1357-2725(05)00198-6
DO - https://dx.doi.org/10.1016/j.biocel.2005.06.014
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 16099193 [pubmed]
ID - S1357-2725(05)00198-6 [pii]
ID - 10.1016/j.biocel.2005.06.014 [doi]
PP - ppublish
PH - 2005/03/25 [received]
PH - 2005/06/02 [revised]
PH - 2005/01/27 [accepted]
LG - English
EP - 20050811
DP - 2005 Dec
DC - 20051007
EZ - 2005/08/16 09:00
DA - 2005/12/24 09:00
DT - 2005/08/16 09:00
YR - 2005
ED - 20051223
RD - 20161124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=16099193
<354. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 15827334
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Strait KA
AU - Warnick CT
AU - Ford CD
AU - Dabbas B
AU - Hammond EH
AU - Ilstrup SJ
FA - Strait, Kevin A
FA - Warnick, C Terry
FA - Ford, Clyde D
FA - Dabbas, Bashar
FA - Hammond, Elizabeth H
FA - Ilstrup, Sarah J
IN - Strait, Kevin A. Department of Medicine, Laboratory for Molecular Oncology, LDS Hospital, Salt Lake City, Utah 84143, USA. ldkstrai@ihc.com
TI - Histone deacetylase inhibitors induce G2-checkpoint arrest and apoptosis in cisplatinum-resistant ovarian cancer cells associated with overexpression of the Bcl-2-related protein Bad.
SO - Molecular Cancer Therapeutics. 4(4):603-11, 2005 Apr
AS - Mol Cancer Ther. 4(4):603-11, 2005 Apr
NJ - Molecular cancer therapeutics
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 101132535
IO - Mol. Cancer Ther.
SB - Index Medicus
CP - United States
MH - Annexin A5/ch [Chemistry]
MH - Annexin A5/me [Metabolism]
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - *Apoptosis
MH - Blotting, Western
MH - *Carrier Proteins/bi [Biosynthesis]
MH - Cell Differentiation
MH - Cell Line, Tumor
MH - Cell Proliferation
MH - Cell Survival
MH - *Cisplatin/pd [Pharmacology]
MH - Female
MH - Fibroblasts/me [Metabolism]
MH - Flow Cytometry
MH - G1 Phase
MH - G2 Phase
MH - *Histone Deacetylase Inhibitors
MH - Humans
MH - Hydroxamic Acids/pd [Pharmacology]
MH - Immunohistochemistry
MH - Microscopy, Electron
MH - *Mitochondria/me [Metabolism]
MH - Mitosis
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - *Ovarian Neoplasms/me [Metabolism]
MH - Phenotype
MH - *Proto-Oncogene Proteins c-bcl-2/bi [Biosynthesis]
MH - Time Factors
MH - bcl-Associated Death Protein
AB - Trichostatin A produces predominantly G(1) cell-cycle blockade and differentiation of the cisplatinum-sensitive A2780 ovarian cancer cell line. Given the propensity of ovarian tumors to become resistant to cisplatinum, often leading to cross-resistance to other agents, we have extended these observations by examining how the emergence of resistant phenotypes in A2780 cells affects the actions of histone deacetylase (HDAC) inhibitors. Trichostatin A exposure (100 ng/mL, 24 hours) induced ultrastructural differentiation of the "intrinsically" cisplatinum-resistant A2780-9M subline, with the reappearance of intercellular junctions and lumina containing primitive microvilli. Similar trichostatin A exposure in the acquired resistance A2780CP cells produced minimal differentiation consisting of occasional weak intercellular junctions. Independent of the differences in trichostatin A-induced differentiation, in both resistant sublines trichostatin A produced a similar reduction in cell viability, by >90%, within 5 days of treatment. Diminished viability in both A2780-9M and CP cells was associated with the absence of cell cycle arrest in G1, resulting in predominant G2-checkpoint arrest accompanied by a 10- to 20-fold increase in Annexin V binding and the reemergence of apoptosis. Similar cell cycle arrests and apoptosis were also observed using other HDAC inhibitors and in other resistant ovarian cancer cell lines (OVCAR-3 and SK-OV-3). Trichostatin A-induced apoptosis in resistant cells is in sharp contrast to its effects on the parental cisplatinum-sensitive A2780 and normal MRC-5 fibroblast cell lines (predominant cycle arrest in G1 with no detectable apoptosis). Western immunoblot analysis indicated trichostatin A triggers apoptosis in resistant ovarian cancer cells via p53-independent activation of the intrinsic "mitochondrial" pathway, commensurate with induction of the Bcl-2-related protein Bad. These results suggest cisplatinum resistance alters the effects of HDAC inhibition through a shift in cell cycle arrest from the G1 to the G2 checkpoint and reactivation of the intrinsic mitochondrial apoptotic cascade.
RN - 0 (Annexin A5)
RN - 0 (Antineoplastic Agents)
RN - 0 (BAD protein, human)
RN - 0 (Carrier Proteins)
RN - 0 (Histone Deacetylase Inhibitors)
RN - 0 (Hydroxamic Acids)
RN - 0 (Proto-Oncogene Proteins c-bcl-2)
RN - 0 (bcl-Associated Death Protein)
RN - 3X2S926L3Z (trichostatin A)
RN - Q20Q21Q62J (Cisplatin)
IS - 1535-7163
IL - 1535-7163
DI - 4/4/603
DO - https://dx.doi.org/10.1158/1535-7163.MCT-04-0107
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 15827334 [pubmed]
ID - 4/4/603 [pii]
ID - 10.1158/1535-7163.MCT-04-0107 [doi]
PP - ppublish
LG - English
DP - 2005 Apr
DC - 20050413
EZ - 2005/04/14 09:00
DA - 2005/10/07 09:00
DT - 2005/04/14 09:00
YR - 2005
ED - 20051006
RD - 20131121
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=15827334
<355. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 15990723
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wasko R
AU - Jankowska A
AU - Waligorska-Stachura J
AU - Andrusiewicz M
AU - Jaskula M
AU - Sowinski J
FA - Wasko, Ryszard
FA - Jankowska, Anna
FA - Waligorska-Stachura, Joanna
FA - Andrusiewicz, Miroslaw
FA - Jaskula, Magdalena
FA - Sowinski, Jerzy
IN - Wasko, Ryszard. University of Medical Sciences in Ponzan, Department of Endocrinology, Metabolism and Internal Diseases, Poland. rwasko@amp.edu.pl
TI - Survivin expression in pituitary adenomas.
SO - Neuroendocrinology Letters. 26(3):209-12, 2005 Jun
AS - Neuroendocrinol Lett. 26(3):209-12, 2005 Jun
NJ - Neuro endocrinology letters
PI - Journal available in: Print
PI - Citation processed from: Print
JC - d1z, 8008373
IO - Neuro Endocrinol. Lett.
SB - Index Medicus
CP - Sweden
MH - Acromegaly/ge [Genetics]
MH - Acromegaly/pp [Physiopathology]
MH - Adenoma/ge [Genetics]
MH - *Adenoma/pp [Physiopathology]
MH - Adult
MH - Aged
MH - *Biomarkers, Tumor/ge [Genetics]
MH - Female
MH - *Gene Expression Regulation, Neoplastic
MH - HeLa Cells
MH - Humans
MH - Inhibitor of Apoptosis Proteins
MH - Male
MH - *Microtubule-Associated Proteins/ge [Genetics]
MH - Middle Aged
MH - *Neoplasm Proteins/ge [Genetics]
MH - Pituitary Neoplasms/ge [Genetics]
MH - *Pituitary Neoplasms/pp [Physiopathology]
MH - Predictive Value of Tests
MH - Prognosis
MH - Prolactinoma/ge [Genetics]
MH - Prolactinoma/pp [Physiopathology]
MH - RNA, Messenger/an [Analysis]
AB - UNLABELLED: Survivin has received great attention due to its expression in many human tumours and its potential as a therapeutic target in cancer. Its expression is developmentally regulated: present during fetal development, it is undetectable in terminally differentiated normal adult tissue. Survivin expression has been described to be cell cycle-dependent and restricted to the G2-M checkpoint, where it inhibits apoptosis in proliferating cells.
AB - OBJECTIVES: The aim of our study was to determine the survivin expression in different types of pituitary adenomas.
AB - METHODS: Tissue samples were obtained during surgical removal of the tumour from 12 patients with diagnosed: acromegaly in seven cases, non-functioning pituitary tumours in four cases and prolactinoma in one case. Six patients with acromegaly received long-acting somatostatin analogues before tumour resection. After RNA extraction and cDNA synthesis, the amplification of specific survivin's gene fragment was performed.
AB - RESULTS: In agreement with the current view that survivin is a tumor-associated antigen, highly expressed in various tumours, we found the presence of survivin expression as a characteristic feature of human pituitary adenomas. The findings of our study demonstrated the presence of an active survivin gene in all twelve analysed pituitary tumours.
AB - CONCLUSIONS: Based on these findings, we conclude that the estimation of survivin expression in human pituitary tumours may help predict tumour growth and prognosis.
RN - 0 (BIRC5 protein, human)
RN - 0 (Biomarkers, Tumor)
RN - 0 (Inhibitor of Apoptosis Proteins)
RN - 0 (Microtubule-Associated Proteins)
RN - 0 (Neoplasm Proteins)
RN - 0 (RNA, Messenger)
IS - 0172-780X
IL - 0172-780X
DI - NEL260305A03
PT - Journal Article
ID - 15990723 [pubmed]
ID - NEL260305A03 [pii]
PP - ppublish
PH - 2005/03/20 [received]
PH - 2005/04/15 [accepted]
LG - English
DP - 2005 Jun
DC - 20050701
EZ - 2005/07/02 09:00
DA - 2005/10/06 09:00
DT - 2005/07/02 09:00
YR - 2005
ED - 20051005
RD - 20151119
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=15990723
<356. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 15786490
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Whitfield JF
FA - Whitfield, James F
IN - Whitfield, James F. Institute for Biological Sciences, Montreal Road Campus, National Research Council of Canada, Ottawa, Ontario, K1A 0R6 Canada. pthosteo@rogers.com
TI - Osteogenic PTHs and vascular ossification-Is there a danger for osteoporotics?. [Review] [60 refs]
SO - Journal of Cellular Biochemistry. 95(3):437-44, 2005 Jun 01
AS - J Cell Biochem. 95(3):437-44, 2005 Jun 01
NJ - Journal of cellular biochemistry
PI - Journal available in: Print
PI - Citation processed from: Print
JC - hnf, 8205768
IO - J. Cell. Biochem.
SB - Index Medicus
CP - United States
MH - Animals
MH - Arteries/me [Metabolism]
MH - Arteries/pa [Pathology]
MH - Calcinosis/ci [Chemically Induced]
MH - *Calcinosis/me [Metabolism]
MH - Calcinosis/pa [Pathology]
MH - Female
MH - Heart Ventricles/me [Metabolism]
MH - Heart Ventricles/pa [Pathology]
MH - Humans
MH - Osteoporosis, Postmenopausal/co [Complications]
MH - Osteoporosis, Postmenopausal/dt [Drug Therapy]
MH - *Osteoporosis, Postmenopausal/me [Metabolism]
MH - Parathyroid Hormone-Related Protein/ad [Administration & Dosage]
MH - Parathyroid Hormone-Related Protein/ae [Adverse Effects]
MH - *Parathyroid Hormone-Related Protein/me [Metabolism]
MH - Vascular Diseases/ci [Chemically Induced]
MH - *Vascular Diseases/me [Metabolism]
MH - Vascular Diseases/pa [Pathology]
AB - Inflammation in vascular (mostly arterial) walls and heart valves triggered by the trans-endothelial influx of LDL particles and the action of subsequently modified (e.g., by oxidation) LDL particles can trigger true bone formation by valvar fibroblasts, by a subpopulation of re-differentiation-competent VSMCs (vascular smooth muscle cells) or by vascular pericytes. Vascular ossification can lead to heart failure and death. Elderly osteoporotic women who need osteogenic drugs to restore their lost skeletal bone are paradoxically prone to vascular ossification-the "calcification paradox." The recent introduction into the clinic of a potently osteogenic parathyroid hormone peptide, Lilly's rhPTH-(1-34)OH (Forteotrade mark), to reverse skeletal bone loss raises the question of whether this and other potently osteogenic PTHs still in clinical trial might also stimulate vascular ossification in such osteoporotic women. Indeed the VSMCs in human and rat atherosclerotic lesions hyperexpress PTHrP and the PTHR1 (or PTH1R) receptor as do maturing osteoblasts. And the evidence indicates that endogenous PTHrP with its NLS (nuclear/nucleolar localization sequence) does stimulate VSMC proliferation (a prime prerequisite for atheroma formation and ossification) via intranuclear targets that inactivate pRb, the inhibitory G1/S checkpoint regulator, by stimulating its hyperphosphorylation. But neither externally added full-length PTHrP nor the NLS-lacking PTHrP-(1-34)OH gets into the VSMC nucleus and instead they inhibit proliferation and calcification by only activating the cell's PTHR1 receptors. No PTH has an NLS and, as expected from the observations on the externally added PTHrPs, hPTH-(1-34)OH inhibits calcification by VSMCs and cannot stimulate vascular ossification in a diabetic mouse model. Encouraging though this may be for osteoporotics with their "calcification paradox," more work is needed to be sure that the skeletally osteogenic PTHs do not promote vascular ossification with its cardiovascular consequences.
AB - Copyright (c) 2005 Wiley-Liss, Inc. [References: 60]
RN - 0 (Parathyroid Hormone-Related Protein)
IS - 0730-2312
IL - 0730-2312
DO - https://dx.doi.org/10.1002/jcb.20424
PT - Journal Article
PT - Review
ID - 15786490 [pubmed]
ID - 10.1002/jcb.20424 [doi]
PP - ppublish
LG - English
DP - 2005 Jun 01
DC - 20050516
EZ - 2005/03/24 09:00
DA - 2005/09/01 09:00
DT - 2005/03/24 09:00
YR - 2005
ED - 20050831
RD - 20051116
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=15786490
<357. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 15913739
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Belanger S
AU - Cote M
AU - Lane D
AU - L'Esperance S
AU - Rancourt C
AU - Piche A
FA - Belanger, Sylvie
FA - Cote, Marceline
FA - Lane, Denis
FA - L'Esperance, Sylvain
FA - Rancourt, Claudine
FA - Piche, Alain
IN - Belanger, Sylvie. Departement de Microbiologie et Infectiologie, Faculte de Medecine, Universite de Sherbrooke, 3001, 12ieme Avenue Nord, Sherbooke, Canada J1H 5N1.
TI - Bcl-2 decreases cell proliferation and promotes accumulation of cells in S phase without affecting the rate of apoptosis in human ovarian carcinoma cells.
SO - Gynecologic Oncology. 97(3):796-806, 2005 Jun
AS - Gynecol Oncol. 97(3):796-806, 2005 Jun
NJ - Gynecologic oncology
PI - Journal available in: Print
PI - Citation processed from: Print
JC - fxc, 0365304
IO - Gynecol. Oncol.
SB - Index Medicus
CP - United States
MH - *Apoptosis/ph [Physiology]
MH - Cell Division/ph [Physiology]
MH - Cell Growth Processes/ph [Physiology]
MH - Cell Line, Tumor
MH - Female
MH - G2 Phase/ph [Physiology]
MH - Humans
MH - Immunoglobulin Fragments/pd [Pharmacology]
MH - Immunoglobulin Variable Region/pd [Pharmacology]
MH - Ovarian Neoplasms/me [Metabolism]
MH - *Ovarian Neoplasms/pa [Pathology]
MH - Proto-Oncogene Proteins c-bcl-2/ai [Antagonists & Inhibitors]
MH - Proto-Oncogene Proteins c-bcl-2/bi [Biosynthesis]
MH - Proto-Oncogene Proteins c-bcl-2/im [Immunology]
MH - *Proto-Oncogene Proteins c-bcl-2/ph [Physiology]
MH - *S Phase/ph [Physiology]
AB - OBJECTIVES: The Bcl-2 protein is an important regulator of the apoptotic cascade and promotes cell survival. Bcl-2 can also delay entry into the cell cycle from quiescence. In the present study, we used two isogenic human ovarian carcinoma cell lines, which expressed differential levels of Bcl-2 proteins, to demonstrate that Bcl-2 may regulate the growth rates of adenocarcinoma cells.
AB - METHODS: The growth rates of two isogenic ovarian cancer cell lines were determined by XTT assays and flow cytometry combined with PI staining. Bcl-2-overexpressing SKOV3 cells were modified to express a doxycycline-inducible anti-Bcl-2 single-chain antibody and the effects of Bcl-2 protein inhibition on cell proliferation and apoptosis were assessed.
AB - RESULTS: We demonstrate that Bcl-2 promotes the accumulation of proliferating carcinoma cells in S phase. The Bcl-2-overexpressing SKOV3 cell line proliferates markedly faster and shows delayed progression to G2M phase compared to its low Bcl-2-expressing counterpart SKOV3.ip1 cell line. Single-chain antibody-mediated inhibition of Bcl-2 in SKOV3 cells was associated with increased growth rates and more rapid cell cycle progression. Treatment with cisplatin resulted in more cells accumulating in S phase in Bcl-2-overexpressing SKOV3 cells, while the inhibition of Bcl-2 abolished delayed entry into G2M phase without affecting cisplatin-induced apoptosis.
AB - CONCLUSIONS: Our results suggest that, in ovarian cancer cells, Bcl-2 delays cell cycle progression by promoting accumulation of cells in S phase without affecting the rate of apoptosis. Thus, in addition to its known role at the G0/G1 checkpoint, we demonstrate for the first time that Bcl-2 also regulates the S phase.
RN - 0 (Immunoglobulin Fragments)
RN - 0 (Immunoglobulin Variable Region)
RN - 0 (Proto-Oncogene Proteins c-bcl-2)
IS - 0090-8258
IL - 0090-8258
DI - S0090-8258(05)00130-7
DO - https://dx.doi.org/10.1016/j.ygyno.2005.02.018
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 15913739 [pubmed]
ID - S0090-8258(05)00130-7 [pii]
ID - 10.1016/j.ygyno.2005.02.018 [doi]
PP - ppublish
PH - 2004/10/26 [received]
PH - 2005/02/02 [revised]
PH - 2005/02/10 [accepted]
LG - English
DP - 2005 Jun
DC - 20050609
EZ - 2005/05/26 09:00
DA - 2005/08/12 09:00
DT - 2005/05/26 09:00
YR - 2005
ED - 20050811
RD - 20061115
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=15913739
<358. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 15897900
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Kim D
AU - Pemberton H
AU - Stratford AL
AU - Buelaert K
AU - Watkinson JC
AU - Lopes V
AU - Franklyn JA
AU - McCabe CJ
FA - Kim, Dae
FA - Pemberton, Helen
FA - Stratford, Anna L
FA - Buelaert, Kristien
FA - Watkinson, John C
FA - Lopes, Victor
FA - Franklyn, Jayne A
FA - McCabe, Chris J
IN - Kim, Dae. Division of Medical Sciences, 2nd Floor IBR, University of Birmingham, Edgbaston, Birmingham B12 5TT, UK. daekim72@yahoo.co.uk
TI - Pituitary tumour transforming gene (PTTG) induces genetic instability in thyroid cells.
SO - Oncogene. 24(30):4861-6, 2005 Jul 14
AS - Oncogene. 24(30):4861-6, 2005 Jul 14
NJ - Oncogene
PI - Journal available in: Print
PI - Citation processed from: Print
JC - onc, 8711562
IO - Oncogene
SB - Index Medicus
CP - England
MH - Caspase 3
MH - Caspase 7
MH - Caspases/me [Metabolism]
MH - Cell Line
MH - *Genomic Instability
MH - Humans
MH - *Neoplasm Proteins/ge [Genetics]
MH - *Neoplasm Proteins/me [Metabolism]
MH - RNA, Messenger/ge [Genetics]
MH - RNA, Messenger/me [Metabolism]
MH - Securin
MH - *Thyroid Gland/me [Metabolism]
MH - *Thyroid Gland/pa [Pathology]
MH - *Thyroid Neoplasms/ge [Genetics]
MH - Thyroid Neoplasms/pa [Pathology]
AB - Cancer reflects the progressive accumulation of genetic alterations and subsequent genetic instability of cells. Cytogenetic studies have demonstrated the importance of aneuploidy in differentiated thyroid cancer development. The pituitary tumour transforming gene (PTTG), also known as securin, is a mitotic checkpoint protein which inhibits sister chromatid separation during mitosis. PTTG is highly expressed in many cancers and overexpression of PTTG induces aneuploidy in vitro. Using fluorescent intersimple sequence repeat PCR (FISSR-PCR), we investigated the relationship between PTTG expression and the degree of genetic instability in normal and tumorous thyroid samples. The genomic instability index (GI index) was 6.7-72.7% higher in cancers than normal thyroid tissues. Follicular thyroid tumours exhibited greater genetic instability than papillary tumours (27.6% (n=9) versus 14.5% (n=10), P=0.03). We also demonstrated a strong relationship between PTTG expression and the degree of genetic instability in thyroid cancers (R2=0.80, P=0.007). To further investigate PTTG's role in genetic instability, we transfected FTC133 thyroid follicular cells and observed increased genetic instability in cells overexpressing PTTG compared with vector-only-transfected controls (n=3, GI Index VO=29.7+/-5.2 versus PTTG=63.7+/-6.4, P=0.013). Further, we observed a dose response in genetic instability and PTTG expression (GI Index low dose (0.5 microg DNA/ six-well plate) PTTG=15.3%+/-1.7 versus high dose (3 microg DNA) PTTG=50.8%+/-3.3, P=0.006). Overall, we describe the first use of FISSR-PCR in human cancers, and demonstrate that PTTG expression correlates with genetic instability in vivo, and induces genetic instability in vitro. We conclude that PTTG may be an important gene in the mutator phenotype development in thyroid cancer.
RN - 0 (Neoplasm Proteins)
RN - 0 (RNA, Messenger)
RN - 0 (Securin)
RN - 0 (pituitary tumor-transforming protein 1, human)
RN - EC 3-4-22 (CASP3 protein, human)
RN - EC 3-4-22 (CASP7 protein, human)
RN - EC 3-4-22 (Caspase 3)
RN - EC 3-4-22 (Caspase 7)
RN - EC 3-4-22 (Caspases)
IS - 0950-9232
IL - 0950-9232
DI - 1208659
DO - https://dx.doi.org/10.1038/sj.onc.1208659
PT - Journal Article
ID - 15897900 [pubmed]
ID - 1208659 [pii]
ID - 10.1038/sj.onc.1208659 [doi]
PP - ppublish
LG - English
DP - 2005 Jul 14
DC - 20050714
EZ - 2005/05/18 09:00
DA - 2005/08/09 09:00
DT - 2005/05/18 09:00
YR - 2005
ED - 20050808
RD - 20131121
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=15897900
<359. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 15254743
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Zhong X
AU - Li X
AU - Wang G
AU - Zhu Y
AU - Hu G
AU - Zhao J
AU - Neace C
AU - Ding H
AU - Reed E
AU - Li QQ
FA - Zhong, Xiaosong
FA - Li, Xiping
FA - Wang, Gangduo
FA - Zhu, Yunfeng
FA - Hu, Guodong
FA - Zhao, Jinshun
FA - Neace, Cheryl
FA - Ding, Hong
FA - Reed, Eddie
FA - Li, Qingdi Q
IN - Zhong, Xiaosong. Mary Babb Randolph Cancer Center, and Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine and Robert C. Byrd Health Sciences Center, Morgantown, WV 26506, USA.
TI - Mechanisms underlying the synergistic effect of SU5416 and cisplatin on cytotoxicity in human ovarian tumor cells.
SO - International Journal of Oncology. 25(2):445-51, 2004 Aug
AS - Int J Oncol. 25(2):445-51, 2004 Aug
NJ - International journal of oncology
PI - Journal available in: Print
PI - Citation processed from: Print
JC - cx5, 9306042
IO - Int. J. Oncol.
SB - Index Medicus
CP - Greece
MH - Angiogenesis Inhibitors/pd [Pharmacology]
MH - Angiogenesis Inhibitors/tu [Therapeutic Use]
MH - *Angiogenesis Inhibitors/to [Toxicity]
MH - Antineoplastic Agents/pd [Pharmacology]
MH - Antineoplastic Agents/tu [Therapeutic Use]
MH - *Antineoplastic Agents/to [Toxicity]
MH - Apoptosis
MH - Cell Cycle Proteins/me [Metabolism]
MH - Cell Line
MH - Cisplatin/pd [Pharmacology]
MH - Cisplatin/tu [Therapeutic Use]
MH - *Cisplatin/to [Toxicity]
MH - Cyclin-Dependent Kinase Inhibitor p21
MH - Cyclin-Dependent Kinase Inhibitor p27
MH - Drug Synergism
MH - Female
MH - Humans
MH - I-kappa B Proteins/me [Metabolism]
MH - Indoles/pd [Pharmacology]
MH - Indoles/tu [Therapeutic Use]
MH - *Indoles/to [Toxicity]
MH - JNK Mitogen-Activated Protein Kinases/me [Metabolism]
MH - MAP Kinase Kinase 4
MH - Mitogen-Activated Protein Kinase Kinases/me [Metabolism]
MH - NF-KappaB Inhibitor alpha
MH - Ovarian Neoplasms/dt [Drug Therapy]
MH - *Ovarian Neoplasms/me [Metabolism]
MH - Proto-Oncogene Proteins/me [Metabolism]
MH - Pyrroles/pd [Pharmacology]
MH - Pyrroles/tu [Therapeutic Use]
MH - *Pyrroles/to [Toxicity]
MH - Transcription Factor AP-1/me [Metabolism]
MH - Tumor Suppressor Protein p53/me [Metabolism]
MH - Tumor Suppressor Proteins/me [Metabolism]
MH - Up-Regulation
AB - SU5416 is a selective inhibitor of vascular endothelial growth factor (VEGF) receptors with anti-angiogenesis activity for human cancers. We have previously reported that SU5416 sensitizes ovarian cancer cells to cisplatin via suppression of nucleotide excision repair activity. This study sought to gain further insights into the mechanisms underlying the synergistic effect of SU5416 and cisplatin on cytotoxicity in human ovarian tumor cells. Here, we show that SU5416 inhibited the expression of G1 cell cycle checkpoint regulators, p53, p21, p27 and MDM2 in ovarian carcinoma cells. We also demonstrate that SU5416 triggered the apoptosis of these cells, in addition to augmenting the apoptosis induced by cisplatin, as determined by a Sub-G1 profile analysis using a flow cytometer. Furthermore, we show that SU5416-induced apoptosis is associated with a decrease in the expression of the apoptosis inhibitors, MDM2 and Bcl-2, and an increase in the level of NF-kappaB inhibitor, IkappaBalpha. NF-kappaB is an anti-apoptotic transcription factor, which induces the apoptosis inhibitors, Bcl-XL and IAPs (inhibitor of apoptosis proteins), and IkappaBalpha is an inhibitor of NF-kappaB, which binds to the NF-kappaB and retains it in the cytoplasm. Finally, the compound was found to block cisplatin-induced increases in AP-1 expression and JNK activity, as well as Raf-1 protein level in these cells. Together, these results suggest that the chemosensitizing effect of SU5416 on ovarian tumor cells may be mediated, at least in part, through inhibiting G1 checkpoint control and up-regulating the apoptotic response to cisplatin.
RN - 0 (Angiogenesis Inhibitors)
RN - 0 (Antineoplastic Agents)
RN - 0 (CDKN1A protein, human)
RN - 0 (Cell Cycle Proteins)
RN - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN - 0 (I-kappa B Proteins)
RN - 0 (Indoles)
RN - 0 (NFKBIA protein, human)
RN - 0 (Proto-Oncogene Proteins)
RN - 0 (Pyrroles)
RN - 0 (Transcription Factor AP-1)
RN - 0 (Tumor Suppressor Protein p53)
RN - 0 (Tumor Suppressor Proteins)
RN - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN - 71IA9S35AJ (Semaxinib)
RN - EC 2-7-11-24 (JNK Mitogen-Activated Protein Kinases)
RN - EC 2-7-12-2 (MAP Kinase Kinase 4)
RN - EC 2-7-12-2 (Mitogen-Activated Protein Kinase Kinases)
RN - Q20Q21Q62J (Cisplatin)
IS - 1019-6439
IL - 1019-6439
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Research Support, U.S. Gov't, P.H.S.
ID - 15254743 [pubmed]
PP - ppublish
GI - No: P20 RR016440
Organization: (RR) *NCRR NIH HHS*
Country: United States
No: P20RR16440-010003
Organization: (RR) *NCRR NIH HHS*
Country: United States
LG - English
DP - 2004 Aug
DC - 20040715
EZ - 2004/07/16 05:00
DA - 2005/01/26 09:00
DT - 2004/07/16 05:00
YR - 2004
ED - 20050125
RD - 20161124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=15254743
<360. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 15452549
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Clarke PA
AU - Pestell KE
AU - Di Stefano F
AU - Workman P
AU - Walton MI
FA - Clarke, P A
FA - Pestell, K E
FA - Di Stefano, F
FA - Workman, P
FA - Walton, M I
IN - Clarke, P A. Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey SM2 5NG, UK.
TI - Characterisation of molecular events following cisplatin treatment of two curable ovarian cancer models: contrasting role for p53 induction and apoptosis in vivo.
SO - British Journal of Cancer. 91(8):1614-23, 2004 Oct 18
AS - Br J Cancer. 91(8):1614-23, 2004 Oct 18
NJ - British journal of cancer
PI - Journal available in: Print
PI - Citation processed from: Print
JC - av4, 0370635
IO - Br. J. Cancer
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409921
SB - Index Medicus
CP - England
MH - Adenocarcinoma/dt [Drug Therapy]
MH - Adenocarcinoma/me [Metabolism]
MH - Adenocarcinoma/pa [Pathology]
MH - Animals
MH - *Antineoplastic Agents/tu [Therapeutic Use]
MH - *Apoptosis/de [Drug Effects]
MH - Cell Cycle
MH - *Cisplatin/tu [Therapeutic Use]
MH - DNA Adducts
MH - DNA Damage
MH - Disease Models, Animal
MH - Endodermal Sinus Tumor/dt [Drug Therapy]
MH - Endodermal Sinus Tumor/me [Metabolism]
MH - Endodermal Sinus Tumor/pa [Pathology]
MH - Female
MH - Gene Expression Profiling
MH - Humans
MH - In Situ Nick-End Labeling
MH - Mice
MH - Mice, Nude
MH - Mutation
MH - Oligonucleotide Array Sequence Analysis
MH - *Ovarian Neoplasms/dt [Drug Therapy]
MH - *Ovarian Neoplasms/me [Metabolism]
MH - Ovarian Neoplasms/pa [Pathology]
MH - Transplantation, Heterologous
MH - Tumor Suppressor Protein p53/ge [Genetics]
MH - *Tumor Suppressor Protein p53/me [Metabolism]
AB - The detailed molecular basis and determinants of in vivo tumour sensitivity to conventional anticancer agents remain unclear. We examined the cellular and molecular consequences of cisplatin treatment using two ovarian tumour xenograft models that had not been previously adapted to culture in vitro. Both xenografts were curable with clinically relevant multiple doses of cisplatin. Following a single dose of cisplatin (6 mg kg(-1) i.p.) growth delays of 25 and 75 days were obtained for pxn100 and pxn65, respectively. This difference in response was not due to differences in DNA damage. Pxn100 tumours had a functional p53 response and a wild-type p53 sequence, whereas pxn65 harboured a mutant p53 and lacked a functional p53 response. Microarray analysis revealed the induction of p53-regulated genes and regulators of checkpoint control and apoptosis in pxn100 tumours following cisplatin-treatment. By contrast, there was no p53-dependent response and only limited changes in gene expression were detected in the pxn65 tumours. TUNEL analysis demonstrated high levels of apoptosis in the pxn100 tumours following cisplatin treatment, but there was no detectable apoptosis in the pxn65 tumours. Our observations show that a marked in vivo response to cisplatin can occur via p53-dependent apoptosis or independently of p53 status in human ovarian xenografts.
RN - 0 (Antineoplastic Agents)
RN - 0 (DNA Adducts)
RN - 0 (Tumor Suppressor Protein p53)
RN - Q20Q21Q62J (Cisplatin)
IS - 0007-0920
IL - 0007-0920
DI - 6602167
DO - https://dx.doi.org/10.1038/sj.bjc.6602167
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 15452549 [pubmed]
ID - 10.1038/sj.bjc.6602167 [doi]
ID - 6602167 [pii]
ID - PMC2409921 [pmc]
PP - ppublish
LG - English
DP - 2004 Oct 18
DC - 20041013
EZ - 2004/09/29 05:00
DA - 2004/11/17 09:00
DT - 2004/09/29 05:00
YR - 2004
ED - 20041116
RD - 20140608
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=15452549
<361. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 15073049
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Guweidhi A
AU - Kleeff J
AU - Giese N
AU - El Fitori J
AU - Ketterer K
AU - Giese T
AU - Buchler MW
AU - Korc M
AU - Friess H
FA - Guweidhi, Ahmed
FA - Kleeff, Jorg
FA - Giese, Nathalia
FA - El Fitori, Jamael
FA - Ketterer, Knut
FA - Giese, Thomas
FA - Buchler, Markus W
FA - Korc, Murray
FA - Friess, Helmut
IN - Guweidhi, Ahmed. Department of General Surgery, University of Heidelberg, Germany.
TI - Enhanced expression of 14-3-3sigma in pancreatic cancer and its role in cell cycle regulation and apoptosis.
SO - Carcinogenesis. 25(9):1575-85, 2004 Sep
AS - Carcinogenesis. 25(9):1575-85, 2004 Sep
NJ - Carcinogenesis
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - c9t, 8008055
IO - Carcinogenesis
SB - Index Medicus
CP - England
MH - 14-3-3 Proteins
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - *Apoptosis
MH - *Biomarkers, Tumor/me [Metabolism]
MH - Blotting, Southern
MH - Blotting, Western
MH - CDC2 Protein Kinase/me [Metabolism]
MH - *Carcinoma, Pancreatic Ductal/me [Metabolism]
MH - Carcinoma, Pancreatic Ductal/pa [Pathology]
MH - Carrier Proteins/me [Metabolism]
MH - Case-Control Studies
MH - *Cell Cycle
MH - *Exonucleases/me [Metabolism]
MH - Exoribonucleases
MH - Female
MH - Humans
MH - Lasers
MH - Male
MH - Middle Aged
MH - *Neoplasm Proteins/me [Metabolism]
MH - Oligonucleotide Array Sequence Analysis
MH - Pancreas/me [Metabolism]
MH - Pancreas/pa [Pathology]
MH - *Pancreatic Neoplasms/me [Metabolism]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Precipitin Tests
MH - Proto-Oncogene Proteins/me [Metabolism]
MH - *Proto-Oncogene Proteins c-bcl-2
MH - Reverse Transcriptase Polymerase Chain Reaction
MH - bcl-2-Associated X Protein
MH - bcl-Associated Death Protein
AB - 14-3-3sigma belongs to the 14-3-3 family of proteins, which are involved in the modulation of diverse signal transduction pathways. Loss of 14-3-3sigma expression has been observed in a number of human cancers, suggesting that it may have a role as a tumor suppressor gene. The aim of the study was to investigate the expression and the functional role of 14-3-3sigma in pancreatic ductal adenocarcinoma (PDAC). Expression of 14-3-3sigma was analyzed using laser capture microdissection (LCM), quantitative real-time-PCR (QRT-PCR), DNA arrays, immunohistochemistry and western blot analysis. The role of 14-3-3sigma in apoptosis and cell cycle regulation was evaluated by western blotting, immunoprecipitation and FACS analysis. By QRT-PCR, 14-3-3sigma mRNA levels were 54-fold increased in pancreatic adenocarcinoma in comparison with normal pancreatic samples and localized in pancreatic cancer cells as determined by LCM. In pancreatic cancer cells, the degree of 14-3-3sigma expression was not decisive for the maintenance of G(2)/M cell cycle checkpoint or induction of apoptosis. Responses to radiation or apoptosis-inducing agents were neither accompanied by a significant 14-3-3sigma accumulation nor by a change in association of 14-3-3sigma with cdc2, bad and bax. In conclusion, the marked over-expression of 14-3-3sigma in PADC together with multiple known genetic and epigenetic alterations of potential 14-3-3sigma interacting partners suggests an important role of aberrant 14-3-3sigma downstream signaling in pancreatic cancer.
RN - 0 (14-3-3 Proteins)
RN - 0 (BAD protein, human)
RN - 0 (BAX protein, human)
RN - 0 (Biomarkers, Tumor)
RN - 0 (Carrier Proteins)
RN - 0 (Neoplasm Proteins)
RN - 0 (Proto-Oncogene Proteins)
RN - 0 (Proto-Oncogene Proteins c-bcl-2)
RN - 0 (bcl-2-Associated X Protein)
RN - 0 (bcl-Associated Death Protein)
RN - EC 2-7-11-22 (CDC2 Protein Kinase)
RN - EC 3-1 (Exonucleases)
RN - EC 3-1 (Exoribonucleases)
RN - EC 3-1 (SFN protein, human)
IS - 0143-3334
IL - 0143-3334
DI - bgh159
DO - https://dx.doi.org/10.1093/carcin/bgh159
PT - Comparative Study
PT - Journal Article
ID - 15073049 [pubmed]
ID - 10.1093/carcin/bgh159 [doi]
ID - bgh159 [pii]
PP - ppublish
LG - English
EP - 20040408
DP - 2004 Sep
DC - 20040817
EZ - 2004/04/10 05:00
DA - 2004/10/06 09:00
DT - 2004/04/10 05:00
YR - 2004
ED - 20041005
RD - 20151119
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=15073049
<362. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 12915687
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Chung HK
AU - Yi YW
AU - Jung NC
AU - Kim D
AU - Suh JM
AU - Kim H
AU - Park KC
AU - Kim DW
AU - Hwang ES
AU - Song JH
AU - Ku BJ
AU - Han HJ
AU - Ro HK
AU - Kim JM
AU - Shong M
FA - Chung, Hyo Kyun
FA - Yi, Yong-Weon
FA - Jung, Neon-Cheol
FA - Kim, Daegun
FA - Suh, Jae Mi
FA - Kim, Ho
FA - Park, Ki Cheol
FA - Kim, Dong Wook
FA - Hwang, Eun Suk
FA - Song, Jeong Hun
FA - Ku, Bon-Jeong
FA - Han, Hee Jung
FA - Ro, Heung Kyu
FA - Kim, Jin Man
FA - Shong, Minho
IN - Chung, Hyo Kyun. Laboratory of Endocrine Cell Biology, National Research Laboratory Program, Chungnam National University College of Medicine, Daejeon 301-721, Korea.
TI - Gadd45gamma expression is reduced in anaplastic thyroid cancer and its reexpression results in apoptosis.
SO - Journal of Clinical Endocrinology & Metabolism. 88(8):3913-20, 2003 Aug
AS - J Clin Endocrinol Metab. 88(8):3913-20, 2003 Aug
NJ - The Journal of clinical endocrinology and metabolism
PI - Journal available in: Print
PI - Citation processed from: Print
JC - hrb, 0375362
IO - J. Clin. Endocrinol. Metab.
SB - Core Clinical Journals (AIM)
SB - Index Medicus
CP - United States
MH - Adenoviridae/ge [Genetics]
MH - Animals
MH - *Apoptosis/ge [Genetics]
MH - Blotting, Northern
MH - Blotting, Western
MH - Carcinoma/ge [Genetics]
MH - *Carcinoma/me [Metabolism]
MH - *Gene Expression Regulation, Neoplastic/ge [Genetics]
MH - Genes, p53/ge [Genetics]
MH - Genetic Therapy
MH - Humans
MH - Immunohistochemistry
MH - Indicators and Reagents
MH - Intracellular Signaling Peptides and Proteins
MH - Mice
MH - Mice, Nude
MH - Neoplasm Transplantation
MH - *Protein Biosynthesis
MH - Proteins/ge [Genetics]
MH - RNA, Neoplasm/bi [Biosynthesis]
MH - Tetrazolium Salts
MH - Thiazoles
MH - Thyroid Neoplasms/ge [Genetics]
MH - *Thyroid Neoplasms/me [Metabolism]
MH - Transduction, Genetic
MH - Transplantation, Heterologous
MH - Tumor Cells, Cultured
AB - Anaplastic thyroid carcinomas are a highly aggressive and extremely lethal form of human cancer, but the biological characteristics related to their aggressive nature are not understood. Moreover, Gadd45 family proteins have been implicated in a variety of growth-regulatory mechanisms, including DNA replication and repair, G(2)/M checkpoint control, and apoptosis. In this study we found that Gadd45gamma RNA was present at significantly lower levels in anaplastic cancer cells, compared with normal primary cultured thyrocytes. In addition, the adenovirus-mediated reexpression of Gadd45gamma significantly inhibited the proliferation of anaplastic thyroid carcinoma cells, ARO, FRO, and NPA cells, which was attributed to apoptosis. Furthermore, the adenovirus-mediated delivery of Gadd45gamma gene in anaplastic thyroid cancer resulted in the inhibition of tumor growth in vivo. This in vitro and in vivo activity of the adenovirus-mediated transduction of CR6/Gadd45gamma, on anaplastic thyroid cancer cell growth suppression, was reminiscent of the effects of p53. This study demonstrates that the Gadd45gamma gene has potential use as a candidate gene for gene therapy in anaplastic thyroid cancer.
RN - 0 (GADD45 protein)
RN - 0 (Indicators and Reagents)
RN - 0 (Intracellular Signaling Peptides and Proteins)
RN - 0 (Proteins)
RN - 0 (RNA, Neoplasm)
RN - 0 (Tetrazolium Salts)
RN - 0 (Thiazoles)
RN - EUY85H477I (thiazolyl blue)
IS - 0021-972X
IL - 0021-972X
DO - https://dx.doi.org/10.1210/jc.2002-022031
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 12915687 [pubmed]
ID - 10.1210/jc.2002-022031 [doi]
PP - ppublish
LG - English
DP - 2003 Aug
DC - 20030813
EZ - 2003/08/14 05:00
DA - 2003/09/13 05:00
DT - 2003/08/14 05:00
YR - 2003
ED - 20030911
RD - 20161124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=12915687
<363. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 12754734
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Spierings DC
AU - de Vries EG
AU - Vellenga E
AU - de Jong S
FA - Spierings, Diana C J
FA - de Vries, Elisabeth G E
FA - Vellenga, Edo
FA - de Jong, Steven
IN - Spierings, Diana C J. Departments of Medical Oncology and Haematology, University of Groningen, The Netherlands.
TI - The attractive Achilles heel of germ cell tumours: an inherent sensitivity to apoptosis-inducing stimuli. [Review] [159 refs]
SO - Journal of Pathology. 200(2):137-48, 2003 Jun
AS - J Pathol. 200(2):137-48, 2003 Jun
NJ - The Journal of pathology
PI - Journal available in: Print
PI - Citation processed from: Print
JC - jlb, 0204634
IO - J. Pathol.
SB - Index Medicus
CP - England
MH - Antigens, CD95/ph [Physiology]
MH - *Apoptosis
MH - Cell Cycle
MH - Cyclin-Dependent Kinase Inhibitor p21
MH - Cyclins/ph [Physiology]
MH - *Germinoma/pa [Pathology]
MH - Humans
MH - Male
MH - Neoplasm Proteins/ph [Physiology]
MH - Proto-Oncogene Proteins c-bcl-2/ph [Physiology]
MH - *Testicular Neoplasms/pa [Pathology]
AB - Testicular germ cell tumours (TGCTs) are extremely sensitive to cisplatin-containing chemotherapy. The rapid time course of apoptosis induction after exposure to cisplatin suggests that TGCT cells are primed to undergo programmed cell death as an inherent property of the cell of origin. In fact, apoptosis induction of germ cells in the testis is an important physiological mechanism to control the quality and quantity of the gametes produced. Although p53 protein is highly expressed in the majority of TGCTs, almost no p53 mutations have been detected. Interestingly, p53 overexpression is associated with loss of p21 and gain of mdm2 expression, which might indicate a partial loss in functionality of the p53 regulatory pathway in TGCTs. Besides p21, TGCTs often show low expression of other proteins involved in the regulation of cell cycle progression, such as the retinoblastoma protein and members of the INK4 family. It can be postulated that the deregulated G(1)-S phase checkpoint results in premature entry into the S phase upon DNA damage. In addition to Bcl-2 family members that are involved in the regulation of germ cell apoptosis in the normal testis via the mitochondrial death pathway, the Fas death pathway is also known to regulate apoptosis of germ cells in the testis. Since chemotherapy has been shown to activate the Fas death pathway and TGCTs co-express both Fas and its ligand FasL, TGCT cells might undergo apoptosis upon cisplatin treatment via autocrine or paracrine activation of the Fas system by FasL. The hypothesis suggested here is that the lack of cell cycle arrest following a cisplatin-containing treatment, together with the activation of the Fas death pathway and the mitochondrial death pathway, explains the rapid and efficient apoptosis of TGCT cells. Defining the mechanisms involved in the cisplatin sensitivity of TGCTs will provide tools to increase cisplatin sensitivity in other human tumours with acquired or intrinsic resistance.
AB - Copyright 2003 John Wiley & Sons, Ltd. [References: 159]
RN - 0 (Antigens, CD95)
RN - 0 (CDKN1A protein, human)
RN - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN - 0 (Cyclins)
RN - 0 (Neoplasm Proteins)
RN - 0 (Proto-Oncogene Proteins c-bcl-2)
IS - 0022-3417
IL - 0022-3417
DO - https://dx.doi.org/10.1002/path.1373
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 12754734 [pubmed]
ID - 10.1002/path.1373 [doi]
PP - ppublish
LG - English
DP - 2003 Jun
DC - 20030519
EZ - 2003/05/20 05:00
DA - 2003/07/19 05:00
DT - 2003/05/20 05:00
YR - 2003
ED - 20030718
RD - 20061115
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=12754734
<364. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 12372342
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Sun D
AU - Urrabaz R
AU - Buzello C
AU - Nguyen M
FA - Sun, Daekyu
FA - Urrabaz, Rheanna
FA - Buzello, Christoph
FA - Nguyen, Myhanh
IN - Sun, Daekyu. Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, Texas 78245, USA. sun@pharmacy.arizona.edu
TI - Induction of DNA ligase I by 1-beta-D-arabinosylcytosine and aphidicolin in MiaPaCa human pancreatic cancer cells.
SO - Experimental Cell Research. 280(1):90-6, 2002 Oct 15
AS - Exp Cell Res. 280(1):90-6, 2002 Oct 15
NJ - Experimental cell research
PI - Journal available in: Print
PI - Citation processed from: Print
JC - epb, 0373226
IO - Exp. Cell Res.
SB - Index Medicus
CP - United States
MH - Antimetabolites, Antineoplastic/pk [Pharmacokinetics]
MH - *Antimetabolites, Antineoplastic/pd [Pharmacology]
MH - Aphidicolin/pk [Pharmacokinetics]
MH - *Aphidicolin/pd [Pharmacology]
MH - Caffeine/pd [Pharmacology]
MH - Cell Count
MH - Cell Division/de [Drug Effects]
MH - Cell Line
MH - Cell Survival/de [Drug Effects]
MH - Cytarabine/pk [Pharmacokinetics]
MH - *Cytarabine/pd [Pharmacology]
MH - DNA Ligase ATP
MH - *DNA Ligases/bi [Biosynthesis]
MH - DNA Ligases/ge [Genetics]
MH - DNA Repair/de [Drug Effects]
MH - DNA, Neoplasm/bi [Biosynthesis]
MH - DNA-Directed DNA Polymerase/an [Analysis]
MH - Dose-Response Relationship, Drug
MH - Enzyme Inhibitors/pk [Pharmacokinetics]
MH - *Enzyme Inhibitors/pd [Pharmacology]
MH - Humans
MH - Nucleic Acid Synthesis Inhibitors/pd [Pharmacology]
MH - *Pancreatic Neoplasms/en [Enzymology]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - Pancreatic Neoplasms/pa [Pathology]
MH - Phosphodiesterase Inhibitors/pd [Pharmacology]
MH - RNA, Messenger/me [Metabolism]
MH - Tumor Cells, Cultured
AB - Exposure of MiaPaCa cells to 1-beta-D-arabinosylcytosine (ara-C) resulted in an increase in DNA ligase levels up to threefold compared to that in the untreated control cells, despite significant growth inhibition. Increased levels of DNA ligase I protein appear to correlate with the appearance of increased mRNA levels. The [(3)H]thymidine incorporation experiment and the biochemical assay of total polymerase activity revealed that an increase in DNA ligase I levels after treatment with ara-C was not accompanied by an increase of DNA synthesis or an increased presence of DNA polymerase activity inside cells. When cells resumed DNA synthesis after drug treatment, DNA ligase I levels began to drop, indicating that increased DNA ligase I is not required for DNA synthesis. An increase in DNA ligase I was also observed in cells treated with aphidicolin, another inhibitor of DNA synthesis that inhibits DNA polymerases without incorporating itself into DNA, indicating that an increase in DNA ligase I levels could be caused by the arrest of DNA replication by these agents. Interestingly, caffeine, which is a well-known inhibitor of DNA damage checkpoint kinases, abrogated the increase in DNA ligase I in MiaPaCa cells treated with ara-C and aphidicolin, suggesting that caffeine-sensitive kinases might be important mediators in the pathway leading to the increase in DNA ligase I levels in response to anticancer drugs, including ara-C and aphidicolin. We propose that ara-C and aphidicolin induce damage to the DNA strand by arresting DNA replication forks and subsequently increase DNA ligase I levels to facilitate repair of DNA damage.
RN - 0 (Antimetabolites, Antineoplastic)
RN - 0 (DNA, Neoplasm)
RN - 0 (Enzyme Inhibitors)
RN - 0 (LIG1 protein, human)
RN - 0 (Nucleic Acid Synthesis Inhibitors)
RN - 0 (Phosphodiesterase Inhibitors)
RN - 0 (RNA, Messenger)
RN - 04079A1RDZ (Cytarabine)
RN - 38966-21-1 (Aphidicolin)
RN - 3G6A5W338E (Caffeine)
RN - EC 2-7-7-7 (DNA-Directed DNA Polymerase)
RN - EC 6-5-1 (DNA Ligases)
RN - EC 6-5-1-1 (DNA Ligase ATP)
IS - 0014-4827
IL - 0014-4827
DI - S0014482702956259
PT - Comparative Study
PT - Journal Article
PT - Research Support, U.S. Gov't, P.H.S.
ID - 12372342 [pubmed]
ID - S0014482702956259 [pii]
PP - ppublish
GI - No: CA78715
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2002 Oct 15
DC - 20021009
EZ - 2002/10/10 04:00
DA - 2002/11/26 04:00
DT - 2002/10/10 04:00
YR - 2002
ED - 20021107
RD - 20161124
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=12372342
<365. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 11745415
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Deplanque G
AU - Ceraline J
AU - Mah-Becherel MC
AU - Cazenave JP
AU - Bergerat JP
AU - Klein-Soyer C
FA - Deplanque, G
FA - Ceraline, J
FA - Mah-Becherel, M C
FA - Cazenave, J P
FA - Bergerat, J P
FA - Klein-Soyer, C
IN - Deplanque, G. Laboratoire de Cancerologie Experimentale et de Radiobiologie, Institut de Recherche contre les Cancers de l'Appareil Digestif, Hopitaux Universitaires de Strasbourg, Strasbourg, France.
TI - Caffeine and the G2/M block override: a concept resulting from a misleading cell kinetic delay, independent of functional p53.
SO - International Journal of Cancer. 94(3):363-9, 2001 Nov 01
AS - Int J Cancer. 94(3):363-9, 2001 Nov 01
NJ - International journal of cancer
PI - Journal available in: Print
PI - Citation processed from: Print
JC - gqu, 0042124
IO - Int. J. Cancer
SB - Index Medicus
CP - United States
MH - Antineoplastic Agents, Phytogenic/pd [Pharmacology]
MH - *Caffeine/pd [Pharmacology]
MH - Cell Cycle
MH - Cell Division
MH - Cell Line, Transformed
MH - *Central Nervous System Stimulants/pd [Pharmacology]
MH - DNA/me [Metabolism]
MH - Demecolcine/pd [Pharmacology]
MH - Dose-Response Relationship, Drug
MH - Fibroblasts/me [Metabolism]
MH - *G2 Phase/de [Drug Effects]
MH - G2 Phase/re [Radiation Effects]
MH - Gamma Rays
MH - Genes, Dominant
MH - Humans
MH - Kinetics
MH - *Mitosis/de [Drug Effects]
MH - Mitosis/re [Radiation Effects]
MH - Mutation
MH - Phenotype
MH - Purines/me [Metabolism]
MH - Pyrimidines/me [Metabolism]
MH - Time Factors
MH - Tumor Cells, Cultured
MH - *Tumor Suppressor Protein p53/ph [Physiology]
AB - In the literature the sensitization of DNA to radiation-induced damage by caffeine has been attributed to an override of the G2/M block. This process was supposed to involve the tumor suppressor gene p53 as it was described that p53 negative cells were more sensitive to checkpoint inhibition by caffeine than the wildtype phenotype. We have recently shown that caffeine does not cause an override of the G2/M block induced by radiation in normal human fibroblasts. We demonstrate here that this also applies to a human transformed cell line, the thyroid carcinoma K1, when submitted to gamma- rays irradiation. Within 9 hr after irradiation over 70% of the cells accumulated in the G2/M phase. This block persisted at 16 hr. In caffeine containing cultures the percentage of cells attaining the G2/M phase was reduced by over 30% at 16 hr. This was reflected in an accumulation of the cells in G1 phase and an inhibition of the S phase traverse. Cell cycle analyses from further time points combined with cell proliferation measurements confirmed these data. These results were independent of p53 status as experiments performed with variant K1 cell lines having defective p53 functions, led to similar conclusions. In addition, caffeine restored a G1 delay after irradiation in the cell lines with abrogated p53 functions. The effects of caffeine undeniably cumulate with damages induced by irradiation but probably by inhibiting DNA repair mechanisms or by intervening with purine and pyrimidine metabolisms and not by causing a G2/M block override.
AB - Copyright 2001 Wiley-Liss, Inc.
RN - 0 (Antineoplastic Agents, Phytogenic)
RN - 0 (Central Nervous System Stimulants)
RN - 0 (Purines)
RN - 0 (Pyrimidines)
RN - 0 (Tumor Suppressor Protein p53)
RN - 3G6A5W338E (Caffeine)
RN - 9007-49-2 (DNA)
RN - K8CXK5Q32L (pyrimidine)
RN - W60KTZ3IZY (purine)
RN - Z01IVE25KI (Demecolcine)
IS - 0020-7136
IL - 0020-7136
DI - 10.1002/ijc.1478
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 11745415 [pubmed]
ID - 10.1002/ijc.1478 [pii]
PP - ppublish
LG - English
DP - 2001 Nov 01
DC - 20011217
EZ - 2001/12/18 10:00
DA - 2002/01/10 10:01
DT - 2001/12/18 10:00
YR - 2001
ED - 20020107
RD - 20160303
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=11745415
<366. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 11409710
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Rothe H
AU - Ito Y
AU - Kolb H
FA - Rothe, H
FA - Ito, Y
FA - Kolb, H
IN - Rothe, H. Institute of Diabetes Research, Munich, Germany. helga.rothe@lrz.uni-muenchen.de
TI - Disease resistant, NOD-related strains reveal checkpoints of immunoregulation in the pancreas.
SO - Journal of Molecular Medicine. 79(4):190-7, 2001 May
AS - J Mol Med. 79(4):190-7, 2001 May
NJ - Journal of molecular medicine (Berlin, Germany)
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 9504370, b8c
IO - J. Mol. Med.
SB - Index Medicus
CP - Germany
MH - Animals
MH - Cyclophosphamide/pd [Pharmacology]
MH - *Diabetes Mellitus, Type 1/im [Immunology]
MH - Female
MH - Humans
MH - Immunity, Innate
MH - Immunosuppressive Agents/pd [Pharmacology]
MH - Interferon-gamma/ge [Genetics]
MH - Interferon-gamma/me [Metabolism]
MH - Interleukins/ge [Genetics]
MH - Interleukins/me [Metabolism]
MH - Islets of Langerhans/im [Immunology]
MH - Mice
MH - Mice, Inbred NOD
MH - Mice, Inbred Strains
MH - Pancreas/de [Drug Effects]
MH - *Pancreas/im [Immunology]
MH - Polymerase Chain Reaction
MH - Th1 Cells/im [Immunology]
MH - Th2 Cells/im [Immunology]
AB - The autoimmune diabetic NOD mouse serves as a model for human type 1 diabetes. Disease development is due to islet beta cell destruction in the context of immune cell infiltration of islets and inflammatory changes throughout the pancreas. In the present study we tried to identify immune reactivity patterns in the pancreas associated with diabetes resistance in NOD-related mouse strains. The pancreata of diabetes-prone female NOD/LtJ, NOD/Bom and of genetically related but diabetes-resistant strains; NOR, NON, NON.NOD-H2g7, NOD.NON-H-2nbl were obtained at the age of 70 days for semiquantitative analysis of insulitis and of mRNA expression by reverse transcriptase PCR. In addition, the response to a single dose of cyclophosphamide for synchronizing and accelerating the progression of insulitis was determined. The progression of insulitis and immune gene expression in response to cyclophosphamide revealed characteristic differences between the six strains. NOD/LtJ and NOD/Bom mice were found significantly to upregulate pancreatic IL-12p40 and IL-18 expression after cyclophosphamide treatment, followed by an increase in IFN-gamma mRNA levels. In contrast, the two MHC-haplotype H-2nbl expressing strains either up-regulated neither IL-12/IL-18 nor IFN-gamma gene expression. The two strains sharing MHC haplotype H-2g7 expression with NOD did respond to cyclophosphamide with IL-12p40/IL-18 gene expression. However, NON.NOD-H-2g7 mice failed to progress to IFN-gamma gene expression. NOR mice progressed to IFN-gamma expression but exhibited sustained IL-4 gene expression. Only severe intra-insulitis was associated with the expression of inducible NO synthase. The comparison of diabetes-prone and diabetes-resistant strains revealed three checkpoints of immune regulation in the pancreas. The earliest checkpoint is the induction of an IL-12p40/IL-18 response in innate immune or antigen-presenting cells. The next level of control is at the induction of IFN-gamma gene expression, and a third checkpoint is the maintenance or loss of antagonistic Th2 type reactions.
RN - 0 (Immunosuppressive Agents)
RN - 0 (Interleukins)
RN - 82115-62-6 (Interferon-gamma)
RN - 8N3DW7272P (Cyclophosphamide)
IS - 0946-2716
IL - 0946-2716
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 11409710 [pubmed]
PP - ppublish
LG - English
DP - 2001 May
DC - 20010618
EZ - 2001/06/21 10:00
DA - 2002/01/05 10:01
DT - 2001/06/21 10:00
YR - 2001
ED - 20011212
RD - 20131121
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=11409710
<367. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 10935512
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Song SY
AU - Meszoely IM
AU - Coffey RJ
AU - Pietenpol JA
AU - Leach SD
FA - Song, S Y
FA - Meszoely, I M
FA - Coffey, R J
FA - Pietenpol, J A
FA - Leach, S D
IN - Song, S Y. Department of Surgery, Vanderbilt University Medical Center and Nashville VAMC, TN 37232-2736, USA.
TI - K-Ras-independent effects of the farnesyl transferase inhibitor L-744,832 on cyclin B1/Cdc2 kinase activity, G2/M cell cycle progression and apoptosis in human pancreatic ductal adenocarcinoma cells.
SO - Neoplasia (New York). 2(3):261-72, 2000 May-Jun
AS - Neoplasia. 2(3):261-72, 2000 May-Jun
NJ - Neoplasia (New York, N.Y.)
PI - Journal available in: Print
PI - Citation processed from: Print
JC - dru, 100886622
IO - Neoplasia
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1507570
SB - Index Medicus
CP - United States
MH - *Antineoplastic Agents/pd [Pharmacology]
MH - *Apoptosis/de [Drug Effects]
MH - *Carcinoma, Ductal, Breast/pa [Pathology]
MH - *Cyclin B/me [Metabolism]
MH - Cyclin B1
MH - *Enzyme Inhibitors/pd [Pharmacology]
MH - G2 Phase/de [Drug Effects]
MH - *Genes, ras/ph [Physiology]
MH - Humans
MH - *Methionine/aa [Analogs & Derivatives]
MH - Methionine/pd [Pharmacology]
MH - Mitosis/de [Drug Effects]
MH - *Pancreatic Neoplasms/pa [Pathology]
AB - Pancreatic ductal adenocarcinoma is a highly lethal malignancy that is resistant to traditional cytotoxic therapy. High rates of activating codon 12 K-Ras mutations in this disease have generated considerable interest in the therapeutic application of novel farnesyl transferase inhibitors (FTIs). However, a comprehensive analysis of the effects of FTI treatment on pancreatic cancer cells has not been performed. Treatment of five different human pancreatic cancer cell lines with FTI L-744,832 resulted in inhibition of anchorage-dependent growth, with wide variation in sensitivity among different lines. Effective growth inhibition by L-744,832 correlated with accumulation of cells with a tetraploid (4N) DNA content and high levels of cyclin B1/cdc2 kinase activity, implying cell cycle arrest downstream from the DNA damage-inducible G2/M cell cycle checkpoint. In addition, sensitive cell lines underwent apoptosis as evidenced by changes in nuclear morphology and internucleosomal DNA fragmentation. L-744,832 at a concentration of 1 microM additively enhanced the cytotoxic effect of ionizing radiation, apparently by overriding G2/M checkpoint activation. The effects of FTI treatment on cell growth and cell cycle regulation were associated with changes in posttranslational processing of H-Ras and N-Ras, but not K-Ras. The results confirm the potential therapeutic efficacy of FTI treatment in pancreatic cancer, and suggest that farnesylated proteins other than K-Ras may act as important regulators of G2/M cell cycle kinetics.
RN - 0 (Antineoplastic Agents)
RN - 0 (CCNB1 protein, human)
RN - 0 (Cyclin B)
RN - 0 (Cyclin B1)
RN - 0 (Enzyme Inhibitors)
RN - 0 (L 744832)
RN - AE28F7PNPL (Methionine)
IS - 1522-8002
IL - 1476-5586
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Research Support, U.S. Gov't, Non-P.H.S.
PT - Research Support, U.S. Gov't, P.H.S.
ID - 10935512 [pubmed]
ID - PMC1507570 [pmc]
PP - ppublish
GI - No: F32 CA076698
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA046413
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA46413
Organization: (CA) *NCI NIH HHS*
Country: United States
No: CA76698
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2000 May-Jun
DC - 20000817
EZ - 2000/08/10 11:00
DA - 2000/08/19 11:00
DT - 2000/08/10 11:00
YR - 2000
ED - 20000817
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=10935512
<368. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 10210535
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - King TC
AU - Estalilla OC
AU - Safran H
FA - King, T C
FA - Estalilla, O C
FA - Safran, H
IN - King, T C. Departments of Pathology and Laboratory Medicine, Lifespan, Providence, RI, USA.
TI - Role of p53 and p16 gene alterations in determining response to concurrent paclitaxel and radiation in solid tumor. [Review] [58 refs]
SO - Seminars in Radiation Oncology. 9(2 Suppl 1):4-11, 1999 Apr
AS - Semin Radiat Oncol. 9(2 Suppl 1):4-11, 1999 Apr
NJ - Seminars in radiation oncology
PI - Journal available in: Print
PI - Citation processed from: Print
JC - c1y, 9202882
IO - Semin Radiat Oncol
SB - Index Medicus
CP - United States
MH - Animals
MH - *Antineoplastic Agents, Phytogenic/tu [Therapeutic Use]
MH - Apoptosis
MH - Carcinoma, Non-Small-Cell Lung/dt [Drug Therapy]
MH - Carcinoma, Non-Small-Cell Lung/ge [Genetics]
MH - *Carcinoma, Non-Small-Cell Lung/rt [Radiotherapy]
MH - Cell Cycle/ph [Physiology]
MH - Combined Modality Therapy
MH - Genes, cdc/ge [Genetics]
MH - *Genes, p16/ge [Genetics]
MH - *Genes, p53/ge [Genetics]
MH - Humans
MH - Lung Neoplasms/dt [Drug Therapy]
MH - Lung Neoplasms/ge [Genetics]
MH - *Lung Neoplasms/rt [Radiotherapy]
MH - Mutation
MH - *Paclitaxel/tu [Therapeutic Use]
MH - Pancreatic Neoplasms/dt [Drug Therapy]
MH - Pancreatic Neoplasms/ge [Genetics]
MH - *Pancreatic Neoplasms/rt [Radiotherapy]
MH - *Radiation-Sensitizing Agents/tu [Therapeutic Use]
MH - Stomach Neoplasms/dt [Drug Therapy]
MH - Stomach Neoplasms/ge [Genetics]
MH - *Stomach Neoplasms/rt [Radiotherapy]
AB - Molecular genetic alterations that disturb cell cycle regulation in tumor cells can affect their response to chemotherapeutic agents and radiation. Many genes that regulate the critical cell cycle checkpoint at G1S are altered in human tumors. These genetic changes can result in uncontrolled cellular proliferation, genetic instability, and altered response to radiation and chemotherapy. The p53 tumor suppressor gene serves a critical role at the G1S transition, where it can either block entry into S phase or activate programmed cell death (apoptosis) in response to DNA damage. p53 Gene mutations are common in human tumors and interfere with the activation of apoptosis in response to most chemotherapeutic agents. Paclitaxel is a potent chemotherapeutic agent that interferes with mitotic spindle function to block cells at G2M, the most radiosensitive phase of the cell cycle. Utilization of paclitaxel as a radiation sensitizer in vivo to treat aggressive, locally advanced neoplasms has resulted in high response rates and acceptable toxicity in protocols for non-small cell lung carcinoma, upper gastrointestinal tract carcinoma, and other malignancies. Recent evidence suggests that paclitaxel is unique in its ability to activate apoptosis in tumor cells with p53 mutations in vitro and in vivo. The p16(INK4a) (MTS-1, CDKN2) gene product acts in the same pathway as p53 to inhibit cell cycle progression at G1/S. p16(INK4a) is deleted and/or mutated in a significant fraction of human tumors, including pancreatic carcinoma. The effects of p16(INK4a) alterations in response to paclitaxel/radiation and the risk of systemic relapse are currently being evaluated. Information about molecular genetic alterations in individual tumors ultimately may be a critical factor in choosing between therapeutic options. [References: 58]
RN - 0 (Antineoplastic Agents, Phytogenic)
RN - 0 (Radiation-Sensitizing Agents)
RN - P88XT4IS4D (Paclitaxel)
IS - 1053-4296
IL - 1053-4296
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Review
ID - 10210535 [pubmed]
PP - ppublish
LG - English
DP - 1999 Apr
DC - 19990713
EZ - 1999/04/21 00:00
DA - 1999/04/21 00:01
DT - 1999/04/21
YR - 1999
ED - 19990713
RD - 20151119
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=10210535
<369. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 10094876
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Wolf JK
AU - Kim TE
AU - Fightmaster D
AU - Bodurka D
AU - Gershenson DM
AU - Mills G
AU - Wharton JT
FA - Wolf, J K
FA - Kim, T E
FA - Fightmaster, D
FA - Bodurka, D
FA - Gershenson, D M
FA - Mills, G
FA - Wharton, J T
IN - Wolf, J K. Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030, USA.
TI - Growth suppression of human ovarian cancer cell lines by the introduction of a p16 gene via a recombinant adenovirus.
SO - Gynecologic Oncology. 73(1):27-34, 1999 Apr
AS - Gynecol Oncol. 73(1):27-34, 1999 Apr
NJ - Gynecologic oncology
PI - Journal available in: Print
PI - Citation processed from: Print
JC - fxc, 0365304
IO - Gynecol. Oncol.
SB - Index Medicus
CP - United States
MH - *Adenoviruses, Human/ge [Genetics]
MH - Cell Division
MH - DNA, Recombinant
MH - Female
MH - *Genes, p16
MH - *Genetic Therapy
MH - Humans
MH - *Ovarian Neoplasms/pa [Pathology]
MH - *Ovarian Neoplasms/th [Therapy]
MH - Tumor Cells, Cultured
AB - OBJECTIVE: The cell cycle regulatory protein p16 (CDKN2/cyclin dependent kinase 4 inhibitor/multiple tumor suppressor-1) causes cell cycle arrest at the G1 checkpoint by inhibiting activity of cyclin D-CDK4 complexes. The purpose of this study is to assess the effect of introduction of the p16 gene into two ovarian cancer cell lines via a recombinant adenoviral vector (Ad5CMV-p16).
AB - METHODS: Cells lines used were SKOV3, which has a p16 deletion, and OVCA420, which has normal p16. Transduction efficiency was established by infecting cells with an adenovirus containing the Escherichia coli beta-galactosidase gene (Ad5CMV-beta-gal) at multiplicity of infection from 0 to 1000 and staining for X-gal. Cells were infected with Ad5CMV-p16 and cell growth was assessed by counting cells every other day for up to 7 days. Western blotting was done to assess for p16 expression after infection. Fluorescence-activated cell sorting after staining with propidium iodide was done to assess the effect of p16 on the cell cycle.
AB - RESULTS: The SKOV3 cell line was transduced with the adenovirus at a slightly lower MOI than the OVCA420 cell line. Growth of the Ad5CMV-p16-infected cells was suppressed 75-80% by cell count in both cell lines and caused morphologic changes of the cells consistent with apoptosis. The p16 protein expression was seen to increase within 24 h after introduction of the p16 gene. G1 arrest of cells occurred beginning 24 h after introduction of the p16 gene.
AB - CONCLUSIONS: These results suggest that Ad5CMV-p16 may be further studied as a potential therapeutic agent for ovarian cancer as introduction of the p16 gene into ovarian cancer cell lines causes a G1 arrest and attenuation of growth, regardless of the endogenous p16 status of the cells.
AB - Copyright 1999 Academic Press.
RN - 0 (DNA, Recombinant)
IS - 0090-8258
IL - 0090-8258
DI - S0090-8258(98)95259-3
DO - https://dx.doi.org/10.1006/gyno.1998.5259
PT - Journal Article
ID - 10094876 [pubmed]
ID - S0090-8258(98)95259-3 [pii]
ID - 10.1006/gyno.1998.5259 [doi]
PP - ppublish
LG - English
DP - 1999 Apr
DC - 19990513
EZ - 1999/03/30 00:00
DA - 1999/03/30 00:01
DT - 1999/03/30
YR - 1999
ED - 19990513
RD - 20121115
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=10094876
<370. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 8855976
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - MEDLINE
AU - Schuyer M
AU - van Staveren IL
AU - Klijn JG
AU - vd Burg ME
AU - Stoter G
AU - Henzen-Logmans SC
AU - Foekens JA
AU - Berns EM
FA - Schuyer, M
FA - van Staveren, I L
FA - Klijn, J G
FA - vd Burg, M E
FA - Stoter, G
FA - Henzen-Logmans, S C
FA - Foekens, J A
FA - Berns, E M
IN - Schuyer, M. Division of Endocrine Oncology (Department of Medical Oncology), Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
TI - Sporadic CDKN2 (MTS1/p16ink4) gene alterations in human ovarian tumours.
SO - British Journal of Cancer. 74(7):1069-73, 1996 Oct
AS - Br J Cancer. 74(7):1069-73, 1996 Oct
NJ - British journal of cancer
PI - Journal available in: Print
PI - Citation processed from: Print
JC - av4, 0370635
IO - Br. J. Cancer
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077110
SB - Index Medicus
CP - England
MH - *Adenocarcinoma/ge [Genetics]
MH - Adult
MH - Aged
MH - Aged, 80 and over
MH - *Carrier Proteins/ge [Genetics]
MH - Cyclin-Dependent Kinase Inhibitor p16
MH - Exons/ge [Genetics]
MH - Female
MH - *Genes, Tumor Suppressor/ge [Genetics]
MH - Humans
MH - Middle Aged
MH - *Ovarian Neoplasms/ge [Genetics]
MH - Point Mutation
MH - Polymerase Chain Reaction
MH - Polymorphism, Single-Stranded Conformational
MH - Sequence Deletion
MH - Tumor Cells, Cultured
AB - The cell cycle regulatory proteins p16 and p21 cause cell cycle arrest at the G1 checkpoint by inhibiting activity of cyclin D-CDK4 complexes. The TP53 gene, regulating the p21 protein, is mutated at high frequency in ovarian cancer. The CDKN2 gene, encoding the p16 protein, has been mapped to chromosome 9p21 and encompasses three exons. To establish the frequency of CDKN2 gene abnormalities in ovarian tumour specimens, we have studied this gene in five ovarian cancer cell lines and in 32 primary and five metastatic ovarian adenocarcinomas. Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing techniques both exon 1 and 2 of the CDKN2 gene, encompassing 97% of the coding sequence, were analysed. In addition, the TP53 gene was studied for the presence of mutations. The cell line HOC-7 showed a 16 bp deletion in exon 2 of the CDKN2 gene, resulting in a stop codon, whereas in cell line SK-OV-3 this gene was found to be homozygously deleted. Nine primary tumour specimens showed a migration shift on SSCP. Sequencing revealed a common polymorphism (Ala148Thr) in seven of these ovarian tumour specimens. The two other tumour samples were found to contain silent mutations, one at codon 23 (GGT-->GGA) and the other at codon 67 (GGC-->GGT). Mutations in the TP53 gene were observed in 46% of the ovarian tumour specimens. We conclude that CDKN2 gene alterations are rare events in human ovarian cancer. The low prevalence of these alterations do not allow for analysis of an association of this gene with prognosis.
RN - 0 (Carrier Proteins)
RN - 0 (Cyclin-Dependent Kinase Inhibitor p16)
IS - 0007-0920
IL - 0007-0920
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
ID - 8855976 [pubmed]
ID - PMC2077110 [pmc]
PP - ppublish
LG - English
DP - 1996 Oct
DC - 19961101
EZ - 1996/10/01 00:00
DA - 1996/10/01 00:01
DT - 1996/10/01
YR - 1996
ED - 19961101
RD - 20130918
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=8855976
<371. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28702249
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Faje A
AI - Faje, Alexander; ORCID: https://orcid.org/0000-0002-4092-5409
AI - Faje, Alexander; GRID: grid.32224.35
AI - Faje, Alexander; ISNI: grid.32224.35
FA - Faje, Alexander
IN - Faje, Alexander. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114 USA.
TI - Hypophysitis: Evaluation and Management. [Review]
SO - Clinical Diabetes & Endocrinology. 2:15, 2016
AS - Clin. diabetes endocrinol.. 2:15, 2016
NJ - Clinical diabetes and endocrinology
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101669619
IO - Clin Diabetes Endocrinol
CP - England
KW - Diabetes insipidus; Hypophysitis; Hypopituitarism
AB - Hypophysitis is the acute or chronic inflammation of the pituitary gland. The spectrum of hypophysitis has expanded in recent years with the addition of two histologic subtypes and recognition as a complication of treatment with immune checkpoint inhibitors. Despite the increased number of published cases, the pathogenesis of hypophysitis is poorly understood, and treatment strategies are diverse and controversial. The diagnosis of hypophysitis generally requires histopathologic confirmation. The presentation and clinical course of hypophysitis varies. Hypophysitis can resolve spontaneously, relapse may occur, and some cases can be refractory to treatment.
IS - 2055-8260
IL - 2055-8260
DI - 34
DO - https://dx.doi.org/10.1186/s40842-016-0034-8
PT - Journal Article
PT - Review
ID - 10.1186/s40842-016-0034-8 [doi]
ID - 34 [pii]
ID - PMC5471685 [pmc]
PP - epublish
PH - 2016/07/01 [received]
PH - 2016/08/26 [accepted]
LG - English
EP - 20160906
DP - 2016
DC - 20170713
EZ - 2017/07/14 06:00
DA - 2017/07/14 06:01
DT - 2017/07/14 06:00
YR - 2016
RD - 20170716
UP - 20170717
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28702249
<372. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28533473
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Larkins E
AU - Blumenthal GM
AU - Yuan W
AU - He K
AU - Sridhara R
AU - Subramaniam S
AU - Zhao H
AU - Liu C
AU - Yu J
AU - Goldberg KB
AU - McKee AE
AU - Keegan P
AU - Pazdur R
FA - Larkins, Erin
FA - Blumenthal, Gideon M
FA - Yuan, Weishi
FA - He, Kun
FA - Sridhara, Rajeshwari
FA - Subramaniam, Sriram
FA - Zhao, Hong
FA - Liu, Chao
FA - Yu, Jingyu
FA - Goldberg, Kirsten B
FA - McKee, Amy E
FA - Keegan, Patricia
FA - Pazdur, Richard
IN - Larkins, Erin. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA erin.larkins@fda.hhs.gov.
IN - Blumenthal, Gideon M. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Yuan, Weishi. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - He, Kun. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Sridhara, Rajeshwari. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Subramaniam, Sriram. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Zhao, Hong. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Liu, Chao. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Yu, Jingyu. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Goldberg, Kirsten B. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - McKee, Amy E. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Keegan, Patricia. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Pazdur, Richard. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
TI - FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy.
SO - Oncologist. 22(7):873-878, 2017 Jul
AS - Oncologist. 22(7):873-878, 2017 Jul
NJ - The oncologist
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dd5, 9607837
IO - Oncologist
CP - United States
KW - Immunotherapy; Pembrolizumab; Programmed cell death 1 receptor; Squamous cell carcinoma of the head and neck; U.S. Food and Drug Administration
AB - On August 5, 2016, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA injection, Merck Sharp & Dohme Corp., Kenilworth, NJ) for treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. Approval was based on the objective response rate (ORR) and duration of response (DoR) in a cohort of patients in a nonrandomized multi-cohort trial (KEYNOTE-012) that included 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. Patients received either intravenous pembrolizumab 10 mg/kg every 2 weeks or 200 mg every 3 weeks. ORR was determined by independent review according to Response Evaluation Criteria in Solid Tumors 1.1. ORR was 16% (95% confidence interval 11, 22) with a complete response rate of 5%. DoR ranged from 2.4+ months to 27.7+ months. Twenty-three of 28 responding patients (82%) had response durations of >=6 months. Safety was evaluated in 192 patients with HNSCC receiving at least one dose of pembrolizumab. Frequent (>=2%) serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders. The benefit-risk profile of pembrolizumab was considered acceptable in this patient population. As a condition of accelerated approval, Merck is required to conduct a confirmatory trial; this trial, KEYNOTE-040, is ongoing.
AB - IMPLICATIONS FOR PRACTICE: This accelerated approval expands the U.S. Food and Drug Administration-approved indications for pembrolizumab, providing health care providers with new information regarding pembrolizumab for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. Pembrolizumab is the first drug to receive approval for treatment of patients with HNSCC since cetuximab was approved for this indication in 2006.
Copyright Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
CI - Disclosures of potential conflicts of interest may be found at the end of this article.
ES - 1549-490X
IL - 1083-7159
DI - theoncologist.2016-0496
DO - https://dx.doi.org/10.1634/theoncologist.2016-0496
PT - Journal Article
ID - theoncologist.2016-0496 [pii]
ID - 10.1634/theoncologist.2016-0496 [doi]
ID - PMC5507654 [pmc]
PP - ppublish
PH - 2016/12/13 [received]
PH - 2017/02/21 [accepted]
LG - English
EP - 20170522
DP - 2017 Jul
DC - 20170523
EZ - 2017/05/24 06:00
DA - 2017/05/24 06:00
DT - 2017/05/24 06:00
YR - 2017
RD - 20170716
UP - 20170717
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28533473
<373. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28211040
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Wallberg M
AU - Recino A
AU - Phillips J
AU - Howie D
AU - Vienne M
AU - Paluch C
AU - Azuma M
AU - Wong FS
AU - Waldmann H
AU - Cooke A
AI - Wallberg, Maja; ORCID: http://orcid.org/0000-0001-8297-7859
FA - Wallberg, Maja
FA - Recino, Asha
FA - Phillips, Jenny
FA - Howie, Duncan
FA - Vienne, Margaux
FA - Paluch, Christopher
FA - Azuma, Miyuki
FA - Wong, F Susan
FA - Waldmann, Herman
FA - Cooke, Anne
IN - Wallberg, Maja. Department of Pathology, University of Cambridge, Cambridge, UK.
IN - Recino, Asha. Department of Pathology, University of Cambridge, Cambridge, UK.
IN - Phillips, Jenny. Department of Pathology, University of Cambridge, Cambridge, UK.
IN - Howie, Duncan. Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
IN - Vienne, Margaux. Department of Pathology, University of Cambridge, Cambridge, UK.
IN - Paluch, Christopher. Department of Pathology, University of Cambridge, Cambridge, UK.
IN - Azuma, Miyuki. Department of Molecular Immunology Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
IN - Wong, F Susan. Diabetes Research Group, Institute of Molecular and Experimental Medicine, Cardiff School of Medicine, Cardiff University, Cardiff, UK.
IN - Waldmann, Herman. Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
IN - Cooke, Anne. Department of Pathology, University of Cambridge, Cambridge, UK.
TI - Anti-CD3 treatment up-regulates programmed cell death protein-1 expression on activated effector T cells and severely impairs their inflammatory capacity.[Erratum appears in Immunology. 2017 Aug;151(4):481; PMID: 28699309]
SO - Immunology. 151(2):248-260, 2017 Jun
AS - Immunology. 151(2):248-260, 2017 Jun
NJ - Immunology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - gh7, 0374672
IO - Immunology
CP - England
KW - antibodies; diabetes; tolerance/suppression/anergy; transgenic/knockout mouse
AB - T cells play a key role in the pathogenesis of type 1 diabetes, and targeting the CD3 component of the T-cell receptor complex provides one therapeutic approach. Anti-CD3 treatment can reverse overt disease in spontaneously diabetic non-obese diabetic mice, an effect proposed to, at least in part, be caused by a selective depletion of pathogenic cells. We have used a transfer model to further investigate the effects of anti-CD3 treatment on green fluorescent protein (GFP)+ islet-specific effector T cells in vivo. The GFP expression allowed us to isolate the known effectors at different time-points during treatment to assess cell presence in various organs as well as gene expression and cytokine production. We find, in this model, that anti-CD3 treatment does not preferentially deplete the transferred effector cells, but instead inhibits their metabolic function and their production of interferon-gamma. Programmed cell death protein 1 (PD-1) expression was up-regulated on the effector cells from anti-CD3-treated mice, and diabetes induced through anti-PD-L1 antibody could only be reversed with anti-CD3 antibody if the anti-CD3 treatment lasted beyond the point when the anti-PD-L1 antibody was washed out of the system. This suggests that PD-1/PD-L1 interaction plays an important role in the anti-CD3 antibody mediated protection. Our data demonstrate an additional mechanism by which anti-CD3 therapy can reverse diabetogenesis.
Copyright © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd.
ES - 1365-2567
IL - 0019-2805
DO - https://dx.doi.org/10.1111/imm.12729
PT - Journal Article
ID - 10.1111/imm.12729 [doi]
ID - PMC5418468 [pmc]
PP - ppublish
PH - 2016/11/24 [received]
PH - 2017/02/03 [revised]
PH - 2017/02/13 [accepted]
LG - English
EP - 20170316
DP - 2017 Jun
DC - 20170217
EZ - 2017/02/18 06:00
DA - 2017/02/18 06:00
DT - 2017/02/18 06:00
YR - 2017
RD - 20170716
UP - 20170717
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28211040
<374. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28680756
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Layer JP
AU - Kronmuller MT
AU - Quast T
AU - van den Boorn-Konijnenberg D
AU - Effern M
AU - Hinze D
AU - Althoff K
AU - Schramm A
AU - Westermann F
AU - Peifer M
AU - Hartmann G
AU - Tuting T
AU - Kolanus W
AU - Fischer M
AU - Schulte J
AU - Holzel M
FA - Layer, Julian P
FA - Kronmuller, Marie T
FA - Quast, Thomas
FA - van den Boorn-Konijnenberg, Debby
FA - Effern, Maike
FA - Hinze, Daniel
FA - Althoff, Kristina
FA - Schramm, Alexander
FA - Westermann, Frank
FA - Peifer, Martin
FA - Hartmann, Gunther
FA - Tuting, Thomas
FA - Kolanus, Waldemar
FA - Fischer, Matthias
FA - Schulte, Johannes
FA - Holzel, Michael
IN - Layer, Julian P. Unit for RNA Biology, Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
IN - Kronmuller, Marie T. Division of Molecular Immunology and Cell Biology, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
IN - Quast, Thomas. Division of Molecular Immunology and Cell Biology, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
IN - van den Boorn-Konijnenberg, Debby. Unit for RNA Biology, Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
IN - Effern, Maike. Unit for RNA Biology, Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
IN - Effern, Maike. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunology, The University of Melbourne, Melbourne, Victoria, Australia.
IN - Hinze, Daniel. Unit for RNA Biology, Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
IN - Althoff, Kristina. Pediatric Oncology and Hematology, University Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany.
IN - Schramm, Alexander. Pediatric Oncology and Hematology, University Children's Hospital Essen, University of Duisburg-Essen, Essen, Germany.
IN - Schramm, Alexander. Molecular Oncology, Internal Medicine/Cancer Research Unit, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
IN - Westermann, Frank. Neuroblastoma Genomics B087, German Cancer Research Center (DKFZ), Heidelberg, Germany.
IN - Peifer, Martin. Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Cologne, Germany.
IN - Peifer, Martin. Center for Molecular Medicine Cologne, Medical Faculty, University of Cologne, Cologne, Germany.
IN - Hartmann, Gunther. Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
IN - Tuting, Thomas. Laboratory of Experimental Dermatology, Department of Dermatology, University of Magdeburg, Magdeburg, Germany.
IN - Tuting, Thomas. Laboratory of Experimental Dermatology, Department of Dermatology, University of Bonn, Bonn, Germany.
IN - Kolanus, Waldemar. Division of Molecular Immunology and Cell Biology, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
IN - Fischer, Matthias. Center for Molecular Medicine Cologne, Medical Faculty, University of Cologne, Cologne, Germany.
IN - Fischer, Matthias. Department of Experimental Pediatric Hematology and Oncology, University of Cologne, Cologne, Germany.
IN - Fischer, Matthias. Max Planck Institute for Metabolism Research, Cologne, Germany.
IN - Schulte, Johannes. Department of Pediatric Hematology, Oncology and SCT, Charite - University Hospital Berlin, Campus Virchow-Klinikum, Berlin, Germany.
IN - Holzel, Michael. Unit for RNA Biology, Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
TI - Amplification of N-Myc is associated with a T-cell-poor microenvironment in metastatic neuroblastoma restraining interferon pathway activity and chemokine expression.
SO - Oncoimmunology. 6(6):e1320626, 2017
AS - Oncoimmunology. 6(6):e1320626, 2017
NJ - Oncoimmunology
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101570526
IO - Oncoimmunology
CP - United States
KW - Chemokine; Cxcl10; N-Myc; STING; immunotherapy; infiltration; interferoninfiltration; neuroblastoma
AB - Immune checkpoint inhibitors have significantly improved the treatment of several cancers. T-cell infiltration and the number of neoantigens caused by tumor-specific mutations are correlated to favorable responses in cancers with a high mutation load. Accordingly, checkpoint immunotherapy is thought to be less effective in tumors with low mutation frequencies such as neuroblastoma, a neuroendocrine tumor of early childhood with poor outcome of the high-risk disease group. However, spontaneous regressions and paraneoplastic syndromes seen in neuroblastoma patients suggest substantial immunogenicity. Using an integrative transcriptomic approach, we investigated the molecular characteristics of T-cell infiltration in primary neuroblastomas as an indicator of pre-existing immune responses and potential responsiveness to checkpoint inhibition. Here, we report that a T-cell-poor microenvironment in primary metastatic neuroblastomas is associated with genomic amplification of the MYCN (N-Myc) proto-oncogene. These tumors exhibited lower interferon pathway activity and chemokine expression in line with reduced immune cell infiltration. Importantly, we identified a global role for N-Myc in the suppression of interferon and pro-inflammatory pathways in human and murine neuroblastoma cell lines. N-Myc depletion potently enhanced targeted interferon pathway activation by a small molecule agonist of the cGAS-STING innate immune pathway. This promoted chemokine expression including Cxcl10 and T-cell recruitment in microfluidics migration assays. Hence, our data suggest N-Myc inhibition plus targeted IFN activation as adjuvant strategy to enforce cytotoxic T-cell recruitment in MYCN-amplified neuroblastomas.
IS - 2162-4011
IL - 2162-4011
DI - 1320626
DO - https://dx.doi.org/10.1080/2162402X.2017.1320626
PT - Journal Article
ID - 10.1080/2162402X.2017.1320626 [doi]
ID - 1320626 [pii]
ID - PMC5486176 [pmc]
PP - epublish
PH - 2016/12/13 [received]
PH - 2017/03/26 [revised]
PH - 2017/04/13 [accepted]
PH - 2018/04/28 [pmc-release]
LG - English
EP - 20170428
DP - 2017
DC - 20170706
EZ - 2017/07/07 06:00
DA - 2017/07/07 06:00
DT - 2017/07/07 06:00
YR - 2017
RD - 20170717
UP - 20170717
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28680756
<375. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28638725
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Petersen CT
AU - Li JM
AU - Waller EK
FA - Petersen, Christopher T
FA - Li, Jian-Ming
FA - Waller, Edmund K
IN - Petersen, Christopher T. Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA, USA.
IN - Li, Jian-Ming. Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA, USA.
IN - Waller, Edmund K. Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA, USA.
TI - Administration of a vasoactive intestinal peptide antagonist enhances the autologous anti-leukemia T cell response in murine models of acute leukemia.
SO - Oncoimmunology. 6(5):e1304336, 2017
AS - Oncoimmunology. 6(5):e1304336, 2017
NJ - Oncoimmunology
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101570526
IO - Oncoimmunology
CP - United States
KW - Antagonist; T cells; checkpoint blockade; co-stimulation; leukemia
AB - Vasoactive intestinal peptide (VIP) is a neuroendocrine peptide hormone that has potent anti-inflammatory activities. VIP signaling through its receptor VPAC1 on T cells leads to reduced proliferation and a reduction in pro-inflammatory cytokine secretion. We report here that inhibition of the VIP pathway with a peptide antagonist significantly enhances a T-cell-dependent, autologous anti-leukemia response in murine models of acute myeloid leukemia and T lymphoblastic leukemia. Subcutaneous administration of the VIP antagonist, VIPhyb, resulted in reduced tumor burden and significantly enhanced survival (30-50% survival) over vehicle-treated controls (0-20% survival). The T cells in mice treated with VIPhyb expressed lower levels of the co-inhibitory PD-1 and secreted higher levels of IFNgamma. Furthermore, T cells from VIPhyb-treated survivors were protective against C1498 following adoptive transfer. These data highlight the potential for the VIP pathway as a novel target for immunomodulation in settings of hematological malignancies.
IS - 2162-4011
IL - 2162-4011
DI - 1304336
DO - https://dx.doi.org/10.1080/2162402X.2017.1304336
PT - Journal Article
ID - 10.1080/2162402X.2017.1304336 [doi]
ID - 1304336 [pii]
ID - PMC5467986 [pmc]
PP - epublish
PH - 2016/10/18 [received]
PH - 2017/03/02 [revised]
PH - 2017/03/03 [accepted]
PH - 2018/03/16 [pmc-release]
LG - English
EP - 20170316
DP - 2017
DC - 20170622
EZ - 2017/06/23 06:00
DA - 2017/06/24 06:00
DT - 2017/06/24 06:00
YR - 2017
RD - 20170717
UP - 20170717
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28638725
<376. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28611636
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Li L
AU - Masood A
AU - Bari S
AU - Yavuz S
AU - Grosbach AB
FA - Li, Li
FA - Masood, Awais
FA - Bari, Shahla
FA - Yavuz, Sahzene
FA - Grosbach, Alan B
IN - Li, Li. aDivision of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, Florida, USA.
IN - Li, Li. dDivision of Hematology and Oncology, Malcom Randall VA Medical Center, Gainesville, Florida, USA.
IN - Masood, Awais. bDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida, Gainesville, Florida, USA.
IN - Masood, Awais. eDivision of Endocrinology, Malcom Randall VA Medical Center, Gainesville, Florida, USA.
IN - Bari, Shahla. cDepartment of Medicine, University of Florida, Gainesville, Florida, USA.
IN - Yavuz, Sahzene. bDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Florida, Gainesville, Florida, USA.
IN - Yavuz, Sahzene. eDivision of Endocrinology, Malcom Randall VA Medical Center, Gainesville, Florida, USA.
IN - Grosbach, Alan B. aDivision of Hematology and Oncology, Department of Medicine, University of Florida, Gainesville, Florida, USA.
IN - Grosbach, Alan B. dDivision of Hematology and Oncology, Malcom Randall VA Medical Center, Gainesville, Florida, USA.
TI - Autoimmune Diabetes and Thyroiditis Complicating Treatment with Nivolumab.
SO - Case Reports Oncology. 10(1):230-234, 2017 Jan-Apr
AS - Case rep., oncol.. 10(1):230-234, 2017 Jan-Apr
NJ - Case reports in oncology
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101517601
IO - Case Rep Oncol
CP - Switzerland
KW - Autoimmune diabetes; Nivolumab; PD-1 inhibitor
AB - Programmed cell death-1 (PD-1) ligand inhibitors have gained popularity in the treatment of advanced non-small-cell lung cancer. The immune system is regulated by stimulatory and inhibitory signaling and aims to achieve the balance between activation and inhibition. Treatment with immune checkpoint inhibitors enhances immune response, but is also known to diminish immune tolerance and increase autoimmune toxicity. Here we present a case of a patient with advanced squamous cell lung cancer who developed type I diabetes and thyroiditis after treatment with PD-1 checkpoint inhibitor nivolumab. The presence of autoimmune diabetes mellitus and thyroiditis were confirmed by markedly elevated titers of the glutamic acid decarboxylase autoantibody and thyroid peroxidase antibody, respectively. This report serves to heighten awareness of potential autoimmune toxicities related to anti-PD-1 therapy, especially as these toxicities are manageable if identified in a timely manner.
IS - 1662-6575
IL - 1662-6575
DI - cro-0010-0230
DO - https://dx.doi.org/10.1159/000456540
PT - Journal Article
ID - 10.1159/000456540 [doi]
ID - cro-0010-0230 [pii]
ID - PMC5465653 [pmc]
PP - epublish
PH - 2017/01/16 [received]
PH - 2017/01/16 [accepted]
LG - English
EP - 20170302
DP - 2017 Jan-Apr
DC - 20170614
EZ - 2017/06/15 06:00
DA - 2017/06/15 06:01
DT - 2017/06/15 06:00
YR - 2017
RD - 20170717
UP - 20170717
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28611636
<377. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27775076
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Chen F
AU - Zhang Y
AU - Parra E
AU - Rodriguez J
AU - Behrens C
AU - Akbani R
AU - Lu Y
AU - Kurie JM
AU - Gibbons DL
AU - Mills GB
AU - Wistuba II
AU - Creighton CJ
FA - Chen, F
FA - Zhang, Y
FA - Parra, E
FA - Rodriguez, J
FA - Behrens, C
FA - Akbani, R
FA - Lu, Y
FA - Kurie, J M
FA - Gibbons, D L
FA - Mills, G B
FA - Wistuba, I I
FA - Creighton, C J
IN - Chen, F. Dan L. Duncan Comprehensive Cancer Center, Division of Biostatistics, Baylor College of Medicine, Houston, TX, USA.
IN - Zhang, Y. Dan L. Duncan Comprehensive Cancer Center, Division of Biostatistics, Baylor College of Medicine, Houston, TX, USA.
IN - Parra, E. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer, Houston, TX, USA.
IN - Rodriguez, J. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer, Houston, TX, USA.
IN - Behrens, C. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer, Houston, TX, USA.
IN - Akbani, R. Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
IN - Lu, Y. Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
IN - Kurie, J M. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
IN - Gibbons, D L. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
IN - Gibbons, D L. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
IN - Mills, G B. Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
IN - Wistuba, I I. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer, Houston, TX, USA.
IN - Wistuba, I I. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
IN - Creighton, C J. Dan L. Duncan Comprehensive Cancer Center, Division of Biostatistics, Baylor College of Medicine, Houston, TX, USA.
IN - Creighton, C J. Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
IN - Creighton, C J. Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
TI - Multiplatform-based molecular subtypes of non-small-cell lung cancer.
SO - Oncogene. 36(10):1384-1393, 2017 Mar
AS - Oncogene. 36(10):1384-1393, 2017 Mar
NJ - Oncogene
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - onc, 8711562
IO - Oncogene
CP - England
AB - Non-small-cell lung cancer (NSCLC) demonstrates remarkable molecular diversity. With the completion of The Cancer Genome Atlas (TCGA), there is opportunity for systematic analyses of the entire TCGA NSCLC cohort, including comparisons and contrasts between different disease subsets. On the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy, and RNA and protein expression), 1023 NSCLC cases-519 from TCGA adenocarcinoma (AD) project and 504 from TCGA squamous cell carcinoma (SQCC) project-were classified using a 'cluster-of-clusters' analytic approach. Patterns from TCGA NSCLC subsets were examined in independent external databases, including the PROSPECT (Profiling of Resistance patterns and Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax) NSCLC data set. Nine genomic subtypes of NSCLC were identified, three within SQCC and six within AD. SQCC subtypes were associated with transcriptional targets of SOX2 or p63. One predominately AD subtype (with a large proportion of SQCC) shared molecular features with neuroendocrine tumors. Two AD subtypes manifested a CpG island methylator phenotype. Three AD subtypes showed high p38 and mTOR pathway activation. AD subtypes associated with low differentiation showed relatively worse prognosis. SQCC subtypes and two of the AD subtypes expressed cancer testis antigen genes, whereas three AD subtypes expressed several immune checkpoint genes including PDL1 and PDL2, corresponding with patterns of greater immune cell infiltration. Subtype associations for several immune-related markers-including PD1, PDL1, CD3 and CD8-were confirmed in the PROSPECT cohort using immunohistochemistry. NSCLC molecular subtypes have therapeutic implications and lend support to a personalized approach to NSCLC management based on molecular characterization.
ES - 1476-5594
IL - 0950-9232
DI - onc2016303
DO - https://dx.doi.org/10.1038/onc.2016.303
PT - Journal Article
ID - onc2016303 [pii]
ID - 10.1038/onc.2016.303 [doi]
ID - PMC5344748 [pmc]
ID - NIHMS804251 [mid]
PP - ppublish
PH - 2016/05/23 [received]
PH - 2016/07/12 [revised]
PH - 2016/07/15 [accepted]
GI - No: P30 CA016672
Organization: (CA) *NCI NIH HHS*
Country: United States
No: U24 CA210950
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA125123
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA070907
Organization: (CA) *NCI NIH HHS*
Country: United States
No: U24 CA210949
Organization: (CA) *NCI NIH HHS*
Country: United States
No: U24 CA143883
Organization: (CA) *NCI NIH HHS*
Country: United States
No: U24 CA199461
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20161024
DP - 2017 Mar
DC - 20161024
EZ - 2016/10/25 06:00
DA - 2016/10/25 06:00
DT - 2016/10/25 06:00
YR - 2017
RD - 20170717
UP - 20170717
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27775076
<378. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27398650
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Kwok G
AU - Yau TC
AU - Chiu JW
AU - Tse E
AU - Kwong YL
FA - Kwok, Gerry
FA - Yau, Thomas C C
FA - Chiu, Joanne W
FA - Tse, Eric
FA - Kwong, Yok-Lam
IN - Kwok, Gerry. a Department of Medicine , Queen Mary Hospital , Hong Kong.
IN - Yau, Thomas C C. a Department of Medicine , Queen Mary Hospital , Hong Kong.
IN - Chiu, Joanne W. a Department of Medicine , Queen Mary Hospital , Hong Kong.
IN - Tse, Eric. a Department of Medicine , Queen Mary Hospital , Hong Kong.
IN - Kwong, Yok-Lam. a Department of Medicine , Queen Mary Hospital , Hong Kong.
TI - Pembrolizumab (Keytruda).
SO - Human vaccines & Immunotherapeutics. 12(11):2777-2789, 2016 Nov
AS - Hum Vaccin Immunother. 12(11):2777-2789, 2016 Nov
NJ - Human vaccines & immunotherapeutics
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101572652
IO - Hum Vaccin Immunother
CP - United States
KW - PD1; PDL1; PDL2; lymphoma; melanoma; non-small cell lung cancer; pembrolizumab; solid tumors
AB - The programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. PD1 expression is an important mechanism contributing to the exhausted effector T-cell phenotype. The expression of PD1 on effector T-cells and PDL1 on neoplastic cells enables tumor cells to evade anti-tumor immunity. Blockade of PD1 is an important immunotherapeutic strategy for cancers. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD1 antibody that has been extensively investigated in numerous malignancies. In melanoma refractory to targeted therapy, pembrolizumab induced overall response rates (ORRs) of 21-34%. It was superior to another immune checkpoint inhibitor ipilimumab (Yervoy) in stage III/IV unresectable melanoma. In refractory non-small cell lung cancer (NSCLC), pembrolizumab induced ORRs of 19-25%. Based on these results, pembrolizumab was approved by the USA FDA for the treatment of advanced melanoma and NSCLC. Tumor cell PDL1 expression may be a valid response predictor. Molecular analysis also showed that tumors with high gene mutation burdens, which might result in the formation of more tumor-related neo-antigens, had better responses to pembrolizumab. In malignancies including lymphomas and other solid tumors, preliminary data showed that ORRs of around 20-50 % could be achieved. Adverse events occurred in up to 60% of patients, but grade 3/4 toxicities were observed in <10% of cases. Immune-related adverse events including thyroid dysfunction, hepatitis and pneumonitis are more serious and may lead to cessation of treatment.
ES - 2164-554X
IL - 2164-5515
DO - https://dx.doi.org/10.1080/21645515.2016.1199310
PT - Journal Article
ID - 10.1080/21645515.2016.1199310 [doi]
ID - PMC5137544 [pmc]
PP - ppublish
LG - English
EP - 20160711
DP - 2016 Nov
DC - 20160711
EZ - 2016/07/12 06:00
DA - 2016/07/12 06:00
DT - 2016/07/12 06:00
YR - 2016
RD - 20170717
UP - 20170717
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27398650
<379. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27306911
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Gonzalez-Rodriguez E
AU - Rodriguez-Abreu D
AU - Spanish Group for Cancer Immuno-Biotherapy (GETICA)
FA - Gonzalez-Rodriguez, Elisa
FA - Rodriguez-Abreu, Delvys
FA - Spanish Group for Cancer Immuno-Biotherapy (GETICA)
IN - Gonzalez-Rodriguez, Elisa. Section of Endocrinology and Nutrition, Hospital Universitario de Gran Canaria Doctor Negrin, Las Palmas de Gran Canaria, Spain elisaglezrguez@gmail.com.
IN - Rodriguez-Abreu, Delvys. Section of Medical Oncology, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain.
TI - Immune Checkpoint Inhibitors: Review and Management of Endocrine Adverse Events. [Review]
SO - Oncologist. 21(7):804-16, 2016 Jul
AS - Oncologist. 21(7):804-16, 2016 Jul
NJ - The oncologist
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dd5, 9607837
IO - Oncologist
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4943391
SB - Index Medicus
CP - United States
KW - Autoimmune hypophysitis; Cytotoxic T-lymphocyte antigen 4; Monoclonal antibodies; Programmed cell death 1 receptor; Thyroiditis
AB - UNLABELLED: : In recent years, immune checkpoint inhibitors have emerged as effective therapies for advanced neoplasias. As new checkpoint target blockers become available and additional tumor locations tested, their use is expected to increase within a short time. Immune-related adverse events (irAEs) affecting the endocrine system are among the most frequent and complex toxicities. Some may be life-threatening if not recognized; hence, appropriate guidance for oncologists is needed. Despite their high incidence, endocrine irAEs have not been fully described for all immunotherapy agents available. This article is a narrative review of endocrinopathies associated with cytotoxic T lymphocyte-associated antigen-4, blockade of programmed death receptor 1 and its ligand inhibitors, and their combination. Thyroid dysfunction is the most frequent irAE reported, and hypophysitis is characteristic of ipilimumab. Incidence, timing patterns, and clinical presentation are discussed, and practical recommendations for clinical management are suggested. Heterogeneous terminology and lack of appropriate resolution criteria in clinical trials make adequate evaluation of endocrine AEs difficult. It is necessary to standardize definitions to contrast incidences and characterize toxicity patterns. To provide optimal care, a multidisciplinary team that includes endocrinology specialists is recommended.
AB - IMPLICATIONS FOR PRACTICE: Immune checkpoint inhibitors are already part of oncologists' therapeutic arsenal as effective therapies for otherwise untreatable neoplasias, such as metastatic melanoma or lung cancer. Their use is expected to increase exponentially in the near future as additional agents become available and their approval is extended to different tumor types. Adverse events affecting the endocrine system are among the most frequent and complex toxicities oncologists may face, and some may be life-threatening if not recognized. This study reviews endocrinopathies associated to immune checkpoint inhibitors available to date. Incidence, timing patterns, and clinical presentation are discussed, and practical recommendations for management are proposed.
Copyright ©AlphaMed Press.
ES - 1549-490X
IL - 1083-7159
DI - theoncologist.2015-0509
DO - https://dx.doi.org/10.1634/theoncologist.2015-0509
PT - Journal Article
PT - Review
ID - theoncologist.2015-0509 [pii]
ID - 10.1634/theoncologist.2015-0509 [doi]
ID - PMC4943391 [pmc]
PP - ppublish
PH - 2015/12/12 [received]
PH - 2016/02/19 [accepted]
LG - English
EP - 20160615
DP - 2016 Jul
DC - 20160714
EZ - 2016/06/17 06:00
DA - 2016/06/17 06:00
DT - 2016/06/17 06:00
YR - 2016
RD - 20170717
UP - 20170717
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27306911
<380. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28682883
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Chen YH
AU - Liu FC
AU - Hsu CH
AU - Chian CF
FA - Chen, Yu-Hsiu
FA - Liu, Feng-Cheng
FA - Hsu, Chang-Hung
FA - Chian, Chih-Feng
IN - Chen, Yu-Hsiu. aDivision of Rheumatology/Immunology/Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center bDepartment of Neurology, Tri-Service General Hospital, National Defense Medical Center cDivision of Pulmonary Medicine, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
TI - Nivolumab-induced myasthenia gravis in a patient with squamous cell lung carcinoma: Case report.
SO - Medicine. 96(27):e7350, 2017 Jul
AS - Medicine (Baltimore). 96(27):e7350, 2017 Jul
NJ - Medicine
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - mny, 2985248r
IO - Medicine (Baltimore)
CP - United States
AB - RATIONALE: Nivolumab (Nivo) is an immune checkpoint inhibitor that has been used to treat advanced melanoma, nonsmall cell lung carcinoma, and renal cell carcinoma since 2015. Nivo is associated with several side effects, including hepatitis, pneumonitis, acute renal failure, endocrine disorder, and other immune-related adverse events. Here, we describe the case of a 65-year-old man with squamous cell lung carcinoma who developed myasthenia gravis (MG) after a third Nivo infusion.
AB - PATIENT CONCERNS: A 65-year-old man with advanced squamous cell lung carcinoma developed ptosis, diplopia, drop head, and general weakness 5 days after a third Nivo infusion.
AB - DIAGNOSES, INTERVENTIONS, AND OUTCOMES: We diagnosed him with Nivo-related MG and myositis based on clinical symptoms, elevation of muscle enzymes, negativity for autoantibodies and exclusion of other diagnoses. Steroid treatment with methylprednisolone 1 mg/kg/d and pyridostigmine 60 mg twice a day was administered beginning at admission; however, the patient's condition progressively worsened, despite treatment. Respiratory failure developed 2 weeks after admission, and his family declined the use of a mechanical ventilator. The patient died on day 27 after the third Nivo infusion.
AB - LESSONS: Nivo-related MG should be highly suspected in patients who develop ptosis, diplopia, and general weakness. The corresponding treatments include discontinuation of Nivo and steroid treatment with plasmapheresis. The disease course may be rapid and fatal. This report stresses the importance of awareness of this rare and lethal adverse effect while using nivolomab immunotherapy.
ES - 1536-5964
IL - 0025-7974
DI - 00005792-201707070-00025
DO - https://dx.doi.org/10.1097/MD.0000000000007350
PT - Journal Article
ID - 10.1097/MD.0000000000007350 [doi]
ID - 00005792-201707070-00025 [pii]
PP - ppublish
LG - English
DP - 2017 Jul
DC - 20170706
EZ - 2017/07/07 06:00
DA - 2017/07/07 06:00
DT - 2017/07/07 06:00
YR - 2017
RD - 20170706
UP - 20170707
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28682883
<381. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28537531
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Yamauchi I
AU - Sakane Y
AU - Fukuda Y
AU - Fujii T
AU - Taura D
AU - Hirata M
AU - Hirota K
AU - Ueda Y
AU - Kanai Y
AU - Yamashita Y
AU - Kondo E
AU - Sone M
AU - Yasoda A
AU - Inagaki N
FA - Yamauchi, Ichiro
FA - Sakane, Yoriko
FA - Fukuda, Yorihide
FA - Fujii, Toshihito
FA - Taura, Daisuke
FA - Hirata, Masakazu
FA - Hirota, Keisho
FA - Ueda, Yohei
FA - Kanai, Yugo
FA - Yamashita, Yui
FA - Kondo, Eri
FA - Sone, Masakatsu
FA - Yasoda, Akihiro
FA - Inagaki, Nobuya
IN - Yamauchi, Ichiro. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
IN - Sakane, Yoriko. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
IN - Sakane, Yoriko. 2 Preemptive Medicine and Lifestyle Disease Research Center, Kyoto University Hospital , Kyoto, Japan .
IN - Fukuda, Yorihide. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
IN - Fujii, Toshihito. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
IN - Taura, Daisuke. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
IN - Hirata, Masakazu. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
IN - Hirota, Keisho. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
IN - Ueda, Yohei. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
IN - Kanai, Yugo. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
IN - Yamashita, Yui. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
IN - Kondo, Eri. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
IN - Sone, Masakatsu. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
IN - Yasoda, Akihiro. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
IN - Inagaki, Nobuya. 1 Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine , Kyoto, Japan .
TI - Clinical Features of Nivolumab-Induced Thyroiditis: A Case Series Study.
SO - Thyroid. 27(7):894-901, 2017 Jul
AS - Thyroid. 27(7):894-901, 2017 Jul
NJ - Thyroid : official journal of the American Thyroid Association
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - bjw, 9104317
IO - Thyroid
CP - United States
KW - PD-1; immune checkpoint inhibitor; nivolumab; painless thyroiditis; thyrotoxicosis
AB - BACKGROUND: The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. It consists of the PD-1 receptor and its two ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Nivolumab is an anti-PD-1 monoclonal antibody approved for malignant melanoma, advanced non-small cell lung cancer, and advanced renal cell carcinoma in Japan. Thyrotoxicosis and hypothyroidism have both been reported in international Phase 3 studies and national post-marketing surveillance of nivolumab in Japan.
AB - METHODS: This study analyzed five consecutive cases with thyroid dysfunction associated with nivolumab therapy. Second, it examined the mRNA and protein expressions of PD-L1 and PD-L2 by reverse transcription polymerase chain reaction and Western blotting.
AB - RESULTS: All patients were diagnosed with painless thyroiditis. Thyrotoxicosis developed within four weeks from the first administration of nivolumab and normalized within four weeks of onset in three of the five patients. Hypothyroidism after transient thyrotoxicosis developed in two patients, and preexisting hypothyroidism persisted in one patient. The other two patients were treated with glucocorticoids and discontinued nivolumab therapy for comorbid adverse events. One did not develop hypothyroidism, and the other developed mild, transient hypothyroidism. In addition, it was verified that normal thyroid tissue expresses PD-L1 and PD-L2 mRNA and those proteins.
AB - CONCLUSIONS: In the present cases, nivolumab-induced thyrotoxicosis seemed to be associated with painless thyroiditis, while no patient with Graves' disease was observed. A transient and rapid course with subsequent hypothyroidism was observed in nivolumab-induced thyroiditis. In addition, it was verified that PD-L1 and PD-L2 are expressed in normal thyroid tissue. This suggests that nivolumab therapy reduces immune tolerance, even in normal thyroid tissue, and leads to the development of thyroiditis. Treating thyrotoxicosis with only supportive care and considering levothyroxine replacement therapy once subsequent hypothyroidism occurs is proposed. Further investigations are required to confirm whether glucocorticoid therapy and discontinuation of nivolumab therapy prevent subsequent hypothyroidism.
ES - 1557-9077
IL - 1050-7256
DO - https://dx.doi.org/10.1089/thy.2016.0562
PT - Journal Article
ID - 10.1089/thy.2016.0562 [doi]
PP - ppublish
LG - English
EP - 20170621
DP - 2017 Jul
DC - 20170524
EZ - 2017/05/25 06:00
DA - 2017/05/26 06:00
DT - 2017/05/26 06:00
YR - 2017
RD - 20170706
UP - 20170707
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28537531
<382. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28043983
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Telo GH
AU - Carvalhal GF
AU - Cauduro CGS
AU - Webber VS
AU - Barrios CH
AU - Fay AP
FA - Telo, G H
FA - Carvalhal, G F
FA - Cauduro, C G S
FA - Webber, V S
FA - Barrios, C H
FA - Fay, A P
IN - Telo, G H. Endocrinology Department, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre.
IN - Carvalhal, G F. School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90619-900, Brazil.
IN - Cauduro, C G S. School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90619-900, Brazil.
IN - Webber, V S. Clinical Research Center, PUCRS, Porto Alegre, Brazil.
IN - Barrios, C H. School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90619-900, Brazil.
IN - Barrios, C H. Clinical Research Center, PUCRS, Porto Alegre, Brazil.
IN - Barrios, C H. Medical Oncology, Hospital do Cancer Mae de Deus, Porto Alegre, Brazil.
IN - Barrios, C H. Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil.
IN - Fay, A P. School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90619-900, Brazil.
IN - Fay, A P. Clinical Research Center, PUCRS, Porto Alegre, Brazil.
IN - Fay, A P. Medical Oncology, Hospital do Cancer Mae de Deus, Porto Alegre, Brazil.
IN - Fay, A P. Latin American Cooperative Oncology Group (LACOG), Porto Alegre, Brazil.
TI - Fulminant type 1 diabetes caused by dual immune checkpoint blockade in metastatic renal cell carcinoma.
SO - Annals of Oncology. 28(1):191-192, 2017 01 01
AS - Ann Oncol. 28(1):191-192, 2017 01 01
NJ - Annals of oncology : official journal of the European Society for Medical Oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - ayf, 9007735
IO - Ann. Oncol.
CP - England
ES - 1569-8041
IL - 0923-7534
DI - mdw447
DO - https://dx.doi.org/10.1093/annonc/mdw447
PT - Journal Article
ID - mdw447 [pii]
ID - 10.1093/annonc/mdw447 [doi]
PP - ppublish
LG - English
DP - 2017 01 01
DC - 20170103
EZ - 2017/01/04 06:00
DA - 2017/01/04 06:00
DT - 2017/01/04 06:00
YR - 2017
RD - 20170704
UP - 20170705
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28043983
<383. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27998967
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Osorio JC
AU - Ni A
AU - Chaft JE
AU - Pollina R
AU - Kasler MK
AU - Stephens D
AU - Rodriguez C
AU - Cambridge L
AU - Rizvi H
AU - Wolchok JD
AU - Merghoub T
AU - Rudin CM
AU - Fish S
AU - Hellmann MD
FA - Osorio, J C
FA - Ni, A
FA - Chaft, J E
FA - Pollina, R
FA - Kasler, M K
FA - Stephens, D
FA - Rodriguez, C
FA - Cambridge, L
FA - Rizvi, H
FA - Wolchok, J D
FA - Merghoub, T
FA - Rudin, C M
FA - Fish, S
FA - Hellmann, M D
IN - Osorio, J C. Department of Medicine, Weill Cornell Medical College, New York.
IN - Ni, A. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 485 Lexington Ave., New York, NY 10017, USA.
IN - Chaft, J E. Department of Medicine, Weill Cornell Medical College, New York.
IN - Chaft, J E. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
IN - Pollina, R. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
IN - Kasler, M K. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
IN - Stephens, D. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
IN - Rodriguez, C. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
IN - Cambridge, L. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
IN - Rizvi, H. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
IN - Wolchok, J D. Department of Medicine, Weill Cornell Medical College, New York.
IN - Wolchok, J D. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
IN - Wolchok, J D. Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering, New York.
IN - Wolchok, J D. Ludwig Institute for Cancer Research, New York, USA.
IN - Merghoub, T. Department of Medicine, Weill Cornell Medical College, New York.
IN - Merghoub, T. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
IN - Merghoub, T. Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering, New York.
IN - Merghoub, T. Ludwig Institute for Cancer Research, New York, USA.
IN - Rudin, C M. Department of Medicine, Weill Cornell Medical College, New York.
IN - Rudin, C M. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
IN - Fish, S. Department of Medicine, Weill Cornell Medical College, New York.
IN - Fish, S. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
IN - Hellmann, M D. Department of Medicine, Weill Cornell Medical College, New York.
IN - Hellmann, M D. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
IN - Hellmann, M D. Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering, New York.
TI - Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer.
SO - Annals of Oncology. 28(3):583-589, 2017 03 01
AS - Ann Oncol. 28(3):583-589, 2017 03 01
NJ - Annals of oncology : official journal of the European Society for Medical Oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - ayf, 9007735
IO - Ann. Oncol.
CP - England
KW - *PD-1; *hypothyroidism; *non-small cell lung cancer; *pembrolizumab; *thyroid dysfunction
AB - Background: Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described.
AB - Patient and methods: Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n=51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and anti-thyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated.
AB - Results: Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 [21%, 95% confidence interval (CI) 10% to 35%] patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%, P<0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09-0.94; P=0.04).
AB - Conclusions: Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.
ES - 1569-8041
IL - 0923-7534
DI - mdw640
DO - https://dx.doi.org/10.1093/annonc/mdw640
PT - Journal Article
ID - mdw640 [pii]
ID - 10.1093/annonc/mdw640 [doi]
PP - ppublish
LG - English
DP - 2017 03 01
DC - 20161221
EZ - 2016/12/22 06:00
DA - 2016/12/22 06:00
DT - 2016/12/22 06:00
YR - 2017
RD - 20170704
UP - 20170705
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27998967
<384. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28554108
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Peng TR
AU - Tsai FP
AU - Wu TW
FA - Peng, Tzu-Rong
FA - Tsai, Fang-Pei
FA - Wu, Ta-Wei
IN - Peng, Tzu-Rong. Department of Pharmacy, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
IN - Tsai, Fang-Pei. Department of Pharmacy, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
IN - Wu, Ta-Wei. Department of Pharmacy, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei City, Taiwan. Electronic address: tawei@tzuchi.com.tw.
TI - Indirect comparison between pembrolizumab and nivolumab for the treatment of non-small cell lung cancer: A meta-analysis of randomized clinical trials.
SO - International Immunopharmacology. 49:85-94, 2017 Aug
AS - Int Immunopharmacol. 49:85-94, 2017 Aug
NJ - International immunopharmacology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - d17, 100965259
IO - Int. Immunopharmacol.
CP - Netherlands
KW - Adverse effects; Nivolumab; Non-small cell lung cancer; Pembrolizumab; Pneumonitis
AB - OBJECTIVE: The purpose of this study is to evaluate the efficacy and adverse effects of nivolumab and pembrolizumab for the treatment of advanced non-small-cell lung cancer (NSCLC) by meta-analysis.
AB - MATERIALS AND METHODS: This meta-analysis of randomized controlled trials (RCTs) was performed after searching PubMed, EMBASE, and American Society of Clinical Oncology meeting abstracts, clinicaltrial gov, and Cochrane library databases. Two reviewers independently assessed the quality of the trials. Outcomes analysis was overall response rates (ORR), overall survival (OS), progression- free survival (PFS) and major adverse effects with odds ratio (OR) or hazard ratio (HR) and 95% confidence intervals (CI).
AB - RESULTS: Results reported from three RCTs involving 1,887 patients are included in this analysis. Indirect comparison between pembrolizumab and nivolumab in advanced NSCLC shows no statistically significant difference in ORR (OR: 1.14, 95% CI, 0.60-2.01), OS (HR: 0.98, 95% CI, 0.35-2.74) and PFS (HR: 1.12, 95% CI, 0.70-1.77). The incidence of grades>=3 adverse effects is higher with pembrolizumab as compared with nivolumab (OR: 3.44, 95% CI, 1.87-6.32). There are no significant statistical differences between severe adverse effects, such as pneumonitis and hypothyroidism, of the two drugs.
AB - CONCLUSIONS: This study has demonstrated that pembrolizumab and nivolumab have similar survival outcomes in patients with advanced NSCLC, but pembrolizumab has a higher incidence of grades>=3 adverse effects than nivolumab.
Copyright © 2017 Elsevier B.V. All rights reserved.
ES - 1878-1705
IL - 1567-5769
DI - S1567-5769(17)30191-1
DO - https://dx.doi.org/10.1016/j.intimp.2017.05.019
PT - Journal Article
ID - S1567-5769(17)30191-1 [pii]
ID - 10.1016/j.intimp.2017.05.019 [doi]
PP - ppublish
PH - 2017/03/17 [received]
PH - 2017/05/11 [revised]
PH - 2017/05/17 [accepted]
LG - English
EP - 20170527
DP - 2017 Aug
DC - 20170529
EZ - 2017/05/30 06:00
DA - 2017/05/30 06:00
DT - 2017/05/30 06:00
YR - 2017
RD - 20170630
UP - 20170630
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28554108
<385. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28653941
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - van Kooten MJ
AU - van den Berg G
AU - Glaudemans AWJM
AU - Hiltermann TJN
AU - Groen HJM
AU - Rutgers A
AU - Links TP
FA - van Kooten, M J
FA - van den Berg, G
FA - Glaudemans, A W J M
FA - Hiltermann, T J N
FA - Groen, H J M
FA - Rutgers, A
FA - Links, T P
IN - van Kooten, M J. Department of Endocrinology, University of Groningen, University Medical CenterGroningen, Groningen, the Netherlands.
TI - Transient thyrotoxicosis during nivolumab treatment.
SO - Netherlands Journal of Medicine. 75(5):204-207, 2017 Jun
AS - Neth J Med. 75(5):204-207, 2017 Jun
NJ - The Netherlands journal of medicine
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - nwy, 0356133
IO - Neth J Med
CP - Netherlands
AB - Two patients presented with transient thyrotoxicosis within 2-4 weeks after starting treatment with nivolumab. This thyrotoxicosis turned into hypothyroidism within 6-8 weeks. Temporary treatment with a beta blocker may be sufficient.
ES - 1872-9061
IL - 0300-2977
PT - Journal Article
PP - ppublish
LG - English
DP - 2017 Jun
DC - 20170627
EZ - 2017/06/28 06:00
DA - 2017/06/28 06:00
DT - 2017/06/28 06:00
YR - 2017
RD - 20170627
UP - 20170628
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28653941
<386. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28489679
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Yildirim S
AU - Deniz K
AU - Dogan E
AU - Baskol M
AU - Gursoy S
AU - Ozkan M
FA - Yildirim, Sumeyra
FA - Deniz, Kemal
FA - Dogan, Ender
FA - Baskol, Mevlut
FA - Gursoy, Sebnem
FA - Ozkan, Metin
IN - Yildirim, Sumeyra. Departments of aGastroenterology bPathology cOncology, Erciyes University, Kayseri, Turkey.
TI - Ipilimumab-associated cholestatic hepatitis: a case report and literature review.
SO - Melanoma Research. 27(4):380-382, 2017 Aug
AS - Melanoma Res. 27(4):380-382, 2017 Aug
NJ - Melanoma research
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - bjr, 9109623
IO - Melanoma Res.
CP - England
AB - Ipilimumab is a monoclonal antibody that exerts its effects by inhibiting the cytotoxic T-lymphocyte-associated protein 4 receptor on cytotoxic T lymphocytes. It is frequently used for the treatment of unresectable or metastatic melanoma. Ipilimumab may lead to several immune-related disease including colitis, thyroiditis, pneumonia, hepatitis, or pancreatitis as a side effect. Limited number of cases with hepatic damage as an ipilimumab-related adverse event has been reported in the literature. This agent has been implicated in causing acute hepatitis-like liver injury. Here, we presented a case in which cholestatic hepatitis developed during ipilimumab use for the treatment of metastatic melanoma.
ES - 1473-5636
IL - 0960-8931
DO - https://dx.doi.org/10.1097/CMR.0000000000000366
PT - Journal Article
ID - 10.1097/CMR.0000000000000366 [doi]
PP - ppublish
LG - English
DP - 2017 Aug
DC - 20170510
EZ - 2017/05/11 06:00
DA - 2017/05/11 06:00
DT - 2017/05/11 06:00
YR - 2017
RD - 20170627
UP - 20170628
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28489679
<387. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28434648
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - El-Khoueiry AB
AU - Sangro B
AU - Yau T
AU - Crocenzi TS
AU - Kudo M
AU - Hsu C
AU - Kim TY
AU - Choo SP
AU - Trojan J
AU - Welling TH Rd
AU - Meyer T
AU - Kang YK
AU - Yeo W
AU - Chopra A
AU - Anderson J
AU - Dela Cruz C
AU - Lang L
AU - Neely J
AU - Tang H
AU - Dastani HB
AU - Melero I
FA - El-Khoueiry, Anthony B
FA - Sangro, Bruno
FA - Yau, Thomas
FA - Crocenzi, Todd S
FA - Kudo, Masatoshi
FA - Hsu, Chiun
FA - Kim, Tae-You
FA - Choo, Su-Pin
FA - Trojan, Jorg
FA - Welling, Theodore H Rd
FA - Meyer, Tim
FA - Kang, Yoon-Koo
FA - Yeo, Winnie
FA - Chopra, Akhil
FA - Anderson, Jeffrey
FA - Dela Cruz, Christine
FA - Lang, Lixin
FA - Neely, Jaclyn
FA - Tang, Hao
FA - Dastani, Homa B
FA - Melero, Ignacio
IN - El-Khoueiry, Anthony B. USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA. Electronic address: elkhouei@med.usc.edu.
IN - Sangro, Bruno. Clinica Universidad de Navarra and CIBEREHD, Pamplona, Spain.
IN - Yau, Thomas. University of Hong Kong, Hong Kong Special Administrative Region, China.
IN - Crocenzi, Todd S. Providence Cancer Center, Portland, OR, USA.
IN - Kudo, Masatoshi. Kindai University Faculty of Medicine, Osaka, Japan.
IN - Hsu, Chiun. National Taiwan University Hospital, Taipei, Taiwan.
IN - Kim, Tae-You. Seoul National University Hospital, Seoul, South Korea.
IN - Choo, Su-Pin. National Cancer Center, Singapore.
IN - Trojan, Jorg. Goethe University Hospital and Cancer Center, Frankfurt, Germany.
IN - Welling, Theodore H Rd. University of Michigan School of Medicine, Ann Arbor, MI, USA.
IN - Meyer, Tim. Royal Free Hospital, London, UK.
IN - Kang, Yoon-Koo. Asan Medical Center, University of Ulsan, Seoul, South Korea.
IN - Yeo, Winnie. Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
IN - Chopra, Akhil. Johns Hopkins Singapore International Medical Centre, Singapore.
IN - Anderson, Jeffrey. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Dela Cruz, Christine. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Lang, Lixin. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Neely, Jaclyn. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Tang, Hao. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Dastani, Homa B. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Melero, Ignacio. Biomedical Research Network in Oncology (CIBERONC), Pamplona, Spain; Center for Applied Medical Research (CIMA), Pamplona, Spain.
TI - Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial.
SO - Lancet. 389(10088):2492-2502, 2017 Jun 24
AS - Lancet. 389(10088):2492-2502, 2017 Jun 24
NJ - Lancet (London, England)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 2985213r, l0s, 0053266
IO - Lancet
CP - England
AB - BACKGROUND: For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis.
AB - METHODS: We did a phase 1/2, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (>=18 years) with histologically confirmed advanced hepatocellular carcinoma with or without hepatitis C or B (HCV or HBV) infection. Previous sorafenib treatment was allowed. A dose-escalation phase was conducted at seven hospitals or academic centres in four countries or territories (USA, Spain, Hong Kong, and Singapore) and a dose-expansion phase was conducted at an additional 39 sites in 11 countries (Canada, UK, Germany, Italy, Japan, South Korea, Taiwan). At screening, eligible patients had Child-Pugh scores of 7 or less (Child-Pugh A or B7) for the dose-escalation phase and 6 or less (Child-Pugh A) for the dose-expansion phase, and an Eastern Cooperative Oncology Group performance status of 1 or less. Patients with HBV infection had to be receiving effective antiviral therapy (viral load <100 IU/mL); antiviral therapy was not required for patients with HCV infection. We excluded patients previously treated with an agent targeting T-cell costimulation or checkpoint pathways. Patients received intravenous nivolumab 0.1-10 mg/kg every 2 weeks in the dose-escalation phase (3+3 design). Nivolumab 3 mg/kg was given every 2 weeks in the dose-expansion phase to patients in four cohorts: sorafenib untreated or intolerant without viral hepatitis, sorafenib progressor without viral hepatitis, HCV infected, and HBV infected. Primary endpoints were safety and tolerability for the escalation phase and objective response rate (Response Evaluation Criteria In Solid Tumors version 1.1) for the expansion phase. This study is registered with ClinicalTrials.gov, number NCT01658878.
AB - FINDINGS: Between Nov 26, 2012, and Aug 8, 2016, 262 eligible patients were treated (48 patients in the dose-escalation phase and 214 in the dose-expansion phase). 202 (77%) of 262 patients have completed treatment and follow-up is ongoing. During dose escalation, nivolumab showed a manageable safety profile, including acceptable tolerability. In this phase, 46 (96%) of 48 patients discontinued treatment, 42 (88%) due to disease progression. Incidence of treatment-related adverse events did not seem to be associated with dose and no maximum tolerated dose was reached. 12 (25%) of 48 patients had grade 3/4 treatment-related adverse events. Three (6%) patients had treatment-related serious adverse events (pemphigoid, adrenal insufficiency, liver disorder). 30 (63%) of 48 patients in the dose-escalation phase died (not determined to be related to nivolumab therapy). Nivolumab 3 mg/kg was chosen for dose expansion. The objective response rate was 20% (95% CI 15-26) in patients treated with nivolumab 3 mg/kg in the dose-expansion phase and 15% (95% CI 6-28) in the dose-escalation phase.
AB - INTERPRETATION: Nivolumab had a manageable safety profile and no new signals were observed in patients with advanced hepatocellular carcinoma. Durable objective responses show the potential of nivolumab for treatment of advanced hepatocellular carcinoma.
AB - FUNDING: Bristol-Myers Squibb.
Copyright © 2017 Elsevier Ltd. All rights reserved.
ES - 1474-547X
IL - 0140-6736
DI - S0140-6736(17)31046-2
DO - https://dx.doi.org/10.1016/S0140-6736(17)31046-2
PT - Journal Article
ID - S0140-6736(17)31046-2 [pii]
ID - 10.1016/S0140-6736(17)31046-2 [doi]
PP - ppublish
PH - 2016/11/23 [received]
PH - 2017/02/17 [revised]
PH - 2017/02/23 [accepted]
LG - English
EP - 20170420
DP - 2017 Jun 24
DC - 20170424
EZ - 2017/04/25 06:00
DA - 2017/04/25 06:00
DT - 2017/04/25 06:00
YR - 2017
RD - 20170628
UP - 20170628
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28434648
<388. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28419059
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Diamantopoulos PT
AU - Gaggadi M
AU - Kassi E
AU - Benopoulou O
AU - Anastasopoulou A
AU - Gogas H
FA - Diamantopoulos, Panagiotis T
FA - Gaggadi, Maria
FA - Kassi, Eva
FA - Benopoulou, Olga
FA - Anastasopoulou, Amalia
FA - Gogas, Helen
IN - Diamantopoulos, Panagiotis T. aFirst Department of Internal Medicine, National and Kapodistrian University of Athens bDepartment of Pneumology, Laikon General Hospital, Athens, Greece.
TI - Late-onset nivolumab-mediated pneumonitis in a patient with melanoma and multiple immune-related adverse events.
SO - Melanoma Research. 27(4):391-395, 2017 Aug
AS - Melanoma Res. 27(4):391-395, 2017 Aug
NJ - Melanoma research
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - bjr, 9109623
IO - Melanoma Res.
CP - England
AB - Immune-related adverse effects (AEs) of PD-1 inhibitors can affect almost every organ, but the skin, intestine, lung, eye, and liver are the most commonly affected organs. Here, we present the case of a 62-year-old female patient with stage IIIc melanoma treated with nivolumab in an adjuvant setting who sequentially developed hyperthyroidism, hypothyroidism, acute hepatitis, and pneumonitis. Six months before the emergence of pneumonitis, the patient had discontinued treatment with nivolumab because of acute hepatitis. Information on pneumonitis after nivolumab discontinuation in the literature is scarce, whereas most of the cases emerge during the first 2.5 months of treatment. Patients with multiple immune-related AEs comprise a group of special interest as the identification of factors affecting the susceptibility of patients to immune-related AEs of PD-1 inhibitors may lead to a more rational use of these drugs. Human leukocyte antigen haplotype and Fcgamma receptor polymorphisms are possible targets of the relevant research.
ES - 1473-5636
IL - 0960-8931
DO - https://dx.doi.org/10.1097/CMR.0000000000000355
PT - Journal Article
ID - 10.1097/CMR.0000000000000355 [doi]
PP - ppublish
LG - English
DP - 2017 Aug
DC - 20170418
EZ - 2017/04/19 06:00
DA - 2017/04/19 06:00
DT - 2017/04/19 06:00
YR - 2017
RD - 20170627
UP - 20170628
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28419059
<389. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28363614
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Win MA
AU - Thein KZ
AU - Qdaisat A
AU - Yeung SJ
FA - Win, Myint Aung
FA - Thein, Kyaw Zin
FA - Qdaisat, Aiham
FA - Yeung, Sai-Ching Jim
IN - Win, Myint Aung. Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
IN - Thein, Kyaw Zin. Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States; Department of Hematology Oncology, Texas Tech University Health Sciences Center, Lubbock, TX, United States.
IN - Qdaisat, Aiham. Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
IN - Yeung, Sai-Ching Jim. Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States; Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, United States. Electronic address: syeung@mdanderson.org.
TI - Acute symptomatic hypocalcemia from immune checkpoint therapy-induced hypoparathyroidism.
SO - American Journal of Emergency Medicine. 35(7):1039.e5-1039.e7, 2017 Jul
AS - Am J Emerg Med. 35(7):1039.e5-1039.e7, 2017 Jul
NJ - The American journal of emergency medicine
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - aa2, 8309942
IO - Am J Emerg Med
CP - United States
KW - Hypocalcemia; Hypoparathyroidism; Ipilimumab; Melanoma; Nivolumab; Thyroiditis
AB - BACKGROUND: Ipilimumab (a monoclonal antibody against CTLA-4) and nivolumab (a humanized antibody against PD-1) target these immune checkpoint pathways and are used for treatment of melanoma and an increasing number of other cancers. However, they may cause immune-related adverse effects (IRAEs). Although many endocrinopathies are known to be IRAEs, primary hypoparathyroidism with severe hypocalcemia has never been reported. This is the first case of hypoparathyroidism as an IRAE presenting to an Emergency Department with acute hypocalcemia.
AB - CASE DESCRIPTION: A 73-year-old man with metastatic melanoma presented to the Emergency Department for the chief complaints of imbalance, general muscle weakness, abdominal pain and tingling in extremities. He had wide spread metastasis, and begun immunotherapy with concurrent ipilimumab and nivolumab 1.5months ago. At presentation, he had ataxia, paresthesia in the hands and feet, and abdominal cramping. Magnetic resonance imaging of the brain was unremarkable. He was found to be hypocalcemic with undetectable plasma parathyroid hormone. He was admitted for treatment of symptomatic hypocalcemia and was diagnosed with primary hypoparathyroidism. Shortly afterwards, he had thyrotoxicosis manifesting as tachycardia and anxiety, followed by development of primary hypothyroidism. At 4months after the Emergency Department visit, his parathyroid function and thyroid function had not recovered, and required continued thyroid hormone replacement and calcium and vitamin D treatment for hypocalcemia.
AB - CONCLUSIONS: Primary hypoparathyroidism caused by ipilimumab and nivolumab may acute manifest with severe symptomatic hypocalcemia. Emergency care providers should be aware of hypoparathyroidism as a new IRAE in this new era of immuno-oncology.
Copyright © 2017 Elsevier Inc. All rights reserved.
ES - 1532-8171
IL - 0735-6757
DI - S0735-6757(17)30161-4
DO - https://dx.doi.org/10.1016/j.ajem.2017.02.048
PT - Journal Article
ID - S0735-6757(17)30161-4 [pii]
ID - 10.1016/j.ajem.2017.02.048 [doi]
PP - ppublish
PH - 2017/02/10 [received]
PH - 2017/02/25 [accepted]
LG - English
EP - 20170227
DP - 2017 Jul
DC - 20170401
EZ - 2017/04/02 06:00
DA - 2017/04/02 06:00
DT - 2017/04/02 06:00
YR - 2017
RD - 20170626
UP - 20170626
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28363614
<390. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28643173
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Lehman JM
AU - Gwin ME
AU - Massion PP
FA - Lehman, Jonathan M
FA - Gwin, Mary E
FA - Massion, Pierre P
IN - Lehman, Jonathan M. Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN, 37232, USA.
IN - Gwin, Mary E. Vanderbilt University, PMB 353746, 2301 Vanderbilt Place, Nashville, TN, 37235, USA.
IN - Massion, Pierre P. Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, 2220 Pierce Avenue, Preston Research Building, 640, Nashville, TN, USA. pierre.massion@vanderbilt.edu.
IN - Massion, Pierre P. Cancer Early Detection and Prevention Initiative, Vanderbilt-Ingram Cancer Center, 2220 Pierce Avenue, Nashville, TN, 37232, USA. pierre.massion@vanderbilt.edu.
IN - Massion, Pierre P. US Department of Veterans Affairs, Tennessee Valley Healthcare System, 1310 24th Avenue South, Nashville, TN, 37212, USA. pierre.massion@vanderbilt.edu.
TI - Immunotherapy and Targeted Therapy for Small Cell Lung Cancer: There Is Hope. [Review]
SO - Current Oncology Reports. 19(7):49, 2017 Jul
AS - Curr Oncol Rep. 19(7):49, 2017 Jul
NJ - Current oncology reports
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 100888967, dyp
IO - Curr Oncol Rep
CP - United States
KW - Antibody drug conjugates; BCL2; CTLA4; Immunotherapy; PARP inhibitor; PDL1; Peptide receptor radionuclide therapy; Small cell lung cancer
AB - Small cell lung cancer (SCLC) is a devastating and aggressive neuroendocrine carcinoma of the lung. It accounts for ~15% of lung cancer mortality and has had no improvement in standard treatment options for nearly 30 years. However, there is now hope for change with new therapies and modalities of therapy. Immunotherapies and checkpoint inhibitors are entering clinical practice, selected targeted therapies show promise, and "smart bomb"-based drug/radioconjugates have led to good response in early clinical trials. Additionally, new research insights into the genetics and tumor heterogeneity of SCLC alongside the availability of new tools such as patient-derived or circulating tumor cell xenografts offer the potential to shine light on this beshadowed cancer.
ES - 1534-6269
IL - 1523-3790
DI - 10.1007/s11912-017-0609-2
DO - https://dx.doi.org/10.1007/s11912-017-0609-2
PT - Journal Article
PT - Review
ID - 10.1007/s11912-017-0609-2 [doi]
ID - 10.1007/s11912-017-0609-2 [pii]
PP - ppublish
LG - English
DP - 2017 Jul
DC - 20170623
EZ - 2017/06/24 06:00
DA - 2017/06/24 06:00
DT - 2017/06/24 06:00
YR - 2017
RD - 20170623
UP - 20170626
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28643173
<391. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28550027
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Sharabi A
AU - Kim SS
AU - Kato S
AU - Sanders PD
AU - Patel SP
AU - Sanghvi P
AU - Weihe E
AU - Kurzrock R
FA - Sharabi, Andrew
FA - Kim, Sangwoo Shawn
FA - Kato, Shumei
FA - Sanders, Philip D
FA - Patel, Sandip Pravin
FA - Sanghvi, Parag
FA - Weihe, Elizabeth
FA - Kurzrock, Razelle
IN - Sharabi, Andrew. Department of Radiation Medicine and Applied Sciences, UC San Diego Moores Cancer Center, San Diego, California, USA sharabi@ucsd.edu.
IN - Kim, Sangwoo Shawn. School of Medicine, University of California San Diego, California, USA.
IN - Kato, Shumei. Division of Hematology & Oncology and Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, San Diego, California, USA.
IN - Sanders, Philip D. Department of Radiation Medicine and Applied Sciences, UC San Diego Moores Cancer Center, San Diego, California, USA.
IN - Patel, Sandip Pravin. Division of Hematology & Oncology and Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, San Diego, California, USA.
IN - Sanghvi, Parag. Department of Radiation Medicine and Applied Sciences, UC San Diego Moores Cancer Center, San Diego, California, USA.
IN - Weihe, Elizabeth. Department of Radiology, University of California San Diego, California, USA.
IN - Kurzrock, Razelle. Division of Hematology & Oncology and Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, San Diego, California, USA.
TI - Exceptional Response to Nivolumab and Stereotactic Body Radiation Therapy (SBRT) in Neuroendocrine Cervical Carcinoma with High Tumor Mutational Burden: Management Considerations from the Center For Personalized Cancer Therapy at UC San Diego Moores Cancer Center.
SO - Oncologist. 22(6):631-637, 2017 Jun
AS - Oncologist. 22(6):631-637, 2017 Jun
NJ - The oncologist
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dd5, 9607837
IO - Oncologist
CP - United States
AB - Neuroendocrine carcinoma of the cervix is an ultra-rare malignancy with a poor prognosis and limited treatment options. Checkpoint blockade immunotherapy has rapidly developed into an emerging standard of care for several common disease types. Interestingly, in preclinical and retrospective clinical data, radiation therapy has been demonstrated to synergize with checkpoint inhibitors. Here we report a patient with metastatic, chemotherapy-refractory neuroendocrine carcinoma who presented with partial bowel obstruction due to a large tumor burden. Genomic analysis demonstrated a high number of alterations on liquid biopsy (circulating tumor DNA [ctDNA]), which prompted treatment with stereotactic body radiation therapy (SBRT) combined with anti-programmed cell death protein 1 antibody. Tissue rebiopsy and comprehensive genomic profiling confirmed high tumor mutational burden and a mismatch repair gene defect. The patient manifested near-complete systemic resolution of disease, ongoing at 10+ months. We discuss the novel treatment modality of SBRT combined with a checkpoint inhibitor and the implications of molecular profiling and tumor mutational burden as potential predictors of response.
AB - KEY POINTS: High-grade, large-cell neuroendocrine carcinoma of the cervix is an ultra-rare malignancy that carries a grim prognosis.Next-generation sequencing may reveal key mutations in MSH2 genes amongst others. MSH2 mutations target the DNA mismatch repair process and can predispose patients to malignancies with high mutational burdens.Immunotherapy combined with radiation therapy can elicit a significant response, both within and outside the field of radiation. The latter is termed the "abscopal" effect, perhaps mediated by radiation-induced cross presentation of tumor antigens resulting in immune activation.Sequencing of blood-derived ctDNA showed a high number of alterations, and tissue sequencing confirmed a high tumor mutational burden as a consequence of a mismatch repair gene defect. This observation led to a therapeutic "match" with an anti- programmed cell death protein 1 antibody combined with SBRT, resulting in a durable (10+ months), near-complete remission in a patient with advanced chemotherapy-refractory disease.
AB - Copyright © AlphaMed Press 2017.
CI - Disclosures of potential conflicts of interest may be found at the end of this article.
ES - 1549-490X
IL - 1083-7159
DI - theoncologist.2016-0517
DO - https://dx.doi.org/10.1634/theoncologist.2016-0517
PT - Journal Article
ID - theoncologist.2016-0517 [pii]
ID - 10.1634/theoncologist.2016-0517 [doi]
ID - PMC5469598 [pmc]
PP - ppublish
PH - 2016/12/28 [received]
PH - 2017/03/20 [accepted]
PH - 2017/12/01 [pmc-release]
GI - No: P30 CA016672
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20170526
DP - 2017 Jun
DC - 20170527
EZ - 2017/05/28 06:00
DA - 2017/05/28 06:00
DT - 2017/05/28 06:00
YR - 2017
RD - 20170621
UP - 20170621
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28550027
<392. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28625622
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Tsuruoka K
AU - Horinouchi H
AU - Goto Y
AU - Kanda S
AU - Fujiwara Y
AU - Nokihara H
AU - Yamamoto N
AU - Asakura K
AU - Nakagawa K
AU - Sakurai H
AU - Watanabe SI
AU - Tsuta K
AU - Ohe Y
FA - Tsuruoka, Kenjiro
FA - Horinouchi, Hidehito
FA - Goto, Yasushi
FA - Kanda, Shintaro
FA - Fujiwara, Yutaka
FA - Nokihara, Hiroshi
FA - Yamamoto, Noboru
FA - Asakura, Keisuke
FA - Nakagawa, Kazuo
FA - Sakurai, Hiroyuki
FA - Watanabe, Shun-Ichi
FA - Tsuta, Koji
FA - Ohe, Yuichiro
IN - Tsuruoka, Kenjiro. Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
IN - Horinouchi, Hidehito. Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan. Electronic address: hhoriou@ncc.go.jp.
IN - Goto, Yasushi. Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
IN - Kanda, Shintaro. Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
IN - Fujiwara, Yutaka. Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
IN - Nokihara, Hiroshi. Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
IN - Yamamoto, Noboru. Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
IN - Asakura, Keisuke. Division of Thoracic Surgery, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
IN - Nakagawa, Kazuo. Division of Thoracic Surgery, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
IN - Sakurai, Hiroyuki. Division of Thoracic Surgery, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
IN - Watanabe, Shun-Ichi. Division of Thoracic Surgery, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
IN - Tsuta, Koji. Division of Pathology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan; Department of Pathology and Laboratory Medicine, Kansai Medical University, Shinmachi 2-3-1, Hirakata, Osaka 573-1191, Japan.
IN - Ohe, Yuichiro. Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
TI - PD-L1 expression in neuroendocrine tumors of the lung.
SO - Lung Cancer. 108:115-120, 2017 Jun
AS - Lung Cancer. 108:115-120, 2017 Jun
NJ - Lung cancer (Amsterdam, Netherlands)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - b3u, 8800805
IO - Lung Cancer
CP - Ireland
KW - Carcinoid; Clone E1L3N; Immunohistochemistry; LCNEC; Neuroendocrine; PD-1; PD-L1; Small cell lung cancer
AB - BACKGROUND: Various tumors express programmed cell death ligand 1 (PD-L1), an immune checkpoint ligand, the expression of which correlates with certain effects of anti-programmed cell death 1 (PD-1)/PD-L1 drugs. The aim of this study was to assess the frequency of PD-L1 expression in each of the types of neuroendocrine tumors of the lung.
AB - METHODS: The subjects enrolled in this study were patients who had been diagnosed with neuroendocrine tumors of the lung and had been treated at the National Cancer Center Hospital (Tokyo, Japan) between 1982 and 2010. We performed immunohistochemical analysis on a tissue microarray (TMA) of the surgical specimens using the validated PD-L1 antibody clone, E1L3N. Tumor PD-L1 expression scores were calculated semiquantitatively (staining intensity [0-3]xstained area [0-100%]). A score of 1 was used as a cut-off to determine the presence or absence of PD-L1 expression.
AB - RESULTS: Among the 227 patients included in this study, the patient demographics were as follows: median age (range), 65 years (19-84); sex (male/female), 168/59; pStage (IA, IB, IIA, IIB, IIIA, IIIB, IV): 79, 36, 25, 29, 47, 6, 5, respectively; and histology was typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), small cell lung cancer (SCLC): 46, 6, 106, 69, respectively. The numbers (proportions) of PD-L1-expression tumors were as follows: TC/AC/LCNEC/SCLC, 0/0/11 (10.4%)/4 (5.8%).
AB - CONCLUSIONS: PD-L1 expression was apparent in 10.4% of LCNEC and 5.8% of SCLC tumors, and was not observed in carcinoid tumors.
AB - Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
ES - 1872-8332
IL - 0169-5002
DI - S0169-5002(17)30260-X
DO - https://dx.doi.org/10.1016/j.lungcan.2017.03.006
PT - Journal Article
ID - S0169-5002(17)30260-X [pii]
ID - 10.1016/j.lungcan.2017.03.006 [doi]
PP - ppublish
PH - 2017/01/06 [received]
PH - 2017/03/11 [revised]
PH - 2017/03/14 [accepted]
LG - English
EP - 20170324
DP - 2017 Jun
DC - 20170619
EZ - 2017/06/20 06:00
DA - 2017/06/20 06:00
DT - 2017/06/20 06:00
YR - 2017
RD - 20170619
UP - 20170620
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28625622
<393. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28424325
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Ning YM
AU - Suzman D
AU - Maher VE
AU - Zhang L
AU - Tang S
AU - Ricks T
AU - Palmby T
AU - Fu W
AU - Liu Q
AU - Goldberg KB
AU - Kim G
AU - Pazdur R
FA - Ning, Yang-Min
FA - Suzman, Daniel
FA - Maher, V Ellen
FA - Zhang, Lijun
FA - Tang, Shenghui
FA - Ricks, Tiffany
FA - Palmby, Todd
FA - Fu, Wentao
FA - Liu, Qi
FA - Goldberg, Kirsten B
FA - Kim, Geoffrey
FA - Pazdur, Richard
IN - Ning, Yang-Min. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Springs, Maryland, USA ningy@cder.fda.gov.
IN - Suzman, Daniel. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Springs, Maryland, USA.
IN - Maher, V Ellen. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Springs, Maryland, USA.
IN - Zhang, Lijun. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Springs, Maryland, USA.
IN - Tang, Shenghui. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Springs, Maryland, USA.
IN - Ricks, Tiffany. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Springs, Maryland, USA.
IN - Palmby, Todd. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Springs, Maryland, USA.
IN - Fu, Wentao. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Springs, Maryland, USA.
IN - Liu, Qi. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Springs, Maryland, USA.
IN - Goldberg, Kirsten B. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Springs, Maryland, USA.
IN - Kim, Geoffrey. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Springs, Maryland, USA.
IN - Pazdur, Richard. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Springs, Maryland, USA.
TI - FDA Approval Summary: Atezolizumab for the Treatment of Patients with Progressive Advanced Urothelial Carcinoma after Platinum-Containing Chemotherapy.
SO - Oncologist. 22(6):743-749, 2017 Jun
AS - Oncologist. 22(6):743-749, 2017 Jun
NJ - The oncologist
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dd5, 9607837
IO - Oncologist
CP - United States
KW - Atezolizumab; Bladder cancer; Immunotherapy; Locally advanced or metastatic urothelial carcinoma; Platinum-containing chemotherapy
AB - Until recently in the United States, no products were approved for second-line treatment of advanced urothelial carcinoma. On May 18, 2016, the U.S. Food and Drug Administration approved atezolizumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Atezolizumab is a programmed death-ligand 1 (PD-L1) blocking antibody and represents the first approved product directed against PD-L1. This accelerated approval was based on results of a single-arm trial in 310 patients with locally advanced or metastatic urothelial carcinoma who had disease progression after prior platinum-containing chemotherapy. Patients received atezolizumab 1,200 mg intravenously every 3 weeks until disease progression or unacceptable toxicity. Key efficacy measures were objective response rate (ORR), as assessed by Independent Review per RECIST 1.1, and duration of response (DoR). With a median follow-up of 14.4 months, confirmed ORR was 14.8% (95% CI: 11.1, 19.3) in all treated patients. Median DoR was not reached and response durations ranged from 2.1+ to 13.8+ months. Of the 46 responders, 37 patients had an ongoing response for >=6 months. The most common adverse reactions (>=20%) were fatigue, decreased appetite, nausea, urinary tract infection, pyrexia, and constipation. Infection and immune-related adverse events also occurred, including pneumonitis, hepatitis, colitis, endocrine disorders, and rashes. Overall, the benefit-risk assessment was favorable to support accelerated approval. The observed clinical benefits need to be verified in confirmatory trial(s).
AB - IMPLICATIONS FOR PRACTICE: This accelerated approval of atezolizumab for second-line use in advanced urothelial carcinoma provides patients with an effective, novel treatment option for the management of their disease. This represents the first immunotherapy approved in this disease setting.
AB - Copyright Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
ES - 1549-490X
IL - 1083-7159
DI - theoncologist.2017-0087
DO - https://dx.doi.org/10.1634/theoncologist.2017-0087
PT - Journal Article
ID - theoncologist.2017-0087 [pii]
ID - 10.1634/theoncologist.2017-0087 [doi]
ID - PMC5469588 [pmc]
PP - ppublish
PH - 2017/02/14 [received]
PH - 2017/02/16 [accepted]
PH - 2018/06/01 [pmc-release]
LG - English
EP - 20170419
DP - 2017 Jun
DC - 20170420
EZ - 2017/04/21 06:00
DA - 2017/04/21 06:00
DT - 2017/04/21 06:00
YR - 2017
RD - 20170620
UP - 20170620
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28424325
<394. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28031819
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Lowe JR
AU - Perry DJ
AU - Salama AK
AU - Mathews CE
AU - Moss LG
AU - Hanks BA
FA - Lowe, Jared R
FA - Perry, Daniel J
FA - Salama, April K S
FA - Mathews, Clayton E
FA - Moss, Larry G
FA - Hanks, Brent A
IN - Lowe, Jared R. Department of Medicine, Duke University Medical Center, Durham, NC 27710 USA.
IN - Perry, Daniel J. Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610 USA.
IN - Salama, April K S. Department of Medicine, Division of Medical Oncology, Melanoma Program, Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710 USA.
IN - Mathews, Clayton E. Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610 USA.
IN - Moss, Larry G. Department of Medicine, Division of Endocrinology, Metabolism, & Nutrition, Duke University Medical Center, Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, Durham, NC 27701 USA.
IN - Hanks, Brent A. Department of Medicine, Division of Medical Oncology, Melanoma Program, Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710 USA.
TI - Genetic risk analysis of a patient with fulminant autoimmune type 1 diabetes mellitus secondary to combination ipilimumab and nivolumab immunotherapy.
SO - Journal for Immunotherapy of Cancer. 4:89, 2016
AS - J Immunother Cancer. 4:89, 2016
NJ - Journal for immunotherapy of cancer
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Internet
JC - 101620585
IO - J Immunother Cancer
CP - England
KW - Advanced melanoma; Autoimmune endocrinopathy; Genetic risk analysis; HLA risk allele; Ipilimumab; Nivolumab; Single nucleotide polymorphism; Type I diabetes
AB - BACKGROUND: Checkpoint inhibitor immunotherapy is becoming an effective treatment modality for an increasing number of malignancies. As a result, autoinflammatory side-effects are also being observed more commonly in the clinic. We are currently unable to predict which patients will develop more severe toxicities associated with these treatment regimens.
AB - CASE PRESENTATION: We present a patient with stage IV melanoma that developed rapid onset autoimmune type 1 diabetes (T1D) in response to combination ipilimumab and nivolumab immunotherapy. At the time of the patient's presentation with diabetes ketoacidosis, a confirmed anti-GAD antibody seroconversion was noted. Longer-term follow-up of this patient has demonstrated a durable complete response based on PET CT imaging along with a persistently undetectable C-peptide level. Single nucleotide polymorphism gene sequencing and HLA risk allele analysis has revealed the patient to lack any established genetic predisposition to the development of autoimmune T1D.
AB - CONCLUSIONS: While larger studies are necessary to better understand the role of genetic risk factors for the development of autoimmune toxicities in those patients undergoing checkpoint inhibitor immunotherapy, these results suggest that pre-screening patients for known T1D risk alleles may not be indicated. Additional investigation is needed to determine whether an approach such as T cell receptor clonotypic analysis to identify the presence of autoreactive T cell clones may be an effective approach for predicting which patients are at risk for the development of autoinflammatory toxicities while undergoing checkpoint inhibitor immunotherapy.
ES - 2051-1426
IL - 2051-1426
DI - 196
DO - https://dx.doi.org/10.1186/s40425-016-0196-z
PT - Journal Article
ID - 10.1186/s40425-016-0196-z [doi]
ID - 196 [pii]
ID - PMC5170902 [pmc]
PP - epublish
PH - 2016/08/15 [received]
PH - 2016/11/17 [accepted]
GI - No: K08 CA191063
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20161220
DP - 2016
DC - 20161229
EZ - 2016/12/30 06:00
DA - 2016/12/30 06:01
DT - 2016/12/30 06:00
YR - 2016
RD - 20170619
UP - 20170619
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28031819
<395. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28407743
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Kroschinsky F
AU - Stolzel F
AU - von Bonin S
AU - Beutel G
AU - Kochanek M
AU - Kiehl M
AU - Schellongowski P
AU - Intensive Care in Hematological and Oncological Patients (iCHOP) Collaborative Group
FA - Kroschinsky, Frank
FA - Stolzel, Friedrich
FA - von Bonin, Simone
FA - Beutel, Gernot
FA - Kochanek, Matthias
FA - Kiehl, Michael
FA - Schellongowski, Peter
FA - Intensive Care in Hematological and Oncological Patients (iCHOP) Collaborative Group
IN - Kroschinsky, Frank. Dresden University Hospital, Medical Department I, Fetscherstr. 74, 01307, Dresden, Germany. frank.kroschinsky@uniklinikum-dresden.de.
IN - Stolzel, Friedrich. Dresden University Hospital, Medical Department I, Fetscherstr. 74, 01307, Dresden, Germany.
IN - von Bonin, Simone. Dresden University Hospital, Medical Department I, Fetscherstr. 74, 01307, Dresden, Germany.
IN - Beutel, Gernot. Department for Hematology/Oncology/Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
IN - Kochanek, Matthias. Department I of Internal Medicine, University Hospital Koln, Koln, Germany.
IN - Kiehl, Michael. Medical Department I and Stem Cell Transplant Center, Hospital Frankfurt/Oder, Frankfurt/Oder, Germany.
IN - Schellongowski, Peter. General Hospital Department of Medicine I, Medical University of Vienna, Vienna, Austria.
TI - New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management. [Review]
SO - Critical Care (London, England). 21(1):89, 2017 04 14
AS - Crit Care. 21(1):89, 2017 04 14
NJ - Critical care (London, England)
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 9801902
IO - Crit Care
CP - England
KW - *Cancer; *Immunotherapy; *Interdisciplinary management; *Targeted therapy; *Toxicity
AB - Pharmacological and cellular treatment of cancer is changing dramatically with benefits for patient outcome and comfort, but also with new toxicity profiles. The majority of adverse events can be classified as mild or moderate, but severe and life-threatening complications requiring ICU admission also occur. This review will focus on pathophysiology, symptoms, and management of these events based on the available literature.While standard antineoplastic therapy is associated with immunosuppression and infections, some of the recent approaches induce overwhelming inflammation and autoimmunity. Cytokine-release syndrome (CRS) describes a complex of symptoms including fever, hypotension, and skin reactions as well as lab abnormalities. CRS may occur after the infusion of monoclonal or bispecific antibodies (MABs, BABs) targeting immune effectors and tumor cells and is a major concern in recipients of chimeric antigen receptor (CAR) modified T lymphocytes as well. BAB and CAR T-cell treatment may also be compromised by central nervous system (CNS) toxicities such as encephalopathy, cerebellar alteration, disturbed consciousness, or seizures. While CRS is known to be induced by exceedingly high levels of inflammatory cytokines, the pathophysiology of CNS events is still unclear. Treatment with antibodies against inhibiting immune checkpoints can lead to immune-related adverse events (IRAEs); colitis, diarrhea, and endocrine disorders are often the cause for ICU admissions.Respiratory distress is the main reason for ICU treatment in cancer patients and is attributable to infectious agents in most cases. In addition, some of the new drugs are reported to cause non-infectious lung complications. While drug-induced interstitial pneumonitis was observed in a substantial number of patients treated with phosphoinositol-3-kinase inhibitors, IRAEs may also affect the lungs.Inhibitors of angiogenetic pathways have increased the antineoplastic portfolio. However, vessel formation is also essential for regeneration and tissue repair. Therefore, severe vascular side effects, including thromboembolic events, gastrointestinal bleeding or perforation, hypertension, and congestive heart failure, compromise antitumor efficacy.The limited knowledge of the pathophysiology and management of life-threatening complications relating to new cancer drugs presents a need to provide ICU staff, oncologists, and organ specialists with evidence-based algorithms.
ES - 1466-609X
IL - 1364-8535
DI - 10.1186/s13054-017-1678-1
DO - https://dx.doi.org/10.1186/s13054-017-1678-1
PT - Journal Article
PT - Review
PT - Research Support, Non-U.S. Gov't
ID - 10.1186/s13054-017-1678-1 [doi]
ID - 10.1186/s13054-017-1678-1 [pii]
ID - PMC5391608 [pmc]
PP - epublish
LG - English
EP - 20170414
DP - 2017 04 14
DC - 20170414
EZ - 2017/04/15 06:00
DA - 2017/04/15 06:00
DT - 2017/04/15 06:00
YR - 2017
RD - 20170615
UP - 20170616
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28407743
<396. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28557813
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Leonardi GC
AU - Oxnard GR
AU - Haas A
AU - Lang JP
AU - Williams JS
AU - Awad MM
FA - Leonardi, Giulia C
FA - Oxnard, Geoffrey R
FA - Haas, Andrea
FA - Lang, Joshua P
FA - Williams, Jonathan S
FA - Awad, Mark M
IN - Leonardi, Giulia C. *Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute +Division of Endocrinology, Diabetes and Hypertension ++Department of Medicine, Brigham and Women's Hospital, Boston, MA.
TI - Diabetic Ketoacidosis as an Immune-related Adverse Event from Pembrolizumab in Non-Small Cell Lung Cancer.
SO - Journal of Immunotherapy. 40(6):249-251, 2017 Jul/Aug
AS - J Immunother. 40(6):249-251, 2017 Jul/Aug
NJ - Journal of immunotherapy (Hagerstown, Md. : 1997)
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - cuq, 9706083
IO - J. Immunother.
CP - United States
AB - Programmed cell death protein 1 pathway inhibitors are now routinely administered to patients with non-small cell lung cancer, and prompt recognition of immune-related adverse events is critical to managing serious drug toxicities. Here, we describe a 66-year-old man with no known history of diabetes who presented with diabetic ketoacidosis after receiving 3 doses of pembrolizumab for lung adenocarcinoma. Autoimmune diabetes is a rare but potentially life-threatening complication of programmed cell death protein 1 inhibitors.
ES - 1537-4513
IL - 1524-9557
DO - https://dx.doi.org/10.1097/CJI.0000000000000173
PT - Journal Article
ID - 10.1097/CJI.0000000000000173 [doi]
PP - ppublish
LG - English
DP - 2017 Jul/Aug
DC - 20170530
EZ - 2017/05/31 06:00
DA - 2017/05/31 06:00
DT - 2017/05/31 06:00
YR - 2017
RD - 20170613
UP - 20170614
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28557813
<397. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28603207
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Okiyama N
AU - Tanaka R
FA - Okiyama, Naoko
FA - Tanaka, Ryota
IN - Okiyama, Naoko. Department of Dermatology, Faculty of Medicine, University of Tsukuba.
IN - Tanaka, Ryota. Department of Dermatology, Faculty of Medicine, University of Tsukuba.
TI - Varied immuno-related adverse events induced by immune-check point inhibitors - Nivolumab-associated psoriasiform dermatitis related with increased serum level of interleukin-6.
SO - Nihon Rinsho Meneki Gakkai Kaishi. 40(2):95-101, 2017
AS - Nihon Rinsho Meneki Gakkai Kaishi. 40(2):95-101, 2017
NJ - Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - ccm, 9505992
IO - Nihon Rinsho Meneki Gakkai Kaishi
CP - Japan
KW - immuno-related adverse events; interleukin-6; polyradiculoneuropathy; psoriasiform dermatitis; thyroiditis
AB - Nivolumab is a standard recombinant antibody treatment for patients with malignant melanoma (MM), which functions as an immune checkpoint inhibitor by blocking the programmed cell death-1 (PD-1) pathway in T cells. However, it leads to various immune-related adverse events (irAEs), and also exacerbates underlying autoimmune diseases. Herein we report cases of MM with irAE. Case 1: A 69-year-old woman with MM developed destructive thyroiditis resulting in hypothyroidism after 3 doses of nivolumab, and had been treated with thyroid gland auxiliary therapy. Case 2: A 80-year-old man with MM developed an acute onset of hyperthyroidism after 4 doses of nivolumab. Case 3: A 85-year-old woman with MM developed polyradiculoneuropathy resulting in somatosensory disorder and muscle weakness after 2 doses of nivolumab, and had been treated with intravenous immunoglobulin and oral predonisolone (40 mg/day). Case 4: A 77-year-old man with MM developed psoriasiform dermatitis after local injections of IFN-beta and 11 doses of nivolumab. Case 5: Case 2 also developed psoriasiform dermatitis. We analyzed serum levels of inflammatory cytokines in MM patients before/after treatments with nivolumab. All six patients who developed psoriasiform dermatitis with/without anamnesis of psoriasis after treatment with nivolumab, and all seven patients with other irAE exhibited increased serum IL-6 levels after nivolumab treatment, while decreased serum levels of IL-6 were observed in 5 of 7 non-afflicted MM patients. In addition, MM patients who achieved good responses to nivolumab significantly exhibited decreased serum TNF-alpha levels after nivolumab treatment compared to progressive MM patients.
ES - 1349-7413
IL - 0911-4300
DO - https://dx.doi.org/10.2177/jsci.40.95
PT - Journal Article
ID - 10.2177/jsci.40.95 [doi]
PP - ppublish
LG - English
DP - 2017
DC - 20170612
EZ - 2017/06/13 06:00
DA - 2017/06/13 06:00
DT - 2017/06/13 06:00
YR - 2017
RD - 20170612
UP - 20170613
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28603207
<398. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28603206
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Iwama S
AU - Arima H
FA - Iwama, Shintaro
FA - Arima, Hiroshi
IN - Iwama, Shintaro. Research Center of Health, Physical Fitness and Sports, Nagoya University.
IN - Arima, Hiroshi. Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine.
TI - Clinical practice and mechanism of endocrinological adverse events associated with immune checkpoint inhibitors.
SO - Nihon Rinsho Meneki Gakkai Kaishi. 40(2):90-94, 2017
AS - Nihon Rinsho Meneki Gakkai Kaishi. 40(2):90-94, 2017
NJ - Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - ccm, 9505992
IO - Nihon Rinsho Meneki Gakkai Kaishi
CP - Japan
KW - Hypophysitis; hypopituitarism; ipilimumab; nivolumab; pituitary
AB - Immune checkpoint inhibitors, used for cancer immunotherapy, show anti-tumor effects through T cell activations. Monoclonal antibodies against cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death (PD)-1, or PD-ligand 1 which is a ligand of PD-1 have been shown to be effective in the treatments of advanced cancers including malignant melanoma, non-small cell lung cancer, and renal cell carcinoma. However, these drugs also have immune-related adverse events (irAEs). The irAEs, which have unique characteristics different from those seen in conventional cytotoxic anti-tumor medicines, are observed in the several tissues such as skin, gastrointestinal tract, liver, lung, muscle, nerve and endocrine systems. To safely use immune checkpoint inhibitors, it is quite important to understand the characteristics of irAEs and to manage them in clinical practice. In this review, we focus on clinical characteristics and pathogenesis of adverse events in the pituitary gland.
ES - 1349-7413
IL - 0911-4300
DO - https://dx.doi.org/10.2177/jsci.40.90
PT - Journal Article
ID - 10.2177/jsci.40.90 [doi]
PP - ppublish
LG - English
DP - 2017
DC - 20170612
EZ - 2017/06/13 06:00
DA - 2017/06/13 06:00
DT - 2017/06/13 06:00
YR - 2017
RD - 20170612
UP - 20170613
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28603206
<399. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28603205
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Kadono T
FA - Kadono, Takafumi
IN - Kadono, Takafumi. Department of Dermatology, St. Marianna University School of Medicine.
TI - Immune-related adverse events by immune checkpoint inhibitors.
SO - Nihon Rinsho Meneki Gakkai Kaishi. 40(2):83-89, 2017
AS - Nihon Rinsho Meneki Gakkai Kaishi. 40(2):83-89, 2017
NJ - Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - ccm, 9505992
IO - Nihon Rinsho Meneki Gakkai Kaishi
CP - Japan
KW - immune checkpoint inhibitor; immune-related adverse event; ipilimumab; nivolumab; vitiligo
AB - Recent introduction of immune checkpoint inhibitors represented by anti-PD-1 antibodies such as nivolumab and pembrolizumab, and anti-CTLA-4 antibody such as ipilimumab had a great impact on cancer immunotherapy especially for melanoma, non-small cell lung cancer, renal cell carcinoma, and Hodgkin's lymphoma. On the other hand, immune checkpoint inhibitors have their own distinctive adverse events, which are collectively named as "immune-related adverse events". Although immune-related adverse events may occur at any part of the body, interstitial pneumonia, colitis, hypothyroidism, liver dysfunction, skin rash, vitiligo, hypophysitis, type 1 diabetes, renal dysfunction, myasthenia gravis, neuropathy, myositis, and uveitis are representative. The onset of these immune-related adverse events varies. As for ipilimumab, cutaneous and mucous complications appear relatively early, and subsequently digestive symptoms emerge. As for nivolumab, most immune-related adverse events start around a few months after its administration. These immune-related adverse events are basically managed according to the algorism. Prompt consultation to the experts are of great importance and the grade of immune-related adverse events and patients' disease conditions need to be carefully evaluated to decide the optimal measures. As immune-related adverse events could affect various organs, cooperation with many experts from various fields is critical and it is important to organize a cooperative system within a hospital.
ES - 1349-7413
IL - 0911-4300
DO - https://dx.doi.org/10.2177/jsci.40.83
PT - Journal Article
ID - 10.2177/jsci.40.83 [doi]
PP - ppublish
LG - English
DP - 2017
DC - 20170612
EZ - 2017/06/13 06:00
DA - 2017/06/13 06:00
DT - 2017/06/13 06:00
YR - 2017
RD - 20170612
UP - 20170613
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28603205
<400. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28595520
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Araujo M
AU - Ligeiro D
AU - Costa L
AU - Marques F
AU - Trindade H
AU - Correia JM
AU - Fonseca C
FA - Araujo, Manuel
FA - Ligeiro, Dario
FA - Costa, Luis
FA - Marques, Filipa
FA - Trindade, Helder
FA - Correia, Jose Manuel
FA - Fonseca, Candida
IN - Araujo, Manuel. Internal Medicine Department & Hospital Dia, Hospital Sao Francisco Xavier - Centro Hospitalar de Lisboa Ocidental, NOVA Medical School, Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal.
IN - Ligeiro, Dario. Immunogenetics Laboratory - Centro de Sangue e Transplantacao de Lisboa, Instituto Portugues de Sangue e Transplantacao, IP, Lisbon, Portugal.
IN - Costa, Luis. Internal Medicine Department & Hospital Dia, Hospital Sao Francisco Xavier - Centro Hospitalar de Lisboa Ocidental, NOVA Medical School, Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal.
IN - Marques, Filipa. Internal Medicine Department & Hospital Dia, Hospital Sao Francisco Xavier - Centro Hospitalar de Lisboa Ocidental, NOVA Medical School, Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal.
IN - Trindade, Helder. Immunogenetics Laboratory - Centro de Sangue e Transplantacao de Lisboa, Instituto Portugues de Sangue e Transplantacao, IP, Lisbon, Portugal.
IN - Correia, Jose Manuel. Pneumology Department, Hospital Egas Moniz - Centro Hospitalar de Lisboa Ocidental, NOVA Medical School, Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal.
IN - Fonseca, Candida. Internal Medicine Department & Hospital Dia, Hospital Sao Francisco Xavier - Centro Hospitalar de Lisboa Ocidental, NOVA Medical School, Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal.
TI - A case of fulminant Type 1 diabetes following anti-PD1 immunotherapy in a genetically susceptible patient.
SO - Immunotherapy. 9(7):531-535, 2017 Jun
AS - Immunotherapy. 9(7):531-535, 2017 Jun
NJ - Immunotherapy
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101485158
IO - Immunotherapy
CP - England
AB - Programmed cell death-1 protein (PD-1) is an immune checkpoint that has gained popularity in the treatment of several advanced cancers. Inhibiting this checkpoint is known to enhance immune response, but is also known to diminish immune tolerance and to increase autoimmune toxicity. We discuss a case of rapid onset fulminant Type 1 diabetes induced by treatment with anti-programmed cell death-1 monoclonal antibody, nivolumab, in a patient with late-stage non-small-cell lung adenocarcinoma. The patient had no history of previous diabetes but did reveal a high-risk genotype for Type 1 diabetes development (DR3-DQ2; DR4-DQ8). This finding supports that acute Type 1 diabetes can be an important adverse effect of immunotherapies targeting T-cell activation regulation. Because of the severity of this adverse effect, physicians should be aware of it, and studies directed to the detection of new biomarkers for early risk stratification (e.g., HLA) should be sought.
ES - 1750-7448
IL - 1750-743X
DO - https://dx.doi.org/10.2217/imt-2017-0020
PT - Journal Article
ID - 10.2217/imt-2017-0020 [doi]
PP - ppublish
LG - English
DP - 2017 Jun
DC - 20170609
EZ - 2017/06/10 06:00
DA - 2017/06/10 06:00
DT - 2017/06/10 06:00
YR - 2017
RD - 20170609
UP - 20170612
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28595520
<401. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28228726
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Kumar V
AU - Chaudhary N
AU - Garg M
AU - Floudas CS
AU - Soni P
AU - Chandra AB
FA - Kumar, Vivek
FA - Chaudhary, Neha
FA - Garg, Mohit
FA - Floudas, Charalampos S
FA - Soni, Parita
FA - Chandra, Abhinav B
IN - Kumar, Vivek. Department of Medicine, Maimonides Medical Center Brooklyn, NY, USA.
IN - Chaudhary, Neha. Department of Pediatrics, Maimonides Medical Center Brooklyn, NY, USA.
IN - Garg, Mohit. Department of Medicine, Maimonides Medical Center Brooklyn, NY, USA.
IN - Floudas, Charalampos S. Department of Medicine, Maimonides Medical Center Brooklyn, NY, USA.
IN - Soni, Parita. Department of Medicine, Maimonides Medical Center Brooklyn, NY, USA.
IN - Chandra, Abhinav B. Medical Director, Yuma Regional Cancer Center Yuma, AZ, USA.
TI - Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy. [Review][Erratum appears in Front Pharmacol. 2017 May 31;8:311; PMID: 28579959]
SO - Frontiers in Pharmacology. 8:49, 2017
AS - Front Pharmacol. 8:49, 2017
NJ - Frontiers in pharmacology
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101548923
IO - Front Pharmacol
CP - Switzerland
KW - *checkpoint blockade; *immune related adverse events; *ipilimumab; *irAEs; *nivolumab; *pembrolizumab
AB - The indications of immune checkpoint inhibitors (ICIs) are set to rise further with the approval of newer agent like atezolimumab for use in patients with advanced stage urothelial carcinoma. More frequent use of ICIs has improved our understanding of their unique side effects, which are known as immune-related adverse events (irAEs). The spectrum of irAEs has expanded beyond more common manifestations such as dermatological, gastrointestinal and endocrine effects to rarer presentations involving nervous, hematopoietic and urinary systems. There are new safety data accumulating on ICIs in patients with previously diagnosed autoimmune conditions. It is challenging for clinicians to continuously update their working knowledge to diagnose and manage these events successfully. If diagnosed timely, the majority of events are completely reversible, and temporary immunosuppression with glucocorticoids, infliximab or other agents is warranted only in the most severe grade illnesses. The same principles of management will possibly apply as newer anti- cytotoxic T lymphocytes-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1/PD-L1) antibodies are introduced. The current focus of research is for prophylaxis and for biomarkers to predict the onset of these toxicities. In this review we summarize the irAEs of ICIs and emphasize their growing spectrum and their management algorithms, to update oncology practitioners.
IL - 1663-9812
DO - https://dx.doi.org/10.3389/fphar.2017.00049
PT - Journal Article
PT - Review
ID - 10.3389/fphar.2017.00049 [doi]
ID - PMC5296331 [pmc]
PP - epublish
PH - 2016/08/16 [received]
PH - 2017/01/23 [accepted]
LG - English
EP - 20170208
DP - 2017
DC - 20170223
EZ - 2017/02/24 06:00
DA - 2017/02/24 06:00
DT - 2017/02/24 06:00
YR - 2017
RD - 20170609
UP - 20170609
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28228726
<402. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27943234
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Zarbo A
AU - Belum VR
AU - Sibaud V
AU - Oudard S
AU - Postow MA
AU - Hsieh JJ
AU - Motzer RJ
AU - Busam KJ
AU - Lacouture ME
AI - Zarbo, A; ORCID: http://orcid.org/0000-0002-2256-7492
AI - Belum, V R; ORCID: http://orcid.org/0000-0003-3628-3412
FA - Zarbo, A
FA - Belum, V R
FA - Sibaud, V
FA - Oudard, S
FA - Postow, M A
FA - Hsieh, J J
FA - Motzer, R J
FA - Busam, K J
FA - Lacouture, M E
IN - Zarbo, A. Department of Dermatology and Transitional Year Program, Henry Ford Hospital, Detroit, MI, 48202, U.S.A.
IN - Belum, V R. Department of Dermatology Service, Memorial Sloan Kettering Cancer Center, 60th Street Outpatient Center, Suite 407, Room 4315 16 East 60th Street, New York, NY, 10022, U.S.A.
IN - Sibaud, V. Department of Oncodermatology, Institut Universitaire du Cancer, Toulouse Oncopole, Toulouse, 31100, France.
IN - Oudard, S. Department of Medical Oncology, Hopital Europeen Georges Pompidou, Assistance Publique Hopitaux de Paris, 75015, France.
IN - Postow, M A. Melanoma & Immunotherapeutics Service, Weill Cornell Medical College, New York, NY, U.S.A.
IN - Hsieh, J J. Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, 60th Street Outpatient Center, Suite 407, Room 4315 16 East 60th Street, New York, NY, 10022, U.S.A.
IN - Motzer, R J. Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, 60th Street Outpatient Center, Suite 407, Room 4315 16 East 60th Street, New York, NY, 10022, U.S.A.
IN - Busam, K J. Department of Pathology, Memorial Sloan Kettering Cancer Center, 60th Street Outpatient Center, Suite 407, Room 4315 16 East 60th Street, New York, NY, 10022, U.S.A.
IN - Lacouture, M E. Department of Dermatology Service, Memorial Sloan Kettering Cancer Center, 60th Street Outpatient Center, Suite 407, Room 4315 16 East 60th Street, New York, NY, 10022, U.S.A.
TI - Immune-related alopecia (areata and universalis) in cancer patients receiving immune checkpoint inhibitors.
SO - British Journal of Dermatology. 176(6):1649-1652, 2017 Jun
AS - Br J Dermatol. 176(6):1649-1652, 2017 Jun
NJ - The British journal of dermatology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - aw0, 0004041
IO - Br. J. Dermatol.
CP - England
AB - Cytotoxic T-lymphocyte-associated protein-4, programmed cell death protein and programmed cell death protein ligand 1 monoclonal antibodies (immune checkpoint inhibitors), are used to treat various malignancies. Their mechanism of action involves the inhibition of negative regulators of immune activation, resulting in immune-related adverse events (irAEs) including endocrinopathies, pneumonitis, colitis, hepatitis and dermatological events. Dermatological irAEs include maculopapular rash, pruritus, vitiligo, blistering disorders, mucocutaneous lichenoid eruptions, rosacea and the exacerbation of psoriasis. Alopecia secondary to immune checkpoint inhibitors has been reported in 1.0-2.0% of treated patients. Our objective is to characterize for the first time the clinicopathology of patients with alopecia areata (AA) secondary to immune checkpoint inhibitors, including the first report of anti-PD-L1 therapy-induced AA, and review of the literature. Four cases of patients who developed partial or complete alopecia during treatment with immune checkpoint inhibitors for underlying cancer were identified from our clinics. Methods include the review of the history and clinicopathologic features. Three patients (75%) had AA and one had universalis. Two patients had a resolution after topical, oral or intralesional therapies and one had a resolution after immunotherapy was discontinued; all regrown hair exhibited poliosis. One of the four patients had coincident onychodystrophy. This report describes a series of four patients who developed partial or complete alopecia (i.e. areata and universalis) during treatment with immune checkpoint inhibitor therapies for cancer. The recognition and management of hair-related irAEs are important for pretherapy counselling and interventions that contribute to maintaining optimal health-related quality of life in patients.
AB - Copyright © 2016 British Association of Dermatologists.
ES - 1365-2133
IL - 0007-0963
DO - https://dx.doi.org/10.1111/bjd.15237
PT - Case Reports
ID - 10.1111/bjd.15237 [doi]
ID - PMC5459625 [pmc]
ID - NIHMS836795 [mid]
PP - ppublish
PH - 2016/12/02 [accepted]
PH - 2018/06/01 [pmc-release]
GI - No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20170424
DP - 2017 Jun
DC - 20161212
EZ - 2016/12/13 06:00
DA - 2016/12/13 06:00
DT - 2016/12/13 06:00
YR - 2017
RD - 20170607
UP - 20170609
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27943234
<403. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27442441
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Yu D
AU - Leja-Jarblad J
AU - Loskog A
AU - Hellman P
AU - Giandomenico V
AU - Oberg K
AU - Essand M
FA - Yu, Di
FA - Leja-Jarblad, Justyna
FA - Loskog, Angelica
FA - Hellman, Per
FA - Giandomenico, Valeria
FA - Oberg, Kjell
FA - Essand, Magnus
IN - Yu, Di. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
TI - Preclinical Evaluation of AdVince, an Oncolytic Adenovirus Adapted for Treatment of Liver Metastases from Neuroendocrine Cancer.
SO - Neuroendocrinology. 105(1):54-66, 2017
AS - Neuroendocrinology. 105(1):54-66, 2017
NJ - Neuroendocrinology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ny8, 0035665
IO - Neuroendocrinology
CP - Switzerland
KW - AdVince; Immunotherapy; Liver metastases; Neuroendocrine cancer; Oncolytic adenovirus
AB - Cancer immunotherapy is becoming a cornerstone in the clinical care of cancer patients due to the breakthrough trials with immune checkpoint blockade antibodies and chimeric antigen receptor T cells. The next breakthrough in cancer immunotherapy is likely to be oncolytic viruses engineered to selectively kill tumor cells and deceive the immune system to believe that the tumor is a foreign entity that needs to be eradicated. We have developed AdVince, an oncolytic adenovirus for treatment of liver metastases from neuroendocrine tumor (NET). AdVince includes the gene promoter from human chromogranin A for selective replication in neuroendocrine cells, miR122 target sequences for reduced liver toxicity, and a cell-penetrating peptide in the capsid for increased infectivity of tumor cells and optimized spread within tumors. This paper describes the preclinical evaluation of AdVince on freshly isolated human gastrointestinal NET cells resected from liver metastases and freshly isolated human hepatocytes as well as in fresh human blood. AdVince selectively replicates in and kills NET cells. Approximately 73-fold higher concentration of AdVince is needed to induce a similar level of cytotoxicity in NET cells as in hepatocytes. AdVince did not activate complement or induce considerable amount of proinflammatory cytokines or chemokines in human blood. The data presented herein indicate that AdVince can be safely evaluated in a phase I/IIa clinical trial for patients with liver-dominant NET.
AB - Copyright © 2016 S. Karger AG, Basel.
ES - 1423-0194
IL - 0028-3835
DI - 000448430
DO - https://dx.doi.org/10.1159/000448430
PT - Journal Article
ID - 000448430 [pii]
ID - 10.1159/000448430 [doi]
PP - ppublish
PH - 2016/03/14 [received]
PH - 2016/07/17 [accepted]
LG - English
EP - 20160721
DP - 2017
DC - 20160721
EZ - 2016/07/22 06:00
DA - 2016/07/22 06:00
DT - 2016/07/22 06:00
YR - 2017
RD - 20170606
UP - 20170608
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27442441
<404. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28267244
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Maruyama D
AU - Hatake K
AU - Kinoshita T
AU - Fukuhara N
AU - Choi I
AU - Taniwaki M
AU - Ando K
AU - Terui Y
AU - Higuchi Y
AU - Onishi Y
AU - Abe Y
AU - Kobayashi T
AU - Shirasugi Y
AU - Tobinai K
AI - Maruyama, Dai; ORCID: http://orcid.org/0000-0003-0654-6920
FA - Maruyama, Dai
FA - Hatake, Kiyohiko
FA - Kinoshita, Tomohiro
FA - Fukuhara, Noriko
FA - Choi, Ilseung
FA - Taniwaki, Masafumi
FA - Ando, Kiyoshi
FA - Terui, Yasuhito
FA - Higuchi, Yusuke
FA - Onishi, Yasushi
FA - Abe, Yasunobu
FA - Kobayashi, Tsutomu
FA - Shirasugi, Yukari
FA - Tobinai, Kensei
IN - Maruyama, Dai. Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
IN - Hatake, Kiyohiko. Department of Hematology and Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
IN - Kinoshita, Tomohiro. Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan.
IN - Fukuhara, Noriko. Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
IN - Choi, Ilseung. Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
IN - Taniwaki, Masafumi. Department of Hematology and Oncology, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan.
IN - Ando, Kiyoshi. Department of Hematology and Oncology, Tokai University, Isehara, Japan.
IN - Terui, Yasuhito. Department of Hematology and Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
IN - Higuchi, Yusuke. Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan.
IN - Onishi, Yasushi. Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
IN - Abe, Yasunobu. Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
IN - Kobayashi, Tsutomu. Department of Hematology and Oncology, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan.
IN - Shirasugi, Yukari. Department of Hematology and Oncology, Tokai University, Isehara, Japan.
IN - Tobinai, Kensei. Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
TI - Multicenter phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma.
SO - Cancer Science. 108(5):1007-1012, 2017 May
AS - Cancer Sci. 108(5):1007-1012, 2017 May
NJ - Cancer science
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101168776
IO - Cancer Sci.
CP - England
KW - Hodgkin lymphoma; Japanese; immunotherapy; nivolumab; programmed death-1
AB - Overexpression of programmed death-1 (PD-1) ligands contributes to an immunosuppressive microenvironment. Nivolumab is a PD-1-blocking antibody that inhibits the PD-1 pathway and showed good efficacy in several types of malignancy. This phase II study examined the efficacy and safety of nivolumab in 17 Japanese patients with refractory/relapsed classical Hodgkin lymphoma previously treated with brentuximab vedotin. Sixteen patients were included in efficacy analyses and 17 in safety analyses. The primary endpoint was the centrally assessed objective response rate (ORR). The study was commenced in March 2015. We report data obtained at a cutoff of 16 March 2016, at which time 11 patients were still receiving nivolumab. The median (range) duration of treatment and follow-up were 7.0 (1.4-10.6) months and 9.8 (6.0-11.1) months, respectively. All 17 patients had previously received brentuximab vedotin. The ORR was 81.3% (95% confidence interval [CI]: 54.4-96.0%; 13/16 patients), with complete remission and partial remission in 4 and 9 patients, respectively. The overall survival (OS) and progression-free survival (PFS) rates at 6 months were 100 and 60.0% (95% CI: 31.8-79.7%), respectively; the median OS and PFS were not reached. The most common adverse events (AE) were pyrexia (41.2%), pruritus (35.3%), rash (35.3%) and hypothyroidism (29.4%). Four patients (23.5%) experienced grade 3 or 4 AE, but most AE were of grade 1 or 2. In conclusion, nivolumab is a potentially effective and tolerable treatment option for Japanese patients with relapsed/refractory classical Hodgkin lymphoma previously treated with brentuximab vedotin.
AB - Copyright © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
ES - 1349-7006
IL - 1347-9032
DO - https://dx.doi.org/10.1111/cas.13230
PT - Journal Article
ID - 10.1111/cas.13230 [doi]
ID - PMC5448600 [pmc]
PP - ppublish
PH - 2017/01/09 [received]
PH - 2017/02/27 [revised]
PH - 2017/03/01 [accepted]
LG - English
EP - 20170519
DP - 2017 May
DC - 20170307
EZ - 2017/03/08 06:00
DA - 2017/03/08 06:00
DT - 2017/03/08 06:00
YR - 2017
RD - 20170602
UP - 20170605
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28267244
<405. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27852042
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Costa R
AU - Carneiro BA
AU - Agulnik M
AU - Rademaker AW
AU - Pai SG
AU - Villaflor VM
AU - Cristofanilli M
AU - Sosman JA
AU - Giles FJ
FA - Costa, Ricardo
FA - Carneiro, Benedito A
FA - Agulnik, Mark
FA - Rademaker, Alfred W
FA - Pai, Sachin G
FA - Villaflor, Victoria M
FA - Cristofanilli, Massimo
FA - Sosman, Jeffrey A
FA - Giles, Francis J
IN - Costa, Ricardo. Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
IN - Costa, Ricardo. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.
IN - Carneiro, Benedito A. Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
IN - Carneiro, Benedito A. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.
IN - Agulnik, Mark. Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
IN - Agulnik, Mark. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.
IN - Rademaker, Alfred W. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.
IN - Rademaker, Alfred W. Northwestern University Department of Preventive Medicine, Chicago, Illinois, USA.
IN - Pai, Sachin G. Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
IN - Pai, Sachin G. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.
IN - Villaflor, Victoria M. Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
IN - Villaflor, Victoria M. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.
IN - Cristofanilli, Massimo. Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
IN - Cristofanilli, Massimo. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.
IN - Sosman, Jeffrey A. Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
IN - Sosman, Jeffrey A. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.
IN - Giles, Francis J. Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
IN - Giles, Francis J. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.
TI - Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. [Review]
SO - Oncotarget. 8(5):8910-8920, 2017 Jan 31
AS - Oncotarget. 8(5):8910-8920, 2017 Jan 31
NJ - Oncotarget
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101532965
IO - Oncotarget
CP - United States
KW - adverse events; anti-PD1 antibodies; hypothyroidism; meta-analysis; pruritus
AB - PURPOSE: Nivolumab and pembrolizumab are antibodies against the programmed-death-receptor- 1 (PD-1) which are associated with distinct immune related adverse effects (AEs). This meta-analysis of randomized clinical trials aims to summarize current knowledge regarding the toxicity profile of these agents.
AB - METHODS: PubMed search was conducted in February of 2016. The randomized trials needed to have at least one of the study arms consisting of nivolumab or pembrolizumab monotherapy and a control arm containing no anti-PD-1 therapy. Data were analyzed using random effects meta-analysis for risk ratios. Heterogeneity across studies was analyzed using Q and I2 statistics.
AB - RESULTS: Nine randomized trials and 5,353 patients were included in our meta-analysis. There was evidence of significant heterogeneity between studies. The pooled relative risk (RR) for treatment-related all grade AEs and grade 3/4 AEs was 0.88 (95% CI 0.81-0.95;P=0.002) and 0.39 (95% CI 0.29-0.53; P<0.001) respectively favoring anti-PD-1 therapy versus standard of care approach. The RR of treatment-related death was 0.45 (95% CI 0.19-1.09; P=0.076). Patients treated with PD-1 inhibitors had an increased risk of hyperthyroidism [RR of 3.44 (95% CI 1.98-5.99; P<0.001)] and hypothyroidism [RR of 6.79 (95% CI 3.10-14.84; P<0.001)]. All grade pruritus and vitiligo were also more common among these patients. The pooled absolute risks of pneumonitis and hypophysitis were 2.65% and 0.47% respectively.
AB - CONCLUSION: Approved PD-1 inhibitors are well tolerated, associated with significant low risk of severe treatment-related AEs and increased risk of thyroid dysfunction, pruritus, and vitiligo.
ES - 1949-2553
IL - 1949-2553
DI - 13315
DO - https://dx.doi.org/10.18632/oncotarget.13315
PT - Journal Article
PT - Review
ID - 13315 [pii]
ID - 10.18632/oncotarget.13315 [doi]
ID - PMC5352453 [pmc]
PP - ppublish
PH - 2016/09/20 [received]
PH - 2016/10/13 [accepted]
GI - No: P30 CA060553
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2017 Jan 31
DC - 20161116
EZ - 2016/11/17 06:00
DA - 2016/11/17 06:00
DT - 2016/11/17 06:00
YR - 2017
RD - 20170526
UP - 20170530
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27852042
<406. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28515940
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Godwin JL
AU - Jaggi S
AU - Sirisena I
AU - Sharda P
AU - Rao AD
AU - Mehra R
AU - Veloski C
AI - Godwin, James Luke; ISNI: 0000 0004 0456 6466
AI - Godwin, James Luke; GRID: 0000 0004 0456 6466
AI - Jaggi, Shuchie; ISNI: 0000 0004 0456 652X
AI - Jaggi, Shuchie; GRID: 0000 0004 0456 652X
AI - Sirisena, Imali; ISNI: 0000 0004 0456 652X
AI - Sirisena, Imali; GRID: 0000 0004 0456 652X
AI - Sharda, Pankaj; ISNI: 0000 0004 0456 6466
AI - Sharda, Pankaj; GRID: 0000 0004 0456 6466
AI - Rao, Ajay D; ISNI: 0000 0004 0456 652X
AI - Rao, Ajay D; GRID: 0000 0004 0456 652X
AI - Veloski, Colleen; ISNI: 0000 0004 0456 6466
AI - Veloski, Colleen; GRID: 0000 0004 0456 6466
FA - Godwin, James Luke
FA - Jaggi, Shuchie
FA - Sirisena, Imali
FA - Sharda, Pankaj
FA - Rao, Ajay D
FA - Mehra, Ranee
FA - Veloski, Colleen
IN - Godwin, James Luke. Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA USA.
IN - Jaggi, Shuchie. Department of Medicine, Section of Metabolism, Diabetes and Endocrinology, Temple University Hospital, Philadelphia, PA USA.
IN - Sirisena, Imali. Department of Medicine, Section of Metabolism, Diabetes and Endocrinology, Temple University Hospital, Philadelphia, PA USA.
IN - Sharda, Pankaj. Department of Medicine, Section of Endocrinology, Fox Chase Cancer Center, Philadelphia, PA USA.
IN - Rao, Ajay D. Department of Medicine, Section of Metabolism, Diabetes and Endocrinology, Temple University Hospital, Philadelphia, PA USA.
IN - Mehra, Ranee. Department of Oncology, Johns Hopkins Hospital/Sidney Kimmel Comprehensive Cancer Center, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Baltimore, MD USA.
IN - Veloski, Colleen. Department of Medicine, Section of Endocrinology, Fox Chase Cancer Center, Philadelphia, PA USA.
TI - Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis in a patient with metastatic lung cancer.
SO - Journal for Immunotherapy of Cancer. 5:40, 2017
AS - J Immunother Cancer. 5:40, 2017
NJ - Journal for immunotherapy of cancer
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Internet
JC - 101620585
IO - J Immunother Cancer
CP - England
KW - Autoimmune diabetes; Diabetic ketoacidosis (DKA); Immune related adverse events (irAE); Nivolumab; Non-small cell lung cancer (NSCLC); PD-1 inhibitor
AB - BACKGROUND: Advances in cancer immunotherapy have generated encouraging results in multiple malignancies refractory to standard chemotherapies. As the use of immune checkpoint inhibitors (ICI) proliferates, the incidence of autoimmune side effects associated with these agents, termed immune related adverse events (irAE), is expected to increase. The frequency of significant irAE in ICI treated patients is about 10-20% and early recognition is critical to prevent serious morbidity and even mortality. New onset autoimmune diabetes mellitus (DM) associated with immune checkpoint inhibitor treatment is extremely rare, occurring in less than 1% of patients. Autoimmune DM often presents as diabetic ketoacidosis, a medical emergency requiring immediate treatment. We describe the first reported case of a patient with lung cancer who developed autoimmune diabetes after nivolumab treatment and was found to have three diabetes related (islet) autoantibodies present before ICI treatment and seroconversion of another after ICI treatment and onset of autoimmune DM.
AB - CASE PRESENTATION: A 34 year old African American woman with metastatic non-small cell lung cancer (NSCLC) was treated with nivolumab in the second line setting after disease progression following standard chemoradiation therapy. After receiving two doses of nivolumab, the patient developed abrupt onset of hyperglycemia and diabetic ketoacidosis. Autoimmune diabetes was diagnosed on the basis of undetectable C-peptide levels, seropositivity of three diabetes related (islet) autoantibodies and absolute insulin dependence. The patient eventually required use of continuous subcutaneous insulin infusion (insulin pump) due to erratic glycemic excursions and multiple readmissions for DKA. Human leucocyte antigen (HLA) genoyping revealed none of the high risk haplotypes associated with the development of type 1 diabetes. Interestingly, a frozen blood sample obtained prior to treatment with nivolumab tested positive for three of the four diabetes related (islet) autoantibodies despite no prior history of diabetes and no family history of diabetes. Notably, at the time of manuscript preparation, the patient is without evidence of NSCLC recurrence with no further treatment since the nivolumab therapy.
AB - CONCLUSION: New onset autoimmune diabetes mellitus associated with nivolumab has been described only in case reports and occurs at rates of<1% in the large clinical trials which garnered FDA approval in the second line setting for NSCLC. As ICI use continues to expand across a wide variety of malignancies, clinicians must maintain a high index of suspicion for irAE, including autoimmune DM and other endocrinopathies. A multidisciplinary team and thorough education of the patient are recommended to optimize management of new onset adult autoimmune DM. Our patient may have been at greater risk for the development of ICI related autoimmune diabetes due to the presence of three diabetes related autoantibodies prior to therapy; however, about half of the reported cases of autoimmune DM after anti-PD-1 therapy occurred in patients with no detectable diabetes related autoantibodies. Further studies are needed to delineate genetic and immunologic biomarkers that may be useful in identifying patients at risk of developing ICI related autoimmune DM.
ES - 2051-1426
IL - 2051-1426
DI - 245
DO - https://dx.doi.org/10.1186/s40425-017-0245-2
PT - Journal Article
ID - 10.1186/s40425-017-0245-2 [doi]
ID - 245 [pii]
ID - PMC5433051 [pmc]
PP - epublish
PH - 2016/11/18 [received]
PH - 2017/04/26 [accepted]
LG - English
EP - 20170516
DP - 2017
DC - 20170518
EZ - 2017/05/19 06:00
DA - 2017/05/19 06:00
DT - 2017/05/19 06:00
YR - 2017
RD - 20170521
UP - 20170523
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28515940
<407. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28512413
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Imafuku K
AU - Yoshino K
AU - Yamaguchi K
AU - Tsuboi S
AU - Ohara K
AU - Hata H
FA - Imafuku, Keisuke
FA - Yoshino, Koji
FA - Yamaguchi, Kei
FA - Tsuboi, Satoshi
FA - Ohara, Kuniaki
FA - Hata, Hiroo
IN - Imafuku, Keisuke. aTokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
IN - Yoshino, Koji. aTokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
IN - Yamaguchi, Kei. aTokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
IN - Tsuboi, Satoshi. aTokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
IN - Ohara, Kuniaki. aTokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
IN - Hata, Hiroo. bDepartment of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
TI - Two Cases of Nivolumab Re-Administration after Pneumonitis as Immune-Related Adverse Events.
SO - Case Reports Oncology. 10(1):296-300, 2017 Jan-Apr
AS - Case rep., oncol.. 10(1):296-300, 2017 Jan-Apr
NJ - Case reports in oncology
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101517601
IO - Case Rep Oncol
CP - Switzerland
KW - Cryptogenic organizing pneumonia; Diffuse alveolar damage; Immune-related adverse event; Nivolumab; Pneumonitis; Re-administration; Unresectable malignant melanoma
AB - Nivolumab is a recently approved medication for the treatment of unresectable malignant melanoma. Many immune-related adverse events (irAEs) associated with nivolumab have been reported, such as pneumonitis, hepatitis, dermatitis, and thyroiditis. Prednisolone can effectively treat irAEs. However, it is unclear how or if nivolumab should be administered to patients after they have experienced an irAE. Herein, we show 2 patients who underwent pneumonitis as irAE. Case 1 demonstrated a cryptogenic organizing pneumonia pattern in the CT scan and case 2 had a diffuse alveolar damage (DAD) pattern. Oral corticosteroids improved chest shadow of CT scan in both cases. However, when nivolumab was re-administrated, case 1 demonstrated no symptoms, but case 2 demonstrated pneumonia again. From our cases, it is difficult to re-administrate nivolumab for the patients with pneumonitis which shows a DAD pattern in CT, even if oral corticosteroids improve their symptoms.
IL - 1662-6575
DI - cro-0010-0296
DO - https://dx.doi.org/10.1159/000463379
PT - Journal Article
ID - 10.1159/000463379 [doi]
ID - cro-0010-0296 [pii]
ID - PMC5422733 [pmc]
PP - epublish
PH - 2017/02/13 [received]
PH - 2017/02/13 [accepted]
LG - English
EP - 20170404
DP - 2017 Jan-Apr
DC - 20170517
EZ - 2017/05/18 06:00
DA - 2017/05/18 06:01
DT - 2017/05/18 06:00
YR - 2017
RD - 20170521
UP - 20170523
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28512413
<408. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28476618
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Xiao ZX
AU - Chen RQ
AU - Hu DX
AU - Xie XQ
AU - Yu SB
AU - Chen XQ
FA - Xiao, Zui Xuan
FA - Chen, Ruo Qiao
FA - Hu, Dian Xing
FA - Xie, Xiao Qiang
FA - Yu, Shang Bin
FA - Chen, Xiao Qian
IN - Xiao, Zui Xuan. Department of Endocrinology, Jingzhou First People's Hospital, The First Clinical Medical College, Yangtze University, Jingzhou 434100, China.
IN - Chen, Ruo Qiao. School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
IN - Hu, Dian Xing. Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Neurological Diseases, Ministry of Education, Hubei Provincial Key Laboratory of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
IN - Xie, Xiao Qiang. Department of Pathology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou 434020, China. Electronic address: slideabc@hotmail.com.
IN - Yu, Shang Bin. Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Neurological Diseases, Ministry of Education, Hubei Provincial Key Laboratory of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: yushangbin@tjmu.edu.cn.
IN - Chen, Xiao Qian. Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Neurological Diseases, Ministry of Education, Hubei Provincial Key Laboratory of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: chenxq@mails.tjmu.edu.cn.
TI - Identification of repaglinide as a therapeutic drug for glioblastoma multiforme.
SO - Biochemical & Biophysical Research Communications. 488(1):33-39, 2017 Jun 17
AS - Biochem Biophys Res Commun. 488(1):33-39, 2017 Jun 17
NJ - Biochemical and biophysical research communications
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9y8, 0372516
IO - Biochem. Biophys. Res. Commun.
CP - United States
KW - Bioinformatics; Brain tumor; Cancer therapy; Drug repositioning; Glioma; Repaglinide
AB - Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a median survival time of only 14 months after treatment. It is urgent to find new therapeutic drugs that increase survival time of GBM patients. To achieve this goal, we screened differentially expressed genes between long-term and short-term survived GBM patients from Gene Expression Omnibus database and found gene expression signature for the long-term survived GBM patients. The signaling networks of all those differentially expressed genes converged to protein binding, extracellular matrix and tissue development as revealed in BiNGO and Cytoscape. Drug repositioning in Connectivity Map by using the gene expression signature identified repaglinide, a first-line drug for diabetes mellitus, as the most promising novel drug for GBM. In vitro experiments demonstrated that repaglinide significantly inhibited the proliferation and migration of human GBM cells. In vivo experiments demonstrated that repaglinide prominently prolonged the median survival time of mice bearing orthotopic glioma. Mechanistically, repaglinide significantly reduced Bcl-2, Beclin-1 and PD-L1 expression in glioma tissues, indicating that repaglinide may exert its anti-cancer effects via apoptotic, autophagic and immune checkpoint signaling. Taken together, repaglinide is likely to be an effective drug to prolong life span of GBM patients.
AB - Copyright © 2017. Published by Elsevier Inc.
ES - 1090-2104
IL - 0006-291X
DI - S0006-291X(17)30846-X
DO - https://dx.doi.org/10.1016/j.bbrc.2017.04.157
PT - Journal Article
ID - S0006-291X(17)30846-X [pii]
ID - 10.1016/j.bbrc.2017.04.157 [doi]
PP - ppublish
PH - 2017/04/26 [received]
PH - 2017/04/30 [accepted]
LG - English
EP - 20170502
DP - 2017 Jun 17
DC - 20170506
EZ - 2017/05/07 06:00
DA - 2017/05/10 06:00
DT - 2017/05/10 06:00
YR - 2017
RD - 20170521
UP - 20170523
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28476618
<409. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28421272
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Koelzer VH
AU - Glatz K
AU - Bubendorf L
AU - Weber A
AU - Gaspert A
AU - Cathomas G
AU - Lugli A
AU - Zippelius A
AU - Kempf W
AU - Mertz KD
FA - Koelzer, V H
FA - Glatz, K
FA - Bubendorf, L
FA - Weber, A
FA - Gaspert, A
FA - Cathomas, G
FA - Lugli, A
FA - Zippelius, A
FA - Kempf, W
FA - Mertz, K D
IN - Koelzer, V H. Institut fur Pathologie, Kantonsspital Baselland, Muhlemattstrase 11, 4410, Liestal, Schweiz.
IN - Koelzer, V H. Translational Research Unit (TRU), Institut fur Pathologie, Universitat Bern, Bern, Schweiz.
IN - Glatz, K. Institut fur Pathologie, Universitatsspital Basel, Basel, Schweiz.
IN - Bubendorf, L. Institut fur Pathologie, Universitatsspital Basel, Basel, Schweiz.
IN - Weber, A. Institut fur Pathologie und Molekularpathologie, Universitat Zurich und Universitatsspital Zurich, Zurich, Schweiz.
IN - Gaspert, A. Institut fur Pathologie und Molekularpathologie, Universitat Zurich und Universitatsspital Zurich, Zurich, Schweiz.
IN - Cathomas, G. Institut fur Pathologie, Kantonsspital Baselland, Muhlemattstrase 11, 4410, Liestal, Schweiz.
IN - Lugli, A. Klinische Pathologie, Institut fur Pathologie, Universitat Bern, Bern, Schweiz.
IN - Zippelius, A. Klinik fur Onkologie, Universitatsspital Basel, Basel, Schweiz.
IN - Kempf, W. Kempf und Pfaltz Histologische Diagnostik, Research Unit, Zurich, Schweiz.
IN - Mertz, K D. Institut fur Pathologie, Kantonsspital Baselland, Muhlemattstrase 11, 4410, Liestal, Schweiz. kirsten.mertz@ksbl.ch.
TI - [The pathology of adverse events with immune checkpoint inhibitors]. [German]
OT - Pathologie der Nebenwirkungen von Immune-Checkpoint-Inhibitoren.
SO - Pathologe. 38(3):197-208, 2017 May
AS - Pathologe. 38(3):197-208, 2017 May
NJ - Der Pathologe
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - plk, 8006541
IO - Pathologe
CP - Germany
KW - Adverse drug event; Autoimmunity; Immunotherapy; Personalized medicine
AB - BACKGROUND: Immunotherapy has gained importance with the development of new effective cancer treatments. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that promote T-cell mediated tumor immune rejection. Checkpoint blockade also carries the risk of inducing autoimmune reactions ("immune related adverse events", irAEs). The diagnosis and classification of irAEs constitute a new and important field in pathology.
AB - AIM: Practice-oriented review of the diagnosis and classification of irAEs.
AB - MATERIALS AND METHODS: Structured, selective literature review based on PubMed und UpToDate online.
AB - RESULTS: The most common irAEs affect the skin, the gastrointestinal tract, the liver, and the respiratory system. The correct diagnosis and classification of irAEs by an interdisciplinary care team is essential for appropriate therapy and the prevention of long-term sequelae. Other important irAEs affect the endocrine organs, the heart, the joints, the kidneys and the nervous system. Because of their rarity and/or limited options for bioptic diagnosis, only limited data on the morphology and pathophysiology of these irAEs are currently available. Autopsies carried out after ICI therapy constitute an important element of quality control and allow better documentation of the incidence and pathogenesis of irAEs.
AB - DISCUSSION: Pathology plays a central role in the diagnosis and treatment of irAEs. Future studies may contribute to a better mechanistic understanding of irAEs for individualized knowledge-based risk assessment.
ES - 1432-1963
IL - 0172-8113
DI - 10.1007/s00292-017-0281-1
DO - https://dx.doi.org/10.1007/s00292-017-0281-1
PT - English Abstract
PT - Journal Article
ID - 10.1007/s00292-017-0281-1 [doi]
ID - 10.1007/s00292-017-0281-1 [pii]
PP - ppublish
LG - German
DP - 2017 May
DC - 20170419
EZ - 2017/04/20 06:00
DA - 2017/04/20 06:00
DT - 2017/04/20 06:00
YR - 2017
RD - 20170518
UP - 20170519
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28421272
<410. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27401894
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Weber JS
AU - Postow M
AU - Lao CD
AU - Schadendorf D
FA - Weber, Jeffrey S
FA - Postow, Michael
FA - Lao, Christopher D
FA - Schadendorf, Dirk
IN - Weber, Jeffrey S. Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York, USA jeffrey.weber2@nyumc.org.
IN - Postow, Michael. Memorial Sloan Kettering Cancer Center, New York, New York, USA Weill Cornell Medical College, New York, New York, USA.
IN - Lao, Christopher D. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
IN - Schadendorf, Dirk. University Hospital Essen, Essen, Germany.
TI - Management of Adverse Events Following Treatment With Anti-Programmed Death-1 Agents. [Review]
SO - Oncologist. 21(10):1230-1240, 2016 Oct
AS - Oncologist. 21(10):1230-1240, 2016 Oct
NJ - The oncologist
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dd5, 9607837
IO - Oncologist
CP - United States
KW - Drug-related side effects and adverse reactions; Melanoma; Nivolumab; Pembrolizumab; Programmed cell death 1 receptor
AB - : Immune checkpoint inhibitors have emerged as a mainstay of melanoma therapy and are playing an increasingly important role in the treatment of other tumor types. The clinical benefit afforded by these treatments can be accompanied by a unique spectrum of adverse events, called immune-related adverse events (irAEs), which reflect the drug's immune-based mechanism of action. IrAEs typically originate in the skin, gastrointestinal tract, liver, and endocrine system, although other organ systems may also be affected. This article provides an overview of irAEs associated with anti-programmed death-1 (anti-PD-1) antibodies (nivolumab and pembrolizumab) as monotherapy or in combination with anti-cytotoxic T-lymphocyte antigen-4 inhibition (ipilimumab), followed by a discussion of irAEs of special clinical interest based on the potential for morbidity, frequent steroid use, and inpatient admission. We review clinical trial data and provide recommendations on how to manage irAEs associated with anti-PD-1 agents based on clinical experience and established management guidelines. We further illustrate the practical considerations of managing irAEs by presenting three cases of immune-related toxicity in melanoma patients treated with nivolumab or pembrolizumab. A better understanding of the identification and management of irAEs will help inform health care providers about the risks associated with anti-PD-1 treatment, to ensure the safe and appropriate use of these important new treatments.
AB - IMPLICATIONS FOR PRACTICE: Immune checkpoint inhibitors have demonstrated significant clinical benefit in advanced melanoma and other tumor types. These treatments are associated with immune-related adverse events (irAEs), which most commonly affect the skin and gastrointestinal tract, and, to a lesser extent, the liver, endocrine system, and other organs. This review focuses on the management of irAEs after treatment with anti-programmed death-1 (anti-PD-1) antibodies (nivolumab or pembrolizumab) as monotherapy or in combination with anti-cytotoxic T-lymphocyte antigen-4 inhibition (ipilimumab) in patients with advanced melanoma. A better understanding of the management of irAEs will help ensure the safe and appropriate use of anti-PD-1 agents in melanoma and other tumor types.
AB - Copyright ©AlphaMed Press.
CI - of potential conflicts of interest may be found at the end of this article.
ES - 1549-490X
IL - 1083-7159
DI - theoncologist.2016-0055
DO - https://dx.doi.org/10.1634/theoncologist.2016-0055
PT - Review
PT - Journal Article
ID - theoncologist.2016-0055 [pii]
ID - 10.1634/theoncologist.2016-0055 [doi]
ID - PMC5061539 [pmc]
PP - ppublish
PH - 2016/02/12 [received]
PH - 2016/05/02 [accepted]
PH - 2017/10/01 [pmc-release]
GI - No: P30 CA008748
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20160708
DP - 2016 Oct
DC - 20160712
EZ - 2016/07/13 06:00
DA - 2016/07/13 06:00
DT - 2016/07/13 06:00
YR - 2016
RD - 20170518
UP - 20170519
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27401894
<411. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28499411
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Gambichler T
AU - Strutzmann S
AU - Tannapfel A
AU - Susok L
AI - Gambichler, Thilo; ORCID: http://orcid.org/0000-0001-7862-3695
FA - Gambichler, Thilo
FA - Strutzmann, Stefanie
FA - Tannapfel, Andrea
FA - Susok, Laura
IN - Gambichler, Thilo. Department of Dermatology, Ruhr-University Bochum, Gudrunstr. 56, 44791, Bochum, Germany. t.gambichler@klinikum-bochum.de.
IN - Strutzmann, Stefanie. Department of Dermatology, Ruhr-University Bochum, Gudrunstr. 56, 44791, Bochum, Germany.
IN - Tannapfel, Andrea. Institute of Pathology, Ruhr-University Bochum, Burkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
IN - Susok, Laura. Department of Dermatology, Ruhr-University Bochum, Gudrunstr. 56, 44791, Bochum, Germany.
TI - Paraneoplastic acral vascular syndrome in a patient with metastatic melanoma under immune checkpoint blockade.
SO - BMC Cancer. 17(1):327, 2017 May 12
AS - BMC Cancer. 17(1):327, 2017 May 12
NJ - BMC cancer
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 100967800
IO - BMC Cancer
CP - England
KW - Digital ischemia; Gangrene; Immune-checkpoint blockade, ipilimumab, nivolumab; Melanoma
AB - BACKGROUND: Paraneoplastic acral vascular syndrome (PAVS) is a rare phenomenon which is observed in patients with adenocarcinomas and other malignancies. Various potential pathogenic mechanisms such as tumour invasion of sympathetic nerves, hyperviscosity, hypercoagulability, vasoactive tumour-secreted substances, and immunological mechanisms have been suggested.
AB - CASE PRESENTATION: We report a 60-year-old Caucasian male attended our hospital with a bulky lymph node mass in the right axilla. Extirpation of a lymph node conglomerate revealed 5 melanoma lymph node metastases. Computed tomography showed a liver metastasis (diameter: 3.8 cm), several retroperitoneal metastases, bilateral metastases in the lung hilus, and prepectoral subcutaneous metastases (Stage IV; pTx, N3, M1c). Lactate dehydrogenase and S100B were slightly elevated. Combination therapy of nivolumab (1 mg/kg BW) and ipilimumab (3 mg/kg BW) was started. Three weeks after the first combination therapy he developed progressive erythema, paraesthesia and pain on the fingertips of both hands. Both cold and warmth was not well tolerated by the patient. Complete work-up excluded associated conditions or factors such as haematological disorders, rheumatologic disorders, hypertension, diabetes or smoking. Treatment was initiated with prostacyclin 20 mug twice daily and oral prednisolone 50 mg in tapering dosage. However, prostacyclin was stopped after the first applications because the pain increased during infusion. The second course of nivolumab and ipilimumab was administered. About 2 weeks later, the patient presented with increased pain and small subungual necrosis. We treated the patient with oral analgetics and intravenous prednisolone 500 mg in tapering dosage. On digital substraction angiography occlusion of all arteries of the fingers was demonstrated. Further rheologic and anti-melanoma treatments were refused by the patient. About 2 months after the second course of nivolumab and ipilimumab combination therapy several fingers showed severe gangrene which finally led to amputations of end phalanges of several fingers. Histopathology did not reveal evidence for vasculitis or other primary vascular pathologies. During the following 2 months the patient experienced dramatic progress of his metastatic disease and finally died at multi-organ failure.
AB - CONCLUSION: Presence of rapidly progressive digital ischemia in an elderly patient with cancer should always raise clinical suspicion of a paraneoplastic phenomenon when other possible causes have been excluded. In patients treated with immune checkpoint inhibitors such as CTLA-4 and PD-L1 blockers PVAS-like events have not been reported so far. However, it is debatable whether immune checkpoint blockade may play a pathogenetic role in the development of PAVS in patients with malignancies.
ES - 1471-2407
IL - 1471-2407
DI - 10.1186/s12885-017-3313-6
DO - https://dx.doi.org/10.1186/s12885-017-3313-6
PT - Journal Article
ID - 10.1186/s12885-017-3313-6 [doi]
ID - 10.1186/s12885-017-3313-6 [pii]
ID - PMC5429577 [pmc]
PP - epublish
PH - 2016/12/21 [received]
PH - 2017/05/01 [accepted]
LG - English
EP - 20170512
DP - 2017 May 12
DC - 20170513
EZ - 2017/05/14 06:00
DA - 2017/05/14 06:00
DT - 2017/05/14 06:00
YR - 2017
RD - 20170516
UP - 20170518
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28499411
<412. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28438889
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Kasamon YL
AU - de Claro RA
AU - Wang Y
AU - Shen YL
AU - Farrell AT
AU - Pazdur R
FA - Kasamon, Yvette L
FA - de Claro, R Angelo
FA - Wang, Yaping
FA - Shen, Yuan Li
FA - Farrell, Ann T
FA - Pazdur, Richard
IN - Kasamon, Yvette L. Office of Hematology and Oncology Products and Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA Yvette.Kasamon@fda.hhs.gov.
IN - de Claro, R Angelo. Office of Hematology and Oncology Products and Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Wang, Yaping. Office of Hematology and Oncology Products and Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Shen, Yuan Li. Office of Hematology and Oncology Products and Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Farrell, Ann T. Office of Hematology and Oncology Products and Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Pazdur, Richard. Office of Hematology and Oncology Products and Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
TI - FDA Approval Summary: Nivolumab for the Treatment of Relapsed or Progressive Classical Hodgkin Lymphoma.
SO - Oncologist. 22(5):585-591, 2017 May
AS - Oncologist. 22(5):585-591, 2017 May
NJ - The oncologist
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dd5, 9607837
IO - Oncologist
CP - United States
KW - Hodgkin lymphoma; Nivolumab; Programmed cell death 1 inhibitor; Programmed death-ligand 1
AB - On May 17, 2016, after an expedited priority review, the U.S. Food and Drug Administration granted accelerated approval to nivolumab for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin (BV). Nivolumab in cHL had been granted breakthrough therapy designation. Accelerated approval was based on two single-arm, multicenter trials in adults with cHL. In 95 patients with relapsed or progressive cHL after autologous HSCT and post-transplantation BV, nivolumab, dosed at 3 mg/kg intravenously every 2 weeks, produced a 65% (95% confidence interval: 55%-75%) objective response rate (58% partial remission, 7% complete remission). The estimated median duration of response was 8.7 months, with 4.6-month median follow-up for response duration. The median time to response was 2.1 (range: 0.7-5.7) months. Among 263 patients with cHL treated with nivolumab, 21% reported serious adverse reactions (ARs). The most common all-grade ARs (reported in >=20%) were fatigue, upper respiratory tract infection, cough, pyrexia, diarrhea, elevated transaminases, and cytopenias. Infusion-related reaction and hypothyroidism or thyroiditis occurred in >10% of patients; other immune-mediated ARs, occurring in 1%-5%, included rash, pneumonitis, hepatitis, hyperthyroidism, and colitis. A new Warning and Precaution was issued for complications of allogeneic HSCT after nivolumab, including severe or hyperacute graft-versus-host disease, other immune-mediated ARs, and transplant-related mortality. Continued approval for the cHL indication may be contingent upon verification of clinical benefit in a randomized trial. The Oncologist 2017;22:585-591 IMPLICATIONS FOR PRACTICE: Based on response rate and duration in single-arm studies, nivolumab is a new treatment option for patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed despite autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin. This was the first U.S. Food and Drug Administration marketing application for a programmed cell death 1 inhibitor in hematologic malignancies. The use of immune checkpoint blockade in cHL represents a new treatment paradigm. The safety of allogeneic HSCT after nivolumab requires further evaluation, as does the safety of nivolumab after allogeneic HSCT.
AB - Copyright © AlphaMed Press 2017.
ES - 1549-490X
IL - 1083-7159
DI - theoncologist.2017-0004
DO - https://dx.doi.org/10.1634/theoncologist.2017-0004
PT - Journal Article
ID - theoncologist.2017-0004 [pii]
ID - 10.1634/theoncologist.2017-0004 [doi]
ID - PMC5423515 [pmc]
PP - ppublish
PH - 2017/01/06 [received]
PH - 2017/02/08 [accepted]
PH - 2018/05/01 [pmc-release]
LG - English
EP - 20170424
DP - 2017 May
DC - 20170425
EZ - 2017/04/26 06:00
DA - 2017/04/26 06:00
DT - 2017/04/26 06:00
YR - 2017
RD - 20170512
UP - 20170515
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28438889
<413. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28359784
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Ascierto PA
AU - Del Vecchio M
AU - Robert C
AU - Mackiewicz A
AU - Chiarion-Sileni V
AU - Arance A
AU - Lebbe C
AU - Bastholt L
AU - Hamid O
AU - Rutkowski P
AU - McNeil C
AU - Garbe C
AU - Loquai C
AU - Dreno B
AU - Thomas L
AU - Grob JJ
AU - Liszkay G
AU - Nyakas M
AU - Gutzmer R
AU - Pikiel J
AU - Grange F
AU - Hoeller C
AU - Ferraresi V
AU - Smylie M
AU - Schadendorf D
AU - Mortier L
AU - Svane IM
AU - Hennicken D
AU - Qureshi A
AU - Maio M
FA - Ascierto, Paolo A
FA - Del Vecchio, Michele
FA - Robert, Caroline
FA - Mackiewicz, Andrzej
FA - Chiarion-Sileni, Vanna
FA - Arance, Ana
FA - Lebbe, Celeste
FA - Bastholt, Lars
FA - Hamid, Omid
FA - Rutkowski, Piotr
FA - McNeil, Catriona
FA - Garbe, Claus
FA - Loquai, Carmen
FA - Dreno, Brigitte
FA - Thomas, Luc
FA - Grob, Jean-Jacques
FA - Liszkay, Gabriella
FA - Nyakas, Marta
FA - Gutzmer, Ralf
FA - Pikiel, Joanna
FA - Grange, Florent
FA - Hoeller, Christoph
FA - Ferraresi, Virginia
FA - Smylie, Michael
FA - Schadendorf, Dirk
FA - Mortier, Laurent
FA - Svane, Inge Marie
FA - Hennicken, Delphine
FA - Qureshi, Anila
FA - Maio, Michele
IN - Ascierto, Paolo A. Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy. Electronic address: paolo.ascierto@gmail.com.
IN - Del Vecchio, Michele. Medical Oncology, National Cancer Institute, Milan, Italy.
IN - Robert, Caroline. Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.
IN - Mackiewicz, Andrzej. Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan Medical University, Poznan, Poland.
IN - Chiarion-Sileni, Vanna. IOV-IRCCS, Melanoma Oncology Unit, Padova, Italy.
IN - Arance, Ana. Hospital Clinic and Institut d'Investigacions Biomediques August Pi I Sunyer, Barcelona, Spain.
IN - Lebbe, Celeste. AP-HP Dermatology CIC Departments, Saint-Louis Hospital, INSERM U976, Universite Paris Diderot, Paris, France.
IN - Bastholt, Lars. Odense University Hospital, Odense, Denmark.
IN - Hamid, Omid. The Angeles Clinic and Research Institute, Los Angeles, CA, USA.
IN - Rutkowski, Piotr. Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland.
IN - McNeil, Catriona. Chris O'Brien Lifehouse and Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Melanoma Institute Australia, Sydney, NSW, Australia.
IN - Garbe, Claus. Eberhard Karls University, Tubingen, Germany.
IN - Loquai, Carmen. University Medical Center, Mainz, Germany.
IN - Dreno, Brigitte. Department of Oncodermatology, INSERM Research Unit 892, Nantes University Hospital, Nantes, France.
IN - Thomas, Luc. Department of Dermatology, Centre Hospitalier Lyon-Sud, Pierre-Benite, France.
IN - Grob, Jean-Jacques. Hospital de la Timone, Marseille, France.
IN - Liszkay, Gabriella. National Institute of Oncology, Budapest, Hungary.
IN - Nyakas, Marta. Oslo University Hospital, Oslo, Norway.
IN - Gutzmer, Ralf. Medizinische Hochschule Hannover, Hannover, Germany.
IN - Pikiel, Joanna. Wojewodzkie Centrum Oncologii, Gdansk, Poland.
IN - Grange, Florent. Department of Dermatology, Reims University Hospital, Reims, France.
IN - Hoeller, Christoph. Medical University of Vienna, Vienna, Austria.
IN - Ferraresi, Virginia. Istituti Fisioterapici Ospitalieri, Rome, Italy.
IN - Smylie, Michael. Cross Cancer Institute, Edmonton, AB, Canada.
IN - Schadendorf, Dirk. University Hospital Essen, Essen, Germany.
IN - Mortier, Laurent. Hospital Claude Huriez, Lille, France.
IN - Svane, Inge Marie. Herlev Hospital, University of Copenhagen, Herlev, Denmark.
IN - Hennicken, Delphine. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Qureshi, Anila. Bristol-Myers Squibb, Princeton, NJ, USA.
IN - Maio, Michele. University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy.
TI - Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial.
SO - Lancet Oncology. 18(5):611-622, 2017 May
AS - Lancet Oncol. 18(5):611-622, 2017 May
NJ - The Lancet. Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 100957246
IO - Lancet Oncol.
CP - England
AB - BACKGROUND: A phase 2 trial suggested increased overall survival and increased incidence of treatment-related grade 3-4 adverse events with ipilimumab 10 mg/kg compared with ipilimumab 3 mg/kg in patients with advanced melanoma. We report a phase 3 trial comparing the benefit-risk profile of ipilimumab 10 mg/kg versus 3 mg/kg.
AB - METHODS: This randomised, double-blind, multicentre, phase 3 trial was done in 87 centres in 21 countries worldwide. Patients with untreated or previously treated unresectable stage III or IV melanoma, without previous treatment with BRAF inhibitors or immune checkpoint inhibitors, were randomly assigned (1:1) with an interactive voice response system by the permuted block method using block size 4 to ipilimumab 10 mg/kg or 3 mg/kg, administered by intravenous infusion for 90 min every 3 weeks for four doses. Patients were stratified by metastasis stage, previous treatment for metastatic melanoma, and Eastern Cooperative Oncology Group performance status. The patients, investigators, and site staff were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population and safety was assessed in all patients who received at least one dose of study treatment. This study is completed and was registered with ClinicalTrials.gov, number NCT01515189.
AB - FINDINGS: Between Feb 29, and July 9, 2012, 727 patients were enrolled and randomly assigned to ipilimumab 10 mg/kg (365 patients; 364 treated) or ipilimumab 3 mg/kg (362 patients; all treated). Median follow-up was 14.5 months (IQR 4.6-42.3) for the ipilimumab 10 mg/kg group and 11.2 months (4.9-29.4) for the ipilimumab 3 mg/kg group. Median overall survival was 15.7 months (95% CI 11.6-17.8) for ipilimumab 10 mg/kg compared with 11.5 months (9.9-13.3) for ipilimumab 3 mg/kg (hazard ratio 0.84, 95% CI 0.70-0.99; p=0.04). The most common grade 3-4 treatment-related adverse events were diarrhoea (37 [10%] of 364 patients in the 10 mg/kg group vs 21 [6%] of 362 patients in the 3 mg/kg group), colitis (19 [5%] vs nine [2%]), increased alanine aminotransferase (12 [3%] vs two [1%]), and hypophysitis (ten [3%] vs seven [2%]). Treatment-related serious adverse events were reported in 133 (37%) patients in the 10 mg/kg group and 66 (18%) patients in the 3 mg/kg group; four (1%) versus two (<1%) patients died from treatment-related adverse events.
AB - INTERPRETATION: In patients with advanced melanoma, ipilimumab 10 mg/kg resulted in significantly longer overall survival than did ipilimumab 3 mg/kg, but with increased treatment-related adverse events. Although the treatment landscape for advanced melanoma has changed since this study was initiated, the clinical use of ipilimumab in refractory patients with unmet medical needs could warrant further assessment.
AB - FUNDING: Bristol-Myers Squibb.
AB - Copyright © 2017 Elsevier Ltd. All rights reserved.
ES - 1474-5488
IL - 1470-2045
DI - S1470-2045(17)30231-0
DO - https://dx.doi.org/10.1016/S1470-2045(17)30231-0
PT - Journal Article
ID - S1470-2045(17)30231-0 [pii]
ID - 10.1016/S1470-2045(17)30231-0 [doi]
PP - ppublish
PH - 2016/12/09 [received]
PH - 2017/01/31 [revised]
PH - 2017/02/03 [accepted]
LG - English
EP - 20170327
DP - 2017 May
DC - 20170331
EZ - 2017/04/01 06:00
DA - 2017/04/01 06:00
DT - 2017/04/01 06:00
YR - 2017
RD - 20170512
UP - 20170515
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28359784
<414. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28291584
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Alley EW
AU - Lopez J
AU - Santoro A
AU - Morosky A
AU - Saraf S
AU - Piperdi B
AU - van Brummelen E
FA - Alley, Evan W
FA - Lopez, Juanita
FA - Santoro, Armando
FA - Morosky, Anne
FA - Saraf, Sanatan
FA - Piperdi, Bilal
FA - van Brummelen, Emilie
IN - Alley, Evan W. Hematology and Oncology Division, Penn Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia, PA, USA. Electronic address: evan.alley@uphs.upenn.edu.
IN - Lopez, Juanita. Drug Development Unit, Institute of Cancer Research, London, UK.
IN - Santoro, Armando. Humanitas Cancer Center, Humanitas University, Milan, Italy.
IN - Morosky, Anne. Merck, Kenilworth, NJ, USA.
IN - Saraf, Sanatan. Merck, Kenilworth, NJ, USA.
IN - Piperdi, Bilal. Merck, Kenilworth, NJ, USA.
IN - van Brummelen, Emilie. Netherlands Cancer Institute, Amsterdam, Netherlands.
TI - Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial.
SO - Lancet Oncology. 18(5):623-630, 2017 May
AS - Lancet Oncol. 18(5):623-630, 2017 May
NJ - The Lancet. Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 100957246
IO - Lancet Oncol.
CP - England
AB - BACKGROUND: Malignant pleural mesothelioma is a highly aggressive cancer with poor prognosis and few treatment options following progression on platinum-containing chemotherapy. We assessed the safety and efficacy of pembrolizumab (an anti-programmed cell death receptor 1 [PD-1] antibody) in advanced solid tumours expressing programmed cell death ligand 1 (PD-L1) and report here on the interim analysis of the malignant pleural mesothelioma cohort.
AB - METHODS: Previously treated patients with PD-L1-positive malignant pleural mesothelioma were enrolled from 13 centres in six countries. Patients received pembrolizumab (10 mg/kg every 2 weeks) for up to 2 years or until confirmed progression or unacceptable toxicity. Key eligibility criteria included measurable disease, failure of standard therapy, and Eastern Cooperative Oncology Group performance status of 0 or 1. PD-L1 positivity was defined as expression in 1% or more of tumour cells by immunohistochemistry. Response was assessed based on investigator review using the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Primary endpoints were safety and tolerability, analysed in the all-patients-as-treated population, and objective response, analysed for the full-analysis set. This trial is registered with ClinicalTrials.gov, number NCT02054806, and is ongoing but not recruiting participants.
AB - FINDINGS: As of June 20, 2016, 25 patients received pembrolizumab. 16 (64%) patients reported a treatment-related adverse event; the most common adverse event were fatigue (six [24%]), nausea (six [24%]), and arthralgia (five [20%]). Five (20%) patients reported grade 3 treatment-related adverse events. Three (12%) patients required dose interruption because of immune-related adverse events: one (4%) of 25 each had grade 3 rhabdomyolysis and grade 2 hypothyroidism; grade 3 iridocyclitis, grade 1 erythema multiforme, and grade 3 erythema; and grade 2 infusion-related reaction. No treatment-related deaths or discontinuations occurred. Five (20%) patients had a partial response, for an objective response of 20% (95% CI 6.8-40.7), and 13 (52%) of 25 had stable disease. Responses were durable (median response duration 12.0 months [95% CI 3.7 to not reached]); two patients remained on treatment at data cutoff.
AB - INTERPRETATION: Pembrolizumab appears to be well tolerated and might confer anti-tumour activity in patients with PD-L1-positive malignant pleural mesothelioma. Response durability and efficacy in this patient population warrants further investigation.
AB - FUNDING: Merck.
AB - Copyright © 2017 Elsevier Ltd. All rights reserved.
ES - 1474-5488
IL - 1470-2045
DI - S1470-2045(17)30169-9
DO - https://dx.doi.org/10.1016/S1470-2045(17)30169-9
PT - Journal Article
ID - S1470-2045(17)30169-9 [pii]
ID - 10.1016/S1470-2045(17)30169-9 [doi]
PP - ppublish
PH - 2016/11/08 [received]
PH - 2017/01/11 [revised]
PH - 2017/01/18 [accepted]
LG - English
EP - 20170311
DP - 2017 May
DC - 20170314
EZ - 2017/03/15 06:00
DA - 2017/03/16 06:00
DT - 2017/03/16 06:00
YR - 2017
RD - 20170512
UP - 20170515
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28291584
<415. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28246107
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - De Velasco G
AU - Je Y
AU - Bosse D
AU - Awad MM
AU - Ott PA
AU - Moreira RB
AU - Schutz F
AU - Bellmunt J
AU - Sonpavde GP
AU - Hodi FS
AU - Choueiri TK
FA - De Velasco, Guillermo
FA - Je, Youjin
FA - Bosse, Dominick
FA - Awad, Mark M
FA - Ott, Patrick A
FA - Moreira, Raphael B
FA - Schutz, Fabio
FA - Bellmunt, Joaquim
FA - Sonpavde, Guru P
FA - Hodi, F Stephen
FA - Choueiri, Toni K
IN - De Velasco, Guillermo. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
IN - De Velasco, Guillermo. Department of Medical Oncology, University Hospital 12 de Octubre, Madrid, Spain.
IN - Je, Youjin. Department of Food and Nutrition, College of Human Ecology, Kyung Hee University, Seoul, Korea.
IN - Bosse, Dominick. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
IN - Awad, Mark M. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
IN - Ott, Patrick A. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
IN - Moreira, Raphael B. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
IN - Schutz, Fabio. Department of Medical Oncology, Hospital Sao Jose, Beneficencia Portuguesa de Sao Paulo, Brazil.
IN - Bellmunt, Joaquim. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
IN - Sonpavde, Guru P. Division of Oncology and Hematology, University of Alabama, Birmingham, Alabama.
IN - Hodi, F Stephen. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
IN - Choueiri, Toni K. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. toni_choueiri@dfci.harvard.edu.
TI - Comprehensive Meta-analysis of Key Immune-Related Adverse Events from CTLA-4 and PD-1/PD-L1 Inhibitors in Cancer Patients.
SO - Cancer Immunology Research. 5(4):312-318, 2017 Apr
AS - Cancer Immunol Res. 5(4):312-318, 2017 Apr
NJ - Cancer immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101614637
IO - Cancer Immunol Res
CP - United States
AB - Immune-related adverse events (irAE) have been described with immune checkpoint inhibitors (ICI), but the incidence and relative risk (RR) of irAEs associated with these drugs remains unclear. We selected five key irAEs from treatments with approved cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed death ligand 1 (PD-L1) inhibitors (ipilimumab, nivolumab, or pembrolizumab, and atezolizumab, respectively) to better characterize their safety profile. We performed a meta-analysis of randomized phase II/III immunotherapy trials, with non-ICI control arms, conducted between 1996 and 2016. We calculated the incidence and RR of selected all-grade and high-grade gastrointestinal, liver, skin, endocrine, and pulmonary irAEs across the trials using random-effect models. Twenty-one trials were included, totaling 11,454 patients, of whom 6,528 received an ICI (nivolumab, 1,534; pembrolizumab, 1,522; atezolizumab, 751; and ipilimumab, 2,721) and 4,926 had not. Compared with non-ICI arms, ICIs were associated with more all-grade colitis (RR 7.66, P < 0.001), aspartate aminotransferase (AST) elevation (RR 1.80; P = 0.020), rash (RR 2.50; P = 0.001), hypothyroidism (RR 6.81; P < 0.001), and pneumonitis (RR 4.14; P = 0.012). Rates of high-grade colitis (RR 5.85; P < 0.001) and AST elevation (RR 2.79; P = 0.014) were higher in the ICI arms. Ipilimumab was associated with a higher risk of all-grade rash (P = 0.006) and high-grade colitis (P = 0.021) compared with PD-1/PD-L1 ICIs. Incidence of fatal irAE was < 1%. This meta-analysis offers substantial evidence that ICIs are associated with a small but significant increase in risk of selected all-grade irAEs and high-grade gastrointestinal and liver toxicities. Although fatal irAEs remain rare, AEs should be recognized promptly as early interventions may alleviate future complications. Cancer Immunol Res; 5(4); 312-8. ©2017 AACR.
AB - Copyright ©2017 American Association for Cancer Research.
ES - 2326-6074
IL - 2326-6066
DI - 2326-6066.CIR-16-0237
DO - https://dx.doi.org/10.1158/2326-6066.CIR-16-0237
PT - Journal Article
ID - 2326-6066.CIR-16-0237 [pii]
ID - 10.1158/2326-6066.CIR-16-0237 [doi]
ID - PMC5418853 [pmc]
ID - NIHMS856814 [mid]
PP - ppublish
PH - 2016/09/12 [received]
PH - 2016/10/17 [revised]
PH - 2017/02/23 [accepted]
PH - 2017/10/01 [pmc-release]
GI - No: P50 CA101942
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20170228
DP - 2017 Apr
DC - 20170301
EZ - 2017/03/02 06:00
DA - 2017/03/02 06:00
DT - 2017/03/02 06:00
YR - 2017
RD - 20170507
UP - 20170509
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28246107
<416. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28334791
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Kitajima K
AU - Ashida K
AU - Wada N
AU - Suetsugu R
AU - Takeichi Y
AU - Sakamoto S
AU - Uchi H
AU - Matsushima T
AU - Shiratsuchi M
AU - Ohnaka K
AU - Furue M
AU - Nomura M
FA - Kitajima, Keiko
FA - Ashida, Kenji
FA - Wada, Naoko
FA - Suetsugu, Ryoko
FA - Takeichi, Yukina
FA - Sakamoto, Shohei
FA - Uchi, Hiroshi
FA - Matsushima, Takamitsu
FA - Shiratsuchi, Motoaki
FA - Ohnaka, Keizo
FA - Furue, Masutaka
FA - Nomura, Masatoshi
IN - Kitajima, Keiko. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
IN - Kitajima, Keiko. Department of Metabolism and Endocrinology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka.
IN - Ashida, Kenji. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
IN - Wada, Naoko. Department of Dermatology, Kyushu University Hospital, Fukuoka.
IN - Suetsugu, Ryoko. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
IN - Suetsugu, Ryoko. Department of Metabolism and Endocrinology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka.
IN - Takeichi, Yukina. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
IN - Sakamoto, Shohei. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
IN - Uchi, Hiroshi. Department of Dermatology, Kyushu University Hospital, Fukuoka.
IN - Matsushima, Takamitsu. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
IN - Shiratsuchi, Motoaki. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
IN - Ohnaka, Keizo. Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
IN - Furue, Masutaka. Department of Dermatology, Kyushu University Hospital, Fukuoka.
IN - Nomura, Masatoshi. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
TI - Isolated ACTH deficiency probably induced by autoimmune-related mechanism evoked with nivolumab.
SO - Japanese Journal of Clinical Oncology. 47(5):463-466, 2017 May 01
AS - Jpn J Clin Oncol. 47(5):463-466, 2017 May 01
NJ - Japanese journal of clinical oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - kin, 0313225
IO - Jpn. J. Clin. Oncol.
CP - England
KW - dermatology; endocrine-med; immunotherapy
AB - Nivolumab, an anti-programmed death-1 antibody, is a breakthrough treatment for several malignancies. Its specific adverse effects caused by autoimmunity are termed immune-related adverse events, which involve several endocrine dysfunctions. Herein, we report two cases of isolated adrenocorticotropic hormone (ACTH) deficiency induced by nivolumab for the treatment of metastatic malignant melanoma. Case 1 was a 39-year-old man and Case 2 was a 50-year-old woman, both of whom presented with progressive melanoma. After 13 courses of nivolumab administration, both cases were diagnosed with adrenal insufficiency. Despite their basal serum ACTH and cortisol levels being low with little response to corticotropin-releasing hormone loading, other anterior pituitary hormone levels were preserved. Based on these endocrinological data, isolated ACTH deficiency was diagnosed. Magnetic resonance imaging showed normal pituitary glands, excluding hypophysitis. Finally, hydrocortisone replacement enabled the patients to continue nivolumab treatment. Therefore, it is important to consider isolated ACTH syndrome as a possible and potentially severe immune-related adverse event of nivolumab, even when head magnetic resonance imaging of affected cases does not show enlargement. We should not misdiagnose hidden immune-related adverse events behind general complaints of malignancies such as general malaise and appetite loss, to allow successful treatment using this beneficial immune checkpoint inhibitor.
AB - Copyright © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
ES - 1465-3621
IL - 0368-2811
DI - 3003225
DO - https://dx.doi.org/10.1093/jjco/hyx018
PT - Journal Article
ID - 3003225 [pii]
ID - 10.1093/jjco/hyx018 [doi]
PP - ppublish
PH - 2016/08/06 [received]
PH - 2017/01/31 [accepted]
LG - English
DP - 2017 May 01
DC - 20170323
EZ - 2017/03/24 06:00
DA - 2017/03/24 06:00
DT - 2017/03/24 06:00
YR - 2017
RD - 20170505
UP - 20170508
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28334791
<417. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26068559
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Sheldon CA
AU - Kharlip J
AU - Tamhankar MA
FA - Sheldon, Claire A
FA - Kharlip, Julia
FA - Tamhankar, Madhura A
IN - Sheldon, Claire A. *Scheie Eye Institute, Department of Ophthalmology, and +Departments of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.
TI - Inflammatory Orbitopathy Associated With Ipilimumab.
SO - Ophthalmic Plastic & Reconstructive Surgery. 33(3S Suppl 1):S155-S158, 2017 May/Jun
AS - Ophthal Plast Reconstr Surg. 33(3S Suppl 1):S155-S158, 2017 May/Jun
NJ - Ophthalmic plastic and reconstructive surgery
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - ay2, 8508431
IO - Ophthal Plast Reconstr Surg
CP - United States
AB - In this case report, the clinical presentation of an inflammatory orbitopathy seen following treatment with ipilimumab is described. After 3 rounds of ipilimumab (10 mg/kg) treatment for Stage III metastatic melanoma, the subject of this case report developed acute eye pain and proptosis. At initial presentation, she had marked proptosis and diffuse severe ophthalmoparesis. After treatment with high-dose steroids, over a period of 6 months, the symptoms gradually resolved fully. Although the condition may mimic thyroid-associated orbitopathy, imaging and laboratory features suggest that the orbitopathy associated with ipilimumab is not a secondary effect of thyroid dysfunction but a distinct inflammatory condition. The authors conclude that immune-related side effects can occur with biologic agents used to treat malignancies and these side-effects can involve the eye. This case illustrates the occurrence of an inflammatory orbitopathy associated with ipilimumab treatment.
ES - 1537-2677
IL - 0740-9303
DO - https://dx.doi.org/10.1097/IOP.0000000000000509
PT - Journal Article
ID - 10.1097/IOP.0000000000000509 [doi]
PP - ppublish
LG - English
DP - 2017 May/Jun
DC - 20150612
EZ - 2015/06/13 06:00
DA - 2015/06/13 06:00
DT - 2015/06/13 06:00
YR - 2017
RD - 20170505
UP - 20170508
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=26068559
<418. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27941003
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Scharping NE
AU - Menk AV
AU - Whetstone RD
AU - Zeng X
AU - Delgoffe GM
FA - Scharping, Nicole E
FA - Menk, Ashley V
FA - Whetstone, Ryan D
FA - Zeng, Xue
FA - Delgoffe, Greg M
IN - Scharping, Nicole E. Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
IN - Scharping, Nicole E. Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania.
IN - Menk, Ashley V. Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
IN - Whetstone, Ryan D. Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
IN - Whetstone, Ryan D. Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania.
IN - Zeng, Xue. Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
IN - Delgoffe, Greg M. Tumor Microenvironment Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. delgoffeg@upmc.edu.
IN - Delgoffe, Greg M. Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania.
TI - Efficacy of PD-1 Blockade Is Potentiated by Metformin-Induced Reduction of Tumor Hypoxia.
SO - Cancer Immunology Research. 5(1):9-16, 2017 Jan
AS - Cancer Immunol Res. 5(1):9-16, 2017 Jan
NJ - Cancer immunology research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101614637
IO - Cancer Immunol Res
CP - United States
AB - Blockade of the coinhibitory checkpoint molecule PD-1 has emerged as an effective treatment for many cancers, resulting in remarkable responses. However, despite successes in the clinic, most patients do not respond to PD-1 blockade. Metabolic dysregulation is a common phenotype in cancer, but both patients and tumors are metabolically heterogeneous. We hypothesized that the deregulated oxidative energetics of tumor cells present a metabolic barrier to antitumor immunity through the generation of a hypoxic microenvironment and that normalization of tumor hypoxia might improve response to immunotherapy. We show that the murine tumor lines B16 and MC38 differed in their ability to consume oxygen and produce hypoxic environments, which correlated with their sensitivity to checkpoint blockade. Metformin, a broadly prescribed type II diabetes treatment, inhibited oxygen consumption in tumor cells in vitro and in vivo, resulting in reduced intratumoral hypoxia. Although metformin monotherapy had little therapeutic benefit in highly aggressive tumors, combination of metformin with PD-1 blockade resulted in improved intratumoral T-cell function and tumor clearance. Our data suggest tumor hypoxia acts as a barrier to immunotherapy and that remodeling the hypoxic tumor microenvironment has potential to convert patients resistant to immunotherapy into those that receive clinical benefit. Cancer Immunol Res; 5(1); 9-16. ©2016 AACR.
AB - Copyright ©2016 American Association for Cancer Research.
ES - 2326-6074
IL - 2326-6066
DI - 2326-6066.CIR-16-0103
DO - https://dx.doi.org/10.1158/2326-6066.CIR-16-0103
PT - Journal Article
ID - 2326-6066.CIR-16-0103 [pii]
ID - 10.1158/2326-6066.CIR-16-0103 [doi]
ID - PMC5340074 [pmc]
ID - NIHMS835819 [mid]
PP - ppublish
PH - 2016/05/11 [received]
PH - 2016/10/20 [revised]
PH - 2016/11/10 [accepted]
PH - 2018/01/01 [pmc-release]
GI - No: P30 CA047904
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA097190
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P50 CA121973
Organization: (CA) *NCI NIH HHS*
Country: United States
No: T32 CA082084
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20161209
DP - 2017 Jan
DC - 20161212
EZ - 2016/12/13 06:00
DA - 2016/12/13 06:00
DT - 2016/12/13 06:00
YR - 2017
RD - 20170502
UP - 20170503
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27941003
<419. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28343398
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Zhao P
AU - Atanackovic D
AU - Dong S
AU - Yagita H
AU - He X
AU - Chen M
AI - Chen, Mingnan; ORCID: http://orcid.org/0000-0002-7080-9804
FA - Zhao, Peng
FA - Atanackovic, Djordje
FA - Dong, Shuyun
FA - Yagita, Hideo
FA - He, Xiao
FA - Chen, Mingnan
IN - Zhao, Peng. Department of Pharmaceutics and Pharmaceutical Chemistry, The University of Utah , Salt Lake City, Utah 84112, United States.
IN - Atanackovic, Djordje. University of Utah School of Medicine , Salt Lake City, Utah 84112, United States.
IN - Dong, Shuyun. Department of Pharmaceutics and Pharmaceutical Chemistry, The University of Utah , Salt Lake City, Utah 84112, United States.
IN - Yagita, Hideo. Department of Immunology, Juntendo University School of Medicine , Tokyo, Japan.
IN - He, Xiao. Department of Pathology, The University of Utah , Salt Lake City, Utah 84112, United States.
IN - Chen, Mingnan. Department of Pharmaceutics and Pharmaceutical Chemistry, The University of Utah , Salt Lake City, Utah 84112, United States.
TI - An Anti-Programmed Death-1 Antibody (alphaPD-1) Fusion Protein That Self-Assembles into a Multivalent and Functional alphaPD-1 Nanoparticle.
SO - Molecular Pharmaceutics. 14(5):1494-1500, 2017 May 01
AS - Mol Pharm. 14(5):1494-1500, 2017 May 01
NJ - Molecular pharmaceutics
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101197791
IO - Mol. Pharm.
CP - United States
KW - anti-programmed death-1 antibody; diabetes; multivalency; nanoparticle; recombinant anti-programmed death-1 antibody fusion
AB - Cancer immune checkpoint therapy has achieved remarkable clinical successes in various cancers. However, current immune checkpoint inhibitors block the checkpoint of not only the immune cells that are important to cancer therapy but also the immune cells that are irrelevant to the therapy. Such an indiscriminate blockade limits the efficacy and causes the autoimmune toxicity of the therapy. It might be beneficial to use a carrier to target immune checkpoint inhibitors to cancer-reactive immune cells. Here, we explore a method to load the inhibitors into carriers. We used the anti-programmed death-1 antibody (alphaPD-1) as a model immune checkpoint inhibitor. First, we generated a recombinant single-chain variable fragment (scFv) of alphaPD-1. Then, we designed and generated a fusion protein consisting of the scFv and an amphiphilic immune-tolerant elastin-like polypeptide (iTEP). Because of the amphiphilic iTEP, the fusion was able to self-assemble into a nanoparticle (NP). The NP was proved to block the PD-1 immune checkpoint in vitro and in vivo. Particularly, the NP exacerbated diabetes development in nonobese diabetic mice as effectively as natural, intact alphaPD-1. In summary, we successfully expressed alphaPD-1 as a recombinant protein and linked alphaPD-1 to a NP, which lays a foundation to develop a delivery system to target alphaPD-1 to a subpopulation of immune cells.
ES - 1543-8392
IL - 1543-8384
DO - https://dx.doi.org/10.1021/acs.molpharmaceut.6b01021
PT - Journal Article
ID - 10.1021/acs.molpharmaceut.6b01021 [doi]
PP - ppublish
LG - English
EP - 20170419
DP - 2017 May 01
DC - 20170327
EZ - 2017/03/28 06:00
DA - 2017/03/28 06:00
DT - 2017/03/28 06:00
YR - 2017
RD - 20170501
UP - 20170502
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28343398
<420. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28073132
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Alhusseini M
AU - Samantray J
FA - Alhusseini, M
FA - Samantray, J
IN - Alhusseini, M. Division of Endocrinology, University Health Center, Wayne State University School of Medicine, Detroit, USA.
IN - Samantray, J. Division of Endocrinology, University Health Center, Wayne State University School of Medicine, Detroit, USA.
TI - Hypothyroidism in Cancer Patients on Immune Checkpoint Inhibitors with anti-PD1 Agents: Insights on Underlying Mechanisms.
SO - Experimental & Clinical Endocrinology & Diabetes. 125(4):267-269, 2017 Apr
AS - Exp Clin Endocrinol Diabetes. 125(4):267-269, 2017 Apr
NJ - Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ccv, 9505926
IO - Exp. Clin. Endocrinol. Diabetes
CP - Germany
AB - Background: Immune therapy using monoclonal antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) for various cancers have been reported to cause thyroid dysfunction. Little is known, however, about the underlying pathogenic mechanisms and the course of hypothyroidism that subsequently develops. In this report, we use the change in thyroglobulin and thyroid antibody levels in patients on immune therapy who develop hypothyroidism to better understand its pathogenesis as well as examine the status of hypothyroidism in the long term. Methods: We report a case series of 10 patients who developed hypothyroidism after initiation of immune therapy (either anti-PD-1 alone or in combination with anti-CTLA-4). Available thyroid antibodies including anti-thyroglobulin (anti-Tg), anti-thyroid peroxidase (anti-TPO), and thyroid stimulating immunoglobulin (TSI) were noted during the initial thyroiditis phase as well as the hypothyroid phase. Persistence or remission of hypothyroidism was noted at 6 months. Summary: During the thyroiditis phase, 50% of the patients had elevated Tg titers, 40% had elevated anti-Tg, and 40% had elevated TSI. All of these titers decreased during the hypothyroid phase. Permanent hypothyroidism was noted in 80% of the cases. Conclusion: Hypothyroidism following initiation of immune therapy has immunologic and non-immunologic mediated mechanisms and is likely to be persistent.
AB - Copyright © Georg Thieme Verlag KG Stuttgart . New York.
ES - 1439-3646
IL - 0947-7349
DO - https://dx.doi.org/10.1055/s-0042-119528
PT - Journal Article
ID - 10.1055/s-0042-119528 [doi]
PP - ppublish
LG - English
EP - 20170110
DP - 2017 Apr
DC - 20170110
EZ - 2017/01/11 06:00
DA - 2017/01/11 06:00
DT - 2017/01/11 06:00
YR - 2017
RD - 20170426
UP - 20170427
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28073132
<421. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28421161
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Maughan BL
AU - Bailey E
AU - Gill DM
AU - Agarwal N
FA - Maughan, Benjamin L
FA - Bailey, Erin
FA - Gill, David M
FA - Agarwal, Neeraj
IN - Maughan, Benjamin L. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
IN - Maughan, Benjamin L. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
IN - Bailey, Erin. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
IN - Gill, David M. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
IN - Agarwal, Neeraj. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
IN - Agarwal, Neeraj. Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
TI - Incidence of Immune-Related Adverse Events with Program Death Receptor-1- and Program Death Receptor-1 Ligand-Directed Therapies in Genitourinary Cancers. [Review]
SO - Frontiers in Oncology. 7:56, 2017
AS - Front. oncol.. 7:56, 2017
NJ - Frontiers in oncology
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101568867
IO - Front Oncol
CP - Switzerland
KW - autoimmune; checkpoint blockade; immune-related adverse events; immunotherapy; toxicity; treatment
AB - Program death receptor-1 (PD-1) and program death receptor-1 ligand (PD-L1) inhibitors are increasingly being used in the clinic to treat a growing number of malignancies, including many genitourinary (GU) malignancies. These immune-based therapies have demonstrated a distinct toxicity profile compared to traditional chemotherapy and the targeted therapies directed at the vascular endothelial growth factor pathway or the mammalian target of rapamycin pathway. Autoimmune toxicity targeting the skin, gastrointestinal tract, or the endocrine organs are some of the more common adverse events (AEs) noted with these therapies. Here in, we report the results of a systematic review of the incidence of toxicities in GU cancers reported in the phase II or phase III clinical trials using single-agent PD-1 or PD-L1 inhibitors. Overall, the rate of serious (grades 3-4) AEs was noted in approximately 15% of patients. The AEs noted were similar between all the agents tested, highlighting the overall class effect of these therapies. The incidence in GU cancers is similar to those seen in other malignancies. Given the widespread and high volume real-world use of these agents, it is important for oncologists to be familiar with these side effects to minimize the risks for patients while undergoing therapy.
IL - 2234-943X
DO - https://dx.doi.org/10.3389/fonc.2017.00056
PT - Journal Article
PT - Review
ID - 10.3389/fonc.2017.00056 [doi]
ID - PMC5377000 [pmc]
PP - epublish
PH - 2017/01/30 [received]
PH - 2017/03/14 [accepted]
LG - English
EP - 20170403
DP - 2017
DC - 20170419
EZ - 2017/04/20 06:00
DA - 2017/04/20 06:00
DT - 2017/04/20 06:00
YR - 2017
RD - 20170423
UP - 20170425
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28421161
<422. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28088513
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Karasaki T
AU - Nagayama K
AU - Kuwano H
AU - Nitadori JI
AU - Sato M
AU - Anraku M
AU - Hosoi A
AU - Matsushita H
AU - Morishita Y
AU - Kashiwabara K
AU - Takazawa M
AU - Ohara O
AU - Kakimi K
AU - Nakajima J
FA - Karasaki, Takahiro
FA - Nagayama, Kazuhiro
FA - Kuwano, Hideki
FA - Nitadori, Jun-Ichi
FA - Sato, Masaaki
FA - Anraku, Masaki
FA - Hosoi, Akihiro
FA - Matsushita, Hirokazu
FA - Morishita, Yasuyuki
FA - Kashiwabara, Kosuke
FA - Takazawa, Masaki
FA - Ohara, Osamu
FA - Kakimi, Kazuhiro
FA - Nakajima, Jun
IN - Karasaki, Takahiro. Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
IN - Nagayama, Kazuhiro. Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
IN - Kuwano, Hideki. Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
IN - Nitadori, Jun-Ichi. Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
IN - Sato, Masaaki. Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
IN - Anraku, Masaki. Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
IN - Hosoi, Akihiro. Department of Immunotherapeutics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Medinet Co. Ltd., Yokohama, Japan.
IN - Matsushita, Hirokazu. Department of Immunotherapeutics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
IN - Morishita, Yasuyuki. Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
IN - Kashiwabara, Kosuke. Department of Biostatistics, School of Public Health, The University of Tokyo, Tokyo, Japan.
IN - Takazawa, Masaki. Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan.
IN - Ohara, Osamu. Department of Technology Development, Kazusa DNA Research Institute, Kisarazu, Japan.
IN - Kakimi, Kazuhiro. Department of Immunotherapeutics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: kakimi@m.u-tokyo.ac.jp.
IN - Nakajima, Jun. Department of Thoracic Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
TI - An Immunogram for the Cancer-Immunity Cycle: Towards Personalized Immunotherapy of Lung Cancer.
SO - Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer. 12(5):791-803, 2017 May
AS - J Thorac Oncol. 12(5):791-803, 2017 May
NJ - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101274235
IO - J Thorac Oncol
CP - United States
KW - Cancer-immunity cycle; Immunogram; Lung cancer; Neoantigen; Transcriptome
AB - INTRODUCTION: The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of antitumor immunity as a dynamic spatiotemporal process is required for each individual patient. To this end, we developed an immunogram for the cancer-immunity cycle by using next-generation sequencing.
AB - METHODS: Whole exome sequencing and RNA sequencing were performed in 20 patients with NSCLC (12 with adenocarcinoma, seven with squamous cell carcinoma, and one with large cell neuroendocrine carcinoma). Mutated neoantigens and cancer germline antigens expressed in the tumor were assessed for predicted binding to patients' human leukocyte antigen molecules. The expression of genes related to cancer immunity was assessed and normalized to construct a radar chart composed of eight axes reflecting seven steps in the cancer-immunity cycle.
AB - RESULTS: Three immunogram patterns were observed in patients with lung cancer: T-cell-rich, T-cell-poor, and intermediate. The T-cell-rich pattern was characterized by gene signatures of abundant T cells, regulatory T cells, myeloid-derived suppressor cells, checkpoint molecules, and immune-inhibitory molecules in the tumor, suggesting the presence of antitumor immunity dampened by an immunosuppressive microenvironment. The T-cell-poor phenotype reflected lack of antitumor immunity, inadequate dendritic cell activation, and insufficient antigen presentation in the tumor. Immunograms for both the patients with adenocarcinoma and the patients with nonadenocarcinoma tumors included both T-cell-rich and T-cell-poor phenotypes, suggesting that histologic type does not necessarily reflect the cancer immunity status of the tumor.
AB - CONCLUSIONS: The patient-specific landscape of the tumor microenvironment can be appreciated by using immunograms as integrated biomarkers, which may thus become a valuable resource for optimal personalized immunotherapy.
AB - Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
ES - 1556-1380
IL - 1556-0864
DI - S1556-0864(17)30008-4
DO - https://dx.doi.org/10.1016/j.jtho.2017.01.005
PT - Journal Article
ID - S1556-0864(17)30008-4 [pii]
ID - 10.1016/j.jtho.2017.01.005 [doi]
PP - ppublish
PH - 2016/08/31 [received]
PH - 2016/11/21 [revised]
PH - 2017/01/04 [accepted]
LG - English
EP - 20170111
DP - 2017 May
DC - 20170115
EZ - 2017/01/16 06:00
DA - 2017/01/16 06:00
DT - 2017/01/16 06:00
YR - 2017
RD - 20170424
UP - 20170425
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28088513
<423. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28017788
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Usui Y
AU - Udagawa H
AU - Matsumoto S
AU - Imai K
AU - Ohashi K
AU - Ishibashi M
AU - Kirita K
AU - Umemura S
AU - Yoh K
AU - Niho S
AU - Osame K
AU - Goto K
FA - Usui, Yuko
FA - Udagawa, Hibiki
FA - Matsumoto, Shingo
FA - Imai, Kenjiro
FA - Ohashi, Ken
FA - Ishibashi, Masayuki
FA - Kirita, Keisuke
FA - Umemura, Shigeki
FA - Yoh, Kiyotaka
FA - Niho, Seiji
FA - Osame, Keiichiro
FA - Goto, Koichi
IN - Usui, Yuko. Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan. Electronic address: yusui@east.ncc.go.jp.
IN - Udagawa, Hibiki. Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan.
IN - Matsumoto, Shingo. Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan.
IN - Imai, Kenjiro. Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.
IN - Ohashi, Ken. Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.
IN - Ishibashi, Masayuki. Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan.
IN - Kirita, Keisuke. Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan.
IN - Umemura, Shigeki. Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan.
IN - Yoh, Kiyotaka. Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan.
IN - Niho, Seiji. Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan.
IN - Osame, Keiichiro. Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.
IN - Goto, Koichi. Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan.
TI - Association of Serum Anti-GAD Antibody and HLA Haplotypes with Type 1 Diabetes Mellitus Triggered by Nivolumab in Patients with Non-Small Cell Lung Cancer.
SO - Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer. 12(5):e41-e43, 2017 May
AS - J Thorac Oncol. 12(5):e41-e43, 2017 May
NJ - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101274235
IO - J Thorac Oncol
CP - United States
ES - 1556-1380
IL - 1556-0864
DI - S1556-0864(16)33605-X
DO - https://dx.doi.org/10.1016/j.jtho.2016.12.015
PT - Journal Article
ID - S1556-0864(16)33605-X [pii]
ID - 10.1016/j.jtho.2016.12.015 [doi]
PP - ppublish
PH - 2016/10/17 [received]
PH - 2016/12/08 [revised]
PH - 2016/12/16 [accepted]
LG - English
EP - 20161223
DP - 2017 May
DC - 20161226
EZ - 2016/12/27 06:00
DA - 2016/12/27 06:00
DT - 2016/12/27 06:00
YR - 2017
RD - 20170424
UP - 20170425
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28017788
<424. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28344807
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - King J
AU - de la Cruz J
AU - Lutzky J
AI - de la Cruz, Javier; ISNI: 0000 0004 0430 4458
AI - de la Cruz, Javier; GRID: 0000 0004 0430 4458
FA - King, Jeanelle
FA - de la Cruz, Javier
FA - Lutzky, Jose
IN - King, Jeanelle. Mount Sinai Comprehensive Cancer Center, Division of Hematology/Oncology, 4306 Alton Road, Miami Beach, FL 33140 USA.
IN - de la Cruz, Javier. Mount Sinai Medical Center, Department of Internal Medicine, 4300 Alton Road, Miami Beach, FL 33140 USA.
IN - Lutzky, Jose. Mount Sinai Comprehensive Cancer Center, Division of Hematology/Oncology, 4306 Alton Road, Miami Beach, FL 33140 USA.
TI - Ipilimumab-induced thrombotic thrombocytopenic purpura (TTP).
SO - Journal for Immunotherapy of Cancer. 5:19, 2017
AS - J Immunother Cancer. 5:19, 2017
NJ - Journal for immunotherapy of cancer
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Internet
JC - 101620585
IO - J Immunother Cancer
CP - England
AB - BACKGROUND: CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4) was the first immune checkpoint receptor clinically targeted for use in cancer treatment. It is expressed exclusively on T-cells where its primary role is to regulate the amplitude of the early stages of T-cell activation.1 Ipilimumab, a CTLA-4 blocking antibody, has been widely used for the treatment of patients with high risk and metastatic melanoma. Given its mechanism of action and consequent immune activation, the side effect profile of this drug greatly differs from that of standard cytotoxic chemotherapy. Adverse events are from the most part immune-mediated, ranging from the more common, such as rash and fatigue, to the less common, such as immune endocrinopathy and colitis.
AB - CASE PRESENTATION: We describe a case of immune-mediated thrombotic thrombocytopenic purpura (TTP) in a 68 year-old woman with high risk, stage III melanoma occurring after 3 cycles of adjuvant treatment with ipilimumab as part of a clinical trial.
AB - CONCLUSION: The range of immune-mediated adverse events during treatment with ipilimumab is wide and varied and clinicians should have a high degree of suspicion when managing these patients.
ES - 2051-1426
IL - 2051-1426
DI - 224
DO - https://dx.doi.org/10.1186/s40425-017-0224-7
PT - Journal Article
ID - 10.1186/s40425-017-0224-7 [doi]
ID - 224 [pii]
ID - PMC5360069 [pmc]
PP - epublish
PH - 2016/07/26 [received]
PH - 2017/02/13 [accepted]
LG - English
EP - 20170321
DP - 2017
DC - 20170327
EZ - 2017/03/28 06:00
DA - 2017/03/28 06:00
DT - 2017/03/28 06:00
YR - 2017
RD - 20170421
UP - 20170424
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28344807
<425. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28239466
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Khan U
AU - Rizvi H
AU - Sano D
AU - Chiu J
AU - Hadid T
AI - Khan, Uqba; ORCID: https://orcid.org/0000-0002-4740-2256
AI - Khan, Uqba; GRID: grid.416413.5
AI - Rizvi, Humaira; GRID: grid.416413.5
AI - Sano, Dahlia; GRID: grid.416413.5
AI - Chiu, Jane; GRID: grid.416413.5
AI - Hadid, Tarik; GRID: grid.416413.5
FA - Khan, Uqba
FA - Rizvi, Humaira
FA - Sano, Dahlia
FA - Chiu, Jane
FA - Hadid, Tarik
IN - Khan, Uqba. Department of Hematology/Oncology, St. John Hospital and Medical Center, 19229 Mack Ave Suite 23 Grosse Pointe Woods, Detroit, 48236 Michigan USA.
IN - Rizvi, Humaira. Department of Hematology/Oncology, St. John Hospital and Medical Center, 19229 Mack Ave Suite 23 Grosse Pointe Woods, Detroit, 48236 Michigan USA.
IN - Sano, Dahlia. Department of Hematology/Oncology, St. John Hospital and Medical Center, 19229 Mack Ave Suite 23 Grosse Pointe Woods, Detroit, 48236 Michigan USA.
IN - Chiu, Jane. Department of Hematology/Oncology, St. John Hospital and Medical Center, 19229 Mack Ave Suite 23 Grosse Pointe Woods, Detroit, 48236 Michigan USA.
IN - Hadid, Tarik. Department of Hematology/Oncology, St. John Hospital and Medical Center, 19229 Mack Ave Suite 23 Grosse Pointe Woods, Detroit, 48236 Michigan USA.
TI - Nivolumab induced myxedema crisis.
SO - Journal for Immunotherapy of Cancer. 5:13, 2017
AS - J Immunother Cancer. 5:13, 2017
NJ - Journal for immunotherapy of cancer
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Internet
JC - 101620585
IO - J Immunother Cancer
CP - England
KW - Hyperthyroidism; Immunotherapy; Myxedema crisis; Nivolumab
AB - BACKGROUND: Nivolumab is an anti-programmed cell death (anti-PD-1) monoclonal antibody that is approved by Food and Drug Administration for treatment of metastatic non-small cell lung cancer, metastatic melanoma, relapsed Hodgkin lymphoma and advanced renal cell cancer. We report a rare case of myxedema crisis induced by nivolumab in a patient with metastatic squamous cell carcinoma of lung.
AB - CASE PRESENTATION: Fifty three-year old woman with metastatic squamous cell carcinoma currently on treatment with nivolumab presented with diffuse facial and tongue swelling, slurred speech, depressed mentation, fatigue and weakness. Initial evaluation revealed severe hypothyroidism with thyroid stimulating hormone of 237 micro Unit/mL (Normal Reference range: 0.27-4.20 micro unit/mL) and undetectable free T4. Patient was diagnosed with nivolumab induced myxedema crisis. She was treated successfully with levothyroxine with complete resolution of her symptoms. Nivolumab was safely restarted once the symptoms of myxedema resolved.
AB - CONCLUSION: Nivolumab can cause immune-mediated endocrinopathies including thyroiditis, hypophysitis, adrenal insufficiency and type 1 diabetes mellitus. High index of suspicion and periodic measurement of thyroid function tests are recommended in patients receiving nivolumab therapy. Our case also suggests that once the myxedema crisis is treated and symptoms are resolved, nivolumab can be safely re-challenged.
ES - 2051-1426
IL - 2051-1426
DI - 213
DO - https://dx.doi.org/10.1186/s40425-017-0213-x
PT - Journal Article
ID - 10.1186/s40425-017-0213-x [doi]
ID - 213 [pii]
ID - PMC5319087 [pmc]
PP - epublish
PH - 2016/09/30 [received]
PH - 2017/01/23 [accepted]
LG - English
EP - 20170221
DP - 2017
DC - 20170227
EZ - 2017/02/28 06:00
DA - 2017/02/28 06:00
DT - 2017/02/28 06:00
YR - 2017
RD - 20170421
UP - 20170424
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28239466
<426. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28174665
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Paraghamian SE
AU - Longoria TC
AU - Eskander RN
AI - Paraghamian, Sarah E; ISNI: 0000 0004 0434 883X
AI - Paraghamian, Sarah E; GRID: 0000 0004 0434 883X
AI - Longoria, Teresa C; ISNI: 0000 0004 0434 883X
AI - Longoria, Teresa C; GRID: 0000 0004 0434 883X
AI - Eskander, Ramez N; ISNI: 0000 0004 0434 883X
AI - Eskander, Ramez N; GRID: 0000 0004 0434 883X
FA - Paraghamian, Sarah E
FA - Longoria, Teresa C
FA - Eskander, Ramez N
IN - Paraghamian, Sarah E. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of California Irvine Medical Center, 33 City Blvd. West #1400, Orange, CA 92868 USA.
IN - Longoria, Teresa C. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of California Irvine Medical Center, 33 City Blvd. West #1400, Orange, CA 92868 USA.
IN - Eskander, Ramez N. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of California Irvine Medical Center, 33 City Blvd. West #1400, Orange, CA 92868 USA.
TI - Metastatic small cell neuroendocrine carcinoma of the cervix treated with the PD-1 inhibitor, nivolumab: a case report.
SO - Gynecologic Oncology Research and Practice. 4:3, 2017
AS - Gynecol Oncol Res Pract. 4:3, 2017
NJ - Gynecologic oncology research and practice
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101676223
IO - Gynecol Oncol Res Pract
CP - England
KW - Cervical cancer; Immunotherapy; Nivolumab; PD-1 inhibitor; Small cell neuroendocrine carcinoma
AB - BACKGROUND: Nivolumab is an immune checkpoint inhibitor specific for the programmed death 1 (PD-1) receptor that has led to clinical responses in many cancer types. Identifying biomarkers predictive of response to PD-1 blockade is an area of active investigation.
AB - CASE PRESENTATION: We present a patient with recurrent, metastatic, PD-L1-negative small cell neuroendocrine carcinoma of the cervix (SCNEC) who experienced a complete response to nivolumab. Though nivolumab was discontinued over 4 months ago due to treatment-related adverse events, she continues to have no evidence of disease.
AB - CONCLUSIONS: Immune checkpoint inhibitors may be active in neuroendocrine cervical cancer, with potential for dramatic responses in a modest subset of patients.
IL - 2053-6844
DI - 38
DO - https://dx.doi.org/10.1186/s40661-017-0038-9
PT - Journal Article
ID - 10.1186/s40661-017-0038-9 [doi]
ID - 38 [pii]
ID - PMC5290639 [pmc]
PP - epublish
PH - 2016/12/31 [received]
PH - 2017/01/21 [accepted]
LG - English
EP - 20170202
DP - 2017
DC - 20170208
EZ - 2017/02/09 06:00
DA - 2017/02/09 06:00
DT - 2017/02/09 06:00
YR - 2017
RD - 20170421
UP - 20170424
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28174665
<427. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28275115
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Nishijima TF
AU - Shachar SS
AU - Nyrop KA
AU - Muss HB
FA - Nishijima, Tomohiro F
FA - Shachar, Shlomit S
FA - Nyrop, Kirsten A
FA - Muss, Hyman B
IN - Nishijima, Tomohiro F. UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA Tomohiro.Nishijima@unchealth.unc.edu.
IN - Shachar, Shlomit S. Division of Oncology, Rambam Health Care Campus, Haifa, Israel.
IN - Nyrop, Kirsten A. UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA.
IN - Muss, Hyman B. UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA.
TI - Safety and Tolerability of PD-1/PD-L1 Inhibitors Compared with Chemotherapy in Patients with Advanced Cancer: A Meta-Analysis. [Review]
SO - Oncologist. 22(4):470-479, 2017 Apr
AS - Oncologist. 22(4):470-479, 2017 Apr
NJ - The oncologist
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dd5, 9607837
IO - Oncologist
CP - United States
KW - Chemotherapy; Meta-analysis; PD-1/PD-L1 inhibitor; Systematic review; Toxicity
AB - BACKGROUND: Compared with chemotherapy, significant improvement in survival outcomes with the programmed death receptor-1 (PD-1) inhibitors nivolumab and pembrolizumab and the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab has been shown in several types of advanced solid tumors. We conducted a systematic review and meta-analysis to compare safety and tolerability between PD-1/PD-L1 inhibitors and chemotherapy.
AB - METHODS: PubMed and American Society of Clinical Oncology (ASCO) databases were searched 1966 to September 2016. Eligible studies included randomized controlled trials (RCTs) comparing single-agent U.S. Food and Drug Administration-approved PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, or atezolizumab) with chemotherapy in cancer patients reporting any all-grade (1-4) or high-grade (3-4) adverse events (AEs), all- or high-grade treatment-related symptoms, hematologic toxicities and immune-related AEs, treatment discontinuation due to toxicities, or treatment-related deaths. The summary incidence, relative risk, and 95% confidence intervals were calculated.
AB - RESULTS: A total of 3,450 patients from 7 RCTs were included in the meta-analysis: 4 nivolumab, 2 pembrolizumab, and 1 atezolizumab trials. The underlying malignancies included were non-small cell lung cancer (4 trials) and melanoma (3 trials). Compared with chemotherapy, the PD-1/PD-L1 inhibitors had a significantly lower risk of all- and high-grade fatigue, sensory neuropathy, diarrhea and hematologic toxicities, all-grade anorexia, nausea, and constipation, any all- and high-grade AEs, and treatment discontinuation. There was an increased risk of all-grade rash, pruritus, colitis, aminotransferase elevations, hypothyroidism, and hyperthyroidism, and all- and high-grade pneumonitis with PD1/PD-L1 inhibitors.
AB - CONCLUSION: PD-1/PD-L1 inhibitors are overall better tolerated than chemotherapy. Our results provide further evidence supporting the favorable risk/benefit ratio for PD-1/PD-L1 inhibitors. The Oncologist 2017;22:470-479 IMPLICATIONS FOR PRACTICE: We conducted a systematic review and meta-analysis to compare summary toxicity endpoints and clinically relevant adverse events between programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy. PD1/PD-L1 inhibitors were associated with a lower risk of treatment-related symptoms (fatigue, anorexia, nausea, diarrhea, constipation, and sensory neuropathy) but a higher risk of immune-related adverse events (AEs). Summary toxicity endpoints favor PD1/PD-L1 inhibitors (any all- and high-grade AEs and treatment discontinuation). PD1/PD-L1 inhibitors are overall better tolerated than chemotherapy. In addition to efficacy data from trials, our findings provide useful information for clinicians for well-balanced discussions with their patients on the risks and benefits of treatment options for advanced cancer.
AB - Copyright © AlphaMed Press 2017.
ES - 1549-490X
IL - 1083-7159
DI - theoncologist.2016-0419
DO - https://dx.doi.org/10.1634/theoncologist.2016-0419
PT - Journal Article
PT - Review
ID - theoncologist.2016-0419 [pii]
ID - 10.1634/theoncologist.2016-0419 [doi]
ID - PMC5388381 [pmc]
PP - ppublish
PH - 2016/10/22 [received]
PH - 2016/12/16 [accepted]
PH - 2018/04/01 [pmc-release]
LG - English
EP - 20170308
DP - 2017 Apr
DC - 20170309
EZ - 2017/03/10 06:00
DA - 2017/03/10 06:00
DT - 2017/03/10 06:00
YR - 2017
RD - 20170416
UP - 20170418
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28275115
<428. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28393006
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Imakita T
AU - Fujita K
AU - Kanai O
AU - Terashima T
AU - Mio T
FA - Imakita, Takuma
FA - Fujita, Kohei
FA - Kanai, Osamu
FA - Terashima, Tsuyoshi
FA - Mio, Tadashi
IN - Imakita, Takuma. Division of Respiratory Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan; Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Hyogo, Japan.
IN - Fujita, Kohei. Division of Respiratory Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
IN - Kanai, Osamu. Division of Respiratory Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
IN - Terashima, Tsuyoshi. Division of Clinical Pathology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
IN - Mio, Tadashi. Division of Respiratory Medicine, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
TI - Small cell lung cancer transformation during immunotherapy with nivolumab: A case report.
SO - Respiratory Medicine Case Reports. 21:52-55, 2017
AS - Respir Med Case Rep. 21:52-55, 2017
NJ - Respiratory medicine case reports
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101604463
IO - Respir Med Case Rep
CP - England
KW - Immune checkpoint inhibitor; NSCLC; Nivolumab; SCLC transformation
AB - We report a rare case of transformation of non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC), without epidermal growth factor receptor (EGFR) gene mutation, during immunotherapy treatment with nivolumab. A 75-year-old man was referred to our hospital following the observation of a 64 mm mass in a chest computed tomography (CT) scan. A transbronchial biopsy of the mass identified the pathological presence of poorly differentiated NSCLC, with no histological signs of SCLC. No mutations were identified in the EGFR gene. A clinical diagnosis of NSCLC (cT3N3M1a, stage IV) was made following a positron emission tomography (PET)-CT scan and enhanced brain magnetic resonance imaging. Docetaxel and bevacizumab were selected as the first-line chemotherapy regimen; however, after two cycles, the patient developed a gastrointestinal perforation, and discontinuation of cytotoxic chemotherapy was recommended. Owing to gradual disease progression, immunotherapy with nivolumab was selected as the second-line regimen. During the immunotherapy, the tumor continued to progress and some subcutaneous tumors emerged. Biopsy of a subcutaneous tumor revealed SCLC, with positive immunostaining for cluster of differentiation 56, synaptophysin, and thyroid transcription factor-1. Serum tumor markers of SCLC were also elevated. Based on these results, we concluded that in this case NSCLC had transformed to SCLC during immunotherapy with nivolumab.
IL - 2213-0071
DI - S2213-0071(17)30096-5
DO - https://dx.doi.org/10.1016/j.rmcr.2017.03.019
PT - Journal Article
ID - 10.1016/j.rmcr.2017.03.019 [doi]
ID - S2213-0071(17)30096-5 [pii]
ID - PMC5376266 [pmc]
PP - epublish
PH - 2017/03/14 [received]
PH - 2017/03/26 [revised]
PH - 2017/03/27 [accepted]
LG - English
EP - 20170329
DP - 2017
DC - 20170410
EZ - 2017/04/11 06:00
DA - 2017/04/11 06:00
DT - 2017/04/11 06:00
YR - 2017
RD - 20170413
UP - 20170417
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28393006
<429. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27934619
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Ishikawa K
AU - Shono-Saito T
AU - Yamate T
AU - Kai Y
AU - Sakai T
AU - Shimizu F
AU - Yamada Y
AU - Mori H
AU - Noso S
AU - Ikegami H
AU - Kojima H
AU - Tanaka H
AU - Fujiwara S
AU - Hatano Y
FA - Ishikawa, Kazushi
FA - Shono-Saito, Tomoko
FA - Yamate, Tomoko
FA - Kai, Yoshitaka
FA - Sakai, Takashi
FA - Shimizu, Fumiaki
FA - Yamada, Yasunari
FA - Mori, Hiromu
FA - Noso, Shinsuke
FA - Ikegami, Hiroshi
FA - Kojima, Hiroto
FA - Tanaka, Hidenori
FA - Fujiwara, Sakuhei
FA - Hatano, Yutaka
IN - Ishikawa, Kazushi. Department of Dermatology.
IN - Shono-Saito, Tomoko. Department of Dermatology.
IN - Yamate, Tomoko. Department of Dermatology.
IN - Kai, Yoshitaka. Department of Dermatology.
IN - Sakai, Takashi. Department of Dermatology.
IN - Shimizu, Fumiaki. Department of Plastic Surgery.
IN - Yamada, Yasunari. Department of Radiology Faculty of Medicine, Oita University 1-1 Idaigaoka, Hasama-machi Yufu 879-5593, Japan.
IN - Mori, Hiromu. Department of Radiology Faculty of Medicine, Oita University 1-1 Idaigaoka, Hasama-machi Yufu 879-5593, Japan.
IN - Noso, Shinsuke. Department of Endocrinology Metabolism and Diabetes, Kindai University Faculty of Medicine 377-2 Ohno-higashi, Osaka-sayama Osaka 589-8511, Japan.
IN - Ikegami, Hiroshi. Department of Endocrinology Metabolism and Diabetes, Kindai University Faculty of Medicine 377-2 Ohno-higashi, Osaka-sayama Osaka 589-8511, Japan.
IN - Kojima, Hiroto. HLA Foundation Laboratory Kyoto, Japan.
IN - Tanaka, Hidenori. HLA Foundation Laboratory Kyoto, Japan.
IN - Fujiwara, Sakuhei. Department of Dermatology.
IN - Hatano, Yutaka. Department of Dermatology.
TI - A case of fulminant type 1 diabetes mellitus, with a precipitous decrease in pancreatic volume, induced by nivolumab for malignant melanoma: analysis of HLA and CTLA-4 polymorphisms.
SO - European Journal of Dermatology. 27(2):184-185, 2017 Apr 01
AS - Eur J Dermatol. 27(2):184-185, 2017 Apr 01
NJ - European journal of dermatology : EJD
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - c4s, 9206420
IO - Eur J Dermatol
CP - France
ES - 1952-4013
IL - 1167-1122
DI - ejd.2016.2923
DO - https://dx.doi.org/10.1684/ejd.2016.2923
PT - Journal Article
ID - ejd.2016.2923 [pii]
ID - 10.1684/ejd.2016.2923 [doi]
PP - ppublish
LG - English
DP - 2017 Apr 01
DC - 20161209
EZ - 2016/12/10 06:00
DA - 2016/12/10 06:00
DT - 2016/12/10 06:00
YR - 2017
RD - 20170412
UP - 20170413
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27934619
<430. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28246759
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Foller S
AU - Oppel-Heuchel H
AU - Fetter I
AU - Winkler Y
AU - Grimm MO
FA - Foller, S
FA - Oppel-Heuchel, H
FA - Fetter, I
FA - Winkler, Y
FA - Grimm, M-O
IN - Foller, S. Urologische Klinik und Poliklinik, Universitatsklinikum Jena, Lessingstrase 1, 07743, Jena, Deutschland. Susan.Foller@med.uni-jena.de.
IN - Oppel-Heuchel, H. Urologische Klinik und Poliklinik, Universitatsklinikum Jena, Lessingstrase 1, 07743, Jena, Deutschland.
IN - Fetter, I. Urologische Klinik und Poliklinik, Universitatsklinikum Jena, Lessingstrase 1, 07743, Jena, Deutschland.
IN - Winkler, Y. Urologische Klinik und Poliklinik, Universitatsklinikum Jena, Lessingstrase 1, 07743, Jena, Deutschland.
IN - Grimm, M-O. Urologische Klinik und Poliklinik, Universitatsklinikum Jena, Lessingstrase 1, 07743, Jena, Deutschland.
TI - [Adverse events of immune checkpoint inhibitors]. [German]
OT - Nebenwirkungen der Immun-Checkpoint-Inhibitoren.
SO - Urologe (Ausg. A). 56(4):486-491, 2017 Apr
AS - Urologe A. 56(4):486-491, 2017 Apr
NJ - Der Urologe. Ausg. A
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - wsj, 1304110
IO - Urologe A
CP - Germany
KW - Adverse events, immune-mediated; Corticosteroids; Immunotherapy; PD-1 inhibitor; PD-L1 inhibitor
AB - After immune checkpoint inhibitor therapy was approved for renal cell carcinoma last year, this new immune therapy has spread to urology. Further approvals (atezolizumab, nivolumab, pembrolizumab) are expected in 2017 for metastatic urothelial carcinoma that has progressed following treatment with platinum-based chemotherapy. With expanding use of immune checkpoint inhibitors, experience in diagnosing and managing immune-mediated adverse events increases. Although of low incidence, grade 3/4 toxicities play a central role. Organs most common for immune-mediated adverse events are skin, liver (hepatitis), kidneys (nephritis), gastrointestinal tract (diarrhea and colitis), lungs (pneumonitis), and endocrine organs (hyper-, hypothyroidism and hypophysitis). Diagnostic workup includes routine laboratory tests (including liver function tests) and may be supplemented with hormone values. In cases of pneumonitis or hypophysitis, imaging (high-resolution CT, MRI) can confirm diagnoses. Immune-mediated toxicities are treated with therapy interruption and administration of corticosteroids (and in individual cases additional immunosuppression). Dose modification is not intended!
ES - 1433-0563
IL - 0340-2592
DI - 10.1007/s00120-017-0342-3
DO - https://dx.doi.org/10.1007/s00120-017-0342-3
PT - English Abstract
PT - Journal Article
ID - 10.1007/s00120-017-0342-3 [doi]
ID - 10.1007/s00120-017-0342-3 [pii]
PP - ppublish
LG - German
DP - 2017 Apr
DC - 20170301
EZ - 2017/03/02 06:00
DA - 2017/03/02 06:00
DT - 2017/03/02 06:00
YR - 2017
RD - 20170408
UP - 20170410
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28246759
<431. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27825291
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Shi RL
AU - Qu N
AU - Luo TX
AU - Xiang J
AU - Liao T
AU - Sun GH
AU - Wang Y
AU - Wang YL
AU - Huang CP
AU - Ji QH
FA - Shi, Rong-Liang
FA - Qu, Ning
FA - Luo, Ting-Xian
FA - Xiang, Jun
FA - Liao, Tian
FA - Sun, Guo-Hua
FA - Wang, Yu
FA - Wang, Yu-Long
FA - Huang, Cai-Ping
FA - Ji, Qing-Hai
IN - Shi, Rong-Liang. 1 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University , Shanghai, China .
IN - Shi, Rong-Liang. 2 Department of General Surgery, Minhang Hospital, Fudan University , Shanghai, China .
IN - Qu, Ning. 1 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University , Shanghai, China .
IN - Luo, Ting-Xian. 1 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University , Shanghai, China .
IN - Xiang, Jun. 1 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University , Shanghai, China .
IN - Liao, Tian. 1 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University , Shanghai, China .
IN - Sun, Guo-Hua. 1 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University , Shanghai, China .
IN - Wang, Yu. 1 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University , Shanghai, China .
IN - Wang, Yu-Long. 1 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University , Shanghai, China .
IN - Huang, Cai-Ping. 1 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University , Shanghai, China .
IN - Ji, Qing-Hai. 1 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University , Shanghai, China .
TI - Programmed Death-Ligand 1 Expression in Papillary Thyroid Cancer and Its Correlation with Clinicopathologic Factors and Recurrence.
SO - Thyroid. 27(4):537-545, 2017 Apr
AS - Thyroid. 27(4):537-545, 2017 Apr
NJ - Thyroid : official journal of the American Thyroid Association
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - bjw, 9104317
IO - Thyroid
CP - United States
KW - biological marker; papillary thyroid cancer; programmed death-ligand 1; survival analysis
AB - BACKGROUND: Programmed death-ligand 1 (PD-L1) expression has been reported in several malignancies, but the expression of PD-L1 in papillary thyroid cancer (PTC) has been characterized rarely. The aim of this study was to assess the significance of PD-L1 expression and its associations with clinicopathologic factors and disease outcome in PTC.
AB - METHODS: Immunohistochemistry staining was conducted retrospectively to evaluate the expression of PD-L1 in a total of 260 PTC tumors and corresponding non-tumor tissues. The correlations between PD-L1 expressions with clinicopathologic features and recurrence-free survival (RFS) were analyzed.
AB - RESULTS: PD-L1 expression was positive in 52.3% (136/260) of PTC tumor tissues, which was significantly higher than in corresponding non-tumor thyroid tissues. In clinicopathologic analyses, this positive staining of PD-L1 was positively linked to multifocality (p=0.001) and extrathyroidal extension (p=0.001). In multivariate Cox regression analysis, positive PD-L1 expression in tumor tissue was significantly associated with worse RFS (hazard ratio 2.825 [confidence interval 1.149-6.943], p=0.024). In subgroup analyses based on clinicopathologic factors, positive PD-L1 staining of tumor tissue was associated with worse RFS in males (p=0.001), older patients (>=45 years; p=0.001), and patients with a primary tumor size >4cm (p=0.002), multifocal tumors (p=0.031), extrathyroidal extension (p=0.012), and lymph node metastasis (p=0.004). In contrast, positive PD-L1 staining predicted worse RFS in the subgroup of patients without Hashimoto's thyroiditis (p=0.001) and treated with total thyroidectomy (p=0.019).
AB - CONCLUSIONS: PD-L1 is important in determining aggressiveness of PTC and could predict the prognosis of patients. Therefore, inhibition of PD-L1 is suggested as a potential strategy for the treatment of advanced PTC with high expression of PD-L1.
ES - 1557-9077
IL - 1050-7256
DO - https://dx.doi.org/10.1089/thy.2016.0228
PT - Journal Article
ID - 10.1089/thy.2016.0228 [doi]
PP - ppublish
LG - English
EP - 20170124
DP - 2017 Apr
DC - 20161109
EZ - 2016/11/10 06:00
DA - 2016/11/09 06:00
DT - 2016/11/09 06:00
YR - 2017
RD - 20170404
UP - 20170406
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27825291
<432. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28345313
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Hwangbo Y
AU - Lee EK
AI - Lee, Eun Kyung; ORCID: http://orcid.org/0000-0003-0098-0873
FA - Hwangbo, Yul
FA - Lee, Eun Kyung
IN - Hwangbo, Yul. Department of Internal Medicine, Center for Thyroid Cancer, National Cancer Center, Goyang, Korea.
IN - Lee, Eun Kyung. Department of Internal Medicine, Center for Thyroid Cancer, National Cancer Center, Goyang, Korea. waterfol@ncc.re.kr.
TI - Acute Hyperglycemia Associated with Anti-Cancer Medication. [Review]
SO - Endocrinology and Metabolism. 32(1):23-29, 2017 Mar
AS - Endocrinol Metab (Seoul). 32(1):23-29, 2017 Mar
NJ - Endocrinology and metabolism (Seoul, Korea)
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 101554139
IO - Endocrinol Metab (Seoul)
CP - Korea (South)
KW - Cytotoxic chemotherapy; Drug therapy; Hyperglycemia; Immunotherapy; Mammalian target of rapamycin inhibitor; Neoplasms
AB - Hyperglycemia during chemotherapy occurs in approximately 10% to 30% of patients. Glucocorticoids and L-asparaginase are well known to cause acute hyperglycemia during chemotherapy. Long-term hyperglycemia is also frequently observed, especially in patients with hematologic malignancies treated with L-asparaginase-based regimens and total body irradiation. Glucocorticoid-induced hyperglycemia often develops because of increased insulin resistance, diminished insulin secretion, and exaggerated hepatic glucose output. Screening strategies for this condition include random glucose testing, hemoglobin A1c testing, oral glucose loading, and fasting plasma glucose screens. The management of hyperglycemia starts with insulin or sulfonylurea, depending on the type, dose, and delivery of the glucocorticoid formulation. Mammalian target of rapamycin (mTOR) inhibitors are associated with a high incidence of hyperglycemia, ranging from 13% to 50%. Immunotherapy, such as anti-programmed death 1 (PD-1) antibody treatment, induces hyperglycemia with a prevalence of 0.1%. The proposed mechanism of immunotherapy-induced hyperglycemia is an autoimmune process (insulitis). Withdrawal of the PD-1 inhibitor is the primary treatment for severe hyperglycemia. The efficacy of glucocorticoid therapy is not fully established and the decision to resume PD-1 inhibitor therapy depends on the severity of the hyperglycemia. Diabetic patients should achieve optimized glycemic control before initiating treatment, and glucose levels should be monitored periodically in patients initiating mTOR inhibitor or PD-1 inhibitor therapy. With regard to hyperglycemia caused by anti-cancer therapy, frequent monitoring and proper management are important for promoting the efficacy of anti-cancer therapy and improving patients' quality of life.
AB - Copyright © 2017 Korean Endocrine Society.
CI - No potential conflict of interest relevant to this article was reported.
IS - 2093-596X
IL - 2093-596X
DI - 32.23
DO - https://dx.doi.org/10.3803/EnM.2017.32.1.23
PT - Journal Article
PT - Review
ID - 32.23 [pii]
ID - 10.3803/EnM.2017.32.1.23 [doi]
ID - PMC5368117 [pmc]
PP - ppublish
PH - 2017/01/16 [received]
PH - 2017/02/01 [revised]
PH - 2017/02/16 [accepted]
LG - English
DP - 2017 Mar
DC - 20170327
EZ - 2017/03/28 06:00
DA - 2017/03/28 06:00
DT - 2017/03/28 06:00
YR - 2017
RD - 20170403
UP - 20170404
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28345313
<433. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28255845
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Hickmott L
AU - De La Pena H
AU - Turner H
AU - Ahmed F
AU - Protheroe A
AU - Grossman A
AU - Gupta A
AI - Hickmott, Laura; ORCID: http://orcid.org/0000-0002-5119-6416
FA - Hickmott, Laura
FA - De La Pena, Hugo
FA - Turner, Helen
FA - Ahmed, Fathelrahman
FA - Protheroe, Andrew
FA - Grossman, Ashley
FA - Gupta, Avinash
IN - Hickmott, Laura. Department of Oncology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK. laura.hickmott@nhs.net.
IN - De La Pena, Hugo. Department of Oncology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK.
IN - Turner, Helen. Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK.
IN - Ahmed, Fathelrahman. Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK.
IN - Protheroe, Andrew. Department of Oncology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK.
IN - Grossman, Ashley. Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK.
IN - Gupta, Avinash. Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, M20 4BX, UK.
TI - Anti-PD-L1 atezolizumab-Induced Autoimmune Diabetes: a Case Report and Review of the Literature. [Review]
SO - Targeted Oncology. 12(2):235-241, 2017 Apr
AS - Target. oncol.. 12(2):235-241, 2017 Apr
NJ - Targeted oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101270595
IO - Target Oncol
CP - France
AB - Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors trigger an immune-mediated anti-tumour response by promoting the activation of cytotoxic T lymphocytes. Although proven to be highly effective in the treatment of several malignancies they can induce significant immune-related adverse events (irAEs) including endocrinopathies, most commonly hypophysitis and thyroid dysfunction, and rarely autoimmune diabetes. Here we present the first case report of a patient with a primary diagnosis of urothelial cancer developing PD-L1 inhibitor-induced autoimmune diabetes. A euglycemic 57 year old male presented to clinic with dehydration after the fifth cycle of treatment with the novel PD-L1 inhibitor atezolizumab. Blood tests demonstrated rapid onset hyperglycaemia (BM 24 mmol/L), ketosis and a low C-peptide level (0.65 ng/mL) confirming the diagnosis of type 1 diabetes. He responded well to insulin therapy and was discharged with stable blood glucose levels. Due to the widening use of PD-1/PD-L1 inhibitors in cancer treatment clinicians need to be aware of this rare yet treatable irAE. Given the morbidity and mortality associated with undiagnosed autoimmune diabetes we recommend routine HbA1c and plasma glucose testing in all patients prior to and during treatment with PD-1/PD-L1 inhibitors until more evidence has accumulated on identifying those patients with a pre-treatment risk of such irAEs.
ES - 1776-260X
IL - 1776-2596
DI - 10.1007/s11523-017-0480-y
DO - https://dx.doi.org/10.1007/s11523-017-0480-y
PT - Journal Article
PT - Review
ID - 10.1007/s11523-017-0480-y [doi]
ID - 10.1007/s11523-017-0480-y [pii]
PP - ppublish
LG - English
DP - 2017 Apr
DC - 20170303
EZ - 2017/03/04 06:00
DA - 2017/03/04 06:00
DT - 2017/03/04 06:00
YR - 2017
RD - 20170329
UP - 20170330
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28255845
<434. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28315541
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Vazquez A
FA - Vazquez, Adrienne
IN - Vazquez, Adrienne. University of Miami.
TI - Hypophysitis: Nursing Management of Immune-Related Adverse Events.
SO - Clinical Journal of Oncology Nursing. 21(2):154-156, 2017 Apr 01
AS - Clin J Oncol Nurs. 21(2):154-156, 2017 Apr 01
NJ - Clinical journal of oncology nursing
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - czm, 9705336
IO - Clin J Oncol Nurs
CP - United States
KW - hypophysitis; immune-related adverse events; immunotherapy; pituitary gland; steroids
AB - Immunotherapy can treat cancer and prevent future cancer relapse by enhancing the body's immune system. With novel immunotherapeutic agents like checkpoint inhibitors come unique immune-related adverse events. Hypophysitis, one of the lesser known immune-related complications, may be observed in patients receiving checkpoint inhibitors. Although the acute symptoms of immune-related hypophysitis may be managed with attentive monitoring and high-dose corticosteroids, lifelong hormone substitution therapy may be warranted. Oncology nurses are responsible for educating themselves and their patients on the complications of immunotherapy..
ES - 1538-067X
IL - 1092-1095
DO - https://dx.doi.org/10.1188/17.CJON.154-156
PT - Journal Article
ID - 10.1188/17.CJON.154-156 [doi]
PP - ppublish
LG - English
DP - 2017 Apr 01
DC - 20170318
EZ - 2017/03/19 06:00
DA - 2017/03/21 06:00
DT - 2017/03/21 06:00
YR - 2017
RD - 20170318
UP - 20170322
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28315541
<435. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28028828
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Morganstein DL
AU - Lai Z
AU - Spain L
AU - Diem S
AU - Levine D
AU - Mace C
AU - Gore M
AU - Larkin J
AI - Morganstein, D L; ORCID: http://orcid.org/0000-0003-1565-8617
FA - Morganstein, D L
FA - Lai, Z
FA - Spain, L
FA - Diem, S
FA - Levine, D
FA - Mace, C
FA - Gore, M
FA - Larkin, J
IN - Morganstein, D L. Skin Unit, Royal Marsden Hospital, London, UK.
IN - Morganstein, D L. Department of Endocrinology, Chelsea and Westminster Hospital, London, UK.
IN - Lai, Z. Skin Unit, Royal Marsden Hospital, London, UK.
IN - Lai, Z. Department of Endocrinology, Chelsea and Westminster Hospital, London, UK.
IN - Spain, L. Skin Unit, Royal Marsden Hospital, London, UK.
IN - Diem, S. Skin Unit, Royal Marsden Hospital, London, UK.
IN - Diem, S. Department of Oncology/Hematology, Cantonal Hospital St. Gallen, Switzerland, Switzerland.
IN - Diem, S. Department of Oncology/Hematology, Hospital Grabs, Switzerland.
IN - Levine, D. Department of Nuclear Medicine, Royal Marsden Hospital, London, UK.
IN - Mace, C. Department of Endocrinology, Chelsea and Westminster Hospital, London, UK.
IN - Gore, M. Skin Unit, Royal Marsden Hospital, London, UK.
IN - Larkin, J. Skin Unit, Royal Marsden Hospital, London, UK.
TI - Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma.
SO - Clinical Endocrinology. 86(4):614-620, 2017 Apr
AS - Clin Endocrinol (Oxf). 86(4):614-620, 2017 Apr
NJ - Clinical endocrinology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dci, 0346653
IO - Clin. Endocrinol. (Oxf)
CP - England
AB - CONTEXT: Checkpoint inhibitors are emerging as important cancer therapies but are associated with a high rate of immune side effects, including endocrinopathy.
AB - OBJECTIVE: To determine the burden of thyroid dysfunction in patients with melanoma treated with immune checkpoint inhibitors and describe the clinical course.
AB - DESIGN AND PATIENTS: Consecutive patients with melanoma treated with either ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab were identified. Baseline thyroid function tests were used to exclude those with pre-existing thyroid abnormalities, and thyroid function tests during treatment used to identify those with thyroid dysfunction.
AB - RESULTS: Rates of overt thyroid dysfunction were in keeping with the published phase 3 trials. Hypothyroidism occurred in 13.0% treated with a programmed death receptor-1 (PD-1) inhibitor and 22.2% with a combination of PD-1 inhibitor and ipilimumab. Transient subclinical hyperthyroidism was observed in 13.0% treated with a PD-1 inhibitor, 15.9% following a PD-1 inhibitor, and 22.2% following combination treatment with investigations suggesting a thyroiditic mechanism rather than Graves' disease, and a high frequency of subsequent hypothyroidism. Any thyroid abnormality occurred in 23.0% following ipilimumab, 39.1% following a PD-1 inhibitor and 50% following combination treatment. Abnormal thyroid function was more common in female patients.
AB - CONCLUSION: Thyroid dysfunction occurs commonly in patients with melanoma treated with immune checkpoint inhibitors, with rates, including subclinical dysfunction, occurring in up to 50%.
AB - Copyright © 2016 John Wiley & Sons Ltd.
ES - 1365-2265
IL - 0300-0664
DO - https://dx.doi.org/10.1111/cen.13297
PT - Journal Article
ID - 10.1111/cen.13297 [doi]
PP - ppublish
PH - 2016/08/15 [received]
PH - 2016/11/14 [revised]
PH - 2016/12/19 [revised]
PH - 2016/12/20 [accepted]
LG - English
EP - 20170127
DP - 2017 Apr
DC - 20161228
EZ - 2016/12/29 06:00
DA - 2016/12/29 06:00
DT - 2016/12/29 06:00
YR - 2017
RD - 20170316
UP - 20170317
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28028828
<436. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27879975
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Walocko FM
AU - Scheier BY
AU - Harms PW
AU - Fecher LA
AU - Lao CD
FA - Walocko, Frances M
FA - Scheier, Benjamin Y
FA - Harms, Paul W
FA - Fecher, Leslie A
FA - Lao, Christopher D
IN - Walocko, Frances M. University of Michigan Medical School, Ann Arbor, MI USA.
IN - Scheier, Benjamin Y. Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, C451 Med Inn, 1500 East Medical Center Drive, Ann Arbor, MI 48109 USA.
IN - Harms, Paul W. Department of Pathology, University of Michigan, Ann Arbor, MI USA ; Department of Dermatology, University of Michigan, Ann Arbor, MI USA.
IN - Fecher, Leslie A. Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, C451 Med Inn, 1500 East Medical Center Drive, Ann Arbor, MI 48109 USA.
IN - Lao, Christopher D. Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, C451 Med Inn, 1500 East Medical Center Drive, Ann Arbor, MI 48109 USA.
TI - Metastatic Merkel cell carcinoma response to nivolumab.[Erratum appears in J Immunother Cancer. 2017 Mar 6;5:27; PMID: 28286652]
SO - Journal for Immunotherapy of Cancer. 4:79, 2016
AS - J Immunother Cancer. 4:79, 2016
NJ - Journal for immunotherapy of cancer
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Internet
JC - 101620585
IO - J Immunother Cancer
CP - England
KW - Case report; Immunotherapy; Merkel cell carcinoma; Nivolumab; PD-L1; Polyomavirus
AB - BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy with limited treatment options. Several lines of evidence support the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis as a likely contributor to immune evasion in MCC.
AB - CASE PRESENTATION: We report a case of a patient with metastatic MCC with a significant and durable response to nivolumab, a humanized IgG4 monoclonal anti-PD-1 antibody.
AB - CONCLUSION: Immunotherapy with PD-1/PD-L1 inhibitors has become a rational and promising treatment option for MCC in the advanced or metastatic disease. Clinical trials are currently in progress to further evaluate these novel therapeutic agents.
ES - 2051-1426
IL - 2051-1426
DI - 186
DO - https://dx.doi.org/10.1186/s40425-016-0186-1
PT - Journal Article
ID - 10.1186/s40425-016-0186-1 [doi]
ID - 186 [pii]
ID - PMC5109712 [pmc]
PP - epublish
PH - 2016/08/22 [received]
PH - 2016/11/01 [accepted]
LG - English
EP - 20161115
DP - 2016
DC - 20161123
EZ - 2016/11/24 06:00
DA - 2016/11/24 06:00
DT - 2016/11/24 06:00
YR - 2016
RD - 20170313
UP - 20170314
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27879975
<437. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27829150
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Jiang TT
AU - Martinov T
AU - Xin L
AU - Kinder JM
AU - Spanier JA
AU - Fife BT
AU - Way SS
FA - Jiang, Tony T
FA - Martinov, Tijana
FA - Xin, Lijun
FA - Kinder, Jeremy M
FA - Spanier, Justin A
FA - Fife, Brian T
FA - Way, Sing Sing
IN - Jiang, Tony T. Division of Infectious Diseases and Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Immunology Graduate Program, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
IN - Martinov, Tijana. Center for Immunology, Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA.
IN - Xin, Lijun. Division of Infectious Diseases and Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
IN - Kinder, Jeremy M. Division of Infectious Diseases and Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA; Immunology Graduate Program, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
IN - Spanier, Justin A. Center for Immunology, Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA.
IN - Fife, Brian T. Center for Immunology, Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA. Electronic address: bfife@umn.edu.
IN - Way, Sing Sing. Division of Infectious Diseases and Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA. Electronic address: singsing.way@cchmc.org.
TI - Programmed Death-1 Culls Peripheral Accumulation of High-Affinity Autoreactive CD4 T Cells to Protect against Autoimmunity.
SO - Cell Reports. 17(7):1783-1794, 2016 Nov 08
AS - Cell Rep. 17(7):1783-1794, 2016 Nov 08
NJ - Cell reports
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101573691
IO - Cell Rep
CP - United States
KW - T cell activation; autoimmunity; costimulation; peripheral immune tolerance
AB - Self-reactive CD4 T cells are incompletely deleted during thymic development, and their peripheral seeding highlights the need for additional safeguards to avert autoimmunity. Here, we show an essential role for the coinhibitory molecule programmed death-1 (PD-1) in silencing the activation of high-affinity autoreactive CD4 T cells. Each wave of self-reactive CD4 T cells that escapes thymic deletion autonomously upregulates PD-1 to maintain self-tolerance. By tracking the progeny derived from individual autoreactive CD4 T cell clones, we demonstrate that self-reactive cells with the greatest autoimmune threat and highest self-antigen affinity express the most PD-1. Reciprocally, PD-1 deprivation unleashes high-affinity self-reactive CD4 T cells in target tissues to exacerbate neuronal inflammation and autoimmune diabetes. Reliance on PD-1 to actively maintain self-tolerance may explain why exploiting this pathway by cancerous cells and invasive microbes efficiently subverts protective immunity, and why autoimmune side effects can develop after PD-1-neutralizing checkpoint therapies.
AB - Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
ES - 2211-1247
DI - S2211-1247(16)31462-0
DO - https://dx.doi.org/10.1016/j.celrep.2016.10.042
PT - Journal Article
ID - S2211-1247(16)31462-0 [pii]
ID - 10.1016/j.celrep.2016.10.042 [doi]
ID - PMC5108556 [pmc]
ID - NIHMS824882 [mid]
PP - ppublish
PH - 2016/07/25 [received]
PH - 2016/09/25 [revised]
PH - 2016/10/13 [accepted]
GI - No: R01 AI120202
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: HHSN272201300006C
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: R01 AI106791
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: F30 DK107199
Organization: (DK) *NIDDK NIH HHS*
Country: United States
No: T32 GM063483
Organization: (GM) *NIGMS NIH HHS*
Country: United States
No: T32 DK007203
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG - English
DP - 2016 Nov 08
DC - 20161109
EZ - 2016/11/10 06:00
DA - 2016/11/10 06:00
DT - 2016/11/10 06:00
YR - 2016
RD - 20170311
UP - 20170313
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27829150
<438. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28231723
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Shang YH
AU - Zhang Y
AU - Li JH
AU - Li P
AU - Zhang X
FA - Shang, Yan Hong
FA - Zhang, Yu
FA - Li, Jing Hua
FA - Li, Peng
FA - Zhang, Xi
IN - Shang, Yan Hong. Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding 071000, P R China.
IN - Zhang, Yu. Department of internal Medicine, Baoding Children's Hospital, Baoding 071000, P R China.
IN - Li, Jing Hua. Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, Baoding 071000, P R China.
IN - Li, Peng. Departments of Ultrasound, Affiliated Hospital of Hebei University, Baoding 071000, P R China.
IN - Zhang, Xi. Department of Radiation Oncology, Affiliated Hospital of Hebei University, 212 East Yuhua Road, Baoding 071000, Hebei, P R China.
TI - Risk of endocrine adverse events in cancer patients treated with PD-1 inhibitors: a systematic review and meta-analysis.
SO - Immunotherapy. 9(3):261-272, 2017 Mar
AS - Immunotherapy. 9(3):261-272, 2017 Mar
NJ - Immunotherapy
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101485158
IO - Immunotherapy
CP - England
KW - PD-1 inhibitors; cancer; hyperthyroidism; hypophysitis; hypothyroidism
AB - AIM: We conducted this meta-analysis to investigate the overall incidence and risk of endocrine complications in cancer patients treated with PD-1 inhibitors.
AB - METHODS: Pubmed, Embase and oncology conference proceedings were searched for relevant studies.
AB - RESULTS: In comparison with chemotherapy or everolimus or cetuximab control, PD-1 inhibitors significantly increased the risk of all grade hypothyroidism (relative risk: 6.38; 95% CI: 3.78-10.77; p < 0.001) and hyperthyroidism (relative risk: 5.08; 95% CI: 2.55-10.14; p < 0.001), but not for hypophysitis. When compared with ipilimumab control, the risk of all grade hyperthyroidism and hypothyroidism with PD-1 inhibitors monotherapy seemed to be higher than ipilimumab, while the risk of hypophysitis was lower than ipilimumab.
AB - CONCLUSION: Treatment with PD-1 inhibitors is associated with an increased risk of developing hypothyroidism and hyperthyroidism, but not for hypophysitis.
ES - 1750-7448
IL - 1750-743X
DO - https://dx.doi.org/10.2217/imt-2016-0147
PT - Journal Article
ID - 28231723 [pubmed]
ID - 10.2217/imt-2016-0147 [doi]
PP - ppublish
LG - English
DP - 2017 Mar
DC - 20170224
EZ - 2017/02/25 06:00
DA - 2017/02/25 06:00
DT - 2017/02/25 06:00
YR - 2017
RD - 20170224
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28231723
<439. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28070057
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Cho KY
AU - Miyoshi H
AU - Nakamura A
AU - Kurita T
AU - Atsumi T
FA - Cho, Kyu Yong
FA - Miyoshi, Hideaki
FA - Nakamura, Akinobu
FA - Kurita, Takashi
FA - Atsumi, Tatsuya
IN - Cho, Kyu Yong. Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
TI - Hyponatremia can be a powerful predictor of the development of isolated ACTH deficiency associated with nivolumab treatment [Letter to the Editor].
SO - Endocrine Journal. 64(2):235-236, 2017 Feb 27
AS - Endocr J. 64(2):235-236, 2017 Feb 27
NJ - Endocrine journal
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - bt5, 9313485
IO - Endocr. J.
CP - Japan
ES - 1348-4540
IL - 0918-8959
DO - https://dx.doi.org/10.1507/endocrj.EJ16-0596
PT - Journal Article
ID - 28070057 [pubmed]
ID - 10.1507/endocrj.EJ16-0596 [doi]
PP - ppublish
LG - English
EP - 20170106
DP - 2017 Feb 27
DC - 20170110
EZ - 2017/01/11 06:00
DA - 2017/01/11 06:00
DT - 2017/01/11 06:00
YR - 2017
RD - 20170227
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28070057
<440. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28101034
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Mertz AT
AU - Ojemuyiwa MA
FA - Mertz, Andrew T
FA - Ojemuyiwa, Michelle A
IN - Mertz, Andrew T. Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
IN - Ojemuyiwa, Michelle A. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, MD, USA.
TI - A Case of Poorly Differentiated Large-Cell Neuroendocrine Carcinoma of the Cecum: A Rare Malignancy, with Review of the Literature.
SO - Case Reports Oncology. 9(3):847-853, 2016 Sep-Dec
AS - Case rep., oncol.. 9(3):847-853, 2016 Sep-Dec
NJ - Case reports in oncology
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101517601
IO - Case Rep Oncol
CP - Switzerland
KW - Gastroenteropancreatic neuroendocrine tumors; Immunotherapy; Neuroendocrine carcinomas; Programmed death-ligand 1; Small-cell lung cancer
AB - Poorly differentiated neuroendocrine carcinomas (NECs) are rare tumors that can arise anywhere along the gastrointestinal tract. They often present in advanced stage and portend a poor prognosis when compared to adenocarcinomas of the same stage. Characterization of these tumors is best accomplished with tissue biopsy, as peripheral tumor markers commonly used in NECs are of little utility. Therapeutic strategies often involve chemotherapeutic regimens that have been used to treat small-cell lung cancer. Recent studies have shown that programmed death-ligand 1 (PD-L1) expression within poorly differentiated NECs is a poor prognostic indicator. However, PD-L1 expression may represent a possible target for immunotherapy drugs, often called checkpoint inhibitors, such as anti-PD-1 inhibitors.
CI - The authors declare no conflicts of interest and have no disclosures.
IL - 1662-6575
DI - cro-0009-0847
DO - https://dx.doi.org/10.1159/000452655
PT - Journal Article
ID - 28101034 [pubmed]
ID - 10.1159/000452655 [doi]
ID - cro-0009-0847 [pii]
ID - PMC5216239 [pmc]
PP - epublish
PH - 2016/10/17 [received]
PH - 2016/10/18 [accepted]
LG - English
EP - 20161214
DP - 2016 Sep-Dec
DC - 20170119
EZ - 2017/01/20 06:00
DA - 2017/01/20 06:01
DT - 2017/01/20 06:00
YR - 2016
RD - 20170224
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28101034
<441. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28101032
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Khokhar MO
AU - Kettle J
AU - Palla AR
FA - Khokhar, Muhammad O
FA - Kettle, Jacob
FA - Palla, Amruth R
IN - Khokhar, Muhammad O. Division of Hematology and Oncology, Department of Medicine, Ellis Fischel Cancer Center, University of Missouri Columbia, Columbia, MO, USA.
IN - Kettle, Jacob. Division of Hematology and Oncology, Department of Pharmacy, Ellis Fischel Cancer Center, University of Missouri Columbia, Columbia, MO, USA.
IN - Palla, Amruth R. Division of Hematology and Oncology, Department of Medicine, Ellis Fischel Cancer Center, University of Missouri Columbia, Columbia, MO, USA.
TI - Debilitating Skin Toxicity Associated with Pembrolizumab Therapy in an 81-Year-Old Female with Malignant Melanoma.
SO - Case Reports Oncology. 9(3):833-839, 2016 Sep-Dec
AS - Case rep., oncol.. 9(3):833-839, 2016 Sep-Dec
NJ - Case reports in oncology
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101517601
IO - Case Rep Oncol
CP - Switzerland
KW - Immune checkpoint inhibitors; Pembrolizumab; Skin toxicity
AB - Frequently described immune-mediated adverse effects of immune therapy include dermatological complications, hepatitis, colitis, pneumonitis, and endocrinopathies. As utilization of pembrolizumab and related agents continues to expand both in the available indications as well as duration of exposure, there remains a significant potential to uncover previously undescribed adverse events. From a dermatological standpoint, 39% of patients receiving pembrolizumab therapy experience some form of skin-related drug toxicity [Naidoo et al.: Ann Oncol 2015;26: 2375-2391]. We describe a case of pembrolizumab-induced disabling autoimmune ectodermal toxicity.
CI - None of the authors have any conflicts of interest to disclose. All the authors have read the manuscript and agree to its publication in this form. We assure whoever is concerned that this paper is not under simultaneous consideration by any other publication.
IL - 1662-6575
DI - cro-0009-0833
DO - https://dx.doi.org/10.1159/000452944
PT - Journal Article
ID - 28101032 [pubmed]
ID - 10.1159/000452944 [doi]
ID - cro-0009-0833 [pii]
ID - PMC5216251 [pmc]
PP - epublish
PH - 2016/10/31 [received]
PH - 2016/10/31 [accepted]
LG - English
EP - 20161208
DP - 2016 Sep-Dec
DC - 20170119
EZ - 2017/01/20 06:00
DA - 2017/01/20 06:01
DT - 2017/01/20 06:00
YR - 2016
RD - 20170224
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28101032
<442. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28085094
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Yu LY
AU - Tang J
AU - Zhang CM
AU - Zeng WJ
AU - Yan H
AU - Li MP
AU - Chen XP
FA - Yu, Lin-Yu
FA - Tang, Jie
FA - Zhang, Cong-Min
FA - Zeng, Wen-Jing
FA - Yan, Han
FA - Li, Mu-Peng
FA - Chen, Xiao-Ping
IN - Yu, Lin-Yu. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. yulinhui19910530@163.com.
IN - Yu, Lin-Yu. Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China. yulinhui19910530@163.com.
IN - Tang, Jie. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. jietang@csu.edu.cn.
IN - Tang, Jie. Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China. jietang@csu.edu.cn.
IN - Zhang, Cong-Min. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. ZhangCM126126@126.com.
IN - Zhang, Cong-Min. Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China. ZhangCM126126@126.com.
IN - Zeng, Wen-Jing. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. wenjinganne@126.com.
IN - Zeng, Wen-Jing. Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China. wenjinganne@126.com.
IN - Yan, Han. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. yanhan501@126.com.
IN - Yan, Han. Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China. yanhan501@126.com.
IN - Li, Mu-Peng. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. elskesunny@163.com.
IN - Li, Mu-Peng. Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China. elskesunny@163.com.
IN - Chen, Xiao-Ping. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China. chenxp74@hotmail.com.
IN - Chen, Xiao-Ping. Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China. chenxp74@hotmail.com.
TI - New Immunotherapy Strategies in Breast Cancer. [Review]
SO - International Journal of Environmental Research & Public Health [Electronic Resource]. 14(1), 2017 Jan 12
AS - Int J Environ Res Public Health. 14(1), 2017 Jan 12
NJ - International journal of environmental research and public health
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101238455
IO - Int J Environ Res Public Health
CP - Switzerland
KW - bispecific antibodies; breast cancer; cancer vaccines; immune checkpoint inhibitors; immunotherapy; stimulatory molecule agonists
AB - Breast cancer is the most commonly diagnosed cancer among women. Therapeutic treatments for breast cancer generally include surgery, chemotherapy, radiotherapy, endocrinotherapy and molecular targeted therapy. With the development of molecular biology, immunology and pharmacogenomics, immunotherapy becomes a promising new field in breast cancer therapies. In this review, we discussed recent progress in breast cancer immunotherapy, including cancer vaccines, bispecific antibodies, and immune checkpoint inhibitors. Several additional immunotherapy modalities in early stages of development are also highlighted. It is believed that these new immunotherapeutic strategies will ultimately change the current status of breast cancer therapies.
CI - The authors declare no conflict of interest.
ES - 1660-4601
IL - 1660-4601
DI - E68
DI - ijerph14010068
DO - https://dx.doi.org/10.3390/ijerph14010068
PT - Review
PT - Journal Article
ID - 28085094 [pubmed]
ID - ijerph14010068 [pii]
ID - 10.3390/ijerph14010068 [doi]
ID - PMC5295319 [pmc]
PP - epublish
PH - 2016/10/09 [received]
PH - 2017/01/05 [revised]
PH - 2017/01/09 [accepted]
LG - English
EP - 20170112
DP - 2017 Jan 12
DC - 20170113
EZ - 2017/01/14 06:00
DA - 2017/01/14 06:00
DT - 2017/01/14 06:00
YR - 2017
RD - 20170224
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28085094
<443. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28068177
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Weber JS
AU - Hodi FS
AU - Wolchok JD
AU - Topalian SL
AU - Schadendorf D
AU - Larkin J
AU - Sznol M
AU - Long GV
AU - Li H
AU - Waxman IM
AU - Jiang J
AU - Robert C
FA - Weber, Jeffrey S
FA - Hodi, F Stephen
FA - Wolchok, Jedd D
FA - Topalian, Suzanne L
FA - Schadendorf, Dirk
FA - Larkin, James
FA - Sznol, Mario
FA - Long, Georgina V
FA - Li, Hewei
FA - Waxman, Ian M
FA - Jiang, Joel
FA - Robert, Caroline
IN - Weber, Jeffrey S. Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James Larkin, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and Paris-Sud University, Villejuif-Paris Sud, France.
IN - Hodi, F Stephen. Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James Larkin, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and Paris-Sud University, Villejuif-Paris Sud, France.
IN - Wolchok, Jedd D. Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James Larkin, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and Paris-Sud University, Villejuif-Paris Sud, France.
IN - Topalian, Suzanne L. Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James Larkin, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and Paris-Sud University, Villejuif-Paris Sud, France.
IN - Schadendorf, Dirk. Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James Larkin, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and Paris-Sud University, Villejuif-Paris Sud, France.
IN - Larkin, James. Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James Larkin, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and Paris-Sud University, Villejuif-Paris Sud, France.
IN - Sznol, Mario. Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James Larkin, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and Paris-Sud University, Villejuif-Paris Sud, France.
IN - Long, Georgina V. Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James Larkin, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and Paris-Sud University, Villejuif-Paris Sud, France.
IN - Li, Hewei. Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James Larkin, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and Paris-Sud University, Villejuif-Paris Sud, France.
IN - Waxman, Ian M. Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James Larkin, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and Paris-Sud University, Villejuif-Paris Sud, France.
IN - Jiang, Joel. Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James Larkin, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and Paris-Sud University, Villejuif-Paris Sud, France.
IN - Robert, Caroline. Jeffrey S. Weber, H. Lee Moffitt Cancer Center, Tampa, FL; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center, New York, NY; Suzanne L. Topalian, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; Hewei Li, Ian M. Waxman, and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ; Dirk Schadendorf, University of Essen, Essen, Germany; James Larkin, Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Georgina V. Long, Melanoma Institute Australia and University of Sydney, Sydney, New South Wales, Australia; and Caroline Robert, Gustave Roussy and Paris-Sud University, Villejuif-Paris Sud, France.
TI - Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma.
SO - Journal of Clinical Oncology. 35(7):785-792, 2017 Mar
AS - J Clin Oncol. 35(7):785-792, 2017 Mar
NJ - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - jco, 8309333
IO - J. Clin. Oncol.
CP - United States
AB - Purpose We conducted a retrospective analysis to assess the safety profile of nivolumab monotherapy in patients with advanced melanoma and describe the management of adverse events (AEs) using established safety guidelines. Patients and Methods Safety data were pooled from four studies, including two phase III trials, with patients who received nivolumab 3 mg/kg once every 2 weeks. We evaluated rate of treatment-related AEs, time to onset and resolution of select AEs (those with potential immunologic etiology), and impact of select AEs and suppressive immune-modulating agents (IMs) on antitumor efficacy. Results Among 576 patients, 71% (95% CI, 67% to 75%) experienced any-grade treatment-related AEs (most commonly fatigue [25%], pruritus [17%], diarrhea [13%], and rash [13%]), and 10% (95% CI, 8% to 13%) experienced grade 3 to 4 treatment-related AEs. No drug-related deaths were reported. Select AEs (occurring in 49% of patients) were most frequently skin related, GI, endocrine, and hepatic; grade 3 to 4 select AEs occurred in 4% of patients. Median time to onset of select AEs ranged from 5 weeks for skin to 15 weeks for renal AEs. Approximately 24% of patients received systemic IMs to manage select AEs, which in most cases resolved. Adjusting for number of doses, objective response rate (ORR) was significantly higher in patients who experienced treatment-related select AEs of any grade compared with those who did not. ORRs were similar in patients who did and patients who did not receive systemic IMs. Conclusion Treatment-related AEs with nivolumab monotherapy were primarily low grade, and most resolved with established safety guidelines. Use of IMs did not affect ORR, although treatment-related select AEs of any grade were associated with higher ORR, but no progression-free survival benefit.
ES - 1527-7755
IL - 0732-183X
DI - 10.1200/JCO.2015.66.1389
DO - https://dx.doi.org/10.1200/JCO.2015.66.1389
PT - Journal Article
ID - 28068177 [pubmed]
ID - 10.1200/JCO.2015.66.1389 [doi]
ID - 10.1200/JCO.2015.66.1389 [pii]
PP - ppublish
LG - English
EP - 20161114
DP - 2017 Mar
DC - 20170109
EZ - 2017/01/10 06:00
DA - 2017/01/10 06:00
DT - 2017/01/10 06:00
YR - 2017
RD - 20170224
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28068177
<444. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28029020
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - PubMed-not-MEDLINE
AU - Topliss DJ
AI - Topliss, Duncan J; ORCID: http://orcid.org/0000-0003-4763-3385
FA - Topliss, Duncan J
IN - Topliss, Duncan J. Department of Endocrinology and Diabetes, The Alfred, Melbourne, Australia.
IN - Topliss, Duncan J. Department of Medicine, Monash University, Melbourne, Australia. duncan.topliss@monash.edu.
TI - Clinical Update in Aspects of the Management of Autoimmune Thyroid Diseases. [Review]
SO - Endocrinology and Metabolism. 31(4):493-499, 2016 Dec
AS - Endocrinol Metab (Seoul). 31(4):493-499, 2016 Dec
NJ - Endocrinology and metabolism (Seoul, Korea)
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 101554139
IO - Endocrinol Metab (Seoul)
CP - Korea (South)
KW - Hashimoto disease; Immunoglobulin G; Immunomodulation; Iodine; Thyroxine
AB - Aspects of autoimmune thyroid disease updated in this review include: immunoglobulin G4 (IgG4)-related thyroid disease (Riedel's thyroiditis, fibrosing variant of Hashimoto's thyroiditis, IgG4-related Hashimoto's thyroiditis, and Graves' disease with elevated IgG4 levels); recent epidemiological studies from China and Denmark indicating that excess iodine increases the incidence of Hashimoto's thyroiditis and hypothyroidism; immunomodulatory agents (ipilimumab, pembrolizumab, nivolumab) activate immune response by inhibiting T-cell surface receptors which down-regulate immune response, i.e., cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 pathways; alemtuzumab is a humanised monoclonal antibody to CD52 which causes immune depletion and thyroid autoimmune disease especially Graves' hyperthyroidism; small molecule ligand (SML) agonists which activate receptors, SML neutral antagonists, which inhibit receptor activation by agonists, and SML inverse agonists which inhibit receptor activation by agonists and inhibit constitutive agonist independent signaling have been identified. SML antagonism of thyroid-stimulating hormone-receptor stimulatory antibody could treat Graves' hyperthyroidism and Graves' ophthalmopathy; and thyroxine treatment of subclinical hypothyroidism can produce iatrogenic subclinical hyperthyroidism with the risk of atrial fibrillation and osteoporosis. The increased risk of harm from subclinical hyperthyroidism may be stronger than the potential benefit from treatment of subclinical hypothyroidism.
CI - The author has been a presenter at a Sanofi-Aventis (Genzyme) seminar to neurologists on alemtuzumab (Lemtrada) and received an honorarium for this.
IS - 2093-596X
IL - 2093-596X
DI - 31.493
DO - https://dx.doi.org/10.3803/EnM.2016.31.4.493
PT - Review
PT - Journal Article
ID - 28029020 [pubmed]
ID - 31.493 [pii]
ID - 10.3803/EnM.2016.31.4.493 [doi]
ID - PMC5195823 [pmc]
PP - ppublish
PH - 2016/10/29 [received]
PH - 2016/11/11 [revised]
PH - 2016/11/17 [accepted]
LG - English
DP - 2016 Dec
DC - 20161228
EZ - 2016/12/29 06:00
DA - 2016/12/29 06:01
DT - 2016/12/29 06:00
YR - 2016
RD - 20170224
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28029020
<445. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27904651
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Schmid TA
AU - Gore ME
FA - Schmid, Thomas A
FA - Gore, Martin E
IN - Schmid, Thomas A. Royal Marsden NHS Foundation Trust, Fulham Road, London, SW3 6JJ, UK.
IN - Gore, Martin E. Royal Marsden NHS Foundation Trust, London, UK.
TI - Sunitinib in the treatment of metastatic renal cell carcinoma. [Review]
SO - Therapeutic Advances in Urology. 8(6):348-371, 2016 Dec
AS - Ther Adv Urol. 8(6):348-371, 2016 Dec
NJ - Therapeutic advances in urology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - 101487328
IO - Ther Adv Urol
CP - England
KW - renal cell cancer; sunitinib; targeted therapy; tyrosine kinase inhibitor
AB - Sunitinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that targets various receptors, including vascular endothelial growth factor receptors (VEGFRs). Sunitinib received approval in 2006 and became a standard treatment option in the first-line treatment of metastatic renal cell cancer (mRCC) after a phase III trial showed superiority compared with interferon alpha (IFN-alpha). Sunitinib has also shown activity in second-line treatment in several trials. Most of the combination trials with sunitinib with various agents have led to considerable toxicity without improving efficacy. Sunitinib alone causes significant side effects and has a distinct profile with diarrhoea, hypertension, skin effects hypothyroidism, fatigue and nausea of special interest. The recommended dose of sunitinib in mRCC is 50 mg orally daily for 4 weeks, followed by 2 weeks off treatment (4/2 schedule). An alternative 2 weeks on, 1 week off schedule (2/1 schedule) seems to be of similar efficacy and better tolerability and could be more widely used in the future. An intermittent treatment strategy with a stop in remission and re-induction after progression showed efficacy in smaller trials and is currently being evaluated in a phase III trial. Direct comparison of sunitinib with pazopanib in first-line treatment showed a similar efficacy for both TKIs with a distinct toxicity profile. Data from two phase II trials showed that sunitinib has also activity in non-clear cell cancer and is an option due to a lack of better alternatives. Currently, after immune checkpoint inhibitors have shown very promising results in the second-line treatment of RCC, they are being tested in a number of phase III trials in the first-line setting. The future will show the position of sunitinib in the first-line treatment of RCC in the era of the immune checkpoint inhibitors.
CI - The authors declare that there is no conflict of interest.
IS - 1756-2872
IL - 1756-2872
DI - 10.1177_1756287216663979
DO - https://dx.doi.org/10.1177/1756287216663979
PT - Review
PT - Journal Article
ID - 27904651 [pubmed]
ID - 10.1177/1756287216663979 [doi]
ID - 10.1177_1756287216663979 [pii]
ID - PMC5117167 [pmc]
PP - ppublish
LG - English
EP - 20160823
DP - 2016 Dec
DC - 20161201
EZ - 2016/12/02 06:00
DA - 2016/12/03 06:00
DT - 2016/12/03 06:00
YR - 2016
RD - 20170224
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27904651
<446. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27429197
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Graff JN
AU - Alumkal JJ
AU - Drake CG
AU - Thomas GV
AU - Redmond WL
AU - Farhad M
AU - Cetnar JP
AU - Ey FS
AU - Bergan RC
AU - Slottke R
AU - Beer TM
FA - Graff, Julie N
FA - Alumkal, Joshi J
FA - Drake, Charles G
FA - Thomas, George V
FA - Redmond, William L
FA - Farhad, Mohammad
FA - Cetnar, Jeremy P
FA - Ey, Frederick S
FA - Bergan, Raymond C
FA - Slottke, Rachel
FA - Beer, Tomasz M
IN - Graff, Julie N. Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
IN - Graff, Julie N. VA Portland Health Care System, Portland, OR, USA.
IN - Alumkal, Joshi J. Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
IN - Drake, Charles G. Sidney Kimmel Comprehensive Cancer Center and the Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
IN - Thomas, George V. Pathology and Laboratory Medicine, Oregon Health and Science University, Portland, OR, USA.
IN - Redmond, William L. Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA.
IN - Farhad, Mohammad. Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR, USA.
IN - Farhad, Mohammad. Cell, Developmental, and Cancer Biology Department, Oregon Health and Science University, Portland, OR, USA.
IN - Cetnar, Jeremy P. Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
IN - Ey, Frederick S. Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
IN - Bergan, Raymond C. Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
IN - Slottke, Rachel. Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
IN - Beer, Tomasz M. Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
TI - Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer.
SO - Oncotarget. 7(33):52810-52817, 2016 Aug 16
AS - Oncotarget. 7(33):52810-52817, 2016 Aug 16
NJ - Oncotarget
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101532965
IO - Oncotarget
CP - United States
KW - Immune response; Immunity; Immunology and Microbiology Section; PD-1; enzalutamide; immunotherapy; prostate cancer
AB - While programmed cell death 1 (PD-1) inhibitors have shown clear anti-tumor efficacy in several solid tumors, prior results in men with metastatic castration resistant prostate cancer (mCRPC) showed no evidence of activity. Here we report unexpected antitumor activity seen in mCRPC patients treated with the anti-PD-1 antibody pembrolizumab. Patients with evidence of progression on enzalutamide were treated with pembrolizumab 200 mg IV every 3 weeks for 4 doses; pembrolizumab was added to standard dose enzalutamide. Three of the first ten patients enrolled in this ongoing phase II trial experienced rapid prostate specific antigen (PSA) reductions to <= 0.2 ng/ml. Two of these three patients had measurable disease upon study entry; both achieved a partial response. There were three patients with significant immune-related adverse events. One had grade 2 myositis, one had grade 3 hypothyroidism, and one had grade 2 hypothyroidism. None of these patients had a response. Two of the three responders had a baseline tumor biopsy. Immunohistochemistry from those biopsies showed the presence of CD3+, CD8+, and CD163+ leukocyte infiltrates and PD-L1 expression. Genetic analysis of the two responders revealed markers of microsatellite instability in one. The surprising and robust responses seen in this study should lead to re-examination of PD-1 inhibition in prostate cancer.
CI - JNG has received honoraria from Astellas/Medivation. She has received research funding from Astellas/Medivation and Merck. CGD has received research funding from Bristol Myers Squibb (BMS). He has received consulting fees from BMS, Merck, Astra Zeneca (AZ) and Medimmune. He has patents licensed to AZ, BMS and Medimmune. WLR has received research grants, consulting fees, and/or royalties from Bristol-Myers Squibb, Merck, Galectin Therapeutics, and Nektar Therapeutics. TMB Research funding from Astellas and Medivation; consulting fees from Astellas. JJA, GVT, MF, JPC, FSE, RCB and RS have no conflicts. This research was funded by Merck Sharp & Dohme Corporation. Funds from the Bloomberg Kimmel Institute (BKI) supported a portion of the laboratory work. Additional laboratory funding was funded by Merck.
ES - 1949-2553
IL - 1949-2553
DI - 10547
DO - https://dx.doi.org/10.18632/oncotarget.10547
PT - Journal Article
ID - 27429197 [pubmed]
ID - 10547 [pii]
ID - 10.18632/oncotarget.10547 [doi]
ID - PMC5288150 [pmc]
PP - ppublish
PH - 2016/05/31 [received]
PH - 2016/06/17 [accepted]
LG - English
DP - 2016 Aug 16
DC - 20160718
EZ - 2016/07/19 06:00
DA - 2016/07/19 06:00
DT - 2016/07/19 06:00
YR - 2016
RD - 20170224
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27429197
<447. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27418145
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Cives M
AU - Simone V
AU - Rizzo FM
AU - Silvestris F
FA - Cives, Mauro
FA - Simone, Valeria
FA - Rizzo, Francesca Maria
FA - Silvestris, Franco
IN - Cives, Mauro. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari "Aldo Moro", Bari, Italy.
IN - Simone, Valeria. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari "Aldo Moro", Bari, Italy.
IN - Rizzo, Francesca Maria. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari "Aldo Moro", Bari, Italy.
IN - Silvestris, Franco. Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari "Aldo Moro", Bari, Italy.
TI - NETs: organ-related epigenetic derangements and potential clinical applications. [Review]
SO - Oncotarget. 7(35):57414-57429, 2016 Aug 30
AS - Oncotarget. 7(35):57414-57429, 2016 Aug 30
NJ - Oncotarget
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101532965
IO - Oncotarget
CP - United States
KW - ATRX; DAXX; DNA methylation; MEN1; carcinoid tumors
AB - High-throughput next-generation sequencing methods have recently provided a detailed picture of the genetic landscape of neuroendocrine tumors (NETs), revealing recurrent mutations of chromatin-remodeling genes and little-to-no pathogenetic role for oncogenes commonly mutated in cancer. Concurrently, multiple epigenetic modifications have been described across the whole spectrum of NETs, and their putative function as tumorigenic drivers has been envisaged. As result, it is still unclear whether or not NETs are epigenetically-driven, rather than genetically-induced malignancies. Although the NET epigenome profiling has led to the identification of molecularly-distinct tumor subsets, validation studies in larger cohorts of patients are needed to translate the use of NET epitypes in clinical practice. In the precision medicine era, recognition of subpopulations of patients more likely to respond to therapeutic agents is critical, and future studies testing epigenetic biomarkers are therefore awaited. Restoration of the aberrant chromatin remodeling machinery is an attractive approach for future treatment of cancer and in several hematological malignancies a few epigenetic agents have been already approved. Although clinical outcomes of epigenetic therapies in NETs have been disappointing so far, further clinical trials are required to investigate the efficacy of these drugs. In this context, given the immune-stimulating effects of epidrugs, combination therapies with immune checkpoint inhibitors should be tested. In this review, we provide an overview of the epigenetic changes in both hereditary and sporadic NETs of the gastroenteropancreatic and bronchial tract, focusing on their diagnostic, prognostic and therapeutic implications.
CI - The Authors declare no affiliation with industries or organizations with a financial interest, direct or indirect, that may affect the conduct or reporting of the work submitted.
ES - 1949-2553
IL - 1949-2553
DI - 10598
DO - https://dx.doi.org/10.18632/oncotarget.10598
PT - Review
PT - Journal Article
ID - 27418145 [pubmed]
ID - 10598 [pii]
ID - 10.18632/oncotarget.10598 [doi]
ID - PMC5302998 [pmc]
PP - ppublish
PH - 2016/04/06 [received]
PH - 2016/06/30 [accepted]
LG - English
DP - 2016 Aug 30
DC - 20160726
EZ - 2016/07/16 06:00
DA - 2016/07/16 06:00
DT - 2016/07/16 06:00
YR - 2016
RD - 20170224
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27418145
<448. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27086918
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Chowdhury S
AU - Veyhl J
AU - Jessa F
AU - Polyakova O
AU - Alenzi A
AU - MacMillan C
AU - Ralhan R
AU - Walfish PG
FA - Chowdhury, Subrata
FA - Veyhl, Joe
FA - Jessa, Fatima
FA - Polyakova, Olena
FA - Alenzi, Ahmed
FA - MacMillan, Christina
FA - Ralhan, Ranju
FA - Walfish, Paul G
IN - Chowdhury, Subrata. Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
IN - Veyhl, Joe. Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
IN - Jessa, Fatima. Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
IN - Polyakova, Olena. Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
IN - Polyakova, Olena. Department of Medicine, Endocrine Division, Mount Sinai Hospital and University of Toronto Medical School, Toronto, Ontario, Canada.
IN - Alenzi, Ahmed. Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
IN - Alenzi, Ahmed. Department of Medicine, Endocrine Division, Mount Sinai Hospital and University of Toronto Medical School, Toronto, Ontario, Canada.
IN - MacMillan, Christina. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
IN - MacMillan, Christina. Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
IN - Ralhan, Ranju. Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
IN - Ralhan, Ranju. Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery Program, Mount Sinai Hospital, Toronto, Ontario, Canada.
IN - Ralhan, Ranju. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
IN - Ralhan, Ranju. Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada.
IN - Ralhan, Ranju. Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada.
IN - Ralhan, Ranju. Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
IN - Walfish, Paul G. Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
IN - Walfish, Paul G. Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery Program, Mount Sinai Hospital, Toronto, Ontario, Canada.
IN - Walfish, Paul G. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
IN - Walfish, Paul G. Department of Medicine, Endocrine Division, Mount Sinai Hospital and University of Toronto Medical School, Toronto, Ontario, Canada.
IN - Walfish, Paul G. Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
TI - Programmed death-ligand 1 overexpression is a prognostic marker for aggressive papillary thyroid cancer and its variants.
SO - Oncotarget. 7(22):32318-28, 2016 May 31
AS - Oncotarget. 7(22):32318-28, 2016 May 31
NJ - Oncotarget
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101532965
IO - Oncotarget
SB - Index Medicus
CP - United States
KW - benign nodule; programmed death-ligand 1; protein biomarkers; subcellular localization; thyroid cancer
AB - Programmed death-ligand 1(PD-L1) expression on tumor cells is emerging as a potential predictive biomarker in anti-PD-L1 directed cancer immunotherapy. We analyzed PD-L1 expression in papillary thyroid carcinoma (PTC) and its variants and determined its prognostic potential to predict clinical outcome in these patients. This study was conducted at an academic oncology hospital which is a prime referral centre for thyroid diseases. Immunohistochemical subcellular localization (IHC) analyses of PD-L1 protein was retrospectively performed on 251 archived formalin fixed and paraffin embedded (FFPE) surgical tissues (66 benign thyroid nodules and 185 PTCs) using a rabbit monoclonal anti-PD-L1 antibody (E1L3N, Cell Signaling Technology) and detected using VECTASTAIN rapid protocol with diaminobenzidine (DAB) as the chromogen. The clinical-pathological factors and disease outcome over 190 months were assessed; immunohistochemical subcellular localization of PD-L1 was correlated with disease free survival (DFS) using Kaplan Meier survival and Cox multivariate regression analysis. Increased PD-L1 immunostaining was predominantly localized in cytoplasm and occasionally in plasma membrane of tumor cells. Among all combined stages of PTC, patients with increased PD-L1 membrane or cytoplasmic positivity had significantly shorter median DFS (36 months and 49 months respectively) as compared to those with PD-L1 negative tumors (DFS, both 186 months with p < 0.001 and p < 0.01 respectively). Comparison of PD-L1+ and PD-L1- patients with matched staging showed increased cytoplasmic positivity in all four stages of PTC that correlated with a greater risk of recurrence and a poor prognosis, but increased membrane positivity significantly correlated with a greater risk of metastasis or death only in Stage IV patients. In conclusion, PD-L1 positive expression in PTC correlates with a greater risk of recurrence and shortened disease free survival supporting its potential application as a prognostic marker for PTC.
CI - PGW and RR are shareholders in Proteocyte Diagnostics Inc. All the other authors (SC, JV, FJ, OP, AA and CM) have nothing to disclose.
ES - 1949-2553
IL - 1949-2553
DI - 8698
DO - https://dx.doi.org/10.18632/oncotarget.8698
PT - Journal Article
ID - 27086918 [pubmed]
ID - 8698 [pii]
ID - 10.18632/oncotarget.8698 [doi]
ID - PMC5078015 [pmc]
PP - ppublish
PH - 2016/03/23 [received]
PH - 2016/03/26 [accepted]
LG - English
DP - 2016 May 31
DC - 20160915
EZ - 2016/04/19 06:00
DA - 2016/04/19 06:00
DT - 2016/04/19 06:00
YR - 2016
RD - 20170224
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27086918
<449. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27008709
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Soliman HH
AU - Minton SE
AU - Han HS
AU - Ismail-Khan R
AU - Neuger A
AU - Khambati F
AU - Noyes D
AU - Lush R
AU - Chiappori AA
AU - Roberts JD
AU - Link C
AU - Vahanian NN
AU - Mautino M
AU - Streicher H
AU - Sullivan DM
AU - Antonia SJ
FA - Soliman, Hatem H
FA - Minton, Susan E
FA - Han, Hyo Sook
FA - Ismail-Khan, Roohi
FA - Neuger, Anthony
FA - Khambati, Fatema
FA - Noyes, David
FA - Lush, Richard
FA - Chiappori, Alberto A
FA - Roberts, John D
FA - Link, Charles
FA - Vahanian, Nicholas N
FA - Mautino, Mario
FA - Streicher, Howard
FA - Sullivan, Daniel M
FA - Antonia, Scott J
IN - Soliman, Hatem H. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
IN - Minton, Susan E. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
IN - Han, Hyo Sook. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
IN - Ismail-Khan, Roohi. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
IN - Neuger, Anthony. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
IN - Khambati, Fatema. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
IN - Noyes, David. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
IN - Lush, Richard. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
IN - Chiappori, Alberto A. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
IN - Roberts, John D. Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.
IN - Link, Charles. NewLink Genetics Inc., Ames, Iowa, USA.
IN - Vahanian, Nicholas N. NewLink Genetics Inc., Ames, Iowa, USA.
IN - Mautino, Mario. NewLink Genetics Inc., Ames, Iowa, USA.
IN - Streicher, Howard. Cancer Therapeutics Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA.
IN - Sullivan, Daniel M. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
IN - Antonia, Scott J. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
TI - A phase I study of indoximod in patients with advanced malignancies.
SO - Oncotarget. 7(16):22928-38, 2016 Apr 19
AS - Oncotarget. 7(16):22928-38, 2016 Apr 19
NJ - Oncotarget
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101532965
IO - Oncotarget
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008412
SB - Index Medicus
CP - United States
KW - 1-methyl-D-tryptophan; 3 dioxygenase; immunomodulator; indoleamine 2; indoximod
AB - PURPOSE: Indoximod is an oral inhibitor of the indoleamine 2,3-dioxygenase pathway, which causes tumor-mediated immunosuppression. Primary endpoints were maximum tolerated dose (MTD) and toxicity for indoximod in patients with advanced solid tumors. Secondary endpoints included response rates, pharmacokinetics, and immune correlates.
AB - EXPERIMENTAL DESIGN: Our 3+3 phase I trial comprised 10 dose levels (200, 300, 400, 600, and 800 mg once/day; 600, 800, 1200, 1600, and 2000 mg twice/day). Inclusion criteria were measurable metastatic solid malignancy, age >=18 years, and adequate organ/marrow function. Exclusion criteria were chemotherapy <= 3 weeks prior, untreated brain metastases, autoimmune disease, or malabsorption.
AB - RESULTS: In 48 patients, MTD was not reached at 2000 mg twice/day. At 200 mg once/day, 3 patients previously treated with checkpoint inhibitors developed hypophysitis. Five patients showed stable disease >6 months. Indoximod plasma AUC and Cmax plateaued above 1200mg. Cmax (~12 muM at 2000 mg twice/day) occurred at 2.9 hours, and half-life was 10.5 hours. C reactive protein (CRP) levels increased across multiple dose levels.
AB - CONCLUSIONS: Indoximod was safe at doses up to 2000 mg orally twice/day. Best response was stable disease >6 months in 5 patients. Induction of hypophysitis, increased tumor antigen autoantibodies and CRP levels were observed.
CI - Charles Link, Nicholas Vahanian, W. Jay Ramsey, and Mario Mautino all have ownership/employment relationships with NewLink Genetics Inc., which is developing indoximod. Hatem Soliman is the lead investigator on a phase 2 clinical trial sponsored by NewLink Genetics.
ES - 1949-2553
IL - 1949-2553
DI - 8216
DO - https://dx.doi.org/10.18632/oncotarget.8216
PT - Journal Article
ID - 27008709 [pubmed]
ID - 8216 [pii]
ID - 10.18632/oncotarget.8216 [doi]
ID - PMC5008412 [pmc]
PP - ppublish
PH - 2016/02/11 [received]
PH - 2016/03/10 [accepted]
GI - No: HHSN261201100100C
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA016059
Organization: (CA) *NCI NIH HHS*
Country: United States
No: P30 CA076292
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2016 Apr 19
DC - 20160725
EZ - 2016/03/24 06:00
DA - 2016/03/24 06:00
DT - 2016/03/24 06:00
YR - 2016
RD - 20170224
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27008709
<450. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27206299
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Anonymous
TI - Programmed Death-1 Inhibition in Cancer With a Focus on Non-Small Cell Lung Cancer: Rationale, Nursing Implications, and Patient Management Strategies.
SO - Clinical Journal of Oncology Nursing. 20(3):319-26, 2016 Jun 01
AS - Clin J Oncol Nurs. 20(3):319-26, 2016 Jun 01
NJ - Clinical journal of oncology nursing
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - czm, 9705336
IO - Clin J Oncol Nurs
SB - Nursing Journal
CP - United States
KW - PD-1; immune checkpoint blockade; immuno-oncology; nivolumab; pembrolizumab
AB - BACKGROUND: Programmed death-1 (PD-1) immune checkpoint inhibitors are novel immuno-oncology agents. Unlike chemotherapy or targeted agents, which inhibit tumor cell proliferation or induce tumor cell death, immune checkpoint inhibitors are designed to stimulate a patient's own immune system to eliminate tumors. As a result of their mechanism of action, PD-1 pathway inhibitors are associated with adverse events (AEs) with immunologic etiologies, termed immune-mediated AEs (imAEs). These include skin and gastrointestinal AEs, and endocrine, hepatic, renal, and respiratory AEs, including pneumonitis. Most imAEs can be effectively managed with treatment interruption/discontinuation and/or steroids or other immunosuppressive agents. A specialist consult may be required in some cases, and endocrine imAEs may require permanent hormone replacement therapy.
AB - OBJECTIVES: This article provides an overview of PD-1 inhibitors, including the potential mechanism of action, key clinical trial data, and strategies for managing patients who may receive PD-1 inhibitors for the treatment of non-small cell lung cancer.
AB - METHODS: Information in the article comes from PubMed literature searches and the author's experience with these agents in clinical trials.
AB - FINDINGS: Oncology clinicians must thoroughly assess baseline functioning and symptoms and be vigilant for imAEs, which require prompt diagnosis and management. A good understanding of the clinical profile of PD-1 pathway inhibitors is instrumental in helping clinicians manage patients receiving these new therapies.
ES - 1538-067X
IL - 1092-1095
DO - https://dx.doi.org/10.1188/16.CJON.319-326
PT - Journal Article
ID - 27206299 [pubmed]
ID - 10.1188/16.CJON.319-326 [doi]
PP - ppublish
LG - English
DP - 2016 Jun 01
DC - 20160521
EZ - 2016/05/21 06:00
DA - 2016/05/21 06:00
DT - 2016/05/21 06:00
YR - 2016
RD - 20170208
UP - 20170209
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27206299
<451. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28093480
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Ahn S
AU - Kim TH
AU - Kim SW
AU - Ki CS
AU - Jang HW
AU - Kim JS
AU - Kim JH
AU - Choe JH
AU - Shin JH
AU - Hahn SY
AU - Oh YL
AU - Chung JH
FA - Ahn, Soomin
FA - Kim, Tae Hyuk
FA - Kim, Sun Wook
FA - Ki, Chang Seok
FA - Jang, Hye Won
FA - Kim, Jee Soo
FA - Kim, Jung Han
FA - Choe, Jun-Ho
FA - Shin, Jung Hee
FA - Hahn, Soo Yeon
FA - Oh, Young Lyun
FA - Chung, Jae Hoon
IN - Ahn, Soomin. Department of PathologyEwha Womans University School of Medicine, Seoul, Korea.
IN - Kim, Tae Hyuk. Division of Endocrinology and MetabolismDepartment of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
IN - Kim, Sun Wook. Division of Endocrinology and MetabolismDepartment of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
IN - Ki, Chang Seok. Department of Laboratory Medicine and GeneticsSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
IN - Jang, Hye Won. Department of Medical EducationSungkyunkwan University School of Medicine, Seoul, Korea.
IN - Kim, Jee Soo. Division of Breast and Endocrine SurgeryDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
IN - Kim, Jung Han. Division of Breast and Endocrine SurgeryDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
IN - Choe, Jun-Ho. Division of Breast and Endocrine SurgeryDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
IN - Shin, Jung Hee. Department of Radiology and Center for Imaging ScienceSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
IN - Hahn, Soo Yeon. Department of Radiology and Center for Imaging ScienceSamsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
IN - Oh, Young Lyun. Department of Pathology and Translational genomicsSungkyunkwan University School of Medicine, Seoul, Korea bijou@skku.edu thyroid@skku.edu.
IN - Chung, Jae Hoon. Division of Endocrinology and MetabolismDepartment of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea bijou@skku.edu thyroid@skku.edu.
TI - Comprehensive screening for PD-L1 expression in thyroid cancer.
SO - Endocrine-Related Cancer. 24(2):97-106, 2017 Feb
AS - Endocr Relat Cancer. 24(2):97-106, 2017 Feb
NJ - Endocrine-related cancer
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 9436481, dgr
IO - Endocr. Relat. Cancer
CP - England
KW - PD1; PDL1; TERT; anaplastic carcinoma; thyroid
AB - PD-L1 expression is being considered a potential biomarker for response of anti-PD-1 or anti-PD-L1 agents in various tumors. The reported frequency of PD-L1 positivity varies in thyroid carcinomas, and multiple factors may contribute to the variability in PD-L1 positivity. We evaluated the PD-L1 expression in various thyroid cancers on a large scale. A total of 407 primary thyroid cancers with a median 13.7-year of follow-up were included. We evaluated the frequency of PD-L1 expression using a rabbit monoclonal antibody (clone SP142). In addition, we analyzed the relationships between PD-L1 expression and clinicopathologic factors, including TERT promoter, BRAF status and disease progression. Tumoral PD-L1 was expressed in 6.1% of papillary thyroid carcinomas, 7.6% of follicular thyroid carcinomas and 22.2% of anaplastic thyroid carcinomas. The distribution of PD-L1 positivity was different according to cancer histology types (P<0.001). All PD-L1-positive cases of follicular thyroid carcinoma and anaplastic thyroid carcinoma showed strong intensity. The proportions of positivity in PD-L1 positive anaplastic thyroid carcinomas were more than 80%. PD-L1 in immune cells was positive in 28.5% of papillary thyroid carcinoma, 9.1% of follicular thyroid carcinomas and 11.1% of anaplastic thyroid carcinomas. There was no significant association between clinicopathologic variables, disease progression, oncogenic mutation and PD-L1 expression. PD-L1 was highly expressed in a subset of patients with advanced thyroid cancer, such as follicular and anaplastic thyroid carcinoma. Identification of PD-L1 expression may have direct therapeutic relevance to patients with refractory thyroid cancer.
AB - Copyright © 2017 Society for Endocrinology.
ES - 1479-6821
IL - 1351-0088
DI - 24/2/97
DO - https://dx.doi.org/10.1530/ERC-16-0421
PT - Journal Article
ID - 28093480 [pubmed]
ID - 24/2/97 [pii]
ID - 10.1530/ERC-16-0421 [doi]
PP - ppublish
PH - 2016/11/30 [received]
PH - 2016/12/13 [accepted]
LG - English
DP - 2017 Feb
DC - 20170117
EZ - 2017/01/18 06:00
DA - 2017/01/18 06:00
DT - 2017/01/18 06:00
YR - 2017
RD - 20170117
UP - 20170119
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=28093480
<452. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27761609
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Chae YK
AU - Chiec L
AU - Mohindra N
AU - Gentzler R
AU - Patel J
AU - Giles F
FA - Chae, Young Kwang
FA - Chiec, Lauren
FA - Mohindra, Nisha
FA - Gentzler, Ryan
FA - Patel, Jyoti
FA - Giles, Francis
IN - Chae, Young Kwang. Developmental Therapeutics Program of the Division of Hematology/Oncology, Northwestern University, Chicago, IL, 60611, USA. young.chae@northwestern.edu.
IN - Chae, Young Kwang. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, 60611, USA. young.chae@northwestern.edu.
IN - Chae, Young Kwang. Feinberg School of Medicine, Northwestern University, 645 N. Michigan Ave, Suite 1006, Chicago, IL, 60611, USA. young.chae@northwestern.edu.
IN - Chiec, Lauren. Feinberg School of Medicine, Northwestern University, 645 N. Michigan Ave, Suite 1006, Chicago, IL, 60611, USA.
IN - Mohindra, Nisha. Developmental Therapeutics Program of the Division of Hematology/Oncology, Northwestern University, Chicago, IL, 60611, USA.
IN - Mohindra, Nisha. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, 60611, USA.
IN - Mohindra, Nisha. Feinberg School of Medicine, Northwestern University, 645 N. Michigan Ave, Suite 1006, Chicago, IL, 60611, USA.
IN - Gentzler, Ryan. University of Virginia School of Medicine, Charlottesville, VA, 22908-0395, USA.
IN - Patel, Jyoti. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, 60611, USA.
IN - Patel, Jyoti. Feinberg School of Medicine, Northwestern University, 645 N. Michigan Ave, Suite 1006, Chicago, IL, 60611, USA.
IN - Patel, Jyoti. The University of Chicago Medicine, Chicago, IL, 60637, USA.
IN - Giles, Francis. Developmental Therapeutics Program of the Division of Hematology/Oncology, Northwestern University, Chicago, IL, 60611, USA.
IN - Giles, Francis. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, 60611, USA.
IN - Giles, Francis. Feinberg School of Medicine, Northwestern University, 645 N. Michigan Ave, Suite 1006, Chicago, IL, 60611, USA.
TI - A case of pembrolizumab-induced type-1 diabetes mellitus and discussion of immune checkpoint inhibitor-induced type 1 diabetes.
SO - Cancer Immunology, Immunotherapy. 66(1):25-32, 2017 Jan
AS - Cancer Immunol Immunother. 66(1):25-32, 2017 Jan
NJ - Cancer immunology, immunotherapy : CII
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cn3, 8605732
IO - Cancer Immunol. Immunother.
CP - Germany
KW - Diabetes mellitus; Immune-related adverse effect; Immunomodulatory; Ipilimumab; Nivolumab; Pembrolizumab
AB - Immune checkpoint inhibitors such as pembrolizumab, ipilimumab, and nivolumab, now FDA-approved for use in treating several types of cancer, have been associated with immune-related adverse effects. Specifically, the antibodies targeting the programmed-cell death-1 immune checkpoint, pembrolizumab and nivolumab, have been rarely reported to induce the development of type 1 diabetes mellitus. Here we describe a case of a patient who developed antibody-positive type 1 diabetes mellitus following treatment with pembrolizumab in combination with systemic chemotherapy for metastatic adenocarcinoma of the lung. We will also provide a brief literature review of other rarely reported cases of type 1 diabetes presenting after treatment with pembrolizumab and nivolumab, as well as discussion regarding potential mechanisms of this adverse effect and its importance as these drugs continue to become even more widespread.
ES - 1432-0851
IL - 0340-7004
DI - 10.1007/s00262-016-1913-7
DO - https://dx.doi.org/10.1007/s00262-016-1913-7
PT - Journal Article
ID - 27761609 [pubmed]
ID - 10.1007/s00262-016-1913-7 [doi]
ID - 10.1007/s00262-016-1913-7 [pii]
PP - ppublish
PH - 2016/03/29 [received]
PH - 2016/10/01 [accepted]
LG - English
EP - 20161019
DP - 2017 Jan
DC - 20161020
EZ - 2016/10/21 06:00
DA - 2016/10/21 06:00
DT - 2016/10/21 06:00
YR - 2017
RD - 20170110
UP - 20170111
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27761609
<453. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27913998
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Spellman A
AU - Tang SC
FA - Spellman, Alison
FA - Tang, Shou-Ching
IN - Spellman, Alison. Georgia Regents University Cancer Center, 1411 Laney Walker Boulevard, Augusta, GA, 30912, USA.
IN - Tang, Shou-Ching. Georgia Regents University Cancer Center, 1411 Laney Walker Boulevard, Augusta, GA, 30912, USA. stang@gru.edu.
IN - Tang, Shou-Ching. Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin, 300060, China. stang@gru.edu.
TI - Immunotherapy for breast cancer: past, present, and future.
SO - Cancer & Metastasis Reviews. 35(4):525-546, 2016 Dec
AS - Cancer Metastasis Rev. 35(4):525-546, 2016 Dec
NJ - Cancer metastasis reviews
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - c9h, 8605731
IO - Cancer Metastasis Rev.
CP - Netherlands
KW - Biomarkers; Breast cancer; Checkpoint inhibitor; Clinical trials; Immunotherapy; Review
AB - Immunotherapy has shown promise in many solid tumors including melanoma and non-small cell lung cancer with an evolving role in breast cancer. Immunotherapy encompasses a wide range of therapies including immune checkpoint inhibition, monoclonal antibodies, bispecific antibodies, vaccinations, antibody-drug conjugates, and identifying other emerging interventions targeting the tumor microenvironment. Increasing efficacy of these treatments in breast cancer patients requires identification of better biomarkers to guide patient selection; recognizing when to initiate these therapies in multi-modality treatment plans; establishing novel assays to monitor immune-mediated responses; and creating combined systemic therapy options incorporating conventional treatments such as chemotherapy and endocrine therapy. This review will focus on the current role and future directions of many of these immunotherapies in breast cancer, as well as highlighting clinical trials that are investigating several of these active issues.
ES - 1573-7233
IL - 0167-7659
DI - 10.1007/s10555-016-9654-9
DO - https://dx.doi.org/10.1007/s10555-016-9654-9
PT - Journal Article
ID - 27913998 [pubmed]
ID - 10.1007/s10555-016-9654-9 [doi]
ID - 10.1007/s10555-016-9654-9 [pii]
PP - ppublish
LG - English
DP - 2016 Dec
DC - 20161203
EZ - 2016/12/04 06:00
DA - 2016/12/04 06:00
DT - 2016/12/04 06:00
YR - 2016
RD - 20170105
UP - 20170106
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27913998
<454. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27966604
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Zhou J
AU - Jin JO
AU - Kawai T
AU - Yu Q
FA - Zhou, Jing
FA - Jin, Jun-O
FA - Kawai, Toshihisa
FA - Yu, Qing
IN - Zhou, Jing. Department of Immunology and Infectious Diseases, the Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA.
IN - Zhou, Jing. Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA.
IN - Jin, Jun-O. Department of Immunology and Infectious Diseases, the Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA.
IN - Kawai, Toshihisa. Department of Immunology and Infectious Diseases, the Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA.
IN - Kawai, Toshihisa. Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA.
IN - Yu, Qing. Department of Immunology and Infectious Diseases, the Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA.
IN - Yu, Qing. Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA.
TI - Endogenous programmed death ligand-1 restrains the development and onset of Sjogren's syndrome in non-obese diabetic mice.
SO - Scientific Reports. 6:39105, 2016 Dec 14
AS - Sci. rep.. 6:39105, 2016 Dec 14
NJ - Scientific reports
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 101563288
IO - Sci Rep
CP - England
AB - Programmed death-ligand 1 (PD-L1) down-modulates various immune responses by engaging the co-inhibitory receptor programmed death-1. Expression of PD-L1 and programmed death-1 is elevated in the salivary glands of patients with Sjogren's syndrome (SS). The objective of this study is to define the role of endogenous PD-L1 in SS pathogenesis in non-obese diabetic (NOD) mouse model of this disease. We inhibited endogenous PD-L1 function by intraperitoneal administration of a blocking antibody to 6 week-old female NOD/ShiLtJ mice repeatedly during a 9-day period. PD-L1 blockade accelerated leukocyte infiltration and caspase-3 activation in the submandibular gland (SMG), production of antinuclear and anti-M3 muscarinic acetylcholine receptor (M3R) autoantibodies and impairment of saliva secretion, indicative of accelerated development and onset of SS. The effect of PD-L1 blockade was associated with increased T- and B cells and T helper 1 cytokine IFN-gamma in the SMG. Local administration of exogenous IFN-gamma to the SMG led to impaired salivary secretion accompanied by down-regulation of aquaporin 5 and an increase in anti-M3R autoantibodies. Conversely, neutralization of IFN-gamma markedly improved salivary secretion and aquaporin 5 expression in anti-PD-L1-treated NOD/ShiLtJ mice. Hence, endogenous PD-L1 hinders the development and onset of SS in NOD mice, in part by suppressing IFN-gamma production.
ES - 2045-2322
IL - 2045-2322
DI - srep39105
DO - https://dx.doi.org/10.1038/srep39105
PT - Journal Article
ID - 27966604 [pubmed]
ID - srep39105 [pii]
ID - 10.1038/srep39105 [doi]
ID - PMC5155421 [pmc]
PP - epublish
PH - 2016/07/22 [received]
PH - 2016/11/17 [accepted]
GI - No: P30 DE020751
Organization: (DE) *NIDCR NIH HHS*
Country: United States
No: R01 DE023838
Organization: (DE) *NIDCR NIH HHS*
Country: United States
LG - English
EP - 20161214
DP - 2016 Dec 14
DC - 20161214
EZ - 2016/12/15 06:00
DA - 2016/12/15 06:00
DT - 2016/12/15 06:00
YR - 2016
RD - 20161222
UP - 20161223
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27966604
<455. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27373241
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Kahler KC
AU - Hassel JC
AU - Heinzerling L
AU - Loquai C
AU - Mossner R
AU - Ugurel S
AU - Zimmer L
AU - Gutzmer R
AU - "Cutaneous Side Effects" Committee of the Work Group Dermatological Oncology (ADO)
FA - Kahler, Katharina C
FA - Hassel, Jessica C
FA - Heinzerling, Lucie
FA - Loquai, Carmen
FA - Mossner, Rotraut
FA - Ugurel, Selma
FA - Zimmer, Lisa
FA - Gutzmer, Ralf
FA - "Cutaneous Side Effects" Committee of the Work Group Dermatological Oncology (ADO)
IN - Kahler, Katharina C. Department of Dermatology, Venereology, and Allergology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
IN - Hassel, Jessica C. Department of Dermatology, and National Cancer Center, University Hospital Heidelberg, Heidelberg, Germany.
IN - Heinzerling, Lucie. Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
IN - Loquai, Carmen. Department of Dermatology, Medical Faculty, University of Mainz, Mainz, Germany.
IN - Mossner, Rotraut. Department of Dermatology, Venereology, and Allergology, University Medicine Gottingen, Gottingen, Germany.
IN - Ugurel, Selma. Department of Dermatology, Venereology and Allergology, University Hospital Essen, Essen, Germany.
IN - Zimmer, Lisa. Department of Dermatology, Venereology and Allergology, University Hospital Essen, Essen, Germany.
IN - Gutzmer, Ralf. Hanover Skin Cancer Center, Department of Dermatology, Venereology, and Allergology, Hanover Medical College, Hanover, Germany.
TI - Management of side effects of immune checkpoint blockade by anti-CTLA-4 and anti-PD-1 antibodies in metastatic melanoma.
SO - Journal der Deutschen Dermatologischen Gesellschaft. 14(7):662-81, 2016 Jul
AS - J.Deutschen Dermatologischen Gesellschaft. 14(7):662-81, 2016 Jul
NJ - Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101164708
IO - J Dtsch Dermatol Ges
SB - Index Medicus
CP - Germany
KW - CTLA-4 antibody; PD-1 antibody; autoimmune side effects; immune checkpoint blockade; melanoma; side effect management
AB - CTLA-4 and PD-1 are potential targets for tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint-modifying monoclonal antibodies oppose these effects, inducing T cell-mediated immune responses to various tumors including melanoma. Both anti-CTLA-4 and anti-PD-1 antibodies modify the interaction between tumor, antigen-presenting cells, and T lymphocytes. With respect to overall survival, clinical studies have shown a major benefit for the anti-CTLA-4 antibody ipilimumab as well as the two anti-PD-1 antibodies nivolumab and pembrolizumab. Following approval of ipilimumab in 2011, the latter two achieved market authorization in the summer of 2015. Immune responses thus induced and enhanced inevitably entail autoimmune phenomena, affecting various organs to varying degrees. Knowledge of these side effects is crucial with regard to prevention and management by treating physicians. Typically occurring early on and presenting with pronounced and persistent diarrhea, colitis represents a major and severe side effect. Other immune-mediated disorders include dermatitis, hypophysitis, thyroiditis, hepatitis, iridocyclitis as well as other less common autoimmune phenomena. Early recognition and initiation of treatment can reduce risks and sequelae for patients. This review describes the mechanisms of action of immune checkpoint blockade as well as its clinical effects in metastatic melanoma, with a detailed focus on the spectrum of adverse events and their therapeutic management.
AB - Copyright © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.
ES - 1610-0387
IL - 1610-0379
DO - https://dx.doi.org/10.1111/ddg.13047
PT - Journal Article
ID - 27373241 [pubmed]
ID - 10.1111/ddg.13047 [doi]
PP - ppublish
LG - English
DP - 2016 Jul
DC - 20160704
EZ - 2016/07/05 06:00
DA - 2016/07/05 06:00
DT - 2016/07/05 06:00
YR - 2016
RD - 20161219
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27373241
<456. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27229364
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Bonnet C
AU - Beinse G
AU - Cabel L
AU - Cochereau D
AU - Lavaud P
AU - Rochefort P
AU - Tabouret E
AU - Turpin A
AU - Verlingue L
AU - Vicier C
AU - Massard C
FA - Bonnet, Clement
FA - Beinse, Guillaume
FA - Cabel, Luc
FA - Cochereau, Delphine
FA - Lavaud, Pernelle
FA - Rochefort, Pauline
FA - Tabouret, Emeline
FA - Turpin, Anthony
FA - Verlingue, Loic
FA - Vicier, Cecile
FA - Massard, Christophe
IN - Bonnet, Clement. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Beinse, Guillaume. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Cabel, Luc. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Cochereau, Delphine. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Lavaud, Pernelle. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Rochefort, Pauline. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Tabouret, Emeline. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Turpin, Anthony. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Verlingue, Loic. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Vicier, Cecile. AERIO, 149, avenue du Maine, 75014 Paris, France.
IN - Massard, Christophe. AERIO, 149, avenue du Maine, 75014 Paris, France; DITEP, Gustave-Roussy, 94805 Villejuif, France. Electronic address: christophe.massard@gustaveroussy.fr.
TI - [ESMO ECCO 2015: The highlights of immunotherapy and targeted therapies]. [French]
OT - ESMO ECCO 2015 : les temps forts de l'immunotherapie et des therapies ciblees.
SO - Bulletin du Cancer. 103(6):594-603, 2016 Jun
AS - Bull Cancer. 103(6):594-603, 2016 Jun
NJ - Bulletin du cancer
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 0072416
IO - Bull Cancer
SB - Index Medicus
CP - France
KW - Early phase studies; Essai de phases precoces; Immunotherapies; Immunotherapies; Medecine personnalisee; Personalized medicine; Targeted therapies; Therapies ciblees
AB - The ESMO/ECC congress (European Society for Medical Oncology/European Cancer Congress) took place in Vienna, Austria, September 25-29. The main topic of the conference was immunotherapies especially in advanced kidney cancer with nivolumab in phase III and in metastatic lung cancer with atezolizumab in phase II. Targeted therapies were also highlighted with cabozantinib proposed in advanced renal cancer or everolimus in differenciated neuroendocrine tumors grade 1 or 2. Furthermore the current challenges remain unchanged: improving patients' care through better selection and finding biomarkers using simple samples (blood or urine). Also early phases and personalized medicine found their place in the different presentations and were highlighted largely bringing new approaches in the treatment of metastatic patients.
AB - Copyright © 2016.
ES - 1769-6917
IL - 0007-4551
DI - S0007-4551(16)30039-X
DO - https://dx.doi.org/10.1016/j.bulcan.2016.04.001
PT - English Abstract
PT - Journal Article
ID - 27229364 [pubmed]
ID - S0007-4551(16)30039-X [pii]
ID - 10.1016/j.bulcan.2016.04.001 [doi]
PP - ppublish
PH - 2016/04/01 [received]
PH - 2016/04/09 [accepted]
LG - French
EP - 20160524
DP - 2016 Jun
DC - 20160617
EZ - 2016/05/28 06:00
DA - 2016/05/28 06:00
DT - 2016/05/28 06:00
YR - 2016
RD - 20161219
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27229364
<457. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27146870
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Oppel-Heuchel H
AU - Grimm MO
FA - Oppel-Heuchel, H
FA - Grimm, M-O
IN - Oppel-Heuchel, H. Urologische Klinik und Poliklinik, Universitatsklinikum Jena, Lessingsstrase 1, 07743, Jena, Deutschland. Harriet.Oppel@med.uni-jena.de.
IN - Grimm, M-O. Urologische Klinik und Poliklinik, Universitatsklinikum Jena, Lessingsstrase 1, 07743, Jena, Deutschland.
TI - [Therapy monitoring and management of adverse events in PD-1/PD-L1 immune checkpoint inhibition]. [German]
OT - Therapiemonitoring und Nebenwirkungsmanagement bei PD-1/PD-L1-Immuncheckpoint-Inhibition.
SO - Urologe (Ausg. A). 55(5):677-90, 2016 May
AS - Urologe A. 55(5):677-90, 2016 May
NJ - Der Urologe. Ausg. A
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - wsj, 1304110
IO - Urologe A
SB - Index Medicus
CP - Germany
KW - Immune-mediated adverse events; Immunotherapy; Nivolumab; PD-1 inhibitor; PD-L1 inhibitor
AB - Nivolumab was recently approved as the first inhibitor of the programmed death 1 (PD-1) receptor and its ligand (PD-L1) for the treatment of urological cancer, namely metastasized renal cell carcinoma after prior therapy. The use of this new immunotherapy requires special therapy monitoring and management of side effects. An increase of immune cells around the tumor can initially mimic progression (so-called pseudoprogression). Treatment-associated side effects of higher grade according to the common terminology criteria for adverse events (CTCAE grades 3 or 4) are relatively rare; however, new immune-mediated side effects can occur and affect the skin, liver (hepatitis), kidneys (nephritis), gastrointestinal tract (diarrhea and colitis), lungs (pneumonitis) and endocrine organs (hyperthyroidism, hypothyroidism and hypophysitis). Treatment has to be delayed or discontinued depending on the kind and degree of side effects; furthermore, corticosteroids can be administered as immunosuppressants. When recognized in time and with correct management, immune-mediated side effects are basically reversible.
ES - 1433-0563
IL - 0340-2592
DI - 10.1007/s00120-016-0109-2
DO - https://dx.doi.org/10.1007/s00120-016-0109-2
PT - English Abstract
PT - Journal Article
ID - 27146870 [pubmed]
ID - 10.1007/s00120-016-0109-2 [doi]
ID - 10.1007/s00120-016-0109-2 [pii]
PP - ppublish
LG - German
DP - 2016 May
DC - 20160514
EZ - 2016/05/06 06:00
DA - 2016/05/06 06:00
DT - 2016/05/06 06:00
YR - 2016
RD - 20161219
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27146870
<458. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25712627
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Abdallah AO
AU - Herlopian A
AU - Ravilla R
AU - Bansal M
AU - Chandra-Reddy S
AU - Mahmoud F
AU - Ong S
AU - Gokden M
AU - Hutchins L
FA - Abdallah, Al-Ola
FA - Herlopian, Aline
FA - Ravilla, Rahul
FA - Bansal, Meghana
FA - Chandra-Reddy, Sowmya
FA - Mahmoud, Fade
FA - Ong, Shirley
FA - Gokden, Murat
FA - Hutchins, Laura
IN - Abdallah, Al-Ola. Department of Internal Medicine, Division of Hematology and Oncology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.
IN - Herlopian, Aline. Department of Internal Medicine, Division of Neurology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.
IN - Ravilla, Rahul. Department of Internal Medicine, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.
IN - Bansal, Meghana. Department of Internal Medicine, Division of Hematology and Oncology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.
IN - Chandra-Reddy, Sowmya. Department of Internal Medicine, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.
IN - Mahmoud, Fade. Department of Internal Medicine, Division of Hematology and Oncology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.
IN - Ong, Shirley. Department of Internal Medicine, Division of Neurology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.
IN - Gokden, Murat. Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA.
IN - Hutchins, Laura. Department of Internal Medicine, Division of Hematology and Oncology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, USA HutchinsLauraF@uams.edu.
TI - Ipilimumab-induced necrotic myelopathy in a patient with metastatic melanoma: A case report and review of literature.
SO - Journal of Oncology Pharmacy Practice. 22(3):537-42, 2016 Jun
AS - J Oncol Pharm Pract. 22(3):537-42, 2016 Jun
NJ - Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9511372
IO - J Oncol Pharm Pract
SB - Index Medicus
CP - England
KW - Ipilimumab; immune-related adverse events; progressive necrotic myelopathy
AB - Ipilimumab is a novel humanized monoclonal antibody directed against cytotoxic T lymphocyte antigen 4, a T-cell surface molecule involved in down-regulation and suppression of the T cell response to stimuli. Patients treated with ipilimumab are at risk for immune-related adverse events involving the skin, digestive tract, liver and endocrine organs. Few case reports of immune-related adverse effects involving central or peripheral nervous system due to ipilimumab are published. These include inflammatory myopathy, aseptic meningitis, severe meningo-radiculo-neuritis, temporal arteritis, Guillain-Barre syndrome, and posterior reversible encephalopathy syndrome. We report the first case of ipilimumab-induced progressive necrotic myelopathy.
AB - Copyright © The Author(s) 2015.
ES - 1477-092X
IL - 1078-1552
DI - 1078155215572932
DO - https://dx.doi.org/10.1177/1078155215572932
PT - Journal Article
ID - 25712627 [pubmed]
ID - 1078155215572932 [pii]
ID - 10.1177/1078155215572932 [doi]
PP - ppublish
LG - English
EP - 20150223
DP - 2016 Jun
DC - 20160423
EZ - 2015/02/26 06:00
DA - 2015/02/26 06:00
DT - 2015/02/26 06:00
YR - 2016
RD - 20161219
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=25712627
<459. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 25694346
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Eryilmaz MK
AU - Mutlu H
AU - Salim DK
AU - Musri FY
AU - Tural D
AU - Bassorgun I
AU - Coskun HS
FA - Eryilmaz, Melek Karakurt
FA - Mutlu, Hasan
FA - Salim, Derya Kivrak
FA - Musri, Fatma Yalcin
FA - Tural, Deniz
FA - Bassorgun, Ibrahim
FA - Coskun, Hasan Senol
IN - Eryilmaz, Melek Karakurt. Department of Medical Oncology, Akdeniz University School of Medicine, Antalya, Turkey drangelkarakurt@hotmail.com.
IN - Mutlu, Hasan. Department of Medical Oncology, Akdeniz University School of Medicine, Antalya, Turkey.
IN - Salim, Derya Kivrak. Department of Medical Oncology, Akdeniz University School of Medicine, Antalya, Turkey.
IN - Musri, Fatma Yalcin. Department of Medical Oncology, Akdeniz University School of Medicine, Antalya, Turkey.
IN - Tural, Deniz. Department of Medical Oncology, Akdeniz University School of Medicine, Antalya, Turkey.
IN - Bassorgun, Ibrahim. Department of Pathology, Akdeniz University School of Medicine, Antalya, Turkey.
IN - Coskun, Hasan Senol. Department of Medical Oncology, Akdeniz University School of Medicine, Antalya, Turkey.
TI - Ipilimumab may increase the severity of cutenaous toxicity related to radiotherapy.
SO - Journal of Oncology Pharmacy Practice. 22(3):533-6, 2016 Jun
AS - J Oncol Pharm Pract. 22(3):533-6, 2016 Jun
NJ - Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9511372
IO - J Oncol Pharm Pract
SB - Index Medicus
CP - England
KW - Melanoma; cytotoxic T-lymphocyte antigen-4; dermatitis; ipilimumab; radiotherapy
AB - Ipilimumab, monoclonal antibody against cytotoxic T-lymphocyte antigen-4 and, radiotherapy are commonly used to treat unresectable and metastatic melanoma. As a result of upregulation of immune system with ipilimumab, many immune-related adverse effects, such as dermatitis, colitis, hepatitis, and hypophysitis, have been previously reported in literature. Typically, these effects are treated with high-dose steroids and mostly heal up. Here, we report a case who was receiving radiotherapy due to metastatic malignant melanoma with atypical generalized rash, which was enlarged with concurrent ipilimumab treatment.
AB - Copyright © The Author(s) 2015.
ES - 1477-092X
IL - 1078-1552
DI - 1078155215572930
DO - https://dx.doi.org/10.1177/1078155215572930
PT - Journal Article
ID - 25694346 [pubmed]
ID - 1078155215572930 [pii]
ID - 10.1177/1078155215572930 [doi]
PP - ppublish
LG - English
EP - 20150217
DP - 2016 Jun
DC - 20160423
EZ - 2015/02/20 06:00
DA - 2015/02/20 06:00
DT - 2015/02/20 06:00
YR - 2016
RD - 20161219
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=25694346
<460. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27554835
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Kushnir I
AU - Wolf I
FA - Kushnir, Igal
FA - Wolf, Ido
IN - Kushnir, Igal. Oncology Division, Tel Aviv Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
TI - Nivolumab-Induced Pericardial Tamponade: A Case Report and Discussion.
SO - Cardiology. 136(1):49-51, 2017
AS - Cardiology. 136(1):49-51, 2017
NJ - Cardiology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - coi, 1266406
IO - Cardiology
CP - Switzerland
AB - Nivolumab, a programmed death 1 (PD1) inhibitor, belongs to a family of drugs known as immune checkpoint inhibitors that share a similar toxicity profile, which includes rash, pruritus, colitis, hepatitis, pneumonitis and thyroid dysfunction. Nivolumab has a proven efficacy in the treatment of malignant melanoma, non-small cell lung cancer and renal cell carcinoma. We present the case of a 67-year-old male patient with metastatic squamous cell carcinoma of the lung who suffered from a massive pericardial effusion secondary to treatment with nivolumab, which he began in June 2015. After five cycles the patient was hospitalized due to acute respiratory failure requiring mechanical ventilation. An echocardiogram revealed a massive pericardial effusion with tamponade. After pericardiocentesis and corticosteroid treatment, the patient's condition improved rapidly. A CT scan revealed a response of the tumor. Although anti-PD1 treatment is usually regarded as less toxic than chemotherapy, a wide spectrum of life-threatening immune-related side effects may still occur and clinical vigilance is required.
AB - Copyright © 2016 S. Karger AG, Basel.
ES - 1421-9751
IL - 0008-6312
DI - 000447053
DO - https://dx.doi.org/10.1159/000447053
PT - Journal Article
ID - 27554835 [pubmed]
ID - 000447053 [pii]
ID - 10.1159/000447053 [doi]
PP - ppublish
PH - 2016/05/23 [received]
PH - 2016/05/24 [accepted]
LG - English
EP - 20160824
DP - 2017
DC - 20160824
EZ - 2016/08/25 06:00
DA - 2016/08/25 06:00
DT - 2016/08/25 06:00
YR - 2017
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27554835
<461. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27117582
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Duchnowska R
AU - Peksa R
AU - Radecka B
AU - Mandat T
AU - Trojanowski T
AU - Jarosz B
AU - Czartoryska-Arlukowicz B
AU - Olszewski WP
AU - Och W
AU - Kalinka-Warzocha E
AU - Kozlowski W
AU - Kowalczyk A
AU - Loi S
AU - Biernat W
AU - Jassem J
AU - Polish Brain Metastasis Consortium
FA - Duchnowska, Renata
FA - Peksa, Rafal
FA - Radecka, Barbara
FA - Mandat, Tomasz
FA - Trojanowski, Tomasz
FA - Jarosz, Bozena
FA - Czartoryska-Arlukowicz, Bogumila
FA - Olszewski, Wojciech P
FA - Och, Waldemar
FA - Kalinka-Warzocha, Ewa
FA - Kozlowski, Wojciech
FA - Kowalczyk, Anna
FA - Loi, Sherene
FA - Biernat, Wojciech
FA - Jassem, Jacek
FA - Polish Brain Metastasis Consortium
IN - Duchnowska, Renata. Department of Oncology, Military Institute of Medicine, Szaserow St 128, 04-141, Warsaw, Poland. rdtt@wp.pl.
IN - Peksa, Rafal. Department of Pathology, Medical University of Gdansk, 7 Debinki St, 80-211, Gdansk, Poland.
IN - Radecka, Barbara. Department of Oncology, Regional Oncology Center, 66a Katowicka St, 45-060, Opole, Poland.
IN - Mandat, Tomasz. Department of Neurosurgery, Oncology Center-Institute, 5 Roentgena St, 02-781, Warsaw, Poland.
IN - Trojanowski, Tomasz. Department of Neurosurgery, Medical University of Lublin, 1 Al. Raclawickie, 20-059, Lublin, Poland.
IN - Jarosz, Bozena. Department of Neurosurgery, Medical University of Lublin, 1 Al. Raclawickie, 20-059, Lublin, Poland.
IN - Czartoryska-Arlukowicz, Bogumila. Department of Oncology, Regional Oncology Center, 12 Ogrodowa St, 15-027, Bialystok, Poland.
IN - Olszewski, Wojciech P. Department of Pathology, Oncology Center-Institute, 5 Roentgena St, 02-781, Warsaw, Poland.
IN - Och, Waldemar. Department of Neurosurgery, Regional Hospital, 18 Zolnierska St, 10-561, Olsztyn, Poland.
IN - Kalinka-Warzocha, Ewa. Department of Oncology, Regional Oncology Center, 62 Pabianicka St, 93-513, Lodz, Poland.
IN - Kozlowski, Wojciech. Department of Pathology, Military Institute of Medicine, Szaserow St 128, 04-141, Warsaw, Poland.
IN - Kowalczyk, Anna. Department of Oncology and Radiotherapy, Medical University of Gdansk, 7 Debinki St, 80-211, Gdansk, Poland.
IN - Loi, Sherene. Division of Cancer Medicine and Research, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, East Melbourne, VIC, 8006, Australia.
IN - Biernat, Wojciech. Department of Pathology, Medical University of Gdansk, 7 Debinki St, 80-211, Gdansk, Poland.
IN - Jassem, Jacek. Department of Oncology and Radiotherapy, Medical University of Gdansk, 7 Debinki St, 80-211, Gdansk, Poland.
TI - Immune response in breast cancer brain metastases and their microenvironment: the role of the PD-1/PD-L axis.
SO - Breast Cancer Research. 18(1):43, 2016 Apr 27
AS - Breast Cancer Res. 18(1):43, 2016 Apr 27
NJ - Breast cancer research : BCR
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 100927353, dyz
IO - Breast Cancer Res.
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847231
SB - Index Medicus
CP - England
KW - Brain metastases; Breast cancer; Lymphocytes; PD-1; PD-L
AB - BACKGROUND: A better understanding of immune response in breast cancer brain metastases (BCBM) may prompt new preventive and therapeutic strategies.
AB - METHODS: Immunohistochemical expression of stromal tumor-infiltrating lymphocytes (TILs: CD4, CD8, CTLA4), macrophage/microglial cells (CD68), programmed cell death protein 1 receptor (PD-1), programmed cell death protein 1 receptor ligand (PD-L)1, PD-L2 and glial fibrillary acid protein was assessed in 84 BCBM and their microenvironment.
AB - RESULTS: Median survival after BCBM excision was 18.3 months (range 0-99). Median number of CD4+, CD8+ TILs and CD68+ was 49, 69 and 76 per 1 mm(2), respectively. PD-L1 and PD-L2 expression in BCBM was present in 53 % and 36 % of cases, and was not related to BCBM phenotype. PD-1 expression on TILs correlated positively with CD4+ and CD8+ TILs (r=0.26 and 0.33), and so did CD68+ (r=0.23 and 0.27, respectively). In the multivariate analysis, survival after BCBM excision positively correlated with PD-1 expression on TILs (hazard ratio (HR)=0.3, P=0.003), CD68+ infiltration (HR=0.2, P<0.001), brain radiotherapy (HR=0.1, P<0.001), endocrine therapy (HR=0.1, P<0.001), and negatively with hormone-receptor-negative/human epidermal growth factor receptor 2 (HER2)-positive phenotype of primary tumor (HR=2.6, P=0.01), HER2 expression in BCBM (HR=4.9, P=0.01).
AB - CONCLUSIONS: PD-L1 and PD-L2 expression is a common occurrence in BCBM, irrespective of primary tumor and BCBM phenotype. Favorable prognostic impact of PD-1 expression on TILs suggests a beneficial effect of preexisting immunity and implies a potential therapeutic role of immune checkpoint inhibitors in BCBM.
ES - 1465-542X
IL - 1465-5411
DI - 10.1186/s13058-016-0702-8
DO - https://dx.doi.org/10.1186/s13058-016-0702-8
PT - Journal Article
ID - 27117582 [pubmed]
ID - 10.1186/s13058-016-0702-8 [doi]
ID - 10.1186/s13058-016-0702-8 [pii]
ID - PMC4847231 [pmc]
PP - epublish
PH - 2015/12/08 [received]
PH - 2016/04/04 [accepted]
LG - English
EP - 20160427
DP - 2016 Apr 27
DC - 20160427
EZ - 2016/04/28 06:00
DA - 2016/04/28 06:00
DT - 2016/04/28 06:00
YR - 2016
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27117582
<462. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27000274
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Shimizu T
AU - Seto T
AU - Hirai F
AU - Takenoyama M
AU - Nosaki K
AU - Tsurutani J
AU - Kaneda H
AU - Iwasa T
AU - Kawakami H
AU - Noguchi K
AU - Shimamoto T
AU - Nakagawa K
FA - Shimizu, Toshio
FA - Seto, Takashi
FA - Hirai, Fumihiko
FA - Takenoyama, Mitsuhiro
FA - Nosaki, Kaname
FA - Tsurutani, Junji
FA - Kaneda, Hiroyasu
FA - Iwasa, Tsutomu
FA - Kawakami, Hisato
FA - Noguchi, Kazuo
FA - Shimamoto, Takashi
FA - Nakagawa, Kazuhiko
IN - Shimizu, Toshio. Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan. jcog9511@hotmail.co.jp.
IN - Seto, Takashi. Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.
IN - Hirai, Fumihiko. Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.
IN - Takenoyama, Mitsuhiro. Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.
IN - Nosaki, Kaname. Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.
IN - Tsurutani, Junji. Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
IN - Kaneda, Hiroyasu. Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
IN - Iwasa, Tsutomu. Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
IN - Kawakami, Hisato. Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
IN - Noguchi, Kazuo. MSD K.K., Kitanomaru square, 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, 102-8667, Japan.
IN - Shimamoto, Takashi. MSD K.K., Kitanomaru square, 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, 102-8667, Japan.
IN - Nakagawa, Kazuhiko. Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
TI - Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors.
SO - Investigational New Drugs. 34(3):347-54, 2016 Jun
AS - Invest New Drugs. 34(3):347-54, 2016 Jun
NJ - Investigational new drugs
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - gwj, 8309330
IO - Invest New Drugs
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859860
SB - Index Medicus
CP - United States
KW - Anti-PD-1 therapy; PD-L1; Pembrolizumab; Pharmacokinetics; Phase I study
AB - Background This phase I study evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics, immunogenicity, and antitumor activity of pembrolizumab in Japanese patients with advanced solid tumors. Methods Following an initial dose and a 28-day rest (cycle 1), pembrolizumab was administered as an intravenous infusion at escalating doses (2 or 10 mg/kg) every 2 weeks (Q2W) until disease progression or unacceptable toxicity. Adverse events (AEs) were assessed using CTCAE v4.0, and tumor response was assessed using both RECIST v1.1 and immune-related response criteria (irRC). Full pharmacokinetic sampling was performed during cycle 1. Results Three patients received pembrolizumab at 2.0 mg/kg and seven at 10 mg/kg. No dose-limiting toxicities were observed during cycle 1. Eighty percent of patients experienced drug-related AEs (mostly grade 1 or 2); the most common drug-related AEs were nausea, malaise, pyrexia, and aspartate aminotransferase/alanine transaminase (AST/ALT) elevations (n=2 each). No drug-related grade 4 or 5 AEs occurred. Immune-related AEs comprised grade 3 ALT elevation (n=1), grade 3 AST elevation (n=1), grade 1 pneumonitis (n=1), and grade 1 thyroid-stimulating hormone elevation (n=1). The safety and pharmacokinetic profiles of Japanese patients were similar to those previously reported for Caucasian patients. A partial tumor response was observed in one patient with non-small-cell lung cancer (NSCLC) and in one patient with melanoma. Conclusions Pembrolizumab at both 2 and 10 mg/kg Q2W was well tolerated in Japanese patients with advanced solid tumors and showed encouraging anti-tumor activity against melanoma and NSCLC.
ES - 1573-0646
IL - 0167-6997
DI - 10.1007/s10637-016-0347-6
DO - https://dx.doi.org/10.1007/s10637-016-0347-6
PT - Journal Article
ID - 27000274 [pubmed]
ID - 10.1007/s10637-016-0347-6 [doi]
ID - 10.1007/s10637-016-0347-6 [pii]
ID - PMC4859860 [pmc]
PP - ppublish
PH - 2016/03/09 [received]
PH - 2016/03/16 [accepted]
LG - English
EP - 20160322
DP - 2016 Jun
DC - 20160507
EZ - 2016/03/23 06:00
DA - 2016/03/24 06:00
DT - 2016/03/24 06:00
YR - 2016
RD - 20161215
UP - 20161222
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27000274
<463. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27842767
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Bunchorntavakul C
AU - Reddy KR
FA - Bunchorntavakul, Chalermrat
FA - Reddy, K Rajender
IN - Bunchorntavakul, Chalermrat. Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, HUP, Philadelphia, PA 19104, USA; Division of Gastroenterology and Hepatology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Rajavithi Road, Ratchathewi, Bangkok 10400, Thailand.
IN - Reddy, K Rajender. Liver Transplantation, Viral Hepatitis Center, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, HUP, Liver Transplant Office, Philadelphia, PA 19104, USA. Electronic address: rajender.reddy@uphs.upenn.edu.
TI - Drug Hepatotoxicity: Newer Agents. [Review]
SO - Clinics in Liver Disease. 21(1):115-134, 2017 Feb
AS - Clin Liver Dis. 21(1):115-134, 2017 Feb
NJ - Clinics in liver disease
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dw6, 9710002
IO - Clin Liver Dis
CP - United States
KW - Antibiotics; Anticoagulants; Antiplatelet; Antiretrovirals; Drug-induced liver injury; Hepatotoxicity; Monoclonal antibodies; Tyrosine kinase inhibitors
AB - Idiosyncratic hepatotoxicity is one of the most common reasons for an approved drug being restricted. This article focuses on hepatotoxicity of selected and recently introduced agents, such as, tyrosine kinase inhibitors, monoclonal antibodies, novel oral anticoagulants, newer antiplatelets, antibiotics, anti-diabetics, anti-epileptics, anti-depressants, anti-psychotics and anti-retrovirals. Overall, the incidence of clinically relevant hepatotoxicity from newer agents seems to be lower than that of the older agents. Nevertheless, cases of severe hepatotoxicity have been reported due to some of these newer agents, including, trastuzumab, ipilimumab, infliximab, imatinib, bosutinib, dasatinib, gefitinib, erlotinib, sunitinib, ponatinib, lapatinib, vemurafenib, dabigatran, rivaroxaban, felbamate, lamotrigine, levetiracetam, venlafaxine, duloxetine, darunavir, and maraviroc.
AB - Copyright © 2016 Elsevier Inc. All rights reserved.
ES - 1557-8224
IL - 1089-3261
DI - S1089-3261(16)30068-X
DO - https://dx.doi.org/10.1016/j.cld.2016.08.009
PT - Review
PT - Journal Article
ID - 27842767 [pubmed]
ID - S1089-3261(16)30068-X [pii]
ID - 10.1016/j.cld.2016.08.009 [doi]
PP - ppublish
LG - English
EP - 20161014
DP - 2017 Feb
DC - 20161115
EZ - 2016/11/16 06:00
DA - 2016/11/16 06:00
DT - 2016/11/16 06:00
YR - 2017
RD - 20161116
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27842767
<464. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27818005
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Wachsmann JW
AU - Ganti R
AU - Peng F
FA - Wachsmann, Jason W
FA - Ganti, Ramapriya
FA - Peng, Fangyu
IN - Wachsmann, Jason W. Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9140. Electronic address: Jason.Wachsmann@UTSouthwestern.edu.
IN - Ganti, Ramapriya. Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9140.
IN - Peng, Fangyu. Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9140; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas.
TI - Immune-mediated Disease in Ipilimumab Immunotherapy of Melanoma with FDG PET-CT. [Review]
SO - Academic Radiology. 24(1):111-115, 2017 Jan
AS - Acad Radiol. 24(1):111-115, 2017 Jan
NJ - Academic radiology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - clv, 9440159
IO - Acad Radiol
CP - United States
KW - FDG; PET-CT; immune-related adverse events; ipilimumab; melanoma
AB - RATIONALE AND OBJECTIVES: The purposes of this study were to provide a case-based overview of various immune-mediated side effects detected by 18F-Fluorodeoxyglucose (F-18 FDG) positron emission tomography-computed tomography (PET-CT) in the patients receiving ipilimumab immunotherapy for treatment of malignant melanoma, and discuss the importance of recognizing immune-mediated side effects in the use of F-18 FDG PET-CT for monitoring therapeutic effects of ipilimumab on metastatic melanoma.
AB - MATERIALS AND METHODS: This is a retrospective case series study of the patients diagnosed with melanoma who were subjected to immunomodulating therapy with ipilimumab. F-18 FDG PET-CT findings were reviewed, and the patients with immune-mediated side effects were selected for further analysis, in conjunction with review of clinical progress notes, the results of laboratory tests, and findings of other imaging tests.
AB - RESULTS: Four patients with immune-mediated side effects were identified among the patients being treated with ipilimumab and subjected to F-18 FDG PET-CT for monitoring therapeutic effects. These immune mediated side effects include new findings of abnormal increased FDG uptake associated with immune-mediated pancreatitis and hypophysitis, as well as immune-mediated thyroiditis and colitis reported previously.
AB - CONCLUSIONS: Various immune-mediated side effects were detected by F-18 FDG PET-CT in the patients subjected to immunomodulating therapy with ipilimumab. It is essential for the interpreting provider to recognize and differentiate abnormal FDG uptake associated with immune-mediated side effects from hypermetabolic malignant lesions when using F-18 FDG PET-CT for monitoring therapeutic effects of ipilimumab on melanoma lesions.
AB - Copyright A© 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.
ES - 1878-4046
IL - 1076-6332
DI - S1076-6332(16)30180-5
DO - https://dx.doi.org/10.1016/j.acra.2016.08.005
PT - Review
PT - Journal Article
ID - 27818005 [pubmed]
ID - S1076-6332(16)30180-5 [pii]
ID - 10.1016/j.acra.2016.08.005 [doi]
PP - ppublish
PH - 2015/11/25 [received]
PH - 2016/08/05 [revised]
PH - 2016/08/07 [accepted]
LG - English
EP - 20161104
DP - 2017 Jan
DC - 20161107
EZ - 2016/11/08 06:00
DA - 2016/11/08 06:00
DT - 2016/11/08 06:00
YR - 2017
RD - 20161205
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27818005
<465. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27876011
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Jung K
AU - Zeng X
AU - Bilusic M
AI - Jung, Kyungsuk; ORCID: http://orcid.org/0000-0003-1306-5180
FA - Jung, Kyungsuk
FA - Zeng, Xu
FA - Bilusic, Marijo
IN - Jung, Kyungsuk. Department of Medicine, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA, 19111, USA. Kyungsuk.Jung@fccc.edu.
IN - Zeng, Xu. Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, 3500N Broad St, Philadelphia, PA, 19140, USA.
IN - Bilusic, Marijo. Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA, 19111, USA.
TI - Nivolumab-associated acute glomerulonephritis: a case report and literature review.
SO - BMC Nephrology. 17(1):188, 2016 Nov 22
AS - BMC Nephrol. 17(1):188, 2016 Nov 22
NJ - BMC nephrology
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 100967793
IO - BMC Nephrol
CP - England
KW - Acute kidney injury; Autoimmune nephritis; Case report; Immunotherapy; Nivolumab; Renal cell carcinoma
AB - BACKGROUND: Immune checkpoint inhibitors are changing the landscape of oncology treatment as they are significantly improving treatment for multiple malignancies. Nivolumab, an anti-programmed death 1 antibody, is a US Food and Drug Administration-approved treatment for melanoma, non-small cell lung cancer, and kidney cancer but can result in a spectrum of autoimmune side effects. Adverse effects can occur within any organ system in the body including the colon, lung, liver, endocrine systems, or kidneys.
AB - CASE PRESENTATION: A 70-year-old male with clear cell kidney cancer was admitted with acute kidney injury while on nivolumab. A kidney biopsy revealed diffuse tubular injury and immune complex-mediated glomerulonephritis. Electron microscopy of the specimen showed hump-like subepithelial deposits. Nivolumab was discontinued and the patient was started on a high dose of steroids. After 5 months of systemic corticosteroids and hemodialysis, the patient's kidney function improved to his baseline level. Despite a prolonged interruption to treatment, immunosuppressive therapy did not compromise the anticancer effects of nivolumab.
AB - CONCLUSION: Immune-related adverse effects in the kidney can cause autoimmune glomerulonephritis as well as tubulointerstitial injury. In the literature, immune-related nephritis generally responded well to systemic corticosteroid treatment. Based on our experience, a prolonged course of a high dose of steroids and hemodialysis may be required to achieve an adequate treatment effect.
ES - 1471-2369
IL - 1471-2369
DI - 10.1186/s12882-016-0408-2
DO - https://dx.doi.org/10.1186/s12882-016-0408-2
PT - Journal Article
ID - 27876011 [pubmed]
ID - 10.1186/s12882-016-0408-2 [doi]
ID - 10.1186/s12882-016-0408-2 [pii]
ID - PMC5120473 [pmc]
PP - epublish
PH - 2016/06/10 [received]
PH - 2016/11/15 [accepted]
LG - English
EP - 20161122
DP - 2016 Nov 22
DC - 20161123
EZ - 2016/11/24 06:00
DA - 2016/11/24 06:00
DT - 2016/11/24 06:00
YR - 2016
RD - 20161129
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27876011
<466. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27857838
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Trainer H
AU - Hulse P
AU - Higham CE
AU - Trainer P
AU - Lorigan P
FA - Trainer, Harris
FA - Hulse, Paul
FA - Higham, Claire E
FA - Trainer, Peter
FA - Lorigan, Paul
IN - Trainer, Harris. Departments of Endocrinology.
IN - Hulse, Paul. Departments of Radiology.
IN - Higham, Claire E. Departments of Endocrinology.
IN - Trainer, Peter. Departments of Endocrinology.
IN - Lorigan, Paul. Departments of Medical Oncology , The Christie NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester , UK.
TI - Hyponatraemia secondary to nivolumab-induced primary adrenal failure.
SO - Endocrinology, Diabetes & Metabolism Case Reports. 2016, 2016
AS - Endocrinol Diabetes Metab Case Rep. 2016, 2016
NJ - Endocrinology, diabetes & metabolism case reports
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - 101618943
IO - Endocrinol Diabetes Metab Case Rep
CP - England
AB - : Checkpoint inhibitors, such as ipilimumab and pembrolizumab, have transformed the prognosis for patients with advanced malignant melanoma and squamous non-small-cell lung cancer, and their use will only expand as experience is gained in a variety of other malignancies, for instance, renal and lymphoma. As the use of checkpoint inhibitors increases, so too will the incidence of their unique side effects, termed immune-related adverse events (irAEs), which can affect dermatological, gastrointestinal, hepatic, endocrine and other systems. Nivolumab is a monoclonal antibody that blocks the human programmed death receptor-1 ligand (PD-L1) found on many cancer cells and is licensed for the treatment of advanced malignant melanoma. We describe the first case of nivolumab-induced adrenalitis resulting in primary adrenal failure presenting with hyponatraemia in a 43-year-old man with malignant melanoma. The case highlights the potentially life-threatening complications of checkpoint inhibitors and the need for patient education and awareness of irAEs among the wider clinical community because such side effects require prompt recognition and treatment.
AB - LEARNING POINTS: Nivolumab can cause primary adrenal insufficiency.Not all cases of hyponatraemia in patients with malignancy are due to SIADH.Any patient on a checkpoint inhibitor becoming unwell should have serum cortisol urgently measured and if in doubt hydrocortisone therapy should be initiated.Although hyponatraemia can occur in patients with ACTH deficiency, the possibility of primary adrenal failure should also be considered and investigated by measurement of renin, aldosterone and ACTH.Patients receiving checkpoint inhibitors require education on the potential risks of hypocortisolaemia.PET imaging demonstrated bilateral increased activity consistent with an autoimmune adrenalitis.
IL - 2052-0573
DI - 16-0108
DI - EDM160108
DO - https://dx.doi.org/10.1530/EDM-16-0108
PT - Journal Article
ID - 27857838 [pubmed]
ID - 10.1530/EDM-16-0108 [doi]
ID - EDM160108 [pii]
ID - PMC5097140 [pmc]
PP - ppublish
PH - 2016/10/04 [received]
PH - 2016/10/14 [accepted]
LG - English
EP - 20161101
DP - 2016
DC - 20161118
EZ - 2016/11/19 06:00
DA - 2016/11/20 06:00
DT - 2016/11/20 06:00
YR - 2016
RD - 20161121
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27857838
<467. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27777775
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Wilson MA
AU - Guld K
AU - Galetta S
AU - Walsh RD
AU - Kharlip J
AU - Tamhankar M
AU - McGettigan S
AU - Schuchter LM
AU - Fecher LA
FA - Wilson, Melissa A
FA - Guld, Kelly
FA - Galetta, Steven
FA - Walsh, Ryan D
FA - Kharlip, Julia
FA - Tamhankar, Madhura
FA - McGettigan, Suzanne
FA - Schuchter, Lynn M
FA - Fecher, Leslie A
IN - Wilson, Melissa A. Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA USA ; Present address: Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY USA.
IN - Guld, Kelly. Department of Medicine, University of Pennsylvania, Philadelphia, PA USA ; Present address: Department of Cardiology, UCSF Medical Center, San Francisco, CA USA.
IN - Galetta, Steven. Department of Neurology, NYU Langone Medical Center, New York, NY USA.
IN - Walsh, Ryan D. Departments of Ophthalmology and Neurology, Medical College of Wisconsin, Milwaukee, WI USA.
IN - Kharlip, Julia. Division of Endocrinology, Department of Medicine, University of Pennsylvania, Philadelphia, PA USA.
IN - Tamhankar, Madhura. Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania Health System, Philadelphia, PA USA.
IN - McGettigan, Suzanne. Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA USA.
IN - Schuchter, Lynn M. Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA USA.
IN - Fecher, Leslie A. Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA USA ; Present address: Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, C366 MIB 1500 E. Medical Center Drive, SPC5848, Ann Arbor, MI 48109 USA.
TI - Acute visual loss after ipilimumab treatment for metastatic melanoma.
SO - Journal for Immunotherapy of Cancer. 4:66, 2016
AS - J Immunother Cancer. 4:66, 2016
NJ - Journal for immunotherapy of cancer
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101620585
IO - J Immunother Cancer
CP - England
KW - Checkpoint inhibitors; Immune; Ipilimumab; Melanoma; Optic neuritis; Side effects
AB - BACKGROUND: Ipilimumab, a humanized CLTA-4 antibody is a standard therapy in the treatment of advanced melanoma. While ipilimumab provides an overall survival benefit to patients, it can be associated with immune related adverse events (IrAEs).
AB - CASE PRESENTATION: Here we describe a patient treated with ipilimumab who experienced known IrAEs, including hypophysitis, as well as a profound vision loss due to optic neuritis. There are rare reports of optic neuritis occurring as an adverse event associated with ipilimumab treatment. Furthermore, the patient experienced multiple complications from high dose steroids used to manage his IrAEs.
AB - CONCLUSIONS: This case highlights the need for recognition of atypical immune mediated processes associated with newer checkpoint inhibitor therapies including ipilimumab.
IL - 2051-1426
DI - 170
DO - https://dx.doi.org/10.1186/s40425-016-0170-9
PT - Journal Article
ID - 27777775 [pubmed]
ID - 10.1186/s40425-016-0170-9 [doi]
ID - 170 [pii]
ID - PMC5067900 [pmc]
PP - epublish
PH - 2016/03/24 [received]
PH - 2016/09/29 [accepted]
GI - No: T32 CA009615
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
EP - 20161018
DP - 2016
DC - 20161025
EZ - 2016/10/26 06:00
DA - 2016/10/26 06:00
DT - 2016/10/26 06:00
YR - 2016
RD - 20161202
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27777775
<468. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27777773
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Ong M
AU - Ibrahim AM
AU - Bourassa-Blanchette S
AU - Canil C
AU - Fairhead T
AU - Knoll G
FA - Ong, Michael
FA - Ibrahim, Andrea Marie
FA - Bourassa-Blanchette, Samuel
FA - Canil, Christina
FA - Fairhead, Todd
FA - Knoll, Greg
IN - Ong, Michael. Department of Medicine, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada ; The Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.
IN - Ibrahim, Andrea Marie. The Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.
IN - Bourassa-Blanchette, Samuel. Department of Medicine, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.
IN - Canil, Christina. Department of Medicine, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.
IN - Fairhead, Todd. Department of Medicine, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.
IN - Knoll, Greg. Department of Medicine, The Ottawa Hospital, 501 Smyth Road, Ottawa, ON K1H 8L6 Canada.
TI - Antitumor activity of nivolumab on hemodialysis after renal allograft rejection.
SO - Journal for Immunotherapy of Cancer. 4:64, 2016
AS - J Immunother Cancer. 4:64, 2016
NJ - Journal for immunotherapy of cancer
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Print
JC - 101620585
IO - J Immunother Cancer
CP - England
KW - Acute allograft rejection; Anti-PD-1 therapy; Hemodialysis; Melanoma; Nivolumab; Organ transplant
AB - BACKGROUND: Nivolumab (OpdivoTM) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer.
AB - CASE PRESENTATION: We illustrate the outcomes of a 63 year-old type I diabetic female patient who developed pulmonary metastatic, BRAF wild-type cutaneous melanoma 10 years after renal transplantation. After downward titration of the patient's immunosuppressive medications and extensive multidisciplinary review, she was treated with nivolumab in the first-line setting. Within 1 week of administration, the patient experienced acute renal allograft rejection, renal failure and concurrent diabetic ketoacidosis due to steroid therapy. Allograft function did not return, but patient made a full clinical recovery after being placed on hemodialysis. Subsequently, the patient had clinical disease progression off therapy and required re-challenge with nivolumab on hemodialysis, resulting in ongoing clinical and radiographic response.
AB - CONCLUSIONS: This case illustrates multiple practical challenges and dangers of administering anti-PD1 immune checkpoint inhibitors to patients with solid-organ transplantation including need for titration of immunosuppressive medications, risks of allograft rejection, and treatment during hemodialysis.
IL - 2051-1426
DI - 171
DO - https://dx.doi.org/10.1186/s40425-016-0171-8
PT - Journal Article
ID - 27777773 [pubmed]
ID - 10.1186/s40425-016-0171-8 [doi]
ID - 171 [pii]
ID - PMC5067882 [pmc]
PP - epublish
PH - 2016/08/03 [received]
PH - 2016/09/29 [accepted]
LG - English
EP - 20161018
DP - 2016
DC - 20161025
EZ - 2016/10/26 06:00
DA - 2016/10/26 06:00
DT - 2016/10/26 06:00
YR - 2016
RD - 20161102
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27777773
<469. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27755140
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Dawood S
AU - Rugo HS
FA - Dawood, Shaheenah
FA - Rugo, Hope S
IN - Dawood, Shaheenah. aDepartment of Medical Oncology, Dubai Hospital, UAE bUniversity of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
TI - Targeting the host immune system: PD-1 and PD-L1 antibodies and breast cancer.
SO - Current Opinion in Supportive & Palliative Care. 10(4):336-342, 2016 Dec
AS - Curr. opin. support. palliat. care. 10(4):336-342, 2016 Dec
NJ - Current opinion in supportive and palliative care
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101297402
IO - Curr Opin Support Palliat Care
CP - United States
AB - PURPOSE OF REVIEW: This article describes the role of the PD-1 axis and reviews current data and future directions inhibiting PD-1 and PD-L1 in breast cancer.
AB - RECENT FINDINGS: Four phase I monotherapy expansion trials in patients with metastatic breast cancer have demonstrated low but durable single agent responses to PD-1 and PD-L1 inhibitors, ranging from 4.8 to 19%. Higher response rates are seen in triple negative breast cancer, compared with hormone receptor positive disease. Variability in requirements for tumor PD-L1 expression, and variations in testing complicate cross trial comparisons. A fifth phase Ib trial reported a 38% response rate in metastatic triple negative breast cancer treated with the combination of a PD-L1 inhibitor and nab-paclitaxel chemotherapy. Treatment is generally well tolerated, with low rates of immune toxicity including hypothyroidism, pneumonitis, hepatitis, colitis, and hypophysitis, occurring even months after the end of therapy.
AB - SUMMARY: Immune checkpoint inhibitor therapy has recently been shown to have clinical efficacy in the treatment of breast cancer. The most compelling data are in the triple negative subtype, with responses documented in hormone receptor positive disease as well. Numerous trials are evaluating various combination strategies and biomarkers in early and late stage disease to enhance immunogenicity and response.
ES - 1751-4266
IL - 1751-4258
DO - https://dx.doi.org/10.1097/SPC.0000000000000243
PT - Journal Article
ID - 27755140 [pubmed]
ID - 10.1097/SPC.0000000000000243 [doi]
PP - ppublish
LG - English
DP - 2016 Dec
DC - 20161018
EZ - 2016/10/27 06:00
DA - 2016/10/27 06:00
DT - 2016/10/27 06:00
YR - 2016
RD - 20161027
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27755140
<470. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27662340
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Diem S
AU - Keller F
AU - Ruesch R
AU - Maillard SA
AU - Speiser DE
AU - Dummer R
AU - Siano M
AU - Urner-Bloch U
AU - Goldinger SM
AU - Flatz L
FA - Diem, Stefan
FA - Keller, Fabienne
FA - Ruesch, Reinhard
FA - Maillard, Samia A
FA - Speiser, Daniel E
FA - Dummer, Reinhard
FA - Siano, Marco
FA - Urner-Bloch, Ursula
FA - Goldinger, Simone M
FA - Flatz, Lukas
IN - Diem, Stefan. Departments of *Oncology ++Ophthalmology #Dermatology/Allergology **Institute of Immunobiology, Kantonal Hospital St Gallen, St Gallen +Department of Oncology, Hospital Grabs, Grabs Ludwig Cancer Research Center, University of Lausanne, Lausanne Department of Dermatology PPrivate Ophthalmic Practice in Cooperation with the Skin Cancer Unit, University Hospital of Zurich, Zurich, Switzerland.
TI - Pembrolizumab-triggered Uveitis: An Additional Surrogate Marker for Responders in Melanoma Immunotherapy?.
SO - Journal of Immunotherapy. 39(9):379-382, 2016 Nov/Dec
AS - J Immunother. 39(9):379-382, 2016 Nov/Dec
NJ - Journal of immunotherapy (Hagerstown, Md. : 1997)
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - cuq, 9706083
IO - J. Immunother.
CP - United States
AB - Immunotherapy leads to significantly prolonged survival of patients with metastatic melanoma. Autoimmune side effects including colitis, dermatitis, and endocrine abnormalities are common in patients treated with ipilimumab [anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4)]. Antibodies such as pembrolizumab that interfere with the PD-1 (programmed cell death 1)/PD-L1 pathway show greater efficacy and less toxicity than ipilimumab. Here we report 2 cases of pembrolizumab-induced uveitis associated with complete or partial tumor response. We suggest that uveitis may serve as a surrogate marker for a tumor response to therapy with pembrolizumab.
ES - 1537-4513
IL - 1524-9557
DO - https://dx.doi.org/10.1097/CJI.0000000000000143
PT - Journal Article
ID - 27662340 [pubmed]
ID - 10.1097/CJI.0000000000000143 [doi]
PP - ppublish
LG - English
DP - 2016 Nov/Dec
DC - 20160923
EZ - 2016/09/24 06:00
DA - 2016/09/24 06:00
DT - 2016/09/24 06:00
YR - 2016
RD - 20161014
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27662340
<471. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27653290
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Hottinger AF
FA - Hottinger, Andreas F
IN - Hottinger, Andreas F. Department of Clinical Neurosciences; Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland.
TI - Neurologic complications of immune checkpoint inhibitors.
SO - Current Opinion in Neurology. 29(6):806-812, 2016 Dec
AS - Curr Opin Neurol. 29(6):806-812, 2016 Dec
NJ - Current opinion in neurology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - bx4, 9319162
IO - Curr. Opin. Neurol.
CP - England
AB - PURPOSE OF REVIEW: In recent years, advances in the understanding of the regulatory mechanisms of the immune system has led to the development of new approaches for cancer treatment. Currently, immune checkpoint inhibitors are the first successful examples of this approach and several agents that target cytotoxic lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) have been approved for various oncologic situations. The aim of this review is to describe the neurologic adverse event profiles for these new immune therapeutic approaches and to discuss their appropriate management.
AB - RECENT FINDINGS: The immune checkpoint inhibitor ipilimumab against CTLA-4 and nivolumab or pembrolizumab against PD-1 show a unique spectrum of toxic effects. The most common toxicities include rash, colitis, hepatitis, endocrinopathies, and pneumonitis. Neurologic side-effects are rare but include cases of immune polyneuropathies, Guillain Barre syndrome, myasthenia gravis, posterior reversible encephalopathy syndrome, aseptic meningitis, enteric neuropathy, transverse myelitis as well as immune encephalitis.
AB - SUMMARY: It is essential that neurologic immune-related adverse events are recognized and treated as soon as possible, as early treatment increases the odds of a complete recovery.
ES - 1473-6551
IL - 1350-7540
DO - https://dx.doi.org/10.1097/WCO.0000000000000391
PT - Journal Article
ID - 27653290 [pubmed]
ID - 10.1097/WCO.0000000000000391 [doi]
PP - ppublish
LG - English
DP - 2016 Dec
DC - 20160922
EZ - 2016/09/23 06:00
DA - 2016/11/03 06:00
DT - 2016/11/03 06:00
YR - 2016
RD - 20161103
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27653290
<472. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27565924
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Semper H
AU - Muehlberg F
AU - Schulz-Menger J
AU - Allewelt M
AU - Grohe C
FA - Semper, H
FA - Muehlberg, F
FA - Schulz-Menger, J
FA - Allewelt, M
FA - Grohe, C
IN - Semper, H. ELK Thorax Center, Lindenberger Weg 27, 13125 Berlin, Germany.
IN - Muehlberg, F. Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, A Joint Cooperation Between the Charite Medical Faculty and the Max-Delbruck Center for Molecular Medicine and HELIOS Hospital Berlin Buch, Department of Cardiology and Nephrology, Schwanebecker Chaussee 50, 13125 Berlin, Germany.
IN - Schulz-Menger, J. Working Group on Cardiovascular Magnetic Resonance, Experimental and Clinical Research Center, A Joint Cooperation Between the Charite Medical Faculty and the Max-Delbruck Center for Molecular Medicine and HELIOS Hospital Berlin Buch, Department of Cardiology and Nephrology, Schwanebecker Chaussee 50, 13125 Berlin, Germany.
IN - Allewelt, M. ELK Thorax Center, Lindenberger Weg 27, 13125 Berlin, Germany.
IN - Grohe, C. ELK Thorax Center, Lindenberger Weg 27, 13125 Berlin, Germany. Electronic address: Christian.grohe@pgdiakonie.de.
TI - Drug-induced myocarditis after nivolumab treatment in a patient with PDL1- negative squamous cell carcinoma of the lung.
SO - Lung Cancer. 99:117-9, 2016 Sep
AS - Lung Cancer. 99:117-9, 2016 Sep
NJ - Lung cancer (Amsterdam, Netherlands)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - b3u, 8800805
IO - Lung Cancer
SB - Index Medicus
CP - Ireland
KW - Drug-induced myocarditis; Immunotherapy; Nivolumab; PDL-1; Pulmonary squamous cell carcinoma
AB - Immunotherapy such as nivolumab is a new promising therapeutic option for advanced stage non small cell lung cancer (NSCLC). Due to the interference with the immune system previously unknown side effects are observed both in clinical studies and experience. Autoimmune phenomena effecting skin, gastrointestinal tract, endocrine glands, kidney and lung have been described. Up to now there is only limited information regarding potential cardiac side effects. We present a case of symptomatic drug induced myocarditis after nine cycles of nivolumab in a patient with efficient anticancer response.
AB - Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
ES - 1872-8332
IL - 0169-5002
DI - S0169-5002(16)30394-4
DO - https://dx.doi.org/10.1016/j.lungcan.2016.06.025
PT - Journal Article
ID - 27565924 [pubmed]
ID - S0169-5002(16)30394-4 [pii]
ID - 10.1016/j.lungcan.2016.06.025 [doi]
PP - ppublish
PH - 2016/04/26 [received]
PH - 2016/06/28 [revised]
PH - 2016/06/30 [accepted]
LG - English
EP - 20160701
DP - 2016 Sep
DC - 20160827
EZ - 2016/08/28 06:00
DA - 2016/08/28 06:00
DT - 2016/08/28 06:00
YR - 2016
RD - 20160827
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27565924
<473. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27543082
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Bickel A
AU - Koneth I
AU - Enzler-Tschudy A
AU - Neuweiler J
AU - Flatz L
AU - Fruh M
FA - Bickel, Angelika
FA - Koneth, Irene
FA - Enzler-Tschudy, Annette
FA - Neuweiler, Jorg
FA - Flatz, Lukas
FA - Fruh, Martin
IN - Bickel, Angelika. Department of Oncology and Haematology, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007, St. Gallen, Switzerland. angelika.bickel@kssg.ch.
IN - Koneth, Irene. Division of Nephrology and Transplantation Medicine, Cantonal Hospital St.Gallen, St. Gallen, Switzerland.
IN - Enzler-Tschudy, Annette. Institute of Pathology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
IN - Neuweiler, Jorg. Institute of Pathology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
IN - Flatz, Lukas. Department of Dermatology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
IN - Fruh, Martin. Department of Oncology and Haematology, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007, St. Gallen, Switzerland.
TI - Pembrolizumab-associated minimal change disease in a patient with malignant pleural mesothelioma.
SO - BMC Cancer. 16:656, 2016 Aug 19
AS - BMC Cancer. 16:656, 2016 Aug 19
NJ - BMC cancer
PI - Journal available in: Electronic
PI - Citation processed from: Internet
JC - 100967800
IO - BMC Cancer
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992260
SB - Index Medicus
CP - England
KW - Immunotherapy; Malignant Pleural Mesothelioma; Minimal change disease; PD-1 antibody; Pembrolizumab
AB - BACKGROUND: Pembrolizumab is an anti- Programmed Death 1 (PD-1) antibody approved in melanoma, non-small cell lung cancer and investigated in malignant pleural mesothelioma. The most frequent immunotherapy related autoimmune reactions include dermatitis, pneumonitis, colitis, hypophysitis, uveitis, hypothyreodism, hepatitis and interstitial nephritis.
AB - CASE PRESENTATION: We describe a 62-year old patient diagnosed with malignant pleural mesothelioma who experienced ten days after the second dose of third line therapy with pembrolizumab sudden onset of generalized edema including legs and eyelids and weight gain of 15 kg resulting from nephrotic syndrome and acute renal failure. Pembrolizumab was discontinued and prednisone, diuretics and angiotensin II receptor blocker were initiated with full recovery of symptoms and renal function. Pembrolizumab-associated minimal change disease (MCD) was confirmed by electron microscopy in the renal biopsy.
AB - CONCLUSION: We are the first to describe pembrolizumab-related minimal change disease (MCD). Physicians should be aware of this side effect in patients presenting with edema and weight gain and initiate prompt renal function testing, serum albumin and urinalysis followed by steroid treatment if pembrolizumab-related MCD is suspected.
ES - 1471-2407
IL - 1471-2407
DI - 10.1186/s12885-016-2718-y
DO - https://dx.doi.org/10.1186/s12885-016-2718-y
PT - Journal Article
ID - 27543082 [pubmed]
ID - 10.1186/s12885-016-2718-y [doi]
ID - 10.1186/s12885-016-2718-y [pii]
ID - PMC4992260 [pmc]
PP - epublish
PH - 2016/04/28 [received]
PH - 2016/08/14 [accepted]
LG - English
EP - 20160819
DP - 2016 Aug 19
DC - 20160820
EZ - 2016/08/21 06:00
DA - 2016/08/21 06:00
DT - 2016/08/21 06:00
YR - 2016
RD - 20160822
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27543082
<474. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27521108
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Perazella MA
FA - Perazella, Mark A
IN - Perazella, Mark A. Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA; Section of Nephrology, Department of Medicine, VA Medical Center, West Haven, Connecticut, USA. Electronic address: Mark.perazella@yale.edu.
TI - Checkmate: kidney injury associated with targeted cancer immunotherapy.
SO - Kidney International. 90(3):474-6, 2016 Sep
AS - Kidney Int. 90(3):474-6, 2016 Sep
NJ - Kidney international
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - kvb, 0323470
IO - Kidney Int.
SB - Index Medicus
CP - United States
AB - Immune checkpoint inhibitors are a class of drugs that utilizes immunotherapy to target various cancers. Included are the anti-CTLA-4 and anti-PD-1 receptor antibodies. By reprogramming the immune system, these agents provide a therapy that destroys cancer cells. However, this approach runs the risk of allowing pathologic autoimmunity and organ injury to develop. Unsurprisingly, immune-related adverse effects are described including pneumonitis, colitis, and various endocrinopathies. Now added to this list is AKI, primarily due to ATIN.
AB - Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
ES - 1523-1755
IL - 0085-2538
DI - S0085-2538(16)30265-4
DO - https://dx.doi.org/10.1016/j.kint.2016.05.024
PT - Journal Article
ID - 27521108 [pubmed]
ID - S0085-2538(16)30265-4 [pii]
ID - 10.1016/j.kint.2016.05.024 [doi]
PP - ppublish
PH - 2016/05/04 [received]
PH - 2016/05/19 [revised]
PH - 2016/05/20 [accepted]
LG - English
DP - 2016 Sep
DC - 20160813
EZ - 2016/08/14 06:00
DA - 2016/08/16 06:00
DT - 2016/08/16 06:00
YR - 2016
RD - 20160813
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27521108
<475. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27517638
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Tripathi A
AU - Kaymakcalan MD
AU - LeBoeuf NR
AU - Harshman LC
FA - Tripathi, Abhishek
FA - Kaymakcalan, Marina D
FA - LeBoeuf, Nicole R
FA - Harshman, Lauren C
IN - Tripathi, Abhishek. aLank Center for Genitourinary Oncology, Dana-Farber Cancer Institute bThe Center for Cutaneous Oncology, Department of Dermatology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
TI - Programmed cell death-1 pathway inhibitors in genitourinary malignancies: specific side-effects and their management.
SO - Current Opinion in Urology. 26(6):548-55, 2016 Nov
AS - Curr Opin Urol. 26(6):548-55, 2016 Nov
NJ - Current opinion in urology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - dgp, 9200621
IO - Curr Opin Urol
SB - Index Medicus
CP - United States
AB - PURPOSE OF REVIEW: Immune checkpoint inhibitors such as those that target the programmed cell death (PD)-1 pathway harness the host immune system to elicit an antitumor response. Their remarkable clinical benefit has led to regulatory approvals in several malignancies including the genitourinary cancers, renal cell carcinoma, and urothelial carcinoma. This review will focus on the management of the toxicities encountered with these agents.
AB - RECENT FINDINGS: Although generally well tolerated, a small proportion of patients (10-20%) treated with PD-1 directed agents as monotherapy can develop severe autoimmune manifestations, also known as, immune-related adverse events. These include but are not limited to rashes, pneumonitis, endocrinopathy, colitis, and immune-mediated hepatic dysfunction. Combining these agents with the anti-CTLA-4 antibody ipilimumab can be associated with a higher incidence of these toxicities. Early initiation of immunosuppression with corticosteroids and other agents when needed can help mitigate these toxicities and to date has not been shown to compromise their clinical benefit.
AB - SUMMARY: The development of immune checkpoint inhibitors represents significant advances in anticancer therapy but their efficacy may come at the cost of autoimmune toxicities secondary to their induction of the immune system. Early recognition of these effects and aggressive upfront management is essential to safely administer these agents in routine clinical practice.
ES - 1473-6586
IL - 0963-0643
DO - https://dx.doi.org/10.1097/MOU.0000000000000332
PT - Journal Article
ID - 27517638 [pubmed]
ID - 10.1097/MOU.0000000000000332 [doi]
PP - ppublish
LG - English
DP - 2016 Nov
DC - 20160928
EZ - 2016/08/13 06:00
DA - 2016/08/16 06:00
DT - 2016/08/16 06:00
YR - 2016
RD - 20160928
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27517638
<476. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27485460
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Latteyer S
AU - Tiedje V
AU - Schilling B
AU - Fuhrer D
FA - Latteyer, S
FA - Tiedje, V
FA - Schilling, B
FA - Fuhrer, D
IN - Latteyer, S. Department of Endocrinology and MetabolismUniversity Hospital Essen, University of Duisburg-Essen, Essen, Germany Endocrine Tumour Center at West German Cancer Center (WTZ)Essen, Germany.
IN - Tiedje, V. Department of Endocrinology and MetabolismUniversity Hospital Essen, University of Duisburg-Essen, Essen, Germany Endocrine Tumour Center at West German Cancer Center (WTZ)Essen, Germany.
IN - Schilling, B. Department of DermatologyVenereology and Allergology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany German Cancer Consortium (DKTK)Heidelberg, Germany.
IN - Fuhrer, D. Department of Endocrinology and MetabolismUniversity Hospital Essen, University of Duisburg-Essen, Essen, Germany Endocrine Tumour Center at West German Cancer Center (WTZ)Essen, Germany Dagmar.fuehrer@uk-essen.de.
TI - Perspectives for immunotherapy in endocrine cancer. [Review]
SO - Endocrine-Related Cancer. 23(10):R469-84, 2016 Oct
AS - Endocr Relat Cancer. 23(10):R469-84, 2016 Oct
NJ - Endocrine-related cancer
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9436481, dgr
IO - Endocr. Relat. Cancer
SB - Index Medicus
CP - England
KW - anti-CTLA-4; anti-PD-1; endocrine and neuroendocrine cancer; immune checkpoint blockade; immunooncology; tumor microenvironment
AB - The fight against cancer has seen major breakthroughs in recent years. More than a decade ago, tyrosine kinase inhibitors targeting constitutively activated signaling cascades within the tumor inaugurated a new era of oncological therapy. Recently, immunotherapy with immune checkpoint inhibitors has started to revolutionize the treatment of several malignancies, most notably malignant melanoma, leading to the renaissance and the long-awaited breakthrough of immunooncology. This review provides an overview of the basis of immunotherapy from its initial concepts of anti-tumor immunity and cell-based therapy to the development of immune checkpoint inhibitors and discusses published studies and the perspectives of immunooncology for the treatment of endocrine malignancies.
AB - Copyright © 2016 Society for Endocrinology.
ES - 1479-6821
IL - 1351-0088
DI - ERC-16-0169
DO - https://dx.doi.org/10.1530/ERC-16-0169
PT - Journal Article
PT - Review
ID - 27485460 [pubmed]
ID - ERC-16-0169 [pii]
ID - 10.1530/ERC-16-0169 [doi]
PP - ppublish
PH - 2016/06/28 [received]
PH - 2016/08/02 [accepted]
LG - English
EP - 20160802
DP - 2016 Oct
DC - 20160909
EZ - 2016/08/04 06:00
DA - 2016/08/04 06:00
DT - 2016/08/04 06:00
YR - 2016
RD - 20160909
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27485460
<477. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27472273
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Abdel-Wahab N
AU - Shah M
AU - Suarez-Almazor ME
FA - Abdel-Wahab, Noha
FA - Shah, Mohsin
FA - Suarez-Almazor, Maria E
IN - Abdel-Wahab, Noha. Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
IN - Abdel-Wahab, Noha. Rheumatology and Rehabilitation Department, Assiut University Hospitals, Assiut, Egypt.
IN - Shah, Mohsin. Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
IN - Suarez-Almazor, Maria E. Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
TI - Adverse Events Associated with Immune Checkpoint Blockade in Patients with Cancer: A Systematic Review of Case Reports.
SO - PLoS ONE [Electronic Resource]. 11(7):e0160221, 2016
AS - PLoS ONE. 11(7):e0160221, 2016
NJ - PloS one
PI - Journal available in: Electronic-eCollection
PI - Citation processed from: Internet
JC - 101285081
IO - PLoS ONE
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966895
SB - Index Medicus
CP - United States
AB - BACKGROUND: Three checkpoint inhibitor drugs have been approved by the US Food and Drug Administration for use in specific types of cancers. While the results are promising, severe immunotherapy-related adverse events (irAEs) have been reported.
AB - OBJECTIVES: To conduct a systematic review of case reports describing the occurrence of irAEs in patients with cancer following checkpoint blockade therapy, primarily to identify potentially unrecognized or unusual clinical findings and toxicity.
AB - DATA SOURCES: We searched Medline, EMBASE, Web of Science, PubMed ePubs, and Cochrane CENTRAL with no restriction through August 2015.
AB - STUDY SELECTION: Studies reporting cases of cancer develop irAEs following treatment with anti CTLA-4 (ipilimumab) or anti PD-1 (nivolumab or pembrolizumab) antibodies were included.
AB - DATA EXTRACTION: We extracted data on patient characteristics, irAEs characteristics, how irAEs were managed, and their outcomes.
AB - DATA SYNTHESIS: 191 publications met inclusion criteria, reporting on 251 cases. Most patients had metastatic melanoma (95.6%), and the majority were treated with ipilimumab (93.2%). Autoimmune colitis, hepatitis, endocrinopathies, and cutaneous irAEs were the most frequently reported irAEs in ipilimumab treated patients. A broad spectrum of toxicities were reported for almost every body system. Moreover, well-defined diseases such as sarcoidosis, polyarthritis, polymyalgia rheumatica/arteritis, lupus, celiac disease, dermatomyositis, and Vogt-Koyanagi-like syndrome were reported. The most frequent irAEs reported with anti-PD1 agents were dermatitis for pembrolizumab, and thyroid disease and pneumonitis for nivolumab. Complete resolution of adverse events occurred in most cases. However, persistent irAEs and death were reported, mainly in patients treated with ipilimumab.
AB - LIMITATIONS: Our study is limited by information available in the original reports.
AB - CONCLUSIONS: Evidence from case reports shows that cancer patients develop irAEs following checkpoint blockade therapy, and can occasionally develop clearly defined autoimmune systemic diseases. While discontinuation of therapy and/or treatment can result in resolution of irAEs, long-term sequelae and death have been reported.
ES - 1932-6203
IL - 1932-6203
DI - PONE-D-16-14449
DO - https://dx.doi.org/10.1371/journal.pone.0160221
PT - Journal Article
ID - 27472273 [pubmed]
ID - 10.1371/journal.pone.0160221 [doi]
ID - PONE-D-16-14449 [pii]
ID - PMC4966895 [pmc]
PP - epublish
PH - 2016/04/25 [received]
PH - 2016/07/17 [accepted]
LG - English
EP - 20160729
DP - 2016
DC - 20160730
EZ - 2016/07/30 06:00
DA - 2016/07/30 06:00
DT - 2016/07/30 06:00
YR - 2016
RD - 20160819
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27472273
<478. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27438388
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Steenbruggen TG
AU - van den Heuvel MM
AU - Blank CU
AU - van Dieren JM
AU - Haanen JB
AU - Kok M
FA - Steenbruggen, T G
FA - van den Heuvel, M M
FA - Blank, C U
FA - van Dieren, J M
FA - Haanen, J B A G
FA - Kok, M
IN - Steenbruggen, T G. Nederlands Kanker Instituut/Antoni van Leeuwenhoek, Amsterdam.
TI - [No hair loss, but colitis or pneumonitis: unique side effects of immune checkpoint inhibitors for cancer]. [Dutch]
OT - Geen haaruitval, maar wel colitis of pneumonitis.
SO - Nederlands Tijdschrift voor Geneeskunde. 160(0):A9873, 2016
AS - Ned Tijdschr Geneeskd. 160(0):A9873, 2016
NJ - Nederlands tijdschrift voor geneeskunde
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - nuk, 0400770
IO - Ned Tijdschr Geneeskd
SB - Index Medicus
CP - Netherlands
AB - Immunotherapy with checkpoint inhibitors is an effective strategy for several cancers. In some patients long-term remissions are seen. However, enhancement of the immune response can be accompanied by immune-related adverse events (irAEs). These patients often present with nonspecific symptoms. The most common irAEs are dermatitis, colitis, pneumonitis, hepatitis and endocrinopathies. IrAEs can occur in every organ, even simultaneously. Furthermore, irAEs can occur weeks or months after discontinuation of checkpoint inhibitors. Most irAEs can be well managed, but life-threatening situations do occur. General management involves supportive care, glucocorticoids and sometimes immunomodulatory drugs, such as infliximab. Early diagnosis and adequate team management can improve the course of irAEs without compromising the cancer treatment. Here, we present two cases: a melanoma patient with an ipilimumab-induced colitis and a lung cancer patient with pneumonitis after anti-PD-1.We then summarise the most common toxicities of checkpoint inhibitors, emphasising the need to familiarise the practitioner with irAEs of approved and emerging immunotherapies.
ES - 1876-8784
IL - 0028-2162
PT - English Abstract
PT - Journal Article
ID - 27438388 [pubmed]
PP - ppublish
LG - Dutch
DP - 2016
DC - 20160721
EZ - 2016/07/21 06:00
DA - 2016/07/22 06:00
DT - 2016/07/22 06:00
YR - 2016
RD - 20160721
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27438388
<479. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27407160
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Banks PD
AU - Sandhu S
AU - Gyorki DE
AU - Johnston ML
AU - Rischin D
FA - Banks, Patricia D
FA - Sandhu, Shahneen
FA - Gyorki, David E
FA - Johnston, Meredith L
FA - Rischin, Danny
IN - Banks, Patricia D. Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
IN - Sandhu, Shahneen. Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
IN - Gyorki, David E. Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
IN - Johnston, Meredith L. Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
IN - Rischin, Danny. Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia danny.rischin@petermac.org.
TI - Recent Insights and Advances in the Management of Merkel Cell Carcinoma. [Review]
SO - Journal of oncology practice/American Society of Clinical Oncology. 12(7):637-46, 2016 Jul
AS - J Oncol Pract. 12(7):637-46, 2016 Jul
NJ - Journal of oncology practice
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101261852
IO - J Oncol Pract
SB - Index Medicus
CP - United States
AB - Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy with a propensity for recurrence and a poor prognosis. Incidence of MCC is on the rise and is known to increase with advanced age, immunosuppression, and UV exposure. Merkel cell polyomavirus is implicated in the pathogenesis of virus-positive MCC and accounts for 80% of MCCs in the northern hemisphere and 25% in southern latitudes. In contrast, tumorigenesis of virus-negative MCC is linked to UV-induced DNA damage. Interplay between ubiquitous Merkel cell polyomavirus skin infections that commonly occur in healthy skin and other established risk factors, such as immunosuppression and UV exposure, remains poorly understood. Surgery and radiotherapy achieves excellent locoregional control; however, invariably, a significant proportion of patients develop disseminated disease that is incurable. Chemotherapy offers a high response rate for metastatic disease, but responses are short-lived and the impact on survival is not established. Recent advances in our understanding of the genetic landscape and immunobiology of MCC has led to investigation of novel treatments, including immune checkpoint inhibitors, which are likely to rapidly transform the way we manage these patients. We review epidemiologic, clinical, and histopathologic features of MCC; describe recent insights in MCC biology; and discuss novel therapeutic approaches.
AB - Copyright © 2016 by American Society of Clinical Oncology.
ES - 1935-469X
IL - 1554-7477
DI - 12/7/637
DO - https://dx.doi.org/10.1200/JOP.2016.013367
PT - Journal Article
PT - Review
ID - 27407160 [pubmed]
ID - 12/7/637 [pii]
ID - 10.1200/JOP.2016.013367 [doi]
PP - ppublish
LG - English
DP - 2016 Jul
DC - 20160713
EZ - 2016/07/14 06:00
DA - 2016/07/14 06:00
DT - 2016/07/14 06:00
YR - 2016
RD - 20161020
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27407160
<480. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27306502
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Kottschade L
AU - Brys A
AU - Peikert T
AU - Ryder M
AU - Raffals L
AU - Brewer J
AU - Mosca P
AU - Markovic S
AU - Midwest Melanoma Partnership
FA - Kottschade, Lisa
FA - Brys, Adam
FA - Peikert, Tobias
FA - Ryder, Mabel
FA - Raffals, Laura
FA - Brewer, Jerry
FA - Mosca, Paul
FA - Markovic, Svetomir
FA - Midwest Melanoma Partnership
IN - Kottschade, Lisa. Division of aMedical Oncology bPulmonary and Critical Care Medicine cEndocrinology dGastroenterology and Hepatology eDermatology fHematology, Mayo Clinic, Rochester, Minnesota gDuke University School of Medicine hDivision of Advance Oncologic and GI Surgery, Duke University, Durham, North Carolina, USA.
TI - A multidisciplinary approach to toxicity management of modern immune checkpoint inhibitors in cancer therapy.
SO - Melanoma Research. 26(5):469-80, 2016 Oct
AS - Melanoma Res. 26(5):469-80, 2016 Oct
NJ - Melanoma research
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - bjr, 9109623
IO - Melanoma Res.
SB - Index Medicus
CP - England
AB - Immune-related Adverse Events (irAEs) are the most significant toxicities associated with the use of checkpoint inhibitors, and result from disinhibition of the host's immune homeostasis. The adverse effects experienced from immunotherapy are significantly different from those of chemotherapy and, to a lesser extent, targeted therapy. Early recognition and diagnosis of these toxicities is often challenging, but is critically important because of the potentially life-threatening nature and associated morbidity. Gastrointestinal, dermatologic, endocrine, and liver toxicities are the most commonly observed. Less commonly, the eyes, pancreas, kidneys, lungs, bone marrow, or nervous system may be affected. Although most irAEs may resolve with supportive care or discontinuation of drug, in severe cases, they may require hospitalization and immune suppressants, such as steroids, and/or may even cause death. The management of immune-related side effects requires a multidisciplinary approach.
ES - 1473-5636
IL - 0960-8931
DO - https://dx.doi.org/10.1097/CMR.0000000000000273
PT - Journal Article
ID - 27306502 [pubmed]
ID - 10.1097/CMR.0000000000000273 [doi]
PP - ppublish
LG - English
DP - 2016 Oct
DC - 20160901
EZ - 2016/06/17 06:00
DA - 2016/06/17 06:00
DT - 2016/06/17 06:00
YR - 2016
RD - 20160901
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27306502
<481. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27262710
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Cassler NM
AU - Merrill D
AU - Bichakjian CK
AU - Brownell I
FA - Cassler, Nicole M
FA - Merrill, Dean
FA - Bichakjian, Christopher K
FA - Brownell, Isaac
IN - Cassler, Nicole M. Department of Dermatology, Walter Reed National Military Medical Center, Bethesda, MD, USA.
IN - Merrill, Dean. University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA.
IN - Bichakjian, Christopher K. Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, USA.
IN - Brownell, Isaac. Dermatology Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD, 20892-1908, USA. Isaac.brownell@nih.gov.
TI - Merkel Cell Carcinoma Therapeutic Update. [Review]
SO - Current Treatment Options in Oncology. 17(7):36, 2016 Jul
AS - Curr Treat Options Oncol. 17(7):36, 2016 Jul
NJ - Current treatment options in oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 100900946
IO - Curr Treat Options Oncol
SB - Index Medicus
CP - United States
KW - AKT; Avelumab; CM2B4; Cabozantinib; FDG-PET; Idelalisib; Imatinib; MCV; MLN0128; Merkel cell carcinoma; Neuroendocrine; Octreotide; PD-1; PD-L1; PI3K; Pazopanib; Pembrolizumab; Polyomavirus; VP1; Vaccine; mTOR
AB - OPINION STATEMENT: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Early-stage disease can be cured with surgical resection and radiotherapy (RT). Sentinel lymph node biopsy (SLNB) is an important staging tool, as a microscopic MCC is frequently identified. Adjuvant RT to the primary excision site and regional lymph node bed may improve locoregional control. However, newer studies confirm that patients with biopsy-negative sentinel lymph nodes may not benefit from regional RT. Advanced MCC currently lacks a highly effective treatment as responses to chemotherapy are not durable. Recent work suggests that immunotherapy targeting the programmed cell death receptor 1/programmed cell death ligand 1 (PD-1/PD-L1) checkpoint holds great promise in treating advanced MCC and may provide durable responses in a portion of patients. At the same time, high-throughput sequencing studies have demonstrated significant differences in the mutational profiles of tumors with and without the Merkel cell polyomavirus (MCV). An important secondary endpoint in the ongoing immunotherapy trials for MCC will be determining if there is a response difference between the virus-positive MCC tumors that typically lack a large mutational burden and the virus-negative tumors that have a large number of somatic mutations and predicted tumor neoantigens. Interestingly, sequencing studies have failed to identify a highly recurrent activated driver pathway in the majority of MCC tumors. This may explain why targeted therapies can demonstrate exceptional responses in case reports but fail when treating all comers with MCC. Ultimately, a precision medicine approach may be more appropriate for treating MCC, where identified driver mutations are used to direct targeted therapies. At a minimum, stratifying patients in future clinical trials based on tumor viral status should be considered as virus-negative tumors are more likely to harbor activating driver mutations.
ES - 1534-6277
IL - 1534-6277
DI - 10.1007/s11864-016-0409-1
DO - https://dx.doi.org/10.1007/s11864-016-0409-1
PT - Journal Article
PT - Review
ID - 27262710 [pubmed]
ID - 10.1007/s11864-016-0409-1 [doi]
ID - 10.1007/s11864-016-0409-1 [pii]
PP - ppublish
LG - English
DP - 2016 Jul
DC - 20160606
EZ - 2016/06/06 06:00
DA - 2016/06/06 06:00
DT - 2016/06/06 06:00
YR - 2016
RD - 20160606
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27262710
<482. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27138570
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Tabchi S
AU - Messier C
AU - Blais N
FA - Tabchi, Samer
FA - Messier, Christine
FA - Blais, Normand
IN - Tabchi, Samer. aDepartment of Hematology - Oncology bDepartment of Pharmacy, Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada.
TI - Immune-mediated respiratory adverse events of checkpoint inhibitors.
SO - Current Opinion in Oncology. 28(4):269-77, 2016 Jul
AS - Curr Opin Oncol. 28(4):269-77, 2016 Jul
NJ - Current opinion in oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - a1v, 9007265
IO - Curr Opin Oncol
SB - Index Medicus
CP - United States
AB - PURPOSE OF REVIEW: Immune checkpoint inhibitors have demonstrated remarkable efficacy with durable responses in the treatment of various malignancies. This new class of therapeutic agents is associated with a toxicity profile that differs from conventional cytotoxic therapy. The present review is focused on one of these toxicities affecting the respiratory system.
AB - RECENT FINDINGS: Many types of immune-related adverse events (irAEs) have been identified since the emergence of checkpoint inhibitors including colitis, nephritis, myasthenia gravis-like syndromes, acute interstitial nephritis, pneumonitis, and endocrinopathies. Although pneumonitis is relatively less frequent than other irAEs, this toxicity is by no means inconsequential as it has led to treatment-related deaths during the initial testing phases.
AB - SUMMARY: Immune-mediated pneumonitis is a potentially serious but relatively infrequent adverse event associated with the use of immune checkpoint inhibitors. IrAEs can be challenging for oncologists who are still unfamiliar with the early presenting symptoms and subsequent management of these toxicities, especially in the context of a rapidly expanding science. A high index of suspicion for pneumonitis must be maintained in patients receiving checkpoint inhibitors and who present new onset respiratory symptoms because this type of toxicity can be severe and potentially fatal.
ES - 1531-703X
IL - 1040-8746
DO - https://dx.doi.org/10.1097/CCO.0000000000000291
PT - Journal Article
ID - 27138570 [pubmed]
ID - 10.1097/CCO.0000000000000291 [doi]
PP - ppublish
LG - English
DP - 2016 Jul
DC - 20160603
EZ - 2016/05/04 06:00
DA - 2016/05/04 06:00
DT - 2016/05/04 06:00
YR - 2016
RD - 20160603
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27138570
<483. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27136136
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Torino F
AU - Corsello SM
AU - Salvatori R
FA - Torino, Francesco
FA - Corsello, Salvatore M
FA - Salvatori, Roberto
IN - Torino, Francesco. aDepartment of Systems Medicine, Chair of Medical Oncology, Tor Vergata University of Rome bEndocrinology Unit, Catholic University of Sacred Heart, Rome, Italy cDivision of Endocrinology and Metabolism and Pituitary Center, Johns Hopkins University, Baltimore, Maryland, USA.
TI - Endocrinological side-effects of immune checkpoint inhibitors.
SO - Current Opinion in Oncology. 28(4):278-87, 2016 Jul
AS - Curr Opin Oncol. 28(4):278-87, 2016 Jul
NJ - Current opinion in oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - a1v, 9007265
IO - Curr Opin Oncol
SB - Index Medicus
CP - United States
AB - PURPOSE OF REVIEW: Three mAbs targeting immune checkpoint proteins are available for the treatment of patients with melanoma, lung, and kidney cancer, and their use will likely expand in the future to additional tumor types. We here update the literature on the incidence and pathophysiology of endocrine toxicities induced by these agents, and discuss management guidance.
AB - RECENT FINDINGS: Immune checkpoint inhibition may trigger autoimmune syndromes involving different organs, including several endocrine glands (pituitary, thyroid, adrenals, and endocrine pancreas). Hypophysitis is more frequently associated with ipilimumab, whereas the incidence of thyroid dysfunction is higher with nivolumab/pembrolizumab. Primary adrenal insufficiency can rarely occur with either treatment. Autoimmune diabetes is very rare. As hypophysitis and adrenalitis may be life-threatening, endocrinological evaluation is essential particularly in patients developing fatigue and other symptoms consistent with adrenal insufficiency. Corticosteroids should be promptly used when hypophysitis-induced adrenal insufficiency or adrenalitis are diagnosed, but not in thyroiditis or diabetes. No impact of corticosteroids on the efficacy/activity of immune checkpoint-inhibiting drugs is reported. Hormonal deficiencies are often permanent.
AB - SUMMARY: In absence of predicting factors, accurate information to patients provided by the oncology care team is essential for early diagnosis and to limit the consequences of checkpoint inhibition-related endocrine toxicity.
ES - 1531-703X
IL - 1040-8746
DO - https://dx.doi.org/10.1097/CCO.0000000000000293
PT - Journal Article
ID - 27136136 [pubmed]
ID - 10.1097/CCO.0000000000000293 [doi]
PP - ppublish
LG - English
DP - 2016 Jul
DC - 20160603
EZ - 2016/05/03 06:00
DA - 2016/05/03 06:00
DT - 2016/05/03 06:00
YR - 2016
RD - 20160603
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27136136
<484. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27136135
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Antoun J
AU - Titah C
AU - Cochereau I
FA - Antoun, Joelle
FA - Titah, Cherif
FA - Cochereau, Isabelle
IN - Antoun, Joelle. aSaint Joseph University, Faculty of Medicine, Beirut, Lebanon bFondation ophtalmologique Adolphe de Rothschild cHopital Bichat Claude Bernard, Faculte de Medecine Diderot Paris 7, France.
TI - Ocular and orbital side-effects of checkpoint inhibitors: a review article.
SO - Current Opinion in Oncology. 28(4):288-94, 2016 Jul
AS - Curr Opin Oncol. 28(4):288-94, 2016 Jul
NJ - Current opinion in oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - a1v, 9007265
IO - Curr Opin Oncol
SB - Index Medicus
CP - United States
AB - PURPOSE OF REVIEW: Checkpoint inhibitors have been increasingly considered as new targets for cancer therapies. Patients receiving checkpoint inhibitors develop many immune-related adverse events (IRAEs). However, ophthalmic IRAEs are rare and have been reported in less than 1% of patients. To date, few case reports evaluating the ophthalmological side-effects of checkpoint inhibitors have been published. In this review, we plan to report the different ocular and orbital side-effects of the checkpoint inhibitors, and to help guide ophthalmologists and oncologists in their management.
AB - RECENT FINDINGS: Ocular side-effects of checkpoint inhibitors include peripheral ulcerative keratitis, uveitis, Vogt-Koyanagi-Harada syndrome, choroidal neovascularization and melanoma-associated retinopathy. Both thyroid-associated orbitopathy and idiopathic orbital inflammation have also been reported in association with checkpoint inhibitors. Mild IRAE can be treated with topical steroids, whereas systemic corticosteroids and discontinuation of checkpoint inhibitors are indicated in more severe ocular and orbital inflammation.
AB - SUMMARY: Physicians involved in the care of oncologic patients should be aware of the ocular and orbital IRAEs that may develop with checkpoint inhibitors. A strong cooperation between oncologists and ophthalmologists is required in the diagnosis and prompt management of these IRAEs.
ES - 1531-703X
IL - 1040-8746
DO - https://dx.doi.org/10.1097/CCO.0000000000000296
PT - Journal Article
ID - 27136135 [pubmed]
ID - 10.1097/CCO.0000000000000296 [doi]
PP - ppublish
LG - English
DP - 2016 Jul
DC - 20160603
EZ - 2016/05/03 06:00
DA - 2016/05/03 06:00
DT - 2016/05/03 06:00
YR - 2016
RD - 20160603
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27136135
<485. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27116334
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Wen X
AU - Wang Y
AU - Ding Y
AU - Li D
AU - Li J
AU - Guo Y
AU - Peng R
AU - Zhao J
AU - Zhang X
AU - Zhang XS
FA - Wen, Xizhi
FA - Wang, Yao
FA - Ding, Ya
FA - Li, Dandan
FA - Li, Jingjing
FA - Guo, Yiqun
FA - Peng, Ruiqing
FA - Zhao, Jingjing
FA - Zhang, Xing
FA - Zhang, Xiao-Shi
IN - Wen, Xizhi. State Key Laboratory of Oncology in South China, Biotherapy Center, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.
TI - Safety of immune checkpoint inhibitors in Chinese patients with melanoma.
SO - Melanoma Research. 26(3):284-9, 2016 Jun
AS - Melanoma Res. 26(3):284-9, 2016 Jun
NJ - Melanoma research
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - bjr, 9109623
IO - Melanoma Res.
SB - Index Medicus
CP - England
AB - This study aimed to determine the tolerability of Chinese melanoma patients, particularly those with hepatitis B virus (HBV) infection, to immune checkpoint inhibitor therapy. Patients with metastatic melanoma who received anti-cytotoxic T lymphocyte-associated antigen-4 antibody (ipilimumab) or anti-programmed death 1 antibody (pembrolizumab) therapy at our hospital between August 2012 and July 2015 were retrospectively reviewed. Adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Twenty-three patients with advanced melanoma were included; nine and 10 patients received infusions of ipilimumab and pembrolizumab, respectively, whereas four patients received concurrent ipilimumab and pembrolizumab therapy. There was no cessation of treatment because of agent-related adverse events in any patient. Immune-related adverse events were observed in 44% (4/9), 60% (6/10), 100% (4/4), and 61% (14/23) of patients receiving ipilimumab, pembrolizumab, concomitant ipilimumab and pembrolizumab, and any treatment, respectively. The most frequent immune-related adverse events were endocrine disorders (39%, 9/23), liver function abnormalities (22%, 5/23), and dermatological events (17%, 4/23). There were no gastrointestinal reactions. Toxicities were usually mild and easily managed; only 13% (3/23) of patients had grade 3 adverse events and none experienced grade 4 events or treatment-related death. No additional toxicity nor severe hepatotoxicity was observed in 11 patients who had previous HBV infection. The recommended anti-cytotoxic T lymphocyte-associated antigen-4 and anti-programmed death 1 antibody doses were well tolerated by Chinese patients. Thus, immune checkpoint inhibitors appear to be effective and safe in metastatic melanoma patients, including those with pre-existing HBV infection.
ES - 1473-5636
IL - 0960-8931
DI - 00008390-201606000-00010
DO - https://dx.doi.org/10.1097/CMR.0000000000000256
PT - Journal Article
ID - 27116334 [pubmed]
ID - 10.1097/CMR.0000000000000256 [doi]
ID - 00008390-201606000-00010 [pii]
PP - ppublish
LG - English
DP - 2016 Jun
DC - 20160427
EZ - 2016/04/27 06:00
DA - 2016/04/27 06:00
DT - 2016/04/27 06:00
YR - 2016
RD - 20160427
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27116334
<486. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27026676
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Sul J
AU - Blumenthal GM
AU - Jiang X
AU - He K
AU - Keegan P
AU - Pazdur R
FA - Sul, Joohee
FA - Blumenthal, Gideon M
FA - Jiang, Xiaoping
FA - He, Kun
FA - Keegan, Patricia
FA - Pazdur, Richard
IN - Sul, Joohee. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA joohee.sul@fda.hhs.gov.
IN - Blumenthal, Gideon M. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Jiang, Xiaoping. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - He, Kun. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Keegan, Patricia. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
IN - Pazdur, Richard. Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
TI - FDA Approval Summary: Pembrolizumab for the Treatment of Patients With Metastatic Non-Small Cell Lung Cancer Whose Tumors Express Programmed Death-Ligand 1.
SO - Oncologist. 21(5):643-50, 2016 May
AS - Oncologist. 21(5):643-50, 2016 May
NJ - The oncologist
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dd5, 9607837
IO - Oncologist
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861368
SB - Index Medicus
CP - United States
KW - Lung cancer; Pembrolizumab; Programmed death-ligand 1; U.S. Food and Drug Administration
AB - UNLABELLED: : On October 2, 2015, the U.S. Food and Drug Administration (FDA) granted accelerated approval for pembrolizumab, a breakthrough therapy-designated drug, for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express programmed death-ligand 1 (PD-L1), as determined by an FDA-approved test, and who have disease progression on or after platinum-containing chemotherapy or targeted therapy against anaplastic lymphoma kinase or epidermal growth factor receptor, if appropriate. This indication was approved concurrently with the PD-L1 immunohistochemistry 22C3 pharmDx, a companion diagnostic test for patient selection based on PD-L1 tumor expression. The accelerated approval was granted based on durable objective response rate (ORR) and an acceptable toxicity profile demonstrated in a multicenter, open-label trial enrolling 550 patients with metastatic NSCLC. The efficacy population comprised 61 patients with tumors identified as strongly positive for PD-L1, and the confirmed ORR as determined by blinded independent central review was 41% (95% confidence interval: 28.6%, 54.3%); all were partial responses. At the time of the analysis, responses were ongoing in 21 of 25 patients (84%), with 11 patients (44%) having response duration of >=6 months. The most commonly occurring (>=20%) adverse reactions included fatigue, decreased appetite, dyspnea, and cough. The most frequent (>=2%) serious adverse drug reactions were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. Immune-mediated adverse reactions occurred in 13% of patients and included pneumonitis, colitis, hypophysitis, and thyroid disorders. The accelerated approval regulations describe approval of drugs and biologic products for serious and life-threatening illnesses based on a surrogate endpoint likely to predict clinical benefit. Under these regulations, a confirmatory trial or trials is required to verify and describe the benefit of pembrolizumab for patients with metastatic NSCLC.
AB - IMPLICATIONS FOR PRACTICE: This report presents key information on the U.S. Food and Drug Administration (FDA) accelerated approval of pembrolizumab for the treatment of patients with metastatic non-small cell lung cancer whose tumors express programmed death-ligand 1, as determined by an FDA-approved test, and who have disease progression on or after platinum-containing chemotherapy or targeted therapy against anaplastic lymphoma kinase or epidermal growth factor receptor, if appropriate. The report discusses the data supporting the approval decision, specifically highlighting the incorporation of a companion diagnostic in the key study and the optimal dose of pembrolizumab.
AB - Copyright ©AlphaMed Press.
ES - 1549-490X
IL - 1083-7159
DI - theoncologist.2015-0498
DO - https://dx.doi.org/10.1634/theoncologist.2015-0498
PT - Journal Article
ID - 27026676 [pubmed]
ID - theoncologist.2015-0498 [pii]
ID - 10.1634/theoncologist.2015-0498 [doi]
ID - PMC4861368 [pmc]
PP - ppublish
PH - 2015/12/08 [received]
PH - 2016/01/15 [accepted]
LG - English
EP - 20160329
DP - 2016 May
DC - 20160510
EZ - 2016/03/31 06:00
DA - 2016/03/31 06:00
DT - 2016/03/31 06:00
YR - 2016
RD - 20160517
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27026676
<487. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26998595
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Joshi MN
AU - Whitelaw BC
AU - Palomar MT
AU - Wu Y
AU - Carroll PV
FA - Joshi, M N
FA - Whitelaw, B C
FA - Palomar, M T P
FA - Wu, Y
FA - Carroll, P V
IN - Joshi, M N. Departments of Endocrinology, Guy's & St Thomas NHS Foundation Trust, London, UK.
IN - Whitelaw, B C. Department of Endocrinology, Kings College London NHS Foundation Trust, London, UK.
IN - Palomar, M T P. Medical Oncology, Guy's & St Thomas NHS Foundation Trust, London, UK.
IN - Wu, Y. Medical Oncology, Guy's & St Thomas NHS Foundation Trust, London, UK.
IN - Carroll, P V. Departments of Endocrinology, Guy's & St Thomas NHS Foundation Trust, London, UK.
TI - Immune checkpoint inhibitor-related hypophysitis and endocrine dysfunction: clinical review. [Review]
SO - Clinical Endocrinology. 85(3):331-9, 2016 Sep
AS - Clin Endocrinol (Oxf). 85(3):331-9, 2016 Sep
NJ - Clinical endocrinology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dci, 0346653
IO - Clin. Endocrinol. (Oxf)
SB - Index Medicus
CP - England
AB - Immune checkpoint inhibitors are a new and effective class of cancer therapy, with ipilimumab being the most established drug in this category. The drugs' mechanism of action includes promoting the effector T cell response to tumours and therefore increased autoimmunity is a predictable side effect. The endocrine effects of these drugs include hypophysitis and thyroid dysfunction, with rare reports of adrenalitis. The overall incidence of hypophysitis with these medications is up to 9%. Primary thyroid dysfunction occurs in up to 15% of patients, with adrenalitis reported in approximately 1%. The mean onset of endocrine side effects is 9 weeks after initiation (range 5-36 weeks). Investigation and/or screening for hypophysitis requires biochemical and radiological assessment. Hypopituitarism is treated with replacement doses of deficient hormones. Since the endocrine effects of immune checkpoint inhibitors are classed as toxic adverse events, most authors recommend both discontinuation of the immune checkpoint inhibiting medication and 'high-dose' glucocorticoid treatment. However, this has been challenged by some authors, particularly if the endocrine effects can be managed (e.g. pituitary hormone deficiency), and the therapy is proving effective as an anticancer agent. This review describes the mechanism of action of immune checkpoint inhibitors and details the key clinical endocrine-related consequences of this novel class of immunotherapies.
AB - Copyright © 2016 John Wiley & Sons Ltd.
ES - 1365-2265
IL - 0300-0664
DO - https://dx.doi.org/10.1111/cen.13063
PT - Journal Article
PT - Review
ID - 26998595 [pubmed]
ID - 10.1111/cen.13063 [doi]
PP - ppublish
PH - 2015/11/26 [received]
PH - 2015/12/23 [revised]
PH - 2016/02/08 [revised]
PH - 2016/03/06 [accepted]
LG - English
EP - 20160413
DP - 2016 Sep
DC - 20160817
EZ - 2016/03/22 06:00
DA - 2016/03/22 06:00
DT - 2016/03/22 06:00
YR - 2016
RD - 20160817
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=26998595
<488. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26943572
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Brauner E
AU - Gunda V
AU - Vanden Borre P
AU - Zurakowski D
AU - Kim YS
AU - Dennett KV
AU - Amin S
AU - Freeman GJ
AU - Parangi S
FA - Brauner, Eran
FA - Gunda, Viswanath
FA - Vanden Borre, Pierre
FA - Zurakowski, David
FA - Kim, Yon Seon
FA - Dennett, Kate Virginia
FA - Amin, Salma
FA - Freeman, Gordon James
FA - Parangi, Sareh
IN - Brauner, Eran. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
IN - Gunda, Viswanath. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
IN - Vanden Borre, Pierre. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
IN - Zurakowski, David. Departments of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
IN - Zurakowski, David. Departments of Anesthesia, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
IN - Kim, Yon Seon. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
IN - Kim, Yon Seon. Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.
IN - Dennett, Kate Virginia. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
IN - Amin, Salma. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
IN - Freeman, Gordon James. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
IN - Parangi, Sareh. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
TI - Combining BRAF inhibitor and anti PD-L1 antibody dramatically improves tumor regression and anti tumor immunity in an immunocompetent murine model of anaplastic thyroid cancer.
SO - Oncotarget. 7(13):17194-211, 2016 Mar 29
AS - Oncotarget. 7(13):17194-211, 2016 Mar 29
NJ - Oncotarget
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 101532965
IO - Oncotarget
PM - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941380
SB - Index Medicus
CP - United States
KW - BRAF inhibitor; MEK inhibitor; anaplastic thyroid cancer; programmed cell death-1; programmed cell death-ligand 1
AB - The interaction of programmed cell death-1 and its ligand is widely studied in cancer. Monoclonal antibodies blocking these molecules have had great success but little is known about them in thyroid cancer. We investigated the role of PD-L1 in thyroid cancer with respect to BRAF mutation and MAP kinase pathway activity and the effect of anti PD-L1 antibody therapy on tumor regression and intra-tumoral immune response alone or in combination with BRAF inhibitor (BRAFi). BRAFV600E cells showed significantly higher baseline expression of PD-L1 at mRNA and protein levels compared to BRAFWT cells. MEK inhibitor treatment resulted in a decrease of PD-L1 expression across all cell lines. BRAFi treatment decreased PD-L1 expression in BRAFV600E cells, but paradoxically increased its expression in BRAFWT cells. BRAFV600E mutated patients samples had a higher level of PD-L1 mRNA compared to BRAFWT (p=0.015). Immunocompetent mice (B6129SF1/J) implanted with syngeneic 3747 BRAFV600E/WT P53-/- murine tumor cells were randomized to control, PLX4720, anti PD-L1 antibody and their combination. In this model of aggressive thyroid cancer, control tumor volume reached 782.3+/-174.6mm3 at two weeks. The combination dramatically reduced tumor volume to 147.3+/-60.8, compared to PLX4720 (439.3+/-188.4 mm3, P=0.023) or PD-L1 antibody (716.7+/-62.1, P<0.001) alone. Immunohistochemistry analysis revealed intense CD8+ CTL infiltration and cytotoxicity and favorable CD8+:Treg ratio compared to each individual treatment. Our results show anti PD-L1 treatment potentiates the effect of BRAFi on tumor regression and intensifies anti tumor immune response in an immunocompetent model of ATC. Clinical trials of this therapeutic combination may be of benefit in patients with ATC.
ES - 1949-2553
IL - 1949-2553
DI - 7839
DO - https://dx.doi.org/10.18632/oncotarget.7839
PT - Journal Article
ID - 26943572 [pubmed]
ID - 7839 [pii]
ID - 10.18632/oncotarget.7839 [doi]
ID - PMC4941380 [pmc]
PP - ppublish
PH - 2015/11/25 [received]
PH - 2016/02/06 [accepted]
GI - No: P01 AI054456
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: P50 CA101942
Organization: (CA) *NCI NIH HHS*
Country: United States
No: R01 CA149738
Organization: (CA) *NCI NIH HHS*
Country: United States
LG - English
DP - 2016 Mar 29
DC - 20160524
EZ - 2016/03/05 06:00
DA - 2016/03/05 06:00
DT - 2016/03/05 06:00
YR - 2016
RD - 20161019
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=26943572
<489. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27265913
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Process
AU - Marques P
AU - Grossman A
FA - Marques, Pedro
FA - Grossman, Ashley
TI - Ipilimumab-Induced Autoimmune Hypophysitis: Diagnostic and Management Challenges Illustrated by a Clinical Case.
SO - Acta Medica Portuguesa. 28(6):775-9, 2015 Nov-Dec
AS - Acta Med Port. 28(6):775-9, 2015 Nov-Dec
NJ - Acta medica portuguesa
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - 7906803
IO - Acta Med Port
SB - Index Medicus
CP - Portugal
AB - Autoimmune hypophysitis has been described in patients on ipilimumab, a humanised monoclonal antibody increasingly used in the treatment of metastatic melanoma. A 67-year-old woman presented with severe fatigue, nausea and headaches following the third dose of ipilimumab, which was being given as treatment for metastatic melanoma (four administrations at three-weekly intervals). Hormonal evaluation confirmed hypocortisolism, with low gonadotrophins and a low thyroid-stimulating hormone with normal free T4 (she was on long-standing levothyroxine because of past surgery for a multinodular goitre). Magnetic resonance imaging scanning revealed pituitary enlargement compatible with autoimmune hypophysitis. She was commenced on replacement with hydrocortisone with significant improvement of her symptoms. The enlarged pituitary was reduced in size 4 months later. The patient is currently asymptomatic on glucocorticoid and levothyroxine replacement. This case highlights relevant clinical, diagnostic and management aspects of ipilimumab-induced autoimmune hypophysitis, and emphasises the need for increasing awareness for potential side-effects of these new immunomodulatory therapies, including autoimmune hypophysitis.
ES - 1646-0758
IL - 0870-399X
PT - Journal Article
ID - 27265913 [pubmed]
PP - ppublish
LG - English
DP - 2015 Nov-Dec
DC - 20160605
EZ - 2016/06/07 06:00
DA - 2016/06/07 06:00
DT - 2016/06/07 06:00
YR - 2015
RD - 20160605
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27265913
<490. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27950718
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - O'Day SJ
AU - Ibrahim R
AU - DePril V
AU - Maio M
AU - Chiarion-Sileni V
AU - Gajewski TF
AU - Pehamberger H
AU - Hoos A
AU - Humphrey R
AU - Wolchock J
FA - O'Day, S J
FA - Ibrahim, R
FA - DePril, V
FA - Maio, M
FA - Chiarion-Sileni, V
FA - Gajewski, T F
FA - Pehamberger, H
FA - Hoos, A
FA - Humphrey, R
FA - Wolchock, J
IN - O'Day, S J. The Angeles Clinic and Research Institute, Santa Monica, CA; Bristol- Myers Squibb; Bristol-Myers Squibb; University Hospital of Siena; Istituto Oncologico del Veneto IOV-IRCSS; University of Chicago; University of Vienna; Memorial Sloan- Kettering Cancer Center.
IN - Ibrahim, R. The Angeles Clinic and Research Institute, Santa Monica, CA; Bristol- Myers Squibb; Bristol-Myers Squibb; University Hospital of Siena; Istituto Oncologico del Veneto IOV-IRCSS; University of Chicago; University of Vienna; Memorial Sloan- Kettering Cancer Center.
IN - DePril, V. The Angeles Clinic and Research Institute, Santa Monica, CA; Bristol- Myers Squibb; Bristol-Myers Squibb; University Hospital of Siena; Istituto Oncologico del Veneto IOV-IRCSS; University of Chicago; University of Vienna; Memorial Sloan- Kettering Cancer Center.
IN - Maio, M. The Angeles Clinic and Research Institute, Santa Monica, CA; Bristol- Myers Squibb; Bristol-Myers Squibb; University Hospital of Siena; Istituto Oncologico del Veneto IOV-IRCSS; University of Chicago; University of Vienna; Memorial Sloan- Kettering Cancer Center.
IN - Chiarion-Sileni, V. The Angeles Clinic and Research Institute, Santa Monica, CA; Bristol- Myers Squibb; Bristol-Myers Squibb; University Hospital of Siena; Istituto Oncologico del Veneto IOV-IRCSS; University of Chicago; University of Vienna; Memorial Sloan- Kettering Cancer Center.
IN - Gajewski, T F. The Angeles Clinic and Research Institute, Santa Monica, CA; Bristol- Myers Squibb; Bristol-Myers Squibb; University Hospital of Siena; Istituto Oncologico del Veneto IOV-IRCSS; University of Chicago; University of Vienna; Memorial Sloan- Kettering Cancer Center.
IN - Pehamberger, H. The Angeles Clinic and Research Institute, Santa Monica, CA; Bristol- Myers Squibb; Bristol-Myers Squibb; University Hospital of Siena; Istituto Oncologico del Veneto IOV-IRCSS; University of Chicago; University of Vienna; Memorial Sloan- Kettering Cancer Center.
IN - Hoos, A. The Angeles Clinic and Research Institute, Santa Monica, CA; Bristol- Myers Squibb; Bristol-Myers Squibb; University Hospital of Siena; Istituto Oncologico del Veneto IOV-IRCSS; University of Chicago; University of Vienna; Memorial Sloan- Kettering Cancer Center.
IN - Humphrey, R. The Angeles Clinic and Research Institute, Santa Monica, CA; Bristol- Myers Squibb; Bristol-Myers Squibb; University Hospital of Siena; Istituto Oncologico del Veneto IOV-IRCSS; University of Chicago; University of Vienna; Memorial Sloan- Kettering Cancer Center.
IN - Wolchock, J. The Angeles Clinic and Research Institute, Santa Monica, CA; Bristol- Myers Squibb; Bristol-Myers Squibb; University Hospital of Siena; Istituto Oncologico del Veneto IOV-IRCSS; University of Chicago; University of Vienna; Memorial Sloan- Kettering Cancer Center.
TI - Efficacy and safety of ipilimumab induction and maintenance dosing in patients with advanced melanoma who progressed on one or more prior therapies.
SO - Journal of Clinical Oncology. 26(15_suppl):9021, 2008 May 20
AS - J Clin Oncol. 26(15_suppl):9021, 2008 May 20
NJ - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - jco, 8309333
IO - J. Clin. Oncol.
CP - United States
AB - 9021 Background: Ipilimumab (ipi) is a monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4. The current study was designed to determine the efficacy and safety of ipi in patients (pts) with advanced melanoma who developed progressive disease (PD) on prior therapies.
AB - METHODS: Advanced melanoma pts with PD during or after >1 prior therapeutic regimen were eligible for enrollment into this single-arm, multicenter, phase II study. Ipi induction was given at 10 mg/kg every 3 weeks (Q3W)x4; eligible pts received maintenance Q12W starting at Week (Wk) 24. The primary objective was to evaluate the best overall response rate (BORR, complete + partial response [CR+PR]). Efficacy endpoints were assessed with modified World Health Organization (mWHO) criteria; the first assessment was at Wk 12. Follow-up tumor evaluation beyond PD (defined by an overall tumor burden increase of >25%) by mWHO and before the administration of non-ipi anticancer therapy was permitted as per protocol.
AB - RESULTS: The study included 155 treated pts. The median number of prior therapies was 2. The BORR as per an Independent Review Committee (IRC) was 5.8% (9/155) [95% CI, 2.7 - 10.7]. The disease control rate (DCR, best response of CR + PR + stable disease [SD]) was 27.1% (42/155) [95% CI, 20.3 - 34.8]. New exploratory response criteria revealed a >25% reduction of measurable total tumor burden in 25.8% of patients. The progression free survival rate at Wk 24 was 49.1% [95% CI 41.2, 57.9]. Immune-related adverse events (irAEs) occurred in 70.3% of pts. Most patients (46.5%) had Grade 1/2 irAEs. The rates of patients with Grade 3/4 irAEs were: gastrointestinal 8.4%; hepatobiliary 7.1%; endocrine 1.3%; and skin 3.2%. Most irAEs were medically manageable. There were no bowel perforations.
AB - CONCLUSIONS: Ipi 10 mg/kg induction/maintenance dosing is effective and well tolerated in pts with PD on prior therapies. Clinical activity, in the form of either objective response or SD occurred in 27% of patients. Based on preliminary results from previous studies (eg, MDX010-15), we expect pts with a BOR of SD or better to remain progression free for months to years. Follow up of these pts is ongoing; survival data will be presented at the meeting. [Table: see text].
ES - 1527-7755
IL - 0732-183X
DI - 10.1200/jco.2008.26.15_suppl.9021
PT - Journal Article
ID - 27950718 [pubmed]
ID - 10.1200/jco.2008.26.15_suppl.9021 [pii]
PP - ppublish
LG - English
DP - 2008 May 20
DC - 20161212
EZ - 2016/12/13 06:00
YR - 2008
RD - 20161212
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27950718
<491. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27948611
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Beer TM
AU - Slovin SF
AU - Higano CS
AU - Tejwani S
AU - Dorff TB
AU - Stankevich E
AU - Lowy I
AU - Prostate Cancer Clinical Trials Consortium
FA - Beer, T M
FA - Slovin, S F
FA - Higano, C S
FA - Tejwani, S
FA - Dorff, T B
FA - Stankevich, E
FA - Lowy, I
FA - Prostate Cancer Clinical Trials Consortium
IN - Beer, T M. Oregon Health & Science University, Portland, OR; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Washington School of Medicine, Seattle, WA; Henry Ford Health System, Detroit, MI; The Angeles Clinic and Research Institute, Santa Monica, CA; Medarex, Inc., Bloomsbury, NJ.
IN - Slovin, S F. Oregon Health & Science University, Portland, OR; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Washington School of Medicine, Seattle, WA; Henry Ford Health System, Detroit, MI; The Angeles Clinic and Research Institute, Santa Monica, CA; Medarex, Inc., Bloomsbury, NJ.
IN - Higano, C S. Oregon Health & Science University, Portland, OR; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Washington School of Medicine, Seattle, WA; Henry Ford Health System, Detroit, MI; The Angeles Clinic and Research Institute, Santa Monica, CA; Medarex, Inc., Bloomsbury, NJ.
IN - Tejwani, S. Oregon Health & Science University, Portland, OR; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Washington School of Medicine, Seattle, WA; Henry Ford Health System, Detroit, MI; The Angeles Clinic and Research Institute, Santa Monica, CA; Medarex, Inc., Bloomsbury, NJ.
IN - Dorff, T B. Oregon Health & Science University, Portland, OR; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Washington School of Medicine, Seattle, WA; Henry Ford Health System, Detroit, MI; The Angeles Clinic and Research Institute, Santa Monica, CA; Medarex, Inc., Bloomsbury, NJ.
IN - Stankevich, E. Oregon Health & Science University, Portland, OR; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Washington School of Medicine, Seattle, WA; Henry Ford Health System, Detroit, MI; The Angeles Clinic and Research Institute, Santa Monica, CA; Medarex, Inc., Bloomsbury, NJ.
IN - Lowy, I. Oregon Health & Science University, Portland, OR; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Washington School of Medicine, Seattle, WA; Henry Ford Health System, Detroit, MI; The Angeles Clinic and Research Institute, Santa Monica, CA; Medarex, Inc., Bloomsbury, NJ.
TI - Phase I trial of ipilimumab (IPI) alone and in combination with radiotherapy (XRT) in patients with metastatic castration resistant prostate cancer (mCRPC).
SO - Journal of Clinical Oncology. 26(15_suppl):5004, 2008 May 20
AS - J Clin Oncol. 26(15_suppl):5004, 2008 May 20
NJ - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - jco, 8309333
IO - J. Clin. Oncol.
CP - United States
AB - 5004 Background: IPI is a fully human, anti-CTLA 4 monoclonal antibody capable of enhancing anti-tumor immunity. In preclinical models, XRT results in tumor antigen release and enhances anti-tumor activity of CTLA-4 blockade.
AB - METHODS: Pts with mCRPC and ECOG PS of 0-1 were treated with escalating doses of IPI every 3 weeks X 4 doses in cohorts of 6 pts at dose levels of 3, 5, and 10 mg/kg. After the 10 mg/kg cohort was completed, a protocol amendment added single fraction XRT prior to IPI starting at the 3 mg/kg dose level. The primary endpoint was safety. Imaging was repeated every 3 months and serum PSA was monitored monthly.
AB - RESULTS: Between 1/2006 and 12/2007, 8, 6, and 6 pts were treated at the 3, 5, and 10 mg/kg dose levels respectively; 6 pts were then treated in the first XRT cohort for a total of 26 pts. 19 pts experienced 29 immune-related adverse events (irAEs) including diarrhea/colitis (14), rash (9), hepatitis (4), endocrinopathy (2). irAEs were >= Grade 3 in 9 pts: GI (6), hepatitis (2), and rash (1) and were generally responsive to immunosuppression. One pt died of opportunistic infections (OI) after 3 months of immunosuppression for colitis; this prompted inclusion of OI prophylaxis within the treatment algorithms. Another pt continues (1yr+) on immunosuppression to suppress colitis. Six pts (23%, 95% CI: 9-44%), all with irAEs, had a confirmed >50% PSA decline (median duration 140d, range 49 to 269+; median time to PSA decline 84d, range 41 to 147). 1 of 7 pts with measurable disease had a PR in nodal metastases and the prostate and achieved an undetectable PSA after treatment with 10 mg/kg IPI. Measurable disease response and PSA decline are both ongoing for 185+, 269+ d, respectively.
AB - CONCLUSIONS: The irAEs seen in this trial are similar in type to those seen in melanoma trials with IPI. Antitumor activity appears associated with irAEs. Both irAEs and PSA declines were seen across dose levels. Addition of XRT to 3 mg/kg appears feasible, and evaluation of radiation with 10 mg/kg of IPI is underway. [Table: see text].
ES - 1527-7755
IL - 0732-183X
DI - 10.1200/jco.2008.26.15_suppl.5004
PT - Journal Article
ID - 27948611 [pubmed]
ID - 10.1200/jco.2008.26.15_suppl.5004 [pii]
PP - ppublish
LG - English
DP - 2008 May 20
DC - 20161212
EZ - 2016/12/13 06:00
YR - 2008
RD - 20161212
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27948611
<492. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27948191
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - In-Data-Review
AU - Gerritsen W
AU - van den Eertwegh AJ
AU - de Gruijl T
AU - van den Berg HP
AU - Scheper RJ
AU - Sacks N
AU - Lowy I
AU - Stankevich E
AU - Hege K
FA - Gerritsen, W
FA - van den Eertwegh, A J
FA - de Gruijl, T
FA - van den Berg, H P
FA - Scheper, R J
FA - Sacks, N
FA - Lowy, I
FA - Stankevich, E
FA - Hege, K
IN - Gerritsen, W. VU Medical Center, Amsterdam, The Netherlands; Cell Genesys, Inc., South San Francisco, CA; Medarex, Bloomsbury, NJ.
IN - van den Eertwegh, A J. VU Medical Center, Amsterdam, The Netherlands; Cell Genesys, Inc., South San Francisco, CA; Medarex, Bloomsbury, NJ.
IN - de Gruijl, T. VU Medical Center, Amsterdam, The Netherlands; Cell Genesys, Inc., South San Francisco, CA; Medarex, Bloomsbury, NJ.
IN - van den Berg, H P. VU Medical Center, Amsterdam, The Netherlands; Cell Genesys, Inc., South San Francisco, CA; Medarex, Bloomsbury, NJ.
IN - Scheper, R J. VU Medical Center, Amsterdam, The Netherlands; Cell Genesys, Inc., South San Francisco, CA; Medarex, Bloomsbury, NJ.
IN - Sacks, N. VU Medical Center, Amsterdam, The Netherlands; Cell Genesys, Inc., South San Francisco, CA; Medarex, Bloomsbury, NJ.
IN - Lowy, I. VU Medical Center, Amsterdam, The Netherlands; Cell Genesys, Inc., South San Francisco, CA; Medarex, Bloomsbury, NJ.
IN - Stankevich, E. VU Medical Center, Amsterdam, The Netherlands; Cell Genesys, Inc., South San Francisco, CA; Medarex, Bloomsbury, NJ.
IN - Hege, K. VU Medical Center, Amsterdam, The Netherlands; Cell Genesys, Inc., South San Francisco, CA; Medarex, Bloomsbury, NJ.
TI - Expanded phase I combination trial of GVAX immunotherapy for prostate cancer and ipilimumab in patients with metastatic hormone-refractory prostate cancer (mHPRC).
SO - Journal of Clinical Oncology. 26(15_suppl):5146, 2008 May 20
AS - J Clin Oncol. 26(15_suppl):5146, 2008 May 20
NJ - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PI - Journal available in: Print
PI - Citation processed from: Internet
JC - jco, 8309333
IO - J. Clin. Oncol.
CP - United States
AB - 5146 Background: A Phase 1 trial is underway to study GVAX immunotherapy for prostate cancer [GVAX immunotherapy (GVAX IT)] and ipilimumab (Ipi) in chemonaive mHRPC patients (pts).
AB - METHODS: Twelve pts were treated in a dose-escalation phase for 24 weeks (wks) with bi-weekly intradermal injections of GVAX IT and monthly Ipi. Pts were enrolled in cohorts of 3; each cohort received an escalating dose of Ipi: 0.3, 1, 3 or 5 mg/kg. Sixteen pts were then enrolled in an expansion cohort to be treated with GVAX IT and 3 mg/kg Ipi.
AB - RESULTS: Escalation Cohort: Median follow-up of 12 pts is 21.2 months (m). Five of six pts at the higher Ipi doses (3 and 5 mg/kg) developed Grade 2 or 3 immune-related adverse events (irAEs), including Grade 2 or 3 hypophysitis and Grade 3 alveolitis. Late onset PSA responses (declines > 50%) were seen in these 5 pts with response durations of 6.7, 8.6, 9.5, 13.8 (on-going), and 23.1 m. Four of these pts had stable disease on bone scan for at least 12 m, and up to 21 m. Multiple tumor-reactive antibodies (abs) induced by treatment were identified by serologic analysis (SEREX), including abs to filamin B, PSMA and NY-ESO-1. Biopsies of injection sites showed T cell infiltration and Granzyme B expression; these T cells are being tested for antigen-specific lytic activity. Expansion Cohort: Sixteen pts were enrolled, 6 have completed treatment, 10 are on-going. Three pts have experienced irAEs of Grade 1 diarrhea, Grade 3 adrenal insufficiency, and a Grade 3 hepatitis that resolved with steroids. With median follow-up of 6.5 months in the 6 pts who have completed treatment, 1 pt had a PSA response (> 50% decline) and 3 obtained stable PSA, accompanied in one pt by pain relief and decrease in alkaline phosphatase.
AB - CONCLUSIONS: The GVAX IT and ipilimumab combination is active in mHRPC in this trial. IrAEs appear manageable and may correlate with anti-tumor activity. The maximum tolerated dose of the combination is not established. Follow-up on the 16 expansion cohort pts will provide data on safety, clinical activity and immunologic correlates. [Table: see text].
ES - 1527-7755
IL - 0732-183X
DI - 10.1200/jco.2008.26.15_suppl.5146
PT - Journal Article
ID - 27948191 [pubmed]
ID - 10.1200/jco.2008.26.15_suppl.5146 [pii]
PP - ppublish
LG - English
DP - 2008 May 20
DC - 20161212
EZ - 2016/12/13 06:00
YR - 2008
RD - 20161212
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=27948191
<493. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28707167
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Rapoport BL
AU - van Eeden R
AU - Sibaud V
AU - Epstein JB
AU - Klastersky J
AU - Aapro M
AU - Moodley D
FA - Rapoport, Bernardo Leon
FA - van Eeden, Ronwyn
FA - Sibaud, Vincent
FA - Epstein, Joel B
FA - Klastersky, Jean
FA - Aapro, Matti
FA - Moodley, Devan
IN - Rapoport, Bernardo Leon. The Medical Oncology Centre of Rosebank129 Oxford Road, Saxonwold 2196, Johannesburg, South Africa. brapoport@rosebankoncology.co.za.
IN - Rapoport, Bernardo Leon. Department of Immunology, Faculty of Health Sciences, University of Pretoria, PO Box 2040, Parklands 2121, Pretoria, 0001, South Africa. brapoport@rosebankoncology.co.za.
IN - van Eeden, Ronwyn. The Medical Oncology Centre of Rosebank129 Oxford Road, Saxonwold 2196, Johannesburg, South Africa.
IN - Sibaud, Vincent. Department of Medical Oncology and Clinical Research Institut Claudius Regaud, Institut Universitaire du Cancer, Toulouse Oncopole, France.
IN - Sibaud, Vincent. Department of Oncodermatology, Institut Claudius Regaud, Institut Universitaire du Cancer, Toulouse Oncopole, France.
IN - Epstein, Joel B. Cedars-Sinai Health System, Samuel Oshin Comprehensive Cancer Institute, Los Angeles, CA, USA.
IN - Klastersky, Jean. Institut Jules Bordet, Universite Libre de Bruxelles, Centre des Tumeurs de l'ULB, Rue Heger Bordet, 1, 1000, Brussels, Belgium.
IN - Aapro, Matti. Institut Multidisciplinaire d'Oncologie, Clinique de Genolier, Genolier, Switzerland.
IN - Moodley, Devan. University of the Witwatersrand and Wits Donald Gordon Medical Center, Johannesburg, South Africa.
TI - Supportive care for patients undergoing immunotherapy.
SO - Supportive Care in Cancer. , 2017 Jul 13
AS - Support Care Cancer. , 2017 Jul 13
NJ - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9302957, b1l
IO - Support Care Cancer
CP - Germany
KW - Anti-CTLA-4; Anti-PD-1; Anti-PDL-1; Colitis; Endocrinopathy; Immune checkpoint inhibitors; Immune-related adverse events; Nephritis; Pneumonitis; Skin rash; Vitiligo; irAE
AB - Immune checkpoint inhibitors, a new class of cancer therapeutic agents, play an important role in the management of melanoma, NSCLC, and other malignancies. A workshop organized by three MASCC Study Groups: Oral Care, Skin Toxicities, and Neutropenia, Infection, and Myelosuppression during the MASCC Annual Meeting held in Adelaide, Australia on 23-25 June, 2016 focused on the new class of anti-cancer therapeutic agents. Topics in the workshop included the mechanism of action and clinical uses of immune anti-CTL4 and anti-PD1 antibodies, checkpoint inhibitor toxicities, including skin adverse events, gastrointestinal toxicities, oral complications, pulmonary toxicities, and endocrinological and immune-related infections. Checkpoint inhibitors have been approved for use in different malignancies including metastatic melanoma, advanced non-small cell lung cancer, metastatic renal cell carcinoma, refractory Hodgkin's lymphoma, metastatic bladder cancer, and advanced head and neck cancer, and the list continues to grow. In general, these agents seem to be better tolerated in most patients and less toxic compared to conventional chemotherapy. However, the toxicities here, termed immune-related adverse events (irAEs), are unique and different from what we have seen in the past. There is no prospective data on these toxicities, and guidelines or recommendations are currently based on symptomatic management from the ongoing clinical trials. Treating oncologists need to be aware and alert themselves to the subtleties in presentation and the big difference in the way we manage the irAEs. Although most irAEs are low-grade and manageable, they have the potential to be life-threatening and extremely severe if not promptly treated. Additionally, irAEs could even lead to death, if managed incorrectly. The MASCC workshop addressed the various irAEs, per organ system, clinical presentation, management recommendations, and individual toxicities.
ES - 1433-7339
IL - 0941-4355
DI - 10.1007/s00520-017-3802-9
DO - https://dx.doi.org/10.1007/s00520-017-3802-9
PT - Journal Article
ID - 10.1007/s00520-017-3802-9 [doi]
ID - 10.1007/s00520-017-3802-9 [pii]
PP - aheadofprint
PH - 2017/03/31 [received]
PH - 2017/06/18 [accepted]
LG - English
EP - 20170713
DP - 2017 Jul 13
DC - 20170714
EZ - 2017/07/15 06:00
DA - 2017/07/15 06:00
DT - 2017/07/15 06:00
YR - 2017
RD - 20170714
UP - 20170717
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28707167
<494. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28689073
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Sznol M
AU - Postow MA
AU - Davies MJ
AU - Pavlick AC
AU - Plimack ER
AU - Shaheen M
AU - Veloski C
AU - Robert C
FA - Sznol, Mario
FA - Postow, Michael A
FA - Davies, Marianne J
FA - Pavlick, Anna C
FA - Plimack, Elizabeth R
FA - Shaheen, Montaser
FA - Veloski, Colleen
FA - Robert, Caroline
IN - Sznol, Mario. Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA. Electronic address: mario.sznol@yale.edu.
IN - Postow, Michael A. Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
IN - Davies, Marianne J. Yale School of Nursing, West Haven, CT, USA.
IN - Pavlick, Anna C. New York University, New York, NY, USA.
IN - Plimack, Elizabeth R. Fox Chase Cancer Center, Temple Health, Philadelphia, PA, USA.
IN - Shaheen, Montaser. University of New Mexico, Albuquerque, NM, USA.
IN - Veloski, Colleen. Fox Chase Cancer Center, Temple Health, Philadelphia, PA, USA.
IN - Robert, Caroline. Gustave Roussy and Paris-Sud University, Villejuif, France.
TI - Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management. [Review]
SO - Cancer Treatment Reviews. 58:70-76, 2017 Jun 22
AS - Cancer Treat Rev. 58:70-76, 2017 Jun 22
NJ - Cancer treatment reviews
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cnn, 7502030
IO - Cancer Treat. Rev.
CP - Netherlands
KW - Hypophysitis; Immune-related adverse events; Ipilimumab; Melanoma; Nivolumab; Thyroiditis
AB - Agents that modulate immune checkpoint proteins, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death receptor-1 (PD-1), have become a mainstay in cancer treatment. The clinical benefit afforded by immune checkpoint inhibitors can be accompanied by immune-related adverse events (irAE) that affect the skin, gastrointestinal tract, liver, and endocrine system. The types of irAEs associated with immune checkpoint inhibitors are generally consistent across tumor types. Immune-related endocrine events can affect the pituitary, thyroid, and adrenal glands, as well as other downstream target organs. These events are unique when compared with other irAEs because the manifestations are often irreversible. Immune-related endocrine events are typically grade 1/2 in severity and often present with non-specific symptoms, making them difficult to diagnose. The mechanisms underlying immune-related target organ damage in select individuals remain mostly undefined. Management includes close patient monitoring, appropriate laboratory testing for endocrine function, replacement of hormones, and consultation with an endocrinologist when appropriate. An awareness of the symptoms and management of immune-related endocrine events may aid in the safe and appropriate use of immune checkpoint inhibitors in clinical practice.
Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
ES - 1532-1967
IL - 0305-7372
DI - S0305-7372(17)30100-7
DO - https://dx.doi.org/10.1016/j.ctrv.2017.06.002
PT - Journal Article
PT - Review
ID - S0305-7372(17)30100-7 [pii]
ID - 10.1016/j.ctrv.2017.06.002 [doi]
PP - aheadofprint
PH - 2017/01/27 [received]
PH - 2017/06/13 [revised]
PH - 2017/06/14 [accepted]
LG - English
EP - 20170622
DP - 2017 Jun 22
DC - 20170709
EZ - 2017/07/10 06:00
DA - 2017/07/10 06:00
DT - 2017/07/10 06:00
YR - 2017
RD - 20170709
UP - 20170710
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28689073
<495. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28666240
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Makarious D
AU - Horwood K
AU - Coward JIG
FA - Makarious, D
FA - Horwood, K
FA - Coward, J I G
IN - Makarious, D. Bond University, School of Medicine, Robina, Australia.
IN - Horwood, K. ICON Cancer Care, Brisbane, Australia.
IN - Coward, J I G. ICON Cancer Care, Brisbane, Australia; Faculty of Medicine, University of Queensland, Australia; Princess Alexandra Hospital, Brisbane, Australia. Electronic address: jim.coward@gmail.com.
TI - Myasthenia gravis: An emerging toxicity of immune checkpoint inhibitors. [Review]
SO - European Journal of Cancer. 82:128-136, 2017 Jun 27
AS - Eur J Cancer. 82:128-136, 2017 Jun 27
NJ - European journal of cancer (Oxford, England : 1990)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - arv, 9005373
IO - Eur. J. Cancer
CP - England
KW - Autoimmunity; CTLA-4; Immune checkpoint inhibitors; Immune-related adverse events; Ipilimumab; Myasthenia gravis; Nivolumab; PD-1; Pembrolizumab
AB - The advent of immunotherapy has heralded a number of significant advances in the treatment of particular malignancies associated with poor prognosis (melanoma, non-small-cell lung, renal and head/neck cancers). The success witnessed with therapeutic agents targeting cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1 and programmed cell death ligand 1 immune checkpoints has inevitably led to an explosion in their clinical application and the subsequent recognition of specific toxicity profiles distinct from those long recognised with chemotherapy. Consequently, as the utility of such therapies broaden, understanding the nature, timing and management of these immune-related adverse events (irAEs) becomes increasingly significant. Although neurological irAEs are considered relatively rare in comparison with hepatitis, colitis, pneumonitis and endocrinopathies, one emerging side-effect is myasthenia gravis (MG). Among the 23 reported cases of immune checkpoint inhibitor-associated MG, 72.7% were de novo presentations, 18.2% were exacerbations of pre-existing MG and 9.1% were exacerbations of subclinical MG. The average onset of symptoms was within 6 weeks (range 2-12 weeks) of treatment initiation. In addition, there was no consistent association with elevated acetylcholine antibody titres and the development of immune checkpoint inhibitor-related MG. Significantly, there was a 30.4% MG-specific-related mortality, which further emphasises the importance of early recognition and robust treatment of this toxicity. In addition to a review of the existing literature, we present a new case of pembrolizumab-induced MG and provide insights into the underlying mechanisms of action of this phenomenon.
Copyright © 2017 Elsevier Ltd. All rights reserved.
ES - 1879-0852
IL - 0959-8049
DI - S0959-8049(17)31017-1
DO - https://dx.doi.org/10.1016/j.ejca.2017.05.041
PT - Journal Article
PT - Review
ID - S0959-8049(17)31017-1 [pii]
ID - 10.1016/j.ejca.2017.05.041 [doi]
PP - aheadofprint
PH - 2017/03/27 [received]
PH - 2017/05/06 [revised]
PH - 2017/05/19 [accepted]
LG - English
EP - 20170627
DP - 2017 Jun 27
DC - 20170630
EZ - 2017/07/01 06:00
DA - 2017/07/01 06:00
DT - 2017/07/01 06:00
YR - 2017
RD - 20170630
UP - 20170703
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28666240
<496. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28661915
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Konda B
AU - Nabhan F
AU - Shah MH
FA - Konda, Bhavana
FA - Nabhan, Fadi
FA - Shah, Manisha H
IN - Konda, Bhavana. aDivision of Medical Oncology, Department of Internal Medicine bDivision of Endocrinology, Diabetes, and Metabolism, The Ohio State University and Arthur G. James Cancer Center, Columbus, Ohio, USA *Bhavana Konda and Fadi Nabhan contributed equally to the article.
TI - Endocrine dysfunction following immune checkpoint inhibitor therapy.
SO - Current Opinion in Endocrinology, Diabetes & Obesity. , 2017 Jun 28
AS - Curr. opin. endocrinol. diabetes obes.. , 2017 Jun 28
NJ - Current opinion in endocrinology, diabetes, and obesity
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101308636
IO - Curr Opin Endocrinol Diabetes Obes
CP - England
AB - PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICI) represent an important milestone in the modern era of antineoplastic therapy and have ushered optimism amongst oncologists and patients alike. These agents, however, are associated with significant potential toxicities, the importance of which cannot be overstated. The clinical presentation, diagnosis, and management strategies of immune-related endocrinopathies associated with ICI use are described in this case-based review.
AB - RECENT FINDINGS: An increasing number of ICI have shown promise in the management of various malignancies in the recent years. These include cytotoxic T lymphocyte antigen-4 inhibitors, programed death 1 antibodies, and programed death-ligand 1 antibodies. Several endocrinopathies, including hypophysitis, thyroid dysfunction, hyperglycemia, and primary adrenal insufficiency, have been associated with the use of these agents. Toxicities may range from mild transient laboratory abnormalities to potentially life-threatening ones, warranting immediate therapeutic intervention. Combination ICI therapies may be associated with a greater risk of endocrine dysfunction when compared with monotherapy. The clinical presentation and laboratory assessment of these patients often pose a diagnostic challenge as they may be confused by the symptoms related to their underlying malignancy or potential associated acute illnesses.
AB - SUMMARY: ICI use is associated with serious endocrinopathies that may have a nonspecific initial presentation. A constant eye for these symptoms and a systematic approach to diagnosis are essential for prompt initiation of therapy and prevention of significant complications.
ES - 1752-2978
IL - 1752-296X
DO - https://dx.doi.org/10.1097/MED.0000000000000357
PT - Journal Article
ID - 10.1097/MED.0000000000000357 [doi]
PP - aheadofprint
LG - English
EP - 20170628
DP - 2017 Jun 28
DC - 20170629
EZ - 2017/06/30 06:00
DA - 2017/07/01 06:00
DT - 2017/07/01 06:00
YR - 2017
RD - 20170629
UP - 20170703
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28661915
<497. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28661901
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Han TS
AU - Gleeson HK
FA - Han, Thang S
FA - Gleeson, Helena K
IN - Han, Thang S. aInstitute of Cardiovascular Research, Royal Holloway, University of London & Ashford and St Peter's Hospitals NHS Foundation Trust, Egham bUniversity Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
TI - Long-term and late treatment consequences: endocrine and metabolic effects.
SO - Current Opinion in Supportive & Palliative Care. , 2017 Jun 28
AS - Curr. opin. support. palliat. care. , 2017 Jun 28
NJ - Current opinion in supportive and palliative care
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101297402
IO - Curr Opin Support Palliat Care
CP - United States
AB - PURPOSE OF REVIEW: Cancer therapies often result in the 'late effect of cancer treatment' whereby secondary health complications emerge years after radiotherapy and chemotherapy. This review focuses on endocrine and metabolic consequences in adult cancer survivors as late treatment effects.
AB - RECENT FINDINGS: Endocrine and metabolic disorders are among the most common late effects. Endocrine disorders include hypopituitarism, which leads to growth hormone deficiency, hypogonadism, adrenal insufficiency and hypothyroidism and related clinical manifestations. Hypogonadism in particular is associated with a wide range of health complications requiring input from the like of endocrine and fertility specialists. Immune checkpoint inhibitors are novel anticancer agents, some of which are uniquely associated with hypophysitis which requires early recognition and management, including steroid replacement. Metabolic syndrome, a significant risk for cardiovascular disease, is highly prevalent. Although the effects of cranial irradiation on the hypothalamic-pituitary system are more apparent, the relationship between chemotherapy and endocrine/metabolic disorders remains to be elucidated. There exist published guidelines for monitoring endocrine and cardiometabolic risk in cancer survivors, but the extent of monitoring appears insufficient.
AB - SUMMARY: Regular monitoring and early management of endocrine/metabolic disorders is required to prevent the elevated rates of health complications after cancer treatment, and thereby improve cancer survivorship.
ES - 1751-4266
IL - 1751-4258
DO - https://dx.doi.org/10.1097/SPC.0000000000000289
PT - Journal Article
ID - 10.1097/SPC.0000000000000289 [doi]
PP - aheadofprint
LG - English
EP - 20170628
DP - 2017 Jun 28
DC - 20170629
EZ - 2017/06/30 06:00
DA - 2017/07/01 06:00
DT - 2017/07/01 06:00
YR - 2017
RD - 20170629
UP - 20170703
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28661901
<498. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28640512
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Chan PY
AU - Hall P
AU - Hay G
AU - Cohen VML
AU - Szlosarek PW
FA - Chan, Pui Ying
FA - Hall, Peter
FA - Hay, Gordon
FA - Cohen, Victoria M L
FA - Szlosarek, Peter W
IN - Chan, Pui Ying. Department of Medical Oncology, St Bartholomew's Hospital, London, UK.
IN - Hall, Peter. Department of Medical Oncology, St Bartholomew's Hospital, London, UK.
IN - Hay, Gordon. Department of Ocular Oncology, Moorfields Eye Hospital, London, UK.
IN - Hay, Gordon. UCL Institute of Ophthalmology, London, UK.
IN - Cohen, Victoria M L. Department of Ocular Oncology, Moorfields Eye Hospital, London, UK.
IN - Cohen, Victoria M L. Department of Ocular Oncology, St Bartholomew's Hospital, London, UK.
IN - Szlosarek, Peter W. Department of Medical Oncology, St Bartholomew's Hospital, London, UK.
IN - Szlosarek, Peter W. Centre for Molecular Oncology, Barts Cancer Institute, London, UK.
TI - A major responder to ipilimumab and nivolumab in metastatic uveal melanoma with concomitant autoimmunity.
SO - Pigment Cell & Melanoma Research. , 2017 Jun 22
AS - Pigment Cell Melanoma Res. , 2017 Jun 22
NJ - Pigment cell & melanoma research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101318927
IO - Pigment Cell Melanoma Res
CP - England
KW - Autoimmunity; immunotherapy; ipilimumab; metastasis; nivolumab; ocular; uveal melanoma
AB - The use of immune checkpoint inhibition has led to major improvements in outcome for patients with metastatic cutaneous melanoma. The combination of ipilimumab and nivolumab has demonstrated greater activity over single agent immunotherapy in phase III trials. Clinical trials of combination CTLA-4 and PD-1 inhibition are underway in uveal melanoma, for which there are currently no data. Here, we present the case of a 74-year-old male patient with metastatic uveal melanoma, who was treated with a combination of ipilimumab and nivolumab. He developed sequential autoimmune transaminitis, diabetes and uveitis, which necessitated discontinuation of maintenance nivolumab 3 months after commencement of treatment. The patient continues to demonstrate an ongoing partial response 10 months from the initial combination immunotherapy, with evidence of depigmentation of the primary ocular tumour. This article is protected by copyright. All rights reserved.
Copyright This article is protected by copyright. All rights reserved.
ES - 1755-148X
IL - 1755-1471
DO - https://dx.doi.org/10.1111/pcmr.12607
PT - Journal Article
ID - 10.1111/pcmr.12607 [doi]
PP - aheadofprint
LG - English
EP - 20170622
DP - 2017 Jun 22
DC - 20170622
EZ - 2017/06/23 06:00
DA - 2017/06/24 06:00
DT - 2017/06/24 06:00
YR - 2017
RD - 20170622
UP - 20170626
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28640512
<499. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28634815
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Gauci ML
AU - Laly P
AU - Vidal-Trecan T
AU - Baroudjian B
AU - Gottlieb J
AU - Madjlessi-Ezra N
AU - Da Meda L
AU - Madelaine-Chambrin I
AU - Bagot M
AU - Basset-Seguin N
AU - Pages C
AU - Mourah S
AU - Boudou P
AU - Lebbe C
AU - Gautier JF
FA - Gauci, Marie-Lea
FA - Laly, Pauline
FA - Vidal-Trecan, Tiphaine
FA - Baroudjian, Barouyr
FA - Gottlieb, Jeremy
FA - Madjlessi-Ezra, Nika
FA - Da Meda, Laetitia
FA - Madelaine-Chambrin, Isabelle
FA - Bagot, Martine
FA - Basset-Seguin, Nicole
FA - Pages, Cecile
FA - Mourah, Samia
FA - Boudou, Philippe
FA - Lebbe, Celeste
FA - Gautier, Jean-Francois
IN - Gauci, Marie-Lea. AP-HP Dermatology Department, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75475, Paris Cedex 10, France. marie-lea.gauci@hotmail.fr.
IN - Gauci, Marie-Lea. INSERM U976, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France. marie-lea.gauci@hotmail.fr.
IN - Laly, Pauline. AP-HP Dermatology Department, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75475, Paris Cedex 10, France.
IN - Laly, Pauline. INSERM U976, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
IN - Vidal-Trecan, Tiphaine. AP-HP Diabetology Department, Lariboisiere Hospital, Paris, France.
IN - Vidal-Trecan, Tiphaine. INSERM U1138, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
IN - Baroudjian, Barouyr. AP-HP Dermatology Department, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75475, Paris Cedex 10, France.
IN - Baroudjian, Barouyr. INSERM U976, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
IN - Gottlieb, Jeremy. AP-HP Dermatology Department, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75475, Paris Cedex 10, France.
IN - Gottlieb, Jeremy. INSERM U976, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
IN - Madjlessi-Ezra, Nika. AP-HP Dermatology Department, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75475, Paris Cedex 10, France.
IN - Madjlessi-Ezra, Nika. INSERM U976, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
IN - Da Meda, Laetitia. AP-HP Dermatology Department, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75475, Paris Cedex 10, France.
IN - Da Meda, Laetitia. INSERM U976, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
IN - Madelaine-Chambrin, Isabelle. INSERM U976, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
IN - Madelaine-Chambrin, Isabelle. AP-HP Pharmacology Department, Saint-Louis Hospital, Paris, France.
IN - Bagot, Martine. AP-HP Dermatology Department, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75475, Paris Cedex 10, France.
IN - Bagot, Martine. INSERM U976, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
IN - Basset-Seguin, Nicole. AP-HP Dermatology Department, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75475, Paris Cedex 10, France.
IN - Basset-Seguin, Nicole. INSERM U976, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
IN - Pages, Cecile. AP-HP Dermatology Department, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75475, Paris Cedex 10, France.
IN - Pages, Cecile. INSERM U976, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
IN - Mourah, Samia. INSERM U976, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
IN - Mourah, Samia. AP-HP Pharmacogenomic Laboratory, Saint-Louis Hospital, Paris, France.
IN - Boudou, Philippe. AP-HP Hormonology Department, Saint-Louis Hospital, Paris, France.
IN - Boudou, Philippe. Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
IN - Lebbe, Celeste. AP-HP Dermatology Department, Saint-Louis Hospital, 1 avenue Claude Vellefaux, 75475, Paris Cedex 10, France.
IN - Lebbe, Celeste. INSERM U976, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
IN - Gautier, Jean-Francois. AP-HP Diabetology Department, Lariboisiere Hospital, Paris, France.
IN - Gautier, Jean-Francois. INSERM U1138, Universite Paris Diderot-Paris VII, Sorbonne Paris Cite, Paris, France.
TI - Autoimmune diabetes induced by PD-1 inhibitor-retrospective analysis and pathogenesis: a case report and literature review.
SO - Cancer Immunology, Immunotherapy. , 2017 Jun 20
AS - Cancer Immunol Immunother. , 2017 Jun 20
NJ - Cancer immunology, immunotherapy : CII
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cn3, 8605732
IO - Cancer Immunol. Immunother.
CP - Germany
KW - Adverse events; Anti-PD-1 antibody; Autoimmune diabetes; Melanoma
AB - Anti-PD-1 antibody treatment is approved in advanced melanoma and provides median overall survival over 24 months. The main treatment-related side effects are immune-related adverse events, which include rash, pruritus, vitiligo, thyroiditis, diarrhoea, hepatitis and pneumonitis. We report a case of autoimmune diabetes related to nivolumab treatment. A 73-year-old man was treated in second line with nivolumab at 3 mg/kg every two weeks for metastatic melanoma. At 6 weeks of treatment, he displayed diabetic ketoacidosis. Nivolumab was withheld 3.5 weeks and insulin therapy was initiated, enabling a normalization of glycaemia and the disappearance of symptoms. Laboratory investigations demonstrated the presence of islet cell autoantibodies, while C-peptide was undetectable. Retrospective explorations on serum banked at week 0 and 3 months before the start of nivolumab, already showed the presence of autoantibodies, but normal insulin, C-peptide secretion and glycaemia. Partial response was obtained at month 3, and nivolumab was then resumed at the same dose. The clinical context and biological investigations before, at and after nivolumab initiation suggest the autoimmune origin of this diabetes, most likely induced by anti-PD-1 antibody in a predisposed patient. The role of PD-1/PD-L1 binding is well known in the pathogenesis of type 1 diabetes. Therefore, this rare side effect can be expected in a context of anti-PD-1 treatment. Glycaemia should be monitored during PD-1/PD-L1 blockade. The presence of autoantibodies before treatment could identify individuals at risk of developing diabetes, but systematic titration may not be relevant considering the rarity of this side effect.
ES - 1432-0851
IL - 0340-7004
DI - 10.1007/s00262-017-2033-8
DO - https://dx.doi.org/10.1007/s00262-017-2033-8
PT - Journal Article
ID - 10.1007/s00262-017-2033-8 [doi]
ID - 10.1007/s00262-017-2033-8 [pii]
PP - aheadofprint
PH - 2017/01/25 [received]
PH - 2017/06/12 [accepted]
LG - English
EP - 20170620
DP - 2017 Jun 20
DC - 20170621
EZ - 2017/06/22 06:00
DA - 2017/06/22 06:00
DT - 2017/06/22 06:00
YR - 2017
RD - 20170621
UP - 20170622
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28634815
<500. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28383817
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Zwaenepoel K
AU - Jacobs J
AU - De Meulenaere A
AU - Silence K
AU - Smits E
AU - Siozopoulou V
AU - Hauben E
AU - Rolfo C
AU - Rottey S
AU - Pauwels P
AI - Zwaenepoel, Karen; ORCID: http://orcid.org/0000-0001-9122-0639
FA - Zwaenepoel, Karen
FA - Jacobs, Julie
FA - De Meulenaere, Astrid
FA - Silence, Karen
FA - Smits, Evelien
FA - Siozopoulou, Vasiliki
FA - Hauben, Esther
FA - Rolfo, Christian
FA - Rottey, Sylvie
FA - Pauwels, Patrick
IN - Zwaenepoel, Karen. Department of Pathology, Antwerp University Hospital, Edegem, Belgium.
IN - Zwaenepoel, Karen. Center for Oncological Research Antwerp, University of Antwerp, Wilrijk, Belgium.
IN - Jacobs, Julie. Department of Pathology, Antwerp University Hospital, Edegem, Belgium.
IN - Jacobs, Julie. Center for Oncological Research Antwerp, University of Antwerp, Wilrijk, Belgium.
IN - De Meulenaere, Astrid. Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium.
IN - Silence, Karen. arGEN-X BVBA, Ghent, Belgium.
IN - Smits, Evelien. Center for Oncological Research Antwerp, University of Antwerp, Wilrijk, Belgium.
IN - Smits, Evelien. Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, University of Antwerp, Wilrijk, Belgium.
IN - Siozopoulou, Vasiliki. Department of Pathology, Antwerp University Hospital, Edegem, Belgium.
IN - Siozopoulou, Vasiliki. Center for Oncological Research Antwerp, University of Antwerp, Wilrijk, Belgium.
IN - Hauben, Esther. Translational Cell and Tissue Research, Leuven University Hospital, Leuven, Belgium.
IN - Rolfo, Christian. Department of Oncology, Antwerp University Hospital, Edegem, Belgium.
IN - Rolfo, Christian. Phase 1-Early Clinical Trials Unit, Antwerp University Hospital, Edegem, Belgium.
IN - Rottey, Sylvie. Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium.
IN - Pauwels, Patrick. Department of Pathology, Antwerp University Hospital, Edegem, Belgium.
IN - Pauwels, Patrick. Center for Oncological Research Antwerp, University of Antwerp, Wilrijk, Belgium.
TI - CD70 and PD-L1 in anaplastic thyroid cancer - promising targets for immunotherapy.
SO - Histopathology. , 2017 Apr 06
AS - Histopathology. , 2017 Apr 06
NJ - Histopathology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - gb4, 7704136
IO - Histopathology
CP - England
KW - BRAF; CD70; PDL1; anaplastic thyroid cancer; immunotherapy
AB - AIMS: During recent years, immune checkpoint inhibition has proved to be effective in several solid malignancies. The aim of this study was to identify novel targets for immunotherapy in anaplastic thyroid cancer by analysis of the expression of tumour antigens for which therapeutic agents are available.
AB - METHOD AND RESULTS: By immunohistochemistry we observed tumoral expression of CD70 in 49% of cases. Expression of its receptor, CD27, was present mainly in lymphocytes surrounding and infiltrating the tumour and observed only rarely in tumour cells. CD70 expression was associated with the presence of a precursor papillary thyroid carcinoma and the presence of BRAF V600E mutations in the anaplastic thyroid cancer lesion. Furthermore, the expression of CD70 seems stable during progression of the disease. Tumoral expression of programmed cell death ligand 1 (PD-L1) was found in 28.6% of the anaplastic thyroid cancer cases. Programmed cell death 1 (PD-1), the receptor of PD-L1, was not expressed on the tumour cells. No association between CD70 expression and PD-L1 expression could be demonstrated.
AB - CONCLUSION: These data suggest that targeted immunotherapy for CD70/CD27 and PD-L1/PD-1 might be promising in anaplastic thyroid cancer. However, as a low amount of tumour-infiltrating lymphocytes was observed in most lesions, combined therapy with agents enhancing the invasion of lymphocytes in the tumour region needs to be considered.
AB - Copyright © 2017 John Wiley & Sons Ltd.
ES - 1365-2559
IL - 0309-0167
DO - https://dx.doi.org/10.1111/his.13230
PT - Journal Article
ID - 10.1111/his.13230 [doi]
PP - aheadofprint
PH - 2017/03/01 [received]
PH - 2017/04/04 [accepted]
LG - English
EP - 20170406
DP - 2017 Apr 06
DC - 20170406
EZ - 2017/04/07 06:00
DA - 2017/04/07 06:00
DT - 2017/04/07 06:00
YR - 2017
RD - 20170616
UP - 20170616
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28383817
<501. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28611199
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Weinstock C
AU - Khozin S
AU - Suzman D
AU - Zhang L
AU - Tang S
AU - Wahby S
AU - Goldberg KB
AU - Kim G
AU - Pazdur R
FA - Weinstock, Chana
FA - Khozin, Sean
FA - Suzman, Daniel
FA - Zhang, Lijun
FA - Tang, Shenghui
FA - Wahby, Sakar
FA - Goldberg, Kirsten B
FA - Kim, Geoffrey
FA - Pazdur, Richard
IN - Weinstock, Chana. Center for Drug Evaluation and Research, FDA Chana.Weinstock@fda.hhs.gov.
IN - Khozin, Sean. Center for Drug Evaluation and Research, FDA.
IN - Suzman, Daniel. Center for Drug Evaluation and Research, FDA.
IN - Zhang, Lijun. Office of Biostatistics, FDA.
IN - Tang, Shenghui. CDER, FDA.
IN - Wahby, Sakar. Center for Drug Evaluation and Research, FDA.
IN - Goldberg, Kirsten B. Center for Drug Evaluation and Research, U.S. Food and Drug Administration.
IN - Kim, Geoffrey. Center for Drug Evaluation and Research, U.S. Food and Drug Administration.
IN - Pazdur, Richard. Office of Oncology Drug Products, U.S. Food and Drug Administration.
TI - U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer.
SO - Clinical Cancer Research. , 2017 Jun 13
AS - Clin Cancer Res. , 2017 Jun 13
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c2h, 9502500
IO - Clin. Cancer Res.
CP - United States
AB - On October 18 2016, the U.S. Food and Drug Administration approved atezolizumab (TECENTRIQ, Genentech Inc.) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose disease progressed during or following platinum-containing chemotherapy. Approval was based on demonstration of clinically meaningful improvements in overall survival (OS) and an acceptable safety profile in two randomized clinical trials (OAK and POPLAR). Median OS in OAK, a phase III trial, was 13.8 months (95% confidence interval [CI] 11.8,15.7) in the atezolizumab arm compared with 9.6 months (95% CI 8.6,11.2) in the docetaxel arm (HR=0.74 [95% CI 0.63,0.87]; p=0.0004). Median OS in POPLAR, a phase II trial, was 12.6 months (95% CI 9.7, 16.0) and 9.7 months (95% CI 8.6, 12.0) (HR=0.69 [95% CI 0.52, 0.92]) for the atezolizumab and docetaxel arms, respectively. In patients treated with atezolizumab, the most common (>=20%) adverse reactions were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation; the most common (>=2%) grade 3-4 adverse events were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, AST increase, ALT increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included 1.4% incidence each of Grade 3-4 pneumonitis, hepatitis, colitis, and thyroid disease.
AB - Copyright ©2017, American Association for Cancer Research.
IS - 1078-0432
IL - 1078-0432
DI - clincanres.0540.2017
DI - 1078-0432.CCR-17-0540
DO - https://dx.doi.org/10.1158/1078-0432.CCR-17-0540
PT - Journal Article
ID - 1078-0432.CCR-17-0540 [pii]
ID - 10.1158/1078-0432.CCR-17-0540 [doi]
PP - aheadofprint
PH - 2017/06/07 [accepted]
PH - 2017/03/09 [received]
PH - 2017/05/01 [revised]
LG - English
EP - 20170613
DP - 2017 Jun 13
DC - 20170614
EZ - 2017/06/15 06:00
DA - 2017/06/15 06:00
DT - 2017/06/15 06:00
YR - 2017
RD - 20170614
UP - 20170615
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28611199
<502. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28609832
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Delivanis DA
AU - Gustafson MP
AU - Bornschlegl S
AU - Merten MM
AU - Kottschade L
AU - Withers S
AU - Dietz AB
AU - Ryder M
FA - Delivanis, Danae A
FA - Gustafson, Michael P
FA - Bornschlegl, Svetlana
FA - Merten, Michele M
FA - Kottschade, Lisa
FA - Withers, Sarah
FA - Dietz, Allan B
FA - Ryder, Mabel
IN - Delivanis, Danae A. Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA
IN - Gustafson, Michael P. Human Cell Therapy Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
IN - Bornschlegl, Svetlana. Department of Laboratory Medicine & Pathology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA
IN - Merten, Michele M. Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA
IN - Kottschade, Lisa. Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA
IN - Withers, Sarah. Department of Laboratory Medicine & Pathology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA
IN - Dietz, Allan B. Human Cell Therapy Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
IN - Ryder, Mabel. Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA
IN - Ryder, Mabel. Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA
TI - Pembrolizumab-induced thyroiditis. Comprehensive clinical review and insights into underlying involved mechanisms.
SO - Journal of Clinical Endocrinology & Metabolism. , 2017 05 09
AS - J Clin Endocrinol Metab. , 2017 05 09
NJ - The Journal of clinical endocrinology and metabolism
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - hrb, 0375362
IO - J. Clin. Endocrinol. Metab.
CP - United States
KW - *hypothyroidism; *fluorodeoxyglucose f18; *cd14 antigen; *cancer; *flow cytometry; *cd56 antigens; *color; *hla-dr antigens; *iodide peroxidase; *natural killer cells; *monocytes; *neural cell adhesion molecules; *thyroid diseases; *thyroiditis; *t-lymphocyte; *antibodies; *thryoxine; *malignant neoplasm of thyroid; *cd16; *radionuclide; *thyroid imaging study; *destructive behavior; *thyroid autoantibodies; *advanced; *adverse event; *laboratory test finding; *infusion procedures; *pembrolizumab
AB - Context: Thyroid immune-related adverse events (irAEs) in patients treated with programmed death receptor-1 (PD-1) blockade are increasingly recognized as one of the most common adverse effects. Our aim was to determine the incidence and examine the potential mechanisms of anti-PD-1 induced thyroid irAEs.
AB - Design: Single center, retrospective cohort study.
AB - Patients and Measurements: We studied 93 patients with advanced cancer (aged 24-82 years; 60% males) who received at least one infusion of pembrolizumab. Thyroid test results and thyroid imaging modalities were reviewed. Comprehensive 10-color flow cytometry of peripheral blood was performed.
AB - Results: Thirteen (14%) thyroid irAEs were observed. Thyroiditis occurred in 7 patients (54%), from which 4 recovered. New onset of hypothyroidism overt/subclinical developed in 3 patients. Levothyroxine dosing required doubling in 3 patients with known history of hypothyroidism. Thyroperoxidase (TPO) antibodies-(abs) were positive in the minority of the patients 4/13 (31%) and diffuse increased 18FDG uptake of the thyroid gland was observed in the majority 7/11 (64%) of patients. We observed an increased number of circulating CD56+CD16+ NK cells and an elevated HLA-DR surface expression in the inflammatory intermediate CD14+CD16+ monocytes in anti-PD-1 treated patients.
AB - Conclusions: Thyroid dysfunction is common in cancer patients treated with pembrolizumab. Reversible destructive thyroiditis as well as overt hypothyroidism are the most common clinical presentations. The mechanism of thyroid destruction appears independent of thyroid autoantibodies and may include T-cell, NK cell, and/or monocyte mediated pathways. As the thyroid is a frequent target of anti-PD-1 therapies, patients with therapeutically refractory thyroid cancer may be ideal candidates for this treatment.
AB - Copyright © 2017 by the Endocrine Society
ES - 1945-7197
IL - 0021-972X
DO - https://dx.doi.org/10.1210/jc.2017-00448
PT - Journal Article
ID - 10.1210/jc.2017-00448 [doi]
PP - aheadofprint
PH - 2017/05/02 [accepted]
PH - 2017/02/16 [received]
LG - English
EP - 20170509
DP - 2017 05 09
DC - 20170613
EZ - 2017/06/15 06:00
DA - 2017/06/15 06:00
DT - 2017/06/15 06:00
YR - 2017
RD - 20170613
UP - 20170615
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28609832
<503. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28604555
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Tchapyjnikov D
AU - Borst AJ
FA - Tchapyjnikov, Dmitry
FA - Borst, Alexandra J
IN - Tchapyjnikov, Dmitry. *Division of Pediatric Neurology +Division of Pediatric Hematology-Oncology, Duke University Medical Center, Durham, NC.
TI - Immune-related Neurological Symptoms in an Adolescent Patient Receiving the Checkpoint Inhibitor Nivolumab.
SO - Journal of Immunotherapy. , 2017 Jun 09
AS - J Immunother. , 2017 Jun 09
NJ - Journal of immunotherapy (Hagerstown, Md. : 1997)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cuq, 9706083
IO - J. Immunother.
CP - United States
AB - Immune checkpoint inhibitors are a novel group of immunotherapeutic agents for the treatment of cancer. Immune-related adverse events, including neurological symptoms, have been associated with these agents. We present the case of an adolescent with refractory Hodgkin lymphoma treated with nivolumab, a PD1 inhibitor, who developed Hashimoto thyroiditis, posterior reversible encephalopathy syndrome causing seizures, as well as urinary retention, truncal/appendicular spasticity, dysphagia, and a progressive encephalopathy that was clinically consistent with a diagnosis of progressive encephalopathy with rigidity and myoclonus, a stiff-person-syndrome spectrum disorder. He showed response and ultimately full recovery to a combination of intravenous steroids, intravenous immunoglobulin, and plasma exchange. To our knowledge, this is the first documented report of an immune-related neurological reaction to nivolumab in an adolescent patient and expands the spectrum of known nivolumab-associated toxicities.
ES - 1537-4513
IL - 1524-9557
DO - https://dx.doi.org/10.1097/CJI.0000000000000177
PT - Journal Article
ID - 10.1097/CJI.0000000000000177 [doi]
PP - aheadofprint
LG - English
EP - 20170609
DP - 2017 Jun 09
DC - 20170612
EZ - 2017/06/13 06:00
DA - 2017/06/13 06:00
DT - 2017/06/13 06:00
YR - 2017
RD - 20170612
UP - 20170613
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28604555
<504. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28604554
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Pushkarevskaya A
AU - Neuberger U
AU - Dimitrakopoulou-Strauss A
AU - Enk A
AU - Hassel JC
FA - Pushkarevskaya, Anna
FA - Neuberger, Ulf
FA - Dimitrakopoulou-Strauss, Antonia
FA - Enk, Alexander
FA - Hassel, Jessica C
IN - Pushkarevskaya, Anna. Departments of *Dermatology and National Center for Tumor Diseases (NCT) +Diagnostic Radiology, University Hospital Heidelberg ++German Cancer Research Center, Clinical Cooperation Unit Nuclear Medicine, Heidelberg, Germany.
TI - Severe Ocular Myositis After Ipilimumab Treatment for Melanoma: A Report of 2 Cases.
SO - Journal of Immunotherapy. , 2017 Jun 09
AS - J Immunother. , 2017 Jun 09
NJ - Journal of immunotherapy (Hagerstown, Md. : 1997)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cuq, 9706083
IO - J. Immunother.
CP - United States
AB - Ipilimumab binds and blocks cytotoxic T-lymphocyte-associated antigen-4, causing enhanced T-cell reaction, antitumor response, and significant improvement of the overall survival of patients with metastatic melanoma. Patients treated with ipilimumab can develop immune-related adverse effects, primarily dermatitis, colitis, hepatitis, and hypophysitis. Although, in phase I-III studies, 64.2% of all patients suffered from immune-related adverse effects, ocular adverse effects occurred in 1.3% only. In the cases reported below, 2 patients with metastatic melanoma developed severe ocular myositis after treatment with ipilimumab. These are the first 2 reports of successful treatment of this condition by use of a combination of methylprednisolone and mycophenolate mofetil, and, in 1 of the cases, additional medication with intravenous immunoglobulin.
ES - 1537-4513
IL - 1524-9557
DO - https://dx.doi.org/10.1097/CJI.0000000000000178
PT - Journal Article
ID - 10.1097/CJI.0000000000000178 [doi]
PP - aheadofprint
LG - English
EP - 20170609
DP - 2017 Jun 09
DC - 20170612
EZ - 2017/06/13 06:00
DA - 2017/06/13 06:00
DT - 2017/06/13 06:00
YR - 2017
RD - 20170612
UP - 20170613
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28604554
<505. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28418115
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Matsumura K
AU - Nagasawa K
AU - Oshima Y
AU - Kikuno S
AU - Hayashi K
AU - Nishimura A
AU - Okubo M
AU - Uruga H
AU - Kishi K
AU - Kobayashi T
AU - Mori Y
AI - Matsumura, Kimio; ORCID: http://orcid.org/0000-0001-7031-5014
FA - Matsumura, Kimio
FA - Nagasawa, Kaoru
FA - Oshima, Yoichi
FA - Kikuno, Shouta
FA - Hayashi, Kyohei
FA - Nishimura, Akihiro
FA - Okubo, Minoru
FA - Uruga, Hironori
FA - Kishi, Kazuma
FA - Kobayashi, Tetsuro
FA - Mori, Yasumichi
IN - Matsumura, Kimio. Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
IN - Nagasawa, Kaoru. Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
IN - Oshima, Yoichi. Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
IN - Kikuno, Shouta. Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
IN - Hayashi, Kyohei. Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
IN - Nishimura, Akihiro. Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
IN - Okubo, Minoru. Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
IN - Okubo, Minoru. Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
IN - Uruga, Hironori. Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
IN - Uruga, Hironori. Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital, Tokyo, Japan.
IN - Kishi, Kazuma. Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
IN - Kishi, Kazuma. Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital, Tokyo, Japan.
IN - Kobayashi, Tetsuro. Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
IN - Mori, Yasumichi. Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, Japan.
IN - Mori, Yasumichi. Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
TI - Aggravation of diabetes, and incompletely deficient insulin secretion in a case with type 1 diabetes-resistant human leukocyte antigen DRB1*15:02 treated with nivolumab.
SO - Journal of Diabetes Investigation. , 2017 Apr 18
AS - J. diabetes investig.. , 2017 Apr 18
NJ - Journal of diabetes investigation
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 101520702
IO - J Diabetes Investig
CP - Japan
KW - Anti-programmed death 1 antibody; Nivolumab; Type 1 Diabetes
AB - Anti-programmed cell death-1 (PD-1) antibody therapy induces various adverse effects, especially in the endocrine system. Several cases of acute-onset insulin-dependent diabetes after anti-PD-1 antibody therapy have been reported. Many of these cases have a susceptible human leukocyte antigen (HLA) genotype for type 1 diabetes, possibly suggesting that HLA might be involved in the onset of diabetes with anti-PD-1 therapy. We describe an atypical case of hyperglycemia after anti-PD-1 antibody administration. A 68-year-old Japanese man with pancreatic diabetes and steroid diabetes was given nivolumab three times for chemoresistant adenocarcinoma of the lung. On day 5 after the third infusion of nivolumab, he had hyperglycemia (blood glucose 330 mg/dL and hemoglobin A1c 8.0%) without ketosis and with incompletely deficient insulin secretion. The patient had both type 1 diabetes susceptible (HLA-A*24:02 and -DRB1*09:01) and resistant (HLA-DRB1*15:02) HLA genotypes. These HLA genotypes differ from those previously reported in anti-PD-1 antibody-induced diabetes, and might have influenced the preservation of insulin secretion after nivolumab administration in the present case.
AB - Copyright © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
ES - 2040-1124
IL - 2040-1116
DO - https://dx.doi.org/10.1111/jdi.12679
PT - Case Reports
ID - 10.1111/jdi.12679 [doi]
PP - aheadofprint
PH - 2017/02/23 [received]
PH - 2017/03/30 [revised]
PH - 2017/04/11 [accepted]
LG - English
EP - 20170418
DP - 2017 Apr 18
DC - 20170418
EZ - 2017/04/19 06:00
DA - 2017/04/19 06:00
DT - 2017/04/19 06:00
YR - 2017
RD - 20170613
UP - 20170613
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28418115
<506. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28598870
VI - 1
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Allen RC
FA - Allen, Richard C
IN - Allen, Richard C. Section of Ophthalmology, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
TI - Molecularly targeted agents in oculoplastic surgery.
SO - Current Opinion in Ophthalmology. , 2017 Jun 08
AS - Curr Opin Ophthalmol. , 2017 Jun 08
NJ - Current opinion in ophthalmology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - bb4, 9011108
IO - Curr Opin Ophthalmol
CP - United States
AB - PURPOSE OF REVIEW: Significant advances have been made in oncology and rheumatology with the introduction of molecularly targeted agents (MTAs). MTAs consist of monoclonal antibodies and small molecule inhibitors. The purpose of this manuscript is to review the recent applications of MTAs to orbital, lacrimal, and eyelid disease.
AB - RECENT FINDINGS: The use of monoclonal antibodies has been described in the treatment of orbital vascular lesions, lymphoma, and squamous cell carcinoma. Inflammatory conditions treated with monoclonal antibodies include thyroid eye disease, IgG4 disease, and granulomatosis with polyangiitis. Immunotherapy with checkpoint inhibitors has also found applications to orbital disease. Use of small molecule inhibitors has been described in the treatment of basal cell carcinoma, squamous cell carcinoma, and Erdheim-Chester disease. There are many orbital, lacrimal, and eyelid side effects of MTAs with which the oculoplastic surgeon should be familiar, including hypertrichosis, edema, and orbital and eyelid inflammation.
AB - SUMMARY: MTAs represent the future of treatment of oncologic and inflammatory conditions. Application of these agents to orbital, lacrimal, and eyelid disease will continue to expand. Elucidating the molecular mechanisms of oculoplastic disorders will facilitate additional potential pathways that could be targeted for therapy.
ES - 1531-7021
IL - 1040-8738
DO - https://dx.doi.org/10.1097/ICU.0000000000000403
PT - Journal Article
ID - 10.1097/ICU.0000000000000403 [doi]
PP - aheadofprint
LG - English
EP - 20170608
DP - 2017 Jun 08
DC - 20170609
EZ - 2017/06/10 06:00
DA - 2017/06/10 06:00
DT - 2017/06/10 06:00
YR - 2017
RD - 20170609
UP - 20170612
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28598870
<507. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28433543
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Kim SH
AU - Li M
AU - Trousil S
AU - Zhang Y
AU - Pasca di Magliano M
AU - Swanson KD
AU - Zheng B
FA - Kim, Sun Hye
FA - Li, Man
FA - Trousil, Sebastian
FA - Zhang, Yaqing
FA - Pasca di Magliano, Marina
FA - Swanson, Kenneth D
FA - Zheng, Bin
IN - Kim, Sun Hye. Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
IN - Li, Man. Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
IN - Trousil, Sebastian. Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
IN - Zhang, Yaqing. Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
IN - Pasca di Magliano, Marina. Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
IN - Swanson, Kenneth D. Department of Neurology, Brain Tumor Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
IN - Zheng, Bin. Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA. Electronic address: bin.zheng@cbrc2.mgh.harvard.edu.
TI - Phenformin Inhibits Myeloid-Derived Suppressor Cells and Enhances the Anti-Tumor Activity of PD-1 Blockade in Melanoma.
SO - Journal of Investigative Dermatology. , 2017 Apr 19
AS - J Invest Dermatol. , 2017 Apr 19
NJ - The Journal of investigative dermatology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ihz, 0426720
IO - J. Invest. Dermatol.
CP - United States
AB - Biguanides, such as the diabetes therapeutics metformin and phenformin, have shown antitumor activity both in vitro and in vivo. However, their potential effects on the tumor microenvironment are largely unknown. Here we report that phenformin selectively inhibits granulocytic myeloid-derived suppressor cells in spleens of tumor-bearing mice and ex vivo. Phenformin induces production of reactive oxygen species in granulocytic myeloid-derived suppressor cells, whereas the antioxidant N-acetylcysteine attenuates the inhibitory effects of phenformin. Co-treatment of phenformin enhances the effect of anti-PD-1 antibody therapy on inhibiting tumor growth in the BRAF V600E/PTEN-null melanoma mouse model. Combination of phenformin and anti PD-1 cooperatively induces CD8+ T-cell infiltration and decreases levels of proteins that are critical for immune suppressive activities of myeloid-derived suppressor cells. Our findings show a selective, inhibitory effect of phenformin on granulocytic myeloid-derived suppressor cell-driven immune suppression and support that phenformin improves the anti-tumor activity of PD-1 blockade immunotherapy in melanoma.
AB - Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
ES - 1523-1747
IL - 0022-202X
DI - S0022-202X(17)31420-3
DO - https://dx.doi.org/10.1016/j.jid.2017.03.033
PT - Journal Article
ID - S0022-202X(17)31420-3 [pii]
ID - 10.1016/j.jid.2017.03.033 [doi]
PP - aheadofprint
PH - 2016/08/19 [received]
PH - 2017/02/27 [revised]
PH - 2017/03/13 [accepted]
LG - English
EP - 20170419
DP - 2017 Apr 19
DC - 20170423
EZ - 2017/04/24 06:00
DA - 2017/04/24 06:00
DT - 2017/04/24 06:00
YR - 2017
RD - 20170531
UP - 20170601
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28433543
<508. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28478512
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Jagersberg M
AU - El Rahal A
AU - Dammann P
AU - Merkler D
AU - Weber DC
AU - Schaller K
AI - Jagersberg, Max; ORCID: http://orcid.org/0000-0002-6208-5121
FA - Jagersberg, Max
FA - El Rahal, Amir
FA - Dammann, Philipp
FA - Merkler, Doron
FA - Weber, Damien Charles
FA - Schaller, Karl
IN - Jagersberg, Max. Division of Neurosurgery, Geneva University Hospitals and University of Geneva, 4, rue Gabrielle-Perret-Gentil, 1211, Geneva, Switzerland. max.jaegersberg@hcuge.ch.
IN - El Rahal, Amir. Division of Neurosurgery, Geneva University Hospitals and University of Geneva, 4, rue Gabrielle-Perret-Gentil, 1211, Geneva, Switzerland.
IN - Dammann, Philipp. Division of Neurosurgery, Geneva University Hospitals and University of Geneva, 4, rue Gabrielle-Perret-Gentil, 1211, Geneva, Switzerland.
IN - Dammann, Philipp. Department of Neurosurgery, Essen University Hospital, University of Duisburg-Essen, Essen, Germany.
IN - Merkler, Doron. Department of Pathology and Immunology, Division of Clinical Pathology, Geneva University Hospitals of Geneva, Geneva, Switzerland.
IN - Weber, Damien Charles. Centre for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland.
IN - Schaller, Karl. Division of Neurosurgery, Geneva University Hospitals and University of Geneva, 4, rue Gabrielle-Perret-Gentil, 1211, Geneva, Switzerland.
TI - Clival chordoma: a single-centre outcome analysis.
SO - Acta Neurochirurgica. , 2017 May 07
AS - Acta Neurochir (Wien). , 2017 May 07
NJ - Acta neurochirurgica
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 0151000
IO - Acta Neurochir (Wien)
CP - Austria
KW - Chemotherapy; Clival chordoma; Maximal safe resection; Multimodal treatment; Radiosurgery; Systemic therapy
AB - BACKGROUND: The treatment of clival chordomas remains challenging. Total tumour resection is often impossible without hampering adjacent anatomical structures and causing functional sequelae. On the other hand, chordomas show limited response to non-surgical treatment modalities. Up to now, no well-established interdisciplinary treatment algorithms for clival chordomas exist. In this regard, we analysed the data from all patients that underwent interdisciplinary treatment for clival chordoma in our institution over the last 10 years.
AB - METHOD: Retrospective report of all patients treated at the authors' institution from 2005 to 2015.
AB - RESULTS: Thirteen patients underwent 24 surgeries, of which 2 (8%) were gross total resections and 22 (92%) incomplete resections. Neurological deterioration, endocrinological disturbances and other surgical complications were observed in six (25%), three (13%) and nine (38%) cases, respectively. Three surgeries (13%) led to an improvement of the initial preoperative neurological condition. All patients were discussed on the interdisciplinary tumour board and all underwent one type of radiotherapy following initial surgery: proton beam in 11 cases (85%) and photon beam in two (15%) cases. In the course of their recurrent disease, three patients (23%) received systemic therapy (imatinib, pazopanib and nivolumab). One patient received a personalised cellular immunotherapy. One patient (8%) was lost to follow-up. Of the remaining 12 patients, four patients (33%) died in the period of analysis; all deaths were chordoma-related. The 5-year cumulative survival rate was 83% (52-97%, CI 95%), 5-year progression-free survival rate was 53% (26-79%, CI 95%). The eight patients (66%) still alive had favourable outcome (KPS, 90 +/- 10.7%). SF36 analysis among the survivors revealed 43 points for the Physical Component Summary (12% above, 38% at and 50% below the general population norm) and 47 points for the Mental Component Summary (25% above, 38% at and 38% below).
AB - CONCLUSIONS: Our patients show a low rate of gross total resection but an outcome well comparable to other published results. This emphasises the importance of interdispiplinary treatment strategies, with surgery supplying maximal safe resection and avoiding severe neurological deficit, allowing patients to undergo adjusted radiotherapy and other treatment options in a good condition.
ES - 0942-0940
IL - 0001-6268
DI - 10.1007/s00701-017-3163-7
DO - https://dx.doi.org/10.1007/s00701-017-3163-7
PT - Journal Article
ID - 10.1007/s00701-017-3163-7 [doi]
ID - 10.1007/s00701-017-3163-7 [pii]
PP - aheadofprint
PH - 2016/11/09 [received]
PH - 2017/03/27 [accepted]
LG - English
EP - 20170507
DP - 2017 May 07
DC - 20170507
EZ - 2017/05/08 06:00
DA - 2017/05/10 06:00
DT - 2017/05/10 06:00
YR - 2017
RD - 20170507
UP - 20170511
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28478512
<509. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28476944
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Betof AS
AU - Nipp RD
AU - Giobbie-Hurder A
AU - Johnpulle RAN
AU - Rubin K
AU - Rubinstein SM
AU - Flaherty KT
AU - Lawrence DP
AU - Johnson DB
AU - Sullivan RJ
FA - Betof, Allison S
FA - Nipp, Ryan D
FA - Giobbie-Hurder, Anita
FA - Johnpulle, Romany A N
FA - Rubin, Krista
FA - Rubinstein, Samuel M
FA - Flaherty, Keith T
FA - Lawrence, Donald P
FA - Johnson, Douglas B
FA - Sullivan, Ryan J
IN - Betof, Allison S. Massachusetts General Hospital Cancer Center & Harvard Medical School, Boston, Massachusetts, USA.
IN - Nipp, Ryan D. Massachusetts General Hospital Cancer Center & Harvard Medical School, Boston, Massachusetts, USA.
IN - Giobbie-Hurder, Anita. Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
IN - Johnpulle, Romany A N. Vanderbilt University Medical Center, Nashville, Tennessee, USA.
IN - Rubin, Krista. Massachusetts General Hospital Cancer Center & Harvard Medical School, Boston, Massachusetts, USA.
IN - Rubinstein, Samuel M. Vanderbilt University Medical Center, Nashville, Tennessee, USA.
IN - Flaherty, Keith T. Massachusetts General Hospital Cancer Center & Harvard Medical School, Boston, Massachusetts, USA.
IN - Lawrence, Donald P. Massachusetts General Hospital Cancer Center & Harvard Medical School, Boston, Massachusetts, USA.
IN - Johnson, Douglas B. Vanderbilt University Medical Center, Nashville, Tennessee, USA.
IN - Sullivan, Ryan J. Massachusetts General Hospital Cancer Center & Harvard Medical School, Boston, Massachusetts, USA RSULLIVAN7@mgh.harvard.edu.
TI - Impact of Age on Outcomes with Immunotherapy for Patients with Melanoma.
SO - Oncologist. , 2017 May 05
AS - Oncologist. , 2017 May 05
NJ - The oncologist
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - dd5, 9607837
IO - Oncologist
CP - United States
KW - Geriatrics; Immunotherapy; Melanoma; Toxicity
AB - BACKGROUND: Monoclonal antibodies (mAb) targeting PD-1/PD-L1 have revolutionized melanoma treatment, yet data regarding effectiveness and tolerability across age groups is limited. We sought to determine the impact of age on overall survival (OS), progression-free survival (PFS), and rates of immune-mediated toxicities in patients treated with anti-PD-1/anti-PD-L1 mAb at two academic medical centers.
AB - METHODS: We retrospectively collected data on all patients with metastatic melanoma treated with anti-PD-1/PD-L1 mAb between May 2009 and April 2015. We used Kaplan-Meier and Cox regression analyses to assess OS and PFS and identify factors associated with these outcomes. We also compared rates of autoimmune toxicity across age groups.
AB - RESULTS: Of 254 patients, 57 (22.4%) were <50 years old, 85 (33.5%) were age 50-64, 65 (25.6%) were age 65-74, and 47 (18.5%) were >=75 years. Across age groups, no differences existed in median OS (age <50: 22.9 months, age 50-64: 25.3 months, age 65-74: 22.0 months, age >=75: 24.3 months) or PFS (age <50: 4.1 months, age 50-64: 6.5 months, age 65-74: 5.4 months, age >=75: 7.9 months). The presence of liver metastases and elevated pre-treatment lactate dehydrogenase (LDH) were associated with reduced OS. Presence of liver metastasis, pretreatment LDH, BRAF mutation, and type of melanoma correlated with PFS. Overall, 110 patients (43.3%) experienced immune-mediated toxicities; 25 (9.8%) had colitis and 26 (10.2%) had endocrine toxicity. Rates of colitis, hepatitis, and pneumonitis did not differ across age groups.
AB - CONCLUSION: We demonstrated that patients could safely tolerate anti-PD1/PDL-1 mAb therapy and achieve similar outcomes regardless of their age. The Oncologist 2017;22:1-8Implications for Practice: Immunotherapy has revolutionized treatment for patients with metastatic melanoma, yet data are lacking regarding the effectiveness and tolerability of these treatments for older patients. In this study, we demonstrated that patients with melanoma safely tolerate immunotherapy and achieve similar outcomes regardless of their age. Specifically, we utilized data from two academic cancer centers and found no significant difference in overall survival, progression free survival, or immune-related toxicities, other than arthritis, across age groups. As the population ages, studies such as this will become critical to help us understand how best to treat older adults with cancer.
AB - Copyright © AlphaMed Press 2017.
CI - Disclosures of potential conflicts of interest may be found at the end of this article.
ES - 1549-490X
IL - 1083-7159
DI - theoncologist.2016-0450
DO - https://dx.doi.org/10.1634/theoncologist.2016-0450
PT - Journal Article
ID - theoncologist.2016-0450 [pii]
ID - 10.1634/theoncologist.2016-0450 [doi]
PP - aheadofprint
PH - 2016/11/12 [received]
PH - 2017/03/03 [accepted]
LG - English
EP - 20170505
DP - 2017 May 05
DC - 20170506
EZ - 2017/05/07 06:00
DA - 2017/05/10 06:00
DT - 2017/05/10 06:00
YR - 2017
RD - 20170506
UP - 20170511
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28476944
<510. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28461396
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Badros A
AU - Hyjek E
AU - Ma N
AU - Lesokhin A
AU - Dogan A
AU - Rapoport AP
AU - Kocoglu M
AU - Lederer E
AU - Philip S
AU - Milliron T
AU - Dell C
AU - Goloubeva O
AU - Singh Z
AI - Badros, Ashraf; ORCID: http://orcid.org/0000-0003-1690-0188
AI - Lesokhin, Alexander; ORCID: http://orcid.org/0000-0001-9321-702X
FA - Badros, Ashraf
FA - Hyjek, Elizabeth
FA - Ma, Ning
FA - Lesokhin, Alexander
FA - Dogan, Ahmet
FA - Rapoport, Aaron P
FA - Kocoglu, Mehmet
FA - Lederer, Emily
FA - Philip, Sunita
FA - Milliron, Todd
FA - Dell, Cameron
FA - Goloubeva, Olga
FA - Singh, Zeba
IN - Badros, Ashraf. University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States; abadros@umm.edu.
IN - Hyjek, Elizabeth. Department of Pathology, University of Chicago, United States.
IN - Ma, Ning. University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States.
IN - Lesokhin, Alexander. Memorial Sloan Kettering Cancer Center, New York, NY, United States.
IN - Dogan, Ahmet. Memorial Sloan Kettering Cancer Center, New York, NY, United States.
IN - Rapoport, Aaron P. University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States.
IN - Kocoglu, Mehmet. University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States.
IN - Lederer, Emily. University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States.
IN - Philip, Sunita. University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States.
IN - Milliron, Todd. University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States.
IN - Dell, Cameron. University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States.
IN - Goloubeva, Olga. University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States.
IN - Singh, Zeba. University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, United States.
TI - Pembrolizumab, pomalidomide and low dose dexamethasone for relapsed/refractory multiple myeloma.
SO - Blood. , 2017 May 01
AS - Blood. , 2017 May 01
NJ - Blood
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - a8g, 7603509
IO - Blood
CP - United States
AB - Programmed death 1 (PD-1) receptor and its ligand (PD-L1) facilitate immune evasion in multiple myeloma (MM). We hypothesized that pembrolizumab, PD-1-antibody, can enhance anti-myeloma cellular immunity generated by pomalidomide leading to improved clinical responses. In this single-center, phase II study, 48 patients with relapsed/refractory MM (RRMM) received 28-days cycles of pembrolizumab, 200 mg intravenously every 2 weeks, pomalidomide 4 mg daily for 21 days and dexamethasone 40 mg weekly. Patients had a median of 3 (range: 2-5) lines of therapy, median age 64 (range: 35-83) years and had received both immune modulatory agent and proteasome inhibitor; (35 [73%] of 48) were refractory to both; (31 [70%]) had received an autologous transplant and (30 [62%]) had high-risk cytogenetics. Adverse events grade 3-4 occurred in (19 [40%] of 48 patients) including hematologic toxicities (19 [40%]), hyperglycemia (12 [25%] and pneumonia (7 [15%]). Autoimmune events included pneumonitis (6 [13%]) and hypothyroidism (5[10%]), mostly <= grade 2. Objective responses occurred in (29 [60%] of 48) patients including: sCR/CR (4 [8%]), VGPR (9 [19%]) and PR (16 [33%]); median duration of response was 14.7 months (95% CI 7.9-17.5). At median follow-up of 15.6 months (95% CI 9.2-17.5), progression free survival (PFS) was 17.4 months (95% CI 11.7-18.8) and overall survival was not reached (95% CI 18.9-NR). Analyses of pretreatment marrow samples revealed a trend for increased expression of PD-L1 in responding patients and longer PFS with increased T-lymphocyte infiltrates, irrespective of PD-1 expression. Pembrolizumab, pomalidomide and low-dose dexamethasone has acceptable safety and durable responses in RRMM patients. This trial was registered at www.clincialtrials.gov as # NCT02289222.
AB - Copyright © 2017 American Society of Hematology.
ES - 1528-0020
IL - 0006-4971
DI - blood-2017-03-775122
DO - https://dx.doi.org/10.1182/blood-2017-03-775122
PT - Journal Article
ID - blood-2017-03-775122 [pii]
ID - 10.1182/blood-2017-03-775122 [doi]
PP - aheadofprint
PH - 2017/03/23 [received]
PH - 2017/04/25 [accepted]
LG - English
EP - 20170501
DP - 2017 May 01
DC - 20170502
EZ - 2017/05/03 06:00
DA - 2017/05/04 06:00
DT - 2017/05/04 06:00
YR - 2017
RD - 20170502
UP - 20170505
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28461396
<511. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28444424
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Wen X
AU - Ding Y
AU - Li J
AU - Zhao J
AU - Peng R
AU - Li D
AU - Zhu B
AU - Wang Y
AU - Zhang X
AU - Zhang X
FA - Wen, Xizhi
FA - Ding, Ya
FA - Li, Jingjing
FA - Zhao, Jingjing
FA - Peng, Ruiqing
FA - Li, Dandan
FA - Zhu, Baoyan
FA - Wang, Yao
FA - Zhang, Xing
FA - Zhang, Xiaoshi
IN - Wen, Xizhi. Biotherapy Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.
IN - Ding, Ya. Biotherapy Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.
IN - Li, Jingjing. Biotherapy Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.
IN - Zhao, Jingjing. Biotherapy Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.
IN - Peng, Ruiqing. Biotherapy Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.
IN - Li, Dandan. Biotherapy Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.
IN - Zhu, Baoyan. Biotherapy Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.
IN - Wang, Yao. Biotherapy Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.
IN - Zhang, Xing. Biotherapy Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.
IN - Zhang, Xiaoshi. Biotherapy Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China. zhangxsh@sysucc.org.cn.
TI - The experience of immune checkpoint inhibitors in Chinese patients with metastatic melanoma: a retrospective case series.
SO - Cancer Immunology, Immunotherapy. , 2017 Apr 25
AS - Cancer Immunol Immunother. , 2017 Apr 25
NJ - Cancer immunology, immunotherapy : CII
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cn3, 8605732
IO - Cancer Immunol. Immunother.
CP - Germany
KW - Acral melanoma; Biomarkers; Chinese patients; Ipilimumab; Mucosal melanoma; Pembrolizumab
AB - Melanomas in Chinese patients show relatively higher rates of acral and mucosal types than in other populations. However, the efficacy of checkpoint inhibitor therapies against these melanoma subtypes is not well defined. We analyzed 52 patients treated with ipilimumab, pembrolizumab, or a combination of both to evaluate the efficacy and safety of checkpoint inhibitors in Chinese patients with advanced melanoma, particularly those with acral and mucosal types. The objective response rates (ORRs) were 0, 25, and 20% for ipilimumab, pembrolizumab, and pembrolizumab plus ipilimumab, respectively. Pembrolizumab contained therapy was as effective in acral and mucosal melanoma patients (ORR 26.7 and 20%, respectively) as in non-acral cutaneous melanoma patients (ORR 26.7%). Baseline lactate dehydrogenase levels and relative lymphocyte counts were independent prognostic factors for PFS and OS. The incidences of grade 3-4 adverse events were 14% in the two monotherapy groups and 30% in the combined therapy group. The most frequent adverse events were elevation of aminotransferase, skin toxicity, thyroid dysfunction, pyrexia, and fatigue. Treatment-related rash or vitiligo was associated with a better prognosis. In summary, pembrolizumab-based therapy resulted in meaningful efficacy and good tolerability in Chinese patients with melanoma, including those with acral and mucosal types.
ES - 1432-0851
IL - 0340-7004
DI - 10.1007/s00262-017-1989-8
DO - https://dx.doi.org/10.1007/s00262-017-1989-8
PT - Journal Article
ID - 10.1007/s00262-017-1989-8 [doi]
ID - 10.1007/s00262-017-1989-8 [pii]
PP - aheadofprint
PH - 2016/09/24 [received]
PH - 2017/03/16 [accepted]
LG - English
EP - 20170425
DP - 2017 Apr 25
DC - 20170426
EZ - 2017/04/27 06:00
DA - 2017/04/27 06:00
DT - 2017/04/27 06:00
YR - 2017
RD - 20170426
UP - 20170428
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28444424
<512. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28431010
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Gay CL
AU - Bosch RJ
AU - Ritz J
AU - Hataye JM
AU - Aga E
AU - Tressler RL
AU - Mason SW
AU - Hwang CK
AU - Grasela DM
AU - Ray N
AU - Cyktor JC
AU - Coffin JM
AU - Acosta EP
AU - Koup RA
AU - Mellors JW
AU - Eron JJ
AU - AIDS Clinical Trials 5326 Study Team
FA - Gay, Cynthia L
FA - Bosch, Ronald J
FA - Ritz, Justin
FA - Hataye, Jason M
FA - Aga, Evgenia
FA - Tressler, Randall L
FA - Mason, Stephen W
FA - Hwang, Carey K
FA - Grasela, Dennis M
FA - Ray, Neelanjana
FA - Cyktor, Josh C
FA - Coffin, John M
FA - Acosta, Edward P
FA - Koup, Richard A
FA - Mellors, John W
FA - Eron, Joseph J
FA - AIDS Clinical Trials 5326 Study Team
IN - Gay, Cynthia L. The University of North Carolina at Chapel Hill, Chapel Hill, NC.
IN - Bosch, Ronald J. Harvard T.H. Chan School of Public Health, Boston, MA.
IN - Ritz, Justin. Harvard T.H. Chan School of Public Health, Boston, MA.
IN - Hataye, Jason M. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD.
IN - Aga, Evgenia. Harvard T.H. Chan School of Public Health, Boston, MA.
IN - Tressler, Randall L. Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD.
IN - Tressler, Randall L. Columbus Technologies, El Segundo, CA.
IN - Mason, Stephen W. Bristol-Myers Squibb, Wallingford, CT.
IN - Hwang, Carey K. Bristol-Myers Squibb, Princeton, NJ.
IN - Grasela, Dennis M. Bristol-Myers Squibb, Princeton, NJ.
IN - Ray, Neelanjana. Bristol-Myers Squibb, Princeton, NJ.
IN - Cyktor, Josh C. University of Pittsburgh, Pittsburgh, PA.
IN - Coffin, John M. Tufts University School of Medicine, Boston, MA.
IN - Acosta, Edward P. University of Alabama School of Medicine, Birmingham, AL.
IN - Koup, Richard A. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD.
IN - Mellors, John W. University of Pittsburgh, Pittsburgh, PA.
IN - Eron, Joseph J. The University of North Carolina at Chapel Hill, Chapel Hill, NC.
TI - Clinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 Infected Participants on Suppressive Antiretroviral Therapy.
SO - Journal of Infectious Diseases. , 2017 Apr 18
AS - J Infect Dis. , 2017 Apr 18
NJ - The Journal of infectious diseases
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - ih3, 0413675
IO - J. Infect. Dis.
CP - United States
KW - BMS-936559.; HIV cure; HIV eradication; HIV-1; anti-PD-L1; checkpoint inhibitors; immune response
AB - Background.: Reversing immune exhaustion with an anti-PD-L1 antibody may improve HIV-1-specific immunity and increase clearance of HIV-1 expressing cells.
AB - Methods.: Phase I, randomized, double-blind, placebo-controlled dose-escalating study of BMS-936559including HIV-1-infected adults >=18 to <=70 years on suppressive antiretroviral therapy with CD4+ counts >=350 cells/muL and detectable plasma HIV-1 RNA by single copy assay. Data on single infusions of BMS-936559 (0.3 mg/kg) versus placebo are described. The primary outcomes were safety defined as any >=Grade 3 or immune-related adverse event (AE) and the change in HIV-1 Gag-specific CD8+ T cells responses from baseline to day 28 post-infusion.
AB - Results.: Eight men enrolled; six received 0.3 mg/kg of BMS-936559 and two received placebo infusions. There were no BMS-936559 related >Grade 3 AEs. In one participant, asymptomatic hypophysitis (a protocol-defined immune-related AE) was identified 266 days following BMS-936559 infusion that resolved over time. The mean percentage of HIV-1 Gag-specific CD8+ T cells expressing IFN-gamma increased from baseline (0.09%) through day 28 (0.20%; p=0.14), driven by substantial increases in two participants who received BMS-936559.
AB - Discussion.: In this first evaluation of an immunologic checkpoint inhibitor in healthy HIV-1-infected persons, single low dose BMS-936559 infusions appeared to enhance HIV-1 specific immunity in a subset of participants.
ES - 1537-6613
IL - 0022-1899
DI - 3738530
DO - https://dx.doi.org/10.1093/infdis/jix191
PT - Journal Article
ID - 3738530 [pii]
ID - 10.1093/infdis/jix191 [doi]
PP - aheadofprint
PH - 2017/02/07 [received]
LG - English
EP - 20170418
DP - 2017 Apr 18
DC - 20170421
EZ - 2017/04/22 06:00
DA - 2017/04/22 06:00
DT - 2017/04/22 06:00
YR - 2017
RD - 20170421
UP - 20170424
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28431010
<513. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28401443
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Brilli L
AU - Danielli R
AU - Ciuoli C
AU - Calabro L
AU - Di Giacomo AM
AU - Cerase A
AU - Paffetti P
AU - Sestini F
AU - Porcelli B
AU - Maio M
AU - Pacini F
FA - Brilli, Lucia
FA - Danielli, Riccardo
FA - Ciuoli, Cristina
FA - Calabro, Luana
FA - Di Giacomo, Anna Maria
FA - Cerase, Alfonso
FA - Paffetti, Patrizia
FA - Sestini, Fausta
FA - Porcelli, Brunetta
FA - Maio, Michele
FA - Pacini, Furio
IN - Brilli, Lucia. Section of Endocrinology, Department of Medical, Surgical and Neurological sciences, University of Siena, Siena, Italy.
IN - Danielli, Riccardo. Medical Oncology and Immunotherapy Unit, Department of Oncology, Istituto Toscano Tumori, University of Siena, Siena, Italy.
IN - Ciuoli, Cristina. Section of Endocrinology, Department of Medical, Surgical and Neurological sciences, University of Siena, Siena, Italy.
IN - Calabro, Luana. Medical Oncology and Immunotherapy Unit, Department of Oncology, Istituto Toscano Tumori, University of Siena, Siena, Italy.
IN - Di Giacomo, Anna Maria. Medical Oncology and Immunotherapy Unit, Department of Oncology, Istituto Toscano Tumori, University of Siena, Siena, Italy.
IN - Cerase, Alfonso. Unit of Neuroimaging and Neurointervention, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
IN - Paffetti, Patrizia. Section of Endocrinology, Department of Medical, Surgical and Neurological sciences, University of Siena, Siena, Italy.
IN - Sestini, Fausta. Section of Endocrinology, Department of Medical, Surgical and Neurological sciences, University of Siena, Siena, Italy.
IN - Porcelli, Brunetta. Department of Medical Biotechnologies, Biochemistry Division, University of Siena, UOC Laboratorio Patologia Clinica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
IN - Maio, Michele. Medical Oncology and Immunotherapy Unit, Department of Oncology, Istituto Toscano Tumori, University of Siena, Siena, Italy.
IN - Pacini, Furio. Section of Endocrinology, Department of Medical, Surgical and Neurological sciences, University of Siena, Siena, Italy. pacini8@unisi.it.
TI - Prevalence of hypophysitis in a cohort of patients with metastatic melanoma and prostate cancer treated with ipilimumab.
SO - Endocrine. , 2017 Apr 12
AS - Endocrine. , 2017 Apr 12
NJ - Endocrine
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9434444, CV9
IO - Endocrine
CP - United States
KW - CTLA-4; Hypophysitis; Ipilimumab; Melanoma
AB - OBJECTIVE: Ipilimumab is a human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4, that has been shown to significantly improve survival in patients with metastatic melanoma. Blocking cytotoxic T-lymphocyte antigen-4 elicits T cell activation, proliferation and anti-tumor response, but can also trigger immune-related adverse events. Among immune-related endocrinopathies, hypophysitis represents the most frequent, with an incidence up to 17% in patients treated with ipilimumab.
AB - DESIGN AND METHODS: We report nine cases of ipilimumab-induced hypophysitis in a cohort of 273 patients treated with ipilimumab between 2006 and 2015, as part of clinical trials or after its marketing. Thyroid function tests were scheduled at screening and during follow up (every 21days) in all patients. Cortisol, adrenocorticotropic hormone, follicle-stimulating hormone, luteinizing hormone, and estradiol (for females) or testosterone (for males), prolactin, growth hormone, insulin-like growth factor 1 were measured only in case of clinical suspicion.
AB - RESULTS: The incidence of hypophysitis was 3.3%. The most frequent pituitary failure was adrenocorticotropic hormone and thyroid stimulating hormone secretion with a complete recovery of thyroid stimulating hormone, but not of adrenocorticotropic hormone during follow up. All patients had negative pituitary antibodies. The main symptoms at diagnosis were fatigue and headache.
AB - CONCLUSION: Clinicians should be aware about the risk of hypophysitis during treatment with immune check-point inhibitors and the necessity of investigating pituitary function during therapy. Pituitary magnetic resonance imaging does not seem pivotal for a definite diagnosis if not performed at the onset of disease.
ES - 1559-0100
IL - 1355-008X
DI - 10.1007/s12020-017-1289-2
DO - https://dx.doi.org/10.1007/s12020-017-1289-2
PT - Journal Article
ID - 10.1007/s12020-017-1289-2 [doi]
ID - 10.1007/s12020-017-1289-2 [pii]
PP - aheadofprint
PH - 2016/11/11 [received]
PH - 2017/03/21 [accepted]
LG - English
EP - 20170412
DP - 2017 Apr 12
DC - 20170412
EZ - 2017/04/13 06:00
DA - 2017/04/13 06:00
DT - 2017/04/13 06:00
YR - 2017
RD - 20170412
UP - 20170414
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28401443
<514. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28355971
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Mahmoud F
AU - Wilkinson JT
AU - Gizinski A
AU - Viswamitra S
AU - Gokden N
AU - Vander Schilden J
FA - Mahmoud, Fade
FA - Wilkinson, John T
FA - Gizinski, Alison
FA - Viswamitra, Sanjaya
FA - Gokden, Neriman
FA - Vander Schilden, John
IN - Mahmoud, Fade. 1 Department of Internal Medicine, Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
IN - Wilkinson, John T. 2 Department of Orthopedics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
IN - Gizinski, Alison. 3 Department of Rheumatology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
IN - Viswamitra, Sanjaya. 4 Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
IN - Gokden, Neriman. 5 Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
IN - Vander Schilden, John. 2 Department of Orthopedics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
TI - Could knee inflammatory synovitis be induced by pembrolizumab?.
SO - Journal of Oncology Pharmacy Practice. :1078155217701292, 2017 Jan 01
AS - J Oncol Pharm Pract. :1078155217701292, 2017 Jan 01
NJ - Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9511372
IO - J Oncol Pharm Pract
CP - England
KW - Pemprolizumab; autoimmune arthritis; melanoma; synovitis
AB - Pembrolizumab, a selective anti-PD-1 humanized monoclonal antibody, reactivates T cells to fight cancer. Immune-related adverse events such as autoimmune colitis, pneumonitis, hepatitis, nephritis, hypophysitis, and thyroiditis may occur during, or weeks to months after therapy. Pemprolizumab-induced synovitis is rarely reported. With the wide use of immunotherapy to treat cancers, physicians need to be aware of this rare immune-related adverse event and provide immediate treatment to avoid permanent joint damage.
ES - 1477-092X
IL - 1078-1552
DO - https://dx.doi.org/10.1177/1078155217701292
PT - Journal Article
ID - 10.1177/1078155217701292 [doi]
PP - aheadofprint
LG - English
EP - 20170101
DP - 2017 Jan 01
DC - 20170330
EZ - 2017/03/31 06:00
DA - 2017/03/31 06:00
DT - 2017/03/31 06:00
YR - 2017
RD - 20170330
UP - 20170403
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28355971
<515. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28280929
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Tafe LJ
FA - Tafe, Laura J
IN - Tafe, Laura J. One Medical Center Drive, Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 03754, USA. Laura.J.Tafe@hitchcock.org.
TI - Molecular mechanisms of therapy resistance in solid tumors: chasing "moving" targets. [Review]
SO - Virchows Archiv. , 2017 Mar 10
AS - Virchows Arch. , 2017 Mar 10
NJ - Virchows Archiv : an international journal of pathology
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - bzd, 9423843
IO - Virchows Arch.
CP - Germany
KW - Breast cancer; Castration-resistant prostate cancer; Checkpoint inhibitors; Drug resistance; EGFR T790M; ESR1 mutation; Epithelial-mesenchymal transition; Non-small cell lung cancer; Resistance mechanisms; Small cell transformation; TKI resistance
AB - The goal of personalized cancer therapy is to treat tumors based on genomic aberrations that drive their survival and progression. Most patients who receive targeted therapies typically develop resistance and disease progression within a year's time. This review focuses on the heterogeneous mechanisms of therapy resistance to tyrosine kinase inhibitors, endocrine/hormone therapy and checkpoint blockade using non-small cell lung cancer, breast and castration-resistant prostate cancer, and melanoma as classical examples, respectively. In addition, testing for resistance mechanisms and therapeutic approaches to overcoming resistance is addressed.
ES - 1432-2307
IL - 0945-6317
DI - 10.1007/s00428-017-2101-7
DO - https://dx.doi.org/10.1007/s00428-017-2101-7
PT - Journal Article
PT - Review
ID - 10.1007/s00428-017-2101-7 [doi]
ID - 10.1007/s00428-017-2101-7 [pii]
PP - aheadofprint
PH - 2017/01/24 [received]
PH - 2017/02/23 [accepted]
LG - English
EP - 20170310
DP - 2017 Mar 10
DC - 20170310
EZ - 2017/03/11 06:00
DA - 2017/03/11 06:00
DT - 2017/03/11 06:00
YR - 2017
RD - 20170310
UP - 20170313
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28280929
<516. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27656680
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Martinov T
AU - Spanier JA
AU - Pauken KE
AU - Fife BT
FA - Martinov, Tijana
FA - Spanier, Justin A
FA - Pauken, Kristen E
FA - Fife, Brian T
IN - Martinov, Tijana. Center for Immunology, Department of Medicine, Division of Rheumatic and Autoimmune Diseases, University of Minnesota, Minneapolis, MN, 55455, USA.
IN - Spanier, Justin A. Center for Immunology, Department of Medicine, Division of Rheumatic and Autoimmune Diseases, University of Minnesota, Minneapolis, MN, 55455, USA.
IN - Pauken, Kristen E. Center for Immunology, Department of Medicine, Division of Rheumatic and Autoimmune Diseases, University of Minnesota, Minneapolis, MN, 55455, USA.
IN - Fife, Brian T. Center for Immunology, Department of Medicine, Division of Rheumatic and Autoimmune Diseases, University of Minnesota, Minneapolis, MN, 55455, USA.
TI - PD-1 pathway-mediated regulation of islet-specific CD4+ T cell subsets in autoimmune diabetes.
SO - Immunoendocrinology. 3, 2016
AS - Immunoendocrinology (Houst). 3, 2016
NJ - Immunoendocrinology (Houston, Tex.)
PI - Journal available in: Print
PI - Citation processed from: Print
JC - 101686763
IO - Immunoendocrinology (Houst)
CP - United States
KW - CD4+ T cells; PD-1; anergy; checkpoint blockade; insulin; type 1 diabetes
AB - Type 1 diabetes (T1D) is a CD4+ T cell-driven autoimmune disease resulting from the destruction of insulin-producing pancreatic beta cells. Clinical evidence and studies in non-obese diabetic (NOD) mice suggest that insulin is a major autoantigen. With this in mind, we developed insulin B10-23:IAg7 tetramer reagents to track insulin-specific CD4+ T cells in mice and interrogated the role of Programmed death-1 (PD-1) for peripheral tolerance. PD-1 is a T cell inhibitory receptor necessary to maintain tolerance and prevent T1D in NOD mice. PD-1 pathway inhibitors are increasingly used in the clinic for treating malignancies, and while many patients benefit, some develop adverse autoimmune events, including T1D. We therefore sought to understand the role of PD-1 in maintaining islet-specific tolerance in diabetes-resistant strains. B6.g7 mice express the same MHC Class II allele as NOD mice, have predominantly naive insulin-specific CD4+ T cells in the periphery, and remain diabetes-free even after PD-1 pathway blockade. Here, we examined the trafficking potential of insulin-specific CD4+ T cells in NOD and B6.g7 mice with or without anti-PD-L1 treatment, and found that PD-L1 blockade preferentially increased the number of CD44highCXCR3+ insulin-specific cells in NOD but not B6.g7 mice. Additionally, we investigated whether pancreatic islets in NOD and B6.g7 mice expressed CXCL10, a lymphocyte homing chemokine and ligand for CXCR3. Anti-PD-L1 treated and control NOD mice had detectable CXCL10 expression in the islets, while B6.g7 islets did not. These data suggest that islet tolerance may be in part attributed to the pancreatic environment and in the absence of pancreas inflammation, chemotactic cytokines may be missing. This, together with our previous data showing that PD-1 pathway blockade preferentially affects effector but not anergic self-specific T cells has implications for the use of checkpoint blockade in treating tumor patients. Our work suggests that determining tumor- and self-specific CD4+ T cell activation status (naive, effector or anergic) prior to initiation of immunotherapy would likely help to stratify individuals who would benefit from this therapy versus those who might have adverse effects or incomplete tumor control.
CI - Conflicting Interests The authors have declared that no conflict of interests exist.
IL - 2378-3079
DI - e1164
DO - https://dx.doi.org/10.14800/ie.1164
PT - Journal Article
ID - 10.14800/ie.1164 [doi]
ID - PMC5027981 [pmc]
ID - NIHMS784558 [mid]
PP - ppublish
GI - No: P01 AI035296
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: R01 AI106791
Organization: (AI) *NIAID NIH HHS*
Country: United States
No: T32 DK007203
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG - English
DP - 2016
DC - 20160922
EZ - 2016/09/23 06:00
DA - 2016/09/23 06:00
DT - 2016/09/23 06:00
YR - 2016
RD - 20170311
UP - 20170313
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=27656680
<517. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28267050
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Bernier M
AU - Guillaume C
AU - Leon N
AU - Alexandre J
AU - Hamel-Senecal L
AU - Chretien B
AU - Lecaignec F
AU - Humbert X
AU - Fedrizzi S
AU - Madelaine J
AU - Sassier M
FA - Bernier, Marjorie
FA - Guillaume, Cyril
FA - Leon, Nathalie
FA - Alexandre, Joachim
FA - Hamel-Senecal, Lea
FA - Chretien, Basile
FA - Lecaignec, Florian
FA - Humbert, Xavier
FA - Fedrizzi, Sophie
FA - Madelaine, Jeannick
FA - Sassier, Marion
IN - Bernier, Marjorie. Departments of *Pharmacology +Pain and Palliative Care ++Rheumatology Pneumology, CHU of Caen Department of General Medicine, Medical School, Normandie University, Caen, France.
TI - Nivolumab Causing a Polymyalgia Rheumatica in a Patient With a Squamous Non-Small Cell Lung Cancer.
SO - Journal of Immunotherapy. , 2017 Mar 06
AS - J Immunother. , 2017 Mar 06
NJ - Journal of immunotherapy (Hagerstown, Md. : 1997)
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - cuq, 9706083
IO - J. Immunother.
CP - United States
AB - The anti-programmed cell-death-1 antibody, nivolumab, has been recently approved for the treatment of advanced non-small cell lung cancer. Although, today, immune-related adverse effects such as dermatologic, digestive, hepatic, and endocrine toxicities are well-known with immune checkpoint inhibitors, rheumatic diseases are less well described. Herein, we report the case of a patient without a history of arthritis who developed polymyalgia rheumatica after 13 cycles of nivolumab used for the treatment of advanced non-small cell lung cancer. Laboratory evidence of inflammatory syndrome, articular echography, and clinical presentation with classical symptoms and also distal manifestations were suggestive of this chronic inflammatory disorder. Because of a relevant pain, clinicians were forced to suspend immunotherapy. Nevertheless, due to glucocorticoid therapy, the patient's symptoms have decreased progressively. Moreover, nivolumab was reintroduced 8 weeks later, whereas prednisone (10 mg) was continued, without any recurrence symptoms. To conclude, our case suggests that polymyalgia rheumatica might be a very disabling anti-programmed cell-death-1 immune-related adverse effect.
ES - 1537-4513
IL - 1524-9557
DO - https://dx.doi.org/10.1097/CJI.0000000000000163
PT - Journal Article
ID - 10.1097/CJI.0000000000000163 [doi]
PP - aheadofprint
LG - English
EP - 20170306
DP - 2017 Mar 06
DC - 20170307
EZ - 2017/03/08 06:00
DA - 2017/03/08 06:00
DT - 2017/03/08 06:00
YR - 2017
RD - 20170308
UP - 20170309
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28267050
<518. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28235882
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Chuk MK
AU - Chang JT
AU - Theoret MR
AU - Sampene E
AU - He K
AU - Weis SL
AU - Helms WS
AU - Jin R
AU - Li H
AU - Yu J
AU - Zhao H
AU - Zhao L
AU - Paciga M
AU - Schmiel D
AU - Rawat R
AU - Keegan P
AU - Pazdur R
FA - Chuk, Meredith K
FA - Chang, Jennie T
FA - Theoret, Marc R
FA - Sampene, Emmanuel
FA - He, Kun
FA - Weis, Shawna L
FA - Helms, Whitney S
FA - Jin, Runyan
FA - Li, Hongshan
FA - Yu, Jingyu
FA - Zhao, Hong
FA - Zhao, Liang
FA - Paciga, Mark
FA - Schmiel, Deborah
FA - Rawat, Rashmi
FA - Keegan, Patricia
FA - Pazdur, Richard
IN - Chuk, Meredith K. Office of Hematology and Oncology Products, FDA Meredith.Chuk@fda.hhs.gov.
IN - Chang, Jennie T. Office of Hematology and Oncology Products, U.S. Food and Drug Administration.
IN - Theoret, Marc R. Surgery Branch, National Cancer Institute.
IN - Sampene, Emmanuel. Office of Biostatistics, U.S. Food and Drug Administration.
IN - He, Kun. Office of Biostatistics, U.S. Food and Drug Administration.
IN - Weis, Shawna L. Office of Hematology and Oncology Products, U.S. Food and Drug Administration.
IN - Helms, Whitney S. Office of Hematology and Oncology Products, Food & Drug Administration/CDER.
IN - Jin, Runyan. OCP, FDA.
IN - Li, Hongshan. OCP, FDA.
IN - Yu, Jingyu. Office of Translational Sciences, U.S. Food and Drug Administration.
IN - Zhao, Hong. Office of Clinical Pharmacology, Food and Drug Administration.
IN - Zhao, Liang. FDA.
IN - Paciga, Mark. Office of Biotechnology Products, U.S. Food and Drug Administration.
IN - Schmiel, Deborah. Office of Biotechnology Products, FDA.
IN - Rawat, Rashmi. Office of Biotechnology Products, U.S. Food and Drug Administration.
IN - Keegan, Patricia. Office of Oncology Drug Products, Office of New Drugs, Food and Drug Administration.
IN - Pazdur, Richard. Office of Oncology Drug Products, U.S. Food and Drug Administration.
TI - FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma.
SO - Clinical Cancer Research. , 2017 Feb 24
AS - Clin Cancer Res. , 2017 Feb 24
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c2h, 9502500
IO - Clin. Cancer Res.
CP - United States
AB - On September 4, 2014, FDA approved pembrolizumab (KEYTRUDA, Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating Phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% CI: 15, 34); with 6 months of follow-up, 86% of responses were ongoing. The most common (>= 20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease, and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection.
AB - Copyright ©2017, American Association for Cancer Research.
IS - 1078-0432
IL - 1078-0432
DI - clincanres.0663.2016
DI - 1078-0432.CCR-16-0663
DO - https://dx.doi.org/10.1158/1078-0432.CCR-16-0663
PT - Journal Article
ID - 28235882 [pubmed]
ID - 1078-0432.CCR-16-0663 [pii]
ID - 10.1158/1078-0432.CCR-16-0663 [doi]
PP - aheadofprint
PH - 2017/02/20 [accepted]
PH - 2016/10/12 [received]
PH - 2017/01/27 [revised]
LG - English
EP - 20170224
DP - 2017 Feb 24
DC - 20170225
EZ - 2017/02/26 06:00
DA - 2017/02/27 06:00
DT - 2017/02/27 06:00
YR - 2017
RD - 20170225
UP - 20170228
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28235882
<519. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28207422
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Nandavaram S
AU - Nadkarni A
FA - Nandavaram, Sravanthi
FA - Nadkarni, Anupa
IN - Nandavaram, Sravanthi. Division of Pulmonary Critical Care, SUNY Upstate Medical University, Syracuse, NY.
TI - Ipilimumab-Induced Sarcoidosis and Thyroiditis.
SO - American Journal of Therapeutics. , 2017 Feb 15
AS - Am J Ther. , 2017 Feb 15
NJ - American journal of therapeutics
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - db7, 9441347
IO - Am J Ther
CP - United States
ES - 1536-3686
IL - 1075-2765
DO - https://dx.doi.org/10.1097/MJT.0000000000000545
PT - Journal Article
ID - 28207422 [pubmed]
ID - 10.1097/MJT.0000000000000545 [doi]
PP - aheadofprint
LG - English
EP - 20170215
DP - 2017 Feb 15
DC - 20170216
EZ - 2017/02/17 06:00
DA - 2017/02/17 06:00
DT - 2017/02/17 06:00
YR - 2017
RD - 20170216
UP - 20170221
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28207422
<520. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28179454
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Barone A
AU - Hazarika M
AU - Theoret MR
AU - Mishra-Kalyani P
AU - Chen H
AU - He K
AU - Sridhara R
AU - Subramaniam S
AU - Pfuma E
AU - Wang Y
AU - Li H
AU - Zhao H
AU - Fourie Zirkelbach J
AU - Keegan P
AU - Pazdur R
FA - Barone, Amy
FA - Hazarika, Maitreyee
FA - Theoret, Marc R
FA - Mishra-Kalyani, Pallavi
FA - Chen, Huanyu
FA - He, Kun
FA - Sridhara, Rajeshwari
FA - Subramaniam, Sriram
FA - Pfuma, Elimika
FA - Wang, Yaning
FA - Li, Hongshan
FA - Zhao, Hong
FA - Fourie Zirkelbach, Jeanne
FA - Keegan, Patricia
FA - Pazdur, Richard
IN - Barone, Amy. Office of Hematology and Oncology Products, U.S. Food and Drug Administration amy.barone@fda.hhs.gov.
IN - Hazarika, Maitreyee. Office of Oncology Drug Products, FDA.
IN - Theoret, Marc R. Surgery Branch, National Cancer Institute.
IN - Mishra-Kalyani, Pallavi. Office of Biostatistics, U.S. Food and Drug Administration.
IN - Chen, Huanyu. Office of Biostatistics, FDA.
IN - He, Kun. Office of Biostatistics, U.S. Food and Drug Administration.
IN - Sridhara, Rajeshwari. Office of Biostatistics, FDA.
IN - Subramaniam, Sriram. Office of Clinical Pharmacology, U.S. Food and Drug Administration.
IN - Pfuma, Elimika. Office of Clinical Pharmacology, Food and Drug Administration.
IN - Wang, Yaning. Office of Clinical Pharmacology, Division of Pharmacometrics, FDA.
IN - Li, Hongshan. OCP, FDA.
IN - Zhao, Hong. Office of Clinical Pharmacology, Food and Drug Administration.
IN - Fourie Zirkelbach, Jeanne. DOP1/OHOP/CDER, Food and Drug Administration.
IN - Keegan, Patricia. Office of Oncology Drug Products, Office of New Drugs, Food and Drug Administration.
IN - Pazdur, Richard. Office of Oncology Drug Products, U.S. Food and Drug Administration.
TI - FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma.
SO - Clinical Cancer Research. , 2017 Feb 08
AS - Clin Cancer Res. , 2017 Feb 08
NJ - Clinical cancer research : an official journal of the American Association for Cancer Research
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - c2h, 9502500
IO - Clin. Cancer Res.
CP - United States
AB - On December 18, 2015, the U.S. Food and Drug Administration (FDA) granted regular approval to pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) for treatment of patients with unresectable or metastatic melanoma, based on results of two randomized, open-label, active-controlled clinical trials. In Trial PN006, 834 patients with ipilimumab-naive metastatic melanoma were randomized (1:1:1) to pembrolizumab 10 mg/kg intravenously (IV) every 2 (q2w) or 3 (q3w) weeks until disease progression or ipilimumab 3 mg/kg q3w for up to four doses. In Trial PN002, 540 patients with ipilimumab-refractory metastatic melanoma were randomized (1:1:1) to pembrolizumab 2 or 10 mg/kg IV q3w or to investigator's choice of chemotherapy. In Trial PN006, patients randomized to pembrolizumab demonstrated statistically significant improvement in overall survival compared to ipilimumab (q2w arm, HR= 0.63 [95%CI: 0.47, 0.83; p<0.001]; q3w arm, HR=0.67 [95%CI: 0.52, 0.90; p=0.004]). In both trials, patients receiving pembrolizumab demonstrated statistically significant improvements in progression-free survival. The most common (>=2%) immune-mediated adverse reactions in a pooled safety analysis were hypothyroidism, pneumonitis, and hyperthyroidism. Key considerations for approval were determination of pembrolizumab dose and interpretation of tumor response-based endpoints using Response Evaluation Criteria in Solid Tumors (RECIST) or immune-related RECIST (irRC).
AB - Copyright ©2017, American Association for Cancer Research.
IS - 1078-0432
IL - 1078-0432
DI - clincanres.0664.2016
DI - 1078-0432.CCR-16-0664
DO - https://dx.doi.org/10.1158/1078-0432.CCR-16-0664
PT - Journal Article
ID - 28179454 [pubmed]
ID - 1078-0432.CCR-16-0664 [pii]
ID - 10.1158/1078-0432.CCR-16-0664 [doi]
PP - aheadofprint
PH - 2016/12/21 [accepted]
PH - 2016/10/26 [received]
PH - 2016/12/19 [revised]
LG - English
EP - 20170208
DP - 2017 Feb 08
DC - 20170209
EZ - 2017/02/10 06:00
DA - 2017/02/10 06:00
DT - 2017/02/10 06:00
YR - 2017
RD - 20170209
UP - 20170213
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28179454
<521. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 28147928
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - March KL
AU - Samarin MJ
AU - Sodhi A
AU - Owens RE
FA - March, Katherine L
FA - Samarin, Michael J
FA - Sodhi, Amik
FA - Owens, Ryan E
IN - March, Katherine L. 1 Department of Pharmacy, Methodist University Hospital, Memphis, TN, USA.
IN - March, Katherine L. 2 Department of Clinical Pharmacy, University of Tennessee Health Science Center, Memphis, TN, USA.
IN - Samarin, Michael J. 1 Department of Pharmacy, Methodist University Hospital, Memphis, TN, USA.
IN - Sodhi, Amik. 1 Department of Pharmacy, Methodist University Hospital, Memphis, TN, USA.
IN - Sodhi, Amik. 3 Division of Pulmonary Critical Care and Sleep Medicine, Department of Medicine, University of Tennessee Health Science Center at Memphis, Memphis, TN, USA.
IN - Owens, Ryan E. 4 Department of Pharmacy: Clinical and Administrative Sciences, University of Oklahoma Health Sciences Center, OK, USA.
TI - Pembrolizumab-induced myasthenia gravis: A fatal case report.
SO - Journal of Oncology Pharmacy Practice. :1078155216687389, 2017 Jan 01
AS - J Oncol Pharm Pract. :1078155216687389, 2017 Jan 01
NJ - Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners
PI - Journal available in: Print-Electronic
PI - Citation processed from: Internet
JC - 9511372
IO - J Oncol Pharm Pract
CP - England
KW - Myasthenia gravis; monoclonal antibody; neurology; oncology; pembrolizumab
AB - Purpose Pembrolizumab, a monoclonal antibody which inhibits the programmed cell death 1 receptor, has been shown to efficaciously enhance pre-existing immune responses to malignancies. However, safety concerns must also be considered as pembrolizumab use has been associated with several life-threatening immune-related adverse events (irAEs). We report a fatal case of pembrolizumab-induced myasthenia gravis in a patient with no prior myasthenia gravis history. Case report A 63-year-old male presented with right eyelid drooping, puffiness, blurred vision, and shortness of breath two weeks after an initial infusion of pembrolizumab. He was subsequently diagnosed with new onset acetylcholine-receptor positive myasthenia gravis. Despite aggressive treatment with corticosteroids, pyridostigmine, intravenous immunoglobulin, and plasmapheresis, the patient clinically deteriorated and ultimately expired from acute respiratory failure after a 12-day hospitalization. Discussion Current package labeling for pembrolizumab warns against various irAEs associated with its use including pneumonitis, colitis, and endocrinopathies. To date, only one case of new onset myasthenia gravis and two case reports of myasthenia gravis exacerbation have been identified. This case further highlights the mortality risk associated with development of irAEs. Conclusion While rare, evidence for the development of MG associated with pembrolizumab is growing. Prompt recognition of symptoms and discontinuation of pembrolizumab is necessary to help improve prognosis.
ES - 1477-092X
IL - 1078-1552
DO - https://dx.doi.org/10.1177/1078155216687389
PT - Journal Article
ID - 28147928 [pubmed]
ID - 10.1177/1078155216687389 [doi]
PP - aheadofprint
LG - English
EP - 20170101
DP - 2017 Jan 01
DC - 20170202
EZ - 2017/02/03 06:00
DA - 2017/02/06 06:00
DT - 2017/02/06 06:00
YR - 2017
RD - 20170202
UP - 20170207
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=28147928
<522. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 27849378
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - McElduff A
FA - McElduff, Aidan
IN - McElduff, Aidan. From: The Discipline of Medicine, The University of Sydney, Sydney, NSW, Australia.
TI - THE EFFECT ON PD-1 INHIBITORS ON ENDOCRINE FUNCTION.
SO - Endocrine Practice. , 2016 Nov 16
AS - Endocr Pract. , 2016 Nov 16
NJ - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - 9607439, dy1
IO - Endocr Pract
CP - United States
IS - 1530-891X
IL - 1530-891X
DO - https://dx.doi.org/10.4158/EP161636.ED
PT - Journal Article
ID - 27849378 [pubmed]
ID - 10.4158/EP161636.ED [doi]
PP - aheadofprint
LG - English
EP - 20161116
DP - 2016 Nov 16
DC - 20161116
EZ - 2016/11/17 06:00
DA - 2016/11/17 06:00
DT - 2016/11/17 06:00
YR - 2016
RD - 20161117
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=27849378
<523. >
VN - Ovid Technologies
DB - Ovid MEDLINE(R)
UI - 26893783
RO - From MEDLINE, a database of the U.S. National Library of Medicine.
ST - Publisher
AU - Khoja L
AU - Atenafu EG
AU - Ye Q
AU - Gedye C
AU - Chappell M
AU - Hogg D
AU - Butler MO
AU - Joshua AM
FA - Khoja, Leila
FA - Atenafu, Eshetu G
FA - Ye, Qian
FA - Gedye, Craig
FA - Chappell, Maryanne
FA - Hogg, David
FA - Butler, Marcus O
FA - Joshua, Anthony M
IN - Khoja, Leila. Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
IN - Atenafu, Eshetu G. Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
IN - Ye, Qian. Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
IN - Gedye, Craig. Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
IN - Chappell, Maryanne. Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
IN - Hogg, David. Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
IN - Butler, Marcus O. Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
IN - Joshua, Anthony M. Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
TI - Real-world efficacy, toxicity and clinical management of ipilimumab treatment in metastatic melanoma.
SO - Oncology Letters. 11(2):1581-1585, 2016 Feb
AS - Oncol. Lett.. 11(2):1581-1585, 2016 Feb
NJ - Oncology letters
PI - Journal available in: Print-Electronic
PI - Citation processed from: Print
JC - ovftdb,1408060, 101531236
IO - Oncol Lett
CP - Greece
KW - checkpoint inhibitors; immune-related adverse events; ipilimumab; melanoma; pembrolizumab; toxicity
AB - Approved by the Food and Drug Administration in 2011, the anti-cytotoxic T-lymphocyte-associated protein 4 checkpoint inhibitor ipilimumab has delivered a survival benefit of >=3 years in a subset of metastatic melanoma patients. After participating in the registration trial, patients were treated with this agent in routine practice. Toxicity and efficacy of agents in "real world" settings may differ from trials. The present study aimed to evaluate, with respect to toxicity and outcome, all patients treated with ipilimumab to date at the Princess Margaret Hospital (Toronto, Canada). Patients treated with ipilimumab between 2008 and 2013 were identified, and patient characteristics (age, gender, tumour burden, oncogenic mutation status, number of treatments received and toxicities from treatment) were collected. Progression-free survival (PFS) and overall survival (OS) were calculated from the commencement of ipilimumab treatment. Associations between clinical characteristics and outcome or toxicity were assessed. Between 2008 and 2013, 129 patients with metastatic cutaneous melanoma were treated. Since, during this period, ipilimumab was approved in the second line setting, ipilimumab was delivered in the second or subsequent line in all patients, and 70% did not receive any further anticancer therapy. Immune-related toxicities were observed, the onset of which varied from 1 to 162 days. The majority resolved within 6 weeks of the final treatment, with the exception of endocrinopathies and bowel related toxicity. The median PFS and OS were 2.83 and 8.44 months, respectively. No pre-treatment factor independently predicted toxicity. The number of infusions (4 vs. <=3) and presence of toxicity were significantly associated with superior survival. The onset of toxicity secondary to ipilimumab could occur later than previously reported. Toxicities were manageable, but required long-term vigilance.
IS - 1792-1074
IL - 1792-1074
DI - OL-0-0-4069
DO - https://dx.doi.org/10.3892/ol.2015.4069
PT - Journal Article
ID - 26893783 [pubmed]
ID - 10.3892/ol.2015.4069 [doi]
ID - OL-0-0-4069 [pii]
ID - PMC4734313 [pmc]
PP - ppublish
PH - 2014/10/09 [received]
PH - 2015/09/30 [accepted]
LG - English
EP - 20151231
DP - 2016 Feb
DC - 20160219
EZ - 2016/02/20 06:00
DA - 2016/02/20 06:00
DT - 2016/02/20 06:00
YR - 2016
RD - 20160222
UP - 20161215
XL - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=26893783