<1. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 29168430
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Stovgaard ES
AU  - Nielsen D
AU  - Hogdall E
AU  - Balslev E
AI  - Stovgaard, Elisabeth Specht; ORCID: http://orcid.org/0000-0002-5784-3610
FA  - Stovgaard, Elisabeth Specht
FA  - Nielsen, Dorte
FA  - Hogdall, Estrid
FA  - Balslev, Eva
IN  - Stovgaard, Elisabeth Specht. a Deparment of Pathology , Herlev and Gentofte Hospital, University of Copenhagen , Herlev , Denmark.
IN  - Nielsen, Dorte. b Department of Oncology , Herlev and Gentofte Hospital, University of Copenhagen , Herlev , Denmark.
IN  - Hogdall, Estrid. c Department of Pathology, Molecular Unit , Herlev and Gentofte Hospital, University of Copenhagen , Herlev , Denmark.
IN  - Balslev, Eva. a Deparment of Pathology , Herlev and Gentofte Hospital, University of Copenhagen , Herlev , Denmark.
TI  - Triple negative breast cancer - prognostic role of immune-related factors: a systematic review. [Review]
SO  - Acta Oncologica. 57(1):74-82, 2018 Jan
AS  - Acta Oncol. 57(1):74-82, 2018 Jan
NJ  - Acta oncologica (Stockholm, Sweden)
VO  - 57
IP  - 1
PG  - 74-82
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Internet
JC  - aon, 8709065
IO  - Acta Oncol
SB  - Index Medicus
CP  - England
MH  - B-Lymphocytes/me [Metabolism]
MH  - B7-H1 Antigen/me [Metabolism]
MH  - Biomarkers/me [Metabolism]
MH  - CD4-Positive T-Lymphocytes/me [Metabolism]
MH  - CD8-Positive T-Lymphocytes/me [Metabolism]
MH  - CTLA-4 Antigen/me [Metabolism]
MH  - Dendritic Cells/me [Metabolism]
MH  - Female
MH  - Humans
MH  - Killer Cells, Natural/me [Metabolism]
MH  - Macrophages/me [Metabolism]
MH  - Myeloid-Derived Suppressor Cells/me [Metabolism]
MH  - Prognosis
MH  - Programmed Cell Death 1 Receptor/me [Metabolism]
MH  - *Triple Negative Breast Neoplasms/me [Metabolism]
MH  - Triple Negative Breast Neoplasms/pa [Pathology]
AB  - PURPOSE: Treatment of breast cancer has been increasingly successful in recent years with the advent of HER2-receptor targeted treatment and endocrine treatment. However, the triple negative subgroup of breast cancer (TNBC) (estrogen-, progesterone- and HER2-receptor negative) still lacks targeted treatment options. TNBC is a type of breast cancer that often affects younger women, and generally has a worse prognosis than other types of breast cancer. Recently, the complex role of the immune system in cancer growth, elimination and metastasis has been the object of increased attention. There is hope that a more detailed understanding of the intricate roles of the constituents of the immune system, will hold potential both as prognostic or predictive markers of cancer progression, but also as treatment targets for a wide range of tumors, including TNBC. The aim of this review is to provide an overview of the cellular immune microenvironment in TNBC, and to highlight areas in which TNBC may differ from other types of breast cancer.
AB  - MATERIAL AND METHODS: A search of PubMed was made using the terms 'triple negative breast cancer' and 'tumor infiltrating lymphocytes', 'CD8', 'CD4', 'B cells', 'natural killer cells', 'macrophages', myeloid derived suppressor cells', 'dendritic cells', 'immune check point inhibitor', 'CTLA-4' and 'PD-L1'.
AB  - RESULTS: We find that whilst factors such as TILs and certain subgroups of TILs (e.g., CD8+and regulator T-cells) have been extensively researched, none of these markers are currently applicable to routine clinical practice. Also, TNBC differs from other types of breast cancer with regards to cellular composition of the immune infiltrate and PD-L1 expression, and the prognostic significance of these.
AB  - CONCLUSIONS: Immune-related factors have the potential as both prognostic and predictive biomarkers for new treatments targeting the immune system in breast cancer. However, multivariate analyses, taking other well-known factors into account, are required to determine the true value of these biomarkers. Also, differences between TNBC and other types of breast cancer may have implications for treatment and use of immune-related factors as biomarkers.
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Biomarkers)
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  - 1651-226X
IL  - 0284-186X
DO  - https://dx.doi.org/10.1080/0284186X.2017.1400180
PT  - Journal Article
PT  - Review
ID  - 10.1080/0284186X.2017.1400180 [doi]
PP  - ppublish
LG  - English
EP  - 20171123
DP  - 2018 Jan
EZ  - 2017/11/24 06:00
DA  - 2018/02/02 06:00
DT  - 2017/11/24 06:00
YR  - 2018
ED  - 20180201
RD  - 20180201
UP  - 20180202
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=29168430

<2. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 26719427
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Farren MR
AU  - Mace TA
AU  - Geyer S
AU  - Mikhail S
AU  - Wu C
AU  - Ciombor K
AU  - Tahiri S
AU  - Ahn D
AU  - Noonan AM
AU  - Villalona-Calero M
AU  - Bekaii-Saab T
AU  - Lesinski GB
FA  - Farren, Matthew R
FA  - Mace, Thomas A
FA  - Geyer, Susan
FA  - Mikhail, Sameh
FA  - Wu, Christina
FA  - Ciombor, Kristen
FA  - Tahiri, Sanaa
FA  - Ahn, Daniel
FA  - Noonan, Anne M
FA  - Villalona-Calero, Miguel
FA  - Bekaii-Saab, Tanios
FA  - Lesinski, Gregory B
IN  - Farren, Matthew R. Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
IN  - Mace, Thomas A. Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
IN  - Geyer, Susan. Health Informatics Institute, University of South Florida, Tampa, Florida.
IN  - Mikhail, Sameh. Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
IN  - Wu, Christina. Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
IN  - Ciombor, Kristen. Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
IN  - Tahiri, Sanaa. Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
IN  - Ahn, Daniel. Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
IN  - Noonan, Anne M. Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
IN  - Villalona-Calero, Miguel. Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
IN  - Bekaii-Saab, Tanios. Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
IN  - Lesinski, Gregory B. Department of Internal Medicine, The Ohio State University, Columbus, Ohio. Gregory.Lesinski@osumc.edu.
TI  - Systemic Immune Activity Predicts Overall Survival in Treatment-Naive Patients with Metastatic Pancreatic Cancer.
SO  - Clinical Cancer Research. 22(10):2565-74, 2016 May 15
AS  - Clin Cancer Res. 22(10):2565-74, 2016 May 15
NJ  - Clinical cancer research : an official journal of the American Association for Cancer Research
VO  - 22
IP  - 10
PG  - 2565-74
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/PMC4867263
OI  - Source: NLM. NIHMS748466 [Available on 05/15/17]
SB  - Index Medicus
CP  - United States
MH  - Adenocarcinoma/im [Immunology]
MH  - Adenocarcinoma/mo [Mortality]
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/im [Immunology]
MH  - CD4-Positive T-Lymphocytes/im [Immunology]
MH  - CD8-Positive T-Lymphocytes/im [Immunology]
MH  - CTLA-4 Antigen/im [Immunology]
MH  - Carcinoma, Pancreatic Ductal/im [Immunology]
MH  - Carcinoma, Pancreatic Ductal/mo [Mortality]
MH  - Female
MH  - Humans
MH  - Interleukin-10/im [Immunology]
MH  - Interleukin-6/im [Immunology]
MH  - Male
MH  - Middle Aged
MH  - Monocytes/im [Immunology]
MH  - Pancreas/im [Immunology]
MH  - *Pancreatic Neoplasms/im [Immunology]
MH  - *Pancreatic Neoplasms/mo [Mortality]
MH  - Survival Rate
AB  - PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a 5-year survival rate <7% and is ultimately refractory to most treatments. To date, an assessment of immunologic factors relevant to disease has not been comprehensively performed for treatment-naive patients. We hypothesized that systemic immunologic biomarkers could predict overall survival (OS) in treatment-naive PDAC patients.
AB  - EXPERIMENTAL DESIGN: Peripheral blood was collected from 73 patients presenting with previously untreated metastatic PDAC. Extensive immunologic profiling was conducted to assess relationships between OS and the level of soluble plasma biomarkers or detailed immune cell phenotypes as measured by flow cytometry.
AB  - RESULTS: Higher baseline levels of the immunosuppressive cytokines IL6 and IL10 were strongly associated with poorer OS (P = 0.008 and 0.026, respectively; HR = 1.16 and 1.28, respectively), whereas higher levels of the monocyte chemoattractant MCP-1 were associated with significantly longer OS (P = 0.045; HR = 0.69). Patients with a greater proportion of antigen-experienced T cells (CD45RO(+)) had longer OS (CD4 P = 0.032; CD8 P = 0.036; HR = 0.36 and 0.61, respectively). Although greater expression of the T-cell checkpoint molecule CTLA-4 on CD8(+) T cells was associated with significantly shorter OS (P = 0.020; HR = 1.53), the TIM3 molecule had a positive association with survival when expressed on CD4(+) T cells (P = 0.046; HR = 0.62).
AB  - CONCLUSIONS: These data support the hypothesis that baseline immune status predicts PDAC disease course and overall patient survival. To our knowledge, this work represents the largest cohort and most comprehensive immune profiling of treatment-naive metastatic PDAC patients to date. Clin Cancer Res; 22(10); 2565-74. ©2015 AACR.

Copyright ©2015 American Association for Cancer Research.
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Interleukin-6)
RN  - 130068-27-8 (Interleukin-10)
IS  - 1078-0432
IL  - 1078-0432
DO  - https://dx.doi.org/10.1158/1078-0432.CCR-15-1732
PT  - Clinical Trial, Phase II
PT  - Journal Article
ID  - 1078-0432.CCR-15-1732 [pii]
ID  - 10.1158/1078-0432.CCR-15-1732 [doi]
ID  - PMC4867263 [pmc]
ID  - NIHMS748466 [mid]
PP  - ppublish
PH  - 2015/07/21 [received]
PH  - 2015/12/14 [accepted]
GI  - No: HHSN261201100070C
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: UM1 CA186712
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: T32 CA165998
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: K12 CA133250
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: T32 CA090223
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: P30 CA016058
Organization: (CA) *NCI NIH HHS*
Country: United States
LG  - English
EP  - 20151230
DP  - 2016 May 15
EZ  - 2016/01/01 06:00
DA  - 2018/01/09 06:00
DT  - 2016/01/01 06:00
YR  - 2016
ED  - 20180108
RD  - 20180108
UP  - 20180109
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medl&AN=26719427

<3. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 27750046
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Caturegli P
AU  - Di Dalmazi G
AU  - Lombardi M
AU  - Grosso F
AU  - Larman HB
AU  - Larman T
AU  - Taverna G
AU  - Cosottini M
AU  - Lupi I
FA  - Caturegli, Patrizio
FA  - Di Dalmazi, Giulia
FA  - Lombardi, Martina
FA  - Grosso, Federica
FA  - Larman, H Benjamin
FA  - Larman, Tatianna
FA  - Taverna, Giacomo
FA  - Cosottini, Mirco
FA  - Lupi, Isabella
IN  - Caturegli, Patrizio. Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland. Electronic address: pcat@jhmi.edu.
IN  - Di Dalmazi, Giulia. Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Medicine, G. D'Annunzio University of Chieti, Chieti, Italy.
IN  - Lombardi, Martina. Endocrinology Unit, Saints Anthony and Biagio, and Cesare Arrigo Hospital, Alessandria, Italy; Oncology Center, Saints Anthony and Biagio, and Cesare Arrigo Hospital, Alessandria, Italy.
IN  - Grosso, Federica. Oncology Center, Saints Anthony and Biagio, and Cesare Arrigo Hospital, Alessandria, Italy.
IN  - Larman, H Benjamin. Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland.
IN  - Larman, Tatianna. Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland.
IN  - Taverna, Giacomo. Department of Radiology, Mesothelioma Unit, Saint Spirit Hospital, Casale Monferrato, Italy.
IN  - Cosottini, Mirco. Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
IN  - Lupi, Isabella. Department of Endocrinology, University of Pisa, Pisa, Italy.
TI  - Hypophysitis Secondary to Cytotoxic T-Lymphocyte-Associated Protein 4 Blockade: Insights into Pathogenesis from an Autopsy Series.
SO  - American Journal of Pathology. 186(12):3225-3235, 2016 Dec
AS  - Am J Pathol. 186(12):3225-3235, 2016 Dec
NJ  - The American journal of pathology
VO  - 186
IP  - 12
PG  - 3225-3235
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Internet
JC  - 3rs, 0370502
IO  - Am. J. Pathol.
SB  - Core Clinical Journals (AIM)
SB  - Index Medicus
CP  - United States
MH  - Adult
MH  - Aged
MH  - *Antibodies, Blocking/ad [Administration & Dosage]
MH  - Antibodies, Blocking/ae [Adverse Effects]
MH  - Antibodies, Monoclonal/ad [Administration & Dosage]
MH  - Antibodies, Monoclonal/ae [Adverse Effects]
MH  - Autopsy
MH  - *CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH  - CTLA-4 Antigen/im [Immunology]
MH  - CTLA-4 Antigen/me [Metabolism]
MH  - Female
MH  - Humans
MH  - *Hypophysitis/et [Etiology]
MH  - Hypophysitis/im [Immunology]
MH  - Hypophysitis/pa [Pathology]
MH  - Male
MH  - Middle Aged
MH  - Pituitary Gland/im [Immunology]
MH  - *Pituitary Neoplasms/dt [Drug Therapy]
MH  - Pituitary Neoplasms/pa [Pathology]
MH  - Pituitary Neoplasms/su [Surgery]
MH  - T-Lymphocytes, Cytotoxic/im [Immunology]
AB  - Hypophysitis that develops in cancer patients treated with monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein 4 (CTLA-4; an inhibitory molecule classically expressed on T cells) is now reported at an incidence of approximately 10%. Its pathogenesis is unknown, in part because no pathologic examination of the pituitary gland has been reported to date. We analyzed at autopsy the pituitary glands of six cancer patients treated with CTLA-4 blockade, one with clinical and pathologic evidence of hypophysitis, one with mild lymphocytic infiltration in the pituitary gland but no clinical signs of hypophysitis, and four with normal pituitary structure and function. CTLA-4 antigen was expressed by pituitary endocrine cells in all patients but at different levels. The highest levels were found in the patient who had clinical and pathologic evidence of severe hypophysitis. This high pituitary CTLA-4 expression was associated with T-cell infiltration and IgG-dependent complement fixation and phagocytosis, immune reactions that induced an extensive destruction of the adenohypophyseal architecture. Pituitary CTLA-4 expression was confirmed in a validation group of 37 surgical pituitary adenomas and 11 normal pituitary glands. The study suggests that administration of CTLA-4 blocking antibodies to patients who express high levels of CTLA-4 antigen in the pituitary can cause an aggressive (necrotizing) form of hypophysitis through type IV (T-cell dependent) and type II (IgG dependent) immune mechanisms.

Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
ES  - 1525-2191
IL  - 0002-9440
DI  - S0002-9440(16)30379-0
DO  - https://dx.doi.org/10.1016/j.ajpath.2016.08.020
PT  - Journal Article
ID  - S0002-9440(16)30379-0 [pii]
ID  - 10.1016/j.ajpath.2016.08.020 [doi]
ID  - PMC5225294 [pmc]
PP  - ppublish
PH  - 2016/04/29 [received]
PH  - 2016/08/08 [revised]
PH  - 2016/08/10 [accepted]
GI  - No: R01 CA194042
Organization: (CA) *NCI NIH HHS*
Country: United States
LG  - English
EP  - 20161015
DP  - 2016 Dec
EZ  - 2016/10/18 06:00
DA  - 2017/09/21 06:00
DT  - 2016/10/18 06:00
YR  - 2016
ED  - 20170920
RD  - 20171201
UP  - 20171204
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medc&AN=27750046

<4. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 25980680
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Pruul K
AU  - Kisand K
AU  - Alnek K
AU  - Metskula K
AU  - Reimand K
AU  - Heilman K
AU  - Peet A
AU  - Varik K
AU  - Peetsalu M
AU  - Einberg U
AU  - Tillmann V
AU  - Uibo R
FA  - Pruul, K
FA  - Kisand, K
FA  - Alnek, K
FA  - Metskula, K
FA  - Reimand, K
FA  - Heilman, K
FA  - Peet, A
FA  - Varik, K
FA  - Peetsalu, M
FA  - Einberg, U
FA  - Tillmann, V
FA  - Uibo, R
IN  - Pruul, K. Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Centre for Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
IN  - Kisand, K. Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Centre for Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
IN  - Alnek, K. Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Centre for Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
IN  - Metskula, K. Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Centre for Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
IN  - Reimand, K. Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Centre for Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
IN  - Heilman, K. Children's Clinic of Tartu University Hospital, N. Lunini 6, Tartu 51014, Estonia; Tallinn Children's Hospital, Tervise 28, Tallinn 13419, Estonia.
IN  - Peet, A. Children's Clinic of Tartu University Hospital, N. Lunini 6, Tartu 51014, Estonia; Department of Paediatrics, University of Tartu, N. Lunini 6, Tartu 51014, Estonia.
IN  - Varik, K. Surgery Clinic, Tartu University Hospital, L. Puusepa 8A, Tartu 51014, Estonia.
IN  - Peetsalu, M. Surgery Clinic, Tartu University Hospital, L. Puusepa 8A, Tartu 51014, Estonia.
IN  - Einberg, U. Tallinn Children's Hospital, Tervise 28, Tallinn 13419, Estonia.
IN  - Tillmann, V. Children's Clinic of Tartu University Hospital, N. Lunini 6, Tartu 51014, Estonia; Department of Paediatrics, University of Tartu, N. Lunini 6, Tartu 51014, Estonia.
IN  - Uibo, R. Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Centre for Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Estonian Academy of Sciences, Kohtu 6, Tallinn 10130, Estonia. Electronic address: raivo.uibo@ut.ee.
TI  - Differences in B7 and CD28 family gene expression in the peripheral blood between newly diagnosed young-onset and adult-onset type 1 diabetes patients.
SO  - Molecular & Cellular Endocrinology. 412:265-71, 2015 Sep 05
AS  - Mol Cell Endocrinol. 412:265-71, 2015 Sep 05
NJ  - Molecular and cellular endocrinology
VO  - 412
PG  - 265-71
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Internet
JC  - 7500844, e69
IO  - Mol. Cell. Endocrinol.
SB  - Index Medicus
CP  - Ireland
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - *B7 Antigens/bl [Blood]
MH  - B7 Antigens/ge [Genetics]
MH  - *CD28 Antigens/bl [Blood]
MH  - CD28 Antigens/ge [Genetics]
MH  - Case-Control Studies
MH  - Child
MH  - Child, Preschool
MH  - *Diabetes Mellitus, Type 1/bl [Blood]
MH  - Diabetes Mellitus, Type 1/di [Diagnosis]
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Transcriptome
MH  - Young Adult
KW  - Adulthood-onset diabetes;  Childhood-onset diabetes;  Gene expression;  Immune synapse;  Type 1 diabetes
AB  - Type-1 diabetes (T1D) is a heterogeneous autoimmune disease, and there are pathogenetic differences between young- and adult-onset T1D patients. We hypothesized that the expressions of genes involved in costimulatory immune system pathways in peripheral blood are differently regulated in young- and adult-onset T1D. Study group I consisted of 80 children, adolescents, and young adults (age range 1.4-21.4 y; 31 controls and 49 T1D patients). Study group II consisted of 48 adults (age range 22.0-78.4 y; 30 controls and 18 T1D patients). The mRNA expression levels of CD86, CD28, CD25, CD226, CD40, BTLA, GITR, PDCD1, FoxP3, TGF-beta, ICOS, sCTLA4, flCTLA4, and CD80 were measured in peripheral blood. Genetic polymorphisms (HLA haplotypes; rs231806, rs231775, and rs3087243 in CTLA4; rs763361 in CD226; and rs706778 in CD25) and T1D-associated autoantibodies were analyzed. In group I, there was significantly lower expression of CD226 in T1D patients than in the controls. In group II, there were significantly higher expression levels of CD86 and TGF-beta in T1D patients than in the controls. In the T1D patients in group I, the upregulated CD80 expression correlated with the expression of both CTLA4 splice variants (sCTLA4 and flCTLA4). In contrast, in group II, upregulated CD86 correlated with TGF-beta and CD25. In group I, the inhibitory CD80-CTLA4 pathway was activated, whereas, in group II, the activation CD86-CD28 pathway and TGF-beta production were activated. These results emphasize the differences between young-onset and adult-onset T1D in the regulation of costimulatory pathways. These differences should be considered when developing novel treatments for T1D. 

Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
RN  - 0 (B7 Antigens)
RN  - 0 (CD28 Antigens)
ES  - 1872-8057
IL  - 0303-7207
DI  - S0303-7207(15)00270-1
DO  - https://dx.doi.org/10.1016/j.mce.2015.05.012
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
ID  - S0303-7207(15)00270-1 [pii]
ID  - 10.1016/j.mce.2015.05.012 [doi]
PP  - ppublish
PH  - 2014/12/10 [received]
PH  - 2015/05/05 [revised]
PH  - 2015/05/05 [accepted]
LG  - English
EP  - 20150514
DP  - 2015 Sep 05
EZ  - 2015/05/20 06:00
DA  - 2016/05/18 06:00
DT  - 2015/05/19 06:00
YR  - 2015
ED  - 20160517
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med8&AN=25980680

<5. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 25382150
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Wijkstrom M
AU  - Bottino R
AU  - Iwase H
AU  - Hara H
AU  - Ekser B
AU  - van der Windt D
AU  - Long C
AU  - Toledo FG
AU  - Phelps CJ
AU  - Trucco M
AU  - Cooper DK
AU  - Ayares D
FA  - Wijkstrom, Martin
FA  - Bottino, Rita
FA  - Iwase, Hayoto
FA  - Hara, Hidetaka
FA  - Ekser, Burcin
FA  - van der Windt, Dirk
FA  - Long, Cassandra
FA  - Toledo, Frederico G S
FA  - Phelps, Carol J
FA  - Trucco, Massimo
FA  - Cooper, David K C
FA  - Ayares, David
IN  - Wijkstrom, Martin. Thomas E. Starzl Transplantation Institute, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
TI  - Glucose metabolism in pigs expressing human genes under an insulin promoter.
SO  - Xenotransplantation. 22(1):70-9, 2015 Jan-Feb
AS  - Xenotransplantation. 22(1):70-9, 2015 Jan-Feb
NJ  - Xenotransplantation
VO  - 22
IP  - 1
PG  - 70-9
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Internet
JC  - c18, 9438793
IO  - Xenotransplantation
PM  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329053
OI  - Source: NLM. NIHMS629776
SB  - Index Medicus
CP  - Denmark
MH  - Abatacept/bi [Biosynthesis]
MH  - *Abatacept/ge [Genetics]
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Antigens, CD/bi [Biosynthesis]
MH  - *Antigens, CD/ge [Genetics]
MH  - Apyrase/bi [Biosynthesis]
MH  - *Apyrase/ge [Genetics]
MH  - Arginine/pd [Pharmacology]
MH  - Blood Glucose/an [Analysis]
MH  - C-Peptide/se [Secretion]
MH  - Cell Line
MH  - Fasting/bl [Blood]
MH  - Fibroblasts
MH  - Galactosyltransferases/df [Deficiency]
MH  - Galactosyltransferases/ge [Genetics]
MH  - Gene Expression Regulation
MH  - Gene Knockout Techniques
MH  - Genes, Synthetic
MH  - Glucagon/se [Secretion]
MH  - *Glucose/me [Metabolism]
MH  - Glucose/pd [Pharmacology]
MH  - Glucose Tolerance Test
MH  - Humans
MH  - *Insulin/ge [Genetics]
MH  - *Islets of Langerhans/me [Metabolism]
MH  - Islets of Langerhans/se [Secretion]
MH  - Lipoproteins/bi [Biosynthesis]
MH  - *Lipoproteins/ge [Genetics]
MH  - Membrane Cofactor Protein/ge [Genetics]
MH  - *Promoter Regions, Genetic
MH  - Recombinant Fusion Proteins/bi [Biosynthesis]
MH  - Recombinant Fusion Proteins/ge [Genetics]
MH  - *Sus scrofa/me [Metabolism]
MH  - Swine
MH  - Transgenes
KW  - C-peptide;  IVGTT;  arginine stimulation test;  genetic engineering;  glucagon;  insulin;  pig;  xenotransplantation
AB  - BACKGROUND: Xenotransplantation of porcine islets can reverse diabetes in non-human primates. The remaining hurdles for clinical application include safe and effective T-cell-directed immunosuppression, but protection against the innate immune system and coagulation dysfunction may be more difficult to achieve. Islet-targeted genetic manipulation of islet-source pigs represents a powerful tool to protect against graft loss. However, whether these genetic alterations would impair islet function is unknown.
AB  - METHODS: On a background of alpha1,3-galactosyltransferase gene-knockout (GTKO)/human (h)CD46, additional genes (hCD39, human tissue factor pathway inhibitor, porcine CTLA4-Ig) were inserted in different combinations under an insulin promoter to promote expression in islets (confirmed by immunofluorescence). Seven pigs were tested for baseline and glucose/arginine-challenged levels of glucose, insulin, C-peptide, and glucagon.
AB  - RESULTS: This preliminary study did not show definite evidence of beta-cell deficiencies, even when three transgenes were expressed under the insulin promoter. Of seven animals, all were normoglycemic at fasting, and five of seven had normal glucose disposal rates after challenge. All animals exhibited insulin, C-peptide, and glucagon responses to both glucose and arginine challenge; however, significant interindividual variation was observed.
AB  - CONCLUSIONS: Multiple islet-targeted transgenic expression was not associated with an overtly detrimental effect on islet function, suggesting that complex genetic constructs designed for islet protection warrants further testing in islet xenotransplantation models.

Copyright © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
RN  - 0 (Antigens, CD)
RN  - 0 (Blood Glucose)
RN  - 0 (C-Peptide)
RN  - 0 (CD46 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Lipoproteins)
RN  - 0 (Membrane Cofactor Protein)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (lipoprotein-associated coagulation inhibitor)
RN  - 7D0YB67S97 (Abatacept)
RN  - 9007-92-5 (Glucagon)
RN  - 94ZLA3W45F (Arginine)
RN  - EC 2-4-1 (Galactosyltransferases)
RN  - EC 2-4-1 (alpha-1,3-galactosyltransferase 1, porcine)
RN  - EC 3-6-1-5 (Apyrase)
RN  - EC 3-6-1-5 (CD39 antigen)
RN  - IY9XDZ35W2 (Glucose)
ES  - 1399-3089
IL  - 0908-665X
DO  - https://dx.doi.org/10.1111/xen.12145
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  - 10.1111/xen.12145 [doi]
ID  - PMC4329053 [pmc]
ID  - NIHMS629776 [mid]
PP  - ppublish
PH  - 2014/07/03 [received]
PH  - 2014/09/13 [accepted]
GI  - No: UL1 TR000005
Organization: (TR) *NCATS NIH HHS*
Country: United States

GI  - No: U19 AI090959-01
Organization: (AI) *NIAID NIH HHS*
Country: United States

GI  - No: T32 AI074490
Organization: (AI) *NIAID NIH HHS*
Country: United States

GI  - No: T32 AI 074490
Organization: (AI) *NIAID NIH HHS*
Country: United States

GI  - No: U01 AI068642
Organization: (AI) *NIAID NIH HHS*
Country: United States

GI  - No: R21 A1074844
Organization: *PHS HHS*
Country: United States

GI  - No: U19 AI090959
Organization: (AI) *NIAID NIH HHS*
Country: United States
LG  - English
EP  - 20141110
DP  - 2015 Jan-Feb
EZ  - 2014/11/11 06:00
DA  - 2016/01/05 06:00
DT  - 2014/11/11 06:00
YR  - 2015
ED  - 20160104
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med8&AN=25382150

<6. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 24907635
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Aglietta M
AU  - Barone C
AU  - Sawyer MB
AU  - Moore MJ
AU  - Miller WH Jr
AU  - Bagala C
AU  - Colombi F
AU  - Cagnazzo C
AU  - Gioeni L
AU  - Wang E
AU  - Huang B
AU  - Fly KD
AU  - Leone F
FA  - Aglietta, M
FA  - Barone, C
FA  - Sawyer, M B
FA  - Moore, M J
FA  - Miller, W H Jr
FA  - Bagala, C
FA  - Colombi, F
FA  - Cagnazzo, C
FA  - Gioeni, L
FA  - Wang, E
FA  - Huang, B
FA  - Fly, K D
FA  - Leone, F
IN  - Aglietta, M. Department of Medical Oncology, University of Torino, Candiolo Cancer Institute-FPO, IRCCS, Turin massimo.aglietta@ircc.it.
IN  - Barone, C. Department of Medical Oncology, Catholic University of the Sacred Heart, Rome, Italy.
IN  - Sawyer, M B. Department of Oncology, University of Alberta, Edmonton.
IN  - Moore, M J. Division of Medical Oncology, Princess Margaret Hospital and University of Toronto, Toronto.
IN  - Miller, W H Jr. Department of Oncology, McGill University, Montreal, Canada.
IN  - Bagala, C. Department of Medical Oncology, Catholic University of the Sacred Heart, Rome, Italy.
IN  - Colombi, F. Department of Medical Oncology, University of Torino, Candiolo Cancer Institute-FPO, IRCCS, Turin.
IN  - Cagnazzo, C. Department of Medical Oncology, University of Torino, Candiolo Cancer Institute-FPO, IRCCS, Turin.
IN  - Gioeni, L. Department of Medical Oncology, University of Torino, Candiolo Cancer Institute-FPO, IRCCS, Turin.
IN  - Wang, E. Pfizer Oncology Global Research and Development, Groton, USA.
IN  - Huang, B. Pfizer Oncology Global Research and Development, Groton, USA.
IN  - Fly, K D. Pfizer Oncology Global Research and Development, Groton, USA.
IN  - Leone, F. Department of Medical Oncology, University of Torino, Candiolo Cancer Institute-FPO, IRCCS, Turin.
TI  - A phase I dose escalation trial of tremelimumab (CP-675,206) in combination with gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer.
SO  - Annals of Oncology. 25(9):1750-5, 2014 Sep
AS  - Ann Oncol. 25(9):1750-5, 2014 Sep
NJ  - Annals of oncology : official journal of the European Society for Medical Oncology
VO  - 25
IP  - 9
PG  - 1750-5
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Internet
JC  - ayf, 9007735
IO  - Ann. Oncol.
SB  - Index Medicus
CP  - England
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  - Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
MH  - *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH  - Deoxycytidine/ae [Adverse Effects]
MH  - *Deoxycytidine/aa [Analogs & Derivatives]
MH  - Deoxycytidine/tu [Therapeutic Use]
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - *Pancreatic Neoplasms/dt [Drug Therapy]
MH  - Pancreatic Neoplasms/mo [Mortality]
KW  - gemcitabine chemotherapy;  immunotherapy;  metastatic pancreatic cancer;  tremelimumab
AB  - BACKGROUND: Tremelimumab (CP-675,206) is a fully human monoclonal antibody binding to cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) on T cells that stimulates the immune system by blocking the CTLA4-negative regulatory signal. Combination with standard chemotherapy may strengthen antitumor therapy. This is a phase Ib, multisite, open-label, nonrandomized dose escalation trial evaluating the safety, tolerability, and maximum tolerated dose (MTD) of tremelimumab combined with gemcitabine in patients with metastatic pancreatic cancer.
AB  - PATIENTS AND METHODS: Gemcitabine (1000 mg/m(2) on days 1, 8, and 15 of each 28-day cycles) was administrated with escalating doses of i.v. tremelimumab (6, 10, or 15 mg/kg) on day 1 of each 84-day cycle for a maximum of 4 cycles. The first 18 patients had an initial 4-week gemcitabine-only lead-in period. Dose-limiting toxicities (DLTs) related to tremelimumab were evaluated during the first 6 weeks after the first dose of tremelimumab.
AB  - RESULTS: From June 2008 to August 2011, 34 patients were enrolled and received at least one dose of tremelimumab. No DLTs related to tremelimumab were observed at any dose, even when the maximum dose established for tremelimumab (15 mg/kg) was used. Most frequent grade 3/4 toxicities were asthenia (11.8%) and nausea (8.8%). Only one patient had a serious drug-related event (diarrhea with dehydration). The median overall survival was 7.4 months (95% confidence interval 5.8-9.4 months). At the end of treatment, two patients achieved partial response. Both patients received tremelimumab 15-mg/kg group (n = 2/19, 10.5%).
AB  - CONCLUSION: Tremelimumab plus gemcitabine demonstrated a safety and tolerability profile, warranting further study in patients with metastatic pancreatic cancer.
AB  - CLINICALTRIALSGOV ID: NCT00556023.

Copyright © The Author 2014. 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 (Antineoplastic Agents)
RN  - 0W860991D6 (Deoxycytidine)
RN  - B76N6SBZ8R (gemcitabine)
RN  - QEN1X95CIX (tremelimumab)
ES  - 1569-8041
IL  - 0923-7534
DO  - https://dx.doi.org/10.1093/annonc/mdu205
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
ID  - mdu205 [pii]
ID  - 10.1093/annonc/mdu205 [doi]
PP  - ppublish
SI  - ClinicalTrials.gov
SA  - ClinicalTrials.gov/NCT00556023
SL  - https://clinicaltrials.gov/search/term=NCT00556023
LG  - English
EP  - 20140606
DP  - 2014 Sep
EZ  - 2014/06/08 06:00
DA  - 2015/06/09 06:00
DT  - 2014/06/08 06:00
YR  - 2014
ED  - 20150608
RD  - 20161017
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med8&AN=24907635

<7. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 24598534
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Poirier N
AU  - Mary C
AU  - Le Bas-Bernardet S
AU  - Daguin V
AU  - Belarif L
AU  - Chevalier M
AU  - Hervouet J
AU  - Minault D
AU  - Ville S
AU  - Charpy V
AU  - Blancho G
AU  - Vanhove B
FA  - Poirier, Nicolas
FA  - Mary, Caroline
FA  - Le Bas-Bernardet, Stephanie
FA  - Daguin, Veronique
FA  - Belarif, Lyssia
FA  - Chevalier, Melanie
FA  - Hervouet, Jeremy
FA  - Minault, David
FA  - Ville, Simon
FA  - Charpy, Vianney
FA  - Blancho, Gilles
FA  - Vanhove, Bernard
IN  - Poirier, Nicolas. Institut National de la Sante Et de la Recherche Medicale Unite Mixte de Recherche; Institut de Transplantation Urologie Nephrologie (ITUN) ; Universite de Nantes; Nantes, France; Effimune SAS; Nantes, France.
IN  - Mary, Caroline. Institut National de la Sante Et de la Recherche Medicale Unite Mixte de Recherche; Institut de Transplantation Urologie Nephrologie (ITUN) ; Universite de Nantes; Nantes, France; Effimune SAS; Nantes, France.
IN  - Le Bas-Bernardet, Stephanie. Institut National de la Sante Et de la Recherche Medicale Unite Mixte de Recherche; Institut de Transplantation Urologie Nephrologie (ITUN) ; Universite de Nantes; Nantes, France; Centre Hospitalier Universitaire; Nantes, France.
IN  - Daguin, Veronique. Institut National de la Sante Et de la Recherche Medicale Unite Mixte de Recherche; Institut de Transplantation Urologie Nephrologie (ITUN) ; Universite de Nantes; Nantes, France.
IN  - Belarif, Lyssia. Institut National de la Sante Et de la Recherche Medicale Unite Mixte de Recherche; Institut de Transplantation Urologie Nephrologie (ITUN) ; Universite de Nantes; Nantes, France.
IN  - Chevalier, Melanie. Institut National de la Sante Et de la Recherche Medicale Unite Mixte de Recherche; Institut de Transplantation Urologie Nephrologie (ITUN) ; Universite de Nantes; Nantes, France.
IN  - Hervouet, Jeremy. Institut National de la Sante Et de la Recherche Medicale Unite Mixte de Recherche; Institut de Transplantation Urologie Nephrologie (ITUN) ; Universite de Nantes; Nantes, France.
IN  - Minault, David. Institut National de la Sante Et de la Recherche Medicale Unite Mixte de Recherche; Institut de Transplantation Urologie Nephrologie (ITUN) ; Universite de Nantes; Nantes, France.
IN  - Ville, Simon. Institut National de la Sante Et de la Recherche Medicale Unite Mixte de Recherche; Institut de Transplantation Urologie Nephrologie (ITUN) ; Universite de Nantes; Nantes, France.
IN  - Charpy, Vianney. Institut National de la Sante Et de la Recherche Medicale Unite Mixte de Recherche; Institut de Transplantation Urologie Nephrologie (ITUN) ; Universite de Nantes; Nantes, France.
IN  - Blancho, Gilles. Institut National de la Sante Et de la Recherche Medicale Unite Mixte de Recherche; Institut de Transplantation Urologie Nephrologie (ITUN) ; Universite de Nantes; Nantes, France; Centre Hospitalier Universitaire; Nantes, France.
IN  - Vanhove, Bernard. Institut National de la Sante Et de la Recherche Medicale Unite Mixte de Recherche; Institut de Transplantation Urologie Nephrologie (ITUN) ; Universite de Nantes; Nantes, France; Effimune SAS; Nantes, France.
TI  - Advantages of Papio anubis for preclinical testing of immunotoxicity of candidate therapeutic antagonist antibodies targeting CD28.
SO  - mAbs. 6(3):697-707, 2014 May-Jun
AS  - MAbs. 6(3):697-707, 2014 May-Jun
NJ  - mAbs
VO  - 6
IP  - 3
PG  - 697-707
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Internet
JC  - 101479829
IO  - MAbs
PM  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011914
SB  - Index Medicus
CP  - United States
MH  - Animals
MH  - Antibodies, Blocking/im [Immunology]
MH  - *Antibodies, Blocking/to [Toxicity]
MH  - *Antibodies, Monoclonal/im [Immunology]
MH  - *Antibodies, Monoclonal/to [Toxicity]
MH  - Antibodies, Monoclonal, Humanized/im [Immunology]
MH  - Antibodies, Monoclonal, Humanized/to [Toxicity]
MH  - *CD28 Antigens/ai [Antagonists & Inhibitors]
MH  - CD28 Antigens/im [Immunology]
MH  - Cytokines/bi [Biosynthesis]
MH  - Drug Evaluation, Preclinical
MH  - Humans
MH  - Immunologic Memory
MH  - Lymphocyte Activation
MH  - Macaca fascicularis
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Knockout
MH  - Mice, SCID
MH  - Models, Animal
MH  - *Papio anubis/im [Immunology]
MH  - Species Specificity
MH  - T-Lymphocytes/im [Immunology]
KW  - CD28;  FR104;  cytokines;  humanized mice;  immunotoxicity;  primate
AB  - Antagonist anti-CD28 antibodies prevent T-cell costimulation and are functionally different from CTLA4Ig since they cannot block CTLA-4 and PDL-1 co-inhibitory signals. They demonstrated preclinical efficacy in suppressing effector T cells while enhancing immunoregulatory mechanisms. Because a severe cytokine release syndrome was observed during the Phase 1 study with the superagonist anti-CD28 TGN1412, development of other anti-CD28 antibodies requires careful preclinical evaluation to exclude any potential immunotoxicity side-effects. The failure to identify immunological toxicity of TGN1412 using macaques led us to investigate more relevant preclinical models. We report here that contrary to macaques, and like in man, all baboon CD4-positive T lymphocytes express CD28 in their effector memory cells compartment, a lymphocyte subtype that is the most prone to releasing cytokines after reactivation. Baboon lymphocytes are able to release pro-inflammatory cytokines in vitro in response to agonist or superagonist anti-CD28 antibodies. Furthermore, we compared the reactivity of human and baboon lymphocytes after transfer into non obese diabetic/severe combined immunodeficiency (NOD/SCID) interleukin-2rgamma knockout mice and confirmed that both cell types could release inflammatory cytokines in situ after injection of agonistic anti-CD28 antibodies. In contrast, FR104, a monovalent antagonistic anti-CD28 antibody, did not elicit T cell activation in these assays, even in the presence of anti-drug antibodies. Infusion to baboons also resulted in an absence of cytokine release. In conclusion, the baboon represents a suitable species for preclinical immunotoxicity evaluation of anti-CD28 antibodies because their effector memory T cells do express CD28 and because cytokine release can be assessed in vitro and trans vivo.
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (CD28 Antigens)
RN  - 0 (Cytokines)
RN  - 0 (TGN-1412 monoclonal antibody)
ES  - 1942-0870
IL  - 1942-0862
DO  - https://dx.doi.org/10.4161/mabs.28375
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
ID  - 28375 [pii]
ID  - 10.4161/mabs.28375 [doi]
ID  - PMC4011914 [pmc]
PP  - ppublish
LG  - English
EP  - 20140305
DP  - 2014 May-Jun
EZ  - 2014/03/07 06:00
DA  - 2015/05/13 06:00
DT  - 2014/03/07 06:00
YR  - 2014
ED  - 20150512
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med8&AN=24598534

<8. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 24676639
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Fiorina P
AU  - Vergani A
AU  - Bassi R
AU  - Niewczas MA
AU  - Altintas MM
AU  - Pezzolesi MG
AU  - D'Addio F
AU  - Chin M
AU  - Tezza S
AU  - Ben Nasr M
AU  - Mattinzoli D
AU  - Ikehata M
AU  - Corradi D
AU  - Schumacher V
AU  - Buvall L
AU  - Yu CC
AU  - Chang JM
AU  - La Rosa S
AU  - Finzi G
AU  - Solini A
AU  - Vincenti F
AU  - Rastaldi MP
AU  - Reiser J
AU  - Krolewski AS
AU  - Mundel PH
AU  - Sayegh MH
FA  - Fiorina, Paolo
FA  - Vergani, Andrea
FA  - Bassi, Roberto
FA  - Niewczas, Monika A
FA  - Altintas, Mehmet M
FA  - Pezzolesi, Marcus G
FA  - D'Addio, Francesca
FA  - Chin, Melissa
FA  - Tezza, Sara
FA  - Ben Nasr, Moufida
FA  - Mattinzoli, Deborah
FA  - Ikehata, Masami
FA  - Corradi, Domenico
FA  - Schumacher, Valerie
FA  - Buvall, Lisa
FA  - Yu, Chih-Chuan
FA  - Chang, Jer-Ming
FA  - La Rosa, Stefano
FA  - Finzi, Giovanna
FA  - Solini, Anna
FA  - Vincenti, Flavio
FA  - Rastaldi, Maria Pia
FA  - Reiser, Jochen
FA  - Krolewski, Andrzej S
FA  - Mundel, Peter H
FA  - Sayegh, Mohamed H
IN  - Fiorina, Paolo. Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Medicine, San Raffaele Scientific Institute, Milan, Italy; paolo.fiorina@childrens.harvard.edu.
IN  - Vergani, Andrea. Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Medicine, San Raffaele Scientific Institute, Milan, Italy;
IN  - Bassi, Roberto. Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Medicine, San Raffaele Scientific Institute, Milan, Italy; DiSTeBA, Universita' del Salento, Lecce, Italy;
IN  - Niewczas, Monika A. Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts;
IN  - Altintas, Mehmet M. Department of Medicine, Rush University Medical Center, Chicago, Illinois;
IN  - Pezzolesi, Marcus G. Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts;
IN  - D'Addio, Francesca. Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Medicine, San Raffaele Scientific Institute, Milan, Italy;
IN  - Chin, Melissa. Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts;
IN  - Tezza, Sara. Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts;
IN  - Ben Nasr, Moufida. Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts;
IN  - Mattinzoli, Deborah. Renal Research Laboratory, Fondazione IRCCS Ospedale Maggiore Policlinico and Fondazione D'Amico per la Ricerca sulle Malattie Renali, Milan, Italy;
IN  - Ikehata, Masami. Renal Research Laboratory, Fondazione IRCCS Ospedale Maggiore Policlinico and Fondazione D'Amico per la Ricerca sulle Malattie Renali, Milan, Italy;
IN  - Corradi, Domenico. Department of Biomedical, Biotechnological and Translational Sciences, Unit of Pathology, University of Parma, Parma, Italy;
IN  - Schumacher, Valerie. Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts;
IN  - Buvall, Lisa. Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts;
IN  - Yu, Chih-Chuan. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;
IN  - Chang, Jer-Ming. Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;
IN  - La Rosa, Stefano. Pathology Department, Ospedale di Circolo, Varese, Italy;
IN  - Finzi, Giovanna. Pathology Department, Ospedale di Circolo, Varese, Italy;
IN  - Solini, Anna. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy;
IN  - Vincenti, Flavio. Kidney Transplant Service, University of San Francisco, San Francisco, California;
IN  - Rastaldi, Maria Pia. Renal Research Laboratory, Fondazione IRCCS Ospedale Maggiore Policlinico and Fondazione D'Amico per la Ricerca sulle Malattie Renali, Milan, Italy;
IN  - Reiser, Jochen. Department of Medicine, Rush University Medical Center, Chicago, Illinois;
IN  - Krolewski, Andrzej S. Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts;
IN  - Mundel, Peter H. Nephrology Division, Massachusetts General Hospital, Boston, Massachusetts;
IN  - Sayegh, Mohamed H. Transplantation Research Center, Brigham and Women's Hospital, Boston, Massachusetts; and American University of Beirut, Beirut, Lebanon.
TI  - Role of podocyte B7-1 in diabetic nephropathy.
SO  - Journal of the American Society of Nephrology. 25(7):1415-29, 2014 Jul
AS  - J Am Soc Nephrol. 25(7):1415-29, 2014 Jul
NJ  - Journal of the American Society of Nephrology : JASN
VO  - 25
IP  - 7
PG  - 1415-29
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Internet
JC  - a6h, 9013836
IO  - J. Am. Soc. Nephrol.
PM  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073425
SB  - Index Medicus
CP  - United States
MH  - Adult
MH  - Aged
MH  - Animals
MH  - *B7-1 Antigen/ph [Physiology]
MH  - *Diabetes Mellitus, Type 1/co [Complications]
MH  - *Diabetic Nephropathies/et [Etiology]
MH  - Female
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - *Podocytes
MH  - Up-Regulation
AB  - Podocyte injury and resulting albuminuria are hallmarks of diabetic nephropathy, but targeted therapies to halt or prevent these complications are currently not available. Here, we show that the immune-related molecule B7-1/CD80 is a critical mediator of podocyte injury in type 2 diabetic nephropathy. We report the induction of podocyte B7-1 in kidney biopsy specimens from patients with type 2 diabetes. Genetic and epidemiologic studies revealed the association of two single nucleotide polymorphisms at the B7-1 gene with diabetic nephropathy. Furthermore, increased levels of the soluble isoform of the B7-1 ligand CD28 correlated with the progression to ESRD in individuals with type 2 diabetes. In vitro, high glucose conditions prompted the phosphatidylinositol 3 kinase-dependent upregulation of B7-1 in podocytes, and the ectopic expression of B7-1 in podocytes increased apoptosis and induced disruption of the cytoskeleton that were reversed by the B7-1 inhibitor CTLA4-Ig. Podocyte expression of B7-1 was also induced in vivo in two murine models of diabetic nephropathy, and treatment with CTLA4-Ig prevented increased urinary albumin excretion and improved kidney pathology in these animals. Taken together, these results identify B7-1 inhibition as a potential therapeutic strategy for the prevention or treatment of diabetic nephropathy.

Copyright © 2014 by the American Society of Nephrology.
RN  - 0 (B7-1 Antigen)
ES  - 1533-3450
IL  - 1046-6673
DO  - https://dx.doi.org/10.1681/ASN.2013050518
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
ID  - ASN.2013050518 [pii]
ID  - 10.1681/ASN.2013050518 [doi]
ID  - PMC4073425 [pmc]
PP  - ppublish
GI  - No: R01 DK057683
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: R01 DK101350
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: P30 DK063720
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: DK101350
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: DK073495
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: R01 DK058549
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: R01 DK089394
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: DK57683
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: DK58549
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: DK089394
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: DK77532
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: DK41526
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: R01 DK077532
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: DK091218
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: R01 DK091218
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: T32 DK007726
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: T32DK007726-28
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: R01 DK062472
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: R01 DK041526
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: R01 DK073495
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: DK062472
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: U01 DP000123
Organization: (DP) *NCCDPHP CDC HHS*
Country: United States
LG  - English
EP  - 20140327
DP  - 2014 Jul
EZ  - 2014/03/29 06:00
DA  - 2014/09/23 06:00
DT  - 2014/03/29 06:00
YR  - 2014
ED  - 20140922
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med8&AN=24676639

<9. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 24779222
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Lacka K
AU  - Fraczek MM
FA  - Lacka, Katarzyna
FA  - Fraczek, Magdalena Maria
TI  - [Classification and etiology of hyperthyroidism]. [Review] [Polish]
OT  - Podzial i etiopatogeneza nadczynnosci tarczycy.
SO  - Polski Merkuriusz Lekarski. 36(213):206-11, 2014 Mar
AS  - Pol Merkuriusz Lek. 36(213):206-11, 2014 Mar
NJ  - Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego
VO  - 36
IP  - 213
PG  - 206-11
PI  - Journal available in: Print
PI  - Citation processed from: Print
JC  - 9705469
IO  - Pol. Merkur. Lekarski
SB  - Index Medicus
CP  - Poland
MH  - Age Factors
MH  - Causality
MH  - Female
MH  - Goiter/ep [Epidemiology]
MH  - Graves Disease/ep [Epidemiology]
MH  - Humans
MH  - Hypersensitivity/ep [Epidemiology]
MH  - *Hyperthyroidism/cl [Classification]
MH  - *Hyperthyroidism/ep [Epidemiology]
MH  - Hyperthyroidism/ge [Genetics]
MH  - Infection/ep [Epidemiology]
MH  - Male
MH  - Pregnancy
MH  - Risk Factors
MH  - Sex Distribution
MH  - Smoking/ep [Epidemiology]
MH  - Stress, Psychological/ep [Epidemiology]
MH  - Thyroid Neoplasms/ep [Epidemiology]
MH  - Thyroiditis, Autoimmune/ep [Epidemiology]
AB  - The prevalence of hyperthyroidism in women is between 0.5-2% and it is 10 times less common in men. The most common causes are Graves' disease, toxic multinodular goiter, and autonomously functioning thyroid adenoma. Rare causes of hyperthyroidisms are as follow: pituitary adenoma, autoimmune thyroiditis (Hashitoxicosis), levothyroxine overdose, inadequate iodine supplementation (including amiodaron induced hyperthyroidism, iodine-based contrast media), hCG excess (pregnancy, gestational trophoblastic disease, germ-cell tumors), drug induced hyperthyroidism, differentiated thyroid carcinomas and/or their metastases, struma ovarii, and familial nonautoimmune hyperthyroidism. This article focuses on the current data of etiopathogenesis of hyperthyroidisms. Genetic factors (like HLA-DR3,CD40, CTLA-4, PTPN22, FOXP3 CD25) and thyroid specific genes (thyroglobulin, TSHR, G(s)alpha) and environmental and endogenous factors (such as age, iodine, selenium, emotional stress, smoking, gender, pregnancy, sex hormones, fetal microchimerism, fetal growth, bacterial infections, viral infections, allergies, drugs (alemtuzumab, interferon alpha, iplimumab/tremelimumab, tyrosine kinase inhibitors, denileukindiftitox, thalidomide/lenalidomide, exposition to fallout and radiotherapy) have been described.
IS  - 1426-9686
IL  - 1426-9686
PT  - English Abstract
PT  - Journal Article
PT  - Review
PP  - ppublish
LG  - Polish
DP  - 2014 Mar
EZ  - 2014/05/02 06:00
DA  - 2014/06/06 06:00
DT  - 2014/05/01 06:00
YR  - 2014
ED  - 20140605
RD  - 20140430
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med8&AN=24779222

<10. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 24517008
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Ahmadi S
AU  - Rostamzadeh J
AU  - Khosravi D
AU  - Shariati P
AU  - Shakiba N
FA  - Ahmadi, Slahadin
FA  - Rostamzadeh, Jalal
FA  - Khosravi, Darya
FA  - Shariati, Parvin
FA  - Shakiba, Nadia
IN  - Ahmadi, Slahadin. Cellular and Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.
IN  - Rostamzadeh, Jalal. Cellular and Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.
IN  - Khosravi, Darya. Cellular and Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.
IN  - Shariati, Parvin. Laboratory of Genetics, Department of Animal Sciences, University of Kurdistan, Sanandaj, Iran.
IN  - Shakiba, Nadia. Kurdistan Diabetes Center, Tohid hospital, Sanandaj, Iran.
TI  - Association of CTLA-4 gene 49A/G polymorphism with the incidence of type 1 diabetes mellitus in the Iranian Kurdish population.
SO  - Pakistan Journal of Biological Sciences. 16(24):1929-35, 2013 Dec 15
AS  - Pak. j. biol. sci.. 16(24):1929-35, 2013 Dec 15
NJ  - Pakistan journal of biological sciences : PJBS
VO  - 16
IP  - 24
PG  - 1929-35
PI  - Journal available in: Print
PI  - Citation processed from: Print
JC  - 101247723
IO  - Pak. J. Biol. Sci.
SB  - Index Medicus
CP  - Pakistan
MH  - *Arabs/ge [Genetics]
MH  - *CTLA-4 Antigen/ge [Genetics]
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 1/eh [Ethnology]
MH  - *Diabetes Mellitus, Type 1/ge [Genetics]
MH  - Diabetes Mellitus, Type 1/im [Immunology]
MH  - Diabetes Mellitus, Type 2/eh [Ethnology]
MH  - Diabetes Mellitus, Type 2/ge [Genetics]
MH  - Diabetes Mellitus, Type 2/im [Immunology]
MH  - Female
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Incidence
MH  - Iran/ep [Epidemiology]
MH  - Male
MH  - Odds Ratio
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
MH  - Risk Factors
MH  - Sex Factors
AB  - Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) has an inhibitory function on T cells and is critical for the induction of peripheral tolerance. CTLA-4 +49 G allele affects the CTLA-4 function and has been reported to be correlated with a higher risk of various autoimmune diseases including type 1 diabetes (T1D). The present study was conducted to investigate the association between the polymorphism of the CTLA-4 exon 1+49 A/G and susceptibility to TID and type 2 diabetes (T2D) in Kurds living in Iranian Kurdistan. The+49 A/G polymorphism was analyzed in 60 patients with T1D, 56 patients with T2D and 107 control subjects using PCR Single-strand Conformation Polymorphism (SSCP) and restriction fragment length polymorphism methods. All studied populations (T1D, T2D and Controls) were in Hardy-Weinberg equilibrium (p, 0.39, 0.94 and 0.89, respectively). Both+49 G allele (p = 0. 015, OR = 1.86) and +49 A/G genotype frequencies (p = 0. 012, OR = 2.31) were significantly higher in T1D patients than control. There was significant over-representation of the G allele in female T1D patients. No significant differences in +49 G allele and +49 A/G genotype frequencies were found between T2D and control subjects. SSCP analysis did not show new mutation in the amplified segment. The results of this study indicate that CTLA-4+49 A/G gene polymorphism confers genetic susceptibility to T1D but not T2D in the Kurdish population living in Iranian Kurdistan and women carrying the +49 G allele are at greater risk of getting T1D than men having the G allele.
RN  - 0 (CTLA-4 Antigen)
IS  - 1028-8880
IL  - 1028-8880
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PP  - ppublish
LG  - English
DP  - 2013 Dec 15
EZ  - 2014/02/13 06:00
DA  - 2014/03/07 06:00
DT  - 2014/02/13 06:00
YR  - 2013
ED  - 20140305
RD  - 20150311
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=24517008

<11. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 23295794
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Ribas A
AU  - Kefford R
AU  - Marshall MA
AU  - Punt CJ
AU  - Haanen JB
AU  - Marmol M
AU  - Garbe C
AU  - Gogas H
AU  - Schachter J
AU  - Linette G
AU  - Lorigan P
AU  - Kendra KL
AU  - Maio M
AU  - Trefzer U
AU  - Smylie M
AU  - McArthur GA
AU  - Dreno B
AU  - Nathan PD
AU  - Mackiewicz J
AU  - Kirkwood JM
AU  - Gomez-Navarro J
AU  - Huang B
AU  - Pavlov D
AU  - Hauschild A
FA  - Ribas, Antoni
FA  - Kefford, Richard
FA  - Marshall, Margaret A
FA  - Punt, Cornelis J A
FA  - Haanen, John B
FA  - Marmol, Maribel
FA  - Garbe, Claus
FA  - Gogas, Helen
FA  - Schachter, Jacob
FA  - Linette, Gerald
FA  - Lorigan, Paul
FA  - Kendra, Kari L
FA  - Maio, Michele
FA  - Trefzer, Uwe
FA  - Smylie, Michael
FA  - McArthur, Grant A
FA  - Dreno, Brigitte
FA  - Nathan, Paul D
FA  - Mackiewicz, Jacek
FA  - Kirkwood, John M
FA  - Gomez-Navarro, Jesus
FA  - Huang, Bo
FA  - Pavlov, Dmitri
FA  - Hauschild, Axel
IN  - Ribas, Antoni. Division of Hematology-Oncology, 11-934 Factor Building, UCLA Medical Center, 10833 Le Conte Ave, Los Angeles, CA 90095-1782, USA. aribas@mednet.ucla.edu
TI  - Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma.
CM  - Comment in: J Clin Oncol. 2013 Aug 1;31(22):2835-6; PMID: 23752103
CM  - Comment in: J Clin Oncol. 2013 Aug 1;31(22):2836-7; PMID: 24058931
SO  - Journal of Clinical Oncology. 31(5):616-22, 2013 Feb 10
AS  - J Clin Oncol. 31(5):616-22, 2013 Feb 10
NJ  - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
VO  - 31
IP  - 5
PG  - 616-22
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Internet
JC  - jco, 8309333
IO  - J. Clin. Oncol.
PM  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878048
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  - Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use]
MH  - Colitis/ci [Chemically Induced]
MH  - Diarrhea/ci [Chemically Induced]
MH  - Drug Administration Schedule
MH  - Drug Eruptions/et [Etiology]
MH  - Fatigue/ci [Chemically Induced]
MH  - Female
MH  - Humans
MH  - Ipilimumab
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Melanoma/dt [Drug Therapy]
MH  - Melanoma/pa [Pathology]
MH  - Middle Aged
MH  - Nausea/ci [Chemically Induced]
MH  - Pruritus/ci [Chemically Induced]
MH  - Salvage Therapy/mt [Methods]
MH  - *Skin Neoplasms/dt [Drug Therapy]
MH  - Skin Neoplasms/pa [Pathology]
MH  - Treatment Outcome
AB  - PURPOSE: In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy.
AB  - PATIENTS AND METHODS: Patients with treatment-naive, unresectable stage IIIc or IV melanoma were randomly assigned at a ratio of one to one to tremelimumab (15 mg/kg once every 90 days) or physician's choice of standard-of-care chemotherapy (temozolomide or dacarbazine).
AB  - RESULTS: In all, 655 patients were enrolled and randomly assigned. The test statistic crossed the prespecified futility boundary at second interim analysis after 340 deaths, but survival follow-up continued. At final analysis with 534 events, median OS by intent to treat was 12.6 months (95% CI, 10.8 to 14.3) for tremelimumab and 10.7 months (95% CI, 9.36 to 11.96) for chemotherapy (hazard ratio, 0.88; P = .127). Objective response rates were similar in the two arms: 10.7% in the tremelimumab arm and 9.8% in the chemotherapy arm. However, response duration (measured from date of random assignment) was significantly longer after tremelimumab (35.8 v 13.7 months; P = .0011). Diarrhea, pruritus, and rash were the most common treatment-related adverse events in the tremelimumab arm; 7.4% had endocrine toxicities. Seven deaths in the tremelimumab arm and one in the chemotherapy arm were considered treatment related by either investigators or sponsor.
AB  - CONCLUSION: This study failed to demonstrate a statistically significant survival advantage of treatment with tremelimumab over standard-of-care chemotherapy in first-line treatment of patients with metastatic melanoma.
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Ipilimumab)
RN  - QEN1X95CIX (tremelimumab)
ES  - 1527-7755
IL  - 0732-183X
DO  - https://dx.doi.org/10.1200/JCO.2012.44.6112
PT  - Clinical Trial, Phase III
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
ID  - JCO.2012.44.6112 [pii]
ID  - 10.1200/JCO.2012.44.6112 [doi]
ID  - PMC4878048 [pmc]
PP  - ppublish
SI  - ClinicalTrials.gov
SA  - ClinicalTrials.gov/NCT00257205
SL  - https://clinicaltrials.gov/search/term=NCT00257205
GI  - No: P50 CA121973
Organization: (CA) *NCI NIH HHS*
Country: United States
LG  - English
EP  - 20130107
DP  - 2013 Feb 10
EZ  - 2013/01/09 06:00
DA  - 2013/03/30 06:00
DT  - 2013/01/09 06:00
YR  - 2013
ED  - 20130329
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=23295794

<12. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 22537512
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Caturegli P
FA  - Caturegli, Patrizio
IN  - Caturegli, Patrizio. Johns Hopkins University, Department of Pathology, Endocrinology and Molecular Microbiology and Immunology, Baltimore, MD 21205, United States. pcat@jhmi.edu
TI  - Autoimmune hypophysitis: autoantigens and association with CTLA-4 blockade.
SO  - Annales d Endocrinologie. 73(2):78, 2012 Apr
AS  - Ann Endocrinol (Paris). 73(2):78, 2012 Apr
NJ  - Annales d'endocrinologie
VO  - 73
IP  - 2
PG  - 78
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Internet
JC  - 54o, 0116744
IO  - Ann. Endocrinol. (Paris)
SB  - Index Medicus
CP  - France
MH  - Autoantigens/im [Immunology]
MH  - *Autoantigens/ph [Physiology]
MH  - *Autoimmune Diseases/co [Complications]
MH  - Autoimmune Diseases/di [Diagnosis]
MH  - Autoimmune Diseases/im [Immunology]
MH  - *CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH  - CTLA-4 Antigen/im [Immunology]
MH  - Humans
MH  - Inflammation/co [Complications]
MH  - Inflammation/di [Diagnosis]
MH  - Inflammation/et [Etiology]
MH  - Pituitary Diseases/di [Diagnosis]
MH  - *Pituitary Diseases/et [Etiology]
MH  - Pituitary Diseases/im [Immunology]
RN  - 0 (Autoantigens)
RN  - 0 (CTLA-4 Antigen)
ES  - 2213-3941
IL  - 0003-4266
DO  - https://dx.doi.org/10.1016/j.ando.2012.04.006
PT  - Journal Article
ID  - S0003-4266(12)00070-4 [pii]
ID  - 10.1016/j.ando.2012.04.006 [doi]
PP  - ppublish
LG  - English
EP  - 20120425
DP  - 2012 Apr
EZ  - 2012/04/28 06:00
DA  - 2012/09/15 06:00
DT  - 2012/04/28 06:00
YR  - 2012
ED  - 20120914
RD  - 20161031
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22537512

<13. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 22218756
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Ryden A
AU  - Bolmeson C
AU  - Jonson CO
AU  - Cilio CM
AU  - Faresjo M
FA  - Ryden, Anna
FA  - Bolmeson, Caroline
FA  - Jonson, Carl-Oscar
FA  - Cilio, Corrado M
FA  - Faresjo, Maria
IN  - Ryden, Anna. Division of Paediatrics & Diabetes Research Centre, Department of Molecular & Clinical Medicine, Linkoping University, Linkoping, Sweden. anna.ryden@liu.se
TI  - Low expression and secretion of circulating soluble CTLA-4 in peripheral blood mononuclear cells and sera from type 1 diabetic children.
SO  - Diabetes/Metabolism Research Reviews. 28(1):84-96, 2012 Jan
AS  - Diabetes Metab Res Rev. 28(1):84-96, 2012 Jan
NJ  - Diabetes/metabolism research and reviews
VO  - 28
IP  - 1
PG  - 84-96
PI  - Journal available in: Print
PI  - Citation processed from: Internet
JC  - dcy, 100883450
IO  - Diabetes Metab. Res. Rev.
SB  - Index Medicus
CP  - England
MH  - Adolescent
MH  - Autoimmunity
MH  - Biomarkers
MH  - Blood Cells
MH  - C-Peptide/me [Metabolism]
MH  - CTLA-4 Antigen/bi [Biosynthesis]
MH  - *CTLA-4 Antigen/bl [Blood]
MH  - CTLA-4 Antigen/ch [Chemistry]
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Mellitus, Type 1/bl [Blood]
MH  - *Diabetes Mellitus, Type 1/im [Immunology]
MH  - Female
MH  - Forkhead Transcription Factors/bi [Biosynthesis]
MH  - *Gene Expression
MH  - Humans
MH  - Longitudinal Studies
MH  - Male
MH  - Protein Isoforms/ge [Genetics]
MH  - *Protein Isoforms/im [Immunology]
MH  - RNA, Messenger/me [Metabolism]
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes, Regulatory/im [Immunology]
MH  - Transcription, Genetic
MH  - Transforming Growth Factor beta/bi [Biosynthesis]
AB  - BACKGROUND: High levels of soluble cytotoxic T-lymphocyte antigen 4 (soluble CTLA-4), an alternative splice form of the regulatory T-cell (Treg) associated CTLA-4 gene, have been associated with type 1 diabetes (T1D) and other autoimmune diseases, such as Grave's disease and myasthenia gravis. At the same time, studies have shown soluble CTLA-4 to inhibit T-cell activation through B7 binding. This study aimed to investigate the role of soluble CTLA-4 in relation to full-length CTLA-4 and other Treg-associated markers in T1D children and in individuals with high or low risk of developing the disease.
AB  - METHODS: T1D children were studied at 4 days, 1 and 2 years after diagnosis in comparison to individuals with high or low risk of developing the disease. Isolated peripheral blood mononuclear cells were stimulated with the T1D-associated glutamic acid decarboxylase 65 and phytohaemagglutinin. Subsequently, soluble CTLA-4, full-length CTLA-4, FOXP3 and TGF-beta mRNA transcription were quantified and protein concentrations of soluble CTLA-4 were measured in culture supernatant and sera.
AB  - RESULTS AND CONCLUSIONS: Low protein concentrations of circulating soluble CTLA-4 and a positive correlation between soluble CTLA-4 mRNA and protein were seen in T1D, in parallel with a negative correlation in healthy subjects. Further, low levels of mitogen-induced soluble CTLA-4 were accompanied by low C-peptide levels. Interestingly, low mitogen-induced soluble CTLA-4 mRNA and low TGF-beta mRNA expression were seen in high risk individuals, suggesting an alteration in activation and down-regulating immune mechanisms during the pre-diabetic phase.

Copyright © 2011 John Wiley & Sons, Ltd.
RN  - 0 (Biomarkers)
RN  - 0 (C-Peptide)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
ES  - 1520-7560
IL  - 1520-7552
DO  - https://dx.doi.org/10.1002/dmrr.1286
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
ID  - 10.1002/dmrr.1286 [doi]
PP  - ppublish
LG  - English
DP  - 2012 Jan
EZ  - 2012/01/06 06:00
DA  - 2012/03/07 06:00
DT  - 2012/01/06 06:00
YR  - 2012
ED  - 20120306
RD  - 20151119
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22218756

<14. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 22013040
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Vaccari M
AU  - Boasso A
AU  - Fenizia C
AU  - Fuchs D
AU  - Hryniewicz A
AU  - Morgan T
AU  - Weiss D
AU  - Doster MN
AU  - Heraud JM
AU  - Shearer GM
AU  - Franchini G
FA  - Vaccari, Monica
FA  - Boasso, Adriano
FA  - Fenizia, Claudio
FA  - Fuchs, Dietmar
FA  - Hryniewicz, Anna
FA  - Morgan, Tia
FA  - Weiss, Deborah
FA  - Doster, Melvin N
FA  - Heraud, Jean Michel
FA  - Shearer, Gene M
FA  - Franchini, Genoveffa
IN  - Vaccari, Monica. Animal Models & Retroviral Vaccines Section, NCI, NIH, Bethesda, Maryland, USA.
TI  - Fatal pancreatitis in simian immunodeficiency virus SIV(mac251)-infected macaques treated with 2',3'-dideoxyinosine and stavudine following cytotoxic-T-lymphocyte-associated antigen 4 and indoleamine 2,3-dioxygenase blockade.
SO  - Journal of Virology. 86(1):108-13, 2012 Jan
AS  - J Virol. 86(1):108-13, 2012 Jan
NJ  - Journal of virology
VO  - 86
IP  - 1
PG  - 108-13
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Internet
JC  - kcv, 0113724
IO  - J. Virol.
PM  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3255892
SB  - Index Medicus
CP  - United States
MH  - AIDS Vaccines/ad [Administration & Dosage]
MH  - AIDS Vaccines/im [Immunology]
MH  - Animals
MH  - *Anti-HIV Agents/ae [Adverse Effects]
MH  - Anti-HIV Agents/tu [Therapeutic Use]
MH  - CTLA-4 Antigen/ai [Antagonists & Inhibitors]
MH  - *Didanosine/ae [Adverse Effects]
MH  - Didanosine/tu [Therapeutic Use]
MH  - Disease Models, Animal
MH  - Drug Evaluation, Preclinical
MH  - Drug Therapy, Combination/ae [Adverse Effects]
MH  - HIV Infections/co [Complications]
MH  - *HIV Infections/dt [Drug Therapy]
MH  - *HIV Infections/im [Immunology]
MH  - HIV Infections/vi [Virology]
MH  - HIV-1/de [Drug Effects]
MH  - HIV-1/im [Immunology]
MH  - HIV-1/ph [Physiology]
MH  - Humans
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/ai [Antagonists & Inhibitors]
MH  - Macaca mulatta
MH  - *Pancreatitis/et [Etiology]
MH  - Pancreatitis/im [Immunology]
MH  - Pancreatitis/mo [Mortality]
MH  - Simian Immunodeficiency Virus/de [Drug Effects]
MH  - Simian Immunodeficiency Virus/im [Immunology]
MH  - *Simian Immunodeficiency Virus/ph [Physiology]
MH  - *Stavudine/ae [Adverse Effects]
MH  - Stavudine/tu [Therapeutic Use]
MH  - Tryptophan/ae [Adverse Effects]
MH  - Tryptophan/aa [Analogs & Derivatives]
MH  - Tryptophan/tu [Therapeutic Use]
AB  - Human immunodeficiency virus (HIV) infection is associated with immune activation, CD4+-T-cell loss, and a progressive decline of immune functions. Antiretroviral therapy (ART) only partially reverses HIV-associated immune dysfunction, suggesting that approaches that target immune activation and improve virus-specific immune responses may be needed. We performed a preclinical study in rhesus macaques infected with the pathogenic simian immunodeficiency virus SIV(mac251) and treated with ART. We tested whether vaccination administered together with cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) blockade and treatment with the indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyl-D-tryptophan (D-1mT), decreased immune activation and improved vaccine efficacy. The treatment did not augment vaccine immunogenicity; rather, it dramatically increased ART-related toxicity, causing all treated animals to succumb to acute pancreatitis and hyperglycemic coma. The onset of fulminant diabetes was associated with severe lymphocyte infiltration of the pancreas and complete loss of the islets of Langerhans. Thus, caution should be used when considering approaches aimed at targeting immune activation during ART.
RN  - 0 (AIDS Vaccines)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 8DUH1N11BX (Tryptophan)
RN  - BO9LE4QFZF (Stavudine)
RN  - K3GDH6OH08 (Didanosine)
ES  - 1098-5514
IL  - 0022-538X
DO  - https://dx.doi.org/10.1128/JVI.05609-11
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
ID  - JVI.05609-11 [pii]
ID  - 10.1128/JVI.05609-11 [doi]
ID  - PMC3255892 [pmc]
PP  - ppublish
GI  - Organization: *Intramural NIH HHS*
Country: United States
LG  - English
EP  - 20111019
DP  - 2012 Jan
EZ  - 2011/10/21 06:00
DA  - 2012/02/15 06:00
DT  - 2011/10/21 06:00
YR  - 2012
ED  - 20120214
RD  - 20161215
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med7&AN=22013040

<15. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 22028949
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - PubMed-not-MEDLINE
AU  - Wang X
AU  - Hao J
AU  - Metzger DL
AU  - Ao Z
AU  - Meloche M
AU  - Verchere CB
AU  - Chen L
AU  - Ou D
AU  - Mui A
AU  - Warnock GL
FA  - Wang, Xiaojie
FA  - Hao, Jianqiang
FA  - Metzger, Daniel L
FA  - Ao, Ziliang
FA  - Meloche, Mark
FA  - Verchere, C Bruce
FA  - Chen, Lieping
FA  - Ou, Dawei
FA  - Mui, Alice
FA  - Warnock, Garth L
IN  - Wang, Xiaojie. Department of Surgery, University of British Columbia, Vancouver, BC, Canada V5Z 4E3.
TI  - B7-H4 Pathway in Islet Transplantation and beta-Cell Replacement Therapies.
SO  - Journal of transplantation. 2011:418902, 2011
AS  - J Transplant. 2011:418902, 2011
NJ  - Journal of transplantation
VO  - 2011
PG  - 418902
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Internet
JC  - 101519118
IO  - J Transplant
PM  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196026
CP  - United States
AB  - Type 1 diabetes (T1D) is a chronic autoimmune disease and characterized by absolute insulin deficiency. beta-cell replacement by islet cell transplantation has been established as a feasible treatment option for T1D. The two main obstacles after islet transplantation are alloreactive T-cell-mediated graft rejection and recurrence of autoimmune diabetes mellitus in recipients. T cells play a central role in determining the outcome of both autoimmune responses and allograft survival. B7-H4, a newly identified B7 homolog, plays a key role in maintaining T-cell homeostasis by reducing T-cell proliferation and cytokine production. The relationship between B7-H4 and allograft survival/autoimmunity has been investigated recently in both islet transplantation and the nonobese diabetic (NOD) mouse models. B7-H4 protects allograft survival and generates donor-specific tolerance. It also prevents the development of autoimmune diabetes. More importantly, B7-H4 plays an indispensable role in alloimmunity in the absence of the classic CD28/CTLA-4:B7 pathway, suggesting a synergistic/additive effect with other agents such as CTLA-4 on inhibition of unwanted immune responses.
ES  - 2090-0015
IL  - 2090-0007
DO  - https://dx.doi.org/10.1155/2011/418902
PT  - Journal Article
ID  - 10.1155/2011/418902 [doi]
ID  - PMC3196026 [pmc]
PP  - ppublish
PH  - 2011/04/21 [received]
PH  - 2011/08/03 [accepted]
LG  - English
EP  - 20111013
DP  - 2011
EZ  - 2011/10/27 06:00
DA  - 2011/10/27 06:01
DT  - 2011/10/27 06:00
YR  - 2011
ED  - 20111110
RD  - 20170220
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=prem&AN=22028949

<16. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 21074065
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Di Giacomo AM
AU  - Biagioli M
AU  - Maio M
FA  - Di Giacomo, Anna Maria
FA  - Biagioli, Maurizio
FA  - Maio, Michele
IN  - Di Giacomo, Anna Maria. Department of Medical Oncology and Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy. a.m.digiacomo@ao-siena.toscana.it
TI  - The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications. [Review]
SO  - Seminars in Oncology. 37(5):499-507, 2010 Oct
AS  - Semin Oncol. 37(5):499-507, 2010 Oct
NJ  - Seminars in oncology
VO  - 37
IP  - 5
PG  - 499-507
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  - *Antigens, CD/im [Immunology]
MH  - *Antineoplastic Agents/ae [Adverse Effects]
MH  - CTLA-4 Antigen
MH  - Chemical and Drug Induced Liver Injury/im [Immunology]
MH  - Chemical and Drug Induced Liver Injury/th [Therapy]
MH  - Drug-Related Side Effects and Adverse Reactions
MH  - Endocrine System Diseases/ci [Chemically Induced]
MH  - Endocrine System Diseases/im [Immunology]
MH  - Endocrine System Diseases/th [Therapy]
MH  - Gastrointestinal Diseases/ci [Chemically Induced]
MH  - Gastrointestinal Diseases/im [Immunology]
MH  - Gastrointestinal Diseases/th [Therapy]
MH  - Humans
MH  - *Immune System Diseases/ci [Chemically Induced]
MH  - Ipilimumab
MH  - Melanoma/dt [Drug Therapy]
MH  - Skin Diseases/ci [Chemically Induced]
MH  - Skin Diseases/im [Immunology]
MH  - Skin Diseases/th [Therapy]
MH  - Skin Neoplasms/dt [Drug Therapy]
AB  - The promising new class of immunomodulating antibodies directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4) has been extensively tested in clinical trials and found to be active against cutaneous melanoma and other tumor histotypes. Inhibition of CTLA-4 characteristically induces well-identified side effects for which the definition "immune-related adverse events" (irAEs) has been proposed. IrAEs mainly include colitis/diarrhea, dermatitis, hepatitis, and endocrinopathies; uveitis, nephritis, and inflammatory myopathy also have been reported occasionally. These unique side effects are likely a direct result of breaking immune tolerance upon CTLA-4 blockade and are generally mild, reversible, and manageable, following specific treatment guidelines that include symptomatic therapies or systemic corticosteroids. However, patient-physician communication and early treatment are also emerging as critical issues to successfully manage irAEs, thus avoiding major complications. The major experience in identifying and managing CTLA-4 treatment-related side effects has derived from studies in melanoma patients; nevertheless, accumulating clinical experiences are clearly demonstrating that irAEs are class-specific events, and that they are fully overlapping in patients with tumors of different histotypes. This review provides an overview of current safety data on CTLA-4 antagonists and of available strategies to optimize their clinical use in cancer patients.

Copyright © 2010 Elsevier Inc. All rights reserved.
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Ipilimumab)
RN  - QEN1X95CIX (tremelimumab)
ES  - 1532-8708
IL  - 0093-7754
DO  - https://dx.doi.org/10.1053/j.seminoncol.2010.09.007
PT  - Journal Article
PT  - Review
ID  - S0093-7754(10)00161-2 [pii]
ID  - 10.1053/j.seminoncol.2010.09.007 [doi]
PP  - ppublish
LG  - English
DP  - 2010 Oct
EZ  - 2010/11/16 06:00
DA  - 2010/12/16 06:00
DT  - 2010/11/16 06:00
YR  - 2010
ED  - 20101214
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=21074065

<17. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 20601803
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Dimou AT
AU  - Syrigos KN
AU  - Saif MW
FA  - Dimou, Anastasios T
FA  - Syrigos, Konstantinos N
FA  - Saif, Muhammad Wasif
IN  - Dimou, Anastasios T. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
TI  - Novel agents for the treatment of pancreatic adenocarcinoma: any light at the end of the tunnel? Highlights from the "2010 ASCO Annual Meeting". Chicago, IL, USA. June 4-8, 2010. [Review] [10 refs]
SO  - Jop: Journal of the Pancreas [Electronic Resource]. 11(4):324-7, 2010 Jul 05
AS  - JOP. 11(4):324-7, 2010 Jul 05
NJ  - JOP : Journal of the pancreas
VO  - 11
IP  - 4
PG  - 324-7
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  - Antineoplastic Agents/ip [Isolation & Purification]
MH  - *Antineoplastic Agents/tu [Therapeutic Use]
MH  - Chicago
MH  - Congresses as Topic
MH  - Humans
MH  - *Medical Oncology/mt [Methods]
MH  - *Medical Oncology/td [Trends]
MH  - *Pancreatic Neoplasms/dt [Drug Therapy]
MH  - Societies, Medical/og [Organization & Administration]
MH  - United States
AB  - Pancreatic cancer is a disease with dismal prognosis and treatment options are limited. Development of novel active compounds is mandatory. A number of pancreatic cancer clinical trials that included a novel agent among their arms were presented at the recent 2010 American Society of Clinical Oncology (ASCO) Annual Meeting. It appears that IGF-1R inhibition might be effective and this should be tested in further trials. Microtubule stabilization with ixabepilone in combination with EGFR does not lead to promising improvement in prognosis whereas nab-paclitaxel in combination with anti-angiogenetic agents is a combination not previously tested that showed an acceptable safety profile. This combination might be worth testing in a phase II clinical trial. Last but not least, CTLA-4 blockade has an acceptable toxicity profile but its efficacy needs to be proven over placebo in phase II and III trials. Finally, understanding of the tumor biology and biomarker analysis from the clinical trials is warranted. [References: 10]
RN  - 0 (Antineoplastic Agents)
ES  - 1590-8577
IL  - 1590-8577
PT  - Evaluation Studies
PT  - Journal Article
PT  - Review
ID  - v11i04a06 [pii]
PP  - epublish
LG  - English
EP  - 20100705
DP  - 2010 Jul 05
EZ  - 2010/07/06 06:00
DA  - 2010/11/06 06:00
DT  - 2010/07/06 06:00
YR  - 2010
ED  - 20101105
RD  - 20100705
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=20601803

<18. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 19512947
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Kaehler KC
AU  - Egberts F
AU  - Lorigan P
AU  - Hauschild A
FA  - Kaehler, Katharina C
FA  - Egberts, Friederike
FA  - Lorigan, Paul
FA  - Hauschild, Axel
IN  - Kaehler, Katharina C. Department of Dermatology, University of Kiel, Germany. kckaehler@yahoo.de
TI  - Anti-CTLA-4 therapy-related autoimmune hypophysitis in a melanoma patient.
SO  - Melanoma Research. 19(5):333-4, 2009 Oct
AS  - Melanoma Res. 19(5):333-4, 2009 Oct
NJ  - Melanoma research
VO  - 19
IP  - 5
PG  - 333-4
PI  - Journal available in: Print
PI  - Citation processed from: Internet
JC  - bjr, 9109623
IO  - Melanoma Res.
SB  - Index Medicus
CP  - England
MH  - *Antibodies, Monoclonal/ae [Adverse Effects]
MH  - Antibodies, Monoclonal/tu [Therapeutic Use]
MH  - *Antigens, CD/im [Immunology]
MH  - Autoimmune Diseases/bl [Blood]
MH  - *Autoimmune Diseases/ci [Chemically Induced]
MH  - Autoimmune Diseases/pa [Pathology]
MH  - CTLA-4 Antigen
MH  - Humans
MH  - Immunosuppressive Agents
MH  - Ipilimumab
MH  - Male
MH  - *Melanoma/co [Complications]
MH  - Melanoma/im [Immunology]
MH  - Melanoma/pa [Pathology]
MH  - Melanoma/sc [Secondary]
MH  - Middle Aged
MH  - Pituitary Diseases/bl [Blood]
MH  - *Pituitary Diseases/ci [Chemically Induced]
MH  - Pituitary Diseases/pa [Pathology]
AB  - Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is an immunoregulatory molecule expressed by activated T cells and resting CD4+CD25 T cells. In patients with advanced melanoma, anti-CTLA-4 antibody therapy achieves cancer regression in 15% of patients. Treatment may be associated with grade III/IV autoimmune manifestations that included dermatitis, enterocolitis, hepatitis, uveitis, and rarely hypophysitis. Many of these toxicities require and respond to brief courses of high-dose corticosteroids. We report on a case of autoimmune hypophysitis with severe clinical symptoms that resolved rapidly after treatment with steroids. It is important to consider both autoimmune hypophysitis and brain metastasis in the differential diagnosis of melanoma patients receiving CTLA-4 blockade who present this constellation of symptoms.
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Ipilimumab)
ES  - 1473-5636
IL  - 0960-8931
DO  - https://dx.doi.org/10.1097/CMR.0b013e32832e0bff
PT  - Case Reports
PT  - Journal Article
ID  - 10.1097/CMR.0b013e32832e0bff [doi]
PP  - ppublish
LG  - English
DP  - 2009 Oct
EZ  - 2009/06/11 09:00
DA  - 2010/01/27 06:00
DT  - 2009/06/11 09:00
YR  - 2009
ED  - 20100126
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=19512947

<19. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 19789309
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Ribas A
AU  - Comin-Anduix B
AU  - Chmielowski B
AU  - Jalil J
AU  - de la Rocha P
AU  - McCannel TA
AU  - Ochoa MT
AU  - Seja E
AU  - Villanueva A
AU  - Oseguera DK
AU  - Straatsma BR
AU  - Cochran AJ
AU  - Glaspy JA
AU  - Hui L
AU  - Marincola FM
AU  - Wang E
AU  - Economou JS
AU  - Gomez-Navarro J
FA  - Ribas, Antoni
FA  - Comin-Anduix, Begona
FA  - Chmielowski, Bartosz
FA  - Jalil, Jason
FA  - de la Rocha, Pilar
FA  - McCannel, Tara A
FA  - Ochoa, Maria Teresa
FA  - Seja, Elizabeth
FA  - Villanueva, Arturo
FA  - Oseguera, Denise K
FA  - Straatsma, Bradley R
FA  - Cochran, Alistair J
FA  - Glaspy, John A
FA  - Hui, Liu
FA  - Marincola, Francesco M
FA  - Wang, Ena
FA  - Economou, James S
FA  - Gomez-Navarro, Jesus
IN  - Ribas, Antoni. Department of Medicine, Division of Hematology/Oncology, University of California at Los Angeles, Los Angeles, California 90095-1782, USA. aribas@mednet.ucla.edu
TI  - Dendritic cell vaccination combined with CTLA4 blockade in patients with metastatic melanoma.
SO  - Clinical Cancer Research. 15(19):6267-76, 2009 Oct 01
AS  - Clin Cancer Res. 15(19):6267-76, 2009 Oct 01
NJ  - Clinical cancer research : an official journal of the American Association for Cancer Research
VO  - 15
IP  - 19
PG  - 6267-76
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/PMC2765061
OI  - Source: NLM. NIHMS134485
SB  - Index Medicus
CP  - United States
MH  - Adult
MH  - Aged
MH  - *Antibodies, Blocking/ad [Administration & Dosage]
MH  - Antibodies, Blocking/ae [Adverse Effects]
MH  - Antibodies, Monoclonal/ad [Administration & Dosage]
MH  - Antibodies, Monoclonal/ae [Adverse Effects]
MH  - *Antigens, CD/im [Immunology]
MH  - Antigens, Neoplasm/ad [Administration & Dosage]
MH  - Antigens, Neoplasm/ch [Chemistry]
MH  - Antigens, Neoplasm/me [Metabolism]
MH  - Antineoplastic Combined Chemotherapy Protocols/ad [Administration & Dosage]
MH  - CTLA-4 Antigen
MH  - *Cancer Vaccines/ad [Administration & Dosage]
MH  - Cancer Vaccines/ae [Adverse Effects]
MH  - Combined Modality Therapy
MH  - Dendritic Cells/im [Immunology]
MH  - Dendritic Cells/me [Metabolism]
MH  - *Dendritic Cells/tr [Transplantation]
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - *Immunotherapy, Adoptive/mt [Methods]
MH  - K562 Cells
MH  - MART-1 Antigen
MH  - Male
MH  - Melanoma/pa [Pathology]
MH  - *Melanoma/th [Therapy]
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Proteins/ad [Administration & Dosage]
MH  - Neoplasm Proteins/ch [Chemistry]
MH  - Neoplasm Proteins/me [Metabolism]
MH  - Peptide Fragments/ad [Administration & Dosage]
MH  - Peptide Fragments/me [Metabolism]
AB  - PURPOSE: Tumor antigen-loaded dendritic cells (DC) are believed to activate antitumor immunity by stimulating T cells, and CTL-associated antigen 4 (CTLA4)-blocking antibodies should release a key negative regulatory pathway on T cells. The combination was tested in a phase I clinical trial in patients with advanced melanoma.
AB  - EXPERIMENTAL DESIGN: Autologous DC were pulsed with MART-1(26-35) peptide and administered with a dose escalation of the CTLA4-blocking antibody tremelimumab. Sixteen patients were accrued to five dose levels. Primary end points were safety and immune effects; clinical efficacy was a secondary end point.
AB  - RESULTS: Dose-limiting toxicities of grade 3 diarrhea and grade 2 hypophysitis developed in two of three patients receiving tremelimumab at 10 mg/kg monthly. Four patients had an objective tumor response, two partial responses and two complete responses, all melanoma free between 2 and 4 years after study initiation. There was no difference in immune monitoring results between patients with an objective tumor response and those without a response. Exploratory gene expression analysis suggested that immune-related gene signatures, in particular for B-cell function, may be important in predicting response.
AB  - CONCLUSION: The combination of MART-1 peptide-pulsed DC and tremelimumab results in objective and durable tumor responses at the higher range of the expected response rate with either agent alone.
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Cancer Vaccines)
RN  - 0 (MART-1 Antigen)
RN  - 0 (MLANA protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Peptide Fragments)
RN  - QEN1X95CIX (tremelimumab)
IS  - 1078-0432
IL  - 1078-0432
DO  - https://dx.doi.org/10.1158/1078-0432.CCR-09-1254
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
ID  - 1078-0432.CCR-09-1254 [pii]
ID  - 10.1158/1078-0432.CCR-09-1254 [doi]
ID  - PMC2765061 [pmc]
ID  - NIHMS134485 [mid]
PP  - ppublish
GI  - No: CA-16042
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: R01 CA129816
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: M01 RR000865
Organization: (RR) *NCRR NIH HHS*
Country: United States

GI  - No: M01-RR-0865
Organization: (RR) *NCRR NIH HHS*
Country: United States

GI  - No: AI-28697
Organization: (AI) *NIAID NIH HHS*
Country: United States

GI  - No: U54 CA119347
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: P50 CA086306
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: P30 CA016042
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: P30 AI028697
Organization: (AI) *NIAID NIH HHS*
Country: United States

GI  - No: P50 CA086306-100006
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: M01 RR000865-338786
Organization: (RR) *NCRR NIH HHS*
Country: United States
LG  - English
EP  - 20090929
DP  - 2009 Oct 01
EZ  - 2009/10/01 06:00
DA  - 2009/12/23 06:00
DT  - 2009/10/01 06:00
YR  - 2009
ED  - 20091222
RD  - 20170220
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=19789309

<20. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 18941200
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Lozanoska-Ochser B
AU  - Klein NJ
AU  - Huang GC
AU  - Alvarez RA
AU  - Peakman M
FA  - Lozanoska-Ochser, Biliana
FA  - Klein, Nigel J
FA  - Huang, Guo C
FA  - Alvarez, Raymond A
FA  - Peakman, Mark
IN  - Lozanoska-Ochser, Biliana. King's College London, Department of Immunobiology, London, United Kingdom.
TI  - Expression of CD86 on human islet endothelial cells facilitates T cell adhesion and migration.
SO  - Journal of Immunology. 181(9):6109-16, 2008 Nov 01
AS  - J Immunol. 181(9):6109-16, 2008 Nov 01
NJ  - Journal of immunology (Baltimore, Md. : 1950)
VO  - 181
IP  - 9
PG  - 6109-16
PI  - Journal available in: Print
PI  - Citation processed from: Internet
JC  - ifb, 2985117r
IO  - J. Immunol.
SB  - Core Clinical Journals (AIM)
SB  - Index Medicus
CP  - United States
MH  - Antigens, CD/bi [Biosynthesis]
MH  - Antigens, CD/ge [Genetics]
MH  - Antigens, CD/me [Metabolism]
MH  - Antigens, CD/ph [Physiology]
MH  - *B7-2 Antigen/bi [Biosynthesis]
MH  - B7-2 Antigen/ge [Genetics]
MH  - B7-2 Antigen/me [Metabolism]
MH  - B7-2 Antigen/ph [Physiology]
MH  - CD4-Positive T-Lymphocytes/cy [Cytology]
MH  - *CD4-Positive T-Lymphocytes/im [Immunology]
MH  - *CD4-Positive T-Lymphocytes/me [Metabolism]
MH  - CTLA-4 Antigen
MH  - Cell Adhesion/im [Immunology]
MH  - Cell Migration Inhibition/im [Immunology]
MH  - *Cell Movement/im [Immunology]
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Endothelium, Vascular/cy [Cytology]
MH  - *Endothelium, Vascular/im [Immunology]
MH  - *Endothelium, Vascular/me [Metabolism]
MH  - Humans
MH  - Immunologic Memory
MH  - Inducible T-Cell Co-Stimulator Ligand
MH  - Islets of Langerhans/cy [Cytology]
MH  - *Islets of Langerhans/im [Immunology]
MH  - *Islets of Langerhans/me [Metabolism]
MH  - Ligands
MH  - Lymph Nodes/cy [Cytology]
MH  - Lymph Nodes/im [Immunology]
MH  - Lymph Nodes/me [Metabolism]
MH  - Lymphocyte Activation/im [Immunology]
MH  - Microcirculation/im [Immunology]
AB  - Pancreatic islet endothelial cells (ECs) form the barrier across which autoreactive T cells transmigrate during the development of islet inflammation in type 1 diabetes. Little is known about the immune phenotype of islet ECs that might shape their molecular interaction with autoreactive T cells before and during the development of islet inflammation. In this study we examined the expression and functional significance of costimulatory molecules by human islet ECs. Freshly isolated human islet ECs constitutively expressed CD86 (B7-2) and ICOS ligand but not CD80 (B7-1) or CD40 costimulatory molecules. The functional activity of islet EC-expressed CD86 was examined by coculture of resting islet ECs with CD4 T cells stimulated by CD3 ligation alone. Marked T cell proliferation in the coculture was completely abrogated by mAb blockade of CD86, confirming that costimulatory properties are conferred on ECs by CD86 expression. In view of its location on the vasculature, we hypothesized a role for CD86 in T cell adhesion/transmigration. In keeping with this, adhesion/transmigration of activated (CD3 ligated) memory (CD45R0(+)) CD4 T cells across islet ECs was completely inhibited in the presence of CD86 blocking mAb. Identical results were obtained for T cell adhesion using either CTLA-4 blocking mAb or CTLA-4Ig (abatacept), indicating CTLA-4 as the T cell ligand for these CD86-mediated effects. These data suggest a novel role for CD86 expression on the microvasculature, whereby ligation of CTLA-4 on CD4 T cells by CD86 on islet ECs is key to the adhesion of recently activated T cells.
RN  - 0 (Antigens, CD)
RN  - 0 (B7-2 Antigen)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (ICOSLG protein, human)
RN  - 0 (Inducible T-Cell Co-Stimulator Ligand)
RN  - 0 (Ligands)
ES  - 1550-6606
IL  - 0022-1767
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
ID  - 181/9/6109 [pii]
PP  - ppublish
GI  - Organization: *Department of Health*
Country: United Kingdom
LG  - English
DP  - 2008 Nov 01
EZ  - 2008/10/23 09:00
DA  - 2009/01/22 09:00
DT  - 2008/10/23 09:00
YR  - 2008
ED  - 20090121
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=18941200

<21. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 18774118
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Caturegli P
AU  - Lupi I
AU  - Landek-Salgado M
AU  - Kimura H
AU  - Rose NR
FA  - Caturegli, Patrizio
FA  - Lupi, Isabella
FA  - Landek-Salgado, Melissa
FA  - Kimura, Hiroaki
FA  - Rose, Noel R
IN  - Caturegli, Patrizio. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States. pcat@jhmi.edu
TI  - Pituitary autoimmunity: 30 years later. [Review] [40 refs]
SO  - Autoimmunity Reviews. 7(8):631-7, 2008 Sep
AS  - Autoimmun Rev. 7(8):631-7, 2008 Sep
NJ  - Autoimmunity reviews
VO  - 7
IP  - 8
PG  - 631-7
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Print
JC  - 101128967
IO  - Autoimmun Rev
PM  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383826
OI  - Source: NLM. NIHMS72537
SB  - Index Medicus
CP  - Netherlands
MH  - Animals
MH  - *Autoimmune Diseases/im [Immunology]
MH  - Autoimmune Diseases/me [Metabolism]
MH  - Humans
MH  - *Pituitary Diseases/im [Immunology]
MH  - *Pituitary Gland/im [Immunology]
MH  - Pituitary Hormones/im [Immunology]
AB  - Pituitary autoimmunity encompasses a spectrum of conditions ranging from histologically proven forms of lymphocytic hypophysitis to the presence of pituitary antibodies in apparently healthy subjects. Hypophysitis is a rare but increasingly recognized disorder that typically presents as a mass in the sella turcica. It mimics clinically and radiologically other non-functioning sellar masses, such as the more common pituitary adenoma. Hypophysitis shows a striking temporal association with pregnancy, and it has been recently described during immunotherapies that block CTLA-4. Several candidate pituitary autoantigens have been described in the last decade, although none has proven useful as a diagnostic tool. This review summarizes the advances made in the field since the publication of the first review on pituitary autoimmunity, and the challenges that await clarification. [References: 40]
RN  - 0 (Pituitary Hormones)
IS  - 1568-9972
IL  - 1568-9972
DO  - https://dx.doi.org/10.1016/j.autrev.2008.04.016
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
ID  - S1568-9972(08)00062-1 [pii]
ID  - 10.1016/j.autrev.2008.04.016 [doi]
ID  - PMC3383826 [pmc]
ID  - NIHMS72537 [mid]
PP  - ppublish
PH  - 2008/03/10 [received]
PH  - 2008/04/11 [accepted]
GI  - No: R01 DK055670
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: R21 DK080351
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: R56 DK055670
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: DK55670
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG  - English
EP  - 20080508
DP  - 2008 Sep
EZ  - 2008/09/09 09:00
DA  - 2008/12/17 09:00
DT  - 2008/09/09 09:00
YR  - 2008
ED  - 20081205
RD  - 20161019
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=18774118

<22. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 18287062
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Hodi FS
AU  - Butler M
AU  - Oble DA
AU  - Seiden MV
AU  - Haluska FG
AU  - Kruse A
AU  - Macrae S
AU  - Nelson M
AU  - Canning C
AU  - Lowy I
AU  - Korman A
AU  - Lautz D
AU  - Russell S
AU  - Jaklitsch MT
AU  - Ramaiya N
AU  - Chen TC
AU  - Neuberg D
AU  - Allison JP
AU  - Mihm MC
AU  - Dranoff G
FA  - Hodi, F Stephen
FA  - Butler, Marcus
FA  - Oble, Darryl A
FA  - Seiden, Michael V
FA  - Haluska, Frank G
FA  - Kruse, Andrea
FA  - Macrae, Suzanne
FA  - Nelson, Marybeth
FA  - Canning, Christine
FA  - Lowy, Israel
FA  - Korman, Alan
FA  - Lautz, David
FA  - Russell, Sara
FA  - Jaklitsch, Michael T
FA  - Ramaiya, Nikhil
FA  - Chen, Teresa C
FA  - Neuberg, Donna
FA  - Allison, James P
FA  - Mihm, Martin C
FA  - Dranoff, Glenn
IN  - Hodi, F Stephen. Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA. stephen_hodi@dfci.harvard.edu
TI  - Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients.
SO  - Proceedings of the National Academy of Sciences of the United States of America. 105(8):3005-10, 2008 Feb 26
AS  - Proc Natl Acad Sci U S A. 105(8):3005-10, 2008 Feb 26
NJ  - Proceedings of the National Academy of Sciences of the United States of America
VO  - 105
IP  - 8
PG  - 3005-10
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/PMC2268575
SB  - Index Medicus
CP  - United States
MH  - Antibodies, Monoclonal/ad [Administration & Dosage]
MH  - Antibodies, Monoclonal/im [Immunology]
MH  - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH  - *Antigens, CD/im [Immunology]
MH  - *Antigens, Differentiation/im [Immunology]
MH  - CTLA-4 Antigen
MH  - Carcinoma/im [Immunology]
MH  - *Carcinoma/th [Therapy]
MH  - Cohort Studies
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/me [Metabolism]
MH  - Humans
MH  - *Immunization, Passive/mt [Methods]
MH  - Ipilimumab
MH  - Melanoma/im [Immunology]
MH  - *Melanoma/th [Therapy]
MH  - Ovarian Neoplasms/im [Immunology]
MH  - *Ovarian Neoplasms/th [Therapy]
MH  - T-Lymphocytes, Regulatory/im [Immunology]
AB  - Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) functions as a negative regulator of endogenous and vaccine-induced antitumor immunity. The administration of fully human anti-CTLA-4 blocking monoclonal antibodies to advanced-cancer patients increases immune-mediated tumor destruction in some subjects. Nonetheless, patients that respond also frequently manifest serious inflammatory pathologies, raising the possibility that the therapeutic and toxic effects of CTLA-4 blockade might be linked. Here we show that periodic infusions of anti-CTLA-4 antibodies after vaccination with irradiated, autologous tumor cells engineered to secrete GM-CSF (GVAX) generate clinically meaningful antitumor immunity without grade 3 or 4 toxicity in a majority of metastatic melanoma patients. The application of this sequential immunotherapy to advanced ovarian carcinoma patients also revealed that tumor destruction and severe inflammatory pathology could be dissociated, although further refinements are required to increase clinical responses and to minimize toxicity in this population. The extent of therapy-induced tumor necrosis was linearly related to the natural logarithm of the ratio of intratumoral CD8(+) effector T cells to FoxP3(+) regulatory T cells (Tregs) in posttreatment biopsies. Together, these findings help clarify the immunologic and clinical effects of CTLA-4 antibody blockade in previously vaccinated patients and raise the possibility that selective targeting of antitumor Tregs may constitute a complementary strategy for combination therapy.
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Ipilimumab)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
ES  - 1091-6490
IL  - 0027-8424
DO  - https://dx.doi.org/10.1073/pnas.0712237105
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
ID  - 0712237105 [pii]
ID  - 10.1073/pnas.0712237105 [doi]
ID  - PMC2268575 [pmc]
PP  - ppublish
GI  - No: R01 CA111506
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: R21 CA105776
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: CA105776
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: CA111506
Organization: (CA) *NCI NIH HHS*
Country: United States
LG  - English
EP  - 20080219
DP  - 2008 Feb 26
EZ  - 2008/02/22 09:00
DA  - 2008/04/30 09:00
DT  - 2008/02/22 09:00
YR  - 2008
ED  - 20080429
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=18287062

<23. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 17982511
VI  - 1
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. 29(7):467-509, 2007 Sep
AS  - Methods Find Exp Clin Pharmacol. 29(7):467-509, 2007 Sep
NJ  - Methods and findings in experimental and clinical pharmacology
VO  - 29
IP  - 7
PG  - 467-509
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  - 12B75, 274150; Abacavir sulfate/lamivudine, Abatacept, Ad2/HIF-1alpha, Adalimumab, Adefovir, Adefovir dipivoxil, AGN-201904-Z, AIDSVAX, Albinterferon alfa-2b, Alemtuzumab, Aliskiren fumarate, Alvimopan hydrate, Amlodipine besylate/atorvastatin calcium, Amlodipine besylate/Olmesartan medoxomil, Ammonium tetrathiomolybdate, Amodiaquine, Apaziquone, Aprepitant, Arsenic trioxide, Artesunate/Amodiaquine, Ascorbic acid, Atazanavir sulfate, Atazanavir/ritonavir, Atomoxetine hydrochloride, Atrigel-Leuprolide, Axitinib; Bevacizumab, Binodenoson, Bortezomib, Bovine lactoferrin; Calcipotriol/betamethasone dipropionate, Carisbamate, Certolizumab pegol, Ciclesonide, Conivaptan hydrochloride, CP-690550, CP-751871, Cypher; Dapivirine, Darbepoetin alfa, Darunavir, Dasatinib, del-1 Genemedicine, Denosumab, Desloratadine, Dexlansoprazole, DiabeCell, Drospirenone/ethinylestradiol, DTaP-HepB-IPV, Duloxetine hydrochloride, Dutasteride; Eculizumab, Eldecalcitol, Eletriptan, Emtricitabine, Entecavir, Eritoran tetrasodium, Ertapenem sodium, Escitalopram oxalate, Eslicarbazepine acetate, Esomeprazole magnesium, Estradiol acetate, Eszopiclone, ETEC vaccine, Etoricoxib, Exenatide, Ezetimibe; Fluticasone furoate, Fosmidomycin, Fosmidomycin/clindamycin; Glutamine; Heat Shock Protein 10, Hepatitis B hyperimmunoglobulin, HIV vaccine, Hochuekki-to, Human Albumin, Human papillomavirus vaccine; Immune globulin subcutaneous [human], IMP-321, Interferon omega, ISIS-301012, Istaroxime; Japanese encephalitis virus vaccine; Latanoprost/timolol maleate, Lenalidomide, Linaclotide acetate, Lumiracoxib, LY-517717; Malaria vaccine, MAS-063D, Meningitis B vaccine, Mepolizumab, Methylnaltrexone bromide, Micafungin sodium, MK-0822A, Morphine glucuronide, Morphine hydrochloride, Mycophenolic acid sodium salt; Natalizumab, Nesiritide, Norelgestromin/ethinyl estradiol, NT-201; Oblimersen sodium, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide, Omalizumab, Otamixaban; Paclitaxel nanoparticles, Panitumumab, Panobinostat, Parathyroid hormone (human recombinant), Parecoxib sodium, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pegvisomant, PI-88, Pimecrolimus, Pneumococcal 7-valent conjugate vaccine, Pneumococcal 9-valent conjugate vaccine, Pneumococcal conjugate vaccine, Poloxamer-188, Prasugrel, Pregabalin, Prulifloxacin; R-109339, Ramipril/amlodipine, Ranolazine, Rasburicase, rHA influenza vaccine, Ro-50-3821, Rosuvastatin calcium, Rotavirus vaccine, Rotigotine, Ruboxistaurin mesilate hydrate; Satavaptan, SC-75416, Solifenacin succinate, Sorafenib, Sugammadex sodium, Sunitinib malate, Synthetic conjugated estrogens B; Tadalafil, Talnetant, Taxus, Tegaserod maleate, Telbivudine, Temsirolimus, Tenofovir disoproxil fumarate, Tetomilast, Tiotropium bromide, Tipifarnib, Tofimilast, Tremelimumab, Trimethoprim; Udenafil, Urocortin 2; Valdecoxib, Vernakalant hydrochloride; XP-828L.

Copyright (c) 2007 Prous Science. All rights reserved.
IS  - 0379-0355
IL  - 0379-0355
PT  - Journal Article
ID  - 3822 [pii]
PP  - ppublish
LG  - English
DP  - 2007 Sep
EZ  - 2007/11/06 09:00
DA  - 2008/01/25 09:00
DT  - 2007/11/06 09:00
YR  - 2007
ED  - 20080124
RD  - 20071105
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=17982511

<24. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 17611158
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Isaacs JD
FA  - Isaacs, John D
IN  - Isaacs, John D. Wilson Horne Immunotherapy Centre and Musculoskeletal Research Group, Institute of Cellular Medicine, Catherine Cookson Building, Framlington Place, Newcastle-upon-Tyne NE2 4HH, United Kingdom. j.d.isaacs@ncl.ac.uk
TI  - T cell immunomodulation--the Holy Grail of therapeutic tolerance. [Review] [48 refs]
SO  - Current Opinion in Pharmacology. 7(4):418-25, 2007 Aug
AS  - Curr Opin Pharmacol. 7(4):418-25, 2007 Aug
NJ  - Current opinion in pharmacology
VO  - 7
IP  - 4
PG  - 418-25
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Print
JC  - 100966133
IO  - Curr Opin Pharmacol
SB  - Index Medicus
CP  - England
MH  - Animals
MH  - *Antibodies, Monoclonal/ad [Administration & Dosage]
MH  - Antibodies, Monoclonal/ae [Adverse Effects]
MH  - Antigens/de [Drug Effects]
MH  - Antigens/im [Immunology]
MH  - *Autoimmune Diseases/dt [Drug Therapy]
MH  - CD3 Complex/de [Drug Effects]
MH  - CD3 Complex/im [Immunology]
MH  - Disease Models, Animal
MH  - Drug Delivery Systems
MH  - Humans
MH  - Immune Tolerance
MH  - Organ Transplantation
MH  - *T-Lymphocytes/de [Drug Effects]
MH  - T-Lymphocytes/im [Immunology]
MH  - Transplantation Immunology
AB  - The concept and practice of therapeutic tolerance has successfully been applied to animal models of autoimmunity and transplantation for more than 2 decades. Finally, there are encouraging signs of its translation to clinical practice. Short courses of anti-CD3 monoclonal antibody therapy have provided lasting benefits in recent-onset type 1 diabetes in association with evidence for the induction of immunoregulatory mechanisms. Co-stimulation blockade with abatacept (CTLA4-Ig) will soon be licensed for the treatment of rheumatoid arthritis - over the past year phase III studies have demonstrated impressive improvement in subjective and objective signs of the disease. T cell depletion is in development for several conditions, again with recent studies demonstrating evidence of immune regulation in some instances. More specific antigen-directed peptide therapies have also been applied to atopic asthma, type 1 diabetes, and adult and juvenile arthritis. The tragic sequelae of the phase I trial of TGN1412 at Northwick Park demonstrated the delicate, but unpredictable, therapeutic ratio of some T-cell-directed treatments and, in the UK, have led to new guidelines for early-phase clinical trials of immune-directed therapies. [References: 48]
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens)
RN  - 0 (CD3 Complex)
IS  - 1471-4892
IL  - 1471-4892
PT  - Journal Article
PT  - Review
ID  - S1471-4892(07)00093-8 [pii]
ID  - 10.1016/j.coph.2007.05.001 [doi]
PP  - ppublish
PH  - 2007/04/13 [received]
PH  - 2007/05/01 [accepted]
LG  - English
EP  - 20070703
DP  - 2007 Aug
EZ  - 2007/07/06 09:00
DA  - 2007/11/09 09:00
DT  - 2007/07/06 09:00
YR  - 2007
ED  - 20071108
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=17611158

<25. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 17463170
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Singh N
AU  - Chandler PR
AU  - Seki Y
AU  - Baban B
AU  - Takezaki M
AU  - Kahler DJ
AU  - Munn DH
AU  - Larsen CP
AU  - Mellor AL
AU  - Iwashima M
FA  - Singh, Nagendra
FA  - Chandler, Phillip R
FA  - Seki, Yoichi
FA  - Baban, Babak
FA  - Takezaki, Mayuko
FA  - Kahler, David J
FA  - Munn, David H
FA  - Larsen, Christian P
FA  - Mellor, Andrew L
FA  - Iwashima, Makio
IN  - Singh, Nagendra. Immunotherapy Center, Medical College of Georgia, Augusta, USA.
TI  - Role of CD28 in fatal autoimmune disorder in scurfy mice.
SO  - Blood. 110(4):1199-206, 2007 Aug 15
AS  - Blood. 110(4):1199-206, 2007 Aug 15
NJ  - Blood
VO  - 110
IP  - 4
PG  - 1199-206
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Print
JC  - a8g, 7603509
IO  - Blood
PM  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1939901
SB  - Core Clinical Journals (AIM)
SB  - Index Medicus
CP  - United States
MH  - Animals
MH  - Antigens, CD/me [Metabolism]
MH  - Antigens, Differentiation/me [Metabolism]
MH  - Autoimmune Diseases/im [Immunology]
MH  - Autoimmune Diseases/mo [Mortality]
MH  - *Autoimmune Diseases/th [Therapy]
MH  - CD28 Antigens/ge [Genetics]
MH  - *CD28 Antigens/ph [Physiology]
MH  - CD4-Positive T-Lymphocytes/me [Metabolism]
MH  - CTLA-4 Antigen
MH  - Cell Proliferation
MH  - Cytokines/me [Metabolism]
MH  - Female
MH  - *Forkhead Transcription Factors/ge [Genetics]
MH  - *Genes, Lethal
MH  - Humans
MH  - Immunoglobulin G/me [Metabolism]
MH  - Interferon-gamma/me [Metabolism]
MH  - Interleukin-10/me [Metabolism]
MH  - Interleukin-4/me [Metabolism]
MH  - Lymphoproliferative Disorders/im [Immunology]
MH  - Lymphoproliferative Disorders/mo [Mortality]
MH  - *Lymphoproliferative Disorders/th [Therapy]
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Mutant Strains
MH  - Polyendocrinopathies, Autoimmune/im [Immunology]
MH  - Polyendocrinopathies, Autoimmune/mo [Mortality]
MH  - Polyendocrinopathies, Autoimmune/th [Therapy]
MH  - T-Lymphocytes, Regulatory/im [Immunology]
AB  - Scurfy mice develop CD4 T-cell-mediated lymphoproliferative disease leading to death within 4 weeks of age. The scurfy mutation causes loss of function of the foxp3 gene (foxp3(sf)), which is essential for development and maintenance of naturally occurring regulatory CD4 T cells (nTregs). In humans, mutations of the foxp3 gene cause immune dysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome (IPEX). In most patients with IPEX and also in scurfy mice, T cells show hyperreactivity and levels of Th1- and Th2-associated cytokines are substantially elevated. We report that removal of CD28 expression rescued scurfy mice from early death. Longer-term surviving CD28-deficient scurfy mice still had lymphoproliferative disorder, but their CD4 T cells showed decreased interferon-gamma and no sign of interleukin-4 or interleukin-10 hyperproduction. Furthermore, injection of CTLA4-Ig to block CD28-B7 interactions substantially improved the survival of scurfy mice by blocking effector T-cell differentiation. These data support the hypothesis that CD28-B7 interactions play a critical role in the etiology of lethal autoimmune disease in scurfy mice by stimulating the differentiation of antigen-activated naive T cells into effector T cells.
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CD28 Antigens)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Ctla4 protein, mouse)
RN  - 0 (Cytokines)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0 (Immunoglobulin G)
RN  - 130068-27-8 (Interleukin-10)
RN  - 207137-56-2 (Interleukin-4)
RN  - 82115-62-6 (Interferon-gamma)
IS  - 0006-4971
IL  - 0006-4971
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
ID  - blood-2006-10-054585 [pii]
ID  - 10.1182/blood-2006-10-054585 [doi]
ID  - PMC1939901 [pmc]
PP  - ppublish
GI  - No: K02 AI049398
Organization: (AI) *NIAID NIH HHS*
Country: United States

GI  - No: R01 AI055022
Organization: (AI) *NIAID NIH HHS*
Country: United States

GI  - No: AI049398
Organization: (AI) *NIAID NIH HHS*
Country: United States

GI  - No: AI055022
Organization: (AI) *NIAID NIH HHS*
Country: United States
LG  - English
EP  - 20070426
DP  - 2007 Aug 15
EZ  - 2007/04/28 09:00
DA  - 2007/09/21 09:00
DT  - 2007/04/28 09:00
YR  - 2007
ED  - 20070920
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=17463170

<26. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 17409339
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Shaw SA
AU  - Camacho LH
AU  - McCutcheon IE
AU  - Waguespack SG
FA  - Shaw, Stephanie A
FA  - Camacho, Luis H
FA  - McCutcheon, Ian E
FA  - Waguespack, Steven G
IN  - Shaw, Stephanie A. FAAP, FACE, Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Boulevard, Unit 435, Houston, Texas 77030, USA.
TI  - Transient hypophysitis after cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade.
SO  - Journal of Clinical Endocrinology & Metabolism. 92(4):1201-2, 2007 Apr
AS  - J Clin Endocrinol Metab. 92(4):1201-2, 2007 Apr
NJ  - The Journal of clinical endocrinology and metabolism
VO  - 92
IP  - 4
PG  - 1201-2
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  - Adult
MH  - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH  - *Antigens, CD/im [Immunology]
MH  - *Antigens, Differentiation/im [Immunology]
MH  - CTLA-4 Antigen
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - *Pituitary Diseases/di [Diagnosis]
MH  - Pituitary Diseases/pa [Pathology]
MH  - *T-Lymphocytes, Cytotoxic/im [Immunology]
MH  - Treatment Outcome
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
IS  - 0021-972X
IL  - 0021-972X
PT  - Case Reports
PT  - Journal Article
ID  - 92/4/1201 [pii]
ID  - 10.1210/jc.2006-2484 [doi]
PP  - ppublish
LG  - English
DP  - 2007 Apr
EZ  - 2007/04/06 09:00
DA  - 2007/09/18 09:00
DT  - 2007/04/06 09:00
YR  - 2007
ED  - 20070917
RD  - 20111117
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=17409339

<27. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 17000707
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Cunninghame Graham DS
AU  - Wong AK
AU  - McHugh NJ
AU  - Whittaker JC
AU  - Vyse TJ
FA  - Cunninghame Graham, D S
FA  - Wong, A K
FA  - McHugh, N J
FA  - Whittaker, J C
FA  - Vyse, Timothy J
IN  - Cunninghame Graham, D S. Imperial College, Molecular Genetics and Rheumatology Section, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
TI  - Evidence for unique association signals in SLE at the CD28-CTLA4-ICOS locus in a family-based study.
SO  - Human Molecular Genetics. 15(21):3195-205, 2006 Nov 01
AS  - Hum Mol Genet. 15(21):3195-205, 2006 Nov 01
NJ  - Human molecular genetics
VO  - 15
IP  - 21
PG  - 3195-205
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Print
JC  - brc, 9208958
IO  - Hum. Mol. Genet.
SB  - Index Medicus
CP  - England
MH  - 3' Flanking Region
MH  - *Antigens, CD/ge [Genetics]
MH  - *Antigens, Differentiation/ge [Genetics]
MH  - Antigens, Differentiation, T-Lymphocyte/ge [Genetics]
MH  - Base Sequence
MH  - CD28 Antigens/ge [Genetics]
MH  - CTLA-4 Antigen
MH  - Chromosome Mapping
MH  - Family
MH  - Female
MH  - Gene Frequency
MH  - Genetic Markers
MH  - Haplotypes
MH  - Humans
MH  - Inducible T-Cell Co-Stimulator Protein
MH  - *Lupus Erythematosus, Systemic/ge [Genetics]
MH  - Male
MH  - Molecular Sequence Data
MH  - Multigene Family
MH  - Polymorphism, Single Nucleotide
AB  - CD28, CTLA4 (cytotoxic T lymphocyte-associated protein 4) and ICOS (inducible T cell co-stimulator) are good candidate genes for systemic lupus erythematosus (SLE) because of their role in regulating T cell activation. CTLA4 inhibits CD28-mediated T cell activation. CTLA4 is expressed on CD4+ and CD8+ activated T cells, and also B cells, but CD28 and ICOS are largely restricted to T cells. An interval encompassing the CD28-CTLA4-ICOS locus on chromosome 2q33 was linked to lupus in two genome-wide linkage scans. This large family-based association study in 532 UK SLE families represents the first high-density genetic screen of 80 SNPs at this locus. There are seven haplotype blocks across the locus. In CTLA4, the strongest signal comes from two variants, located 2.1 kb downstream from the 3'-UTR. These polymorphisms, rs231726 (SNP 43) and rs231726 (SNP 44), are in complete linkage disequilibrium (LD) (r(2)=1) and are associated with SLE P=0.0008 (GH) and P=0.01 (family-based association test). There is also a signal in the distal 3' flanking region of CTLA4/ICOS promoter (P=0.003). There was no confirmation of published associations for SLE in the promoter or coding region of CTLA4. These SLE risk alleles are more distal than those identified in Graves' disease and are in LD with Graves' disease protective alleles identified in both of these regions of CTLA4 (Ueda et al. 2003). These factors suggest an SLE-specific pattern of association. The functional consequences of the associated polymorphisms are likely to influence CTLA4 expression, although it is possible that genetically modulated ICOS expression is involved in SLE susceptibility.
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Antigens, Differentiation, T-Lymphocyte)
RN  - 0 (CD28 Antigens)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Genetic Markers)
RN  - 0 (ICOS protein, human)
RN  - 0 (Inducible T-Cell Co-Stimulator Protein)
IS  - 0964-6906
IL  - 0964-6906
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
ID  - ddl395 [pii]
ID  - 10.1093/hmg/ddl395 [doi]
PP  - ppublish
GI  - Organization: *Wellcome Trust*
Country: United Kingdom
LG  - English
EP  - 20060925
DP  - 2006 Nov 01
EZ  - 2006/09/27 09:00
DA  - 2006/12/22 09:00
DT  - 2006/09/27 09:00
YR  - 2006
ED  - 20061221
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=17000707

<28. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 16224277
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Blansfield JA
AU  - Beck KE
AU  - Tran K
AU  - Yang JC
AU  - Hughes MS
AU  - Kammula US
AU  - Royal RE
AU  - Topalian SL
AU  - Haworth LR
AU  - Levy C
AU  - Rosenberg SA
AU  - Sherry RM
FA  - Blansfield, Joseph A
FA  - Beck, Kimberly E
FA  - Tran, Khoi
FA  - Yang, James C
FA  - Hughes, Marybeth S
FA  - Kammula, Udai S
FA  - Royal, Richard E
FA  - Topalian, Suzanne L
FA  - Haworth, Leah R
FA  - Levy, Catherine
FA  - Rosenberg, Steven A
FA  - Sherry, Richard M
IN  - Blansfield, Joseph A. Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1201, USA.
TI  - Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer.
SO  - Journal of Immunotherapy. 28(6):593-8, 2005 Nov-Dec
AS  - J Immunother. 28(6):593-8, 2005 Nov-Dec
NJ  - Journal of immunotherapy (Hagerstown, Md. : 1997)
VO  - 28
IP  - 6
PG  - 593-8
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/PMC2154350
OI  - Source: NLM. NIHMS35758
SB  - Index Medicus
CP  - United States
MH  - Adult
MH  - Antibodies, Monoclonal/ad [Administration & Dosage]
MH  - *Antibodies, Monoclonal/ae [Adverse Effects]
MH  - Antigens, CD
MH  - *Antigens, Differentiation/im [Immunology]
MH  - Autoimmune Diseases/bl [Blood]
MH  - *Autoimmune Diseases/ci [Chemically Induced]
MH  - Autoimmune Diseases/pa [Pathology]
MH  - Autoimmune Diseases/th [Therapy]
MH  - CTLA-4 Antigen
MH  - Carcinoma, Renal Cell/dt [Drug Therapy]
MH  - Carcinoma, Renal Cell/sc [Secondary]
MH  - Humans
MH  - Kidney Neoplasms/dt [Drug Therapy]
MH  - Kidney Neoplasms/pa [Pathology]
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Melanoma/dt [Drug Therapy]
MH  - Melanoma/sc [Secondary]
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - *Pituitary Gland/de [Drug Effects]
MH  - Pituitary Gland/pa [Pathology]
MH  - Skin Neoplasms/dt [Drug Therapy]
MH  - Skin Neoplasms/pa [Pathology]
AB  - Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is an immunoregulatory molecule expressed by activated T cells and resting CD4CD25 T cells. In patients with advanced melanoma, our group reported that administration of anti-CTLA-4 antibody mediated objective cancer regression in 13% of patients. This study also established that the blockade of CTLA-4 was associated with grade III/IV autoimmune manifestations that included dermatitis, enterocolitis, hepatitis, uveitis, and a single case of hypophysitis. Since this initial report, 7 additional patients with anti-CTLA-4 antibody-induced autoimmune hypophysitis have been accumulated. The characteristics, clinical course, laboratory values, radiographic findings, and treatment of these 8 patients are the focus of this report.
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
IS  - 1524-9557
IL  - 1524-9557
PT  - Clinical Trial
PT  - Journal Article
ID  - 00002371-200511000-00010 [pii]
ID  - PMC2154350 [pmc]
ID  - NIHMS35758 [mid]
PP  - ppublish
GI  - No: Z01 SC003811-32
Organization: *Intramural NIH HHS*
Country: United States
LG  - English
DP  - 2005 Nov-Dec
EZ  - 2005/10/15 09:00
DA  - 2006/04/29 09:00
DT  - 2005/10/15 09:00
YR  - 2005
ED  - 20060428
RD  - 20170219
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=16224277

<29. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 16204013
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Ribas A
AU  - Camacho LH
AU  - Lopez-Berestein G
AU  - Pavlov D
AU  - Bulanhagui CA
AU  - Millham R
AU  - Comin-Anduix B
AU  - Reuben JM
AU  - Seja E
AU  - Parker CA
AU  - Sharma A
AU  - Glaspy JA
AU  - Gomez-Navarro J
FA  - Ribas, Antoni
FA  - Camacho, Luis H
FA  - Lopez-Berestein, Gabriel
FA  - Pavlov, Dmitri
FA  - Bulanhagui, Cecile A
FA  - Millham, Robert
FA  - Comin-Anduix, Begona
FA  - Reuben, James M
FA  - Seja, Elisabeth
FA  - Parker, Charla A
FA  - Sharma, Amarnath
FA  - Glaspy, John A
FA  - Gomez-Navarro, Jesus
IN  - Ribas, Antoni. Department of Medicine, Division of Hematology/Oncology Surgery, University of California at Los Angeles, CA, USA.
TI  - Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206.
CM  - Comment in: J Clin Oncol. 2005 Dec 10;23(35):8926-8; PMID: 16204008
SO  - Journal of Clinical Oncology. 23(35):8968-77, 2005 Dec 10
AS  - J Clin Oncol. 23(35):8968-77, 2005 Dec 10
NJ  - Journal of clinical oncology : official journal of the American Society of Clinical Oncology
VO  - 23
IP  - 35
PG  - 8968-77
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Print
JC  - jco, 8309333
IO  - J. Clin. Oncol.
SB  - Index Medicus
CP  - United States
MH  - Adult
MH  - Aged
MH  - Antibodies, Blocking/ae [Adverse Effects]
MH  - Antibodies, Blocking/im [Immunology]
MH  - *Antibodies, Blocking/tu [Therapeutic Use]
MH  - Antibodies, Monoclonal/im [Immunology]
MH  - Antibodies, Monoclonal/pk [Pharmacokinetics]
MH  - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH  - Antibodies, Neoplasm/im [Immunology]
MH  - *Antibodies, Neoplasm/tu [Therapeutic Use]
MH  - Antigens, CD
MH  - Antigens, Differentiation/im [Immunology]
MH  - Antigens, Neoplasm
MH  - Autoimmune Diseases/et [Etiology]
MH  - Autoimmune Diseases/im [Immunology]
MH  - Autoimmune Diseases/pa [Pathology]
MH  - CTLA-4 Antigen
MH  - Cancer Vaccines/tu [Therapeutic Use]
MH  - Colonic Neoplasms/im [Immunology]
MH  - Colonic Neoplasms/th [Therapy]
MH  - Female
MH  - Humans
MH  - Immune Tolerance/im [Immunology]
MH  - *Immunotherapy/mt [Methods]
MH  - Infusions, Intravenous
MH  - Kidney Neoplasms/im [Immunology]
MH  - Kidney Neoplasms/th [Therapy]
MH  - MART-1 Antigen
MH  - Male
MH  - Melanoma/im [Immunology]
MH  - *Melanoma/th [Therapy]
MH  - Middle Aged
MH  - Neoplasm Proteins/im [Immunology]
MH  - Neoplasms
MH  - Regression Analysis
MH  - T-Lymphocyte Subsets/im [Immunology]
MH  - Treatment Outcome
AB  - PURPOSE: Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with CP-675,206, a fully human anti-CTLA4 monoclonal antibody, may break peripheral immunologic tolerance leading to effective immune responses to cancer in humans. A phase I trial was conducted to test the safety of CP-675,206.
AB  - PATIENTS AND METHODS: Thirty-nine patients with solid malignancies (melanoma, n = 34; renal cell, n = 4; colon, n = 1) received an intravenous (IV) infusion of CP-675,206 at seven dose levels. The primary objective was to determine the maximum-tolerated dose and the recommended phase II dose.
AB  - RESULTS: Dose-limiting toxicities and autoimmune phenomena included diarrhea, dermatitis, vitiligo, panhypopituitarism and hyperthyroidism. Two patients experienced complete responses (maintained for 34+ and 25+ months), and there were two partial responses (26+ and 25+ months) among 29 patients with measurable melanoma. There have been no relapses thus far after objective response to therapy. Four other patients had stable disease at end of study evaluation (16, 7, 7, and 4 months). Additionally, five patients had extended periods without disease progression (36+, 35+, 26+, 24+, and 23+ months) after local treatment of progressive metastases. Longer systemic exposure to CP-675,206 achieved in higher dose cohorts predicted for a higher probability of response.
AB  - CONCLUSION: CP-675,206 can be administered safely to humans as a single IV dose up to 15 mg/kg, resulting in breaking of peripheral immune tolerance to self-tissues and antitumor activity in melanoma.
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Neoplasm)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Cancer Vaccines)
RN  - 0 (MART-1 Antigen)
RN  - 0 (MLANA protein, human)
RN  - 0 (Neoplasm Proteins)
IS  - 0732-183X
IL  - 0732-183X
PT  - Clinical Trial, Phase I
PT  - Journal Article
ID  - JCO.2005.01.109 [pii]
ID  - 10.1200/JCO.2005.01.109 [doi]
PP  - ppublish
LG  - English
EP  - 20051003
DP  - 2005 Dec 10
EZ  - 2005/10/06 09:00
DA  - 2006/01/13 09:00
DT  - 2005/10/06 09:00
YR  - 2005
ED  - 20060112
RD  - 20111117
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=16204013

<30. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 15981202
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Sweeney KJ
AU  - Kell MR
AU  - Ravi N
AU  - Reynolds JV
FA  - Sweeney, K J
FA  - Kell, M R
FA  - Ravi, N
FA  - Reynolds, J V
IN  - Sweeney, K J. Department of Clinical Surgery, St James's Hospital and Trinity College Dublin, Dublin 8, Ireland.
TI  - Major upper gastrointestinal surgery is associated with an antigen-dependent proinflammatory T cell response.
SO  - British Journal of Surgery. 92(8):989-95, 2005 Aug
AS  - Br J Surg. 92(8):989-95, 2005 Aug
NJ  - The British journal of surgery
VO  - 92
IP  - 8
PG  - 989-95
PI  - Journal available in: Print
PI  - Citation processed from: Print
JC  - b34, 0372553
IO  - Br J Surg
SB  - Core Clinical Journals (AIM)
SB  - Index Medicus
CP  - England
MH  - Adult
MH  - Aged
MH  - Antigens, CD/me [Metabolism]
MH  - Antigens, Differentiation, T-Lymphocyte/me [Metabolism]
MH  - Enterotoxins/pd [Pharmacology]
MH  - Esophageal Neoplasms/im [Immunology]
MH  - *Esophageal Neoplasms/su [Surgery]
MH  - Esophagectomy
MH  - Female
MH  - Humans
MH  - Interferon-gamma/me [Metabolism]
MH  - Interleukins/me [Metabolism]
MH  - Lectins, C-Type
MH  - Leukocytes, Mononuclear/im [Immunology]
MH  - Lymphocyte Activation
MH  - Male
MH  - Middle Aged
MH  - Pancreatic Neoplasms/im [Immunology]
MH  - *Pancreatic Neoplasms/su [Surgery]
MH  - Postoperative Complications/im [Immunology]
MH  - Receptors, Interleukin-2/me [Metabolism]
MH  - Receptors, Tumor Necrosis Factor/me [Metabolism]
MH  - *T-Lymphocytes/im [Immunology]
MH  - fas Receptor
AB  - BACKGROUND: T cells play a central role in the immune response to injury. Oesophageal and pancreatic resections are associated with significant risk of systemic inflammatory response syndrome and sepsis. This study involved a detailed analysis of T cell function in a consecutive cohort of patients undergoing such surgery.
AB  - METHODS: Twenty-five patients undergoing major oncological upper gastrointestinal surgery were investigated for T cell expression of Fas and the activation markers CD69 and CD25, as well as interleukin (IL) 2, IL-10 and interferon (IFN) gamma responses to stimulation with staphylococcal enterotoxin B (SEB). T cell activation in healthy volunteer peripheral blood mononuclear cells was studied in co-culture with patients' serum, either alone or with cytotoxic T lymphocyte-associated antigen (CTLA) 4, an inhibitor of antigen presentation.
AB  - RESULTS: T cells expressed significantly raised levels of CD69 and CD25 after surgery, but no change in Fas expression was evident. There was a significant increase in the production of IL-2 after surgery without a concomitant increase in IFN-gamma or IL-10 in response to SEB. Postoperative serum activated healthy volunteer T cells, a response that was inhibited (P = 0.053) by co-incubation with CTLA-4.
AB  - CONCLUSION: Major surgery results in pan-T cell activation via a serum-mediated antigenic mechanism that is independent of Fas expression. Postoperative T cells are primed for an augmented proinflammatory response to superantigen, sustained for at least 1 week, implicating the adaptive immune system in the development of the postoperative systemic immunoinflammatory state.
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, T-Lymphocyte)
RN  - 0 (CD69 antigen)
RN  - 0 (Enterotoxins)
RN  - 0 (FAS protein, human)
RN  - 0 (Interleukins)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Receptors, Interleukin-2)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (fas Receptor)
RN  - 39424-53-8 (enterotoxin B, staphylococcal)
RN  - 82115-62-6 (Interferon-gamma)
IS  - 0007-1323
IL  - 0007-1323
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
ID  - 10.1002/bjs.4844 [doi]
PP  - ppublish
LG  - English
DP  - 2005 Aug
EZ  - 2005/06/28 09:00
DA  - 2005/09/15 09:00
DT  - 2005/06/28 09:00
YR  - 2005
ED  - 20050913
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=15981202

<31. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 14751028
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Takara M
AU  - Kouki T
AU  - DeGroot LJ
FA  - Takara, Masaki
FA  - Kouki, Tsuyoshi
FA  - DeGroot, Leslie J
IN  - Takara, Masaki. Thyroid Study Unit/MC3090, Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA.
TI  - CTLA-4 AT-repeat polymorphism reduces the inhibitory function of CTLA-4 in Graves' disease.
SO  - Thyroid. 13(12):1083-9, 2003 Dec
AS  - Thyroid. 13(12):1083-9, 2003 Dec
NJ  - Thyroid : official journal of the American Thyroid Association
VO  - 13
IP  - 12
PG  - 1083-9
PI  - Journal available in: Print
PI  - Citation processed from: Print
JC  - bjw, 9104317
IO  - Thyroid
SB  - Index Medicus
CP  - United States
MH  - Adenine
MH  - Adult
MH  - Antibodies, Monoclonal/pd [Pharmacology]
MH  - Antigens, CD
MH  - *Antigens, Differentiation/ge [Genetics]
MH  - Antigens, Differentiation/im [Immunology]
MH  - *Antigens, Differentiation/me [Metabolism]
MH  - B-Lymphocytes
MH  - CTLA-4 Antigen
MH  - Case-Control Studies
MH  - Cell Division
MH  - Cell Transformation, Viral
MH  - *Graves Disease/ge [Genetics]
MH  - *Graves Disease/me [Metabolism]
MH  - Graves Disease/pa [Pathology]
MH  - Guanine
MH  - Herpesvirus 4, Human
MH  - Humans
MH  - Monocytes/pa [Pathology]
MH  - *Polymorphism, Genetic
MH  - Repetitive Sequences, Nucleic Acid
MH  - T-Lymphocytes/pa [Pathology]
MH  - Thymine
AB  - Graves' disease (GD) is thought to be an autoimmune disease with a strong genetic component. Candidate genes include human leukocyte antigen (HLA) class II genes and CTLA-4. The CTLA-4 gene has a variable length AT-repeat polymorphism in the 3'-untranslated region. We previously found that the AT-repeat of 104 bp or longer was associated with GD. In this study, we categorized patients with GD and normal controls (NC) by genotyping the CTLA-4 AT-repeat and investigated the function of CTLA-4. Peripheral blood mononuclear cells (PBMC) and DNA were prepared from adult Caucasians (NC = 34, GD = 37). Genotypes of the AT-repeat polymorphism were divided into three groups according to their alleles. We related the CTLA-4 polymorphism in each genotype to augmentation of T-cell proliferation induced by a soluble anti-CTLA-4 antibody during incubation with irradiated Epstein-Barr virus (EBV)-transformed B cells. Proliferation of T cells from subjects with the 86/86 bp (shorter) allele was less than T cells from patients with longer alleles. The length of the AT-repeat allele correlated inversely with augmentation of proliferation after CTLA-4 blockade in subjects with GD. The CTLA-4 AT-repeat polymorphism affects the inhibitory function of CTLA-4. The long AT-repeat allele is associated with reduced control of T-cell proliferation and thus contributes to the pathogenesis of GD.
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 5Z93L87A1R (Guanine)
RN  - JAC85A2161 (Adenine)
RN  - QR26YLT7LT (Thymine)
IS  - 1050-7256
IL  - 1050-7256
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
ID  - 10.1089/10507250360731479 [doi]
PP  - ppublish
GI  - No: 2-R01-DK27384-18A1
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG  - English
DP  - 2003 Dec
EZ  - 2004/01/31 05:00
DA  - 2004/08/05 05:00
DT  - 2004/01/31 05:00
YR  - 2003
ED  - 20040804
RD  - 20131121
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=14751028

<32. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 15141080
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Poirot L
AU  - Benoist C
AU  - Mathis D
FA  - Poirot, Laurent
FA  - Benoist, Christophe
FA  - Mathis, Diane
IN  - Poirot, Laurent. Section on Immunology and Immunogenetics, Joslin Diabetes Center, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
TI  - Natural killer cells distinguish innocuous and destructive forms of pancreatic islet autoimmunity.
SO  - Proceedings of the National Academy of Sciences of the United States of America. 101(21):8102-7, 2004 May 25
AS  - Proc Natl Acad Sci U S A. 101(21):8102-7, 2004 May 25
NJ  - Proceedings of the National Academy of Sciences of the United States of America
VO  - 101
IP  - 21
PG  - 8102-7
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Print
JC  - pv3, 7505876
IO  - Proc. Natl. Acad. Sci. U.S.A.
PM  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC419564
SB  - Index Medicus
CP  - United States
MH  - Animals
MH  - Autoimmune Diseases/co [Complications]
MH  - Autoimmune Diseases/ge [Genetics]
MH  - *Autoimmune Diseases/im [Immunology]
MH  - *Autoimmune Diseases/pa [Pathology]
MH  - Biomarkers/an [Analysis]
MH  - Diabetes Complications
MH  - Diabetes Mellitus/im [Immunology]
MH  - Diabetes Mellitus/pa [Pathology]
MH  - Gene Expression Profiling
MH  - Humans
MH  - Inflammation/co [Complications]
MH  - Inflammation/ge [Genetics]
MH  - Inflammation/im [Immunology]
MH  - Inflammation/pa [Pathology]
MH  - Insulin/ph [Physiology]
MH  - *Islets of Langerhans/im [Immunology]
MH  - *Islets of Langerhans/pa [Pathology]
MH  - Killer Cells, Natural/cy [Cytology]
MH  - *Killer Cells, Natural/im [Immunology]
MH  - Killer Cells, Natural/me [Metabolism]
MH  - Lymphocyte Count
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred NOD
AB  - In both human patients and murine models, the progression from insulitis to diabetes is neither immediate nor inevitable, as illustrated by the innocuous versus destructive infiltrates of BDC2.5 transgenic mice on the nonobese diabetic (NOD) versus C57BL/6.H-2g7 genetic backgrounds. Natural killer (NK)-cell-specific transcripts and the proportion of NK cells were increased in leukocytes from the aggressive BDC2.5/B6.H-2g7 lesions. NK cell participation was also enhanced in the aggressive lesions provoked by CTLA-4 blockade in BDC2.5/NOD mice. In this context, depletion of NK cells significantly inhibited diabetes development. NOD and B6.H-2g7 mice exhibit extensive variation in NK receptor expression, reminiscent of analogous human molecules. NK cells can be important players in type 1 diabetes, a role that was previously underappreciated.
RN  - 0 (Biomarkers)
RN  - 0 (Insulin)
IS  - 0027-8424
IL  - 0027-8424
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
ID  - 10.1073/pnas.0402065101 [doi]
ID  - 0402065101 [pii]
ID  - PMC419564 [pmc]
PP  - ppublish
GI  - No: P01 AI54904-01
Organization: (AI) *NIAID NIH HHS*
Country: United States

GI  - No: 2 P30 DK36836-17
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: P01 AI054904
Organization: (AI) *NIAID NIH HHS*
Country: United States

GI  - No: P30 DK036836
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: P01 AI039671
Organization: (AI) *NIAID NIH HHS*
Country: United States

GI  - No: P01 AI39671-08
Organization: (AI) *NIAID NIH HHS*
Country: United States
LG  - English
EP  - 20040512
DP  - 2004 May 25
EZ  - 2004/05/14 05:00
DA  - 2004/07/10 05:00
DT  - 2004/05/14 05:00
YR  - 2004
ED  - 20040709
RD  - 20161019
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=15141080

<33. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 14609212
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Boden E
AU  - Tang Q
AU  - Bour-Jordan H
AU  - Bluestone JA
FA  - Boden, Elisa
FA  - Tang, Qizhi
FA  - Bour-Jordan, Helene
FA  - Bluestone, Jeffrey A
IN  - Boden, Elisa. UCSF Diabetes Center, University of California, San Francisco, 513 Parnassus Avenue, Box 0540, HSW Room 1114, San Francisco, CA 94143-0540, USA.
TI  - The role of CD28 and CTLA4 in the function and homeostasis of CD4+CD25+ regulatory T cells. [Review] [29 refs]
SO  - Novartis Foundation Symposium. 252:55-63; discussion 63-6, 106-14, 2003
AS  - Novartis Found Symp. 252:55-63; discussion 63-6, 106-14, 2003
NJ  - Novartis Foundation symposium
VO  - 252
PG  - 55-63; discussion 63-6, 106-14
PI  - Journal available in: Print
PI  - Citation processed from: Print
JC  - 9807767, c3y
IO  - Novartis Found. Symp.
SB  - Index Medicus
CP  - England
MH  - Animals
MH  - Antigens, CD
MH  - Antigens, Differentiation/ge [Genetics]
MH  - *Antigens, Differentiation/im [Immunology]
MH  - *CD28 Antigens/im [Immunology]
MH  - *CD4 Antigens/im [Immunology]
MH  - CTLA-4 Antigen
MH  - Diabetes Mellitus, Type 1/ge [Genetics]
MH  - Diabetes Mellitus, Type 1/im [Immunology]
MH  - Gene Deletion
MH  - Homeostasis/im [Immunology]
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Nude
MH  - *Receptors, Interleukin-2/im [Immunology]
MH  - *T-Lymphocytes/im [Immunology]
AB  - CD4+CD25+ T cells regulate a variety of autoimmune and alloimmune responses including the development of autoimmune diabetes in non-obese diabetic (NOD) mice. We have examined the role of CD28/CTLA4/B7 interactions in the expansion and survival of CD4+CD25+ regulatory T cells (T(reg)) in this setting. CD28/ B7 interactions are essential in the development of T(reg) in the thymus and for their survival in the periphery. The CD28-mediated homeostasis of these cells is independent of Il2, OX40, CD40L, and survival factor Bcl-XI. In addition, analysis of T(reg) from CTLA4-deficient mice suggests that CTLA4 expression is not required for their development or function. However, non-activating anti-CTLA4 antibodies blocked the suppressor activity of regulatory cells in vitro. Thus, clinical application of co-stimulatory blockade using agents such as CTLA4Ig in the treatment of autoimmune disease may result in complicated outcomes. [References: 29]
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CD28 Antigens)
RN  - 0 (CD4 Antigens)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Ctla4 protein, mouse)
RN  - 0 (Receptors, Interleukin-2)
IS  - 1528-2511
IL  - 1528-2511
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PP  - ppublish
GI  - No: F32 AI 10360
Organization: (AI) *NIAID NIH HHS*
Country: United States
LG  - English
DP  - 2003
EZ  - 2003/11/12 05:00
DA  - 2004/04/09 05:00
DT  - 2003/11/12 05:00
YR  - 2003
ED  - 20040408
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=14609212

<34. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 12826605
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Phan GQ
AU  - Yang JC
AU  - Sherry RM
AU  - Hwu P
AU  - Topalian SL
AU  - Schwartzentruber DJ
AU  - Restifo NP
AU  - Haworth LR
AU  - Seipp CA
AU  - Freezer LJ
AU  - Morton KE
AU  - Mavroukakis SA
AU  - Duray PH
AU  - Steinberg SM
AU  - Allison JP
AU  - Davis TA
AU  - Rosenberg SA
FA  - Phan, Giao Q
FA  - Yang, James C
FA  - Sherry, Richard M
FA  - Hwu, Patrick
FA  - Topalian, Suzanne L
FA  - Schwartzentruber, Douglas J
FA  - Restifo, Nicholas P
FA  - Haworth, Leah R
FA  - Seipp, Claudia A
FA  - Freezer, Linda J
FA  - Morton, Kathleen E
FA  - Mavroukakis, Sharon A
FA  - Duray, Paul H
FA  - Steinberg, Seth M
FA  - Allison, James P
FA  - Davis, Thomas A
FA  - Rosenberg, Steven A
IN  - Phan, Giao Q. Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
TI  - Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma.
SO  - Proceedings of the National Academy of Sciences of the United States of America. 100(14):8372-7, 2003 Jul 08
AS  - Proc Natl Acad Sci U S A. 100(14):8372-7, 2003 Jul 08
NJ  - Proceedings of the National Academy of Sciences of the United States of America
VO  - 100
IP  - 14
PG  - 8372-7
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Print
JC  - pv3, 7505876
IO  - Proc. Natl. Acad. Sci. U.S.A.
PM  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC166236
SB  - Index Medicus
CP  - United States
MH  - Adult
MH  - Antibodies, Monoclonal/ae [Adverse Effects]
MH  - Antibodies, Monoclonal/im [Immunology]
MH  - *Antibodies, Monoclonal/tu [Therapeutic Use]
MH  - Antibodies, Neoplasm/ae [Adverse Effects]
MH  - Antibodies, Neoplasm/im [Immunology]
MH  - *Antibodies, Neoplasm/tu [Therapeutic Use]
MH  - Antigens, CD
MH  - *Antigens, Differentiation/im [Immunology]
MH  - Antigens, Differentiation/ph [Physiology]
MH  - Antigens, Neoplasm/ad [Administration & Dosage]
MH  - *Antigens, Neoplasm/im [Immunology]
MH  - *Autoimmune Diseases/et [Etiology]
MH  - Autoimmune Diseases/im [Immunology]
MH  - Autoimmune Diseases/pa [Pathology]
MH  - CTLA-4 Antigen
MH  - Colitis/et [Etiology]
MH  - Colitis/im [Immunology]
MH  - Colitis/pa [Pathology]
MH  - Dermatitis/et [Etiology]
MH  - Dermatitis/im [Immunology]
MH  - Dermatitis/pa [Pathology]
MH  - Female
MH  - HLA-A2 Antigen/im [Immunology]
MH  - Hepatitis, Autoimmune/et [Etiology]
MH  - Hepatitis, Autoimmune/im [Immunology]
MH  - Hepatitis, Autoimmune/pa [Pathology]
MH  - Humans
MH  - Immune Tolerance/im [Immunology]
MH  - *Immunotherapy
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Lymphocyte Activation
MH  - Male
MH  - Melanoma/im [Immunology]
MH  - *Melanoma/th [Therapy]
MH  - Membrane Glycoproteins/ch [Chemistry]
MH  - *Membrane Glycoproteins/im [Immunology]
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Proteins/ch [Chemistry]
MH  - *Neoplasm Proteins/im [Immunology]
MH  - Peptide Fragments/ad [Administration & Dosage]
MH  - *Peptide Fragments/im [Immunology]
MH  - Peptides
MH  - Salvage Therapy
MH  - *T-Lymphocyte Subsets/im [Immunology]
MH  - *T-Lymphocytes, Cytotoxic/im [Immunology]
MH  - *Vaccination
MH  - Vitiligo/et [Etiology]
MH  - Vitiligo/im [Immunology]
MH  - Vitiligo/pa [Pathology]
MH  - gp100 Melanoma Antigen
AB  - Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule (expressed on activated T cells and a subset of regulatory T cells) capable of down-regulating T cell activation. Blockade of CTLA-4 has been shown in animal models to improve the effectiveness of cancer immunotherapy. We thus treated 14 patients with metastatic melanoma by using serial i.v. administration of a fully human anti-CTLA-4 antibody (MDX-010) in conjunction with s.c. vaccination with two modified HLA-A*0201-restricted peptides from the gp100 melanoma-associated antigen, gp100:209-217(210M) and gp100:280-288(288V). This blockade of CTLA-4 induced grade III/IV autoimmune manifestations in six patients (43%), including dermatitis, enterocolitis, hepatitis, and hypophysitis, and mediated objective cancer regression in three patients (21%; two complete and one partial responses). This study establishes CTLA-4 as an important molecule regulating tolerance to "self" antigens in humans and suggests a role for CTLA-4 blockade in breaking tolerance to human cancer antigens for cancer immunotherapy.
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Neoplasm)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (PMEL protein, human)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (gp100 Melanoma Antigen)
RN  - 0 (gp100(280-288) melanoma antigen peptide)
IS  - 0027-8424
IL  - 0027-8424
PT  - Clinical Trial
PT  - Journal Article
ID  - 10.1073/pnas.1533209100 [doi]
ID  - 1533209100 [pii]
ID  - PMC166236 [pmc]
PP  - ppublish
GI  - No: Z01 BC010763-01
Organization: *Intramural NIH HHS*
Country: United States

GI  - No: Z99 CA999999
Organization: *Intramural NIH HHS*
Country: United States
LG  - English
EP  - 20030625
DP  - 2003 Jul 08
EZ  - 2003/06/27 05:00
DA  - 2003/09/05 05:00
DT  - 2003/06/27 05:00
YR  - 2003
ED  - 20030904
RD  - 20161025
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=12826605

<35. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 12518898
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Benda B
AU  - Ljunggren HG
AU  - Peach R
AU  - Sandberg JO
AU  - Korsgren O
FA  - Benda, Birgitta
FA  - Ljunggren, Hans-Gustaf
FA  - Peach, Robert
FA  - Sandberg, Jan-Olov
FA  - Korsgren, Olle
IN  - Benda, Birgitta. Section of Clinical Immunology, Department of Oncology, Radiology, and Clinical Immunology, The Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
TI  - Co-stimulatory molecules in islet xenotransplantation: CTLA4Ig treatment in CD40 ligand-deficient mice.
SO  - Cell Transplantation. 11(7):715-20, 2002
AS  - Cell Transplant. 11(7):715-20, 2002
NJ  - Cell transplantation
VO  - 11
IP  - 7
PG  - 715-20
PI  - Journal available in: Print
PI  - Citation processed from: Print
JC  - b02, 9208854
IO  - Cell Transplant
SB  - Index Medicus
CP  - United States
MH  - Abatacept
MH  - Animals
MH  - CD28 Antigens/de [Drug Effects]
MH  - CD28 Antigens/im [Immunology]
MH  - CD40 Antigens/de [Drug Effects]
MH  - CD40 Antigens/im [Immunology]
MH  - CD40 Ligand/ge [Genetics]
MH  - CD40 Ligand/im [Immunology]
MH  - Cells, Cultured
MH  - *Diabetes Mellitus, Type 1/th [Therapy]
MH  - Disease Models, Animal
MH  - Female
MH  - Fetus
MH  - *Graft Rejection/dt [Drug Therapy]
MH  - Graft Rejection/im [Immunology]
MH  - Graft Rejection/pc [Prevention & Control]
MH  - *Graft Survival/de [Drug Effects]
MH  - Graft Survival/im [Immunology]
MH  - Humans
MH  - Immunoconjugates/im [Immunology]
MH  - *Immunoconjugates/pd [Pharmacology]
MH  - Immunoconjugates/tu [Therapeutic Use]
MH  - Immunosuppressive Agents/im [Immunology]
MH  - *Immunosuppressive Agents/pd [Pharmacology]
MH  - Immunosuppressive Agents/tu [Therapeutic Use]
MH  - *Islets of Langerhans Transplantation/im [Immunology]
MH  - Islets of Langerhans Transplantation/mt [Methods]
MH  - Lymphocyte Activation/de [Drug Effects]
MH  - Lymphocyte Activation/im [Immunology]
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Sus scrofa
MH  - T-Lymphocytes/de [Drug Effects]
MH  - T-Lymphocytes/im [Immunology]
MH  - *Transplantation, Heterologous/im [Immunology]
MH  - Transplantation, Heterologous/mt [Methods]
AB  - Previous work has demonstrated that short-term systemic administration of cytotoxic T lymphocyte antigen-4 (CTLA-4) Ig blocks human pancreatic islet xenograft rejection in mice and induces long-term, donor-specific tolerance, whereas studies on pig pancreatic islet rejection in mice have failed to demonstrate a role for CTLA4Ig in preventing rejection. Treatment with anti-CD40 ligand (L) monoclonal antibodies alone is somewhat effective in prolonging the survival of islet xenografts, but ineffective when applied to skin xenografts. However, simultaneous blockade of the CD28 and CD40 co-stimulatory pathways prolongs the survival of pig skin on recipient mice. To evaluate the role of CD28 and CD40 co-stimulatory pathways in pig islet-like cell cluster (ICC) xenograft rejection in mice, CD40L-deficient mice transplanted with fetal porcine ICCs were given posttransplant treatment with human (h) CTLA4Ig or a human IgG1 chimeric mAb (hL6). Xenografts were evaluated 6 or 12 days after transplantation. Fetal porcine ICC xenografts were protected from rejection in hCTLA4Ig-treated CD40L-deficient mice, whereas xenograft rejection persisted in untreated CD40L-deficient mice. Simultaneous blockade of the CD28 and CD40 co-stimulatory pathways is mandatory to inhibit ICC xenograft rejection in the pig-to-mouse model, because the CD28 and CD40 co-stimulatory pathways seem capable of efficiently substituting for one another.
RN  - 0 (CD28 Antigens)
RN  - 0 (CD40 Antigens)
RN  - 0 (Immunoconjugates)
RN  - 0 (Immunosuppressive Agents)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 7D0YB67S97 (Abatacept)
IS  - 0963-6897
IL  - 0963-6897
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PP  - ppublish
LG  - English
DP  - 2002
EZ  - 2003/01/10 04:00
DA  - 2003/06/19 05:00
DT  - 2003/01/10 04:00
YR  - 2002
ED  - 20030618
RD  - 20171116
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=12518898

<36. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 12682289
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Hodi FS
AU  - Mihm MC
AU  - Soiffer RJ
AU  - Haluska FG
AU  - Butler M
AU  - Seiden MV
AU  - Davis T
AU  - Henry-Spires R
AU  - MacRae S
AU  - Willman A
AU  - Padera R
AU  - Jaklitsch MT
AU  - Shankar S
AU  - Chen TC
AU  - Korman A
AU  - Allison JP
AU  - Dranoff G
FA  - Hodi, F Stephen
FA  - Mihm, Martin C
FA  - Soiffer, Robert J
FA  - Haluska, Frank G
FA  - Butler, Marcus
FA  - Seiden, Michael V
FA  - Davis, Thomas
FA  - Henry-Spires, Rochele
FA  - MacRae, Suzanne
FA  - Willman, Ann
FA  - Padera, Robert
FA  - Jaklitsch, Michael T
FA  - Shankar, Sridhar
FA  - Chen, Teresa C
FA  - Korman, Alan
FA  - Allison, James P
FA  - Dranoff, Glenn
IN  - Hodi, F Stephen. Department of Adult Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
TI  - Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients.
SO  - Proceedings of the National Academy of Sciences of the United States of America. 100(8):4712-7, 2003 Apr 15
AS  - Proc Natl Acad Sci U S A. 100(8):4712-7, 2003 Apr 15
NJ  - Proceedings of the National Academy of Sciences of the United States of America
VO  - 100
IP  - 8
PG  - 4712-7
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Print
JC  - pv3, 7505876
IO  - Proc. Natl. Acad. Sci. U.S.A.
PM  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC153621
SB  - Index Medicus
CP  - United States
MH  - Abatacept
MH  - Adult
MH  - Aged
MH  - Animals
MH  - *Antibodies, Blocking/tu [Therapeutic Use]
MH  - Antibodies, Monoclonal/tu [Therapeutic Use]
MH  - Antigen Presentation
MH  - Antigens, CD
MH  - *Antigens, Differentiation/im [Immunology]
MH  - CD8-Positive T-Lymphocytes/im [Immunology]
MH  - CTLA-4 Antigen
MH  - *Cancer Vaccines/tu [Therapeutic Use]
MH  - Female
MH  - Humans
MH  - *Immunoconjugates
MH  - Male
MH  - *Melanoma/im [Immunology]
MH  - Melanoma/pa [Pathology]
MH  - Melanoma/sc [Secondary]
MH  - *Melanoma/th [Therapy]
MH  - Mice
MH  - Middle Aged
MH  - Necrosis
MH  - *Ovarian Neoplasms/im [Immunology]
MH  - Ovarian Neoplasms/pa [Pathology]
MH  - *Ovarian Neoplasms/th [Therapy]
AB  - A large number of cancer-associated gene products evoke immune recognition, but host reactions rarely impede disease progression. The weak immunogenicity of nascent tumors contributes to this failure in host defense. Therapeutic vaccines that enhance dendritic cell presentation of cancer antigens increase specific cellular and humoral responses, thereby effectuating tumor destruction in some cases. The attenuation of T cell activation by cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) further limits the potency of tumor immunity. In murine systems, the administration of antibodies that block CTLA-4 function inhibits the growth of moderately immunogenic tumors and, in combination with cancer vaccines, increases the rejection of poorly immunogenic tumors, albeit with a loss of tolerance to normal differentiation antigens. To gain a preliminary assessment of the biologic activity of antagonizing CTLA-4 function in humans, we infused a CTLA-4 blocking antibody (MDX-CTLA4) into nine previously immunized advanced cancer patients. MDX-CTLA4 stimulated extensive tumor necrosis with lymphocyte and granulocyte infiltrates in three of three metastatic melanoma patients and the reduction or stabilization of CA-125 levels in two of two metastatic ovarian carcinoma patients previously vaccinated with irradiated, autologous granulocyte-macrophage colony-stimulating factor-secreting tumor cells. MDX-CTLA4 did not elicit tumor necrosis in four of four metastatic melanoma patients previously immunized with defined melanosomal antigens. No serious toxicities directly attributable to the antibody were observed, although five of seven melanoma patients developed T cell reactivity to normal melanocytes. These findings suggest that CTLA-4 antibody blockade increases tumor immunity in some previously vaccinated cancer patients.
RN  - 0 (Antibodies, Blocking)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Ctla4 protein, mouse)
RN  - 0 (Immunoconjugates)
RN  - 7D0YB67S97 (Abatacept)
IS  - 0027-8424
IL  - 0027-8424
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
ID  - 10.1073/pnas.0830997100 [doi]
ID  - 0830997100 [pii]
ID  - PMC153621 [pmc]
PP  - ppublish
GI  - No: CA78880
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: R01 CA074886
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: CA39542
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: CA74886
Organization: (CA) *NCI NIH HHS*
Country: United States

GI  - No: P01 CA039542
Organization: (CA) *NCI NIH HHS*
Country: United States
LG  - English
EP  - 20030407
DP  - 2003 Apr 15
EZ  - 2003/04/17 05:00
DA  - 2003/06/18 05:00
DT  - 2003/04/17 05:00
YR  - 2003
ED  - 20030617
RD  - 20161019
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=12682289

<37. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 11086105
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - MEDLINE
AU  - Kouki T
AU  - Sawai Y
AU  - Gardine CA
AU  - Fisfalen ME
AU  - Alegre ML
AU  - DeGroot LJ
FA  - Kouki, T
FA  - Sawai, Y
FA  - Gardine, C A
FA  - Fisfalen, M E
FA  - Alegre, M L
FA  - DeGroot, L J
IN  - Kouki, T. Thyroid Study Unit, Department of Medicine, University of Chicago, Chicago, IL 60637. Fujita Health University, Aichi, Japan.
TI  - CTLA-4 gene polymorphism at position 49 in exon 1 reduces the inhibitory function of CTLA-4 and contributes to the pathogenesis of Graves' disease.
SO  - Journal of Immunology. 165(11):6606-11, 2000 Dec 01
AS  - J Immunol. 165(11):6606-11, 2000 Dec 01
NJ  - Journal of immunology (Baltimore, Md. : 1950)
VO  - 165
IP  - 11
PG  - 6606-11
PI  - Journal available in: Print
PI  - Citation processed from: Print
JC  - ifb, 2985117r
IO  - J. Immunol.
SB  - Core Clinical Journals (AIM)
SB  - Index Medicus
CP  - United States
MH  - Abatacept
MH  - Adenine
MH  - Adjuvants, Immunologic/pd [Pharmacology]
MH  - Alleles
MH  - Antibodies, Monoclonal/pd [Pharmacology]
MH  - Antigens, CD
MH  - Antigens, Differentiation/bi [Biosynthesis]
MH  - *Antigens, Differentiation/ge [Genetics]
MH  - Antigens, Differentiation/im [Immunology]
MH  - Antigens, Differentiation/ph [Physiology]
MH  - CTLA-4 Antigen
MH  - Cell Division/im [Immunology]
MH  - Cell Line
MH  - Dose-Response Relationship, Immunologic
MH  - *Down-Regulation/ge [Genetics]
MH  - *Down-Regulation/im [Immunology]
MH  - Exons/ge [Genetics]
MH  - *Exons/im [Immunology]
MH  - Graves Disease/et [Etiology]
MH  - *Graves Disease/ge [Genetics]
MH  - *Graves Disease/im [Immunology]
MH  - Guanine
MH  - *Immunoconjugates
MH  - *Immunosuppressive Agents/ai [Antagonists & Inhibitors]
MH  - Immunosuppressive Agents/im [Immunology]
MH  - Immunosuppressive Agents/pd [Pharmacology]
MH  - Intracellular Fluid/im [Immunology]
MH  - Intracellular Fluid/me [Metabolism]
MH  - Lymphocyte Activation/im [Immunology]
MH  - Lymphocyte Culture Test, Mixed
MH  - Membrane Proteins/ai [Antagonists & Inhibitors]
MH  - Membrane Proteins/bi [Biosynthesis]
MH  - *Polymorphism, Genetic/im [Immunology]
MH  - Solubility
AB  - Activation of T cells requires at least two signals transduced by the Ag-specific TCR and a costimulatory ligand such as CD28. CTLA-4, expressed on activated T cells, binds to B7 present on APCs and functions as a negative regulator of T cell activation. Our laboratory previously reported the association of Graves' disease (GD) with a specific CTLA-4 gene polymorphism. In theory, reduced expression or function of CTLA-4 might augment autoimmunity. In the present study, we categorized autoimmune thyroid disease patients and normal controls (NC) by genotyping a CTLA-4 exon 1 polymorphism and investigated the function of CTLA-4 in all subjects. PBMCs and DNA were prepared from GD (n = 45), Hashimoto's thyroiditis (HT) (n = 18), and NC (n = 43). There were more GD patients with the G/G or A/G alleles (82.2% vs 65.1% in NC), and significantly fewer patients with the A/A allele (17.8% vs 34.9% in NC). In the presence of soluble blocking anti-human CTLA-4 mAb, T cell proliferation following incubation with allogeneic EBV-transformed B cells was augmented in a dose-dependent manner. Augmentation induced by CTLA-4 mAb was similar in GD and NC (GD, HT, NC = 156%, 164%, 175%, respectively). We related CTLA-4 polymorphism to mAb augmentation of T cell proliferation in each subgroup (GD, HT, NC). Although PBMC from individuals with the G/G alleles showed 132% augmentation, those with the A/A alleles showed 193% augmentation (p = 0.019). CTLA-4 polymorphism affects the inhibitory function of CTLA-4. The G allele is associated with reduced control of T cell proliferation and thus contributes to the pathogenesis of GD and presumably of other autoimmune diseases.
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Immunoconjugates)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Membrane Proteins)
RN  - 5Z93L87A1R (Guanine)
RN  - 7D0YB67S97 (Abatacept)
RN  - JAC85A2161 (Adenine)
IS  - 0022-1767
IL  - 0022-1767
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PP  - ppublish
GI  - No: 2-RO1-DK27384-18A1
Organization: (DK) *NIDDK NIH HHS*
Country: United States

GI  - No: 5-F32-DK09612
Organization: (DK) *NIDDK NIH HHS*
Country: United States
LG  - English
DP  - 2000 Dec 01
EZ  - 2000/11/22 11:00
DA  - 2001/02/28 10:01
DT  - 2000/11/22 11:00
YR  - 2000
ED  - 20010111
RD  - 20151119
UP  - 20171128
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med4&AN=11086105

<38. >
VN  - Ovid Technologies
DB  - Ovid MEDLINE(R)
UI  - 29470611
VI  - 1
RO  - From MEDLINE, a database of the U.S. National Library of Medicine.
ST  - Publisher
AU  - Dubrovsky AM
AU  - Lim MJ
AU  - Lane NE
AI  - Lim, Mie Jin; ORCID: http://orcid.org/0000-0002-7405-8139
FA  - Dubrovsky, Alanna M
FA  - Lim, Mie Jin
FA  - Lane, Nancy E
IN  - Dubrovsky, Alanna M. Center for Musculoskeletal Health, University of California at Davis Medical Center, Sacramento, CA, 95817, USA.
IN  - Lim, Mie Jin. Center for Musculoskeletal Health, University of California at Davis Medical Center, Sacramento, CA, 95817, USA.
IN  - Lim, Mie Jin. Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, Incheon, South Korea.
IN  - Lane, Nancy E. Center for Musculoskeletal Health, University of California at Davis Medical Center, Sacramento, CA, 95817, USA. nelane@ucdavis.edu.
IN  - Lane, Nancy E. Department of Internal Medicine, University of California at Davis Medical Center, 4625 2nd Avenue, Suite 2000, Sacramento, CA, 95817, USA. nelane@ucdavis.edu.
TI  - Osteoporosis in Rheumatic Diseases: Anti-rheumatic Drugs and the Skeleton. [Review]
SO  - Calcified Tissue International.  2018 Feb 22
AS  - Calcif Tissue Int.  2018 Feb 22
NJ  - Calcified tissue international
PI  - Journal available in: Print-Electronic
PI  - Citation processed from: Internet
JC  - cgh, 7905481
IO  - Calcif. Tissue Int.
CP  - United States
KW  - Ankylosing spondylitis;  Anti-osteoporotic medication;  Anti-rheumatic drug;  Bone loss;  Osteoporosis;  Rheumatoid arthritis
AB  - Osteoporosis in rheumatic diseases is a very well-known complication. Systemic inflammation results in both generalized and localized bone loss and erosions. Recently, increased knowledge of inflammatory process in rheumatic diseases has resulted in the development of potent inhibitors of the cytokines, the biologic DMARDs. These treatments reduce systemic inflammation and have some effect on the generalized and localized bone loss. Progression of bone erosion was slowed by TNF, IL-6 and IL-1 inhibitors, a JAK inhibitor, a CTLA4 agonist, and rituximab. Effects on bone mineral density varied between the biological DMARDs. Medications that are approved for the treatment of osteoporosis have been evaluated to prevent bone loss in rheumatic disease patients, including denosumab, cathepsin K, bisphosphonates, anti-sclerostin antibodies and parathyroid hormone (hPTH 1-34), and have some efficacy in both the prevention of systemic bone loss and reducing localized bone erosions. This article reviews the effects of biologic DMARDs on bone mass and erosions in patients with rheumatic diseases and trials of anti-osteoporotic medications in animal models and patients with rheumatic diseases.
ES  - 1432-0827
IL  - 0171-967X
DO  - https://dx.doi.org/10.1007/s00223-018-0401-9
PT  - Journal Article
PT  - Review
ID  - 10.1007/s00223-018-0401-9 [doi]
ID  - 10.1007/s00223-018-0401-9 [pii]
PP  - aheadofprint
PH  - 2017/07/27 [received]
PH  - 2018/02/01 [accepted]
GI  - No: P50 AR063043
Organization: *National Institutes of Health*
LG  - English
EP  - 20180222
DP  - 2018 Feb 22
EZ  - 2018/02/23 06:00
DA  - 2018/02/23 06:00
DT  - 2018/02/23 06:00
YR  - 2018
RD  - 20180222
UP  - 20180223
XL  - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=medp&AN=29470611