Provocative gene therapy strategy for the treatment of hepatocellular carcinoma

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dc.contributor.author Askari, Frederick K. en_US
dc.contributor.author Wilson, James en_US
dc.date.accessioned 2006-04-28T16:55:12Z
dc.date.available 2006-04-28T16:55:12Z
dc.date.issued 1992-07 en_US
dc.identifier.citation Askari, Frederick; Wilson, James (1992)."Provocative gene therapy strategy for the treatment of hepatocellular carcinoma." Hepatology 16(1): 273-274. <http://hdl.handle.net/2027.42/38378> en_US
dc.identifier.issn 0270-9139 en_US
dc.identifier.issn 1527-3350 en_US
dc.identifier.uri http://hdl.handle.net/2027.42/38378
dc.identifier.uri http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=1319955&dopt=citation en_US
dc.description.abstract An approach involving retroviral-mediated gene therapy for the treatment of neoplastic disease is described. This therapeutic approach is called “virus-directed enzyme/prodrug therapy” (VDEPT). The VDEPT approach exploits the transcriptional differences between normal and neoplastic cells to achieve selective killing of neoplastic cells. We now describe development of the VDEPT approach for the treatment of hepatocellular carcinoma. Replication-defective, amphotrophic retroviruses were constructed containing a chimeric varicella-zoster virus thymidine kinase (VZV TK) gene that is transcriptionally regulated by either the hepatoma-associated Α-fetoprotein or liver-associated albumin transcriptional regulatory sequences. Subsequent to retroviral infection, expression of VZV TK was limited to either Α-fetoprotein or albumin-positive cells, respectively. VZV TK metabolically activated the nontoxic prodrug 6-methoxypurine arabinonucleoside (araM), ultimately leading to the formation of the cytotoxic anabolite adenine arabinonucleoside triphosphate (araATP). Cells that selectively expressed VZV TK became selectively sensitive to araM due to the VZV TK-dependent anabolism of araM to araATP. Hence, these retroviral-delivered chimeric genes generated tissue-specific expression of VZV TK, tissue-specific anabolism of araM to araATP, and tissue-specific cytotoxicity due to araM exposure. By utilizing such retroviral vectors, araM was anabolized to araATP in hepatoma cells, producing a selective cytotoxic effect. en_US
dc.format.extent 267822 bytes
dc.format.extent 3118 bytes
dc.format.mimetype application/pdf
dc.format.mimetype text/plain
dc.language.iso en_US
dc.publisher W.B. Saunders en_US
dc.publisher Wiley Periodiocals, Inc. en_US
dc.subject.other Life and Medical Sciences en_US
dc.subject.other Hepatology en_US
dc.title Provocative gene therapy strategy for the treatment of hepatocellular carcinoma en_US
dc.rights.robots IndexNoFollow en_US
dc.subject.hlbsecondlevel Internal Medicine and Specialties en_US
dc.subject.hlbtoplevel Health Sciences en_US
dc.description.peerreviewed Peer Reviewed en_US
dc.contributor.affiliationum Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan, Medical Center Ann Arbor, Michigan 48105 en_US
dc.contributor.affiliationum Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan, Medical Center Ann Arbor, Michigan 48105 en_US
dc.identifier.pmid 1319955 en_US
dc.description.bitstreamurl http://deepblue.lib.umich.edu/bitstream/2027.42/38378/1/1840160141_ftp.pdf en_US
dc.identifier.doi http://dx.doi.org/10.1002/hep.1840160141 en_US
dc.identifier.source Hepatology en_US
dc.owningcollname Interdisciplinary and Peer-Reviewed
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