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Provocative gene therapy strategy for the treatment of hepatocellular carcinoma

dc.contributor.authorAskari, Frederick K.en_US
dc.contributor.authorWilson, Jamesen_US
dc.date.accessioned2006-04-28T16:55:12Z
dc.date.available2006-04-28T16:55:12Z
dc.date.issued1992-07en_US
dc.identifier.citationAskari, 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.issn0270-9139en_US
dc.identifier.issn1527-3350en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/38378
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=1319955&dopt=citationen_US
dc.description.abstractAn 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.extent267822 bytes
dc.format.extent3118 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.language.isoen_US
dc.publisherW.B. Saundersen_US
dc.publisherWiley Periodiocals, Inc.en_US
dc.subject.otherLife and Medical Sciencesen_US
dc.subject.otherHepatologyen_US
dc.titleProvocative gene therapy strategy for the treatment of hepatocellular carcinomaen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelInternal Medicine and Specialtiesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDivision of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan, Medical Center Ann Arbor, Michigan 48105en_US
dc.contributor.affiliationumDivision of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan, Medical Center Ann Arbor, Michigan 48105en_US
dc.identifier.pmid1319955en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/38378/1/1840160141_ftp.pdfen_US
dc.identifier.doihttp://dx.doi.org/10.1002/hep.1840160141en_US
dc.identifier.sourceHepatologyen_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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