Provocative gene therapy strategy for the treatment of hepatocellular carcinoma
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 | https://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.type | Article | 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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