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Induction of sensitivity to ganciclovir in human hepatocellular carcinoma cells by adenovirus-mediated gene transfer of herpes simplex virus thymidine kinase. 1995

C Qian, and R Bilbao, and O Bruña, and J Prieto
Department of Internal Medicine, School of Medicine, University of Navarra, Pamplona, Spain.

We have analyzed the ability of a recombinant replication-defective adenovirus to transfer the thymidine kinase gene of herpes simplex virus (HSV-tk) into hepatocellular carcinoma (HCC) cells to confer sensitivity to ganciclovir. Three HCC cell lines (Hep3B, PLC/PRF/5, and HepG2) were efficiently infected in vitro by a recombinant adenovirus carrying lacZ reporter gene (AdCMVlacZ). Expression of HSV-tk in HCC cells infected with a recombinant adenovirus carrying HSV-tk gene (AdCMVtk) induced sensitivity to ganciclovir in a dose-dependent manner. A bystander killing effect was observed when 90% of uninfected tumor cells were mixed with only 10% of AdCMVtk-infected cells. These data show that recombinant adenoviruses are efficient vectors for transduction of drug-sensitizing genes to HCC cells in vitro. We suggest that a gene therapy approach to hepatocellular carcinoma can be established using adenoviral transfer of HSV-tk to tumor cells and subsequent administration of ganciclovir.

UI MeSH Term Description Entries
D008113 Liver Neoplasms Tumors or cancer of the LIVER. Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D006528 Carcinoma, Hepatocellular A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested. Hepatocellular Carcinoma,Hepatoma,Liver Cancer, Adult,Liver Cell Carcinoma,Liver Cell Carcinoma, Adult,Adult Liver Cancer,Adult Liver Cancers,Cancer, Adult Liver,Cancers, Adult Liver,Carcinoma, Liver Cell,Carcinomas, Hepatocellular,Carcinomas, Liver Cell,Cell Carcinoma, Liver,Cell Carcinomas, Liver,Hepatocellular Carcinomas,Hepatomas,Liver Cancers, Adult,Liver Cell Carcinomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000256 Adenoviridae A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases. Adenoviruses,Ichtadenovirus,Adenovirus,Ichtadenoviruses
D013937 Thymidine Kinase An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. Deoxythymidine Kinase,Deoxypyrimidine Kinase,Kinase, Deoxypyrimidine,Kinase, Deoxythymidine,Kinase, Thymidine
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015774 Ganciclovir An ACYCLOVIR analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. BIOLF-62,BW-759,Cytovene,Ganciclovir Sodium,Ganciclovir, Monosodium Salt,Gancyclovir,RS-21592
D018014 Gene Transfer Techniques The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms. Gene Delivery Systems,Gene Transfer Technique,Transgenesis,Delivery System, Gene,Delivery Systems, Gene,Gene Delivery System,Technique, Gene Transfer,Techniques, Gene Transfer,Transfer Technique, Gene,Transfer Techniques, Gene
D018139 Simplexvirus A genus of the family HERPESVIRIDAE, subfamily ALPHAHERPESVIRINAE, consisting of herpes simplex-like viruses. The type species is HERPESVIRUS 1, HUMAN. Herpes Simplex Virus,Herpesvirus 1, Saimiriine,Herpesvirus 1, Saimirine,Herpesvirus 16, Cercopithecine,Marmoset Virus,Cercopithecine Herpesvirus 16,Herpes Labialis Virus,Herpes-T Virus,Herpesvirus 1 (alpha), Saimirine,Herpesvirus Hominis,Herpesvirus Papio 2,Herpesvirus Platyrhinae,Marmoset Herpesvirus,Saimiriine Herpesvirus 1,Herpes Labialis Viruses,Herpes Simplex Viruses,Herpes T Virus,Herpes-T Viruses,Herpesvirus Homini,Herpesvirus, Marmoset,Herpesviruses, Marmoset,Homini, Herpesvirus,Hominis, Herpesvirus,Labialis Virus, Herpes,Labialis Viruses, Herpes,Marmoset Herpesviruses,Marmoset Viruses,Platyrhinae, Herpesvirus,Saimirine Herpesvirus 1,Simplexviruses,Virus, Herpes Labialis,Viruses, Herpes Labialis

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