title: Adenovirus-mediated thymidine kinase gene transduction in human epithelial ovarian cancer cell lines followed by exposure to ganciclovir.
abstract: In an effort to develop gene therapy for ovarian cancer efficacy and toxicity of adenovirus-mediated transfer of the HSV-TK gene followed by administration of ganciclovir were studied in two human epithelial ovarian cancer cell lines Ov-ca-2774 and Ov-ca-1225. 100% transduction was achieved in both cell lines at MOIs of 7 and 15 as demonstrated by X-Gal staining. No toxicity of virus alone was observed at MOIs up to 30. GCV was not toxic up to 200 micrograms/ml. Cell killing efficacy was shown to be dependent on MOI as well as GCV dose. The "bystander effect" of ADV/RSV-TK was quantified by mixing experiments and found to be dependent on the proportion of ADV/RSV-TK positive cells as well as the GCV dosage. Similar results were observed in both cell lines. ADV/RSV-TK mediated gene therapy may be a promising approach in ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: X W
authors.initials: XW
authors.lastname: Tong
authors.forename: A
authors.initials: A
authors.lastname: Block
authors.forename: S H
authors.initials: SH
authors.lastname: Chen
authors.forename: S L
authors.initials: SL
authors.lastname: Woo
authors.forename: D G
authors.initials: DG
authors.lastname: Kieback
mesh_terms: D000256:Adenoviridae; D000963:Antimetabolites / Q000633:toxicity*; D000998:Antiviral Agents / Q000633:toxicity*; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D015774:Ganciclovir / Q000633:toxicity*; D006801:Humans; D010051:Ovarian Neoplasms; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D018139:Simplexvirus / Q000201:enzymology* / Q000235:genetics; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
chemical_list: D000963:Antimetabolites; D000998:Antiviral Agents; D011994:Recombinant Proteins; D013937:Thymidine Kinase; D015774:Ganciclovir