title: Drug resistance to ganciclovir observed in suicide gene therapy is due to the loss of integrated herpes simplex virus-thymidine kinase gene.
abstract: Human pancreatic cancer cells (AsPC-1) expressing the herpes simplex virus-thymidine kinase (HSV-TK) gene were inoculated into nude mice and ganciclovir (GCV) was administrated for the treatment. At the initial course of treatment we observed a notable reduction of tumor masses. However, therapeutic effect of GCV to the recurrent tumors decreased significantly. This reduced sensitivity of the AsPC-1/HSV-TK cells to GCV was also confirmed by an in vitro test. Examination of HSV-TK gene in the drug resistant cells showed a loss of the integrated gene. These data indicate that repeated GCV administration results in the loss of integrated HSV-TK gene and confers GCV resistance.
authors.affiliation: CHIBA UNIV,SCH MED,DEPT BIOCHEM,CHUO KU,CHIBA 260,JAPAN. CHIBA UNIV,SCH MED,DEPT INTERNAL MED 1,CHUO KU,CHIBA 260,JAPAN. CHIBA CANC RES INST,DIV CHEMOTHERAPY,CHUO KU,CHIBA 260,JAPAN. CHIBA CANC RES INST,DEPT BIOCHEM,CHUO KU,CHIBA 260,JAPAN. TOKYO KASEI UNIV,FAC HOME ECON,ITABASHI KU,TOKYO 173,JAPAN.
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: M
authors.initials: M
authors.lastname: Tagawa
authors.forename: K
authors.initials: K
authors.lastname: Takenaga
authors.forename: A
authors.initials: A
authors.lastname: Nakagawara
authors.forename: K
authors.initials: K
authors.lastname: Horitsu
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: H
authors.initials: H
authors.lastname: Saisho
authors.forename: S
authors.initials: S
authors.lastname: Sakiyama