Adenovirus-mediated suicide-gene therapy in an orthotopic murine bladder tumor model

Jun Cheon, Du Geon Moon, Hyun Yee Cho, Hong Seok Park, Je Jong Kim, Thomas A. Gardner, Chinghai Kao

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)

    Abstract

    Background: Patients with high-grade transitional-cell carcinoma (TCC) of the bladder frequently experience recurrence and progress and have a low response rate to chemotherapy in metastatic TCC. In this study, we evaluated the feasibility and long-term efficacy of suicide-gene therapy using adenovirus (Ad)-mediated herpes simplex virus thymidine kinase gene (HSV-TK) and prodrug ganciclovir (GCV) as a potential therapeutic approach in murine-orthotopic models of TCC. Methods: A replication defective adenoviral vectors containing toxic HSV-TK gene under the transcriptional control of RSV (Rous sarcoma virus) promoter (Ad-RSV-TK) was used. Orthotopic bladder TCC was established with 1 × 106 murine (MBT-2) TCC cells in syngenic C3H/He female mice. Intratumoral injection of Ad-RSV-TK in combination with GCV (20 mg/kg body weight/day i.p. b.i.d. × 7 days) was administered in vivo for the determination of treatment efficacy and long-term host survival in separate controlled experiments. Results: In vivo experiments demonstrated greater than three-fold reductions in MBT-2 tumor growth for the animals treated with Ad-RSV-TK (5 × 108 plaque forming units (pfu)/GCV therapy (P < 0.01)). Central tumor necrosis and apoptosis were revealed by histomorphology and immunohistochemistry compared with other control animals (non-treated, GCV alone, Ad-RSV-TK alone). Direct intratumoral injection with Ad-RSV-TK/GCV also resulted in significantly improved survival over the control groups in separated experiment (log-rank test, P < 0.05). Conclusions: Suicide-gene therapy using Ad-RSV-TK/GCV provides an effective therapy in an experimental murine orthotopic bladder cancer by significantly inhibiting tumor growth and improving long-term host survival.

    Original languageEnglish
    Pages (from-to)261-267
    Number of pages7
    JournalInternational Journal of Urology
    Volume9
    Issue number5
    DOIs
    Publication statusPublished - 2002

    Keywords

    • Adenovirus
    • Bladder neoplasm
    • Gene therapy

    ASJC Scopus subject areas

    • Urology

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