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 journalArticle

7 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 Jun 26

Fingerprint

Rous sarcoma virus
Ganciclovir
Urinary Bladder Neoplasms
Adenoviridae
Genetic Therapy
Suicide
Transitional Cell Carcinoma
Thymidine Kinase
Simplexvirus
Urinary Bladder
Genes
Neoplasms
Investigational Therapies
Injections
Survival
Poisons
Prodrugs
Growth
Necrosis
Immunohistochemistry

Keywords

  • Adenovirus
  • Bladder neoplasm
  • Gene therapy

ASJC Scopus subject areas

  • Urology

Cite this

Adenovirus-mediated suicide-gene therapy in an orthotopic murine bladder tumor model. / Cheon, Jun; Moon, Du Geon; Cho, Hyun Yee; Park, Hong Seok; Kim, Je-Jong; Gardner, Thomas A.; Kao, Chinghai.

In: International Journal of Urology, Vol. 9, No. 5, 26.06.2002, p. 261-267.

Research output: Contribution to journalArticle

Cheon, Jun ; Moon, Du Geon ; Cho, Hyun Yee ; Park, Hong Seok ; Kim, Je-Jong ; Gardner, Thomas A. ; Kao, Chinghai. / Adenovirus-mediated suicide-gene therapy in an orthotopic murine bladder tumor model. In: International Journal of Urology. 2002 ; Vol. 9, No. 5. pp. 261-267.
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AU - Moon, Du Geon

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AU - Gardner, Thomas A.

AU - Kao, Chinghai

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