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Gene Therapy for Bladder Tumor using HSV-tk/GCV System

Research Project

Project/Area Number 07557364
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Urology
Research InstitutionNippon Medical School

Principal Investigator

AKIMOTO Masao  Nippon Medical School, Dept of Urology, Professor., 医学部, 教授 (50089752)

Co-Investigator(Kenkyū-buntansha) SUZUKI Satoru  Nippon Medical School, Dept of Biochemi.2 Instructor, 医学部, 助手 (70246940)
TERASHIMA Yasunori  Nippon Medical School, Dept of Urology, Assistant Professor, 医学部, 講師 (80207480)
SHIMADA Takashi  Nippon Medical School, Dept of Biochemi.2 Professor, 医学部, 教授 (20125074)
清水 宏之  日本医科大学, 医学部, 助手 (80271344)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1996: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsGene Therapy / Adenoviral vector / Bladder tumor / HSV-tk / Ganciclovir / Glycosaminoglican / 膀胱癌 / アデノウィルスベクター / 自殺遺伝子 / GCV
Research Abstract

Cancer gene therapy is extensively studied in both basic and clinical field. We examined efficacy of adenoviral gene therapy using BBN induced rat bladder tumor. Instillation of adenoviral vector carrying lacZ gene to rat bladder showed preferential gene transfer to tumor. Normal bladder showed only small blue spots after X-gal staining. Diffuse and strong blue staining was observed in bladder tumor. We speculated glycosaminoglycan (GAG) might respond to this preferential gene transfer. To remove GAG on bladder mucosa, we wash bladder with Hcl. Then we instilled adeno viral vector (Ad. CAG.lacZ). After washing bladder with HCl, normal bladder was stained blue strongly like as tumor. Alsian blue staining which could detect GAG revealed rack of GAG on both tumor and HCl washed normal bladder surface. These data indicated that rack of GAG on tumor surface induced preferential gene transfer by instillation of adenoviral vector.
We next induced HSV-tk gene to bladder tumor using same method. Sequential treatment with ganciclovir caused marked size reduction of tumor compare to control group. BBN induced rat bladder tumor is very resemble to human superficial bladder tumor. Our experiments showed preferential in vivo gene transfer simple instillation of adenoviral vector. HSV-tk/GCV experiments showed marked anti tumor effect due to growth inhibition or size reduction of tumors. These data were very important to human clinical trial.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (1 results)

All Other

All Publications (1 results)

  • [Publications] Yamamoto,S.,Suzuki,S.et al.: "HSV-TK/GCV mediated killing of tumor cells induces tumor-specific cytotxic T cells in mice." Cancer Gene Therapy. Vol.4 No.1 (in press). (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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