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

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 07557364
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 展開研究
• Research Field: Urology
• Research Institution: Nippon 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)
• Project Period (FY): 1995 – 1997
• Keywords: Gene Therapy / Adenoviral vector / Bladder tumor / HSV-tk / Ganciclovir / Glycosaminoglican

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.