Suicide gene therapy for experimental gastric cancer in dogs and rats.
| Project/Area Number |
10671224
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Nippon Medical School |
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Principal Investigator |
MATSUKURA Norio Department of Surgery I, Nippon Medical School, Associate professor, 医学部, 助教授 (70124427)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Experimental gastric cancer / Dog / Rat / Adenovirus vector / HSV-TK / Gene therapy / Adverse effect / Apoptosis / MNNG / アデノウイルスベクター / 自殺遺伝子 / ENNG / adenovirus vector / HSV-tk / 胃癌 / 肝障害 |
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| Research Abstract |
The aim of this study was to establish a practical method of gene transfer and gene therapy which would be applicable to human gastric cancer. Ad.CAG HSV-TK were transferred in situ by needle through an endoscopic biopsy channel into primary gastric cancer in 3 male beagle dogs that had been treated with ENNG followed by ganciclovir intravenously. Primary gastric cancer and the regional lymph nodes of the stomach were almost completely degenerated. Adverse effect of HSV-TK/ganciclovir gene therapy was acute hepatotoxicity, which was found after high-titer Ad.CAGHSV-TK gene followed by ganciclovir. These findings suggest that in situ gene transfer of a suicide gene followed by prodrug treatment may be applicable not only to primary tumors, but also to lymph node metastases of gastric cancer.
Next, the sequential histopathological changes after suicide gene therapy of MNNG-induced gastric cancer were examined. Gastric tumors were induced by MNNG in 38/73(52%) of Wistar rats. The suicide gene therapy group (14 rats) were subjected to in situ gene transfer with a Ad.CAG HSV-TK in gastric tumor followed by ganciclovir. Apoptosis in the gastric tumors was marked in the 8- and 30-days treatment groups compared to the sham operation controls (p<0.001). Various histopathological changes, degeneration of cancer tissue and fibrosis after necrosis and apoptosis were significantly greater in the 30-day treatment group. The HSV-TK gene was demonstrated by PCR and Southern blot analysis in peripheral blood until 30 days after gene transfer. These results may be useful in devising a method of suicide gene therapy for human.
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Report
(4 results)
Research Products
(25 results)
