| Project/Area Number |
12557050
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Gastroenterology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
SUGIYAMA Toshiro Hokkaido University Graduate School of Medicine, Associate Prof., 大学院・医学研究科, 助教授 (00196768)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAYAMA Fumihiro Institute of Yoshitomi Pharmaceutical Co., Investigator, 開発研究所, 主任研究員
ASAKA Masahiro Hokkaido University Graduate School of Medicine, Prof., 大学院・医学研究科, 教授 (10113507)
穂刈 格 北海道大学, 医学部・附属病院, 助手 (70301885)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2000: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Keywords | HELICOBACTER PYLORI / CATALASE / VACCINATION / GASTRIC CANCER / H.Pylori |
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| Research Abstract |
IARC/WHO concluded in 1994 that H. pylori infection had a causal link to gastric carcinogenesis and is a definite carcinogen in humans. The aim of this study is to investigate the experimental basis on vaccination by H. pylori catalase as immunogen for the prevention of gastric cancer related with H. pylori infection. Mongolian gerbil (MG) models have been established to develop gastric cancer after inoculation of H. pylori and/or administration of chemical carcinogens. Using this animal model, we tested the inhibitory effect of development of gastric cancer by vaccination of H. pylori catalase. The 5-week MGs were immunized by administration of H. pylori recombinant catalase and then were inoculated with H. pylori TN2GF4 strain following with administration of 10 ppm methylnitrosourea(MNU). Antibody response of serum lgG as well as gastric lgA against catalase was confirmed by ELISA. MGs immunized with H. pylori recombinant catalase did not show the development of gastric cancer in 72 week MGs (0% : 0/10 MGs). Comparing 4 experimental groups (vaccination alone, 10 ppm MNU alone, vaccination plus 10 ppm MNU and control), the administration of H. pylori catalase had inhibited the occurrence of gastric cancer via low colonization of H. pylori in the stomach. To confirm the inhibitory effect of vaccination by H. pylori catalase, isogenic mutant strain of H. pylori catalase gene was constructed and inoculated into MGs. Isogenic mutant strain was not able to colonize in the stomach after inoculation. Therefore, H. pylori catalase is essential for colonization of H. pylori and immune response to H. pylori catalase results in the inhibition of occurrence of gastric cancer induced with H. pylori infection in MGs. These results suggest that vaccination by H. pylori catalase is promising for the prevention of gastric cancer related with H. pylori infection.
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