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Basic Research for Development of Vaccination for Gastric Cancer Prevention by Catalase of Helicobacter pylori

Research Project

Project/Area Number 12557050
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Gastroenterology
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

SUGIYAMA Toshiro  Hokkaido University Graduate School of Medicine, Associate Prof., 大学院・医学研究科, 助教授 (00196768)

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)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
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)
KeywordsHELICOBACTER PYLORI / CATALASE / VACCINATION / GASTRIC CANCER / H.Pylori
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.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Nagasako T, Sugiyama T et al.: "Up-regulated Smad5 mediates apoptosis of gastric epithelial cells induced by H.pylori infection"J Biol Chem. 278. 4821-4825 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizushima T, Sugiyama T et al.: "Decreased adherence of cagG deleted Helicobacter pylori to gastric epithelial cells in Japanese clinical isolates"Helicobacter. 7. 22-29 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashi H, Sugiyama T, et al.: "SHP-2 tyrosine phosphatase as an intracellular target of H.pylori CagA protein"Science. 295. 683-686 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama T et al.: "Development of H.pylori-infected animal model and gastric cancer : recent progress and issues"J Gastroenterology. 37. 6-9 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama T et al.: "Sensitivity of biopsy site in evaluating regression of gastric atrophy after Helicobacter pylori eradication treatment"Aliment Pharmacol Ther. 16. 187-190 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama T et al.: "Attributable risk of H.pylori in peptic ulcer disease : Does the declining prevalence of infection in general population explain the increasing frequency of non-H.pylori ulcer?"Dig Dis Sci. 46. 307-310 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagasako T, Sugiyama T, Mizushima T, Miura Y, Asaka M: "Upregulated Smad 5 mediates apoptosis of gastric epithelial cells induced by H. pylori infection"J Biol Chem. 278. 4821-4825 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizushima T, Sugiyama T, Kobayashi T, Komatsu Y, Asaka M: "Decreased adherence of cagG deleted Helicobacter pylori to gastric epithelial cells in Japanese clinical isolates"Helicobacter. 7. 22-29 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashi H, Tsutsumi R, Muto S, Sugiyama T, Azuma T, Asaka M, Hatakeyama M: "SHP-2 tyrosine phosphatase as an intracellular target of H. pylori CagA protein"Science. 295. 683-686 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama T, Hige S, Asaka M: "Development of H. pylori-infected animal model and gastric cancer : recent progress and issues"J Gastroenterology. 37. 6-9 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama T, Sakaki N, Kozawa H, Sato K, Sugano K, et al.: "Sensitivity of biopsy site in evaluating regression of gastric atrophy after Helicobacter pylori eradication treatment"Aliment Pharmacol Ther. 16. 187-190 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama T, Nishikawa K, Asaka M, Freston J.: "Attributable risk of H. pylori in peptic ulcer diseases : Does the declining prevalence of infection in general population explain the increasing frequency of non-H. pylori ulcer?"Dig Dis Sci. 46. 307-310 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagasako T, Sugiyama T et al.: "Up-regulated Smad5 mediates apoptosis of gastric epithelial cells induced by H.pylori infection"J Biol. 278. 4821-4825 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mizushima T, Sugiyama T et al.: "Decreased adherence of cagG deleted Helicobacter pylori to gastric epithelial cells in Japanese clinical isolates"Helicobacter. 7. 22-29 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Higashi H, Sugiyama T, et al.: "SHP-2 tyrosine phosphatase as an intracellular target of H.pylori CagA protein"Science. 295. 683-686 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugiyama T et al.: "Development of H.pylori-infected animal model and gastric cancer : recent progress and issues"J Gastroenterology. 37. 6-9 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugiyama T et al.: "Sensitivity of biopsy site in evaluating regression of gastric atrophy after Helicobacter pylori eradication treatment"Aliment Pharmacol Ther. 16. 187-190 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kaminishi M, Sugiyama T et al.: "Endoscopic classification of chronic gastritis based on a pilot study by the research society for gastritis"Digestive Endoscopy. 14. 138-151 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Higashi H, Sugiyama T, et al.: "SHP-2 tyrosine phosphatase as an intracellular target of H.pylori CagA protein"Science. 295. 683-686 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mizushima T, Sugiyama T. et al.: "Decreased adherence of cagG deleted Helicobacter pylori to gastric epithelial cells in Japanese clinical isolates"Helicobacter. 7(in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mizushima T, Sugiyama T. et al.: "Clinical relevance of the babA2 genotype of Helicobacter pylori in Japanese clinical isolates"J Clin Microbil. 39. 2463-2465 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugiyama T. et al.: "Attributable risk of H.pylori in peptic ulcer diseases : Does the declining prevalence of infection in general population explain the increasing frequency of non-H.pylori ulcer?"Dig Dis Sci. 46. 307-310 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugiyama T. et al.: "API2-MALT1 chimeric transcript is a predictive marker for the responsiveness of H.pylori eradication treatment in low-grade gastric MALT lymphoma"Gastroenterology. 120. 1884-1885 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawahara T, Sugiyama T et al.: "Type I Helicobacter pylori lipopolysaccharides stimulates Toll-like receptor 4 and activates mitogen oxidase 1 in gastric pit cells"Infect Immune. 69. 4382-4389 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugiyama T.et al: "The attributable risk of H. pylori in peptic…"Dig Dis Sci. 45(12)in press. (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sugiyama T.et al: "Direct evidence by DNA fingerprinting…"J.Clin Microbiol. 38. 2381 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hayashi S, Sugiyama T.: "Combined effect of rebamipide and…"Microbiol Immunol. 44. 557 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kato S, Sugiyama T.: "CagA antibody in Japanese children…"J.Clin Microbiol. 38. 68 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nishikawa K, Sugiyama T: "A prospective evaluation of new rapid…"Gastrointestinal Endoscopy. 50. 164 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nishikawa K, Sugiyama T: "Non-H.pylori and non-NSAIDS peptic ulcer…"Eur J Gastroenterol Hepatol. 12. 635 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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