| Project/Area Number |
14370181
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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 | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
SHINOMURA Yasuhisa Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90162619)
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| Co-Investigator(Kenkyū-buntansha) |
KIYOHARA Tatsuya Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (50322178)
FUJIMOTO Takashi Osaka University, Medical School, Medical Staff, 医学部附属病院, 医員(臨床研究)
村山 洋子 大阪大学, 医学系研究科, 助手
宮崎 義司 大阪大学, 医学系研究科, 助手 (30303960)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2004: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | gastric cancer / Helicobacter pylori / gastrin / IL-1 / HB-EGF / gastritis / CD9 / NF-κB / p38-MAPK / メチル化 / PKC |
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| Research Abstract |
We have reported that hypergastrinemia and increased IL-1beta production may contribute to foveolar hyperplasia in Helicobacter pylori-associated enlarged fold gastritis and that gastrin induces heparin binding epidermal growth factor-like growth factor(HB-EGF) and amphiregulin production in the gastric mucosa. The purpose of the present study was to clarify the roles of proinflammatory cytokines and growth factors in gastric carcinogenesis. Gastrin induced IL-8 expression through activation of nuclear factor kappaB in cooperation with IL-1beta. Increased 8-hydroxydeoxyguanosine production and hypermethylation in the region of promoter of tumor suppressor genes were observed in the gastric mucosa of patients with enlarged fold gastritis. HB-EGF expression was associated with CD9 expression in gastric cancer. Anti-CD9 antibody inhibited cell proliferation and induced apoptosis in gastric cancer cells through tyrosine phosphorylation of the p46 Shc isoform. Gastrin and proinflammatory cytokines and growth factors were shown to be involved in gastric carcinogenessis.
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