| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
It is speculated that gastric cancer, especially intestinal type, cancerates through atrophic gastritis, intestinal metaplasia, or adenoma by continuation of the chronic activity gastritis by H.pylori (HP) infection. In addition, a possibility that COX-2 is involving in the tumorigenesis process is high also in the stomach, as in the colon. Then, using i) the gastric adenoma patient with HP Infection and ii) gastric epithelium cell line (MKN28) co-cultured HP infection, we investigated the influence which HP infection has on proliferation and carcinogenesis of gastric epithelium through COX. Furthermore, it aimed at exploring the possibility as chemoprevention of the gastric cancer by HP eradication treatment or NSMDs. The eradication treatment was performed to gastric adenoma patients infected with HP. 12 of 13 cases succeeded in eradication. It observes for an average of 13.1 months after eradication. In five of 12 cases (41.7%), size of the adenoma reduced, although the histological
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grade of atypia did not change. In immunohistochemistry of COX-2, the positive cells were seen focusing on the intestinal cells near the surface mucosa before eradication, and disappeared mostly after eradication. Although the positive cells of MMP-7 were seen focusing on epithelial cells of the adenoma before eradication, it decreased after eradication. Ki67 Labeling index which estimates the proliferation decreased after eradication compared with that before eradication. In MKN28, COX-2 protein was induced by HP infection (Western blot). When MKN28 was co-cultured with HP infection, IL-8 and VEGF in culture medium increased in a time-dependent manner. Furthermore, the increase was suppressed by the selective COX-1 inhibitor (SC560), the selective COX-2 inhibitor (celecoxib), or the non-selective COX inhibitor (indomethacin), respectively. HP eradication may inhibit COX-2 and MMP7 expression and VEGF and IL-8 production which have actions of proliferation and carcinogenesis. On the other hand, NSAIDs may suppress VEGF and IL-8 production who were stimulated with HP infection, through not only COX-2 but COX-1 inhibition. Eradication treatment and NSAIDs suppress carcinogenesis and proliferation of gastric epithelium, and the chemopreventive action to gastric cancer is expected. Less
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