| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2004: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
The aims of this study are to investigate the relationship between gastric carcinogenesis by duodenogastric reflux and cyclooxygenase 2 (COX-2) expression, and to disclose the chemopreventive effect of a specific COX-2 inhibitor, meloxicam (MLX) to the development of gastric cancer. The rats surgically undergoing duodenogastric reflux were allocated to two groups, given commercial chow (Control group) and experimental chow containing MLX (0.5 mg/Kg body weight/day) (MLX group). The animals were sacrificed postoperatively at 20, 30, 40, 50, and 60 weeks. The incidence of gastritis cystica profunda (GCP), precancerous lesion, in the MLX group was significantly lower after the 30th weak than in the control group (32% vs 100%). The incidences of adenoma and adenocarcinoma in the MLX group were also significantly lower than in the control group (0% vs 52%, in adenoma, 0% vs 29%, in adenocarcinoma). The Ki-67 labeling index in the MLX group was significantly higher than in the control group through the whole experimental period. The COX-2 expression was immunohistochemically observed not only in the epithelium of GCP, adenoma and adenocarcinoma, but also in the stroma. The COX-2 mRNA expression did not differ between two groups but the level of PGE2 product in the MLX group was higher than in the control group. These results indicate that a specific COX-2 inhibitor, meloxicam, suppresses the development of GCP, adenoma and adenocarcinoma in the rodent model of gastric carcinogenesis by duodenogastric reflux, suspecting that the drug, which suppresses PGE2 production by COX-2 inhibition, prevents gastric carcinogenesis by reducing epithelial proliferation.
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