| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
1. in vivo analysis
1) Apoptotic cells were extremely rare in normal gastric mucosa, whle a few apoptotic cells were present in deeper portions of the metaplastic glands. The number of apoptotic cells or apoptotic index (AI) was counted in 30 tubular adenomas. AI was higher in the tubular adenomas with severe atypia than in those with mild atypia. AI was analyzed in 15 surgically removed stomachs in which adenoma and carcinoma were found simultaneously. AI was 4.9+2.1 in the former and 3.9+1.1 in the latter, the value being significantly different (P<0.05). On the other hand, proliferative index (PI) was higher in the carcinomas.
2) AI was 3.8+1.4 in 15 gastric cancers carrying wild type p53 and 4.9+1.2 in 15 cancers carrying mutated p53 gene, the value being significantly higher in the latter (P<0.05).
3) AI was significantly lower in 17 EB-virus related gastric carcinomas with lymphoid stroma than other any histological type of gastric carcinomas (P<0.05).
4) AI increased significantly t
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o 6.1+3.6 in 10 patients received continuous intravenous 5-FU at 500mg/day for 7 days preoperatively, compared with 10 patients without 5-FU (3.2+1.8 : P<0.05).
2. in vitro analysis
1) 1mM-5FU variably induced apoptosis in MKN-74 and MKN-45, both of which carries wild type p53 gene, but not MKN28 carrying mutated p53 gene and KATO-III p53 gene being deleted. Western blot analysis showed increasing of P53 and P21 in MKN-74 and MKN-45.
2) Fas was detected to be expressed variably in the six human gastric carcinoma cell lines. The expression level was highest for MKN-74 and MKN-45 carrying wild type p53 gene. Anti-Fas antibody of 100ng/ml induced apoptosis, the value of AI being correlated with the expression levels of FAS antigen.
3) Treatment with taxol of 1 uM arrested in G2/M,followed by apoptosis in the human gastric carcinoma cell lines. Susceptibility to taxol did not correlate with p53 gene status.
These results overall indicate that gastric cancer cells might be variably induced apoptosis by a variety of stimuli, and signal transduction relating apoptosis partly depends on the p53 protein. Less
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