Molecular biology and analysis of related genes of apoptosis in human gastric carcinomas and precancerous lesions

1. 1）正常胃粘膜中凋亡细胞极少，而在化生腺体的深部有少量凋亡细胞。对30例管状腺瘤进行凋亡细胞计数或凋亡指数（AI）测定。重度垂体腺瘤的AI高于轻度垂体腺瘤。对15例同时发现腺瘤和癌的手术切除胃标本进行了AI分析。AI前者为4.9 ± 2.1，后者为3.9 ± 1.1，差异有显著性（P<0.05）。（2）15例p53基因野生型胃癌的增殖指数（AI）为3.8 ± 1.4，15例p53基因突变型胃癌的AI为4.9 ± 1.2，后者的价值要高得多（P<0.05）。3）17例EB病毒相关性胃癌伴淋巴样间质中AI明显低于其他任何组织学类型的胃癌（P<0.05）。4）AI明显增加，与其他组织学类型的胃癌相比（P<0.05）。 ...更多信息 o术前5-FU 500 mg/d持续静脉滴注7天的10例患者为6.1 ± 3.6，未使用5-FU的10例患者为3.2 ± 1.8，差异有统计学意义（P<0.05）.体外分析1）1 mM-5 FU可诱导携带野生型p53基因的MKN-74和MKN-45细胞凋亡，而不诱导携带突变型p53基因和缺失型KATO-Ⅲ p53基因的MKN-28细胞凋亡。Westernblot分析显示MKN-74和MKN-45细胞中P53和P21蛋白表达增加。携带野生型p53基因的MKN-74和MKN-45的表达水平最高。100 ng/ml的抗Fas抗体可诱导胃癌细胞凋亡，其凋亡指数与FAS抗原表达水平相关。3）1 μ M的紫杉醇可使胃癌细胞阻滞于G2/M期，并诱导胃癌细胞凋亡。p53基因状态与胃癌细胞对紫杉醇的敏感性无关，提示多种刺激均可诱导胃癌细胞凋亡，而与凋亡相关的信号转导部分依赖于p53蛋白。少

1. in vivo analysis1) 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 … More 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 analysis1) 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