Effects of neoadjuvant chemotherapy on chemo sensitivity, gene alteration, and apoptosis in gastrointestinal carcinoma

应用胶原凝胶液滴包埋培养法检测40例大肠癌和胃癌对5-氟尿嘧啶（5-FU ra）、丝裂霉素C（MMC）和顺铂（CDDP）的药物敏感性，并探讨p53蛋白表达与p53基因突变的关系。通过T/C比（胶原凝胶中药物暴露后的细胞数与对照组的细胞数之比）评价5-FUra的化学敏感性。采用免疫组化方法检测p53蛋白表达，PCR-SSCP方法检测p53基因第5 ~ 8外显子突变。p53基因突变阳性的病例定义为这些外显子中至少有一个基因突变的病例。p53蛋白阳性组T/C比值为89.1 ± 10.6%，显著高于p53蛋白阴性组的71.3 ± 13.7%，P=0.0261。p53基因突变阳性病例的T/C比值为89.9 ± 8.4%，也显著高于 ...更多信息 p53基因突变阴性者为73.6 ± 15.9%，P=0.0330。p53蛋白阳性和p53基因突变阳性者的T/C比值为93.1 ± 7.0%，显著高于正常对照组（75.5 ± 13.4%，p=0.0147）。而p53蛋白阴性和p53突变阴性者T/C为62.5± 15.6%，明显低于正常对照组。当同时评估p53蛋白表达和基因突变时，对5-FUra的化疗敏感性的预测性最高。p53蛋白阳性和/或p53突变阳性的病例MMC和顺铂的T/C比值均高于阴性病例，但差异无统计学意义。这些结果表明，胃肠道肿瘤对5-FUra的化疗敏感性可以很容易地通过该试验进行评估，并通过检测p53蛋白表达和p53基因突变进行预测。p53状态提供了一个有用的辅助，以确定是否静脉内和/或口服氟嘧啶应作为辅助化疗手术后立即应用。少

Chemosensitivities against 5-fluorouracil (5-FUra), mitomycin C (MMC) and cisplatin (CDDP) were examined using a newly developed collagen-gel droplet embedded culture method (presented in ASCO 2000) in 40 cases with colorectal and stomach cancers and evaluated the relationship between the expression p53 protein and p53 gene mutation. Chemosensitivity of 5-FUra was evaluated by the T/C ratio (the ratio of the cell number after drug exposure in the collagen gels to those of control). Expression of p53 protein was evaluated immunohistochemically and p53 gene mutations in exon 5 through 8 were examined by a PCR-SSCP method. Cases of positive p53 mutation were defined as the cases with at least one gene mutation in these exons examined. T/C ratio of p53 protein positive cases was 89.1+/-10.6%, which was significantly higher than that of p53 protein negative cases (71.3+/-13.7%, P=0.0261). T/C ratio of positive p53 gene mutation cases was 89.9+/-8.4%, which was also significantly higher than … More that of negative p53 gene mutation cases (73.6+/-15.9%, P=0.0330). T/C ratio of cases with positive p53 protein and positive p53 mutation was 93.1+/-7.0%, which was significantly higher that of the remainders (75.5+/-13.4%, p=0.0147). Conversely, T/C ratio of cases with negative p53 protein and negative p53 mutation was 62.5±15.6%, which was significantly lower than that of the remainders. The predictability of the chemosensitivity against 5-FUra was the highest when evaluating the expression of p53 protein and gene mutation, simultaneously. T/C ratios of MMC and cisplatin of cases with p53 protein positive and/or positive p53 mutation were uniformly higher than those of negative cases, but the difference was not statistically significant. These results suggest that chemosensitivity of gastrointestinal cancers against 5-FUra could easily be evaluated by this test and was predictable by examining the expression of p53 protein and p53 gene mutation. p53 status provides a useful adjunct to determine whether intravenous and/or oral fluoropyrimidine should be applied as an adjuvant chemotherapy immediately after surgery. Less