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探讨O6┐甲基鸟嘌呤┐DNA甲基转移酶(MGMT)表达与脑肿瘤对氯乙基亚硝脲(CENUs)耐药的关系。方法采用Westernblot方法检测59例不同类型脑肿瘤组织MGMT蛋白表达水平,对其中30例胶质瘤同时采用RT┐PCR检测其MGMTmRNA表达水平,MGMTmRNA表达水平与MGMT活性进行相关分析。结果MGMTmRNA表达水平与MGMT活性正相关(r=0.911,P<0.01),非胶质瘤及转移癌MGMT蛋白表达阳性率明显较胶质瘤高,分别为90%,78%,7%(P<0.05);不同个体胶质瘤MGMTmRNA表达有较大异质性,范围为0~1.29,平均为0.5±0.37,Mer-率为37%;高、低级别星形细胞瘤MGMTmRNA表达无差异(0.47±0.36和0.44±0.34);髓母细胞瘤有较高的MGMTmRNA表达水平(0.80)。结论胶质瘤MGMT总体水平较低,为此CENUs作为化疗首选药提供了新的理论依据;但半数以上胶质瘤为Mer+表型,提示对CENUs耐药,因而化疗前检测Mer表型以筛选Mer-个体进行化疗将进一步提高疗效。
To investigate the relationship between the expression of methylguanine methylguanine methyltransferase (MGMT) and the resistance of brain tumor to CENUs. Methods Western blot was used to detect the expression of MGMT protein in 59 cases of different types of brain tumors. The expression of MGMT mRNA was detected by RT PCR in 30 gliomas at the same time. The correlation between MGMT mRNA expression and MGMT activity was analyzed. Results The positive expression rate of MGMT mRNA was positively correlated with MGMT activity (r = 0.911, P <0.01). The positive rates of MGMT protein in non-glioma and metastatic MGMT were significantly higher than those in gliomas (90%, 78% 7% (P <0.05). The MGMT mRNA expression in different individual gliomas was highly heterogeneous, ranging from 0 to 1.29 with an average of 0.5 ± 0.37 and a Mer-rate of 37% (0.47 ± 0.36 and 0.44 ± 0.34) in low-grade astrocytomas, and higher MGMT mRNA expression in medulloblastoma (0.80). Conclusions The overall level of MGMT in glioma is relatively low. Therefore, CENUs provide a new theoretical basis for the chemotherapeutic drug of choice. However, more than half of the gliomas are Mer + phenotype, which suggests resistance to CENUs. Therefore, Mer phenotype was detected before screening for screening Mer - individual chemotherapy will further improve the efficacy.