MEASUREMENT OF O6-METHYLGUANINE-DNA TRANSFERASE

亚硝脲是有效的抗肿瘤药物，尤其是在治疗脑癌方面。 然而，由于人类dna的活性，肿瘤往往具有抗药性。 修复酶O6-甲基鸟嘌呤-DNA甲基转移酶(06MT)。结果是 单项检测O6MT水平可预测化疗效果 来自肿瘤活检的细胞，而更合理的治疗方案可能是 都是设计好的。这种方法现在是可行的，因为克隆 人类O6MT基因。第一阶段的研究建议使用多克隆 检测肿瘤标本中O6MT水平的抗体和DNA探针 在第一次活组织检查和第二次手术时拍摄。这个 免疫组织化学和原位DNA探针杂交检测 并与酶活性测定结果进行了比较 O6MT。第二个目标是比较肿瘤样本的O6MT水平 有耐心的回应。患者反应的几个参数将是 收集数据，包括CAT扫描、复发时间和6个月存活期。 初治和失败患者O6MT水平的变化范围 还将对肿瘤进行比较，以确定是否有任何差异。 这将确定这些分析在临床试验中的有效性 预测耐药性和患者对治疗的反应。

Nitrosoureas are effective anti-tumor agents, especially in brain cancer. However, tumors are often resistant due to activity of the human DNA repair enzyme O6-methylguanine-DNA methyltransferase (06MT). The outcome of chemotherapy may e predicted by measuring the levels of O6MT in single cells from tumor biopsies, and a more rational treatment regime may be designed. This approach is now feasible because of the cloning of the human O6MT gene. The Phase I research proposes to use polyclonal antibodies and DNA probes to measure O6MT levels in human tumor samples taken at initial biopsy and at second-look surgery. The immunohistochemical and in situ DNA probe hybridization assay will be developed, and compared with results from the enzyme activity assay for O6MT. A second objective is to compare the O6MT levels of tumor samples with patient response. Several parameters of patient response will be collected, including CAT scan, time to relapse and six-month survival. The range of O6MT levels in initially presented and failed treatment tumors will also be compared to determine if there is any difference. This will establish the usefulness of these assays in a clinical trial to predict drug-resistance and patient response to treatment.