MEASUREMENT OF O6-METHYLGUANINE-DNA TRANSFERASE

亚硝基脲是一种有效的抗肿瘤药物，特别是在脑癌中。 然而，由于人类DNA的活性， 修复酶O 6-甲基鸟嘌呤-DNA甲基转移酶（06 MT）。 成果 通过检测化疗前、化疗后1、2、3、4、6、7、8、12、14、18、19、20、21、22、24、25、26、28、29、2 从肿瘤活检细胞，和一个更合理的治疗方案， 设计了 这种方法现在是可行的，因为克隆了 人O 6 MT基因。 I期研究建议使用多克隆 抗体和DNA探针来测量人类肿瘤样本中的O 6 MT水平 在初次活检和二次手术时进行。 的 免疫组织化学和原位DNA探针杂交分析将 开发，并与酶活性测定的结果进行比较， O6MT。 第二个目的是比较肿瘤样本的O 6 MT水平 病人的反应。 患者反应的几个参数将 包括CAT扫描，复发时间和六个月生存率。 O 6 MT水平的范围在最初提出和失败的治疗 还将比较肿瘤以确定是否存在任何差异。 这将确定这些测定在临床试验中的有用性， 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.