ALKYLTRANSFERASE IN METASTATIC MALIGNANT MELANOMA

这项研究的目的是测量DNA修复蛋白06- 转移性恶性肿瘤活检中的烷基鸟嘌呤-DNA烷基转移酶 黑色素瘤，并将这些水平与患者对 用烷基化氮源处理。 这些药物，如BCNU和 DTIC，产生可由转移酶修复的细胞毒性DNA损伤， 因此DNA修复能力可能是衡量药物 阻力 在这项回顾性研究中，将从以下地点收集切片： 已接受治疗的患者的存档肿瘤块，以及 使用抗人血清的单克隆抗体测量的转移酶水平 转移酶和定量免疫荧光显微镜。 后 烷基转移酶的测量，将返回患者反应数据， 临床反应与转移酶水平相关。 相关性 转移酶水平低，对化疗有积极反应， 证明转移酶测量的预后价值， 转移性恶性黑素瘤 这项研究的创新之处在于， 应用了化疗对DNA损伤的基本科学机制， 转移酶介导的DNA修复与耐药的临床背景 转移性黑素瘤 这项研究的结果将导致 商业开发的诊断测试用于选择最 适当的辅助化疗。 建议的商业应用：该研究将导致 中心站诊断测试用于肿瘤活检的时间， 测定肿瘤组织中转移酶的水平。该测试将用于 预测患者对烷基化化疗的反应， 黑素瘤

The objective of the research is to measure the DNA repair protein 06- alkylguanine-DNA alkyltransferase in biopsies of metastatic malignant melanoma and correlate those levels with the response of patients to treatment with alkylating nitrosources. These drugs, such as BCNU and DTIC, create cytotoxic DNA damage that is reparable by the transferase, and therefore the DNA repair capacity may be a measure of drug resistance. In this retrospective study, slides will be collected from archived tumor blocks from patients who have already been treated, and the levels of transferase measured using monoclonal antibodies against the transferase and quantitative immunofluorescence microscopy. After measurement of alkyltransferase, patient response data will be returned, and the clinical response correlated with transferase levels. Correlation of low transferase levels with positive response to chemotherapy will demonstrate the prognostic value of transferase measurements in metastatic malignant melanoma. This research is innovative in that it applies a basic science mechanism of DNA damage by chemotherapy and DNA repair by transferase to the clinical setting of drug resistance in metastatic melanoma. The results of this research will lead to the commercial development of a diagnostic test used in selection of the most appropriate adjuvant chemotherapy in this disease. PROPOSED COMMERCIAL APPLICATION: The research will lead to a central station diagnostic test used to the time of tumor biopsy to measure the level of transferase in tumor tissue. This test will be used to predict the response of patients to alkylation chemotherapy of melanoma.