MULTIDRUG RESISTANCE GENES--ANALYSIS AND APPLICATIONS

化疗药物耐药性的研究进展 恶性细胞仍然是癌症成功的一个重要问题 心理治疗。一种同时存在的机构的体外分析 传递对多种化疗药物的耐药性 与基因组的特定区域的扩增有关。 分子生物学、细胞生物学和重组技术 逆转录病毒载体将被用来表征这种扩增的 区域和基因在多药耐药细胞中的过表达 台词。来自这个放大区域的分子探针将被用来 加深对乳腺癌化疗方案的认识 未来。多药耐药基因的实际应用 转化为造血干细胞将扩大我们的 关于造血的知识，代表着迈向 利用化疗耐药的造血干细胞 药物是化疗方案中不可或缺的组成部分 和骨髓移植。 这些研究的具体目标是：1)表征 多药相关基因(S)的克隆 抗性，2)S编码蛋白的特性 与多药耐药有关的基因克隆，3) 多药耐药扩增机制的表征 耐药基因，4)对儿童急性白血病治疗的评估 淋巴母细胞性白血病的发展与扩增 多药耐药基因(S)及其与肿瘤的关系 化疗失败，5)体内模型的建立 中国人群多药耐药发展的直接分析 分子水平，6)逆转录病毒载体的构建 包含导致多药耐药的基因，以及7) 携带人外周血造血细胞的体内筛选 多药耐药基因为人类研究开发模型系统 骨髓移植后的造血及保护作用分析 化疗药物。

The development of resistance to chemotherapeutic agents by malignant cells remains a significant problem in successful cancer therapy. In vitro analysis of a mechanism which simultaneously conveys resistance to multiple chemotherapeutic agents has been associated with amplification of a specific region of the genome. The techniques of molecular biology, cell biology and recombinant retroviral vectors will be utilized in characterizing this amplified region and the genes overexpressed in multidrug resistant cell lines. Molecular probes from this amplified region will be used to advance our understanding the chemotherapeutic protocols of the future. The practical application of multidrug resistance genes transduced into hematopoetic stem cells will expand our knowledge of hematopoesis and represents the first step towards utilizing hematopoetic stem cells resistant to chemotherapeutic agents as an integral component of chemotherapeutic regimens and bone marrow transplantation. The specific aims of these studies will be: 1) characterization of the cDNA clones to the gene(s) responsible for multidrug resistance, 2) characterization of the protein(s) encoded by the cDNA clones which are responsible for multidrug resistance, 3) characterization of the mechanism of amplification of multidrug resistance genes, 4) evaluation of children being treated for acute lymphoblastic leukemia for the development of amplification of multidrug resistance gene(s) and its relationship to chemotherapeutic failures, 5) development of in vivo models for the direct analysis of the development of multidrug resistance at the molecular level, 6) construction of a retroviral vector containing the gene responsible for multidrug resistance, and 7) selection in vivo of hematopoetic stem cells carrying the multidrug resistant gene to develop model systems for the analysis of hematopoesis and protection of bone marrow from chemotherapeutic agents.