BIOCHEMICAL PHARMACOLOGY OF ANTINEOPLASTIC AGENTS

描述（改编自申请人的摘要）： 拟议的研究是开发治疗药物方案， 在药理学和生物学基础上用于治疗人类癌症的用途， 关于药物作用机制的生化信息， 肿瘤细胞过程中的信息， 脆弱的蜂窝网站。 为了实现这些目标， 应用将使用诱导的终末分化， 作为治疗剂的化学和/或生物试剂 治疗癌症的方法。 为了实现这些目标， 目的是：（a）表征脂皮质素和类花生酸的作用， 在鳞状细胞癌和白血病细胞的成熟中;（B） 确定从未成熟细胞转变过程中的细胞骨架变化 （c）研究白血病的诱导机制 细胞分化的蒽环类药物;（d）开发和使用在体内 系统来确定分化的治疗效果 诱导剂;（e）评估fos和jun癌基因在 白血病细胞成熟;和（f）研究信号转导的机制 红白血病细胞中促红细胞生成素的转导。 预计 将获得的信息将提供重要的线索， 最终将导致临床方法的发展， 在癌症患者中产生治疗益处的效用， 诱导肿瘤细胞的终末分化，以及 作为提供信息的因素参与调节恶性 细胞生长和分化。

DESCRIPTION (adapted from the applicant's abstract): The objectives of the proposed research are to develop therapeutic drug regimens that will have use in the treatment of cancer in man on the basis of pharmacological and biochemical information on the mechanism of drug action, and fundamental information in processes in neoplastic cells that may be considered cellular sites of vulnerability. To accomplish these objectives, this application will use the induction of terminal differentiation of neoplastic cells by chemical and/or biological agents as a therapeutic approach to the treatment of cancer. To achieve these goals the specific aims are: (a) to characterize the role of the lipocortins and eicosanoids in the maturation of squamous carcinoma and leukemia cells; (b) to determine cytosketal changes during the transition from the immature cell to the mature state; (c) to study the mechanism of induction of leukemia cell differentiation by anthracyclines; (d) to develop and employ in vivo systems to determine the therapeutic effectiveness of differentiation inducing agents; (e) to evaluate the role of fos and jun oncogenes in leukemia cell maturation; and (f) to study the mechanism of signal transduction by erythropoietin in erythroleukemia cells. It is anticipated that information will be obtained which will provide significant leads that will ultimately result in the development of approaches with clinical utility that function to produce therapeutic benefit in cancer patients by the induction of the terminal differentiation of neoplastic cells, as well as provide information on factors involved in the regulation of malignant cell growth and differentiation.