BIOCHEMICAL PHARMACOLOGY OF ANTINEOPLASTIC AGENTS

抗肿瘤药物的生化药理学

• 批准号: 3163111
• 负责人: ALAN CLAYTON SARTORELLI
• 金额: $ 27.7万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-01-01 至 1993-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3163111
• 关键词: annexins; anthracyclines; antineoplastics; basosquamous cell carcinoma; biological signal transduction; cell differentiation; clone cells; cytoskeleton; daunorubicin; disease /disorder model; doxorubicin; drug adverse effect; drug design /synthesis /production; drug metabolism; eicosanoids; enzyme inhibitors; epidermal growth factor; erythroleukemia; erythropoietin; fluorescent dye /probe; gene expression; glucocorticoids; granulocyte; laboratory mouse; leukemia; microtubules; monocyte; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; neoplastic cell; oncogenes; phospholipase A2; phospholipase inhibitor; tissue /cell culture

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.

描述（改编自申请人的摘要）： 拟议的研究是开发将具有的治疗药物治疗方案 根据药理和 有关药物作用机制和基本的生化信息 可以考虑的肿瘤细胞过程中的信息 脆弱性的细胞部位。 为了实现这些目标， 应用将使用诱导的终端分化 化学和/或生物学剂作为治疗性的肿瘤细胞 癌症治疗的方法。 为了实现这些目标 目的是：（a）表征脂皮质蛋白和类花生素的作用 在鳞状癌和白血病细胞的成熟中； （b）到 确定从未成熟细胞过渡期间的胞骨变化 到成熟的状态； （c）研究诱导白血病的机制 蒽环类细胞的细胞分化； （d）在体内开发和使用 确定分化治疗有效性的系统 诱导剂； （e）评估FOS和JUN ONCEGONES在 白血病细胞成熟； （f）研究信号的机制 红细胞炎细胞中红细胞生成素的转导。 预计 将获得该信息，这将提供重要的潜在客户 最终将导致开发临床的方法 通过 诱导肿瘤细胞的末端分化以及 作为提供有关调节恶性的因素的信息 细胞生长和分化。