FOUR WEEK ORAL COMPARATIVE ENDOCRINOLOGY STUDIES

四周口服比较内分泌学研究

• 批准号: 6141470
• 负责人: BARRY S LEVINE
• 金额: $ 1.43万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6141470
• 关键词: FOUR; WEEK; ORAL; COMPARATIVE; ENDOCRINOLOGY

The Chemoprevention Branch of the Division of Cancer Prevention and Control at the National Cancer Institute directs a program to identify and develop drugs for human use that will prevent, ala, or reverse the progression of cellular dysplasia (e.g. intraepithelial neoplasia) to invasive cancer. Part of the drug research and development process involves preclinical toxicology studies. These studies are performed under Good Laboratory Practices according to guidance documents published by the Food and Drug Administration and are used to support Investigational New Drug applications and eventually New Drug Applications to the FDA for the marketing approval of cancer chemopreventive agents. Dehydroepiandrosterone (DHEA) is a major steroid precursor secreted by the adrenal cortex. Inhibitory activity against glucose-6- phosphatedehydrogenase (G6DPH) and protein isoprenylation may help prevent neoplastic proliferation and transformation. Exogenously administered DHEA has efficacy as a chemopreventive agent in a number of carcinogenesis models but estrogenic and androgenic effects seen in preclinical safety studies are a concern for human chemoprevention trials. DHEA analog 8354 (fluasterone) is a fluorinated derivative of DHEA that may be a more potent chemopreventive agent without the hormonal side effects of DHEA. The contractor shall conduct 2 comparative endocrinology studies in rats and dogs of the effects of DHEA and DHEA-F particularly on the mammary and prostate tissues. Agents shall be administered for 4 weeks. Endpoints shall include hormonal measurements, histopathology, and hormone receptor measurements.

癌症预防与治疗部化学预防分支 国家癌症研究所的控制中心指导了一个项目， 开发人类使用的药物，将防止，阿拉，或扭转 细胞发育不良（例如上皮内瘤变）进展至 侵袭性癌症 药物研发过程的一部分 涉及临床前毒理学研究。 进行这些研究 根据已发布的指南文件，遵循药物非临床研究质量管理规范 由食品和药物管理局，并用于支持 研究性新药申请和最终新药申请 申请癌症化学预防剂的上市许可 脱氢表雄酮（DHEA）是由哺乳动物分泌的主要类固醇前体。 肾上腺皮质 对葡萄糖-6- 磷酸脱氢酶（G6 DPH）和蛋白质异戊二烯化可能有助于防止 肿瘤增殖和转化。 外源施用的 脱氢表雄酮作为一种化学预防剂在许多癌症发生中具有功效 模型，但在临床前安全性中观察到雌激素和雄激素效应 研究是人类化学预防试验的关注点。 DHEA类似物8354 （氟甾酮）是DHEA的氟化衍生物，其可能是更好的选择。 有效的化学预防剂，没有DHEA的激素副作用。 承包商应在大鼠中进行2项内分泌学比较研究 DHEA和DHEA-F的作用，特别是对乳腺和 前列腺组织。 药物应给药4周。 端点 应包括激素测量、组织病理学和激素受体 测量.