FOUR WEEK ORAL COMPARATIVE ENDOCRINOLOGY STUDIES

癌症预防和预防司化学预防处 国家癌症研究所的控制中心指导了一项计划，以识别和 开发人类使用的药物，以预防、预防或逆转 细胞异型增生(如上皮内瘤变)进展为 浸润性癌症。药物研发过程的一部分 涉及临床前毒理学研究。这些研究是进行的 根据发布的指导文件，遵循良好的实验室操作规范 由食品和药物管理局提供，用于支持 研究中的新药申请和最终的新药申请 向FDA申请癌症化学预防药物的上市批准。 脱氢表雄酮(DHEA)是一种主要的类固醇前体，由 肾上腺皮质。对葡萄糖-6-的抑制活性 磷酸脱氢酶(G6DPH)和蛋白质异戊二烯基化可能有助于防止 肿瘤的增殖和转化。外源性给药 脱氢表雄酮在多种致癌作用中具有化学预防作用。 模型，但在临床前安全性中看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模拟8354 (氟雄酮)是脱氢表雄酮的氟化衍生物，可能是一种 有效的化学预防药物，无脱氢表雄酮的激素副作用。 承包商应对大鼠进行2项内分泌学比较研究 和狗对DHEA和DHEA-F的影响，特别是对乳房和 前列腺组织。给药时间为4周。端点 应包括激素测量、组织病理学和激素受体 测量。

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.