MAMMARY CHEMOPREVENTION--HORMONES/VITAMIN A/SELENIUM

乳房化学预防——激素/维生素 A/硒

• 批准号: 3187284
• 负责人: Clinton Julian Grubbs
• 金额: $ 12.34万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-06-01 至 1991-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3187284
• 关键词: breast neoplasms; chemical carcinogen; chemical carcinogenesis; combination cancer therapy; disease /disorder model; drug adverse effect; estrogens; haloalkylamine; hormone regulation /control mechanism; hormone therapy; laboratory rat; mammary gland; methylnitrosourea; nutrition related tag; progesterone; retinoids; selenium

The overall objectives of this proposal are to evaluate the concepts that low doses of different micronutrients used together may be more effective than high doses of a single micronutrient and that combining micronutrient interaction with hormonal factors may improve chemopreventive activity since they probably have different mechanisms of action. Carcinogenesis of the mammary gland is unique in that two distinct types of cancers occur, hormone dependent and independent. The use of different classes of agents (i.e., each perhaps specific for the type of cancers that occur) would appear to be a reasonable approach to preventing breast cancer. Using this rationale, studies are proposed to evaluate the effect on mammary cancer prevention of combining hormone, retinyl acetate and selenium treatments. It would be desirable if considerable overlap of these agents occurred (e.g. retinyl acetate is thought to be effective in preventing both hormone dependent and independent cancers). The proposed experiments will use the methylnitrosourea (MNU)-induced mammary cancer model in female Sprague-Dawley rats. The chemopreventive agents used will be short-term, high-dose estrogen plus progesterone, and low doses of retinyl acetate and sodium selenite. Although a major effort of each study is to determine the effect of the agents on prevention of mammary cancers, the possible toxicity of combining treatments will also be extensively investigated. Many classes of compounds have been shown to have chemopreventive activity, but their toxicity precludes their clinical use. The specific studies are designed to develop chemopreventive strategies that will both decrease the susceptibility of the mammary gland to carcinogens (i.e., prevent initiation) and prevent the progression and/or promotion of initiated cells to frank carcinomas. A final experiment is presented that will determine the effect of combining hormones, retinyl acetate, and selenium on reproductive and lactational performance. If chemoprevention of breast cancer is to be advocated in a young population, the agents used must not interfere with these physiological functions.

本提案的总体目标是评估以下概念： 低剂量的不同微量营养素一起使用可能更有效 高剂量的单一微量营养素和复合微量营养素 与激素因子相互作用可提高化学预防活性 因为它们可能有不同的作用机制。 癌变 乳腺的独特之处在于发生两种不同类型的癌症， 激素依赖和非依赖。 使用不同类别的代理 (i.e.,每一种可能对发生的癌症类型是特异性的）将 似乎是预防乳腺癌的合理方法。 使用此 基本原理，建议进行研究以评价对乳腺癌的影响 预防激素、醋酸视黄酯和硒联合治疗。 如果这些药剂有相当大的重叠， (e.g.醋酸视黄酯被认为是有效的， 依赖性和非依赖性癌症）。 拟议的实验将使用甲基亚硝基脲（MNU）诱导的 雌性Sprague-Dawley大鼠乳腺癌模型。 化学预防 使用的药物将是短期、高剂量的雌激素加孕酮， 低剂量的醋酸视黄酯和亚硒酸钠 虽然一项重大努力 每项研究的目的是确定药物对预防 乳腺癌，联合治疗的可能毒性也将是 广泛调查。 许多种类的化合物已被证明， 具有化学预防活性，但其毒性阻碍了其临床应用 使用. 具体的研究旨在开发化学预防 既能降低乳腺癌的易感性， 致癌物（即，防止启动）并防止进展 和/或促进起始细胞转化为恶性肿瘤。 最终 实验提出，将确定结合的效果 激素、醋酸视黄酯和硒对生殖和哺乳的影响 性能 如果要在一个国家提倡乳腺癌的化学预防， 年轻人，使用的药物不得干扰这些 生理功能。