CHEMOPREVENTIVE AGENTS--CARCINOGENESIS INHIBITION

化学预防剂--抑制癌变

• 批准号: 3730900
• 负责人: RICHARD C MOON
• 金额: --
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3730900
• 关键词: benzanthracenes; bioassay; breast neoplasms; cancer prevention; carcinogenesis inhibitor; chemoprevention; disease /disorder model; drug screening /evaluation; laboratory mouse; laboratory rat; mammary gland; medicinal plants; neoplastic transformation; organ culture; plant extracts; skin neoplasms; tumor promoters

The overall objective of this renewal application remains to discover novel chemopreventive agents derived from the natural products. This project will continue to utilize mammary gland organ culture and in vivo carcinogenesis models (skin and mammary) to evaluate biological effectiveness of potential chemopreventive agents identified in the initial screen. As indicated in the theme of this program, extracts or fractions considered as active leads will be first evaluated for its chemopreventive activity against 7,12, dimethylbenz(a)anthracene (DMBA) induced mammary lesions in organ cultures. If the exact shows dramatic activity in the culture system, it will be evaluated against two stage skin carcinogenesis model. Some extracts or isolated fractions will be further characterized and again their activity will be assessed. The newly identified agent which is considered active is again evaluated against mammary lesion formation. The active compound is then synthesized and carcinogenesis studies will be initiated. Brassinin and the extract of Mundulea sericea (P00053) were selected for the carcinogenesis experiments based on the results from the in vitro assays and organ culture experiments (this project). These studies have shown excellent inhibition against skin carcinogenesis. In addition we propose to conduct studies to evaluate activity of newly identified chemopreventive agent for its activity either as an anti-initiator or as an anti-promoter in organ cultures. This will allow us to design in vivo studies to confirm such stage specific effects and to understand the mechanism of action of these agents. A variety of other carcinogenesis models have been established in our laboratory for assessing chemopreventive potential at other target organs, and they will be used as required. In summary, this project will serve to provide a definite biological end point for newly identified potential chemopreventive agents in this program project.

此续订申请的总体目标仍是发现 从天然产物中提取的新型化学预防药物。这 项目将继续利用乳腺器官培养和体内 用于评价生物学的致癌模型(皮肤和乳腺) 研究中确定的潜在化学预防药物的有效性 初始屏幕。如本节目主题所示，摘录或 被视为有效销售线索的部分将首先评估其 7，12，二甲基苯并(A)菲(DMBA)的化学预防作用 器官培养中诱发的乳腺损伤。如果确切地说是戏剧性的 在文化系统中的活动，将对照两个阶段进行评估 皮肤癌模型。一些提取物或分离的部分将是 将进一步确定其特征，并再次评估它们的活动。这个 再次评估被认为有效的新识别的代理 抗乳腺病变形成。然后活性化合物被 将启动合成和致癌研究。油菜素和油菜素 选用丝光绿提取物(P00053)进行了测定。 基于体外检测结果的致癌实验 和器官培养实验(这个项目)。这些研究表明 对皮肤癌有极好的抑制作用。此外，我们建议 进行研究以评估新确定的活动 作为抗引发剂或AS活性的化学预防药物 器官培养中的反启动子。这将使我们能够在活体内设计 确认这种阶段特异性影响的研究并了解 这些药物的作用机制。各种其他致癌作用 我们实验室已经建立了用于评估的模型 其他靶器官的化学预防潜力，它们将被用于 视需要而定。总而言之，这个项目将提供一个明确的 新发现的潜在化学预防的生物终点 此计划项目中的代理。