Comparative Mechanisms of Cancer Chemoprevention

癌症化学预防的比较机制

• 批准号: 7026542
• 负责人: GEORGE S BAILEY
• 金额: $ 119.49万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-17 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7026542
• 关键词: cancer prevention; chemoprevention; chlorophyll; clinical research; cytoprotection; human subject; plant extracts

DESCRIPTION (provided by applicant): This amended program project focuses on cancer chemoprevention by a selected set of phytochemicals: the chlorophylls, indole-3-carbinol, and tea polyphenols. Each of these in natural or derivative form is known to have protective efficacy in some animal models; however, molecular mechanisms and dose-response issues are not fully defined, combined chemopreventive approaches have received relatively little attention, the potential for tumor enhancement (by indole-3-carbinol, for example) is not fully understood, and the role of maternal exposure to these agents in fetal health risk has not been explored. The proposed studies will provide a systematic examination of the molecular mechanisms of cancer chemoprevention by these blocking agents and suppressing agents in standard rat models (mammary, liver), knockout and congenic mouse models (colon, lung), and a multi-organ rainbow trout model (stomach, liver), along with studies in human cell culture models. The results of this comparative approach will be translated into three biomarker intervention and bioavailability studies in human volunteers. In summary, the overall aim of this program project is to conduct highly interactive mechanism, tumorigenesis, and dose-response studies in selected animal models, each having specific advantages for cancer chemoprevention research, and to translate the most promising results into initial human studies that may demonstrate chemoprevention promise in human populations. This goal will be achieved through three complementary, synergistic projects: 1) Chlorophylls as Trans-Species Blocking Agents (G. Bailey, PI); 2) Transplacental Chemoprotection and GI Bioavailability (D. Williams, PI); and 3) The a-Catenin Pathway and Chemoprotection by Tea (R. Dashwood, PI). Investigators will be aided by an Administrative Core (G. Bailey, Director), which oversees inter-project meetings and provides budgetary, reporting, and external advisory needs, and a Service Core, which provides selected animal, preparative chemistry, statistical, and other services (R. Dashwood, director). Dr. George Bailey will serve as Principal Investigator for the program project.

描述（由申请人提供）： 该修订后的项目重点是通过一组选定的植物化学物质进行癌症化学预防：叶绿素、吲哚-3-甲醇和茶多酚。 已知这些天然或衍生物形式中的每一种都在某些动物模型中具有保护功效；然而，分子机制和剂量反应问题尚未完全确定，联合化学预防方法受到的关注相对较少，肿瘤增强的潜力（例如吲哚-3-甲醇）尚未完全了解，并且母体暴露的作用这些药物对胎儿健康的风险尚未被探讨。 拟议的研究将系统地检查这些阻断剂和抑制剂在标准大鼠模型（乳腺、肝脏）、基因敲除和同源小鼠模型（结肠、肺）以及多器官虹鳟鱼中的癌症化学预防的分子机制。模型（胃、肝脏），以及人类细胞培养模型的研究。 这种比较方法的结果将转化为人类志愿者的三种生物标志物干预和生物利用度研究。 总之，该项目的总体目标是在选定的动物模型中进行高度交互的机制、肿瘤发生和剂量反应研究，每种动物模型在癌症化学预防研究方面都有特定的优势，并将最有希望的结果转化为初步的人体研究，可能在人群中展现出化学预防的前景。 这一目标将通过三个互补、协同的项目来实现：1) 叶绿素作为跨物种阻断剂（G. Bailey，PI）； 2) 经胎盘化疗保护和胃肠道生物利用度（D. Williams，PI）； 3) α-连环蛋白途径和茶的化学保护作用（R. Dashwood，PI）。 研究人员将得到行政核心（G. Bailey，主任）和服务核心的协助，行政核心负责监督项目间会议并提供预算、报告和外部咨询需求，服务核心则提供选定的动物、制备化学、统计和其他服务。服务（R. Dashwood，总监）。 乔治·贝利博士将担任该计划项目的首席研究员。