Comparative Mechanisms of Cancer Chemoprevention

癌症化学预防的比较机制

• 批准号: 7189051
• 负责人: Roderick H Dashwood
• 金额: $ 116.03万
• 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 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7189051
• 关键词: Adolescent; Animal Model; Animals; Apoptosis; Attention; Biological Availability; Biological Markers; Cancer Intervention; Carcinogens; Cell Adhesion; Cell Cycle; Chemicals; Chemistry; Chemoprevention; Chemopreventive Agent; Chemoprotection; Chemoprotective Agent; Chlorophyll; Class; Classification; Clinical; Clinical Research; Colon; Comparative Study; Consumption; Cultured Cells; DNA Adducts; Development; Dietary Factors; Dietary Indole; Dose; Epidemiologic Studies; Esophageal Polyp; Exhibits; Exposure to; Fetus; Fishes; General Population; Genus Cola; Goals; Health; Health Food; Histologic; Human; Human Volunteers; Hydrocarbons; Individual; Indole-3-Carbinol; Infant; Intake; Intervention; Intervention Trial; Knock-out; Knowledge; Link; Liver; Lung; Malignant Neoplasms; Malignant neoplasm of liver; Mammals; Mammary Neoplasms; Mammary gland; Maternal Exposure; Mediating; Metabolism; Modeling; Molecular; Oncorhynchus mykiss; Organ; Outcome; Pathway interactions; Pharmaceutical Preparations; Phenotype; Phytochemical; Pigments; Plants; Population; Principal Investigator; Proteins; Range; Rattus; Reporting; Research; Research Personnel; Risk; Role; Salmo trutta; Services; Standards of Weights and Measures; Stomach; Tea; Testing; Translating; Work; adduct; base; cancer chemoprevention; cancer risk; carcinogenesis; comparative; congenic; cruciferous vegetable; design; dietary supplements; epidemiology study; feeding; fetal; fruits and vegetables; gastrointestinal; human study; human subject; mouse model; polyphenol; programs; prospective; response; tumor; tumor initiation; tumorigenesis

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）： 这个修订的计划项目的重点是癌症化学预防的一组选定的植物化学物质：叶绿素，吲哚-3-甲醇，茶多酚。 已知天然或衍生形式的这些中的每一种在一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，通过吲哚-3-甲醇）的作用尚未完全了解，并且尚未探索母体暴露于这些试剂在胎儿健康风险中的作用。 拟定的研究将提供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）和多器官虹鳟鱼模型（胃、肝脏）中癌症化学预防的分子机制的系统检查，沿着人类细胞培养模型的研究。 这种比较方法的结果将转化为三种生物标志物干预和人类志愿者的生物利用度研究。 总之，该计划项目的总体目标是在选定的动物模型中进行高度相互作用的机制，肿瘤发生和剂量反应研究，每种动物模型都具有癌症化学预防研究的特定优势，并将最有前途的结果转化为初步的人类研究，这些研究可能证明人类群体的化学预防前景。 这一目标将通过三个互补的协同项目来实现：1）叶绿素作为跨物种阻断剂（G。Bailey，PI）; 2）经胎盘化学保护和GI生物利用度（D.威廉姆斯，PI）;和3）α-连环蛋白途径和茶的化学保护（R. Dashwood，PI）。 研究人员将得到一个行政核心（G。贝利，主任），负责监督项目间会议，并提供预算，报告和外部咨询需求，和一个服务核心，提供选定的动物，制备化学，统计和其他服务（R。达什伍德，导演）。 乔治贝利博士将担任该项目的主要研究员。