DIETARY PLANT PHENOLICS--EFFECT ON COLONIC BIOMARKERS

描述：（申请人描述）阿司匹林（阿萨）和其他非甾体类药物 抗炎药（NSAID）是典型的结肠癌 化学预防剂 它们影响结肠上皮细胞的关键参数 细胞更新，如细胞分裂和细胞死亡，在体外和体内。 这些可能是NSAID抑制发展的整体过程， 结直肠肿瘤 可以想象，其他结肠癌 化学预防剂也具有这些潜在的作用机制。 水果和蔬菜等植物性食物具有抗肿瘤作用， 包括结肠在内的几个器官系统 虽然活跃的人数 这些食物中含有的抗癌成分可能很丰富， 植物来源的酚类化合物如姜黄素、芦丁和槲皮素， 是特别值得研究的化合物。 这些化合物具有 结肠癌化学预防特性，特别是在动物模型中， 致癌物诱发结肠癌。 它们拮抗肿瘤细胞增殖 体外 有趣的是，它们还具有类似于 NSAIDs。 它们抑制环氧合酶（考克斯）催化活性， 抑制花生四烯酸（AA）代谢另一个主要分支，脂氧合酶 (LOX)活动 本申请概述了一项临床研究， 结直肠癌风险高于平均水平的志愿者，即 在过去有结肠腺瘤，十周的控制， 代谢饮食和植物酚类化合物之一：姜黄素，芦丁，或 槲皮素;或NSAID舒林酸。 将进行连续结肠粘膜活检， 从志愿者身上提取，以确定这些 化合物对结肠上皮细胞的作用。 这些化合物是否：a）影响 结肠粘膜中测量上皮细胞更新的生物标志物， 质量稳态和细胞分化; B）影响结肠粘膜AA 代谢;和c）产生类似于舒林酸的这些参数的变化， 将确定一种典型的化学预防剂。 预计这项研究的结果将提供一个更清晰的 了解结肠癌发生和结肠癌的过程 NSAIDs和天然植物衍生化合物的化学预防。

DESCRIPTION: (Applicant's Description) Aspirin (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs) are prototypical colon cancer chemopreventive agents. They affect key parameters of colonic epithelial cell turnover such as cell division and cell death, in vitro and in vivo. These may be integral processes by which NSAIDs inhibit the development of colorectal neoplasms. It is conceivable that other colon cancer chemopreventive agents share these potential mechanisms of action as well. Plant foods such as fruits and vegetables have anti-neoplastic effects in several organ systems, including the colon. Though the number of active anti-cancer ingredients contained within these foods are likely abundant, the plant-derived phenolic compounds such as curcumin, rutin, and quercetin, are particularly compelling compounds to study. These compounds possess colon cancer chemopreventive properties, notably in animal models of carcinogen induced colon cancer. They antagonize tumor cell proliferation in vitro. Intriguingly, they also have biochemical properties similar to the NSAIDs. They inhibit cyclooxygenase (COX) catalytic activity and also inhibit another major arm of arachidonic acid (AA) metabolism, lipoxygenase (LOX) activity. This application outlines a clinical research study that will treat human volunteers with above average risk for colorectal cancer, i.e. those who have had colon adenomas in the past, for ten weeks with a controlled metabolic diet and one of the plant phenolic compounds: curcumin, rutin, or quercetin; or the NSAID sulindac. Serial colon mucosal biopsies will be taken from the volunteers in order to determine the effect of these compounds on colonic epithelial cells. Whether these compounds: a) affect biomarkers in the colonic mucosa that measure epithelial cell turnover, cell mass homeostasis, and cell differentiation; b) influence colonic mucosal AA metabolism; and c) produce changes in these parameters similar to sulindac, a classical, chemopreventive agent, will be determined. It is anticipated that the results of this study will provide a clearer insight into the process of colon carcinogenesis and colon cancer chemoprevention by both the NSAIDs and natural plant-derived compounds.