DIETARY PLANT PHENOLICS--EFFECT ON COLONIC BIOMARKERS

描述：(申请人描述)阿司匹林(ASA)和其他非类固醇类药物 抗炎药(NSAIDs)是典型的结肠癌 化学防护剂。它们影响结肠上皮的关键参数 细胞周转，如细胞分裂和细胞死亡，在体外和体内。 这些可能是非类固醇抗炎药抑制血管紧张素转换酶抑制剂发展的完整过程 结直肠肿瘤。可以想象，其他结肠癌 化学预防药物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。 几个器官系统，包括结肠。虽然活跃的用户数量 这些食物中含有的抗癌成分很可能是丰富的， 从植物中提取的酚类化合物，如姜黄素、芦丁和栎素， 是特别值得研究的化合物。这些化合物具有 结肠癌的化学预防特性，特别是在动物模型中 致癌物质诱发结肠癌。它们能对抗肿瘤细胞的增殖 在试管中。耐人寻味的是，它们还具有类似于 非甾体抗炎药。它们抑制环氧合酶(COX)的催化活性，还 抑制花生四烯酸(AA)代谢的另一主要臂--脂氧合酶 (LOX)活动。 这项申请概述了一项临床研究，它将治疗人类 患有结直肠癌风险高于平均水平的志愿者，即那些 过去有结肠腺瘤，有10周的对照 代谢饮食和一种植物酚类化合物：姜黄素、芦丁或 或非甾体抗炎药舒林酸。连续的结肠粘膜活检将是 从志愿者身上提取，以确定这些药物的效果 结肠上皮细胞上的化合物。这些化合物是否会：a)影响 结肠粘膜中衡量上皮细胞周转的生物标记物 质量动态平衡和细胞分化；b)影响结肠粘膜AA 代谢；以及c)在这些参数中产生类似于舒林酸的变化， 一种经典的化学预防药物将被确定。 预计这项研究的结果将提供一个更清晰的 对结肠癌发生和结肠癌发生过程的洞察 非甾体抗炎药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.