Ginger for Chemoprevention of Colorectal Cancer

生姜用于结直肠癌的化学预防

• 批准号: 7104889
• 负责人: SUZANNA M. ZICK
• 金额: $ 12.72万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-02 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7104889
• 关键词: adenomatous polyps; alternative medicine; angiosperms; biomarker; cancer prevention; cancer risk; carcinogenesis inhibitor; chemoprevention; clinical research; clinical trial phase I; clinical trial phase II; colorectal neoplasms; dosage; human subject; human therapy evaluation; patient oriented research; pharmacokinetics; plant extracts; prostaglandin E; prostaglandin endoperoxide synthase

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. An estimated 146,940 new cases of CRC will develop in 2004, resulting in 56,730 deaths. Screening methods that detect the early development of CRC, and are thought to reduce CRC mortality by as much as 33 percent, are the goal. Despite these figures, wide spread use of screening remains poor. Consequently, alternative methods to screening that prevent the development of adenomatous polyps and their development to CRC is indicated. Ginger, which has been studied in animal and human models for its chemopreventive potential, shows promise as an agent for preventing CRC. Currently, ginger's chemopreventive mechanisms of action are unknown but are thought to be via inhibition of arachidonate pathways and other mechanisms of cellular proliferative control. However, the bioavailability of ginger as well as the optimal dose and schedule for administering ginger to effect biomarkers of inflammation has not been examined. Also, due to ginger's unique aroma, adequate blinding needs to be examined. Hence, a series of studies using a standardized (5% {6 }-gingerols) ginger product are proposed to explore these questions: (1) a Phase IA study to evaluate the single-dose pharmacokinetics, acute toxicity, and maximum tolerated dose (MTD) of ginger; (2) a study to examine the methods for effectively blinding study participants to ginger's aroma; (3) a Phase IB study to determine the multi-dose pharmacokinetics, chronic toxicity, and effect of ginger on rectal mucosa PGE2; and (4) a Phase IIA randomized, double-blinded, placebo-controlled, clinical trial, to assess the effect of ginger on PGE2 and COX2 levels in colonic mucosa and adenomas in individuals at high risk for developing polyps or CRC. This grant also proposes to train a junior researcher in the essential skills to become an independent investigator in the area of botanicals for cancer chemoprevention. This program of study is designed to develop competencies in: (1) understanding the underlying principles of chemoprevention and the development of chemopreventitive agents; (2) measuring plant metabolites in biological fluids; (3) conducting bioassays to detect inflammatory biomarkers in colonic mucosal tissue; (4) designing pre-clinical and clinical trials in the area of chemoprevention; and (5) identifying polyps and colorectal cancer when seen during colonoscopies.

描述（由申请人提供）：结直肠癌（CRC）是美国癌症死亡的第二大原因。 据估计，2004 年将出现 146,940 例新的结直肠癌病例，导致 56,730 人死亡。 我们的目标是采用筛查方法来检测 CRC 的早期发展，并被认为可以将 CRC 死亡率降低 33%。 尽管有这些数字，筛查的广泛使用仍然很差。 因此，指出了预防腺瘤性息肉发展及其发展为结直肠癌的替代筛查方法。 生姜的化学预防潜力已在动物和人体模型中得到研究，显示出作为预防结直肠癌的药物的前景。 目前，生姜的化学预防作用机制尚不清楚，但被认为是通过抑制花生四烯酸途径和其他细胞增殖控制机制来实现的。 然而，生姜的生物利用度以及服用生姜以影响炎症生物标志物的最佳剂量和时间表尚未得到研究。 另外，由于生姜独特的香气，需要检查是否足够的致盲。 因此，建议使用标准化（5% {6 }-姜酚）生姜产品进行一系列研究来探讨以下问题：（1） IA 期研究，以评估单剂量药代动力学、急性毒性和最大耐受剂量（生姜的MTD； (2) 一项研究，旨在检验如何有效地使研究参与者对生姜的香气致盲； (3) IB期研究，以确定生姜的多剂量药代动力学、慢性毒性以及对直肠粘膜PGE2的影响； (4) 一项 IIA 期随机、双盲、安慰剂对照临床试验，旨在评估生姜对息肉或结直肠癌高危个体结肠粘膜和腺瘤中 PGE2 和 COX2 水平的影响。 这笔赠款还计划培训一名初级研究人员掌握基本技能，使其成为癌症化学预防植物药领域的独立研究人员。 该学习计划旨在培养以下方面的能力：（1）了解化学预防的基本原理和化学预防药物的开发； (2)测定生物体液中的植物代谢物； (3)进行生物测定，检测结肠粘膜组织中的炎症生物标志物； (4) 设计化学预防领域的临床前和临床试验； (5) 在结肠镜检查中发现息肉和结直肠癌。