Ginger for Chemoprevention of Colorectal Cancer

生姜用于结直肠癌的化学预防

• 批准号: 7658810
• 负责人: SUZANNA M. ZICK
• 金额: $ 13.6万
• 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/7658810
• 关键词: Acute; Adenomatous Polyps; Animals; Appearance; Arachidonic Acids; Area; Biological; Biological Assay; Biological Availability; Biological Markers; Botanicals; Cancer Etiology; Cessation of life; Chemoprevention; Chemopreventive Agent; Chronic; Clinical Trials; Cohort Studies; Colonoscopy; Colorectal Cancer; Controlled Clinical Trials; Development; Dinoprostone; Dose; Double-Blind Method; Drug Formulations; Drug Kinetics; Encapsulated; Ginger; Goals; Grant; High Pressure Liquid Chromatography; Human; Individual; Inflammation; Inflammatory; Intervention; Lead; Liquid substance; Maximum Tolerated Dose; Measures; Methods; Modeling; Mucous Membrane; Nutritional; Oral; PTGS2 gene; Participant; Pathway interactions; Pharmacy (field); Phase; Placebo Control; Placebos; Plants; Plastics; Polyps; Population; Prevention; Prostaglandin-Endoperoxide Synthase; Prostaglandins; Randomized; Research Personnel; Schedule; Screening procedure; Series; Taste Perception; Tissues; Toxic effect; Training; United States; adenoma; arachidonate; base; blind; cancer chemoprevention; capsule; design; healthy volunteer; high risk; mortality; pre-clinical; prevent; programs; randomized placebo controlled trial; rectal; skills

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。2004年估计将发生146,940例新的结直肠癌病例，造成56,730例死亡。我们的目标是发现早期结直肠癌发展的筛查方法，并被认为可将结直肠癌死亡率降低33%。尽管有这些数据，但筛查的广泛使用仍然很差。因此，替代筛选方法，以防止发展的腺瘤性息肉和他们的发展为结直肠癌是指。