Ginger for Chemoprevention of Colorectal Cancer

生姜用于结直肠癌的化学预防

• 批准号: 7273724
• 负责人: SUZANNA M. ZICK
• 金额: $ 13.01万
• 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/7273724
• 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; Risk; Schedule; Screening procedure; Series; Taste Perception; Thinking; Tissues; Toxic effect; Training; United States; adenoma; arachidonate; base; blind; cancer chemoprevention; capsule; cyclooxygenase 1; cyclooxygenase 2; design; gingerol; healthy volunteer; 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，估计有146,940例CRC新病例将出现，导致56,730例死亡。 目标是检测CRC早期发展的筛查方法，并被认为将CRC死亡率降低了33％。 尽管有这些数字，筛查的广泛使用仍然很差。 因此，指出了筛查的替代方法，以防止腺瘤息肉的发展及其发展为CRC。 生姜已经在动物和人类模型中研究了其化学预防潜力，它显示出作为预防CRC的药物的希望。 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蛛网膜途径和其他细胞增殖对照机制的方法。 然而，尚未检查生姜的生物利用度以及施用生姜以影响炎症生物标志物的最佳剂量和时间表。 同样，由于姜的独特香气，需要检查足够的盲目性。 因此，提出了一系列使用标准化（5％{6} - 果胶）生姜产物的研究来探讨这些问题：（1）一项IA期研究，以评估姜的单剂量药代动力学，急性毒性和最大耐受剂量（MTD）； （2）一项研究，以研究有效盲目研究参与者的方法的研究； （3）一项IB期研究，以确定多剂量药代动力学，慢性毒性以及生姜对直肠粘膜PGE2的影响； （4）IA期随机，双盲，安慰剂对照，临床试验，以评估生姜对pGE2和COX2水平在结肠粘膜和腺瘤中的影响，对发展息肉或CRC的高风险的个体。 该赠款还建议培训一名初级研究人员的基本技能，以成为植物学化学预防植物学领域的独立研究者。 该研究计划旨在发展：（1）了解化学预防的基本原理和化学预报剂的发展； （2）测量生物液中的植物代谢产物； （3）进行生物测定以检测结肠粘膜组织中的炎性生物标志物； （4）在化学预防区域设计临床前和临床试验； （5）在结肠镜检查中识别息肉和大肠癌。