Curcumin chemoprevention in familial adenomatous polyposis

姜黄素化学预防家族性腺瘤性息肉病

• 批准号: 8545682
• 负责人: FRANCIS M GIARDIELLO
• 金额: $ 45.81万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8545682
• 关键词: APC gene; Adenomatous Polyposis Coli; Adverse effects; Affect; American; Apoptosis; Apoptotic; Asia; Cancer Etiology; Carcinoma; Cessation of life; Chemoprevention; Chemopreventive Agent; Colectomy; Colorectal; Colorectal Adenoma; Colorectal Cancer; Curcuma longa; Curcumin; Development; Disease; Dose; Epithelial; Food Additives; Germ-Line Mutation; Goals; Growth; Health; Herb; Immunohistochemistry; Intestinal Cancer; Intestines; Lead; Lesion; Malignant Neoplasms; Measurement; Messenger RNA; Modeling; Molecular; Mucous Membrane; Ornithine Decarboxylase; PTGS2 gene; Patients; Pigments; Plant Roots; Polyamines; Polyps; Powder dose form; Proliferating Cell Nuclear Antigen; Randomized; Regulation; Reporting; Spices; TdT-Mediated dUTP Nick End Labeling Assay; Testing; Turmeric extract; adenoma; cyclooxygenase 2; double-blind placebo controlled trial; effective therapy; high risk; indexing; insight; prevent; prophylactic; rectal; young adult

DESCRIPTION (provided by applicant): Familial adenomatous polyposis coli (FAP) is an autosomal dominant disorder due to germline mutation of the APC gene and characterized by the formation of hundreds of colorectal adenomatous polyps in young adults. Virtually all affected patients will develop colorectal cancer if prophylactic colectomy is not performed. Presently, the only effective therapy for FAP is colectomy and lifelong surveillance of the intestinal tract. Our long term goal is to discover effective chemopreventative therapy for patients with FAP, representing a model which may provide insights into the molecular regulation of the adenoma-carcinoma sequence in ordinary intestinal cancer. Curcumin is the major yellow pigment extracted from turmeric the powdered root of the herb Curcuma longa. Curcumin has long been used as a spice in Asia and is considered a safe food additive. Curcumin has been reported by our group to regress colorectal and ileal adenomas in 5 patients with FAP without side effects. Our hypothesis is that curcumin can decrease growth of rectal-ileal and the associated epithelial hyperproliferation in FAP patients. Our specific aims are to: a) administer curcumin to FAP patients in a randomized, placebo-controlled, double-blinded trial and sequentially determine rectal-ileal polyp number and size by using videoendoscopy. b) Sequentially assess in flat and polypoid rectal-ileal mucosa markers of epithelial proliferation (ornithine decarboxylase, polyamines and immunohistochemistry for proliferating cell nuclear antigen), apoptosis (apoptotic index by morphologic measurement and TUNEL assay), and cyclooxygenase- 2 levels (immunohistochemistry and qRT-PCR assessment of COX-2 mRNA).

描述（由申请人提供）：家族性腺瘤性息肉大肠杆菌（FAP）是一种常染色体显性疾病，这是由于APC基因的种系突变，其特征是在年轻人中形成了数百种大肠腺瘤息肉。如果没有进行预防性结肠切除术，几乎所有受影响的患者都会患有大肠癌。目前，FAP的唯一有效疗法是结肠切除术和终身监测肠​​道。我们的长期目标是针对FAP患者发现有效的化学预防疗法，代表了一种模型，该模型可以提供对普通肠癌腺瘤 - 癌序列的分子调节的见解。姜黄素是从姜黄中提取的主要黄色颜料是草药姜黄的粉状根。姜黄素长期以来一直被用作亚洲香料，被认为是安全食品添加剂。我们的小组据报道，姜黄素已报告了5例FAP患者的结直肠癌和回肠腺瘤，没有副作用。我们的假设是，姜黄素可以减少FAP患者的直肠 - 足球生长和相关的上皮过度增殖。我们的具体目的是：a）在随机的，安慰剂对照，双盲试验中对FAP患者进行姜黄素，并使用视频调节镜检查顺序确定直肠 - 回落的息肉数量和大小。 b）在上皮增殖的平坦和息肉直肠直肠 - 直肠 - 直肠 - 直肠粘膜标记中（鸟嘌呤脱羧酶，多胺和免疫组织化学，用于增殖细胞核抗原），凋亡，凋亡指数（通过形态学测量和cylogologic Assay and cyclosiss and Quncransem and Quncransem and Quncrantiss and Quncrants-2级）（评估COX-2 mRNA）。