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: 8652528
• 负责人: FRANCIS M GIARDIELLO
• 金额: $ 9.2万
• 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/8652528
• 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

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).

家族性结肠腺瘤性息肉病（FAP）是一种由APC基因的生殖系突变引起的常染色体显性遗传疾病，其特征是在年轻成人中形成数百个结直肠腺瘤性息肉。如果不进行预防性结肠切除术，几乎所有受影响的患者都会发展为结直肠癌。目前，FAP的唯一有效治疗方法是结肠切除术和肠道终身监测。我们的长期目标是为FAP患者发现有效的化学预防治疗，代表一种模型，可以提供对普通肠癌中腺瘤-癌序列的分子调控的见解。 姜黄素是从姜黄中提取的主要黄色色素。姜黄素在亚洲一直被用作香料，被认为是一种安全的食品添加剂。我们的研究小组已经报道了姜黄素在5例FAP患者中使结直肠和回肠腺瘤消退，而没有副作用。我们的假设是，姜黄素可以减少FAP患者的直肠-回肠的生长和相关的上皮过度增殖。 我们的具体目标是：a）在随机、安慰剂对照、双盲试验中向FAP患者施用姜黄素，并通过使用视频内窥镜依次确定直肠-回肠息肉的数量和大小。B）在平坦和息肉样直肠-回肠粘膜中依次评估上皮增殖的标志物（鸟氨酸脱羧酶、多胺和增殖细胞核抗原的免疫组织化学）、凋亡（通过形态学测量和TUNEL测定的凋亡指数）和环氧合酶-2水平（考克斯-2 mRNA的免疫组织化学和qRT-PCR评估）。