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).

家族性腺瘤性结肠息肉病 (FAP) 是一种由 APC 基因种系突变引起的常染色体显性遗传性疾病，其特征是在年轻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患上结直肠癌。目前，FAP 唯一有效的治疗方法是结肠切除术和肠道的终身监测。我们的长期目标是为 FAP 患者发现有效的化学预防疗法，这代表了一个模型，可以为普通肠癌中腺瘤-癌序列的分子调控提供见解。 姜黄素是从姜黄（草本植物姜黄根的粉末根）中提取的主要黄色色素。姜黄素在亚洲长期以来一直被用作香料，被认为是一种安全的食品添加剂。我们小组报告姜黄素使 5 名 FAP 患者的结直肠和回肠腺瘤消退，且没有副作用。我们的假设是姜黄素可以减少 FAP 患者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) 在一项随机、安慰剂对照、双盲试验中对 FAP 患者施用姜黄素，并通过视频内窥镜依次确定直肠回肠息肉的数量和大小。 b) 依次评估扁平状和息肉状直肠回肠粘膜上皮增殖标志物（鸟氨酸脱羧酶、多胺和增殖细胞核抗原的免疫组织化学）、细胞凋亡（形态学测量和 TUNEL 测定的细胞凋亡指数）和环氧合酶-2 水平（免疫组织化学和COX-2 mRNA 的 qRT-PCR 评估）。