SULINDAC CHEMOPREVENTION IN ADENOMATOUS POLYPOSIS COLI

SULINDAC 化学预防腺瘤性结肠息肉病

• 批准号: 3549720
• 负责人: FRANCIS M GIARDIELLO
• 金额: $ 12.83万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-03-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3549720
• 关键词: S adenosylmethionine; adenocarcinoma; adenoma; antiinflammatory agents; autosomal dominant trait; biomarker; biopsy; cancer prevention; cell cycle; colorectal neoplasms; endoscopy; gastrointestinal epithelium; genetic disorder; human subject; human therapy evaluation; hyperplasia; imaging /visualization /scanning; immunocytochemistry; monoclonal antibody; neoplasm /cancer chemotherapy; neoplastic growth; ornithine decarboxylase; placebos; prostaglandin inhibitors; statistics /biometry

Familial adenomatous polyposis coli (FAP) is an autosomal dominant disorder characterized by the formation of hundreds of colorectal adenomatous polyps in young adults. Virtually all individuals with FAP will develop colorectal cancer if prophylactic colectomy is not performed. Moreover, many patients have upper gastrointestinal adenomas which predispose to duodenal carcinoma. Presently, the only effective therapy for FAP is colectomy and lifelong surveillance of the upper gastrointestinal tract. Our long term goal is to discover effective chemopreventative therapy for patients with FAP, representing a model which may provide basic insights into molecular regulation of the adenoma-carcinoma sequence in ordinary colorectal cancer. Sulindac, a nonsteroidal antiinflammatory prostaglandin inhibitor, has been reported anecdotally to resolve adenomatous polyps in 15 FAP patients. Our hypothesis is that sulindac can decrease growth of colorectal adenomas and the associated epithelial hyperproliferation in FAP patients. Our specific aims are to: a) Administer sulindac to FAP patients in a randomized, placebo-controlled, double-blinded trial. b) Sequentially determine colorectal polyp number by video endoscopy and polyp volume by computerized image analysis. c) Sequentially assess in adenomas and nonpolypoid colorectal mucosa the activity of ornithine decarboxylase and S-adenosylmethionine decarboxylase (enzymes important in the regulation of the polyamine pathway), and epithelial proliferation index by immunohistochemistry with Ki-67 antibody to proliferating cell nuclear antigen.

家族性腺瘤性大肠杆菌 (FAP) 是一种常染色体显性遗传疾病 其特征是形成数百个结直肠腺瘤性息肉 在年轻人中。几乎所有患有 FAP 的人都会患上结直肠癌 如果不进行预防性结肠切除术，则会患癌症。而且，很多患者 患有易患十二指肠癌的上消化道腺瘤 癌。目前，FAP唯一有效的治疗方法是结肠切除术和 上胃肠道的终身监测。我们的长期 目标是为患有以下疾病的患者找到有效的化学预防疗法 FAP，代表一个可以提供分子基本见解的模型 普通结直肠癌中腺瘤-癌序列的调节。 舒林酸是一种非甾体类抗炎前列腺素抑制剂 据报道，该药物可治愈 15 名 FAP 患者的腺瘤性息肉。我们的 假设舒林酸可以减少结直肠腺瘤的生长 FAP 患者相关的上皮过度增殖。 我们的具体目标是： a) 对 FAP 患者给予舒林酸 随机、安慰剂对照、双盲试验。 b) 依次 通过视频内窥镜检查确定结直肠息肉数量和息肉体积 计算机图像分析。 c) 依次评估腺瘤和 非息肉样结直肠粘膜鸟氨酸脱羧酶的活性和 S-腺苷甲硫氨酸脱羧酶（在调节 多胺途径）和上皮增殖指数 Ki-67 抗体对增殖细胞核的免疫组织化学 抗原。