SULINDAC CHEMOPREVENTION IN ADENOMATOUS POLYPOSIS COLI

SULINDAC 化学预防腺瘤性结肠息肉病

• 批准号: 3549722
• 负责人: FRANCIS M GIARDIELLO
• 金额: $ 12.75万
• 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/3549722
• 关键词: S adenosylmethionine; adenocarcinoma; adenoma; antiinflammatory agents; autosomal dominant trait; biomarker; biopsy; cell cycle; chemoprevention; 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.

家族性腺瘤性息肉病（FAP）是一种常染色体显性疾病 以数百种结直肠腺瘤息肉形成的特征 在年轻人中。几乎所有患有FAP的人都会发展结直肠 癌症如果未进行预防性结肠切除术。而且，许多患者 具有上层胃肠道腺瘤，使十二指肠易感性 癌。目前，FAP的唯一有效疗法是结肠切除术和 上胃肠道的终身监视。我们的长期 目标是发现有效的化学预防疗法 FAP，代表一个可能为分子提供基本见解的模型 普通大肠癌中腺瘤 - 癌序列的调节。 Sulindac是一种非甾体类抗炎前列腺素抑制剂，一直是 报道了15例FAP患者的腺瘤息肉的报道。我们的 假设是苏莱达克可以减少结直肠腺瘤的生长和 FAP患者的相关上皮过度增殖。 我们的具体目的是：a）在A中管理Sulindac 随机，安慰剂对照，双盲试验。 b）顺序 通过视频内窥镜检查和息肉量确定结直肠息息数 计算机图像分析。 c）依次评估腺瘤和 非型型结直肠粘膜的活性鸟氨酸脱羧酶和 S-腺苷甲硫代氨酸脱羧酶（对调节的重要酶 多胺途径）和上皮增殖指数 用KI-67抗体增殖细胞核的免疫组织化学 抗原。