CHEMOPREVENTION OF GASTRIC DYSPLASIA

胃发育不良的化学预防

• 批准号: 6102057
• 负责人: ELIZABETH T. H. FONTHAM
• 金额: $ 29.8万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-04 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6102057
• 关键词: DNA damage; Helicobacter; antibacterial agents; antioxidants; ascorbate; biopsy; cancer prevention; carotene; chemoprevention; clinical research; clinical trials; combination cancer therapy; dietary supplements; gastritis; gastrointestinal neoplasms; gene expression; gene frequency; human subject; human therapy evaluation; metaplasia; neoplasm /cancer nutrition therapy; nutrition aspect of cancer; nutrition related tag; oxidative stress; preneoplastic state

This project is an extension of an on-going randomized, double-blind, placebo-controlled chemoprevention trial initiated in 1991 in a population at high risk of gastric cancer living in the Colombian Andes mountains. This trial seeks to determine the efficacy of chemoprevention on the progression of premalignant gastric lesions by antioxidant supplementation and/or anti-Helicobacter pylori treatment. Using a factorial design, 863 subjects with histopathologically-determined premalignant lesions (multifocal chronic atrophic gastritis, intestinal metaplasia, mild/moderate dysplasia) were randomly-allocated to treatment with ascorbic acid (2 g/day) or placebo, beta-carotene (30 mg/day) or placebo, and anti-Helicobacter pylori treatment (bismuth plus antibiotics) or no treatment. Study subjects have been treated for a total of 3 years (1991/92-1994/95) with an endoscopy and biopsy after 3 years. They will continue on treatment for an additional three years (1994/95-1997/98) with no interruption of treatment because drugs needed for a 3-year extension have been provided. Study subjects will undergo a final endoscopy with biopsies at the end of six years of treatment. The effects of each treatment versus its placebo will be evaluated by comparing baseline and post-treatment endpoints. The primary endpoint is global histopathology and its progression rate. Secondary endpoints include expression of sulfomucins, degree of cell replication (Ki67), frequency of expression of genetic abnormalities (p53, TPR-MET, microsatellite destabilization), indicators of DNA-damage (8-hydroxyguanine adducts) and the presence and quantity of indicators of oxidative stress (iNOS, nitrotyrosine, and apoptosis).

该项目是正在进行的随机，双盲的扩展 安慰剂控制的化学预防试验于1991年开始 居住在哥伦比亚安第斯山山脉的胃癌的高风险。 该试验旨在确定化学预防的功效 抗氧化剂补充剂的胃病变的进展 和/或幽门螺杆菌治疗。 使用阶乘设计863 患有组织病理学确定性预病变的受试者 （多灶性慢性萎缩性胃炎，肠道化生， 轻度/中度发育异常）随机分配给 抗坏血酸（2克/天）或安慰剂，β-胡萝卜素（30 mg/day）或安慰剂， 和抗幽门螺杆菌幽门螺杆菌治疗（Bismuth加抗生素）或无 治疗。 研究对象已经接受了3年的治疗 （1991/92-1994/95）3年后具有内窥镜检查和活检。 他们会的 继续治疗另外三年（1994/95-1997/98） 没有治疗中断，因为延长了3年的药物 已提供。 研究对象将接受最终的内窥镜检查 六年治疗结束时活检。 每个的影响 治疗与安慰剂的治疗将通过比较基线和 治疗后终点。 主要终点是全球组织病理学 及其进展率。 次要终点包括 亚磺素蛋白，细胞复制程度（KI67），表达频率 遗传异常（p53，TPR-MET，微卫星不稳定）， DNA破坏（8-羟基加合物）的指标和存在和 氧化应激的指标数量（iNOS，亚硝基酪氨酸和 凋亡）。