Barrett's Esophagus: Predictors of Progression

巴雷特食管：进展的预测因素

• 批准号: 6767580
• 负责人: BRIAN J REID
• 金额: $ 225.63万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-16 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6767580
• 关键词: Barretts esophagus; clinical research; human subject; neoplastic process; patient oriented research

DESCRIPTION (provided by applicant) This application brings together an experienced team of investigators into a P01 to study Barrett's esophagus (BE), the only established precursor of esophageal adenocarcinoma (EA), a rapidly increasing, highly lethal malignancy. BE is also a unique in vivo model of human epithelial neoplasia, and the P01 theme of genomic instability: its etiology, manifestations and progression focuses on fundamental mechanisms of human neoplastic progression. Thus, our primary and secondary goals are to (1) reduce morbidity and mortality of EA by early detection, prevention, or both and (2) elucidate mechanisms of human neoplastic progression in vivo that may be shared by other neoplasms whose early stages are less amenable to investigation. Our study design is a prospective investigation of the Seattle Barrett's Esophagus Cohort, one of the largest and best characterized in the world. All data in the P01 will be derived from this cohort, maintained by Core B (Clinical Research). Project 1 (Clonal Evolution) hypothesizes that the evolution of clonal lesions in p16, p53 and ploidy are intrinsic to mechanisms of neoplastic progression. It seeks to determine the extent to which they predict neoplastic progression in BE and to identify transcription patterns that mediate transitions from one stage of progression to another and give rise to EA. Project 2 (Epidemiology) hypothesizes that environmental exposures and host factors, including NSAIDs, serum selenium, bile reflux, high fat, low fruit and vegetable diet and being overweight, modulate progression. It seeks to determine the extent to which these factors are associated with the genetic markers that are developed in Projects 1 and 3, as well as clinical outcome as assessed by Core B. Project 3 (Genetic Instability) hypothesizes that loss of normal mechanisms that insure genomic stability is an early event that contributes to neoplastic progression in BE. The mechanisms that contribute to chromosomal and mitotic instability will be studied, and the utility of measures of genetic instability as predictors of clinical prognosis and as targets for therapeutic intervention will be determined. The P01 is highly collaborative and all projects and cores interact with each other. Thus, the clonal markers and measures of instability provided by Projects 1 and 3, respectively, become shared resources to advance the common goals of the P01. These interactions are facilitated by Core C (Bioinformatics/Biostatistics), which provides a framework for analysis of the complicated datasets of the projects and a vehicle for interproject and core communications.

描述（由申请人提供） 该应用程序汇集了一支经验丰富的调查人员团队 P01研究Barrett的食道（BE），这是唯一建立的先兆 食道腺癌（EA），迅速增加，高度致命 恶性。 Be也是人类上皮肿瘤的体内独特模型， 以及基因组不稳定性的P01主题：其病因，表现和 进展重点是人类肿瘤进展的基本机制。 因此，我们的主要目标和次要目标是（1）降低发病率和 EA通过早期检测，预防或两者的死亡率以及（2）阐明 人类肿瘤进展的机制在体内可能由其他人共享 早期阶段的肿瘤不太适合调查。我们的研究 设计是对西雅图巴雷特食管的前瞻性调查 队列，世界上最大，最佳的特征之一。所有数据输入 P01将源自该队列，由Core B维护（临床 研究）。项目1（克隆进化）假设 p16，p53和倍性的克隆病变与机制固有 肿瘤进展。它试图确定他们的程度 预测BE中的肿瘤进展并确定转录模式 介导从一个进步阶段到另一个阶段的过渡，并给予 崛起到EA。项目2（流行病学）假设环境 暴露和宿主因素，包括NSAID，血清硒，胆汁反流， 高脂肪，低水果和蔬菜饮食以及超重，调节 进展。它试图确定这些因素的程度 与项目1和3中开发的遗传标记有关 以及核心B所评估的临床结果。项目3（遗传 不稳定性）假设丧失了确保基因组的正常机制 稳定性是一个早期事件，有助于BE的肿瘤发展。 导致染色体和有丝分裂不稳定性的机制将是 研究，以及遗传不稳定性的措施作为预测指标 临床预后和作为治疗干预的目标将是 决定。 P01是高度协作的，所有项目和核心 彼此互动。因此，克隆标记和衡量标记 项目1和3分别提供的不稳定性被共享 推进P01的共同目标的资源。这些相互作用是 由Core C（生物信息学/生物统计学）促进，该核心提供了 分析项目复杂数据集的框架和 室内和核心通信的车辆。