BARRETT'S ESOPHAGUS---A UNIQUE PREMALIGNANT LESION FOR ADENOCARCINOMAS

巴雷特食管是一种食管下部 内衬化生柱状上皮，而不是 正常复层鳞状上皮。 它与一个 增加患癌症的风险。 Barrett's引起的癌症 上皮是腺癌而不是通常的鳞状细胞癌 细胞性食管癌 巴雷特是一个独特的， 癌前病变，因为它代表了一个完全不同的 因此，在组织学上， 以确定性来识别。 因此，它提供了一个不寻常的 研究和表征癌前病变的机会， 腺癌 在我们的机构里， 组织学证实的巴雷特食管 一项临床研究，以前瞻性地确定自然史， 这种疾病 新病人的进入速度是 每月约2。 这提供了宝贵的资源 用于实验室和临床研究。 具体 本提案的目的是：（1）建立和 表征来自Barrett上皮的细胞系;（2）使用细胞 研究药物和生物反应调节剂的作用 对巴雷特上皮细胞的生长和分化的影响;和（3） 将我们的初步观察结果 Barrett粘膜中的脱羧酶（ODC）水平，并检测 ODC抑制剂对培养的Barrett细胞的作用。 本研究的长期目标是建立体外模型 癌前病变的腺癌使用巴雷特 粘膜上皮 这种模式的可用性显然将 对致癌作用领域的研究者是有用的， 癌症病因学和预防。 同样重要的是， 短期目标是找到成功的药物治疗方法， 治疗巴雷特食管 从临床角度来看，任何 发现在巴雷特食管中有活性的药剂可 证明在其他癌前病变中是有用的 腺癌

Barrett's esophagus is a condition in which the lower esophagus is lined with metaplastic columnar epithelium rather than the normal stratified squamous epithelium. It is associated with an increased risk of cancer. Cancers arising from Barrett's epithelium are adenocarcinomas rather than the usual squamous cell esophageal cancers. Barrett's is somewhat unique amongst premalignant lesions, since it represents an entirely different epithelium from the normal and, therefore, can be histologically identified with certainty. Consequently, it offers an unusual opportunity to study and characterize premalignant lesions for adenocarcinomas. At our institution we have over 70 patients with histologically confirmed Barrett's esophagus that are part of a clinical study to prospectively define the natural history of the disease. New patients are being entered at a rate of approximately 2 per month. This provides an invaluable resource for combined laboratory and clinical investigations. Specific aims of the present proposal are to: (1) establish and characterize cell lines from Barrett's epithelium; (2) use the cell lines to study the effect of drugs and biologic response modifiers on growth and differentiation of Barrett's epithelial cells; and (3) extend our preliminary observations on elevated ornithine decarboxylase (ODC) levels in Barrett's mucosa and test the effect of ODC inhibitors on cultured Barrett's cells. The long-term goal of this study is to develop an in vitro model of a premalignant lesion for adenocarcinoma using Barrett's mucosal epithelium. Availability of such a model would clearly be of utility to investigators in the field of carcinogenesis, cancer etiology and prevention. The equally important, but shorter term objective, is to find successful medical therapy for treating Barrett's esophagus. From a clinical standpoint, any agents that are found to be active in Barrett's esophagus may prove to be useful in other premalignant lesions of adenocarcinomas.