Biomarkers in Phototherapy of Barrett's Esophagus

巴雷特食管光疗中的生物标志物

• 批准号: 6531392
• 负责人: KENNETH K WANG
• 金额: $ 32.15万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6531392
• 关键词: Barretts esophagus; aneuploidy; biomarker; biopsy; cell proliferation; clinical research; clinical trials; diet therapy; flow cytometry; fluorescent in situ hybridization; gastrointestinal epithelium; gene expression; gene mutation; genetic markers; high performance liquid chromatography; human subject; human therapy evaluation; immunocytochemistry; longitudinal human study; methylation; neoplasm /cancer photoradiation therapy; neoplastic process; oral mucosa; p53 gene /protein; phototherapy; prognosis; tissue /cell culture

DESCRIPTION (provided by applicant): The purpose of this study is to define the role of biomarkers in photodynamic therapy of Barrett's esophagus. Barrett's esophagus is felt to be the predisposing condition for the most rapidly increasing cancer in Caucasian males. This is a randomized prospective trial to determine the effect of photodynamic therapy on biomarkers in Barrett's esophagus and to determine the role of biomarkers in predicting response to therapy. Preliminary studies have indicated that photodynamic therapy appears to be more effective in patients who do not have specific biomarkers. In addition, it appears that patients who undergo photodynamic therapy may have improvement in histology without improvement in biomarkers. Photodynamic therapy may induce mutations in certain genes even in normal appearing tissue. It is the goal of this protocol to determine the effect of photodynamic therapy on biomarkers that have been established to be predictors of progression to neoplasia in Barrett's esophagus. These biomarkers will include assessment of cell proliferation, ploidy, p53 expression, p53 mutations, P16 promoter hypermethylation, P16 loss, and P53 loss. Methods of assessment will include denaturing high pressure liquid chromatography, image cytometry, fluorescent in situ hybridization, and immunohistochemistry. Patients with and without biomarkers will be randomized to receive photodynamic therapy and a proton pump inhibitor or a proton pump inhibitor alone. Patients treated with photodynamic therapy will receive standard dosages of sodium porfimer (2 mg/kg) and photoradiation (130 J/cm fiber) using a balloon light delivery system. Patients will have their biomarkers assessed at six month intervals. Biological sampling will be done by biopsy and cytology to enhance sampling of the mucosal surface. In addition, primary cultures of Barrett's esophagus and squamous epithelium will be assessed for mutagenesis after photodynamic therapy in vitro to determine the rate of mutagenesis of p53. It is hoped that this study will help to define the role of photodynamic therapy in mucosal ablation of Barrett's esophagus in terms of patient selection and biomarkers that may predict response to therapy. These observations can be extended to other forms of ablative therapy in future studies.

描述（由申请人提供）：本研究的目的是定义生物标志物在巴雷特食管的光动力疗法中的作用。巴雷特的食管被认为是高加索男性癌症最快增加的诱人状况。这是一项随机前瞻性试验，旨在确定光动力疗法对Barrett食管中生物标志物的影响，并确定生物标志物在预测治疗反应中的作用。初步研究表明，对于没有特定生物标志物的患者，光动力疗法似乎更有效。此外，看来接受光动力疗法的患者可能会改善组织学，而不会改善生物标志物。即使在正常出现的组织中，光动力疗法也可能诱导某些基因的突变。该方案的目的是确定光动力疗法对已确定为Barrett食管中肿瘤发展的生物标志物的影响。这些生物标志物将包括评估细胞增殖，倍性，p53表达，p53突变，p16启动子高甲基化，p16损失和p53损失。评估方法将包括贬低高压液相色谱，图像细胞仪，荧光原位杂交和免疫组织化学。有或没有生物标志物的患者将被随机分配，以接受光动力疗法和质子泵抑制剂或质子泵抑制剂。接受光动力疗法治疗的患者将使用球囊光递送系统接受标准剂量的钠por饮（2 mg/kg）和光照相（130 J/cm纤维）。患者将以六个月的间隔评估其生物标志物。生物学采样将通过活检和细胞学来增强粘膜表面的采样。此外，将评估Barrett食管和鳞状上皮的原发性培养物在体外光动力疗法后进行诱变，以确定p53的诱变率。希望这项研究将有助于定义光动力疗法在Barrett食管的粘膜消融中的作用，以预测可能预测治疗反应的患者选择和生物标志物。在未来的研究中，这些观察结果可以扩展到其他形式的消融疗法。