Biomarkers in Phototherapy of Barrett's Esophagus

描述(申请人提供)：本研究的目的是确定生物标记物在Barrett‘s食管光动力疗法中的作用。巴雷特食道被认为是高加索男性癌症增长最快的诱因。这是一项随机前瞻性试验，旨在确定光动力治疗对Barrett‘s食道生物标志物的影响，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，光动力疗法似乎对没有特定生物标志物的患者更有效。此外，似乎接受光动力治疗的患者可能在组织学上有所改善，但生物标记物没有改善。光动力疗法可能会导致某些基因发生突变，即使是在外表正常的组织中也是如此。该方案的目的是确定光动力疗法对生物标志物的影响，这些生物标志物已被确定为Barrett‘s食道肿瘤进展的预测因子。这些生物标志物将包括评估细胞增殖、倍体、P53表达、P53突变、P16启动子超甲基化、P16缺失和P53缺失。评估方法将包括变性高压液相色谱、图像细胞术、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随机接受光动力学治疗，并单独接受质子泵抑制剂或质子泵抑制剂。接受光动力治疗的患者将接受标准剂量的异丙酚钠(2 mg/kg)和使用球囊光传递系统的光放射(130 J/cm纤维)。患者将每隔六个月接受一次生物标志物评估。将通过活组织检查和细胞学进行生物采样，以加强对粘膜表面的采样。此外，在体外光动力疗法后，将对Barrett‘s食道和鳞状上皮的原代培养进行诱变评估，以确定P53的突变率。希望这项研究将有助于确定光动力疗法在Barrett‘s食道粘膜消融术中的作用，包括患者的选择和可预测治疗反应的生物标志物。在未来的研究中，这些观察可以扩展到其他形式的消融治疗。

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.