Biomarkers in Phototherapy of Barrett's Esophagus

描述（由申请方提供）：本研究的目的是确定生物标志物在Barrett食管光动力学治疗中的作用。巴雷特食管被认为是高加索男性中最迅速增加的癌症的诱发条件。这是一项随机前瞻性试验，旨在确定光动力疗法对Barrett食管生物标志物的影响，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，似乎接受光动力疗法的患者可能在组织学上有所改善，而生物标志物没有改善。光动力疗法可以诱导某些基因的突变，甚至在正常的组织中。本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食管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、倍性、p53表达、p53突变、P16启动子高甲基化、P16缺失和P53缺失。评估方法包括变性高压液相色谱法、图像细胞术、荧光原位杂交和免疫组织化学。有和无生物标志物的患者将随机接受光动力学治疗和质子泵抑制剂或单独接受质子泵抑制剂。接受光动力疗法治疗的患者将使用球囊光输送系统接受标准剂量的钠离子（2 mg/kg）和光辐射（130 J/cm光纤）。患者将以六个月的间隔评估其生物标志物。将通过活检和细胞学进行生物学采样，以加强粘膜表面的采样。此外，将在体外光动力疗法后评估Barrett食管和鳞状上皮的原代培养物的诱变，以确定p53的诱变率。希望这项研究将有助于确定光动力疗法在Barrett食管粘膜消融中的作用，包括患者选择和可预测治疗反应的生物标志物。这些观察结果可以在未来的研究中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.