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Effects of Telomerase Expression on Photodynamic Therapy of Barrett's Esophagus

机译:端粒酶表达对巴雷特食管光动力治疗的影响

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Photodynamic therapy has been applied to Barrett's esophagus and has been shown in prospective randomized studies to eliminate dysplasia as well as decrease the occurrence of cancer. However, the therapy is not always effective and there are issues with residual areas of Barrett's mucosa despite therapy. There has not been a good explanation for these residual areas and they seem to imply that there may exist a biological mechanism by which these cells may be resistant to photodynamic therapy. It was our aim to determine if known abnormalities in Barrett's mucosa could be correlated with the lack of response of some of these tissues. We examined the tissue from multiple patients who had response to therapy as well as those who did not respond. We assessed the tissue for p53 mutations, inactivation of p16, ploidy status, cell proliferation, telomerase activity, and degree of dysplasia. Interestingly, the only genetic marker than was found to be correlated with lack of response was p53 and telomerase activity. This suggests that cells that have lost mechanisms for cell death such as apoptosis or telomere shortening may be more resstant to photodynamic therapy. In this study, we examined patients before and after PDT for telomerase activity.
机译:光动力疗法已应用于巴雷特食管,并已在前瞻性随机研究中表明,可以消除发育不良并减少癌症的发生。然而,该疗法并不总是有效的,尽管进行了治疗,Barrett粘膜的残留区域仍存在问题。对于这些残留区域还没有很好的解释,它们似乎暗示着可能存在这些细胞可能对光动力疗法产生抗药性的生物学机制。我们的目的是确定巴雷特粘膜的已知异常是否与某些组织缺乏反应有关。我们检查了多位对治疗有反应的患者和无反应的患者的组织。我们评估了组织中的p53突变,p16失活,倍性状态,细胞增殖,端粒酶活性和不典型增生的程度。有趣的是,唯一被发现与缺乏反应相关的遗传标记是p53和端粒酶活性。这表明那些失去细胞死亡机制(例如凋亡或端粒缩短)的细胞可能对光动力疗法更具抵抗力。在这项研究中,我们检查了PDT之前和之后的患者端粒酶活性。

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