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首页> 外文期刊>BJU international >Bad expression influences time to androgen escape in prostate cancer.
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Bad expression influences time to androgen escape in prostate cancer.

机译：错误的表达影响前列腺癌中雄激素逃逸的时间。

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OBJECTIVE To assess the role of selected downstream Bcl-2 family members (Bad, Bax, Bcl-2 and Bcl-xL) in the development of androgen-independent prostate cancer (AIPC), as androgen-deprivation therapy is the treatment of choice in advanced prostate cancer, yet patients generally relapse and progress to an AI state within 18-24 months. PATIENTS, MATERIALS AND METHODS The patient cohort was established by retrospectively selecting patients with prostate cancer who had an initial response to androgen-deprivation therapy, but subsequently relapsed with AIPC. In all, 58 patients with prostate cancer were included with matched androgen-dependent (AD) and AI prostate tumours available for immunohistochemical analysis; two independent observers using a weighted-histoscore method scored the staining. Changes in Bad, Bax, Bcl-2 and Bcl-xL expression during transition to AIPC were evaluated and then correlated to known clinical variables. RESULTS High Bad expression in AD tumours was associated with an increased time to biochemical relapse (P = 0.007) and a trend towards improved overall survival (P = 0.053). There were also trends towards a decrease in Bad (P = 0.068) and Bax (P = 0.055) expression with progression to AIPC. There were no significant results for Bcl-2 or Bcl-xL. CONCLUSION There is evidence to suggest that Bad expression levels at diagnosis influence time to biochemical relapse and overall survival, and that levels of pro-apoptotic proteins Bad and Bax fall during AIPC development. Bad might therefore represent a possible positive prognostic marker and potential therapeutic target for AIPC in the future.
机译：目的评估选定的下游Bcl-2家族成员（Bad，Bax，Bcl-2和Bcl-xL）在雄激素非依赖性前列腺癌（AIPC）的发展中的作用，因为雄激素剥夺疗法是选择的治疗方法晚期前列腺癌，但是患者通常会在18-24个月内复发并发展为AI状态。患者，材料和方法通过回顾性选择对雄激素剥夺疗法起初反应，但随后AIPC复发的前列腺癌患者，建立了患者队列。总共有58例前列腺癌患者包括匹配的雄激素依赖性（AD）和AI前列腺肿瘤，可用于免疫组织化学分析。两名独立的观察者使用加权历史评分法对染色进行评分。评估了向AIPC过渡过程中Bad，Bax，Bcl-2和Bcl-xL表达的变化，然后将其与已知的临床变量相关联。结果AD肿瘤中Bad的高表达与生化复发时间的增加（P = 0.007）和总体生存期的改善（P = 0.053）有关。随着AIPC的发展，Bad（P = 0.068）和Bax（P = 0.055）表达也有下降的趋势。 Bcl-2或Bcl-xL没有明显的结果。结论有证据表明，诊断时Bad的表达水平会影响生化复发和整体生存的时间，而促凋亡蛋白Bad和Bax的水平会在AIPC发育过程中下降。因此，不良可能代表AIPC未来可能的阳性预后标志物和潜在治疗靶标。

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