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卡介苗作为膀胱癌的免疫调节剂

[The bacillus Calmette-Guérin as immunomodulator in bladder cancer].

作者信息

Vázquez-Lavista Luis Gabriel, Flores-Balcázar Christian Haydeé, Llorente Luis

机构信息

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, México, D F.

出版信息

Rev Invest Clin. 2007 Mar-Apr;59(2):146-52.

Abstract

The bacillus Calmette-Guérin (BCG) is regarded as the most successful immunotherapy against superficial bladder carcinoma recurrences to date. BCG intravesical therapy for superficial bladder cancer has shown its efficacy and advantage over classical therapeutic strategies. This efficacy is based on complex and long lasting immune activation. The initial step is the binding of mycobacteria to the urothelial lining, which depends on the interaction of a fibronectin attachment protein on the bacteria surface with fibronectin in the bladder wall. Granulocytes and other immunocompetent mononuclear cells became attracted to the bladder wall and a cascade of proinflammatory cytokines sustains the immune response. In the bladder wall a largely TH1 based cytokine milieu and granuloma-like cellular foci are established. Within this scenario, the most important effector mechanisms might be the direct antitumor activity of interferons and the cytotoxic activity of NK cells. Current treatment consists of an induction phase of 6 weeks and a maintenance dose schedule of 3 weeks every three months up to 36. The majority of patients present adverse events related to dose administration due to bladder inflammatory response and on only a few occasions, there are mayor complications like granulomatous prostatitis. Among all the neoplasms only in superficial bladder cancer the BCG is proved to be effective.

摘要

卡介苗(BCG)被认为是迄今为止针对浅表性膀胱癌复发最成功的免疫疗法。卡介苗膀胱内灌注治疗浅表性膀胱癌已显示出其相对于传统治疗策略的疗效和优势。这种疗效基于复杂且持久的免疫激活。第一步是分枝杆菌与尿路上皮衬里结合,这取决于细菌表面的纤连蛋白附着蛋白与膀胱壁中的纤连蛋白之间的相互作用。粒细胞和其他具有免疫活性的单核细胞被吸引到膀胱壁,一系列促炎细胞因子维持免疫反应。在膀胱壁内建立了主要基于TH1的细胞因子环境和肉芽肿样细胞灶。在这种情况下,最重要的效应机制可能是干扰素的直接抗肿瘤活性和自然杀伤细胞的细胞毒性活性。目前的治疗包括6周的诱导期和每三个月3周的维持剂量方案,持续36周。由于膀胱炎症反应,大多数患者出现与给药相关的不良事件,仅在少数情况下会出现如肉芽肿性前列腺炎等主要并发症。在所有肿瘤中,只有在浅表性膀胱癌中卡介苗被证明是有效的。

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