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吡柔比星膀胱灌注预防非肌层浸润性膀胱癌复发的机制

[Mechanism of intravesical instillation of pirarubicin for preventing recurrence of non-muscle invasive bladder cancer].

作者信息

Li Qing, Xu Tao, Wang Xiao-feng

机构信息

Department of Urology, Peking University People's Hospital, Beijing 100044, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2009 Dec;31(12):904-7.

Abstract

OBJECTIVE

To evaluate the apoptosis-inducing effect of intravesical instillation of pirarubicin (THP) on bladder cancer and normal bladder tissue, and explore the mechanism of such treatment for preventing recurrence of non-muscle invasive bladder cancer.

METHODS

Forty patients with primary non-muscle invasive bladder cancer were treated in our hospital from January 2006 to October 2008. The patients were divided into three groups, including 15 cases treated by intravesical instillation of THP (30 mg/50 ml, 0.5 hours) at 1 hour, 15 cases at 24 hours before transuretheral resection of bladder tumor (TUR-BT), and 10 cases in control group who received TUR-BT only. The THP uptake of the tumor and normal bladder tissues was observed by fluorescence microscopy, the apoptosis was assessed with TUNEL staining, and immunohistochemistry was used to detect the expression of bcl-2 and bax.

RESULTS

Seldom fluorescence of THP in normal bladder tissues and some diffuse fluorescence reaching the muscular layer in the tumor area were observed after THP instillation at 1 hour before TUR-BT. The fluorescence of THP could still be observed in the tumor tissues at 24 hours after THP instillation. The apoptosis indexes (AI) of tumors in the chemotherapy groups were significantly higher than that in the control group (P < 0.01). There was a correlation between bcl-2/bax ratio and AI.

CONCLUSION

Pirarubicin can be uptaken by bladder cancer tissue selectively and induces apoptosis of tumor cells. The changes of expression of bcl-2 and bax and decreasing of the bcl-2/bax ratio may be an important mechanism of action of the intravesical instillation of THP for preventing recurrence of non-muscle invasive bladder cancer.

摘要

目的

评估膀胱内灌注吡柔比星(THP)对膀胱癌及正常膀胱组织的凋亡诱导作用,并探讨该治疗方法预防非肌层浸润性膀胱癌复发的机制。

方法

选取2006年1月至2008年10月在我院治疗的40例原发性非肌层浸润性膀胱癌患者。将患者分为三组,其中15例在经尿道膀胱肿瘤电切术(TUR - BT)前1小时膀胱内灌注THP(30 mg/50 ml,0.5小时),15例在TUR - BT前24小时膀胱内灌注THP,10例为对照组,仅接受TUR - BT。通过荧光显微镜观察肿瘤及正常膀胱组织对THP的摄取情况,采用TUNEL染色评估凋亡情况,免疫组化法检测bcl - 2和bax的表达。

结果

TUR - BT前1小时灌注THP后,正常膀胱组织中THP荧光少见,肿瘤区域有一些弥漫性荧光到达肌层。THP灌注后24小时肿瘤组织中仍可观察到THP荧光。化疗组肿瘤的凋亡指数(AI)显著高于对照组(P < 0.01)。bcl - 2/bax比值与AI之间存在相关性。

结论

吡柔比星可被膀胱癌组织选择性摄取并诱导肿瘤细胞凋亡。bcl - 2和bax表达的变化以及bcl - 2/bax比值的降低可能是膀胱内灌注THP预防非肌层浸润性膀胱癌复发的重要作用机制。

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