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[曲奥舒凡对肾细胞癌原代细胞培养球体显示出细胞毒性作用,且与P-糖蛋白表达无关]

[Treosulfan displays cytotoxic effect on spheroids of primary cell cultures of renal cell carcinoma independent of p-glycoprotein expression].

作者信息

Kugler A, Hemmerlein B, Gross A J, Seseke F, Kallerhoff M, Ringert R H

机构信息

Abteilung Urologie, Georg-August-Universität Göttingen.

出版信息

Urologe A. 1998 Jul;37(4):367-71. doi: 10.1007/s001200050192.

Abstract

Therapy of advanced renal cell carcinoma remains difficult. New therapeutic schemes besides cytokine treatment should be evaluated. The following study analyzes the in vitro toxicity of treosulfan on spheroids of 8 primary cultures of renal cell carcinoma cells. these data were compared to the toxicity of vinblastine. All investigations were performed in regard to the P-glycoprotein (Pgp) expression of the cells, which is one of the main causes of multidrug resistance. Four Pgp positive and four Pgp negative spheroids were incubated with the drugs in increasing doses. Toxicity was measured using the MTT toxicity assay as well as trypan blue exclusion. Significantly higher toxicity of treosulfan compared to vinblastine could be demonstrated. In addition, the effects of treosulfan were not related to Pgp expression. These results are encouraging and a phase II study analyzing the efficacy of treosulfan in patients with advanced renal cell carcinoma has been initiated in our institution.

摘要

晚期肾细胞癌的治疗仍然困难。除细胞因子治疗外,新的治疗方案应进行评估。以下研究分析了苏消安对8种原发性肾癌细胞培养球体的体外毒性。这些数据与长春碱的毒性进行了比较。所有研究均针对细胞的P-糖蛋白(Pgp)表达进行,P-糖蛋白是多药耐药的主要原因之一。将4个Pgp阳性和4个Pgp阴性球体与递增剂量的药物一起孵育。使用MTT毒性测定法以及台盼蓝排斥法测量毒性。结果表明,与长春碱相比,苏消安的毒性明显更高。此外,苏消安的作用与Pgp表达无关。这些结果令人鼓舞,我们机构已启动一项II期研究,分析苏消安对晚期肾细胞癌患者的疗效。

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