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紫杉醇和多西他赛在膀胱癌中的作用:体外活性及尿液稳定性

Taxol and taxotere in bladder cancer: in vitro activity and urine stability.

作者信息

Rangel C, Niell H, Miller A, Cox C

机构信息

Department of Urology, University of Tennessee, Memphis 38163.

出版信息

Cancer Chemother Pharmacol. 1994;33(6):460-4. doi: 10.1007/BF00686501.

Abstract

In this study the antimicrotubular agents taxol, taxotere, and vinblastine were compared for their ability to inhibit the clonal growth of human bladder tumor cell lines using a soft-agar clonogenic assay. The stability of taxol and taxotere was evaluated by high-performance liquid chromatography over a range of pH in human urine. Both taxol and taxotere were shown to maximally inhibit the clonal growth of human bladder cell lines within 1 h of drug incubation. The most active agent in the panel of tumor lines was taxotere, with 6 of 12 lines being sensitive to the agent at 0.01 microM and all cell lines being sensitive at 0.1 microM. Taxol was active in 1 of 12 lines at 0.01 microM and in 11 of 12 at 0.1 microM. Only 2 of 12 cell lines were sensitive to vinblastine over the 0.01- to 0.1-microM dose range. Taxol and taxotere were found to be stable in human urine for 4 h over a pH range of 5-7. At least 85% of both drugs were present during this period of drug incubation. Our findings suggest that both taxol and taxotere may be clinically useful agents for systemic and intravesical use in bladder cancer.

摘要

在本研究中,使用软琼脂克隆形成试验比较了抗微管药物紫杉醇、多西他赛和长春碱抑制人膀胱肿瘤细胞系克隆生长的能力。通过高效液相色谱法在人尿液的一系列pH值范围内评估了紫杉醇和多西他赛的稳定性。紫杉醇和多西他赛均显示在药物孵育1小时内最大程度地抑制人膀胱细胞系的克隆生长。在一组肿瘤细胞系中,最有效的药物是多西他赛,12个细胞系中有6个在0.01微摩尔时对该药物敏感,所有细胞系在0.1微摩尔时均敏感。紫杉醇在0.01微摩尔时对12个细胞系中的1个有活性,在0.1微摩尔时对12个细胞系中的11个有活性。在0.01至0.1微摩尔剂量范围内,12个细胞系中只有2个对长春碱敏感。发现紫杉醇和多西他赛在pH值为5至7的人尿液中4小时内稳定。在药物孵育期间,这两种药物至少有85%存在。我们的研究结果表明,紫杉醇和多西他赛可能是临床上用于膀胱癌全身和膀胱内给药的有用药物。

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