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紫杉醇对连续移植到裸鼠体内的人乳腺癌异种移植物的抗肿瘤活性。

Antitumor activity of paclitaxel against human breast carcinoma xenografts serially transplanted into nude mice.

作者信息

Kubota T, Matsuzaki S W, Hoshiya Y, Watanabe M, Kitajima M, Asanuma F, Yamada Y, Koh J I

机构信息

Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.

出版信息

J Surg Oncol. 1997 Feb;64(2):115-21. doi: 10.1002/(sici)1096-9098(199702)64:2<115::aid-jso5>3.0.co;2-e.

Abstract

BACKGROUND

Paclitaxel (BMS-181339: Taxol) is a promising agent against previously treated breast cancer. The antitumor activity of paclitaxel was evaluated using five human breast carcinoma xenografts in nude mice.

METHODS

Paclitaxel at 20 mg/kg dissolved in 0.2 ml ethanol/cremophor EL solution was administered intraperitoneally daily for 5 days.

RESULTS

Paclitaxel showed significant antitumor activity against MCF-7 and MX-1, but only limited activity against the other three xenografts (R-27, Br-10, and T-61), suggesting its substantially different antitumor spectrum from conventional antibreast cancer drugs. The different sensitivity of xenografts to paclitaxel was successfully reproduced in vitro using the MTT assay, when the cutoff concentration of paclitaxel was 20 microg/ml.

CONCLUSION

Since no significant differences were observed in the pharmacokinetics of paclitaxel in sensitive and resistant tumor cell lines, the efficacy of this agent seemed to depend on the sensitivity of tumor cells rather than the intratumoral concentration of agent.

摘要

背景

紫杉醇(BMS - 181339:泰素)是一种对既往接受过治疗的乳腺癌有前景的药物。在裸鼠中使用五种人乳腺癌异种移植瘤评估了紫杉醇的抗肿瘤活性。

方法

将溶解于0.2 ml乙醇/聚氧乙烯蓖麻油EL溶液中的20 mg/kg紫杉醇每日腹腔注射,共5天。

结果

紫杉醇对MCF - 7和MX - 1显示出显著的抗肿瘤活性,但对其他三种异种移植瘤(R - 27、Br - 10和T - 61)仅显示出有限的活性,提示其抗肿瘤谱与传统抗乳腺癌药物有很大不同。当紫杉醇的临界浓度为20μg/ml时,使用MTT法在体外成功重现了异种移植瘤对紫杉醇的不同敏感性。

结论

由于在敏感和耐药肿瘤细胞系中未观察到紫杉醇药代动力学的显著差异,该药物的疗效似乎取决于肿瘤细胞的敏感性而非肿瘤内药物浓度。

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