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在药物筛选中体内中空纤维测定和异种移植测定的相关性。

Correlative effect between in vivo hollow fiber assay and xenografts assay in drug screening.

机构信息

Kolon Central Research Park, Yongin, Korea.

出版信息

Cancer Res Treat. 2005 Jun;37(3):196-200. doi: 10.4143/crt.2005.37.3.196. Epub 2005 Jun 30.

Abstract

PURPOSE

This study was carried out to assess the usage of an in vivo hollow fiber assay to screen drugs with highly predictive accuracy.

MATERIALS AND METHODS

The assay systems used were the hollow fiber and xenografts assays. The hollow fiber assay was carried out with the following steps; preparation of fibers, preparation of cells, loading and implanting fibers, treatment with drugs, removal of fibers and assaying for the cell viability by the MTT assay. For the xenografts assay, cell suspensions were subcutaneously transplanted into the mice. Therapy was started when the tumor volume reached 100 approximately 200 mm(3). The tumor volumes were calculated using the formula V=[length+(width)(2)]/2, and used for evaluating the efficacy of the drugs. The drug treatment doses used were adriamycin 2.1 mg/kg, mitomycin-C 0.25 mg/kg, 5-fluorouracil 24.5 mg/kg and paclitaxel 2.5 mg/kg, and administrated intravenously five times daily.

RESULTS

The correlation between the xenografts and hollow fiber assays was evaluated in 20 tumor cell lines and 4 anti-cancer agents. In the 20 tumor cell lines, the overall predictive accuracy of the hollow fiber assay for sensitivity was 83%, with a predictive accuracy for resistance of 92%.

CONCLUSION

The hollow fiber assay was assessed as effective in drug efficacy evaluation, and found to be compatible with that of the xenografts assay.

摘要

目的

本研究旨在评估体内中空纤维测定法在高预测准确性药物筛选中的应用。

材料和方法

使用的测定系统包括中空纤维和异种移植测定法。中空纤维测定法按以下步骤进行:纤维制备、细胞制备、纤维装载和植入、药物处理、纤维去除以及通过 MTT 测定法检测细胞活力。对于异种移植测定法,将细胞悬浮液皮下移植到小鼠中。当肿瘤体积达到 100 至 200mm³左右时开始治疗。使用公式 V=[长度+(宽度)²]/2 计算肿瘤体积,并用于评估药物的疗效。使用的药物治疗剂量为阿霉素 2.1mg/kg、丝裂霉素-C 0.25mg/kg、5-氟尿嘧啶 24.5mg/kg 和紫杉醇 2.5mg/kg,每天静脉内给药 5 次。

结果

在 20 种肿瘤细胞系和 4 种抗癌药物中评估了异种移植和中空纤维测定法之间的相关性。在 20 种肿瘤细胞系中,中空纤维测定法对敏感性的总体预测准确性为 83%,对耐药性的预测准确性为 92%。

结论

中空纤维测定法在药物疗效评估中被评估为有效,并与异种移植测定法相兼容。

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