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使用源自非精原细胞瘤性生殖细胞肿瘤和膀胱移行细胞癌的人类细胞系面板在体外筛选新型抗癌药物。

Screening of new anticancer agents in vitro using panels of human cell lines derived from non-seminomatous germ cell tumours and transitional cell carcinomas of the bladder.

作者信息

Masters J R, Jenkins W E, Shoemaker R H

机构信息

University College London, Institute of Urology and Nephrology, U.K.

出版信息

Eur J Cancer. 1992;28A(10):1617-22. doi: 10.1016/0959-8049(92)90054-6.

Abstract

Metastatic testis tumours are cured in over 80% of patients using combination chemotherapy, and this hypersensitivity is retained by the cells in vitro. To determine whether differential toxicity to testis tumour cells is useful in the screening of novel anticancer agents, we compared the toxicities of 12 compounds against panels of human bladder and testis tumour cell lines using a clonogenic assay. The compounds had screened negative against P388 in vivo, and had been retested using the human tumour colony forming assay (HTCFA) and in selected cases against human tumour xenografts. NSC 339004, chloroquinoxaline sulphonamide, was 7-fold more toxic to testis tumour than bladder cancer cells, comparing the mean of the concentrations reducing colony-forming ability by 70%. This was the only one of the compounds selected by the HTCFA shown to have clinical activity. Compound R was selectively toxic to the bladder cancer cells, and might be of value as an intravesical agent. These data indicate that panels of testis and bladder cancer cell lines might be a useful addition to the disease-oriented screening programme.

摘要

采用联合化疗,超过80%的转移性睾丸肿瘤患者可被治愈,且这种超敏反应在体外细胞中得以保留。为了确定对睾丸肿瘤细胞的差异毒性是否有助于新型抗癌药物的筛选,我们使用克隆形成试验比较了12种化合物对人膀胱和睾丸肿瘤细胞系的毒性。这些化合物在体内对P388筛选呈阴性,并已使用人肿瘤集落形成试验(HTCFA)重新测试,在某些情况下还针对人肿瘤异种移植物进行了测试。NSC 339004,氯喹喔啉磺酰胺,对睾丸肿瘤的毒性比对膀胱癌细胞高7倍,比较使集落形成能力降低70%的浓度平均值。这是HTCFA选择的化合物中唯一显示具有临床活性的一种。化合物R对膀胱癌细胞具有选择性毒性,可能作为膀胱内用药具有价值。这些数据表明,睾丸和膀胱癌细胞系组可能是对以疾病为导向的筛选计划的有益补充。

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