Nygren P, Hagberg H, Glimelius B, Sundström C, Kristensen J, Christiansen I, Larsson R
Department of Oncology, University Hospital, University of Uppsala, Sweden.
Ann Oncol. 1994;5 Suppl 1:127-31. doi: 10.1093/annonc/5.suppl_1.s127.
Tumor cell drug sensitivity is an important determinant of chemotherapy response. Its measurement in vitro would aid in therapy individualization and new drug development.
The fluorometric microculture cytotoxicity assay (FMCA), based on production by viable cells of fluorescent fluorescein after 3 days of culture, was used for cytotoxic drug sensitivity testing of 73 samples of tumor cells from patients with non-Hodgkin's lymphoma (NHL).
The technical success rate was 92%, and FMCA data showed good correlation to the Disc assay. NHL samples were considerably more drug sensitive than were samples from in vivo resistant tumors. There was no obvious difference in drug sensitivity for high- vs. low-grade or untreated vs. previously treated low-grade NHL. For 26 patients, clinical outcome was correlated to in vitro response giving a sensitivity and specificity of 93 and 48%, respectively. Cross-resistance between standard drugs was frequent in vitro. Resistance modulators potentiated the effect of vincristine and doxorubicin in 10-29% of the samples, most frequently from previously treated patients.
The FMCA seems to report clinically relevant drug sensitivity data for NHL, and thus it could serve as a tool for optimization of chemotherapy in the future.
肿瘤细胞药物敏感性是化疗反应的重要决定因素。体外测量有助于治疗个体化和新药研发。
荧光微量培养细胞毒性试验(FMCA)基于活细胞在培养3天后产生荧光素进行检测,用于对73例非霍奇金淋巴瘤(NHL)患者的肿瘤细胞样本进行细胞毒性药物敏感性测试。
技术成功率为92%,FMCA数据与纸片扩散法检测结果具有良好相关性。NHL样本比体内耐药肿瘤样本对药物更为敏感。高级别与低级别NHL样本或未治疗与先前治疗的低级别NHL样本在药物敏感性方面无明显差异。对于26例患者,临床结果与体外反应相关,敏感性和特异性分别为93%和48%。标准药物之间的交叉耐药在体外很常见。耐药调节剂在10%至29%的样本中增强了长春新碱和阿霉素的作用,最常见于先前接受过治疗的患者。
FMCA似乎能报告与NHL临床相关的药物敏感性数据,因此未来可作为优化化疗的工具。