Nygren P, Fridborg H, Csoka K, Sundström C, de la Torre M, Kristensen J, Bergh J, Hagberg H, Glimelius B, Rastad J
Department of Oncology, University Hospital, Uppsala University, Sweden.
Int J Cancer. 1994 Mar 1;56(5):715-20. doi: 10.1002/ijc.2910560517.
The semi-automated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) by viable cells, was employed for cytotoxic drug sensitivity testing of tumor cells from patients with hematological or solid tumors. In total, 390 samples from 20 diagnoses were tested with up to 12 standard cytotoxic drugs. The technical success rate for different tumor types ranged from 67 to 95%. Fluorescence was linearly related to cell number but variably steep depending on tumor type. Samples from most solid tumors thus showed higher signal-to-noise ratios than hematological samples. A wide spectrum of in vitro drug activity was obtained, with acute leukemias and non-Hodgkin's lymphomas being sensitive to almost all tested drugs, whereas renal and adrenocortical carcinomas were essentially totally resistant. Between these extremes were samples of breast and ovarian carcinomas and sarcomas. When in vitro response was compared with known clinical response patterns, a good correspondence was observed. The results indicate that the FMCA is a rapid and efficient method for in vitro measurement of tumor-specific drug activity both in hematological and in solid tumors. The assay may be suitable for new drug development and direction of phase-2 trials to suitable patients.
基于活细胞对荧光素二乙酸酯（FDA）进行细胞水解所产生荧光的测量，采用半自动荧光微量培养细胞毒性测定法（FMCA）对血液系统肿瘤或实体瘤患者的肿瘤细胞进行细胞毒性药物敏感性测试。总共对来自20种诊断的390个样本使用了多达12种标准细胞毒性药物进行测试。不同肿瘤类型的技术成功率在67%至95%之间。荧光与细胞数量呈线性相关，但斜率因肿瘤类型而异。因此，大多数实体瘤样本的信噪比高于血液系统样本。获得了广泛的体外药物活性谱，急性白血病和非霍奇金淋巴瘤对几乎所有测试药物敏感，而肾癌和肾上腺皮质癌基本完全耐药。处于这两个极端之间的是乳腺癌、卵巢癌和肉瘤的样本。当将体外反应与已知的临床反应模式进行比较时，观察到了良好的一致性。结果表明，FMCA是一种快速有效的方法，可用于体外测量血液系统肿瘤和实体瘤中肿瘤特异性药物活性。该测定法可能适用于新药开发以及指导对合适患者进行2期试验。
