Rosenblum M L, Gerosa M A, Wilson C B, Barger G R, Pertuiset B F, de Tribolet N, Dougherty D V
J Neurosurg. 1983 Feb;58(2):170-6. doi: 10.3171/jns.1983.58.2.0170.
A stem cell assay for human malignant gliomas has been developed. Cells obtained from tumor biopsies grew into colonies composed of malignant glial cells, as documented by histochemical, immunohistochemical, and immunobiological techniques. Studies suggest that the disaggregated cells are representative of the cells within the solid tumor. Clonogenic cells were obtained from 48 tumors and analyzed for their in vitro sensitivity to graded doses of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The in vitro anti-tumor activity of BCNU at clinically achievable doses was compared to clinical response to the agent based on changes in computerized tomographic scan, radionuclide brain scan, and neurological examinations. Twenty-two patients received nitrosoureas before or after tumor specimen analysis, and were eligible for in vitro-in situ correlations. Clinical tumor sensitivity to nitrosoureas was predicted by culture results in 42% of all evaluable patients, and clinical resistance was predicted in 100%. The capability of the assay can be appreciated best for the 13 patients not treated with BCNU prior to culture; the in vitro prediction of clinical sensitivity and resistance was 71% and 100%, respectively. Preliminary findings show that clinical tumor resistance to BCNU may result from "intrinsic" cell resistance in some patients and from inadequate delivery of drug to tumor cells in other cases. The potential utility of this method to study the reason(s) for tumor cell resistance to drugs, to screen new chemotherapeutic agents, to individualize patient treatment, and to investigate tumor biology is discussed.
已开发出一种用于人类恶性胶质瘤的干细胞检测方法。从肿瘤活检中获取的细胞生长成由恶性神经胶质细胞组成的集落，这已通过组织化学、免疫组织化学和免疫生物学技术得以证实。研究表明，解离后的细胞代表实体瘤内的细胞。从48个肿瘤中获取了克隆形成细胞，并分析了它们对不同剂量1,3 - 双（2 - 氯乙基）- 1 - 亚硝基脲（卡氮芥，BCNU）的体外敏感性。基于计算机断层扫描、放射性核素脑扫描和神经学检查的变化，将临床可达到剂量的BCNU的体外抗肿瘤活性与该药物的临床反应进行了比较。22名患者在肿瘤标本分析之前或之后接受了亚硝基脲治疗，并且符合体外 - 原位相关性分析的条件。在所有可评估的患者中，42%的患者其临床肿瘤对亚硝基脲的敏感性通过培养结果得以预测，而临床耐药性的预测准确率为100%。对于在培养前未接受BCNU治疗的13名患者，该检测方法的能力体现得最为明显；体外对临床敏感性和耐药性的预测分别为71%和100%。初步研究结果表明，临床肿瘤对BCNU的耐药性在某些患者中可能源于“内在”细胞耐药性，而在其他情况下则源于药物向肿瘤细胞的递送不足。本文讨论了该方法在研究肿瘤细胞耐药原因、筛选新化疗药物、实现患者个体化治疗以及研究肿瘤生物学方面的潜在用途。
