Kobayashi T, Kuraishi Y, Aiba K, Inoue K
Gan To Kagaku Ryoho. 1985 Aug;12(8):1566-72.
The human tumor clonogenic assay (HTCA) developed by Hamburger and Salmon was evaluated in 135 fresh samples of breast cancer. Successful tumor colony growth (greater than or equal to 5 colonies/plate) was obtained in 100 (74%) of the 135 samples, and adequate growth for drug testing (greater than or equal to 30 colonies/plate) in 75 (56%). With regard to the success rates of growing colonies categorized by specimen source, tumor sites, histology, prior chemotherapy and estrogen receptor (ER), specimens from solid tumors and primary tumors showed higher success rates than those from pleural effusions and metastatic tumors. The effects of prior chemotherapy, histology type and ER status on the success rate of colony formation were not significant. The overall median plating efficiency was 0.012%. Higher plating efficiencies were found in pleural effusion, metastatic tumors and samples from patients with prior chemotherapy. These findings appeared to indicate that aggressiveness of disease might be related to plating efficiency. Defining a greater than or equal to 50% inhibition of colony formation (ICF) as in vitro drug sensitivity, the in vitro response rates to anticancer drugs tested were as follows: adriamycin 33%, mitomycin C 39%, 5-fluorouracil 32%, methotrexate 42%, L-PAM 31%, cisplatin 38%, vincristine 32%, vinblastine 54%. The group of patients without prior chemotherapy showed higher sensitivity in vitro compared with the group of patients who had prior chemotherapy (38% vs. 27%). Correlation between in vitro drug sensitivity (greater than or equal to 70% ICF) and clinical response in 12 patients treated with the same drugs were analyzed retrospectively. The predictive accuracy was 0% (0/1) for true positive and 91% (10/11) for resistance. Thus, overall predictive accuracy was 83%. Based on these results, HTCA appeared to be useful chemosensitivity test for evaluation of antitumor drugs for human cancers in vitro and prediction of the chemotherapeutic effect in clinical use.
由汉堡和萨尔蒙开发的人类肿瘤克隆形成试验(HTCA)在135份乳腺癌新鲜样本中进行了评估。135份样本中有100份(74%)成功实现肿瘤集落生长(≥5个集落/培养皿),75份(56%)实现了足以进行药物测试的生长(≥30个集落/培养皿)。关于按标本来源、肿瘤部位、组织学、既往化疗和雌激素受体(ER)分类的集落生长成功率,实体瘤和原发肿瘤的标本显示出比胸腔积液和转移瘤更高的成功率。既往化疗、组织学类型和ER状态对集落形成成功率的影响不显著。总体中位接种效率为0.012%。在胸腔积液、转移瘤和既往接受化疗患者的样本中发现了更高的接种效率。这些发现似乎表明疾病的侵袭性可能与接种效率有关。将集落形成抑制率(ICF)≥50%定义为体外药物敏感性,所测试的抗癌药物的体外反应率如下:阿霉素33%、丝裂霉素C 39%、5-氟尿嘧啶32%、甲氨蝶呤42%、苯丙氨酸氮芥31%、顺铂38%、长春新碱32%、长春花碱54%。未接受过既往化疗的患者组在体外显示出比接受过既往化疗的患者组更高的敏感性(38%对27%)。回顾性分析了12例接受相同药物治疗的患者的体外药物敏感性(ICF≥70%)与临床反应之间的相关性。真阳性的预测准确率为0%(0/1),耐药的预测准确率为91%(10/11)。因此,总体预测准确率为83%。基于这些结果,HTCA似乎是一种用于体外评估人类癌症抗肿瘤药物和预测临床化疗效果的有用的化学敏感性试验。