Rofstad E K
Institute for Cancer Research, Norwegian Radium Hospital, Montebello.
Br J Cancer. 1990 Jan;61(1):22-8. doi: 10.1038/bjc.1990.6.
Heat sensitivity and the development of thermotolerance of cells isolated directly from surgical specimens of human breast carcinoma, malignant melanoma and squamous cell carcinoma of the head and neck were studied in vitro using the Courtenay soft agar colony assay. The plating efficiency of some of the tumours was sufficiently high (0.3-20.4%) for survival curves covering up to two to three decades to be established. Experiments repeated with cells stored in liquid nitrogen showed that the survival assay gave highly reproducible results. Heat sensitivity of thermotolerant cells was studied by giving cells a conditioning heat treatment of 43.5 degrees C for 60 min and, after incubation at 37 degrees C for 24 h, second graded heat treatments at 43.5 degrees C. Significant differences in heat sensitivity and development of thermotolerance between the three tumour types were not found. However, the heat sensitivity, whether the cells were thermotolerant or not, differed considerably among individual tumours of each histological category. Do at 43.5 degrees C was found to be in the ranges of 23-59 min (breast carcinoma), 20-63 min (malignant melanoma) and 20-57 min (squamous cell carcinoma) for single-heated cells and 105-476 min (breast carcinoma). 102-455 min (malignant melanoma) and 87-400 min (squamous cell carcinoma) for thermotolerant cells. The heat sensitivity of cells made thermotolerant showed no significant correlation to the surviving fraction after the conditioning heat treatment. The study indicated that histological category is a poor parameter for assessment of clinical heat responsiveness of tumours. Breast carcinoma, malignant melanoma and squamous cell carcinoma are probably, from a thermobiological point of view, equally good candidates for clinical trial aimed at studying the potential usefulness of hyperthermia as an adjunct to radiation therapy and/or chemotherapy. The large differences in heat sensitivity and development of thermotolerance observed among individual tumours, irrespective of histological origin, suggested that an in vitro predictive assay for heat responsiveness would be very useful for stratification purposes in such clinical trials.
利用考特尼软琼脂集落试验，在体外研究了直接从人乳腺癌、恶性黑色素瘤和头颈部鳞状细胞癌手术标本中分离出的细胞的热敏感性和耐热性发展情况。部分肿瘤的接种效率足够高（0.3 - 20.4%），从而能够建立覆盖两到三个数量级的存活曲线。对液氮保存的细胞重复进行实验表明，存活试验结果具有高度可重复性。通过对细胞进行43.5℃、60分钟的预处理热处理，然后在37℃孵育24小时后，再进行43.5℃的二级分级热处理，研究了耐热细胞的热敏感性。未发现三种肿瘤类型在热敏感性和耐热性发展方面存在显著差异。然而，无论细胞是否耐热，每种组织学类型的个体肿瘤之间的热敏感性差异都很大。对于单次加热的细胞，在43.5℃下的加热时间范围为23 - 59分钟（乳腺癌）、20 - 63分钟（恶性黑色素瘤）和20 - 57分钟（鳞状细胞癌）；对于耐热细胞，加热时间范围为105 - 476分钟（乳腺癌）、102 - 455分钟（恶性黑色素瘤）和87 - 400分钟（鳞状细胞癌）。耐热细胞的热敏感性与预处理热处理后的存活分数无显著相关性。该研究表明，组织学类型对于评估肿瘤的临床热反应性是一个较差的参数。从热生物学角度来看，乳腺癌、恶性黑色素瘤和鳞状细胞癌可能同样适合作为旨在研究热疗作为放疗和/或化疗辅助手段潜在效用的临床试验的候选对象。无论组织学来源如何，个体肿瘤之间观察到的热敏感性和耐热性发展的巨大差异表明，体外热反应性预测试验对于此类临床试验的分层目的将非常有用。
