Meyer J L, Van Kersen I, Hahn G M
Cancer Res. 1986 Nov;46(11):5691-5.
We have investigated the effect of increasing numbers of hyperthermia fractions given at 7-day intervals, with or without fractionated radiotherapy, on tumor cure, tumor growth, and cell survival after in vivo or in vitro heat. The murine RIF tumor was treated by capacitive radiofrequency hyperthermia at 44.0 degrees C for 20 min for one to five treatments at weekly intervals (1-5 wk D1). Single treatments (1 wk D1) induced cure in 5% of tumors. Additional treatments (2-5 wk D1) induced similar rates of cure (0-16%, P greater than 0.05 for 1 wk versus 2, 3, 4 or 5 wk D1). 1 wk D1 resulted in marked growth delay compared to controls. Mean tumor diameter doubling times increased from 13.2 days to 27.5 days (P less than or equal to 0.01). 2-5 wk D1 induced little additional growth delay (doubling times, 27.8-32.3 days, P greater than 0.05 for 1 wk versus 2, 3, 4 or 5 wk D1). Fractionated radiotherapy of 3200 rads (400 rads given twice each week) significantly prolonged mean tumor doubling time to 26.2 days. The addition of one hyperthermia session to the fractionated radiotherapy (1 wk D1 + XRT) further increased doubling time to 34.2 days (P less than or equal to 0.01). Additional treatments (2-5 wk D1 + XRT) only modestly increased doubling times (36.0-39.5 days, P greater than 0.05 for 1 wk versus 2, 3, 4 or 5 wk D1). In vitro assay of cells dissociated from tumors 5, 10, or 15 days after 3 wk D1 showed increased survival to 44 degrees C compared to previously untreated controls, and this cellular thermoresistance proved to be transient and noninheritable (i.e., thermotolerance). These results indicate that tumors can develop a prolonged thermal resistance after multiple weekly treatments which significantly modifies the response to subsequent treatment and which is associated with cellular thermotolerance.
我们研究了每隔7天增加热疗次数（无论是否联合分割放疗）对体内或体外加热后肿瘤治愈、肿瘤生长及细胞存活的影响。采用电容式射频热疗，在44.0℃下对小鼠RIF肿瘤治疗20分钟，每周进行1至5次治疗（第1至5周，第1天）。单次治疗（第1周，第1天）可使5%的肿瘤治愈。额外的治疗（第2至5周，第1天）诱导的治愈率相似（0 - 16%，第1周与第2、3、4或5周，第1天相比，P＞0.05）。与对照组相比，第1周，第1天的治疗导致明显的生长延迟。平均肿瘤直径倍增时间从13.2天增加到27.5天（P≤0.01）。第2至5周，第1天的治疗几乎没有额外的生长延迟（倍增时间为27.8 - 32.3天，第1周与第2、3、4或5周，第1天相比，P＞0.05）。3200拉德（每周两次，每次400拉德）的分割放疗显著延长平均肿瘤倍增时间至26.2天。在分割放疗基础上加一次热疗（第1周，第1天 + XRT）可进一步将倍增时间延长至34.2天（P≤0.01）。额外的治疗（第2至5周，第1天 + XRT）仅适度增加倍增时间（36.0 - 39.5天，第1周与第2、3、4或5周，第1天相比，P＞0.05）。对第3周，第1天治疗后5、10或15天从肿瘤中分离出的细胞进行体外检测，结果显示与未治疗的对照组相比，细胞在44℃下的存活率增加，并且这种细胞热抗性被证明是短暂的且不可遗传的（即热耐受）。这些结果表明，肿瘤在多次每周治疗后可产生长期的热抗性，这显著改变了对后续治疗的反应，并且与细胞热耐受有关。
