Urano M, Taradi M, Taradi S K
Department of Radiation Medicine, University of Kentucky, Chandler Medical Center, Lexington 40536.
Int J Hyperthermia. 1991 Jan-Feb;7(1):113-23. doi: 10.3109/02656739109004982.
We have studied the effect of a streptococcal preparation, OK-432, given alone or in combination with hyperthermia on murine tumour and normal tissues. The experimental tumour was a spontaneous non-immunogenic fibrosarcoma FSa-II transplanted in the foot of C3Hf/Sed mice. Local hyperthermia was achieved by immersing the mouse foot into a constant temperature water bath (42-45 degrees C) for various lengths of time. Tumour response was studied by analysing the tumour growth (TG) time. Various doses of OK-432 (1-5 KE/mouse) were injected locally into the tumour. Local administration of OK-432 alone (without hyperthermia) had no effect on the TG time. Thermal enhancement ratio (TER) for combined treatment was independent of drug dose greater than or equal to 2 KE, and the mean TER was 1.48 +/- 0.27 (95% CL). The TER was greater for 6 mm tumours than for 4 mm tumours, and it was greatest if the time interval between hyperthermia and drug administration was 3 h or less. There was no effect if the drug was administrated 4 days before hyperthermia, but its application 9 days prior to hyperthermia caused a slight prolongation of the TG time of non-heated tumours, and a reduction in the TG time of heated tumours. Normal-tissue response was studied by scoring the peak foot reaction and RD50 (the treatment time to induce a specified response in one-half of the treated animals). The effect of OK-432 on the thermal response of the foot was also studied at various temperatures. The mean TER was 1.11 +/- 0.07. Local administration of OK-432 failed to modify significantly the kinetics of thermotolerance. Present experiments demonstrated that OK-432 after local administration enhanced the thermal response of murine tumour and normal tissues. This enhancement was greater for the tumour than for the normal tissue, resulting in a favourable differential effect between normal and malignant tissues (the average therapeutic gain was 1.33 +/- 0.19).
我们研究了链球菌制剂OK-432单独使用或与热疗联合使用对小鼠肿瘤和正常组织的影响。实验性肿瘤是移植到C3Hf/Sed小鼠足部的自发性非免疫原性纤维肉瘤FSa-II。通过将小鼠足部浸入恒温水浴（42-45摄氏度）不同时间来实现局部热疗。通过分析肿瘤生长（TG）时间来研究肿瘤反应。将不同剂量的OK-432（1-5KE/小鼠）局部注射到肿瘤中。单独局部给予OK-432（无热疗）对TG时间没有影响。联合治疗的热增强比（TER）与大于或等于2KE的药物剂量无关，平均TER为1.48±0.27（95%置信区间）。6mm肿瘤的TER大于4mm肿瘤，并且如果热疗和给药之间的时间间隔为3小时或更短，则TER最大。如果在热疗前4天给药则没有效果，但在热疗前9天应用会导致未加热肿瘤的TG时间略有延长，以及加热肿瘤的TG时间缩短。通过对足部反应峰值和RD50（在一半接受治疗的动物中诱导特定反应的治疗时间）进行评分来研究正常组织反应。还在不同温度下研究了OK-432对足部热反应的影响。平均TER为1.11±0.07。局部给予OK-432未能显著改变热耐受动力学。目前的实验表明，局部给药后OK-432增强了小鼠肿瘤和正常组织的热反应。这种增强在肿瘤中比在正常组织中更大，导致正常组织和恶性组织之间产生有利的差异效应（平均治疗增益为1.33±0.19）。
