Enhancement of Hyperthermic Effects Using Rapid Heating

Abstract

Although favorable results have been reported concerning hyperthermic treatment against malignant tumors, there are still problems such as thermometry, determination of heating region, and long treatment time. The present research, which was conducted on laboratory animals, confirmed that the antitumor effect is augmented when the temperature is rapidly increased to the target temperature, regardless of the length of hyperthermic treatment time after the target temperature has been reached. This result suggests that the time of hyperthermic treatment can be shortened. For the experiment, C3H mice were used after subcutaneously inoculating them with SCC-VII tumor in the thigh. Hyperthermic treatment was performed at 43°C and 44°C for 20 and 40min using a warm water bath and an RF heating device. Changes in tissue blood flow before and after heating, the rate of tumor growth after hyperthermic treatment, tissue denaturation by antibody tissue staining, cytokinetic activity, and apoptosis were examined in two groups: a rapid-heating group, in which the heating temperature was increased to the target temperature in 1 min, and a slow-heating group, in which the heating temperature was gradually increased to the target temperature over a period of 10min. Changes in blood flow were not observed in the slow-heating group before or after the hyperthermic treatment in normal tissue or tumor tissue. On the other hand, blood flow in normal tissue was observed to increase significantly in the rapid-heating group after heat treatment, whereas blood flow in tumor tissue was observed to decrease significantly after heat treatment. Tumor growth was significantly delayed in the RF-heating group compared with the warm water-heating group. Although the degree of delay in tumor growth was similar in the rapid-heating group (heating at 43°C for 20 min) and the slow-heating group (43°C for 40min), a strong antitumor effect was observed in the rapid-heating group, suggesting that tratment time could be shortened. Following each hyperthermic treatment, sections of extracted specimens were stained with PCNA antibodies. This method revealed a significant cytokinetic activity in the slow-heating group, suggesting that little damage was caused by heat. Induction of apoptosis, observed by APOTAG antibodies, was significant in the rapid-heating group, with a peak in programmed cell death at 6–12 h following the treatment. In addition, factor-8 antibody stain revealed reduced staining in the rapid-heating group, confirming vascular injury. These results suggested that rapid heating might augment the antitumor effect as well as shorten the time required for hyper-thermic treatment. Slow heating causes little vascular injury, maintains sufficient blood flow to provide ample oxygen and nutrition, and leaves recovery and biophylaxic action intact against injury caused by heat. On the other hand, it is thought that rapid heating can shorten the time required for hyperthermic treatment by incurring vascular disorder and thereby selectively causing fatal disorder in the tumor region.