We here propose an inductive aperture-type applicator consisting of a one-turn, square, column-like coil made of a metal strip. The experiments, using phantom, revealed that this applicator has the following characteristics : 1) It does not heat the fat layer excessively. 2) Deep portions can be heated effectively. 3) The subject can be heated while not in contact with the applicator. 4) Excessive heat generation does not occur in the part of the subject near the edge of the aperture. 5) The aperture size can be changed according to the size of the heating site. 6) The aperture can be modified to fit the shape of the subject. 7) The applicator can be driven at an arbitrary frequency. 8) The size of the subject influences the penetration depth. 9) The heating efficiency is low. On the basis of these results, experinents were performed using terminated and living pigs. In the experiments using the terminated pigs, the penetration depth was 11.5cm. In the experiments using living pigs, heating was performed while cooling the body surface of the chest. In this case, the rectal temperature rose from 39.9°C to 41.9°C after 34 minutes of heating. As to the temperature profile alog the depth, the temperature was 42.5°C at maximum at 3cm under the skin and kept nearly the same temperature into the deep portion, the temperature being 42.3°C at 15cm in depth.

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Intracellular localization of mammalian 70, 000 D heat shock protein (HSP70) in HeLa and rat 3Y1-B cells that had been heat shocked or treated with chemical stressors was investigated using indirect immunofluorescent staining. The antiserum used specifically recognized the HSP70 in HeLa and 3Y1-B cells, and HSP was increased by heating cells at 42°C for 2 or 4 h and by prior treatment with chemical stressors (sodium arsenite, cadmium chloride, 8-hydroxyquinoline and ethanol). There was diffuse cytoplasmic staining at 37°C, whereas nucleoli were stained brightly when cells were heated at 42°C for 2 h. This rapid accumulation of HSP70 in the nucleoli was not inhibited by cycloheximide (50 μg/ml). Translocation of HSP to the nucleoli was specific for heat because no translocation was induced by treatment with chemical stressors. When the cells were returned to 37°C after heating, the HSP in their nucleoli disappeared rapidly and diffuse cytoplasmic staining was present after 4-6 h for 3Y1-B cells and 6-9 h for HeLa cells. Our results suggest that the transient accumulation of HSP70 in the nucleoli that is induced by heat shock is not correlated with the development of thermotolerance.

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The thermometry results of radiofrequency (RF) capacitive hyperthermia for 60 deep-seated tumors in 59 patient are reported. Hyperthermia was administered regionally employing two RF capacitive heating equipments which we have developed in cooperation with Yamamoto Vinyter Co. Ltd.
Thermometry results obtained were summarized as follows. (1) A maximum tumor center temperature over 43°C and 42-43°C was obtained in 23 (38%) and 14 (23%) of the 60 tumors respectively. (2) Temperature variations within a tumor exceeded over 2°C in 81 % of tumors heated over 43°C. The lowest tumor temperature over 42°C was accomplished in 6 of the 53 tumors (11%). Out of 42 tumors in which temperatures of the subcutaneous fat, surrounding normal tissues and the tumor center were compared, 24 (57%) showed the highest temperature in the tumor center and 10 (24%) in the subcutaneous fat. (3) When the heating efficacy was assessed in terms of a maximum tumor center, it greatly depended on the treatment site, tumor size, thickness of subcutaneous fat and tumor type. Tumors in the head and neck, thorax, and pelvis could be heated better than tumors in abdomen. Greater heating efficacy was shown in patients with large, hypovascular tumors and with the subcutaneous fat measuring less than 15mm in thickness. (4) The predominant limiting factor for power elevation was pain associated with heating. Systemic signs including increases in pulse rate and body temperature were not serious and seldom became limiting factors for power elevation.
Our thermometry results indicate that the advantages of deep RF capacitive heating are its applicability to various anatominal sites and negligible systemic effects. The disadvantages are, on the other hand, that its primary usefulness is limited to patients with thin subcutaneous fat and with large or hypovascular tumors.

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In order to heat a deep regional tumor, it was proposed to use a converging spherical microwave generated by four reflectors composed of both a paraboloid and hyperboloid. A spherical dynamic phantom, which contains three vinyl pipes perfused with cooling water, was set at the center of this device and heated by a converging spherical microwave. Temperature rise was localized in the vicinity of center after the steady states were reached, and this steady state temperature distribution was almost consistent with the theoretical analisis. It became clear that effective heating for a human deep tumor may be accomplished by this method.

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B16 melanoma cells were inoculated s.c. on the hind leg of C57BL mice. The tumor bearing mice were applied to the test of metastasis on the 16-22 days after the inoculation. Experimental procedures of 6 groups were as follows; (1) Untreated tumors were excised. (2) The tumors were heated together with legs in water bath at 44°C for 30 min under anesthesia and the tumors were excised immediately after the heating. (3) Heat treatment was the same to the group (2), then the tumors were excised on day 3 after the heating. (4) The same heating was applied once a day for 3 days, then the tumors were excised on the next day of the last heating. (5) A combined treatment with the heat at 44°C for 30 min and with a single dose of 19Gy X-rays immediately after the heating was given to the tumors, then excised day 3 after the treatment. (6) Another combined treatment with the same heating and with the same X-irradiation a day before the heating was given to the tumors, then excised on day 3 after the heating. The incidences of the metastasis in those mice were pursued for 90 days after the inoculation. When tumors were larger than 200mm³, each treated group indicated a slight increase in the incidence of metastasis, but not markedly. When tumors were smaller than 200 mm³, the incidences of those groups (1) - (6) were 6.0% (6/100), 4.2% (1/24), 16.1% (10/58), 28.6% (6/21), 24.6% (15/61) and 19.4% (6/31), respectively. The incidence of metastasis by the heating at 44°C for 30 min was almost the same level to the incidence by a single dose of 19Gy X-rays. In the small tumor, the incidences of metastasis by the combined and 3 fractionated heating were higher than those by X-irradiation alone or heating alone.

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Intratumoral, intravesical and rectal temperatures were measured in 10 patients with bladder cancer during RF-hyperthemia using thermocouples. The temperature measurement study demostrated the temperature distribution as follows : (1) 44.5±1.3°C (mean±SD) in the central area of the tumors, (2) 43.6±1.0°Cin the tumor margin, (3) 42.9±1.2°C in the vesical cavity, (4) 42.4±0.6°Cin the rectal cavity.The temperature of the vesical cavity proved to be useful for estimating the tumor margin temperature. In addition, there was a significant correlation (p<0.01) between the mean output power required for RF-hyperthermia and the intravesical temperature, and also the thickness of the subcutaneous fat tissue.

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