Many heat applicators for hyperthermia have been developed ; however, in treatment of noninvasive cancer they can heat only the body surface. At present, it is difficult to selectively heat deep-seated tumors.
It is desirable to develop an applicator with the potential for heating a limited region, but achieving this objective is impossible with present technology. Therefore, our goal is to develop an applicator that can uniformly heat to deep regions of the human body.
In this paper, we describe fundamental heating characteristics of an RF hyperthermic system using a rectangular resonant cavity applicator for deep-seated tumors. First, electromagnetic and heat-transfer equations were solved to investigate fundamental heating characteristics of the resonant cavity applicator. In the experiments, a torso-shaped dielectric phantom, which has electrical constants close to human muscle, was used. In comparisons of the measured and calculated results, the tendencies of both heat distributions were in accordance. These results indicated the possibility of heating deep regions ; thus, this applicator has the potential to heat deep-seated tumors.

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We first examined whether the increase of glutathione level induced by low-dose γ-ray irradiation is involved in the appearance of enhanced natural killer (NK) activity and antibody-dependent cellular cytotoxicity (ADCC), leading to delayed tumor growth in Ehrlich solid tumor (EST) -bearing mice. NK activity in ICR mouse splenocytes was significantly increased from 4h to 6h after a single whole-body γ-ray irradiation at 0.5 Gy, and thereafter decreased almost to the zero-time level by 24h post-irradiation. ADCC was also increased significantly in a similar way. Reduced glutathione exogenously added to splenocytes obtained from normal mice enhanced both NK activity and ADCC in a dose-dependent manner. The inhibitory effect of the radiation on tumor growth was then examined in EST-bearing mice. Repeated low-dose irradiation (0.5 Gy, four times, before and within an early time after the inoculation) significantly delayed the tumor growth.
Finally, the effect of single low-dose (0.5 Gy), whole-body γ-ray irradiation on immune balance was examined in order to elucidate the mechanism underlying the anti-tumor immunity. The percentage of B cells in blood lymphocytes was selectively decreased after the radiation, concomitantly with an increase in that of helper T cell population. The IFN-γ level in splenocyte culture prepared from EST-bearing mice was significantly increased 48h after the radiation, though the level of IL-4 was unchanged. IL-12 secretion from macrophages was also enhanced by the radiation. These results suggest that low-dose γ-rays induce Th1 polarization and enhance the activities of tumoricidal effector cells, leading to a delay of tumor growth.

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Hyperthermia (HT) is a treatment which obtains the anti-tumor effect by heating at 42.5°C or above. In addition, it is assumed that the effect of anti-cancer medicine is improved by combined with chemotherapy. However, it has been reported that mild-hyperthermia (MHT), under the 42.5°C treatment, makes immunity activate for tumor growth inhibition and MHT can enhance the anti-tumor effect even with chemotherapy treatment. Here, we demonstrate verification and the fundamental mechanism of the anti-tumor effect jointly, using it with MHT and chemotherapy. Moreover, we investigated the blood flow inside the tumor due to heat processing and the quantity of chemotherapeutic drug.
C3H/He mice (male, 8 weeks) were used. 1 × 10⁶ squamous cell carcinoma (SCC-VII) cells were transplanted in the right femoral region of mice and subjected to experiment when the tumor had grown to 7 mm in diameter. For the observation of tumor growth, we divided 6 groups : non processing group, MHT group (Processing temperature : 41.0°C), HT group (Processing temperature : 43.0°C), cis-diamminedichloroplatinum (II) (CDDP) dosage group, MHT combined with CDDP group (CDDP + MHT) and HT combined with CDDP group (CDDP + HT). Further, the tumors were extracted after all experiments were complete and then stained as the pathological specimen of the tumors.
CDDP + MHT group inhibited tumor growth 1.3 times in comparison with the CDDP group and enlarged necrosis range in the tumor by pathology. Also we observed increase of blood flow by MHT and the quantity of CDDP treating with MHT in the tumor. These results suggest that MHT treatment causes anti-tumor effect by enhancing blood flow and chemodrug uptake in the tumor.

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A high-accuracy hot water immersion-type device for hyperthermia has been developed. In order to provide strong evidences that raising body temperature causes heat injuries at higher temperature and enhances immunity at proper combinations of temperature and duration, a series of accurate experimental hyperthermia trials in dogs and cats was carried out using the device. The biological responses to heating were similar in both dogs and cats. A typical sign of heat related injuries, rapid granulocyte collapse (granulocytolysis), was observed while the body was heated at the rectal temperature 42.5°C and more than 42.5°C. In addition, the increase of liver enzymes and the tendency of hemorrhage were notable. Heating at 43.0°C was rather fatal even one hour heating. The degradation of heat shock proteins, HSP90 and Hsc73, was detected on 1 and 3 days post treatment. On the other hand, in the cases of the mild (fever-range) heating less than 42.0°C, the animals were rather stable during the treatment, recovered quickly from anesthesia and showed the good condition and appetite after the treatment. Increase in number and percentage of lymphocytes was remarkable at the proper heating temperature 41.5°C. The enhancement of cellular immunity and the induction of Hsp72 were also confirmed by delayed type hypersensitivity skin test and Hsp72-specific ELISA, respectively. Contrary to our expectations, even the slightly mild heating at the normal body temperature range of these small animals, 38-39°C for 3.5 hours, also provided clear enhancement of immuno-competence. In conclusion, there were no significant differences in biodynamics and immunity in both dogs and cats to heating and we regard fever-range hyperthermia as a mighty immunotherapy.

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