In eukaryotic cells, three major heat shock proteins (hsp 90, hsp 70 and hsp 25) have been well studied. We discovered a novel heat shock protein (hsp 47) in chick embryo fibroblasts and cultured mammary cells as well. Hsp 47 is 1) a basic protein, the isoelectric point of which is about 9.0, 2) a major collagen-binding protein, 3) induced more effectively than other hsps in a lower temperature (42 °C), 4) phosphorylated at serine and threonine residues, and 5) also regulated by transformation using Rous sarcoma virus.
We first reviewed the molecular mechanisms of expression of major hsps including hsp 47 by shift up of temperature, and then the functions of major hsps, mainly of hsp 70 families. We also described the intracellular localization of hsp 47, and discussed possible roles of hsp 47.

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VLF or LF induction heating method for hyperthermia has the advantage of facility of localization of heated zone, simplicity of temperature measurement via thermocouples, and low cost of the apparatus. One drawback of this method is that conductive heat generated by a heating-pad alone is not enough to heat deep tumors.
In this paper, to solve this problem, we present a VLF heating method with needle implantation by the use of magnetic stainless steel needles. By this method, we can maintain a temperature range of 4348°C to 30 mm depth on phantom tests. Some clinical tests have been done successfully for treatment of oral malignancy.

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The last time, to develop a new technique for the therapy of malignant tumor in the deeper part of body, a needle applicator which was converted with one of the bipolar plates was used for localized tissue heating. The result of the experiments which was using radio frequency (13.56 MHz), tissue temperature was kept 4245°C within the spherical space of diamater of 57.5 mm.
This time, bulgy needle applicator was manufactured by way of trial to heat the far space than the last time. The result of experiment which was used for adoheanori phantom in 20, 25 and 30 watts, tissue temperature was kept over the spherical space of diamater 15 mm.

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The antitumor effect ultrasound (ULS) and/or antitumor drugs such as daunomycin (daunorubicin, DNR) and adriamycin (ADM) were determined in the rats bearing Yoshida sarcoma. The ULS transducer that was placed on the tumor was cooled to keep the temperature of the tissue within the nonthermal range. For the choice of the timing of the ULS irradiation after the administration of the drug, the drug concentrations in the tumor and blood were determined and were analyzed pharmacokinetically.
The drugs or ULS showed antitumor effect judged by the growth of the tumor size or the survival time of the rat. The combination treatment of ULS and the drug marked an additional or synergistic effects on Yoshida sarcoma.

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RF capacitive hyperthermia was applied to patients with in operable and recurrent malignant liver tumors. Factors that may affect intratumor temperature were discussed in this study.
Fifty patients who were eligible for the study consisted of 35 with hepatocellular carcinoma (HCC), 4 with cholangiocarcinoma and 11 with metastatic liver tumors. Hyperthermia was performed using an RF capacitive heating equipment (Thermotron RF-8). In some cases, transarterial embolization manipulation (TAE) or radiation therapy was combined with thermotherapy.
Intratumor temperature could be adequately raised above 42°C in most of cholangiocarcinoma and metastatic liver tumors, while in HCC, tumor temperature-rise appeared to be dependent on tumor subtypes, that is, higher temperature levels tended to be achieved in diffuse type than in massive or nodular type. The thickness of subcutaneous fat tissue above 15 mm and the blood flow of portal vein also affected hyperthermia for liver tumors.
As a result, 23% of patients with HCC and 40% of those with cholangiocarcinoma or metastatic liver tumors achieved CR or PR.

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We had studied a temperature distribution under a local hyperthermia by a finite element technique. The distribution had some ambiguities which are caused by the uncertain estimation of the blood flow effects in the bio-heat equation.
In this paper, for the purpose of making more accurate temperature prediction, the quantity and the mechanism of the blood flow are investigated as flollowings.
The thermal clearance technique around the time of power-on and power-off under the local body heating may lead us to the purpose, as the thermal clearance rate is proportional to the blood flow. Examples of clinical hyperthermia therapy give typical informations of the thermal clearance, and then blood flow is estimated by the way described above.
Finally, a model explaning the thermal clearance is proposed.

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