In response to heat shock, cells synthesize a small number of proteins, called “heat shock proteins”, that protect the cells from thermal damage. This heat shock response is observed in cells of organisms from bacteria to man. Interestingly enough, two major heat shock proteins from a variety of organisms are strongly conserved through evolution. The heat shock response is caused not only by heat shock, but also by amino acid analogs, transition metals, oxidizing agents, some poisons, recovery from anoxia, viral infection, and tissue damage. Thus the response seems to be a basic and primitive way by which cells protect themselves against different stressors.
Here, we review recent findings on the biochemistry of the heat shock response.

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An agar phantom possessing a cavity, which simulated the rectum, was employed in the experiment to evaluate temperature distribution at RF-heating. In the phantom, the rising temperature around the cavity at 0 and 6 o'clock, where the prostate is situated, was rather low. The temperature, however, rose prominently when the cavity was filled up with a condom containing 5 % NaCl solution. This suggested that NaCl solution facilitated the heating current around the cavity. These observations are thought to be applicable in cases of other malignancies in cavity organs such as the esophagus and bronchus, as well as prostatic cancer.

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The uptake of hematoporphyrin derivative (HpD) by Ehrlich ascites cancer cells was investigated with measuring of the fluorescence intensity of HpD bound to the cells at various temperatures. It was shown that there are two steps in the HpD binding process by the analysis of the HpD fluorescence emission pattern. (1) Weak binding mode : the fluorescence peak appeared at 617 nm in the early reaction time below 25 °C. (2) Stable binding mode : the fluorescence peak appeared at 630 nm even in the early reaction time above 30 °C and also in later time below 25 °C. Increased amount of HpD molecule was incorporated into the cencer cells at higher temperature and it was considered that the HpD uptake is mainly due to facilitated diffusion. The Arrhenius plots of logarithmic values of the initial velocity and the reciprocal of the absolute temperatures in HpD-uptake reaction was biphasic of which inflexion point being at 28.7 °C. From the plots, the lower activation energy corresponded to the weak binding and the higher one to the stable binding mode. It was considered that critical temperature correlates with the phase change of the membrane lipid to which HpD molecules bind.
Furthermore, it was found that the S and G₂ (+M) phase cells incorporated larger amount of HpD than the G₁ phase cells by the cytofluorometer determinations of the amounts of nuclear DNA (Hoechst 33258) and HpD on a single cells.
Survival curve analysis of the Ehrlich cancer cells in hyperthermia with or without pre-treatment with HpD administration reveald that both incorporated and membrane-bound HpD have a mild protective effect against hyperthermia. Nevertheless, it was suggested that the combination therapy of cancer cells by laser radiation after HpD administration plus hyperthermia might be more effective than that of each single treatment.

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A needle type applicator using heatpipe is proposed for local intracavital or interstitial thermotherapy of malignant neoplasmas. Advantages of heatpipe are as follows : (1) rapid and high heat transfer rate (2) homogenious heating along needle length (3) easy temperature control. Its disadvantages are traumatic and short range of heat transfer in the transaxial direction. But the short range of heating may be a merit to preserve surrounding normal tissues from heat damages and several numbers of heatpipes inserted with appropriate arrdngement may control bulky tumors. Histological studies revealed gradual changes after heat therapy in the trans-axial plane. The tissue close to the heatpipe shows necrosis and between it and viable tumor tissue capillary dilatation with hemorrhage is found. The boundary of tissue damage is so clear that it supports existence of a breaking point in thermal damage in the tissue level.

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RF capacitive type heating has been regarded as a modarity of superficial heating. This heating modarity, however, can be also used for deep heating if some points are taken into account. In this paper, the features of this heating modarity are described and some approaches to the problems of deep heating are discussed.

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To shorten the treatment time of hyperthermia, pulse-heating with high temperature is expected to be as effective as long-time heating with lower temperature. An equipment to pulse out microwave was developed and the temperature distribution in the static phantom was investigated. Surface cooling unit made it possible to heat the deep portion without overheating the surface. The optimum temperature and the interval of pulse should be investigated further.

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We will present a new RF capacitive heating method in order to heat a human deep seated tumor effectively. In our method, a human body is immersed in a water bath and dielectric plates are used to control the RF electric current distribution throughout the human body.
From the computer simulations, it is shown that a deep seated tumor may be heated safely without generating dangerous hot spots, when a subcutaneous fat layer, bone, etc., are shielded electrically by these dielectric plates.

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Sensitivity of tumor cells to heat is increased when heat is combined with chemotherapy. Two human colon cancer cell lines (WiDr Cell and COLO 205, cell) were implanted in nude mice and examined for the sensitivity to heat with or without chemotherapy. 1x10⁷ tumor cells were subcutaneously implanted in the right leg of 4-to 6 week old male BALB/C nu/nu mice. Local heating was applied when the weight of the implatned tumor reached ca. 400 mg. A thermostatistically regulated water bath provided the heat. The anticancer drugs (1/3 of LD 50) were i. p. infused 3 times at 4 days intervals 1 hr before heating : mitomycin C, cis-diamminedichloroplatinum and 5 fluorouracil by 3, 4. 9 and 25 mg/kg body weight, respectively.
The following results were obtained.
1) No antitumor effect was obtained in both tumors by one 30-min thermal session at 42 °C.
2) Two 30-min thermal sessions at 42 °C exerted a significant antitumor effect on COLO 205 tumor.
3) At 43 °C, both tumors showed heat sensitivity in one 30-min thermal session.
4) Heat at 42 °C plus MMC or CDDP produced significantly augmented effects on both tumors by one or two 30-min thermal sessions; heat plus 5 FU was also effectve by two 30-min thermal sessions.

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Surface overheating is a most frequent limiting factor in clinical application of RF capacitive heatig of deep seated tumors. The surface hot spots often occured around the margin of electrodes and were not prevented merely by perfusing cold water into the conventional pads attached to the electrodes. We have designed a new type coolig pad, 33 × 37 cm in size and 2 cm thick, which is put beneath the conventional pad and widely covers the skin surface. In the phantom experiments and clinical trials of deep hyperthermia using Thermotron RF8, the excessive surface heating around the margin of the electrodes completely disappeared by this new cooling pad.

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