Thermosensitive liposomes are microscopic vesicles that can release their contained drugs effectively in response to hyperthermia (HT). Previously we revealed the combination of thermosensitive liposome containing CDDP and local brain heating using RF interstitial antenna showed remarkable antitumor effects against rat malignant gliomas. A new liposome was prepared considering this drug delivery system as a clinical use. While a transition temperature of the conventional liposomes has been 42 or 43°C to enhance the synergistic effect of HT and antitumor drugs, the heated area above 42°C was localized in a narrow portion of human glioma. But the width of lower temperature area increased according to the distance from the RF antenna and the area of 40 °C extended up to the wide portion of the brain tumor. So we prepared a new liposome which can release adriamycin (ADR) above 40°C. As a result, this liposome showed significantly great antitumor effects against rat gliomas with the temperature of 40°C. This procedure 1) helps to deliver the antitumor drugs more widely to glioma and contributes to the synergistic effect of HT and antitumor drugs in the regions above 40 °C, 2) is effective in direct thermal killing in the regions above 43°C, 3) givesagoodchance tomanyantitumordrugs, such as ADR, which have not been used from the problem of blood brain barrier. 4) Moreover this new liposome could, be injected safely intraarterially. In conclusion, the advantage of this plan could outweigh the disadvantages of the conventional thermo-chemotherapy.

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Endogenous tumor necrosis factor (enTNF) participates in intrinsic resistance against heat not only via induction of manganous superoxide dismutase (MnSOD) but also via enhancement of the heat shock element (HSE) -binding activity of heat shock factor 1 (HSF 1) followed by augmentation of HSP 72 expression. These findings suggenst that enTNF may be useful as a predictor of heat sensitivity and that the resistance to heat could be overcome by antisense TNF gene transfer designed to inhibit enTNF expression.

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Metastatic lymphnodes located in the subclavian region were treated with thermoradiotherapy using an ultrasound hyperthermia system. The mean size of tumor was 37mm diameters (range 30-55mm). Two cases were histologically diagnosed adenocarcinoma and one case was squamous cell carcinoma. The radiation dose was 40-64 Gy. The hyperthermia was performed once or twice a week, total number of session was 4 - 6. The ultrasound frequency of applicator was 1.0 MHz or 1.5 MHz. The temperature of tumor center was measured by thermo-couples. In three out of 4 cases the tumor temperature raised over 42.5 °C within about 6 minutes but temperature of skin surface were under 37.0 °C. Three cases had complete response and one case had partial response. Side effects were occurred in two cases, those were pain of clavicle and weakness of affected side arm and blister. The thermoradiotherapy using ultrasound hyperthermia system was considered to be useful modality for subclavian lymphnode metastasis.

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The coaxial-slot antenna is one of the applicators for interstitial microwave hyperthermia. The authors et al. have been developing the antenna to find the proper structural parameters to the clinical application, by means of the phantom experiment and the computer simulation. We have studied heating characteristics (SAR distributions) only in the homogeneous medium whose electrical properties are the same as the muscle tissue. In this paper the numerical analysis of the antenna in the multilayer media (skin-fat-muscle) is described. To calculate the heating characteristics in such complicated structure, the FDTD (Finite Difference Time Domain) method has been introduced.
At first the validity of the analysis model of the antenna was confirmed by comparing the experimental results with the FDTD-calculated ones. Then the heating characteristics of one antenna were studied in the three-layered media, which is a more realistic modeling on the actual human body. In these results, the heating characteristics of the antenna in the three-layered media were showed significant difference from the ones in the homogeneous medium, especially in the region near the antenna insertion point.
Next, the heating characteristics of a four-element array applicator in the three-layered media were calculated. From the results, it was revealed that the hot spot near the antenna insertion point was suppressed and the SAR distributions in the three-layered media were not only different in shape at the antenna insertion points from the ones in the homogeneous medium, but also were different in another regions.
In conclusion, it is clarified by using the FDTD analysis method for calculation, that the effect of the skin and fat layer should be considered to some extent on the evaluation of the heating characteristics of the coaxial-slot antenna as well as an array applicator.

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(1) The effects of benzaldehyde (BA) in the slightly cytotoxic concentration on cell survivals from hyperthermia as observed in colony formation representing markedly enhanced thermosensitivity of Chinese hamster V-79 cells in vitro.
(2) After incubation of benzylidene glucopyranose (BG) under condition of pH 3 for 22 hr, half an amount of BG was hydrolysed to BA as observed with the specific absorbance at 250 nm of BA.
(3) BA is a hydrolysate of amygdaline that enhanced thermosensitivity. Other hand BG did not show any appreciable interaction for thermo-enhancement but showed no more than the additive effect. Adopted concentration of BA or BG was 1.8 mM. BG in 1.8mM was treated under pH 3 for 22 hr, resulting in half a BG was hydrolysed. It was designated BG*.
(4) Indication of BA or its derivatives would be possible thermo-enhancer in human clinical interdisciplinary oncotherapy including hyperthermia.

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(1) The effect of benzaldehyde (BA) on delay in hour in tumor regrowth was investigated after simultaneous treatment with hyperthermia for 3 fold of the initial tumor volume in 50% among a group of mice, TGT₅₀/3 fold. BA was injected directly to transplanted tumor on the right posterior leg of C₃H/He mice. (2) The delay in tumor regrowth time was observed in elongation of TGT₅₀/3 fold dependent on BA concentration and 43°C heating period. (3) These results suggested the appropriate adoption of BA or the derivatives may be indicated as a thermal enhancer in human hyperthermic oncology.

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