In the treatment of malignant tumors, hyperthermia (HT) has been considered to be effective for tumoricidal conditioning in combination with radiation therapy (RT) and/or chemotherapy (CT). Low pH and nutritional deprivation sensitize cells to hyperthermia-induced killing. Furthermore, it is possible that decreased blood flow could further selectively reduce intratumor pH leading to enhanced cytotoxicity. In the experimental studies, the combined effects of flavone acetic acid (FAA) and hyperthermia were investigated on B16 melanoma cells and shown with enhanced cytotoxicity under the condition of their combined treatment regime.
In clinical study, patients with deep seated malignant tumors were treated with HT combined with RT and/or CT. A comparison of these results showed that the long survival was obtained on the groups where patients with tumors originated from breast, soft tissue, colorectal and uterine/ovarian sites and with good local response belonged. Concerning histopathological classification, no definite difference was found on the survival except for sarcoma. The role of hyperthermia, including a thermosimulator, and its current evolution in the multidisciplinary treatment of cancer were discussed especially with emphasis on quality assurance in the hyperthermic treatment.
Finally, possible future perspectives of clinical research on HT combined with RT and/or CT were discussed especially on the election of appropriate clinical sites, selection of suitable HT devices, and design of clinical studies.

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SDI法による継代癌細胞 (KATO III, COLO320) を用いた基礎的研究および腹膜播種巣を用いた臨床的検討から, mitomycin C, cisplatin, etoposideが温熱との相乗効果を有することを確認した.そこでこれらの薬剤を併用して加温生理食塩水で腹腔内温度を42.5℃となるようにして潅流を行う化学温熱腹膜潅流療法 (chemohyperthermic peritoneal perfusion; CHPP) を開発し, 胃癌, 大腸癌などの消化器癌や卵巣癌の腹膜播種の治療に施行した.この結果胃癌においてCHPP施行例の (CR+PR) 率は13/58 (32%) であった.胃癌での治療的CHPP施行群の平均生存期間は1.1年, 非施行群は0.6年であり, 生存曲線は両群間で有意差が認められた (logrank test, p=0.04).しかし播種の肉眼分類別に検討すると, 小結節散布型の腹膜播種において, 治療的CHPP群の方が非施行群より予後が良好であった (logrank test, p=0.04) ものの, 結節散在型, びまん型の播種では予後に差は認められなかった.また大腸癌, 卵巣癌の腹膜播種の (CR+PR) 率はそれぞれ6/12 (50%), 3/5 (60%) であり有効性が示唆された.

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In the patients who receive intaperitoneal hyperthermo-chemotherapy, scald injury on the normal peritoneo-serosal surface is inevitable due to high temperature in the peritoneal cavity. In an attempt to reduce this scald injury, cimetidine (histamine H₂-receptor antagonist) was used for the patients who underwent intraperitoneal hyperthermic perfusion (IPHP), and catheter duodenostomy was placed for these patients in order to decrease postoperative morbidity.
IPHP was performed for 60 advanced gastric cancer patients who were allocated to two groups. One was the cimetidine group of 23 patients who received 50 mg/kg of cimetidine intravenously just before IPHP. The other was the control group of 37 patients who did not receive cimetidine. IPHP was performed just after surgery under hypothermic general anesthesia for 90120 minutes. Heated perfusate which contained 10 μg/ml of mitomycin C was circulated in the peritoneal cavity with the inflow and the outflow temperature of 45.546.5°C and 43.544.5°C respectively. The amount of peritoneal exudate and the amount of protein in it of the cimetidine group were significantly smaller than those of the control group after IPHP. There was no anastomotic leakage in the patients who underwent catheter duodenostomy in the cimetidine group. These results suggest that the side effects of IPHP can be reduced by the use of cimetidine and catheter duodenostomy.

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A considerable study has been carried out to substantiate the selective killing effect of heat on neoplastic versus normal cells, and generally revealed higher thermosensitivity of the former obtained from human or animal tumors. Recently, the neoplastic cells experimentally induced by chemicals, ionizing radiation, tumorigenic viruses or oncogenes has become available and important for the strict analysis. Among tumorigenic viruses, adenovirus is well known to transform rodent cells, whose genome is a linear duplex DNA molecule encoding for 20-30 polypeptides. Oncogenes of adenovirus are identified as E1A and E1B, which are tandemly located on the left end of the template r-strand. The 53k/44k proteins translated from 13S mRNA of E1A immortalize embryonic cells to accomplish the first step of transformation. E1B encodes for the 15-19k and 53-54k proteins which stabilize cellular and viral DNA to be essential for the complete transformation. Very interestingly, the thermosensitivity of adenovirus transformed cells was coincident with E1A expression and on the contrary E1B gene exerted inhibitory effect on the cell death by heat. Moreover, heat-treated E1A cell represented the immediate chromosomal change and the internucleosomal nucleolysis compatible for programmed cell death (apoptosis), while the transformed cells with ElB or E1A + E1B showed the delayed morphological change and the less amount of degraded DNA. Consequently, E1A plays an important role either in cell transforation (immortalization) and in enhancement of thermosensitivity. As it has been evident that E1A interacts some cellular proteins intimately concerned with cell replication, such as pRb (p105), p107, p130 and p300, E1A may function to endow the cells with thermal instability via these proteins.

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マウスの頭部局所を39～51℃の各温度で加温し, ³¹P-MRSでそのエネルギー代謝変化を検討すると共に頭部局所加温における生存限界致死温度を求めた.また, そのハイパーサーミアによる脳の細胞死とアポトーシスの関連を検討した結果, 下記の結論を得た.
1.頭部加温温度の上昇に伴い, 脳の高エネルギー物質の代謝周期が速くなった. (39℃;40分, 42℃;23分, 45℃;12分)
2.45℃加温 (頭部温度 : 43℃) において半数のマウスが60分の加温期間中に死亡した. (LD50/60min)
3.頭部加温温度の上昇に伴い, 生存時間 (MRS'deadtime) が短縮した. (39℃;生存, 42℃;生存, 45℃;死亡マウスでは45.8分, 48℃;24.6分, 51℃;17.2分)
4.頭部加温温度の上昇に伴い, 直腸温が上昇した. (39℃;35.9℃, 42℃;37.9℃, 45℃;39.6℃, 48℃;40.1℃, 51℃;40.2℃)
5.頭部局所加温により, 脳組織にアポトーシス像を認めた.
以上の結果より, 頭部局所加温において加温温度の上昇に伴い高エネルギー物質の代謝周期は速くなり, 頭部温度43℃が生存限界温度と思われた.この時, 加温により脳組織では, アポトーシスが誘導され死亡するものと思われた.

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Retinoblastoma is a hereditary malignant tumor, mostly occurring in infants and children. Although the common treatment is the surgical extraction of eyeball, non-invasive several methods such as chemotherapy, irradiation, and hyperthermia therapy using microwave are conducted as treatments for the disease. The hyperthermia therapy using microwave tends to heat the optic nerve excessively. Therefore an intelligent heater was developed to prevent the above problem. The surface temperature of the intelligent heater was automatically maintained at constant temperatures when the room temperature or the applied voltage was changed. The intelligent heater showed the positive temperature coefficient (PTC) effect. It has conductive carbon-black distributed by grafting of polyethylene glycol as crystalline polymer. The intelligent heater reduces the risk of excessive heating of the optic nerve, because the material itself controls the temperature. Real time evaluation of the temperature distribution in cross section of the eyeball phantom was carried out using the boundary-element method. The surface temperature of the agar phantom imitating eyeball was measured as boundary conditins. The calculated temperature of the imitated eyeball phantom at the mid-point was compared with the measured temperature at thermal equilibrium. The calculated temperature approximately agreed with the measured temperature. The non-invasive temperature estimation of an imitated eyeball cross section was achieved using the boundary-element method. This device appears promising for its safe clinical applications in hyperthermic retinoblastoma therapy.

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Thermotron RF-8を用いた深部加温をより有効にするため, gripping methodを考案し, 臨床的ならびに基礎的に検討した.その結果, 実際の前立腺の加温においてgripping methodをおこなったところ, 皮膚の熱感が著明に軽減し, 温度上昇も従来の方法より高くえることができた.またPhantomを用いた基礎的検討では高周波電圧の低下が軽度認められたが, 従来の方法と較べて大差なかった.
以上よりThermotron RF-8を用いて加温する場合にはgripping methodは有効な方法であると考えられた.

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