Hsp90 is a highly conserved heat shock protein in animal and plants, and exists abundantly in the cytoplasm in unstressed condition, accounting for 1-2 % in cytoplasmic proteins. Main difference of Hsp90 from other Hsps are its substrate that Hsp90 binds to. These substrates include various signal transduction proteins, kinase, steroid receptors and transcription factors, therefore, Hsp90 plays a key role in maintaining cellular signal transduction networks. Many chaperoned proteins (client proteins) of Hsp90 are associated with cellular proliferation or malignant transformation, thus Hsp90 chaperone complex has been focused as targets for cancer therapy. Among the client proteins, there are several molecules that have been defined as targets or factors for determination or enhancement of radiosensitivity or thermosensitivity. Thus, it is easily speculated that Hsp90 chaperone complex inhibitors that disrupt association of Hsp90 and client protein in combination with radiation or/and heat has potential effect on enhancement of radiosensitivity or thermosensitivity. In this paper, possible mechanisms in enhancing radiosensitivity or thermosensitivity according to the client proteins will be summarized.

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To heat a greater volume less invasively and more effectively, we developed a multi-channel RF interstitial hyperthermia system compatible with the high-dose rate Iridium-192 remote after-loading system (Ir-192 RALS). The system is composed of eight channel RF signal generators, which can be controlled individually. Each RF generator can be connected to 1) an internal electrode, which was originally an Ir-192 RALS applicator ; and 2) a shared rectangular external electrode made of aluminum. By means of experiments using an agar phantom and an animal liver, we evaluated the heating characteristics, safety, and feasibility of this system.
Subsequently, we applied trans-perineal RF interstitial hyperthermia and Ir-192 RALS for localized prostate cancer (PC). Under trans-rectal ultrasound guidance, 18 stainless applicators for Ir-192 RALS were inserted into the prostatic gland and seminal vesicles in an optimized pattern. Eight applicators were used as internal electrodes and were electrically insulated along the length of subdermal fat tissue using a vinyl catheter. The temperature inside the prostate and rectum was monitored continuously. Hyperthermia was performed following the first and fourth Ir-192 RALS (total of 24 Gy / 4 fractions). Total doses of 46 Gy were also delivered by linear accelerator.
There were no complications, such as infection, bleeding, fat necrosis, or burns. Histological examination after the treatment revealed cancer cell death and necrosis. MRI and CT images showed a well-demarcated, low-intensity area at the center of the prostate reflecting the necrotic area.
Trans-perineal hyperthermoradiotherapy is a feasible and effective therapeutic alternative for the treatment of patients with localized PC. In addition, our system is compatible with the Ir-192 RALS, allowing for less-invasive interstitial hyperthermoradiotherapy by eliminating the trauma of needle re-insertion.

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Hepatocellular carcinoma (HCC) responds poorly to chemotherapy and radiotherapy, and few patients can undergo surgery due to severe liver dysfunction. Therefore, there is a need for a simple and effective local treatment technique with low mobidity. We evaluated minimally invasive laparoscopic or thoracoscopic radiofrequency ablation for treatment of patients with HCC who had no prospects of resective surgery. Five patients (1 man and 4 women; age range, 58 to 77 years) with HCC nodules of not more than 3.0-cm in diameter underwent radiofrequency ablation treatment. In each patient, the thermal necrosis volume achieved was large enough compared with the tumor volume. Though hepatic dysfunction was severe, postoperative recovery was uneventful in all patients. During the mean followup interval of 9.8 months (range, 4-15 months), no recurrence was found and all the patients are alive. Laparoscopic and thoracoscopic radiofrequency ablation can be considered a useful new treatment for small HCC in patients without surgical prospects. It is simple, effective and safe.

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Two elderly patients with primary malignant gliomas underwent thermoradiotherapy without reductive surgery. Hyperthermia was effectively performed for both patients. In the first case, a 76-year-old male with a left frontal glioblastoma presented with right hemiparesis. A CT scan demonstrated an irregular enhancement lesion in the white matter under the left motor cortex. The patient was treated with 4 sessions of interstitial hyperthermia and external beam radiotherapy of 60 Gy. Stereotactic biopsy and placement of 2 radiofrequency (RF) antennae were performed under local anesthesia. A CT scan showed complete remission (CR) and diminution of local edema four months later. In the second case, an 82-year-old male with an anaplastic astrocytoma in the right putamen presented with left hemiparesis. He was also treated with 3 sessions of interstitial hyperthermia and external beam radiotherapy of 60 Gy. Interstitial hyperthermia hyperthermia technique was same as the first case. Follow-up CT and MRI showed CR and no evidence of brain edema. These two patients experienced no complications during and after hyperthermic treatment, and their results were encouraging. We conclude that thermoradiotherapy for unresectable malignant glioma is technically feasible, even in the elderly, and can be a reductive therapy for malignant glioma.

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