Matrix metalloproteinase-1 (MMP-1) has received a considerable attention as one of factors, enhancing tumor infiltration and metastasis. We determined serum levels of MMP-1 and TIMP-2, a tissue inhibitor of metalloproteinase-2 (a protein that suppresses all MMPs activity). Furthermore, we monitored changes in serum levels of MMP-1 and TIMP-2 after Whole Body Hyperthermia (WBH). Samples were collected from 46 patients with advanced cancers and 20 healthy volunteers were also examined for MMP-1 and TIMP-2. Furthermore, they were monitored for 36 patients undergoing one cycle of WBH, three weeks after completion of WBH. Mean serum level of MMP-1 in patients was increased to a significant extent whereas mean serum level of TIMP-2 was markedly lowered, compared to healthy individuals. MMP-1 activity was assessed by MMP-1/TIMP-2 ratio, and the ratio was 0.43 for cancer patients and 0.15 for healthy individuals, thus showing that cancer patients exhibited an apparently higher MMP-1/TIMP-2 ratio than healthy individuals. MMP-1 activity was nearly normalized in 9 responders after WBH, i .e ., from 0.37 (before) to 0.21 (after), whereas MMP-1 activity was increased from 0.43 (before) to 0.51 (after) in 27 non-responders. MMP-1 activity was increased approximately by 3-fold in patients, compared to healthy individuals. MMP-1 activity was normalized in WBH-responders.

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A thermal treatment method that involves the use of an endoscope equipped with a microwave antenna is recognized as a new therapeutic method for treating bile duct carcinomas. In this treatment, the antenna is inserted into the bile duct through the papilla of Vater noninvasively using the forceps channel of the endoscope, and then, the part of the bile duct that has to be treated is locally heated. The antenna consists of a flexible coaxial cable, and microwave energy is radiated from the antenna slot at the tip. We have evaluated the heating performance of the antenna by heating the extracted organs using the antenna. In order to investigate the effectiveness and safety of this thermal treatment for clinical use, we carried out an animal experiment for evaluating the operability and robustness of the antenna and studying whether the temperature of the bile duct could be increased to 42°C without any tissue coagulation around the antenna slot under the blood flow condition. In the experiment, first, we inserted the antenna into the bile duct invasively by passing it through the duodenum. Next, we used X-ray images to adjust the position of an optical fiber thermosensor such that the distance between the slot of the antenna and the point at which the temperature was measured was not very large. As a result of the measurement, when an input power of 15 W was supplied to the antenna and the irradiating microwave was in the "on" state for 20 s and "off" state for 5 s, the temperature could be maintained at 42°C without any tissue coagulation by using the antenna for 30 min. The measured temperature position was located at the distance of 4.8 mm from the antenna slot. In addition, it was confirmed that the antenna was sufficiently robust, as it did not break down during the experiment. Therefore, we concluded that the antenna is suitable for use in thermal therapy. Further, we also analyze by using numerical simulation, in which the blood flow rate was 2.33×10^-5 m³/kg•s, where the simulation results agreed well with the experimental results. Since the value of the blood flow rate was not quite different with the reference, the result was considered reasonable. Therefore the analytical model employed in this study can be used for improving the antenna structure and evaluating the therapeutic modality.

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The patient was a 63-year-old man who had back pain with no evidence of magnetic resonance imaging (MRI) abnormalities. He had never suffered from cancer. When 50-55 min radio-frequency hyperthermia sessions were administered every other day, the pain showed gradual alleviation as heat was applied. By the end of the 4th session, the pain had completely disappeared. The effect persisted for 5 months.

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