Heat shock triggers signaling events on the cellular membrane that lead to activation of stressactivated protein kinase (SAPK, also known as JNK). The consequence of the JNK signaling pathway is cell death via apoptosis. On the other hand, heat shock induces an adaptive response effected by activation of heat shock factorl (HSF1) which in turn activates gene expression of heat shock proteins (hsps). Hsp70 antagonizes the death signals by inhibiting JNK activation and protects cells from heat injury by refolding the heat-denatured proteins. Moreover, heat shock activates the p53-mediated stress signaling pathway via protein kinase C. p53 acts as a cell cycle checkpoint to maintain the cellular homeostasis by inducing either G₁arrest or apoptosis. p53 physically associates with hsp70 and down regulates hsp70 expression. Thus, these three sets of signaling pathways interact with each other in response to heat shock and together determine the cells' fates. Furthermore, DNA-damaging agents suppress the hsp70 induction by heat shock, indicating that different stresses interfere with each other in the same signaling pathway. All this points to the importance of studies into the mechanisms of cellular signaling in the combined cancer therapy of hyperthermia and radiation.

View full abstract

Reasonable extent of lymphadenectomy in combination with perioperative reliable adjuvant countermeasure to prevent postoperative peritoneal metastasis, as a prophylactic therapy is indispensable to improve the results of surgical treatment of gastric cancer with serosal invasion. Further therapeutic modality should be improved to obtain life prolongation for patients with gastric cancer with disseminating peritoneal metastasis or for gastrectomized patients with postoperative peritoneal metastasis. We believe that intraoperative continuous hyperthermic peritoneal perfusion (CHPP) combined with intraabdominal chemotherpy would be a candidate for the most reliable adjuvant therapy as both prophylactic and therapeutic modalities against peritoneal metastasis from gastric cancer.

View full abstract

The feasibility and efficacy of long duration-low temperature whole body hyperthermia (LL-WBH, at 40°C for 6 h) as adjuvant therapy was investigated in rats bearing highly metastatic mammary adenocarcinoma (MTLn 3). All animals in the non-surgery control group demonstrated a progression of axillary lymph node metastases (ALM) on day 24 after inoculation. In a preoperative treatment study, 67 % of the animals developed ALM in both the treatment and control groups, however, the local recurrence rate was significantly suppressed to 0% in the treated rats compared to the control (67%) (p < 0.05). In a postoperative treatment study, 30% and 33% developed ALM, in treatment and control groups, respectively (p < 0.01, compared to the non-surgery control), however, the incidence of local recurrence was 40% and 11 % for the treatment and control groups, respectively. No significant differences were seen between any of the groups (20-55 %) with respect to tumor cure. The authors thus conclude that LL-WBH appears to be a valuable adjuvant therapy to surgery, however, an ideal therapeutic design still needs to be developed for its clinical application. Therefore, additional studies of LL-WBH as an adjuvant treatment to surgery are called for.

View full abstract

This paper deals with the heating characteristics of transurethral applicators for thermal treatment of benign prostatic hyperplasia (BPH). We proposed a new mathematical model, which provides the near field of Intracavitary applicators of dipole antennas. Using this model, temperature fields taking account of applicator's surface cooling and blood flow effects can be calculated with the finite difference method (FDM). The simulation results of SARs and temperature distributions are compared with the results of phantom experiments simulating the prostate. On the basis of the above results, discussions to make the BPH treatments more suitable to the individual patient's condition are given.

View full abstract

For conventional combination use of RF interstitial heating and RALS, internal electrodes are placed in the guide tubes of Microselectron and an external electrode is placed on the surface of a patient during heating. With this heating method, the temperature distribution pattern around the internal electrode varies in each treatment. This phenomenon may be due to the contact of the internal electrode with the guide tube. The contacting part of the electrode and the guide tube may vary in each treatment. From this supposition, we attempted to fill the gap between the electrode and the guide tube with ethanol which has large permittivity. The results of the present method showed that each pattern of the temperature rise distribution was similar and reproductive.

View full abstract

We analyzed the p53-dependent signal transductions induced by hyperthermia using molecular biology techniques. By the analysis of WAF1 induction, we elucidated the existence of the p53-dependent signal transductions induced by hyperthermia as is the case of ionizing radiation. In addition, we found the suppression of heat-induced p53 and hsp72 accumulation by cisplatin in the p53-dependent manner. It may be due to the confliction of signal transductions induced by heat and cisplatin. We propose that one of the determinants of cellular thermosensitivity is p53 tumor suppressor gene.

View full abstract