Effect of the combination of a local OK-432 injection and hyperthermia on SCC VII tumors in mice.

Hyperthermia is being investigated as a cancer treatment. Many of its basic mechanisms, particularly those related to cell killing, are still poorly understood. We used a transplanted squamous cell carcinoma cell line to investigate the therapeutic effect of hyperthermia. In particular, we examined the effect of OK-432 (biological response modifier) on hyperthermia-induced apoptosis. In the hyperthermia only group the most extensive necrosis occurred on day 3 (70.3%), and the apoptosis index also was highest on that day (69.3). These results suggest that the induction of apoptosis is closely related to the cell death caused by hyperthermia. The percent of necrosis was significantly higher in the groups given hyperthermia and combined OK-432 and hyperthermia treatment than in the OK-432 group (p < 0.05). The apoptosis index was significantly lower in the combined OK-432 and hyperthermia treatment group than in the hyperthermia only group, indicative that the antitumor effect of combined hyperthermia and OK-432 therapy is not ascribable to the induction of apoptosis.

A study of sports-related mandibular angle fracture: relation to the position of the third molars.

Mandibular angle fractures have been considered attributable to the presence of unerupted third molars. We examined the relationship between the incidence of sports-related mandibular angle fractures and the presence of a mandibular third molar with emphasis on the position of the third molar. The incidence of angle fracture was significantly higher in the sports-related injury group than in the group with fracture due to other causes (P < 0.05). The incidence of angle fracture in the athletes with higher impaction scores was significantly higher than that in the subjects with higher scores who did not have sports-related fractures (P < 0.05). The percentage of rugby athletes with third molars was significantly higher than that of those without third molars (P < 0.001), and a high proportion of young athletes (89.5%) was considered to belong to a potential high-risk group for angle fractures. Our findings suggest that mandibular angle fractures are influenced by the presence and characteristics of the third molar in sports-related injuries.

Hsp40, a possible indicator for thermotolerance of murine tumour in vivo.

The relationship between Hsp40/Hsp70 synthesis and the development of thermotolerance was investigated using mouse squamous cell carcinoma in vivo. To examine the thermotolerance, tumours were heated at 44 degrees C for 30 min as conditioning heating. After various intervals they were heated again at 44 degrees C for 90 min as challenge heating. The tumour response to heat was evaluated by the growth delay. Thermotolerance rapidly developed with increasing interval and reached a maximum at 12 h interval. Subsequently, thermotolerance gradually decayed and almost disappeared at 120 h interval. Under this condition, synthesis of Hsp40/Hsp70 increased after conditioning heating, reached a maximum at 12 h interval, then gradually decreased thereafter within 120 h. The kinetics of accumulation and decay of both Hsp40 and Hsp70 were very similar. The extent of thermotolerance was well correlated with the relative amount of Hsp40/Hsp70. These results obtained in vivo were very similar to those in vitro (Kaneko et al. 1995). Our findings suggest that Hsp40 could be a useful indicator of the degree of thermotolerance in addition to Hsp70 in vivo as in vitro.

Thermochemotherapy for cancer of the tongue using magnetic induction hyperthermia (implant heating system: IHS).

A 55-year-old patient with cancer of the tongue (T2N0M0) was treated by thermochemotherapy using interstitial magnetic induction hyperthermia (Implant Heating System: IHS). The patient received 2 courses of hyperthermia, each of which was 45 minutes long. At the same time, the patient received 2 courses of chemotherapy, which included intra-arterial infusion of 100 mg of cisplatin (CDDP) and 25 mg of peplomycin (PEP). The patient showed complete response (CR) to this therapy. To date, 1.5 years after completion of treatment, the patient has shown no recurrence. This therapy, which makes surgery and radiotherapy unnecessary, is promising, because it is expected to improve the quality of life (QOL) of cancer patients.

Preoperative thermochemotherapy of oral cancer using magnetic induction hyperthermia (Implant Heating System: IHS).

Eight patients with primary cancer of the oral cavity were preoperatively treated by combined treatment with hyperthermia and chemotherapy. They received two courses of chemotherapy, which included intra-arterial infusion of 100 mg of cisplatin (CDDP) and 25 mg of peplomycin (PEP) via the superficial temporal artery. The patients also received interstitial hyperthermia for 45 min once a week using the Implant Heating System (IHS) with chemotherapy. IHS consists of ferromagnetic implant, induction coil and generator to produce high frequency magnetic field. The ferromagnetic implant is made of Fe-Pt alloy (Fe: 73%, Pt: 27%), and has a Curie temperature of 68 degrees C. As a result, clinical complete response (CR) was observed in seven patients and partial response (PR) in one, and postoperative pathological examination showed no residual tumour cells in any specimen. Combined interstitial hyperthermia by IHS and chemotherapy is thus found to be an effective therapeutic method for treating oral cancers.

Electron-microscopic and immunohistochemical studies of Langerhans cells and Thy-1-positive cells in mouse tongue epithelium subjected to local hyperthermia.

Local hyperthermia via skin has been used to treat cancer but may suppress local immune responses as a side-effect. To examine effects of heat on immunologically responsive cells in oral mucosa, mouse tongues were heated by an implant system at 43 degrees C for 20 min. The densities of Langerhans cells and Thy-1-positive cells rapidly increased within 3 h after the treatment, then returned to a normal level after 7 days. Electron microscopy confirmed that Langerhans cells in the tongue epithelium formed clusters with lymphocytic cells, suggesting an active response to the hyperthermia.