A joint clinical trial of hyperthermia using a newly developed 8-MHz radiofrequency (RF) capacitive heating device (Thermotron RF-8; developed in cooperation with Yamamoto Vinyter Co. of Osaka) was performed under collaboration of seven institutions. Radiation with 4 Gy twice a week for a total of 40 Gy or 2 Gy five times a week for a total of 50 Gy was delivered. After irradiation, hyperthermia at 42.5 degrees C +/- 0.5 degree C for 40 to 60 minutes was given twice a week for a total of 10 times. Tumors examined in this trial were located in various depths in the body, and included those which were considered refractory to conventional treatments or radioresistant such as malignant melanoma and soft tissue tumors. Of the 63 tumors treated, 52.4% showed complete regression (CR); 19.0% more than 80% regression (PRa); 20.6%, 80% to 50% regression (PRb); and 8.0% no regression (NR). Our joint clinical trial demonstrated that hyperthermia with the use of the Thermotron RF-8 is safe and effective in the treatment of radioresistant tumors located in superficial, subsurface, and in some cases deep regions, if the surface cooling is properly managed by the temperature-controlled saline pad and electrodes of appropriate size are paired.
GPT was feasible and showed high efficacy. Although the number of patients and the follow-up periods are insufficient, the clinical results seem very encouraging.
C3H/He mice bearing the SCC VII tumor were irradiated after being given 10 injections of 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating cells in the tumors, and the tumors were then excised and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (which blocks cytokinesis), and the micronucleus frequency in unlabeled cells was determined using immunofluorescence staining to BrdU. The micronucleus frequency was then used to calculate the surviving fraction of the unlabeled cells, using the regression line relating the micronucleus frequency to the surviving fraction determined separately for the total tumor cell population. Using this technique, a cell survival curve could be determined for the unlabeled cells, which were regarded as the quiescent cells. Assays performed both immediately after and 24 h after irradiation of normally-aerated tumors showed that unlabeled cells were more radioresistant and had a greater capacity for repair of potentially lethal damage than the tumor cell population as a whole. Moreover, when the assay was performed immediately after the irradiation of both normally-aerated and hypoxic tumors, it was found that unlabeled cells had a much higher hypoxic fraction than the tumor cell population as a whole. This appears to be a useful method for determining the responses of quiescent cells in solid tumors to various treatments.
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