The response of kidney to ionizing radiation combined with hyperthermia induced by ultrasound.

Mouse kidneys were made hyperthermic (42.5 degrees C for 30 min) one hour before, during, or one hour after local irradiation to determine the effect of hyperthermia on radiation damage. An ultrasound beam was used to induce hyperthermia. The urinary concentrations of total protein and albumin were used as criteria of kidney injury. Hyperthermia alone did not induce proteinuria. Radiation alone produced proteinuria that was not correlated with dose. Hyperthermia induced during or after irradiation resulted in a thermal enhancement factor of 1.29 +/- .33. Hyperthermia induced one hour before irradiation resulted in a thermal enhancement factor of 0.88 +/- .05, indicating a radioprotective effect. To the authors' knowledge, this is the first time such an effect has been shown.

The influence of warfarin of levamisole on the incidence of metastases following local irradiation of a solid tumor.

KHT sarcomas were implanted in the right rear legs of C3H mice. An x-ray dose of 6000 rad, delivered in ten equal fractions over 12 days, resulted in 60% local tumor control, but 83% of these mice developed metastases. Three strategies to use the tumoricidal effect of x-radiation and reduce the incidence of metastases were compared. A modification of the fractionation scheme to deliver an initial large fraction of 1800 rad followed by seven 600-rad fractions resulted in a decreased incidence of metastases compared with the same dose delivered in ten equal fractions. The use of warfarin anticoagulation during the ten-fraction course of radiation resulted in a small decrease in the incidence of metastases. Immune stimulation with levamisole, injected subcutaneously every second day during the irradiation, also resulted in a decrease in the incidence of metastases. However, when warfarin or levamisole were combined with the eight-fraction radiation scheme there were fewer metastases than following the ten-fraction scheme. The combination of the eight-fraction radiation course with levamisole also produced a significant increase in primary tumor control. In this treatment regimen, therefore, levamisole appears to act as a radiation sensitizer. An hypothesis to explain this action is proposed.

Effect of ultrasound-induced hyperthermia and cis-diamminedichloride platinum II on murine renal function.

Murine renal function was evaluated after ultrasound-induced kidney hyperthermia (42.5 degrees C and 46.5 degrees C for 35 minutes) and the administration of cis-diamminedichloride platinum II (8 mg/kg). A quantitative immunonephelometric technique was employed to determine urinary total protein (TP) and albumin (Alb) 1-180 days post-treatment. Hyperthermia of 46.5 degrees C elevated urinary TP excretion significantly more than that of 42.5 degrees C cis-diamminedichloride platinum (Cis DDP) administration greatly increase urine TP with a peak mean TP concentration of 488 microgram/ml, four days after Cis DDP (normal range was 26-48 microgram/ml). This returned to normal by day 14. The TP excretion after 42.5 degrees C hyperthermia with concurrent Cis DDP was similar to Cis DDP alone, implying there was no potentiation of early or late Cis-DDP-induced renal damage by hyperthermia. Late mouse mortality was greater (P = 0.08) after Cis DDP alone, than Cis DDP with 42.5 degrees C hyperthermia. There was a statistically significant increase (P less than 0.05) in the Alb/TP excretion ratio after the addition of 42.5 degrees C hyperthermia to Cis DDP, implying an alteration in the site or nature of the Cis DDP renal lesion by hyperthermia.

The influence of ICRF-159 and levamisole on the incidence of metastases following local irradiation of a solid tumor.

Courses of irradiation consisting of 6000 rad in ten equal fractions over 12 days delivered to KHT sarcomas in mice controlled 55% of the local tumors but 83% of the mice died from metastases. Three strategies to reduce the risk of metastatic spread were tested. The fractionation scheme was changed to deliver the same total dose using a large initial fraction followed by seven equal portions with the same overall time. ICRF-159 was used with the intention of partially synchronizing the tumor growth fraction in a radiosensitive state of the growth cycle and of promoting normalization of the tumor vasculature. Levamisole was used to stimulate the immune system. The combination of ICRF-159 with the eight-fraction radiation course proved to be effective for both increasing local control and decreasing the incidence of metastases. The addition of levamisole did not improve the results obtained with a combination of ICRF-159 and irradiation.