Hiroaki Hondo

Effects of antineoplastic agents and hyperthermia on cytotoxicity toward chronically hypoxic glioma cells

The effects of hyperthermia and antineoplastic agents on the cytotoxicity to normally oxygenated and chronically hypoxic glioma cells were investigated in vitro. Exposure to temperatures above 43.0 degrees C was less cytotoxic to hypoxic cells which predominantly accumulated in the G0/G1 phase fraction. On the other hand, mitomycin C (MMC) and adriamycin (ADM) were preferentially cytotoxic to hypoxic cells not only at 37 degrees C but also at elevated temperatures (42 degrees C and 43 degrees C). These two agents showed marked synergistic effects with hyperthermia under both oxygenated and hypoxic conditions. In contrast, bleomycin (BLM), cis-diamminedichloroplatinum(II) (CDDP), and vincristine (VCR) were preferentially cytotoxic to oxygenated cells at both 37 degrees C and elevated temperatures. CDDP showed cytotoxic synergism with hyperthermia that appeared to be oxygen-dependent. A nitrosourea derivative, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), showed no major preferential toxicity under either oxygenated or hypoxic conditions. This study suggests that hyperthermia in combination with MMC or ADM would have a greater cytotoxic effect on hypoxic cell subpopulations of malignant gliomas.

Auditory brainstem response during systemic hyperthermia

The relationship between the brain temperature and the latency of ABR was evaluated in a dog model of systemic hyperthermia induced by heating of the blood during extracorporeal circulation. The latency of ABR was shortened and the amplitude was reduced with the elevation of brain temperature. The shortening of the latency was more notable in wave 4 than in wave 1, and this is considered to have been due to greater changes in the conduction velocity in the central nervous system than in peripheral nerves. The latency of ABR, from which the brain temperature can be estimated, is considered to be clinically useful as an index of brain temperature during systemic hyperthermia.