In vitrothermal therapy of AT-1 Dunning prostate tumours

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Abstract
To advance the utility of prostate thermal therapy, this study investigated the thermal thresholds (temperature-time) for prostate tissue destruction in vitro. The AT-1 Dunning prostate tumour model was chosen for the study. Three hundred micron thick sections were subjected to controlled temperature-time heating, which ranged from low (40 degrees C, 15 min) to high thermal exposures (70 degrees C, 2 min) (n = 6). After subsequent tissue culture at 37 degrees C, the sections were evaluated for tissue injury at 3, 24 and 72 h by two independent methods: histology and dye uptake. A graded increase in injury was identified between the low and high thermal exposures. Maximum histologic injury occurred above 70 degrees C, 1 min with >95% of the tissue area undergoing significant cell injury and coagulative necrosis. The control and 40 degrees C, 15 min sections showed histologic evidence of apoptosis following 24 and 72 h in culture. Similar signs of apoptosis were minimal or absent at higher thermal histories. Vital-dye uptake quantitatively confirmed complete cell death after 70 degrees C, 2 min. Using the dye data, Arrhenius analysis showed an apparent breakpoint at 50 degrees C, with activation energies of 135.8 kcal/mole below and 4.7 kcal/mole above the threshold after 3 h in culture. These results can be used as a conservative benchmark for thermal injury in the cancerous prostate. Further characterization of the response to thermal therapy in an animal model and in human tissues will be important in establishing the efficacy of the procedure