HSP 70 induction and thermotolerance following interstitial hyperthermia in the dunning R3327 tumor in vivo

Abstract

We investigated the use of an interstitial temperature self-regulating implant for fractionated hyperthermia delivery for treatment of prostatic disease. Nonuniform heating, lower temperatures between the implants, and lingering thermotolerance for additional hyperthermia treatments are concerns associated with the technique. Thermotolerance of the Dunning R3327 prostate adenocarcinoma to a 1 hour interstitial heating of 42–43°C has been estimated using inducible heat shock protein (HSP) 72 as an assay. The duration of thermotolerance in a nonuniformly heated tumor is necessary for optimization of multiple-treatment planning. HSP 72 expression is increased between 8 and 16 hours posttreatment. Growth curves for conditioned (treated once at 42–43°C minimum) tumors retreated at a minimum temperature of 45°C after 10 hours recovery (where elevated HSP 72 expression is evident) were compared with those retreated after 48 hours recovery (with normal HSP 72 expression) and with conditioned controls; both retreatment groups differed from controls ( p < 0.0001). Growth curves for tumors with elevated HSP 72 expression after 10 hours differed from those retreated after 48 hours ( p ≤ 0.0202). The results indicate that in vivo measurement of HSP 72 expression in the Dunning tumor is an adequate indicator of thermotolerance for optimal sequencing of hyperthermia fractions and that sufficiently high thermal doses are effective against thermotolerant cell populations.