Abstract 5492: The effects of whole body hyperthermia on tumor growth by a novel far infrared emitter

Abstract

Abstract Whole body hyperthermia (WBH) has been used alone or as an adjunct to radio- and/or chemotherapy for the treatment of various malignant diseases. The therapeutic effect of WBH in these conditions has been hypothesized to involve direct or indirect activation of the immune system and heat shock proteins (HSPs). In this study, we investigate the effects of hyperthermia in vitro and in vivo using BioRubber (BR, Yamamoto Bio-Technology Inc., Anaheim, CA), a revolutionary far infrared emitter on tumor growth. BR is a pliable state-of-the-art biomaterial that emits FIR in the 4-25μm spectral ranges. For the in vitro experiments, cell growth assays and cell cycle analysis was performed in a total of twelve different cancer cell lines (HeLa, bladder, prostate and renal) sandwiched between BR. BR had no inhibitory effects on any of the tumor cells grown in vitro. To determine the effects of BR therapy on tumor and normal tissue in vivo, KU7/GFP-bearing nude mice were housed in cages lined with BR for 28 days. Tumor size and core body temperature were recorded weekly. The core body temperatures of mice exposed to BR increased significantly by 1oC (P<0.05) after 2 weeks of exposure to BR. Although not significant, tumors of mice exposed to BR showed a clear tendency in tumor size reduction. Tumors were collected and anlyzed for histopathology, TUNEL and PCNA immunohistochemical analysis. Proliferation and apoptotic rates in tumors from mice exposed to BR were similar to control mice. Further histopathological analysis showed that BR-exposed tumors had remarkable granulocyte infiltration accompanied by increased necrosis. This suggest that BR exposure was indeed able to induce and sustain mild hyperthermia in vivo with reduced tumor growth. However, no direct inhibitory on the tumor cells resulted form BR-induced hyperthermia but rather appeared to have been an indirect effect of immuno-stimulation achieved from sustained WBH. To further investigate the immunological component of hyperthermia-induced immune response, a syngeneic tumor model was carried out using mouse RENCA cells in immunocompetent and immunodeficient mice. Similar tumor growth inhibitory effects were seen in both immunocompetent and immunodeficient mice thus suggesting an innate immune response as a result of sustained WBH. Together, these data suggest that BR may be a promising biomaterial in for use hyperthermia therapy: however, more research has to be conducted to elucidate the specific mechanisms involved in immuno-stimulation and whether the effects from BR-induced hyperthermia can be maximized with combination therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5492.