Abstract 806: Anti-tumor effects of low temperature whole body hyperthermia on human bladder cancer cells in vivo

Abstract

Abstract As a whole, the concept of thermotherapy is still under study. However, there is an abundant amount basic and pre-clinical published reports that have shown the antitumor effects of hyperthermia in various cancer models. Local, regional and whole body hyperthermia (WBH) has been studied and the effectiveness of the treatment depends largely on the temperature achieved and the duration of treatment. High temperatures, low duration (heat shock) will have a direct killing effect on exposed cells. The limitation to this approach is the restriction of tumor location. Low temperature, high duration WBH is generally considered to be the least toxic but requires long exposures that are generally uncomfortable or inconvenient to the patients. In this study we investigate the therapeutic efficacy of a synthetic far-infrared emitting biomaterial (BR), capable of inducing mild whole body hyperthermia, alone or in combination with chemotherapy against bladder cancer cell lines in vivo. Immunocompetent and immunodeficient mice were inoculated with a human superficial bladder cancer cell (KU7/GFP) or mouse bladder cancer cell (NBT2), respectively, and treated with BR alone or in combination with doxorubicin (Dox). Mice exposed to BR increased their core body temperature by 1oC (P<0.05) after 2 weeks of exposure. Both immunocompetent and immunodeficient bearing subcutaneous tumor xenografts treated to WBH demonstrated a clear tendency in the reduction of tumor size. Histological analysis showed that tumors exposed to WBH had remarkable granulocyte infiltration accompanied by increased necrosis. Elevated levels of HSP27, HSP70 and HSP90 were detected in tumors of mice exposed to WBH. Increased levels of C-GSF, GM-CSF, TNFα and IL-12p70 corresponded to exposure to WBH. To determine the synergistic effects of WBH and chemotherapy, a survival study was carried out using immunodeficient mice orthotopically inoculated with KU7/GFP cells. Mice treated with Dox or WBH/Dox demonstrated a reduction in tumor size compared to mice treated with WBH and untreated controls. More interestingly, survival rates for control, WBH, Dox and WBH/Dox groups were 50% (5/10), 70% (7/10), 10% (1/10) and 50% (5/10), respectively. No clear differences were noted in HSP expression or granulocyte infiltration in these mice. Our data suggests that WBH may induce mild antitumor effects; although, the precise mechanism is still unclear, it appears that it may be due to an immuno-stimulatory effect. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 806. doi:10.1158/1538-7445.AM2011-806