Combination therapies have been investigated as a mean to increase efficacy of disease treatment. For example, combinations such as radiation and chemotherapy, surgery and chemotherapy, and two different chemotherapies have become standard treatment for most cancers. Current theories suggest that vascular-mediated injury is an important mechanism of cryosurgical (reviewed in Gage and Baust (1998)) and hyperthermic destruction (Badylak et al., 1985; Dudar and Jain, 1984) in the treatment of solid tumors. These techniques appear complementary. Freezing creates vascular damage and promotes stasis within the vessels (Rabb et al., 1974), whereas hyperthermia creates cell and vascular destruction more effectively with a compromised vasculature (Shakil et al., 1999). Thus, in this study, we investigated the effect of combining these therapies on the vascular and tissue injury from the two therapies. We chose the dorsal skin flap chamber (DSFC) implanted in the Copenhagen rat as the cryosurgical model for this study. This in vivo freezing model allowed us to monitor thermal history and investigate both vascular and tissue injury in response to the combination therapy.

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