Publications [#63227] of Mark W. Dewhirst

Papers Published

1. Jackson, I.L. and Batinic-Haberle, I. and Sonveaux, P. and Dewhirst, M.W. and Vujaskovic, Z., ROS production and angiogenic regulation by macrophages in response to heat therapy, Int. J. Hyperth. (UK), vol. 22 no. 4 (2006), pp. 263 - 73 [02656730600594027]
   (last updated on 2007/04/14)

   Abstract:
   It has been well established that inadequate blood supply combined with high metabolic rates of oxygen consumption results in areas of low oxygen tension (<1%) within malignant tumours and that elevating tumour temperatures above 39°C results in significant improvement in tumour oxygenation. Macrophages play a dual role in tumour initiation and progression having both pro-tumour and anti-tumour effects. However, the response of macrophages to heat within a hypoxic environment has not yet been clearly defined. Raw 264.7 murine macrophages were incubated under normoxia and chronic hypoxia at temperatures ranging from 37-43°C. Under normoxia at 41°C, macrophages start to release significant levels of superoxide. The combination of heat with hypoxia constitutes an additional stimulus leading to increased respiratory burst of macrophages. The high levels of superoxide were found to be associated with changes in macrophage production of pro-angiogenic cytokines. While hypoxia alone (37°C) increased levels of hypoxia inducible factor-1α (HIF-1α) in macrophages, the combination of hypoxia and mild hyperthermia (39-41°C) induced a strong reduction in HIF-1α expression. The HIF-regulated vascular endothelial growth factor (VEGF) decreased simultaneously, revealing that heat inhibits both HIF-1α stabilization and transcriptional activity. The data suggest that temperatures which are readily achievable in the clinic (39-41°C) might be optimal for maximizing hyperthermic response. At higher temperatures, these effects are reversed, thereby limiting the therapeutic benefits of more severe hyperthermic exposure

   Keywords:
   biochemistry;blood vessels;cancer;hyperthermia;oxygen;patient treatment;proteins;tumours;