Publications [#168994] of Mark W. Dewhirst

Papers Published

1. TW Secomb, R Hsu, MW Dewhirst, Synergistic effects of hyperoxic gas breathing and reduced oxygen consumption on tumor oxygenation: a theoretical model., International journal of radiation oncology, biology, physics, United States, vol. 59 no. 2 (June, 2004), pp. 572-8, ISSN 0360-3016
   (last updated on 2009/12/31)

   Abstract:
   PURPOSE: To simulate effects of reduced oxygen consumption combined with hyperoxic gas breathing on tumor oxygenation, and to test for synergistic effects. METHODS AND MATERIALS: Diffusive oxygen transport was simulated for a small region of tumor containing a three-dimensional network of microvessels whose geometry was derived from in vivo observations. Changes in tissue partial pressure of oxygen (PO(2)) and hypoxic fraction (PO(2) < 5 mm Hg) resulting from a 30% reduction in oxygen consumption rate or breathing 100% oxygen were estimated. The synergistic effect was defined as the change in PO(2) with the two treatments combined, minus the sum of the changes with the separate treatments. RESULTS: Predicted hypoxic fractions were 37% in the control state, 11% with reduced consumption, 23% with oxygen breathing alone, and 0% with the combined treatment. The synergistic effect was about 4 mm Hg at tissue points with very low initial PO(2) levels and decreased as initial PO(2) increased. CONCLUSIONS: Reduction of oxygen consumption via the Crabtree effect, by administration of glucose, has been proposed as a means to improve tumor oxygenation during radiation treatment. The results support previous experimental studies showing that this approach is more effective when combined with breathing of hyperoxic gases.

   Keywords:
   Animals • Cell Hypoxia • Cell Respiration • Models, Biological* • Neoplasms • Oxygen • Oxygen Consumption • Partial Pressure • Rats • Regional Blood Flow • administration & dosage • blood supply* • metabolism* • physiology* • physiopathology