publications by Mark W. Dewhirst.
- SA Snyder, JL Lanzen, RD Braun, G Rosner, TW Secomb, J Biaglow, DM Brizel, MW Dewhirst, Simultaneous administration of glucose and hyperoxic gas achieves greater improvement in tumor oxygenation than hyperoxic gas alone.,
International journal of radiation oncology, biology, physics, vol. 51 no. 2
pp. 494-506 .
(last updated on 2013/05/16)
OBJECTIVE: To test the feasibility of hyperglycemic reduction of oxygen consumption combined with oxygen breathing (O(2)), to improve tumor oxygenation. METHODS: Fischer-344 rats bearing 1 cm R3230Ac flank tumors were anesthetized with Nembutal. Mean arterial pressure, heart rate, tumor blood flow ([TBF], laser Doppler flowmetry), pH, and pO(2) were measured before, during, and after glucose (1 or 4 g/kg) and/or O(2). RESULTS: Mean arterial pressure and heart rate were unaffected by treatment. Glucose at 1 g/kg yielded maximum blood glucose of 400 mg/dL, no change in TBF, reduced tumor pH (0.17 unit), and 3 mm Hg pO(2) rise. Glucose at 4 g/kg yielded maximum blood glucose of 900 mg/dL, pH drop of 0.6 unit, no pO(2) change, and reduced TBF (31%). Oxygen tension increased by 5 mm Hg with O(2). Glucose (1 g/Kg) + O(2) yielded the largest change in pO(2) (27 mm Hg); this is highly significant relative to baseline or either treatment alone. The effect was positively correlated with baseline pO(2), but 6 of 7 experiments with baseline pO(2) < 10 mm Hg rose above 10 mm Hg after combined treatment. CONCLUSIONS: We demonstrated the feasibility of combining hyperglycemia with O(2) to improve tumor oxygenation. However, some cell lines are not susceptible to the Crabtree effect, and the magnitude is dependent on baseline pO(2). Additional or alternative manipulations may be necessary to achieve more uniform improvement in pO(2).
Animals • Blood Glucose • Blood Pressure • Cell Hypoxia • Combined Modality Therapy • Extracellular Space • Feasibility Studies • Female • Glucose • Glutamine • Hydrogen-Ion Concentration • Injections, Intravenous • Models, Animal • Neoplasms, Experimental • Oxygen • Oxygen Consumption • Rats • Rats, Inbred F344 • Regional Blood Flow • Time Factors • Tumor Cells, Cultured • administration & dosage* • blood supply • chemistry • drug effects • metabolism • pharmacology • physiology • physiology* • physiopathology*