1: Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):630-5.

Glucocorticoids modulate tumor radiation response through a decrease in tumor
oxygen consumption.

Crokart N, Jordan BF, Baudelet C, Cron GO, Hotton J, Radermacher K, Gregoire V,
Beghein N, Martinive P, Bouzin C, Feron O, Gallez B.

Laboratories of Medicinal Chemistry and Radiopharmacy, Universite Catholique de
Louvain, B-1200 Brussels, Belgium.

PURPOSE: We hypothesized that glucocorticoids may enhance tumor radiosensitivity
by increasing tumor oxygenation (pO(2)) through inhibition of mitochondrial
respiration. EXPERIMENTAL DESIGN: The effect of three glucocorticoids
(hydrocortisone, dexamethasone, and prednisolone) on pO(2) was studied in murine
TLT liver tumors and FSaII fibrosarcomas. At the time of maximum pO(2) (t(max),
30 min after administration), perfusion, oxygen consumption, and radiation
sensitivity were studied. Local pO(2) measurements were done using electron
paramagnetic resonance. The oxygen consumption rate of tumor cells after in vivo
glucocorticoid administration was measured using high-frequency electron
paramagnetic resonance. Tumor perfusion and permeability measurements were
assessed by dynamic contrast-enhanced magnetic resonance imaging. RESULTS: All
glucocorticoids tested caused a rapid increase in pO(2). At t(max), tumor
perfusion decreased, indicating that the increase in pO(2) was not caused by an
increase in oxygen supply. Also at t(max), global oxygen consumption decreased.
When irradiation (25 Gy) was applied at t(max), the tumor radiosensitivity was
enhanced (regrowth delay increased by a factor of 1.7). CONCLUSION: These
results show the potential usefulness of the administration of glucocorticoids
before irradiation.

PMID: 17255286 [PubMed - in process]

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