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BMC Cancer. 2012; 12: 388.
Published online Sep 4, 2012. doi:  10.1186/1471-2407-12-388
PMCID: PMC3489843
Sunitinib treatment does not improve blood supply but induces hypoxia in human melanoma xenografts
Jon-Vidar Gaustad,corresponding author1 Trude G Simonsen,1 Marit N Leinaas,1 and Einar K Rofstad1
1Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Oslo, N-0310, Norway
corresponding authorCorresponding author.
Jon-Vidar Gaustad: Jon.Vidar.Gaustad/at/rr-research.no; Trude G Simonsen: Trude.Golimo.Simonsen/at/rr-research.no; Marit N Leinaas: Marit.Nedkvitne.Leinaas/at/rr-research.no; Einar K Rofstad: Einar.K.Rofstad/at/rr-research.no
Received June 7, 2012; Accepted August 31, 2012.
Abstract
Background
Antiangiogenic agents that disrupt the vascular endothelial growth factor pathway have been demonstrated to normalize tumor vasculature and improve tumor oxygenation in some studies and to induce hypoxia in others. The aim of this preclinical study was to investigate the effect of sunitinib treatment on the morphology and function of tumor vasculature and on tumor oxygenation.
Methods
A-07-GFP and R-18-GFP human melanoma xenografts grown in dorsal window chambers were used as preclinical tumor models. Morphologic parameters of tumor vascular networks were assessed from high-resolution transillumination images, and tumor blood supply time was assessed from first-pass imaging movies recorded after a bolus of 155 kDa tetramethylrhodamine isothiocyanate-labeled dextran had been administered intravenously. Tumor hypoxia was assessed from immunohistochemical preparations of the imaged tissue by use of pimonidazole as a hypoxia marker.
Results
Sunitinib treatment reduced vessel densities, increased vessel segment lengths, did not affect blood supply times, and increased hypoxic area fractions.
Conclusion
Sunitinib treatment did not improve vascular function but induced hypoxia in A-07-GFP and R-18-GFP tumors.
Keywords: Antiangiogenic treatment, Sunitinib, Intravital microscopy, Vascular normalization, Tumor hypoxia
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