title: Sunitinib treatment does not improve blood supply but induces hypoxia in human melanoma xenografts.
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.
  
  
  CONCLUSIONS
  Sunitinib treatment did not improve vascular function but induced hypoxia in A-07-GFP and R-18-GFP tumors.
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, Norway. Jon.Vidar.Gaustad@rr-research.no
authors.forename: Jon-Vidar
authors.initials: JV
authors.lastname: Gaustad
authors.forename: Trude G
authors.initials: TG
authors.lastname: Simonsen
authors.forename: Marit N
authors.initials: MN
authors.lastname: Leinaas
authors.forename: Einar K
authors.initials: EK
authors.lastname: Rofstad
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001485:Basement Membrane / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008545:Melanoma / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D018874:Spheroids, Cellular; D000077210:Sunitinib; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib