title: Vascular abnormalities associated with acute hypoxia in human melanoma xenografts.
abstract: OBJECTIVE
  The fraction of hypoxic cells has been shown to differ substantially among human tumors of the same histological type. In this study, a window chamber model was used to identify possible mechanisms leading to the development of highly different hypoxic fractions in A-07 and R-18 human melanoma xenografts.
  
  
  METHODS
  Chronic and acute hypoxia was assessed in intradermal tumors using an immunohistochemical and a radiobiological assay. Functional and morphological parameters of the vascular networks of tumors growing in dorsal window chambers were assessed with intravital microscopy.
  
  
  RESULTS
  R-18 tumors showed significantly higher hypoxic fractions than A-07 tumors, and the difference was mostly due to acute hypoxia. Compared to A-07 tumors, R-18 tumors showed low vascular densities, low vessel diameters, long vessel segments, low blood flow velocities, frequent fluctuations in blood flow, and a high fraction of narrow vessels with absent or very low and varying flux of red blood cells.
  
  
  CONCLUSIONS
  The high fraction of acute hypoxia in R-18 tumors was a consequence of frequent fluctuations in blood flow and red blood cell flux combined with low vascular density. The fluctuations were most likely caused by high geometric resistance to blood flow in the tumor microvasculature.
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Norway. trude.golimo.simonsen@rr-research.no
authors.forename: Trude G
authors.initials: TG
authors.lastname: Simonsen
authors.forename: Jon-Vidar
authors.initials: JV
authors.lastname: Gaustad
authors.forename: Marit N
authors.initials: MN
authors.lastname: Leinaas
authors.forename: Einar K
authors.initials: EK
authors.lastname: Rofstad
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000098:blood supply* / Q000473:pathology; D051379:Mice; D055806:Microvessels / Q000503:physiopathology; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000098:blood supply* / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured