title: [Uveal Melanoma Cell Under Oxidative Stress - Influence of VEGF and VEGF-Inhibitors].
abstract: BACKGROUND
  The role of oxidative stress in cancer is complex. While the pathological alterations induced by oxidative stress may be involved in the induction of tumours, in the late stages of tumour development, it can facilitate the loss of tumour cells and might even prevent metastasis. Tumour cells show metabolic alterations, often inducing an increased production of reactive oxygen species, which makes these cells particularly vulnerable to additional oxidative stress. This is an important mode of action in the use of many chemotherapeutics and in the application of ionizing radiation. Uveal melanoma is the most frequent primary tumour in the adult eye. For metastasis of this tumour, which affects about 50 % of the patients, no appropriate treatment is currently available. However, the primary tumour can efficiently be treated with ionizing radiation. A frequent side effect of this treatment is radiation retinopathy, which is treated with vascular endothelial growth factor (VEGF) antagonists. A therapy of the primary tumour with VEGF antagonists is under discussion. So far, little data is available on this subject, however, a paradoxical worsening of the situation has been found in a mouse model of uveal melanoma treated with bevacizumab.
  
  
  METHODS
  We have investigated the effect of VEGF and of the VEGF-antagonist bevacizumab on the survival of five different melanoma cell lines under oxidative stress treatment with hydrogen peroxide. In addition, we investigated the expression of relevant proteins and the effect of bevacizumab on the proliferation of the cells as well as its effect on the angiogenic behaviour of endothelial cells, co-cultured with uveal melanoma cells.
  
  
  RESULTS
  Our study showed that not only VEGF but also, paradoxically, the VEGF-antagonist bevacizumab is able to protect uveal melanoma cells from oxidative stress-induced cell death. Bevacizumab did not influence the proliferation of the cells and showed only limited effectiveness to reduce angiogenic structures.
  
  
  CONCLUSIONS
  Considering that oxidative stress is the mode of action for ionizing radiation to induce cell death, a protective effect of bevacizumab on uveal melanoma cells against oxidative stress is worrisome and argues against the use of VEGF in uveal melanoma.
authors.affiliation: Augenklinik, Universitätsklinikum Schleswig-Holstein, Campus Kiel.
authors.forename: M
authors.initials: M
authors.lastname: Dithmer
authors.affiliation: Augenklinik, Universitätsklinikum Schleswig-Holstein, Campus Kiel.
authors.forename: A M
authors.initials: AM
authors.lastname: Kirsch
authors.affiliation: Augenklinik, Universitätsklinikum Schleswig-Holstein, Campus Kiel.
authors.forename: L
authors.initials: L
authors.lastname: Gräfenstein
authors.affiliation: Klinik für Unfallchirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel.
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.affiliation: MetaPhysiol, Essenheim.
authors.forename: H
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Molecular and Clinical Cancer Medicine, Liverpool Ocular Oncology Research Group, University of Liverpool, United Kingdom of Great Britain and Northern Ireland.
authors.forename: S E
authors.initials: SE
authors.lastname: Coupland
authors.affiliation: Klinik für Unfallchirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel.
authors.forename: S
authors.initials: S
authors.lastname: Fuchs
authors.affiliation: Augenklinik, Universitätsklinikum Schleswig-Holstein, Campus Kiel.
authors.forename: J
authors.initials: J
authors.lastname: Roider
authors.affiliation: Augenklinik, Universitätsklinikum Schleswig-Holstein, Campus Kiel.
authors.forename: A K
authors.initials: AK
authors.lastname: Klettner
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors; D000818:Animals; D000068258:Bevacizumab / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress; D014604:Uveal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000502:physiology; D000098943:Uveal Melanoma
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab