title: Febuxostat improves outcome in a rat model of cancer cachexia.
abstract: BACKGROUND
  Activity of xanthine oxidase is induced in cancer cachexia, and its inhibition by allopurinol or oxypurinol improves survival and reduces wasting in the Yoshida hepatoma cancer cachexia model. Here, we tested the effects of the second-generation xanthine oxidase inhibitor febuxostat compared with placebo in the same model as used previously by our group.
  
  
  METHODS
  Wistar rats (~200 g) were treated daily with febuxostat at 5 mg/kg/day or placebo via gavage for a maximum of 17 days. Weight change, quality of life, and body composition were analysed. After sacrifice, proteasome activity in the gastrocnemius muscle was measured. Muscle-specific proteins involved in metabolism were analysed by western blotting.
  
  
  RESULTS
  Treatment of the tumour-bearing rats with febuxostat led to a significantly improved survival compared with placebo (hazard ratio: 0.45, 95% confidence interval: 0.22-0.93, P = 0.03). Loss of body weight was reduced (-26.3 ± 12.4 g) compared with placebo (-50.2 ± 2.1 g, P < 0.01). Wasting of lean mass was attenuated (-12.7 ± 10.8 g) vs. placebo (-31.9 ± 2.1 g, P < 0.05). While we did not see an effect of febuxostat on proteasome activity at the end of the study, the pAkt/Akt ratio was improved by febuxostat (0.94 ± 0.09) vs. placebo (0.41 ± 0.05, P < 0.01), suggesting an increase in protein synthesis.
  
  
  CONCLUSIONS
  Febuxostat attenuated cachexia progression and improved survival of tumour-bearing rats.
authors.affiliation: Division of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Konishi
authors.affiliation: Applied Cachexia Research, Center for Cardiovascular Research, Charité Medical School, Berlin, Germany.|Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Loes
authors.initials: L
authors.lastname: Pelgrim
authors.affiliation: Applied Cachexia Research, Center for Cardiovascular Research, Charité Medical School, Berlin, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Tschirner
authors.affiliation: Applied Cachexia Research, Center for Cardiovascular Research, Charité Medical School, Berlin, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Baumgarten
authors.affiliation: Division of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany.|Department of Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.affiliation: Division of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Palus
authors.affiliation: Center for Stroke Research Berlin, Charité Medical School, Berlin, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
authors.affiliation: Division of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: Division of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany.|Department of Cardiology and Pneumology, University Medical Centre Göttingen, Göttingen, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Springer
keywords: Cancer cachexia; Survival; Wasting; Weight loss; Yoshida hepatoma animal model