title: Erythropoietin improves cardiac wasting and outcomes in a rat model of liver cancer cachexia.
abstract: BACKGROUND
  Erythropoietin administration, which is clinically used in cancer patients with cancer-induced anemia, has also potentially beneficial effects on nonhematopoietic organs. We assessed the effects of erythropoietin on cancer cachexia progression and cardiac wasting compared with placebo using the Yoshida hepatoma model.
  
  
  METHODS
  Wistar rats were divided in a sham group (n=10) and a tumor-bearing group (n=60). The tumor-bearing group was further randomized to placebo (n=28), 500Unit/kg/day (n=16) or 5000Unit/kg/day of erythropoietin (n=16). Body composition was measured using nuclear magnetic resonance spectroscopy, cardiac function using echocardiography, physical activity using infrared monitoring system.
  
  
  RESULTS
  Tumor-bearing rats with high dose erythropoietin led to a significant improvement on survival compared with placebo (hazard ratio: 0.43, 95%CI: 0.20-0.92, p=0.030), though low dose erythropoietin did not reach significance (hazard ratio: 0.46, 95%CI: 0.22-1.02, p=0.056). Loss of body weight, wasting of lean mass, fat mass, and reduced physical activity were ameliorated in rats treated with both low and high doses of erythropoietin (p<0.05, all). Moreover, reduced left ventricular mass and left ventricular systolic function were also ameliorated in rats treated with low and high doses of erythropoietin (p<0.05, respectively).
  
  
  CONCLUSIONS
  Overall, the present data support that cardiac wasting induced by cancer cachexia plays an important role which leads to impaired survival, provided that the erythropoietin could be an effective therapeutic approach for cancer cachexia progression and cardiac wasting.
authors.affiliation: Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany. Electronic address: msaitoh@shi.heart.or.jp.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Saitoh
authors.affiliation: Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany; Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Michiyoshi
authors.initials: M
authors.lastname: Hatanaka
authors.affiliation: Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Konishi
authors.affiliation: Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Junichi
authors.initials: J
authors.lastname: Ishida
authors.affiliation: Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Palus
authors.affiliation: Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ebner
authors.affiliation: Center for Stroke Research Berlin, Charite´ Medical School, Berlin, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Döhner
authors.affiliation: Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.affiliation: Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: Innovative Clinical Trials, Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Springer
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy*; D004921:Erythropoietin / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000150:complications*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D004921:Erythropoietin
keywords: Cancer; Cancer cachexia; Cardiac wasting; Erythropoietin; Survival; Yoshida hepatoma animal model