title: Tandospirone reduces wasting and improves cardiac function in experimental cancer cachexia.
abstract: BACKGROUND
  Cancer cachexia is thought to be the cause of >20% of cancer related deaths. Symptoms of cancer cachexia patients include depression and anorexia significantly worsening their quality of life. Moreover, in rodent models of cancer cachexia atrophy of the heart has been shown to impair cardiac function. Here, we characterize the effects of the antidepressant and anxiolytic drug tandospirone on wasting, cardiac function and survival in experimental cancer cachexia.
  
  
  METHODS
  The well-established Yoshida hepatoma rat model was used and tumor-bearing rats were treated with 1mg/kg/d (LD), 10mg/kg/d (HD) tandospirone or placebo. Weight, body composition (NMR), cardiac function (echocardiography), activity and food intake were assessed. Noradrenalin and cortisol were measured in plasma and caspase activity in skeletal muscle.
  
  
  RESULTS
  Ten mg/kg/d tandospirone decreased the loss of body weight (p=0.0003) compared to placebo animals, mainly due to preservation of muscle mass (p<0.001), while 1mg/kg/d tandospirone was not effective. Locomotor activity (p=0.0007) and food intake (p=0.0001) were increased by HD tandospirone. The weight (p=0.0277) and function of heart (left ventricular mass, fractional shortening, stroke volume, ejection fraction, all p<0.05) were significantly improved. In the HD tandospirone group, plasma levels of noradrenalin and cortisol were significantly reduced by 49% and 52%, respectively, which may have contributed to the lower caspase activity in the gastrocnemius muscle. Most importantly, HD tandospirone significantly improved survival compared to placebo rats (HR: 0.34; 95% CI: 0.13-0.86; p=0.0495).
  
  
  CONCLUSIONS
  Tandospirone showed significant beneficial effects in the Yoshida hepatoma cancer cachexia model and should be further examined as a prospective drug for this syndrome.
authors.affiliation: Applied Cachexia Research, Department of Cardiology, Charité Medical School, Berlin, Germany; Center for Cardiovascular Research, Charite Medical School, Berlin, Germany.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Elkina
authors.forename: Sandra
authors.initials: S
authors.lastname: Palus
authors.forename: Anika
authors.initials: A
authors.lastname: Tschirner
authors.forename: Kai
authors.initials: K
authors.lastname: Hartmann
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
authors.forename: Ulrike
authors.initials: U
authors.lastname: Mayer
authors.forename: Andrew J S
authors.initials: AJ
authors.lastname: Coats
authors.forename: John
authors.initials: J
authors.lastname: Beadle
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Jochen
authors.initials: J
authors.lastname: Springer
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects; D052436:Adipose Tissue, White / Q000187:drug effects; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001823:Body Composition / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D006528:Carcinoma, Hepatocellular / Q000150:complications*; D045744:Cell Line, Tumor; D004452:Echocardiography; D006334:Heart Function Tests / Q000187:drug effects; D054833:Isoindoles / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000150:complications*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D014151:Anti-Anxiety Agents; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; C055267:tandospirone
keywords: Anti-depressant; Body composition; Cancer cachexia; Cardiac function; Survival; Tandospirone