Audrey Loumaye1, Marie de Barsy, Maxime Nachit, Pascale Lause, Lena Frateur, Aline van Maanen, Pierre Trefois, Damien Gruson, Jean-Paul Thissen. 1. Endocrinology, Diabetology, and Nutrition Department (A.L., M.N., P.L., D.G., J-P.T.), Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, 1200 Brussels, Belgium; Endocrinology and Nutrition (A.L., M.d.B., J-P. T.), and Dietetic Departments (L.F.), King Albert II Cancer Institute (L.F., A.v.M.), Medical Imaging (P.T.), and Laboratory Medicine Departments (D.G.), Cliniques Universitaires St-Luc, 1200 Brussels, Belgium.
Abstract
CONTEXT: Cachexia is a multifactorial syndrome, characterized by the loss of skeletal muscle mass and not fully reversible by nutritional support. Recent animal observations suggest that production of Activin A (ActA) and Myostatin (Mstn) by some tumors might contribute to cancer cachexia. OBJECTIVE: Our goal was to investigate the role of ActA and Mstn in the development of the human cancer cachexia. DESIGN/ SETTING: The ACTICA study is a cross-sectional study, which prospectively enrolled patients from a tertiary-care center between January 2012 and March 2014. Subjects/Outcome Measures: One hundred fifty two patients with colorectal or lung cancer had clinical, nutritional and functional assessment. Body composition was measured by CT-scan, anthropometry, and bioimpedance. Plasma concentrations of ActA, Mstn, and Follistatin were determined. RESULTS: Cachexia was associated with reduced lean and fat mass (p < .01 and p < .001), reduced physical function, lower quality of life, and increased symptoms (QLQC30; p < .001). Anorexia (SNAQ score < 14) was more common in cachectic patients (CC) than in noncachectic patients (CNC) (p < .001). ActA concentrations in CC patients were higher than in CNC patients (+40%; p < .001) and were correlated positively with weight loss (R = 0.323; p < .001) and negatively with the SNAQ score (R = -0.225; p < .01). In contrast, Mstn concentrations were decreased in CC patients compared to CNC patients (-35%; p < .001). CONCLUSIONS: These results demonstrate an association between circulating concentrations of ActA and the presence of the anorexia/cachexia syndrome in cancer patients. Given the known muscle atrophic effects of ActA, our study suggests that increased circulating concentrations of ActA may contribute to the development of cachexia in cancer patients.
CONTEXT: Cachexia is a multifactorial syndrome, characterized by the loss of skeletal muscle mass and not fully reversible by nutritional support. Recent animal observations suggest that production of Activin A (ActA) and Myostatin (Mstn) by some tumors might contribute to cancer cachexia. OBJECTIVE: Our goal was to investigate the role of ActA and Mstn in the development of the humancancer cachexia. DESIGN/ SETTING: The ACTICA study is a cross-sectional study, which prospectively enrolled patients from a tertiary-care center between January 2012 and March 2014. Subjects/Outcome Measures: One hundred fifty two patients with colorectal or lung cancer had clinical, nutritional and functional assessment. Body composition was measured by CT-scan, anthropometry, and bioimpedance. Plasma concentrations of ActA, Mstn, and Follistatin were determined. RESULTS:Cachexia was associated with reduced lean and fat mass (p < .01 and p < .001), reduced physical function, lower quality of life, and increased symptoms (QLQC30; p < .001). Anorexia (SNAQ score < 14) was more common in cachectic patients (CC) than in noncachectic patients (CNC) (p < .001). ActA concentrations in CC patients were higher than in CNC patients (+40%; p < .001) and were correlated positively with weight loss (R = 0.323; p < .001) and negatively with the SNAQ score (R = -0.225; p < .01). In contrast, Mstn concentrations were decreased in CC patients compared to CNC patients (-35%; p < .001). CONCLUSIONS: These results demonstrate an association between circulating concentrations of ActA and the presence of the anorexia/cachexia syndrome in cancerpatients. Given the known muscle atrophic effects of ActA, our study suggests that increased circulating concentrations of ActA may contribute to the development of cachexia in cancerpatients.
Authors: Archana S Nagaraja; Robert L Dood; Guillermo Armaiz-Pena; Yu Kang; Sherry Y Wu; Julie K Allen; Nicholas B Jennings; Lingegowda S Mangala; Sunila Pradeep; Yasmin Lyons; Monika Haemmerle; Kshipra M Gharpure; Nouara C Sadaoui; Cristian Rodriguez-Aguayo; Cristina Ivan; Ying Wang; Keith Baggerly; Prahlad Ram; Gabriel Lopez-Berestein; Jinsong Liu; Samuel C Mok; Lorenzo Cohen; Susan K Lutgendorf; Steve W Cole; Anil K Sood Journal: JCI Insight Date: 2017-08-17
Authors: So-Youn Kim; Katherine Ebbert; Marilia H Cordeiro; Megan M Romero; Kelly A Whelan; Adrian A Suarez; Teresa K Woodruff; Takeshi Kurita Journal: Cancer Res Date: 2016-05-09 Impact factor: 12.701
Authors: Jonathan R Davey; Kevin I Watt; Benjamin L Parker; Rima Chaudhuri; James G Ryall; Louise Cunningham; Hongwei Qian; Vittorio Sartorelli; Marco Sandri; Jeffrey Chamberlain; David E James; Paul Gregorevic Journal: JCI Insight Date: 2016-04-21