{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T15:52:23Z","timestamp":1783612343658,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This hypothesis\u2010generating analysis used biospecimens collected from a multi\u2010centre 2\u00a0\u00d7\u00a02 factorial randomized design of 116 patients with stage I\u2013III breast and colorectal cancer who were randomized to 12\u00a0weeks of (1) aerobic exercise (moderate intensity titrated to 220\u00a0min\/week); (2) metformin (850\u00a0mg daily for 2\u00a0weeks and then titrated to 850\u00a0mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were quantified using a multiplex panel. Myokine concentrations were log\u2010transformed, and main effects analyses were conducted using linear mixed\u2010effects regression models. The type I error rate was controlled with the Holm sequential testing procedure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Randomization to exercise increased leukaemia inhibitory factor (1.26\u00a0pg\/mL, 95% confidence interval [CI]: 0.69, 1.84; adjusted <jats:italic>P<\/jats:italic>\u00a0=\u00a00.001) and interleukin\u201015 (2.23\u00a0pg\/mL, 95% CI: 0.87, 3.60; adjusted <jats:italic>P<\/jats:italic>\u00a0=\u00a00.013) compared with randomization to no exercise. Randomization to metformin decreased apelin (\u22122.69\u00a0pg\/mL, 95% CI: \u22124.31, \u22121.07; adjusted <jats:italic>P<\/jats:italic>\u00a0=\u00a00.014) and interleukin\u201015 (\u22121.74\u00a0pg\/mL, 95% CI: \u22122.79, \u22120.69; adjusted <jats:italic>P<\/jats:italic>\u00a0=\u00a00.013) compared with randomization to no metformin. Metformin decreased myostatin, irisin, oncostatin M, fibroblast growth factor 21 and osteocrin; however, these changes were not statistically significant after correction for multiple comparisons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This pilot study demonstrates that randomization to exercise and metformin elicit unique effects on myokine concentrations in cancer patients. This hypothesis\u2010generating observation warrants further basic, translational and clinical investigation and replication.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13509","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T08:35:53Z","timestamp":1718699753000},"page":"1520-1527","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Effects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi\u2010centre factorial randomized trial"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7540-4913","authenticated-orcid":false,"given":"Justin C.","family":"Brown","sequence":"first","affiliation":[{"name":"Pennington Biomedical Research Center  Baton Rouge LA USA"},{"name":"LSU Health Sciences Center New Orleans School of Medicine  New Orleans LA USA"},{"name":"Stanley S. Scott Cancer Center Louisiana State University Health Sciences Center  New Orleans LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Spielmann","sequence":"additional","affiliation":[{"name":"Louisiana State University  Baton Rouge LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengping","family":"Yang","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center  Baton Rouge LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L. E.","family":"Compton","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Center  Baton Rouge LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee W.","family":"Jones","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda L.","family":"Irwin","sequence":"additional","affiliation":[{"name":"Yale University  New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Ligibel","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Meyerhardt","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber Cancer Institute  Boston MA 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