{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T03:14:11Z","timestamp":1792293251661,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T00:00:00Z","timestamp":1522022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["IRG: 09\u2010061\u201004"],"award-info":[{"award-number":["IRG: 09\u2010061\u201004"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Breast cancer patients report a perception of increased muscle fatigue, which can persist following surgery and standardized therapies. In a clinical experiment, we tested the hypothesis that pathways regulating skeletal muscle fatigue are down\u2010regulated in skeletal muscle of breast cancer patients and that different muscle gene expression patterns exist between breast tumour subtypes. In a preclinical study, we tested the hypothesis that mammary tumour growth in mice induces skeletal muscle fatigue and that overexpression of the cytokine interleukin\u201015 (IL\u201015) can attenuate mammary tumour\u2010induced muscle fatigue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Early stage non\u2010metastatic female breast cancer patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a014) and female non\u2010cancer patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a06) provided a muscle biopsy of the\n                      <jats:italic>pectoralis major<\/jats:italic>\n                      muscle during mastectomy, lumpectomy, or breast reconstruction surgeries. The breast cancer patients were diagnosed with either luminal (ER\n                      <jats:sup>+<\/jats:sup>\n                      \/PR\n                      <jats:sup>+<\/jats:sup>\n                      ,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a06), triple positive (ER\n                      <jats:sup>+<\/jats:sup>\n                      \/PR\n                      <jats:sup>+<\/jats:sup>\n                      \/Her2\/neu\n                      <jats:sup>+<\/jats:sup>\n                      ,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a05), or triple negative (ER\n                      <jats:sup>\u2212<\/jats:sup>\n                      \/PR\n                      <jats:sup>\u2212<\/jats:sup>\n                      \/Her2\/neu\n                      <jats:sup>\u2212<\/jats:sup>\n                      ,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a03) breast tumours and were being treated with curative intent either with neoadjuvant chemotherapy followed by surgery or surgery followed by standard post\u2010operative therapy. Biopsies were used for RNA\u2010sequencing to compare the skeletal muscle gene expression patterns between breast cancer patients and non\u2010cancer patients. The C57BL\/6 mouse syngeneic mammary tumour cell line, E0771, was used to induce mammary tumours in immunocompetent mice, and isometric muscle contractile properties and fatigue properties were analysed following 4\u00a0weeks of tumour growth.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RNA\u2010sequencing and subsequent bioinformatics analyses revealed a dysregulation of canonical pathways involved in oxidative phosphorylation, mitochondrial dysfunction, peroxisome proliferator\u2010activated receptor signalling and activation, and IL\u201015 signalling and production. In a preclinical mouse model of breast cancer, the rate of muscle fatigue was greater in mice exposed to mammary tumour growth for 4\u00a0weeks, and this greater muscle fatigue was attenuated in transgenic mice that overexpressed the cytokine IL\u201015.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data identify novel genes and pathways dysregulated in the muscles of breast cancer patients with early stage non\u2010metastatic disease, with particularly aberrant expression among genes that would predispose these patients to greater muscle fatigue. Furthermore, we demonstrate that IL\u201015 overexpression can attenuate muscle fatigue associated with mammary tumour growth in a preclinical mouse model of breast cancer. Therefore, we propose that skeletal muscle fatigue is an inherent consequence of breast tumour growth, and this greater fatigue can be targeted therapeutically.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12294","type":"journal-article","created":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T02:16:09Z","timestamp":1522116969000},"page":"701-714","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Dysregulation of metabolic\u2010associated pathways in muscle of breast cancer patients: preclinical evaluation of interleukin\u201015 targeting fatigue"],"prefix":"10.1002","volume":"9","author":[{"given":"Joseph","family":"Bohlen","sequence":"first","affiliation":[{"name":"Division of Exercise Physiology, Department of Human Performance West Virginia University School of Medicine  Morgantown WV 26506 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah 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