{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T22:56:07Z","timestamp":1794264967518,"version":"4.9.0"},"reference-count":93,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T00:00:00Z","timestamp":1581292800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cancer cachexia is a life\u2010threatening metabolic syndrome that causes significant loss of skeletal muscle mass and significantly increases mortality in cancer patients. Currently, there is an urgent need for better understanding of the molecular pathophysiology of this disease so that effective therapies can be developed. The majority of pre\u2010clinical studies evaluating skeletal muscle's response to cancer have focused on one or two pre\u2010clinical models, and almost all have focused specifically on limb muscles. In the current study, we reveal key differences in the histology and transcriptomic signatures of a limb muscle and a respiratory muscle in orthotopic pancreatic cancer patient\u2010derived xenograft (PDX) mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To create four cohorts of PDX mice evaluated in this study, tumours resected from four pancreatic ductal adenocarcinoma patients were portioned and attached to the pancreas of immunodeficient NSG mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Body weight, muscle mass, and fat mass were significantly decreased in each PDX line. Histological assessment of cryosections taken from the tibialis anterior (TA) and diaphragm (DIA) revealed differential effects of tumour burden on their morphology. Subsequent genome\u2010wide microarray analysis on TA and DIA also revealed key differences between their transcriptomes in response to cancer. Genes up\u2010regulated in the DIA were enriched for extracellular matrix protein\u2010encoding genes and genes related to the inflammatory response, while down\u2010regulated genes were enriched for mitochondria related protein\u2010encoding genes. Conversely, the TA showed up\u2010regulation of canonical atrophy\u2010associated pathways such as ubiquitin\u2010mediated protein degradation and apoptosis, and down\u2010regulation of genes encoding extracellular matrix proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that distinct biological processes may account for wasting in different skeletal muscles in response to the same tumour burden. Further investigation into these differences will be critical for the future development of effective clinical strategies to counter cancer cachexia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12550","type":"journal-article","created":{"date-parts":[[2020,2,10]],"date-time":"2020-02-10T12:23:29Z","timestamp":1581337409000},"page":"820-837","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8347-9501","authenticated-orcid":false,"given":"Rachel L.","family":"Nosacka","sequence":"first","affiliation":[{"name":"Department of Physical Therapy University of Florida Health Science Center  Gainesville USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea 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