{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:29:10Z","timestamp":1792225750356,"version":"4.4.0"},"reference-count":81,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T00:00:00Z","timestamp":1566950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2012\/50079-0"],"award-info":[{"award-number":["2012\/50079-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/13810-9"],"award-info":[{"award-number":["2016\/13810-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/12508-7"],"award-info":[{"award-number":["2016\/12508-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/02780-1"],"award-info":[{"award-number":["2016\/02780-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/12260-8"],"award-info":[{"award-number":["2017\/12260-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Cachexia is a wasting syndrome characterized by the continuous loss of skeletal muscle mass due to imbalance between protein synthesis and degradation, which is related with poor prognosis and compromised quality of life. Dysfunctional mitochondria are associated with lower muscle strength and muscle atrophy in cancer patients, yet poorly described in human cachexia. We herein investigated mitochondrial morphology, autophagy and apoptosis in the skeletal muscle of patients with gastrointestinal cancer-associated cachexia (CC), as compared with a weight-stable cancer group (WSC). CC showed prominent weight loss and increased circulating levels of serum C-reactive protein, lower body mass index and decreased circulating hemoglobin, when compared to WSC. Electron microscopy analysis revealed an increase in intermyofibrillar mitochondrial area in CC, as compared to WSC. Relative gene expression of Fission 1, a protein related to mitochondrial fission, was increased in CC, as compared to WSC. LC3 II, autophagy-related (ATG) 5 and 7 essential proteins for autophagosome formation, presented higher content in the cachectic group. Protein levels of phosphorylated p53 (Ser46), activated caspase 8 (Asp384) and 9 (Asp315) were also increased in the skeletal muscle of CC. Overall, our results demonstrate that human cancer-associated cachexia leads to exacerbated muscle-stress response that may culminate in muscle loss, which is in part due to disruption of mitochondrial morphology, dysfunctional autophagy and increased apoptosis. To the best of our knowledge, this is the first report showing quantitative morphological alterations in skeletal muscle mitochondria in cachectic patients.<\/jats:p>","DOI":"10.3390\/cancers11091264","type":"journal-article","created":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T11:23:18Z","timestamp":1566991398000},"page":"1264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Human Cachexia Induces Changes in Mitochondria, Autophagy and Apoptosis in the Skeletal Muscle"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1758-9857","authenticated-orcid":false,"given":"Gabriela S.","family":"de Castro","sequence":"first","affiliation":[{"name":"Cancer Metabolism Research Group, Department of Cell and Tissue Biology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, 05508-900 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estefania","family":"Simoes","sequence":"additional","affiliation":[{"name":"Cancer Metabolism Research Group, Department of Cell and Tissue Biology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, 05508-900 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna D.C.C.","family":"Lima","sequence":"additional","affiliation":[{"name":"Cancer Metabolism Research Group, Department of Cell and Tissue Biology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, 05508-900 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milene","family":"Ortiz-Silva","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Biophysics, Institute of Biomedical Sciences, University of S\u00e3o Paulo, 05508-900 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4769-0806","authenticated-orcid":false,"given":"William T.","family":"Festuccia","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Biophysics, Institute of Biomedical Sciences, University of S\u00e3o Paulo, 05508-900 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1vio","family":"Tokeshi","sequence":"additional","affiliation":[{"name":"Department of Clinical Surgery, Faculty of Medicine, University of S\u00e3o Paulo, 01246-903 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo S.","family":"Alc\u00e2ntara","sequence":"additional","affiliation":[{"name":"Department of Clinical Surgery, Faculty of Medicine, University of S\u00e3o Paulo, 01246-903 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 P.","family":"Otoch","sequence":"additional","affiliation":[{"name":"Department of Clinical Surgery, Faculty of Medicine, University of S\u00e3o Paulo, 01246-903 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Coletti","sequence":"additional","affiliation":[{"name":"Department of Biological Adaptation and Aging, B2A (CNRS UMR 8256-INSERM ERL U1164-UPMC P6), Sorbonne University, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilia","family":"Seelaender","sequence":"additional","affiliation":[{"name":"Cancer Metabolism Research Group, Department of Cell and Tissue Biology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, 05508-900 S\u00e3o Paulo, Brazil"},{"name":"Department of Clinical Surgery, Faculty of Medicine, University of S\u00e3o Paulo, 01246-903 S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.clnu.2008.06.013","article-title":"Cachexia: A new definition","volume":"27","author":"Evans","year":"2008","journal-title":"Clin. 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