{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:42:37Z","timestamp":1791412957373,"version":"4.3.3"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T00:00:00Z","timestamp":1704499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Breast cancer patients are commonly treated with sequential administrations of epirubicin\u2013cyclophosphamide (EC) and paclitaxel (TAX). The chronic effect of this treatment induces skeletal muscle alterations, but the specific effect of each chemotherapy agent is unknown. This study aimed to investigate the effect of EC or TAX administration on skeletal muscle homeostasis in breast cancer patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty early breast cancer patients undergoing EC followed by TAX chemotherapies were included. Two groups of 10 women were established and performed <jats:italic>vastus lateralis<\/jats:italic> skeletal muscle biopsies either before the first administration (pre) of EC (50\u00a0\u00b1\u00a014\u00a0years) or TAX (50\u00a0\u00b1\u00a016\u00a0years) and 4\u00a0days later (post). Mitochondrial respiratory capacity recording, reactive oxygen species production, western blotting and histological analyses were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Decrease in muscle fibres cross\u2010sectional area was only observed post\u2010EC (\u221225%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), associated with a reduction in mitochondrial respiratory capacity for the complex I (CI)\u2010linked substrate state (\u221232%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.001), oxidative phosphorylation (OXPHOS) by CI (\u221235%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002), CI&amp;CII (\u221226%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.022) and CII (\u221224%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.027). If H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> production was unchanged post\u2010EC, an increase was observed post\u2010TAX for OXPHOS by CII (+25%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.022). We found a decrease in makers of mitochondrial content, as shown post\u2010EC by a decrease in the protein levels of citrate synthase (\u221253%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and VDAC (\u221239%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Despite no changes in markers of mitochondrial fission, a decrease in the expression of a marker of mitochondrial inner\u2010membrane fusion was found post\u2010EC (OPA1; \u221260%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). We explored markers of mitophagy and found reductions post\u2010EC in the protein levels of PINK1 (\u221263%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and Parkin (\u221256%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.005), without changes post\u2010TAX. An increasing trend in Bax protein level was found post\u2010EC (+96%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.068) and post\u2010TAX (+77%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.073), while the Bcl\u20102 level was decreased only post\u2010EC (\u221252%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.007). If an increasing trend in TUNEL\u2010positive signal was observed post\u2010EC (+68%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.082), upregulation was highlighted post\u2010TAX (+86%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), suggesting activation of the apoptosis process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We demonstrated that a single administration of EC induced, in only 4\u00a0days, skeletal muscle atrophy and mitochondrial alterations in breast cancer patients. These alterations were characterized by reductions in mitochondrial function and content as well as impairment of mitochondrial dynamics and an increase in apoptosis. TAX administration did not worsen these alterations as this group had already received EC during the preceding weeks. However, it resulted in an increased apoptosis, likely in response to the increased H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> production.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13414","type":"journal-article","created":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T12:09:59Z","timestamp":1704542999000},"page":"292-305","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["A single chemotherapy administration induces muscle atrophy, mitochondrial alterations and apoptosis in breast cancer patients"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0890-3136","authenticated-orcid":false,"given":"Joris","family":"Mallard","sequence":"first","affiliation":[{"name":"Biomedicine Research Center of Strasbourg (CRBS), UR 3072, \u201cMitochondrie, Stress oxydant et Plasticit\u00e9 musculaire\u201d University of Strasbourg  Strasbourg France"},{"name":"Faculty of Sport Sciences University of Strasbourg  Strasbourg France"},{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyse","family":"Hucteau","sequence":"additional","affiliation":[{"name":"Biomedicine Research Center of Strasbourg (CRBS), UR 3072, \u201cMitochondrie, Stress oxydant et Plasticit\u00e9 musculaire\u201d University of Strasbourg  Strasbourg France"},{"name":"Faculty of Sport Sciences University of Strasbourg  Strasbourg France"},{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bender","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Moinard\u2010Butot","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Rochelle","sequence":"additional","affiliation":[{"name":"Biomedicine Research Center of Strasbourg (CRBS), UR 3072, \u201cMitochondrie, Stress oxydant et Plasticit\u00e9 musculaire\u201d University of Strasbourg  Strasbourg France"},{"name":"Faculty of Sport Sciences University of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laur\u00e9line","family":"Boutonnet","sequence":"additional","affiliation":[{"name":"Biomedicine Research Center of Strasbourg (CRBS), UR 3072, \u201cMitochondrie, Stress oxydant et Plasticit\u00e9 musculaire\u201d University of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Grandperrin","sequence":"additional","affiliation":[{"name":"Biomedicine Research Center of Strasbourg (CRBS), UR 3072, \u201cMitochondrie, Stress oxydant et Plasticit\u00e9 musculaire\u201d University of Strasbourg  Strasbourg France"},{"name":"Faculty of Sport Sciences University of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Schott","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Pflumio","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Trensz","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Kalish\u2010Weindling","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Laure","family":"Charles","sequence":"additional","affiliation":[{"name":"Biomedicine Research Center of Strasbourg (CRBS), UR 3072, \u201cMitochondrie, Stress oxydant et Plasticit\u00e9 musculaire\u201d University of Strasbourg  Strasbourg France"},{"name":"Faculty of medicine University of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"G\u00e9ny","sequence":"additional","affiliation":[{"name":"Biomedicine Research Center of Strasbourg (CRBS), UR 3072, \u201cMitochondrie, Stress oxydant et Plasticit\u00e9 musculaire\u201d University of Strasbourg  Strasbourg France"},{"name":"Faculty of medicine University of Strasbourg  Strasbourg France"},{"name":"Department of Physiology and Functional Explorations University Hospital of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Favret","sequence":"additional","affiliation":[{"name":"Biomedicine Research Center of Strasbourg (CRBS), UR 3072, \u201cMitochondrie, Stress oxydant et Plasticit\u00e9 musculaire\u201d University of Strasbourg  Strasbourg France"},{"name":"Faculty of Sport Sciences University of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Pivot","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Hureau","sequence":"additional","affiliation":[{"name":"Biomedicine Research Center of Strasbourg (CRBS), UR 3072, \u201cMitochondrie, Stress oxydant et Plasticit\u00e9 musculaire\u201d University of Strasbourg  Strasbourg France"},{"name":"Faculty of Sport Sciences University of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan F.","family":"Pagano","sequence":"additional","affiliation":[{"name":"Biomedicine Research Center of Strasbourg (CRBS), UR 3072, \u201cMitochondrie, Stress oxydant et Plasticit\u00e9 musculaire\u201d University of Strasbourg  Strasbourg France"},{"name":"Faculty of Sport Sciences University of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)33326-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.719643"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00002.2018"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700968R"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000432"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13400"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.08.191"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00540.2015"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.286518"},{"key":"e_1_2_7_11_1","first-page":"935","article-title":"Exercise protects against doxorubicin\u2010induced oxidative stress and proteolysis in skeletal muscle","volume":"2011","author":"Smuder AJ","year":"1985","journal-title":"J Appl Physiol Bethesda Md"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12263"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181086"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.105189"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12991"},{"key":"e_1_2_7_16_1","first-page":"1632","article-title":"Fiber typing human skeletal muscle with fluorescent immunohistochemistry","volume":"2019","author":"Murach KA","year":"1985","journal-title":"J Appl Physiol Bethesda Md"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23105489"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(88)90132-3"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2014.01.006"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2004.01.006"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34533"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021115-105011"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12232"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9779"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101191"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2018.11.005"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7343965"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000263010.19273.48"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2007.04.008"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2007.07.003"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1591672"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24611"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-016-1003-9"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01887"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/17461391.2013.823466"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1986.199"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2010.055269"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15086"},{"key":"e_1_2_7_39_1","first-page":"2175","article-title":"Anthracycline and trastuzumab\u2010induced cardiotoxicity in breast cancer","volume":"22","author":"Nicolazzi MA","year":"2018","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-023-05177-5"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12899"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13414","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T02:27:58Z","timestamp":1706840878000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,6]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/jcsm.13414"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13414","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,6]]},"assertion":[{"value":"2023-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}