{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:45:28Z","timestamp":1791989128897,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009394","name":"Faculty of Medicine, Munich University of Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009394","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["TI07.001"],"award-info":[{"award-number":["TI07.001"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNFOC150019050"],"award-info":[{"award-number":["NNFOC150019050"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015606","name":"Helmholtz Alliance for Astroparticle Physics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015606","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["J4224\u2010B34"],"award-info":[{"award-number":["J4224\u2010B34"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["2020 EKSE.23"],"award-info":[{"award-number":["2020 EKSE.23"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB824\/3 2017"],"award-info":[{"award-number":["SFB824\/3 2017"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1321"],"award-info":[{"award-number":["SFB1321"]}],"id":[{"id":"10.13039\/501100001659","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":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cancer cachexia (CCx) is a multifactorial wasting disorder characterized by involuntary loss of body weight that affects many cancer patients and implies a poor prognosis, reducing both tolerance to and efficiency of anticancer therapies. Actual challenges in management of CCx remain in the identification of tumour\u2010derived and host\u2010derived mediators involved in systemic inflammation and tissue wasting and in the discovery of biomarkers that would allow for an earlier and personalized care of cancer patients. The aim of this study was to identify new markers of CCx across different species and tumour entities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Quantitative secretome analysis was performed to identify specific factors characteristic of cachexia\u2010inducing cancer cell lines. To establish the subsequently identified phospholipase PLA2G7 as a marker of CCx, plasma PLA2G7 activity and\/or protein levels were measured in well\u2010established mouse models of CCx and in different cohorts of weight\u2010stable and weight\u2010losing cancer patients with different tumour entities. Genetic PLA2G7 knock\u2010down in tumours and pharmacological treatment using the well\u2010studied PLA2G7 inhibitor darapladib were performed to assess its implication in the pathogenesis of CCx in C26 tumour\u2010bearing mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>High expression and secretion of PLA2G7 were hallmarks of cachexia\u2010inducing cancer cell lines. Circulating PLA2G7 activity was increased in different mouse models of CCx with various tumour entities and was associated with the severity of body wasting. Circulating PLA2G7 levels gradually rose during cachexia development. Genetic PLA2G7 knock\u2010down in C26 tumours only partially reduced plasma PLA2G7 levels, suggesting that the host is also an important contributor. Chronic treatment with darapladib was not sufficient to counteract inflammation and tissue wasting despite a strong inhibition of the circulating PLA2G7 activity. Importantly, PLA2G7 levels were also increased in colorectal and pancreatic cancer patients with CCx.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, our data show that despite no immediate pathogenic role, at least when targeted as a single entity, PLA2G7 is a consistent marker of CCx in both mice and humans. The early increase in circulating PLA2G7 levels in pre\u2010cachectic mice supports future prospective studies to assess its potential as biomarker for cancer patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12758","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:56:28Z","timestamp":1629766588000},"page":"1333-1351","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Association of circulating PLA2G7 levels with cancer cachexia and assessment of darapladib as a therapy"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8001-7069","authenticated-orcid":false,"given":"Pauline","family":"Morigny","sequence":"first","affiliation":[{"name":"Institute for Diabetes and Cancer Helmholtz Center Munich  Neuherberg Germany"},{"name":"Joint Heidelberg\u2010IDC Translational Diabetes Program, Inner Medicine 1 Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Center for Diabetes Research (DZD)  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Kaltenecker","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Cancer Helmholtz Center Munich  Neuherberg Germany"},{"name":"Joint Heidelberg\u2010IDC Translational Diabetes Program, Inner Medicine 1 Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Center for Diabetes Research (DZD)  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Zuber","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Cancer Helmholtz Center Munich  Neuherberg Germany"},{"name":"Joint Heidelberg\u2010IDC Translational Diabetes Program, Inner Medicine 1 Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Center for Diabetes Research (DZD)  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliano","family":"Machado","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Cancer Helmholtz Center Munich  Neuherberg Germany"},{"name":"Joint Heidelberg\u2010IDC Translational Diabetes Program, Inner Medicine 1 Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Center for Diabetes Research (DZD)  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Mehr","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Cancer Helmholtz Center Munich  Neuherberg Germany"},{"name":"Joint Heidelberg\u2010IDC Translational Diabetes Program, Inner Medicine 1 Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Center for Diabetes Research (DZD)  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foivos\u2010Filippos","family":"Tsokanos","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Cancer Helmholtz Center Munich  Neuherberg Germany"},{"name":"Joint Heidelberg\u2010IDC Translational Diabetes Program, Inner Medicine 1 Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Center for Diabetes Research (DZD)  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Kuzi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Klinikum rechts der Isar, School of Medicine Technical University of Munich  Munich Germany"},{"name":"School of Medicine, Institutes of Molecular Immunology and Experimental Oncology Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris D.","family":"Hermann","sequence":"additional","affiliation":[{"name":"School of Medicine, Institutes of Molecular Immunology and Experimental Oncology Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Voelkl","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine University Hospital Ludwig\u2010Maximilian University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"German","family":"Monogarov","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Springfeld","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Center for Tumor Diseases and Internal Medicine VI Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Laurent","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Cancer Helmholtz Center Munich  Neuherberg Germany"},{"name":"Joint Heidelberg\u2010IDC Translational Diabetes Program, Inner Medicine 1 Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Center for Diabetes Research (DZD)  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Engelmann","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine University Hospital Ludwig\u2010Maximilian University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Friess","sequence":"additional","affiliation":[{"name":"Department of Surgery, Klinikum rechts der Isar, School of Medicine Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inka","family":"Z\u00f6rnig","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Center for Tumor Diseases and Internal Medicine VI Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"School of Medicine, Institutes of Molecular Immunology and Experimental Oncology Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Krijgsveld","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ)  Heidelberg Germany"},{"name":"Medical Faculty Heidelberg University  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Prokopchuk","sequence":"additional","affiliation":[{"name":"Department of Surgery, Klinikum rechts der Isar, School of Medicine Technical University of Munich  Munich Germany"},{"name":"School of Medicine, Institutes of Molecular Immunology and Experimental Oncology Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren","family":"Fisker Schmidt","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Cancer Helmholtz Center Munich  Neuherberg Germany"},{"name":"Joint Heidelberg\u2010IDC Translational Diabetes Program, Inner Medicine 1 Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Center for Diabetes Research (DZD)  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rohm","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Cancer Helmholtz Center Munich  Neuherberg Germany"},{"name":"Joint Heidelberg\u2010IDC Translational Diabetes Program, Inner Medicine 1 Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Center for Diabetes Research (DZD)  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Herzig","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Cancer Helmholtz Center Munich  Neuherberg Germany"},{"name":"Joint Heidelberg\u2010IDC Translational Diabetes Program, Inner Medicine 1 Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Center for Diabetes Research (DZD)  Neuherberg Germany"},{"name":"Chair Molecular Metabolic Control Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4670-919X","authenticated-orcid":false,"given":"Mauricio","family":"Berriel Diaz","sequence":"additional","affiliation":[{"name":"Institute for Diabetes and Cancer Helmholtz Center Munich  Neuherberg Germany"},{"name":"Joint Heidelberg\u2010IDC Translational Diabetes Program, Inner Medicine 1 Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Center for Diabetes Research (DZD)  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.105"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70218-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-018-0123-0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604828"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-013-0111-0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-193211000-00002"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201847258"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2018.10.001"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-016-0522-0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00558-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21597"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.enz.2015.09.004"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1315878"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2015.06.003"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.11061"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2014.12.014"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2356"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.04.023"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12626"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2020.106478"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2011.127"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023425"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2017.07.011"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.30.17791"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(97)00295-5"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.03.087"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R045492"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.E052886"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.6.715"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.160.6.809"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10100380"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200012213432504"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beha.2008.12.001"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13612"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-85848-5"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnesp.2018.02.006"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi010"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60319-4"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.151670"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.165.21.2479"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2007.12.001"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjp2.69"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.397"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-34597-z"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12501"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12758","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.12758","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12758","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T03:30:51Z","timestamp":1764041451000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.12758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,23]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/jcsm.12758"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.12758","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,23]]},"assertion":[{"value":"2020-10-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}