{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:25:28Z","timestamp":1789975528030,"version":"4.0.1"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T00:00:00Z","timestamp":1548028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Brenden-Colson Center for Pancreatic Care"},{"name":"NCI R01","award":["CA184324"],"award-info":[{"award-number":["CA184324"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Up to 80% of pancreatic cancer patients suffer from cachexia, a devastating condition that exacerbates underlying disease, reduces quality of life, and increases treatment complications and mortality. Tumour\u2010induced inflammation is linked to this multifactorial wasting syndrome, but mechanisms and effective treatments remain elusive. Myeloid differentiation factor (MyD88), a key component of the innate immune system, plays a pivotal role in directing the inflammatory response to various insults. In this study, we tested whether MyD88 signalling is essential in the development of pancreatic cancer cachexia using a robust mouse tumour model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sex, age, and body weight\u2010matched wide type (WT) and MyD88 knockout (MyD88 KO) mice were orthotopically or intraperitoneally implanted with a pancreatic tumour cell line from a syngeneic C57BL\/6 KRAS<jats:sup>G12D\/+<\/jats:sup> P53<jats:sup>R172H\/+<\/jats:sup> Pdx\u2010Cre (KPC) mouse. We observed the effects of MyD88 signalling during pancreatic ductal adenocarcinoma progression and the cachexia development through behavioural, histological, molecular, and survival aspects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Blocking MyD88 signalling greatly ameliorated pancreatic ductal adenocarcinoma\u2010associated anorexia and fatigue, attenuated lean mass loss, reduced muscle catabolism and atrophy, diminished systemic and central nervous system inflammation, and ultimately improved survival. Our data demonstrate that MyD88 signalling plays a critical role in mediating pancreatic cancer\u2010induced inflammation that triggers cachexia development and therefore represents a promising therapeutic target.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MyD88\u2010dependent inflammation is crucial in the pathophysiology of pancreatic cancer progression and contributes to high mortality. Our findings implicate the importance of innate immune signalling pathways in pancreatic cancer cachexia and a novel therapeutic target.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12377","type":"journal-article","created":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T20:42:41Z","timestamp":1548189761000},"page":"378-390","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["MyD88 signalling is critical in the development of pancreatic cancer cachexia"],"prefix":"10.1002","volume":"10","author":[{"given":"Xinxia","family":"Zhu","sequence":"first","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland OR 97239 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin G.","family":"Burfeind","sequence":"additional","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland OR 97239 USA"},{"name":"Medical Scientist Training Program Oregon Health &amp; Science University  Portland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Michaelis","sequence":"additional","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland OR 97239 USA"},{"name":"Medical Scientist Training Program Oregon Health &amp; Science University  Portland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore P.","family":"Braun","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute Oregon Health &amp; Science University  Portland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brennan","family":"Olson","sequence":"additional","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland OR 97239 USA"},{"name":"Medical Scientist Training Program Oregon Health &amp; Science University  Portland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine R.","family":"Pelz","sequence":"additional","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland OR 97239 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry K.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Pathology Oregon Health &amp; Science University  Portland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Marks","sequence":"additional","affiliation":[{"name":"Pap\u00e9 Family Pediatric Research Institute Oregon Health &amp; Science University  Portland OR 97239 USA"},{"name":"Knight Cancer Institute Oregon Health &amp; Science University  Portland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,21]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Pancreatic Cancer Treatment (PDQ(R)): Health Professional Version, in PDQ Cancer Information Summaries","author":"Board, P.D.Q.A.T.E","year":"2002"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2016-0010"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-9-255"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)79068-1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/89.23.1763"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3829"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2013.804580"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-008-0505-z"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.06.011"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i40.14626"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2012.05.028"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2014.00088"},{"key":"e_1_2_9_14_1","first-page":"157","article-title":"Anorexia\u2010cachexia syndrome in pancreatic cancer: recent development in research and management","volume":"7","author":"Uomo G","year":"2006","journal-title":"JOP"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/oncsis.2016.3"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01322"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-230375"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2311-11.2011"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep29885"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111020"},{"key":"e_1_2_9_21_1","first-page":"629","article-title":"Systemic inflammation in cachexia: is tumor cytokine expression profile the culprit?","volume":"6","author":"Matos\u2010Neto EM","year":"2015","journal-title":"Front Immunol"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2017.03.003"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2012.04.011"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/820934"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00019.2005"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.05.003"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401850"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00367"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12225"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaa5823"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i12.1286"},{"key":"e_1_2_9_32_1","article-title":"Tumor\u2010associated fatigue in cancer patients develops independently of IL1 signaling","author":"Grossberg AJ","year":"2017","journal-title":"Cancer Res"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.12-S1-22"},{"key":"e_1_2_9_34_1","first-page":"352","article-title":"Cancer related fatigue syndrome in neoplastic diseases","volume":"13","author":"Franc M","year":"2014","journal-title":"Prz Menopauzalny"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2012.10.006"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201200231"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/168407"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1477-2574.2010.00178.x"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i28.9476"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-287-2_11"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.103230ml"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13593"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.01.006"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-225433"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0465"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0394"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68523"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01866-w"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1455"},{"key":"e_1_2_9_50_1","first-page":"1432","article-title":"Role of the central melanocortin system in cachexia","volume":"61","author":"Marks DL","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-1680"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022050"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042183"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20777"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgo.2018.03.004"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2006.09.024"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00520-015-2763-0"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2013.11.003"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111706"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.4161\/onci.22567"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv364"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep14246"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12261"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcsm.12377","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12377","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.12377","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12377","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T10:50:18Z","timestamp":1694343018000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.12377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,21]]},"references-count":62,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1002\/jcsm.12377"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.12377","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,21]]},"assertion":[{"value":"2018-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}