{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:54:40Z","timestamp":1791212080485,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,6,27]],"date-time":"2014-06-27T00:00:00Z","timestamp":1403827200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:sec><jats:label\/><jats:p>Cancer cachexia syndrome is observed in 80% of patients with advanced\u2010stage cancer, and it is one of the most frequent causes of death. Severe wasting accounts for more than 80% in patients with advanced pancreatic cancer. Here we wanted to define, by using an microarray approach and the <jats:italic>Pdx1\u2010cre;LSL\u2010Kras<jats:sup>G12D<\/jats:sup>;INK4a\/arf<jats:sup>fl\/fl<\/jats:sup><\/jats:italic> mice model, the pathways involved in muscle, liver, and white adipose tissue wasting. These mice, which develop systematically pancreatic cancer, successfully reproduced many human symptoms afflicted with this disease, and particularly cachexia. Using the profiling analysis of pancreatic cancer\u2010dependent cachectic tissues we found that Jak2\/Stat3 pathways, p53 and NFkB results activated. Thus, our interest was focused on the Jak2 pathways because it is pharmacologically targetable with low toxicity and FDA approved drugs are available. Therefore, <jats:italic>Pdx1\u2010cre;LSL\u2010Kras<jats:sup>G12D<\/jats:sup>;INK4a\/arf<jats:sup>fl\/fl<\/jats:sup><\/jats:italic> mice were treated with the Jak2 inhibitor AG490 compound daily starting at 7 weeks old and for a period of 3 weeks and animals were sacrificed at 10 weeks old. Body weight for control mice was 27.84\u2009\u00b1\u20092.14\u2009g, for untreated <jats:italic>Pdx1\u2010cre;LSL\u2010Kras<jats:sup>G12D<\/jats:sup>;INK4a\/arf<jats:sup>fl\/fl<\/jats:sup><\/jats:italic> was 14.97\u2009\u00b1\u20091.99\u2009g, whereas in animals treated with the AG490 compound the weight loss was significantly less to 24.53\u2009\u00b1\u20092.04\u2009g. Treatment with AG490 compound was efficient since phosphorylation of Jak2 and circulating interleukin\u20106 (IL6) levels were significantly reduced in cachectic tissues and in mice respectively. In conclusion, we found that Jak2\/Stat3\u2010dependent intracellular pathway plays an essential role since its pharmacological inhibition strongly attenuates cachexia progression in a lethal transgenic pancreatic cancer model. J. Cell. Physiol. 229: 1437\u20131443, 2014. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.24580","type":"journal-article","created":{"date-parts":[[2014,2,17]],"date-time":"2014-02-17T09:50:01Z","timestamp":1392630601000},"page":"1437-1443","source":"Crossref","is-referenced-by-count":61,"title":["Pancreatic Cancer\u2010Induced Cachexia Is Jak2\u2010Dependent in Mice"],"prefix":"10.1002","volume":"229","author":[{"given":"Marine","family":"Gilabert","sequence":"first","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM)  INSERM U1068  CNRS UMR 7258  Aix\u2010Marseille Universit\u00e9 and Institut Paoli\u2010Calmettes  Parc Scientifique et Technologique de Luminy Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezequiel","family":"Calvo","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology and Oncology Research Center  CHUL Research Center Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Airoldi","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM)  INSERM U1068  CNRS UMR 7258  Aix\u2010Marseille Universit\u00e9 and Institut Paoli\u2010Calmettes  Parc Scientifique et Technologique de Luminy Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tewfik","family":"Hamidi","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM)  INSERM U1068  CNRS UMR 7258  Aix\u2010Marseille Universit\u00e9 and Institut Paoli\u2010Calmettes  Parc Scientifique et Technologique de Luminy Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Moutardier","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM)  INSERM U1068  CNRS UMR 7258  Aix\u2010Marseille Universit\u00e9 and Institut Paoli\u2010Calmettes  Parc Scientifique et Technologique de Luminy Marseille France"},{"name":"D\u00e9partement de Chirurgie H\u00f4pital Nord Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Turrini","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM)  INSERM U1068  CNRS UMR 7258  Aix\u2010Marseille Universit\u00e9 and Institut Paoli\u2010Calmettes  Parc Scientifique et Technologique de Luminy Marseille France"},{"name":"D\u00e9partement de Chirurgie Institut Paoli\u2010Calmettes Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Iovanna","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM)  INSERM U1068  CNRS UMR 7258  Aix\u2010Marseille Universit\u00e9 and Institut Paoli\u2010Calmettes  Parc Scientifique et Technologique de Luminy Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1158703"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.44.2020"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-008-0505-z"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601273103"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)02064-5"},{"key":"e_1_2_6_7_1","first-page":"223","article-title":"Molecular analysis of xenograft models of human cancer cachexia\u2014Possibilities for therapeutic intervention","volume":"4","author":"Baumgarten AJ","year":"2007","journal-title":"Cancer Genomics Proteomics"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2011.627850"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(01)00297-2"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022538"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00039.2012"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.23.6712"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03985"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201201255"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00591a005"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116897"},{"key":"e_1_2_6_17_1","doi-asserted-by":"crossref","unstructured":"DymockBW SeeCS.2013. Inhibitors of JAK2 and JAK3: An update on the patent literature 2010\u22122012.23:pp449\u2013501.","DOI":"10.1517\/13543776.2013.765862"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-199101000-00005"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70218-7"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.06.011"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.047563"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.10.2447"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1358\/dnp.2005.18.4.908658"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/4.2.249"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.05.032"},{"key":"e_1_2_6_26_1","first-page":"2302","article-title":"The roles of gamma\u2010interferon and tumor necrosis factor alpha in an experimental rat model of cancer cachexia","volume":"51","author":"Langstein HN","year":"1991","journal-title":"Cancer Res"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200161040-00004"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/379645a0"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.412606"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.2202\/1544-6115.1027"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115767"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/00075197-199805000-00003"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc927"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1002028"},{"key":"e_1_2_6_36_1","first-page":"1105","article-title":"The cachectic mediator proteolysis inducing factor activates NF\u2010kappaB and STAT3 in human Kupffer cells and monocytes","volume":"27","author":"Watchorn TM","year":"2005","journal-title":"Int J Oncol"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.07.012"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.24580","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.24580","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T10:47:23Z","timestamp":1696330043000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.24580"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,27]]},"references-count":36,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1002\/jcp.24580"],"URL":"https:\/\/doi.org\/10.1002\/jcp.24580","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,27]]}}}