{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:37:15Z","timestamp":1790905035854,"version":"4.1.0"},"reference-count":272,"publisher":"Portland Press Ltd.","issue":"16","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pancreatic cancer has one of the poorest prognoses of all malignancies, with little improvement in clinical outcome over the past 40 years. Pancreatic ductal adenocarcinoma is responsible for the vast majority of pancreatic cancer cases, and is characterised by the presence of a dense stroma that impacts therapeutic efficacy and drives pro-tumorigenic programs. More specifically, the inflammatory nature of the tumour microenvironment is thought to underlie the loss of anti-tumour immunity and development of resistance to current treatments. Inflammatory pathways are largely mediated by the expression of, and signalling through, cytokines, chemokines, and other cellular messengers. In recent years, there has been much attention focused on dual targeting of cancer cells and the tumour microenvironment. Here we review our current understanding of the role of IL-6, and the broader IL-6 cytokine family, in pancreatic cancer, including their contribution to pancreatic inflammation and various roles in pancreatic cancer pathogenesis. We also summarise potential opportunities for therapeutic targeting of these pathways as an avenue towards combating poor patient outcomes.<\/jats:p>","DOI":"10.1042\/cs20191211","type":"journal-article","created":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T05:34:57Z","timestamp":1597728897000},"page":"2091-2115","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Emerging roles for the IL-6 family of cytokines in pancreatic cancer"],"prefix":"10.1042","volume":"134","author":[{"given":"Gemma","family":"van Duijneveldt","sequence":"first","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, 3052"},{"name":"Department of Medical Biology, The University of Melbourne, Victoria, Australia, 3052"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael\u00a0D.W.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1639-4932","authenticated-orcid":false,"given":"Tracy L.","family":"Putoczki","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia, 3052"},{"name":"Department of Medical Biology, The University of Melbourne, Victoria, Australia, 3052"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,8,18]]},"reference":[{"key":"2021113011150657100_B1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"2021113011150657100_B2","article-title":"Cancer in Australia 2019","volume":"CAN 123","author":"Australian Institute of, H. and Welfare.","year":"2019"},{"key":"2021113011150657100_B3","doi-asserted-by":"publisher","first-page":"10","DOI":"10.14740\/wjon1166","article-title":"Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors","volume":"10","author":"Rawla","year":"2019","journal-title":"World J. Oncol."},{"key":"2021113011150657100_B4","doi-asserted-by":"publisher","first-page":"4846","DOI":"10.3748\/wjg.v24.i43.4846","article-title":"Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes","volume":"24","author":"McGuigan","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"2021113011150657100_B5","volume-title":"WHO report on cancer: setting priorities, investing wisely and providing care for all","author":"World Health, O","year":"2020"},{"key":"2021113011150657100_B6","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1080\/0284186X.2016.1197419","article-title":"More deaths from pancreatic cancer than breast cancer in the EU by 2017","volume":"55","author":"Ferlay","year":"2016","journal-title":"Acta Oncol."},{"key":"2021113011150657100_B7","doi-asserted-by":"publisher","first-page":"2913","DOI":"10.1158\/0008-5472.CAN-14-0155","article-title":"Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States","volume":"74","author":"Rahib","year":"2014","journal-title":"Cancer Res."},{"key":"2021113011150657100_B8","doi-asserted-by":"publisher","first-page":"2649","DOI":"10.1002\/cam4.767","article-title":"Projections of cancer incidence and cancer-related deaths in Germany by 2020 and 2030","volume":"5","author":"Quante","year":"2016","journal-title":"Cancer Med."},{"key":"2021113011150657100_B9","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1002\/ijc.30670","article-title":"Early detection of pancreatic cancer: Where are we now and where are we going?","volume":"141","author":"Zhou","year":"2017","journal-title":"Int. J. Cancer"},{"key":"2021113011150657100_B10","doi-asserted-by":"publisher","DOI":"10.2147\/GICTT.S82103","article-title":"Nab-paclitaxel plus gemcitabine in the treatment of metastatic pancreatic cancer: utility and experience from the clinic","author":"Dragovich","year":"2016","journal-title":"Gastrointestinal Cancer: Targets and Thera."},{"key":"2021113011150657100_B11","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1002\/1097-0142(19871101)60:9%3c2284::AID-CNCR2820600930%3e3.0.CO;2-V","article-title":"Cancer of the pancreas. 50 years of surgery","volume":"60","author":"Gudjonsson","year":"1987","journal-title":"Cancer"},{"key":"2021113011150657100_B12","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1056\/NEJMra1404198","article-title":"Pancreatic adenocarcinoma","volume":"371","author":"Ryan","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"2021113011150657100_B13","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1016\/S0140-6736(04)15841-8","article-title":"Pancreatic cancer","volume":"363","author":"Li","year":"2004","journal-title":"Lancet"},{"key":"2021113011150657100_B14","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.ejso.2008.12.006","article-title":"Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma","volume":"35","author":"Van den Broeck","year":"2009","journal-title":"Eur. J. Surg. Oncol."},{"key":"2021113011150657100_B15","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1097\/SLA.0b013e3181613142","article-title":"Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible?","volume":"247","author":"Schnelldorfer","year":"2008","journal-title":"Ann Surg."},{"key":"2021113011150657100_B16","doi-asserted-by":"publisher","first-page":"50","DOI":"10.21037\/tgh.2019.06.02","article-title":"Pathology of pancreatic cancer","volume":"4","author":"Haeberle","year":"2019","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"2021113011150657100_B17","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2012.00006","article-title":"Current Knowledge on Pancreatic Cancer","volume":"2","author":"Iovanna","year":"2012","journal-title":"Front. Oncol."},{"key":"2021113011150657100_B18","first-page":"2690","article-title":"Morphological lesions associated with human primary invasive nonendocrine pancreas cancer","volume":"36","author":"Cubilla","year":"1976","journal-title":"Cancer Res."},{"key":"2021113011150657100_B19","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1002\/1097-0142(197904)43:4%3c1418::AID-CNCR2820430431%3e3.0.CO;2-O","article-title":"Relation of pancreatic duct hyperplasia to carcinoma","volume":"43","author":"Kozuka","year":"1979","journal-title":"Cancer"},{"key":"2021113011150657100_B20","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1053\/j.gastro.2013.01.074","article-title":"Control of cell identity in pancreas development and regeneration","volume":"144","author":"Stanger","year":"2013","journal-title":"Gastroenterology"},{"key":"2021113011150657100_B21","doi-asserted-by":"publisher","first-page":"18907","DOI":"10.1073\/pnas.0810111105","article-title":"Notch and Kras reprogram pancreatic acinar cells to ductal intraepithelial neoplasia","volume":"105","author":"De La","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011150657100_B22","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.ccr.2009.09.027","article-title":"Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras","volume":"16","author":"Friedlander","year":"2009","journal-title":"Cancer Cell"},{"key":"2021113011150657100_B23","doi-asserted-by":"publisher","first-page":"18913","DOI":"10.1073\/pnas.0810097105","article-title":"Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice","volume":"105","author":"Habbe","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011150657100_B24","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.ccr.2012.10.025","article-title":"Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma","volume":"22","author":"Kopp","year":"2012","journal-title":"Cancer Cell"},{"key":"2021113011150657100_B25","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1097\/01.pas.0000126675.59108.80","article-title":"An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms","volume":"28","author":"Hruban","year":"2004","journal-title":"Am. J. Surg. Pathol."},{"key":"2021113011150657100_B26","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1080\/00365521.2017.1293726","article-title":"Pancreatic cancer stroma: controversies and current insights","volume":"52","author":"Ansari","year":"2017","journal-title":"Scandinavian J. Gastroenterol."},{"key":"2021113011150657100_B27","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1136\/gut.2010.226092","article-title":"Stromal biology and therapy in pancreatic cancer","volume":"60","author":"Neesse","year":"2011","journal-title":"Gut"},{"key":"2021113011150657100_B28","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/nrgastro.2012.115","article-title":"The role of stroma in pancreatic cancer: diagnostic and therapeutic implications","volume":"9","author":"Erkan","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"2021113011150657100_B29","doi-asserted-by":"publisher","first-page":"S44","DOI":"10.1016\/j.cgh.2009.07.039","article-title":"Desmoplasia of pancreatic ductal adenocarcinoma","volume":"7","author":"Pandol","year":"2009","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"2021113011150657100_B30","doi-asserted-by":"publisher","first-page":"676","DOI":"10.3390\/ijms20030676","article-title":"Inflammation and Pancreatic Cancer: Focus on Metabolism, Cytokines, and Immunity","volume":"20","author":"Padoan","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"2021113011150657100_B31","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/S0016-5085(98)70209-4","article-title":"Identification, culture, and characterization of pancreatic stellate cells in rats and humans","volume":"115","author":"Bachem","year":"1998","journal-title":"Gastroenterology"},{"key":"2021113011150657100_B32","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1136\/gut.44.4.534","article-title":"Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis","volume":"44","author":"Apte","year":"1999","journal-title":"Gut"},{"key":"2021113011150657100_B33","doi-asserted-by":"publisher","first-page":"S48","DOI":"10.1016\/j.cgh.2009.07.038","article-title":"Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis","volume":"7","author":"Masamune","year":"2009","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"2021113011150657100_B34","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1136\/gutjnl-2012-302529","article-title":"Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer","volume":"62","author":"Jacobetz","year":"2013","journal-title":"Gut"},{"key":"2021113011150657100_B35","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.ccr.2012.01.007","article-title":"Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma","volume":"21","author":"Provenzano","year":"2012","journal-title":"Cancer Cell"},{"key":"2021113011150657100_B36","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1084\/jem.20162024","article-title":"Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer","volume":"214","author":"\u00d6hlund","year":"2017","journal-title":"J. Exp. Med."},{"key":"2021113011150657100_B37","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1097\/MOG.0000000000000196","article-title":"Pancreatic stellate cell: physiologic role, role in fibrosis and cancer","volume":"31","author":"Apte","year":"2015","journal-title":"Curr. Opin. Gastroenterol."},{"key":"2021113011150657100_B38","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1158\/0008-5472.CAN-07-5714","article-title":"Cancer-associated stromal fibroblasts promote pancreatic tumor progression","volume":"68","author":"Hwang","year":"2008","journal-title":"Cancer Res."},{"key":"2021113011150657100_B39","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1158\/0008-5472.CAN-07-2477","article-title":"Pancreatic stellate cells: partners in crime with pancreatic cancer cells","volume":"68","author":"Vonlaufen","year":"2008","journal-title":"Cancer Res."},{"key":"2021113011150657100_B40","doi-asserted-by":"publisher","first-page":"2585","DOI":"10.2353\/ajpath.2010.090899","article-title":"Role of pancreatic stellate cells in pancreatic cancer metastasis","volume":"177","author":"Xu","year":"2010","journal-title":"Am. J. Pathol."},{"key":"2021113011150657100_B41","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1053\/j.gastro.2004.12.036","article-title":"Pancreatic carcinoma cells induce fibrosis by stimulating proliferation and matrix synthesis of stellate cells","volume":"128","author":"Bachem","year":"2005","journal-title":"Gastroenterology"},{"key":"2021113011150657100_B42","doi-asserted-by":"publisher","first-page":"3085","DOI":"10.18632\/oncotarget.3099","article-title":"Paracrine SDF-1\u03b1 signaling mediates the effects of PSCs on GEM chemoresistance through an IL-6 autocrine loop in pancreatic cancer cells","volume":"6","author":"Zhang","year":"2015","journal-title":"Oncotarget"},{"key":"2021113011150657100_B43","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1158\/2159-8290.CD-19-0094","article-title":"Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts","volume":"9","author":"Elyada","year":"2019","journal-title":"Cancer Discov."},{"key":"2021113011150657100_B44","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01044","article-title":"Pancreatic Ductal Adenocarcinoma: A Strong Imbalance of Good and Bad Immunological Cops in the Tumor Microenvironment","author":"Foucher","year":"2018","journal-title":"Front. Immunol"},{"key":"2021113011150657100_B45","doi-asserted-by":"publisher","first-page":"3007","DOI":"10.1158\/0008-5472.CAN-12-4601","article-title":"Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner","volume":"73","author":"Mace","year":"2013","journal-title":"Cancer Res."},{"key":"2021113011150657100_B46","doi-asserted-by":"publisher","first-page":"6359","DOI":"10.1158\/0008-5472.CAN-13-1558-T","article-title":"Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance","volume":"73","author":"Zhang","year":"2013","journal-title":"Cancer Res."},{"key":"2021113011150657100_B47","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.actbio.2016.10.027","article-title":"Enzyme-mediated stiffening hydrogels for probing activation of pancreatic stellate cells","volume":"48","author":"Liu","year":"2017","journal-title":"Acta Biomater."},{"key":"2021113011150657100_B48","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.suronc.2015.05.002","article-title":"The role of pancreatic stellate cells in pancreatic cancer","volume":"24","author":"Moir","year":"2015","journal-title":"Surg. Oncol."},{"key":"2021113011150657100_B49","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.coph.2009.06.011","article-title":"Inflammation and pancreatic cancer: an evidence-based review","volume":"9","author":"Greer","year":"2009","journal-title":"Curr. Opin. Pharmacol."},{"key":"2021113011150657100_B50","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1097\/PPO.0000000000000288","article-title":"The Pancreatic Cancer Microenvironment","volume":"23","author":"Dougan","year":"2017","journal-title":"Cancer J."},{"key":"2021113011150657100_B51","doi-asserted-by":"crossref","first-page":"e406","DOI":"10.1038\/emm.2017.255","article-title":"Complex roles of the stroma in the intrinsic resistance to gemcitabine in pancreatic cancer: where we are and where we are going","volume":"49","author":"Liang","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"2021113011150657100_B52","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.ccr.2011.05.011","article-title":"Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence","volume":"19","author":"Guerra","year":"2011","journal-title":"Cancer Cell"},{"key":"2021113011150657100_B53","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1136\/gutjnl-2015-309304","article-title":"Stromal biology and therapy in pancreatic cancer: a changing paradigm","volume":"64","author":"Neesse","year":"2015","journal-title":"Gut"},{"key":"2021113011150657100_B54","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.ctrv.2016.01.004","article-title":"Changing the course of pancreatic cancer -Focus on recent translational advances","volume":"44","author":"Javle","year":"2016","journal-title":"Cancer Treatment Rev."},{"key":"2021113011150657100_B55","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/path.4213","article-title":"Understanding the stroma of pancreatic cancer: co-evolution of the microenvironment with epithelial carcinogenesis","volume":"231","author":"Erkan","year":"2013","journal-title":"J. Pathol."},{"key":"2021113011150657100_B56","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12943-018-0927-5","article-title":"Tumor-stromal crosstalk in pancreatic cancer and tissue fibrosis","volume":"18","author":"Thomas","year":"2019","journal-title":"Mol. Cancer"},{"key":"2021113011150657100_B57","first-page":"2140","article-title":"p16 and K-ras Gene Mutations in the Intraductal Precursors of Human Pancreatic Adenocarcinoma","volume":"57","author":"Moskaluk","year":"1997","journal-title":"Cancer Res."},{"key":"2021113011150657100_B58","doi-asserted-by":"publisher","first-page":"6744","DOI":"10.1038\/ncomms7744","article-title":"Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets","volume":"6","author":"Witkiewicz","year":"2015","journal-title":"Nat. Commun."},{"key":"2021113011150657100_B59","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nature14169","article-title":"Whole genomes redefine the mutational landscape of pancreatic cancer","volume":"518","author":"Waddell","year":"2015","journal-title":"Nature"},{"key":"2021113011150657100_B60","doi-asserted-by":"publisher","first-page":"185e113","DOI":"10.1016\/j.ccell.2017.07.007","article-title":"Integrated genomic characterization of pancreatic ductal adenocarcinoma","volume":"32","author":"Raphael","year":"2017","journal-title":"Cancer Cell"},{"key":"2021113011150657100_B61","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/S1535-6108(03)00309-X","article-title":"Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse","volume":"4","author":"Hingorani","year":"2003","journal-title":"Cancer Cell"},{"key":"2021113011150657100_B62","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.ccr.2005.04.023","article-title":"Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice","volume":"7","author":"Hingorani","year":"2005","journal-title":"Cancer Cell"},{"key":"2021113011150657100_B63","doi-asserted-by":"publisher","first-page":"6339","DOI":"10.1158\/1078-0432.CCR-12-1215","article-title":"Clinical significance of the genetic landscape of pancreatic cancer and implications for identification of potential long-term survivors","volume":"18","author":"Yachida","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"2021113011150657100_B64","doi-asserted-by":"publisher","first-page":"1978","DOI":"10.1038\/s41467-018-04383-6","article-title":"Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes","volume":"9","author":"Lomberk","year":"2018","journal-title":"Nat. Commun."},{"key":"2021113011150657100_B65","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1038\/ng.3398","article-title":"Virtual microdissection identifies distinct tumor-and stroma-specific subtypes of pancreatic ductal adenocarcinoma","volume":"47","author":"Moffitt","year":"2015","journal-title":"Nat. Genet."},{"key":"2021113011150657100_B66","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-0133","article-title":"Intraductal transplantation models of human pancreatic ductal adenocarcinoma reveal progressive transition of molecular subtypes","author":"Miyabayashi","year":"2020","journal-title":"Cancer Discov."},{"key":"2021113011150657100_B67","doi-asserted-by":"publisher","first-page":"47M","DOI":"10.1038\/nature16965","article-title":"Genomic analyses identify molecular subtypes of pancreatic cancer","volume":"531","author":"Bailey","year":"2016","journal-title":"Nature"},{"key":"2021113011150657100_B68","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1038\/nm.2344","article-title":"Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy","volume":"17","author":"Collisson","year":"2011","journal-title":"Nat. Med."},{"key":"2021113011150657100_B69","doi-asserted-by":"publisher","first-page":"2727","DOI":"10.1002\/cncr.20672","article-title":"Cytokines in pancreatic carcinoma: correlation with phenotypic characteristics and prognosis","volume":"101","author":"Ebrahimi","year":"2004","journal-title":"Cancer"},{"key":"2021113011150657100_B70","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1245\/s10434-020-08235-w","article-title":"Conditional Survival After Resection for Pancreatic Cancer: A Population-Based Study and Prediction Model","volume":"27","author":"Latenstein","year":"2020","journal-title":"Ann. Surg. Oncol."},{"key":"2021113011150657100_B71","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.01085","article-title":"Neoadjuvant Therapy for Resectable Pancreatic Cancer: An Evolving Paradigm Shift","author":"Chawla","year":"2019","journal-title":"Front. Oncol."},{"key":"2021113011150657100_B72","doi-asserted-by":"publisher","first-page":"20","DOI":"10.21037\/apc.2018.07.05","article-title":"Adjuvant therapeutic strategies for resectable pancreatic adenocarcinoma","volume":"1","author":"Yegya-Raman","year":"2018","journal-title":"Ann Pancreat Cancer"},{"key":"2021113011150657100_B73","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1056\/NEJMoa1809775","article-title":"FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer","volume":"379","author":"Conroy","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"2021113011150657100_B74","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.16272.1","article-title":"Recent advances in radiation therapy of pancreatic cancer","author":"Venkatesulu","year":"2018","journal-title":"F1000Res."},{"key":"2021113011150657100_B75","doi-asserted-by":"publisher","first-page":"186","DOI":"10.4251\/wjgo.v8.i2.186","article-title":"Neoadjuvant radiotherapeutic strategies in pancreatic cancer","volume":"8","author":"Roeder","year":"2016","journal-title":"World J. Gastrointest. Oncol."},{"key":"2021113011150657100_B76","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s13014-019-1277-1","article-title":"Radiation therapy for pancreatic adenocarcinoma, a treatment option that must be considered in the management of a devastating malignancy","volume":"14","author":"Hall","year":"2019","journal-title":"Radiat. Oncol."},{"key":"2021113011150657100_B77","doi-asserted-by":"publisher","first-page":"e15707","DOI":"10.1200\/JCO.2017.35.15_suppl.e15707","article-title":"Effect of palliative surgery, chemotherapy, and radiation in stage IV pancreatic cancer","volume":"35","author":"Vuong","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"2021113011150657100_B78","doi-asserted-by":"publisher","first-page":"E184","DOI":"10.1016\/j.ijrobp.2017.06.1042","article-title":"High Dose Adaptive MRI Guided Radiation Therapy Improves Overall Survival of Inoperable Pancreatic Cancer","volume":"99","author":"Rudra","year":"2017","journal-title":"Int. J. Radiat. Oncol. Biol. hysics"},{"key":"2021113011150657100_B79","doi-asserted-by":"publisher","first-page":"2403","DOI":"10.1200\/JCO.1997.15.6.2403","article-title":"Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial","volume":"15","author":"Burris","year":"1997","journal-title":"J. Clin. Oncol."},{"key":"2021113011150657100_B80","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1056\/NEJMoa1011923","article-title":"FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer","volume":"364","author":"Conroy","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"2021113011150657100_B81","doi-asserted-by":"publisher","first-page":"LBA148","DOI":"10.1200\/jco.2013.31.4_suppl.lba148","article-title":"Randomized phase III study of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic adenocarcinoma of the pancreas (MPACT)","volume":"31","author":"Von Hoff","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"2021113011150657100_B82","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.pan.2016.12.010","article-title":"Microenvironment in determining chemo-resistance in pancreatic cancer: Neighborhood matters","volume":"17","author":"Dauer","year":"2017","journal-title":"Pancreatology"},{"key":"2021113011150657100_B83","first-page":"783","article-title":"The inflammatory milieu within the pancreatic cancer microenvironment correlates with clinicopathologic parameters, chemoresistance and survival","volume":"15","author":"Delitto","year":"2015","journal-title":"Bmc Cancer [Electronic Resource]"},{"key":"2021113011150657100_B84","doi-asserted-by":"publisher","first-page":"e01055","DOI":"10.1016\/j.heliyon.2018.e01055","article-title":"Pancreatic cancer chemo-resistance is driven by tumor phenotype rather than tumor genotype","volume":"4","author":"Swayden","year":"2018","journal-title":"Heliyon"},{"key":"2021113011150657100_B85","first-page":"Cd011044","article-title":"Chemotherapy and radiotherapy for advanced pancreatic cancer","volume":"3","author":"Chin","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"2021113011150657100_B86","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1200\/JCO.2006.07.9525","article-title":"Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group","volume":"25","author":"Moore","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"2021113011150657100_B87","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1097\/CJI.0b013e3181eec14c","article-title":"Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma","volume":"33","author":"Royal","year":"2010","journal-title":"J. Immunother."},{"key":"2021113011150657100_B88","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1056\/NEJMoa1200694","article-title":"Safety and activity of anti-PD-L1 antibody in patients with advanced cancer","volume":"366","author":"Brahmer","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"2021113011150657100_B89","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/S0885-3924(00)00199-8","article-title":"Cytokines and Advanced Cancer","volume":"20","author":"Dunlop","year":"2000","journal-title":"J. Pain Symptom Manag."},{"key":"2021113011150657100_B90","doi-asserted-by":"publisher","first-page":"149185","DOI":"10.1155\/2014\/149185","article-title":"Chronic inflammation and cytokines in the tumor microenvironment","volume":"2014","author":"Landskron","year":"2014","journal-title":"J. Immunol. Res."},{"key":"2021113011150657100_B91","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S1359-6101(96)00025-1","article-title":"The role of cytokines in cancer","volume":"7","author":"Oppenheim","year":"1996","journal-title":"Cytokine Growth Factor Rev."},{"key":"2021113011150657100_B92","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1002\/cncr.11148","article-title":"Role of stromal-derived cytokines and growth factors in bone metastasis","volume":"97","author":"David Roodman","year":"2003","journal-title":"Cancer"},{"key":"2021113011150657100_B93","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.jss.2007.12.757","article-title":"The role of the tumor microenvironment in the progression of pancreatic cancer","volume":"149","author":"Farrow","year":"2008","journal-title":"J. Surg. Res."},{"key":"2021113011150657100_B94","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.coi.2013.01.006","article-title":"Inflammatory networks and immune surveillance of pancreatic carcinoma","volume":"25","author":"Vonderheide","year":"2013","journal-title":"Curr. Opin. Immunol."},{"key":"2021113011150657100_B95","doi-asserted-by":"publisher","first-page":"2678","DOI":"10.3748\/wjg.v22.i9.2678","article-title":"Key players in pancreatic cancer-stroma interaction: Cancer-associated fibroblasts, endothelial and inflammatory cells","volume":"22","author":"Nielsen","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"2021113011150657100_B96","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1016\/j.yexcr.2010.02.045","article-title":"Hallmarks of cancer: interactions with the tumor stroma","volume":"316","author":"Pietras","year":"2010","journal-title":"Exp. Cell Res."},{"key":"2021113011150657100_B97","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.3389\/fimmu.2019.01093","article-title":"Coordination of Immune-Stroma Crosstalk by IL-6 Family Cytokines","volume":"10","author":"West","year":"2019","journal-title":"Front. Immunol."},{"key":"2021113011150657100_B98","doi-asserted-by":"publisher","first-page":"7015","DOI":"10.1158\/1078-0432.CCR-11-0607","article-title":"Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma","volume":"17","author":"Chang","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"2021113011150657100_B99","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1186\/s12943-017-0721-9","article-title":"Tumor-related interleukins: old validated targets for new anti-cancer drug development","volume":"16","author":"Setrerrahmane","year":"2017","journal-title":"Mol. Cancer"},{"key":"2021113011150657100_B100","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.1002\/pro.3519","article-title":"The molecular details of cytokine signaling via the JAK\/STAT pathway","volume":"27","author":"Morris","year":"2018","journal-title":"Protein Sci."},{"key":"2021113011150657100_B101","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028415","article-title":"Interleukin-6 Family Cytokines","author":"Rose-John","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2021113011150657100_B102","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1677\/joe.1.06591","article-title":"Phylogeny and evolution of class-I helical cytokines","volume":"189","author":"Huising","year":"2006","journal-title":"J. Endocrinol."},{"key":"2021113011150657100_B103","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1080\/08977190410001715181","article-title":"New IL-6 (gp130) family cytokine members, CLC\/NNT1\/BSF3 and IL-27","volume":"22","author":"Murakami","year":"2004","journal-title":"Growth Factors (Chur, Switzerland)."},{"key":"2021113011150657100_B104","doi-asserted-by":"publisher","first-page":"4827","DOI":"10.1073\/pnas.0306178101","article-title":"Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor","volume":"101","author":"Derouet","year":"2004","journal-title":"Proceed. Nat. Acad. Sci. United States Am."},{"key":"2021113011150657100_B105","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1146\/annurev.immunol.24.021605.090616","article-title":"Structural biology of shared cytokine receptors","volume":"27","author":"Wang","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"2021113011150657100_B106","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1042\/bj3340297","article-title":"Interleukin-6-type cytokine signalling through the gp130\/Jak\/STAT pathway","volume":"334","author":"Heinrich","year":"1998","journal-title":"Biochem. J."},{"key":"2021113011150657100_B107","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1042\/bj3310695","article-title":"Activation of the signal transducer gp130 by interleukin-11 and interleukin-6 is mediated by similar molecular interactions","volume":"331","author":"Dahmen","year":"1998","journal-title":"Biochemical J."},{"key":"2021113011150657100_B108","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.str.2007.02.006","article-title":"The dynamics of signal triggering in a gp130-receptor complex","volume":"15","author":"Matadeen","year":"2007","journal-title":"Structure (London, England)"},{"key":"2021113011150657100_B109","doi-asserted-by":"publisher","first-page":"36197","DOI":"10.1074\/jbc.M004648200","article-title":"Interleukin-11 signals through the formation of a hexameric receptor complex","volume":"275","author":"Barton","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2021113011150657100_B110","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1042\/bj3000281","article-title":"Soluble receptors for cytokines and growth factors: generation and biological function","volume":"300","author":"Rose-John","year":"1994","journal-title":"Biochemical J."},{"key":"2021113011150657100_B111","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/S0014-5793(99)00477-9","article-title":"A fusion protein of interleukin-11 and soluble interleukin-11 receptor acts as a superagonist on cells expressing gp130","volume":"450","author":"Pflanz","year":"1999","journal-title":"FEBS Lett."},{"key":"2021113011150657100_B112","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/1043-4666(94)90061-2","article-title":"Soluble interleukin 6 receptor in biological fluids from human origin","volume":"6","author":"Frieling","year":"1994","journal-title":"Cytokine"},{"key":"2021113011150657100_B113","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1016\/j.celrep.2016.01.053","article-title":"Proteolytic cleavage governs interleukin-11 trans-signaling","volume":"14","author":"Lokau","year":"2016","journal-title":"Cell Rep."},{"key":"2021113011150657100_B114","first-page":"583","article-title":"The soluble IL-6 receptors: serum levels and biological function","volume":"47","author":"Montero-Julian","year":"2001","journal-title":"Cell. Mol. Biol. (Noisy-le-grand)"},{"key":"2021113011150657100_B115","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1016\/j.ejcb.2011.07.006","article-title":"Signaling by IL-31 and functional consequences","volume":"91","author":"Cornelissen","year":"2012","journal-title":"Eur. J. Cell Biol."},{"key":"2021113011150657100_B116","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.cytogfr.2008.08.003","article-title":"Structures and biological functions of IL-31 and IL-31 receptors","volume":"19","author":"Zhang","year":"2008","journal-title":"Cytokine Growth Factor Rev."},{"key":"2021113011150657100_B117","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.4049\/jimmunol.172.4.2225","article-title":"WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27","volume":"172","author":"Pflanz","year":"2004","journal-title":"J. Immunol."},{"key":"2021113011150657100_B118","doi-asserted-by":"publisher","first-page":"3375","DOI":"10.1172\/JCI57158","article-title":"Therapeutic strategies for the clinical blockade of IL-6\/gp130 signaling","volume":"121","author":"Jones","year":"2011","journal-title":"J. Clin. Invest."},{"key":"2021113011150657100_B119","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1128\/MCB.17.5.2497","article-title":"Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop","volume":"17","author":"Feng","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"2021113011150657100_B120","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/S0092-8674(00)81166-6","article-title":"Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses","volume":"93","author":"Rodig","year":"1998","journal-title":"Cell"},{"key":"2021113011150657100_B121","doi-asserted-by":"publisher","first-page":"848","DOI":"10.4049\/jimmunol.164.2.848","article-title":"The cytoplasmic tyrosine motifs in full-length glycoprotein 130 have different roles in IL-6 signal transduction","volume":"164","author":"Schmitz","year":"2000","journal-title":"J. Immunol."},{"key":"2021113011150657100_B122","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/bj20030407","article-title":"Principles of interleukin (IL)-6-type cytokine signalling and its regulation","volume":"374","author":"Heinrich","year":"2003","journal-title":"Biochem. J."},{"key":"2021113011150657100_B123","doi-asserted-by":"publisher","first-page":"441","DOI":"10.2217\/imt.15.17","article-title":"IL-11 signaling as a therapeutic target for cancer","volume":"7","author":"Putoczki","year":"2015","journal-title":"Immunotherapy"},{"key":"2021113011150657100_B124","doi-asserted-by":"publisher","first-page":"5579","DOI":"10.1158\/1078-0432.CCR-13-2492","article-title":"Molecular pathways: IL11 as a tumor-promoting cytokine-translational implications for cancers","volume":"20","author":"Ernst","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"2021113011150657100_B125","doi-asserted-by":"publisher","first-page":"897","DOI":"10.3390\/cancers6020897","article-title":"STAT3 Target Genes Relevant to Human Cancers","volume":"6","author":"Carpenter","year":"2014","journal-title":"Cancers (Basel)"},{"key":"2021113011150657100_B126","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.ccr.2011.03.002","article-title":"Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression","volume":"19","author":"Fukuda","year":"2011","journal-title":"Cancer Cell"},{"key":"2021113011150657100_B127","doi-asserted-by":"publisher","first-page":"753","DOI":"10.3892\/ijo.2017.3846","article-title":"Regulation of EMT by STAT3 in gastrointestinal cancer (Review)","volume":"50","author":"Li","year":"2017","journal-title":"Int. J. Oncol."},{"key":"2021113011150657100_B128","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1038\/onc.2015.161","article-title":"STAT3 integrates cooperative Ras and TGF-beta signals that induce Snail expression","volume":"35","author":"Saitoh","year":"2016","journal-title":"Oncogene"},{"key":"2021113011150657100_B129","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1016\/S0016-5085(03)01064-3","article-title":"Activated signal transducer and activator of transcription 3 (STAT3) supports the malignant phenotype of human pancreatic cancer","volume":"125","author":"Scholz","year":"2003","journal-title":"Gastroenterology"},{"key":"2021113011150657100_B130","first-page":"115","article-title":"STAT3 as an emerging molecular target in pancreatic cancer","volume":"2014","author":"Sharma","year":"2014","journal-title":"Gastrointest. Cancer: Targets Ther."},{"key":"2021113011150657100_B131","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/sj.onc.1206122","article-title":"Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis","volume":"22","author":"Wei","year":"2003","journal-title":"Oncogene"},{"key":"2021113011150657100_B132","doi-asserted-by":"publisher","first-page":"4124","DOI":"10.1158\/0008-5472.CAN-15-2973","article-title":"FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3\u2013CCL2 Signaling","volume":"76","author":"Yang","year":"2016","journal-title":"Cancer Res."},{"key":"2021113011150657100_B133","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.ejcb.2011.09.010","article-title":"Interleukin-6 signalling: More than Jaks and STATs","volume":"91","author":"Eulenfeld","year":"2012","journal-title":"European J. Cell Biol."},{"key":"2021113011150657100_B134","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1074\/jbc.M210552200","article-title":"SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130","volume":"278","author":"Lehmann","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2021113011150657100_B135","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/S1074-7613(00)80501-4","article-title":"Two signals are necessary for cell proliferation induced by a cytokine receptor gp130: involvement of STAT3 in anti-apoptosis","volume":"5","author":"Fukada","year":"1996","journal-title":"Immunity"},{"key":"2021113011150657100_B136","doi-asserted-by":"publisher","first-page":"6493","DOI":"10.1073\/pnas.100135197","article-title":"Suppressor of cytokine signaling-3 preferentially binds to the SHP-2-binding site on the shared cytokine receptor subunit gp130","volume":"97","author":"Nicholson","year":"2000","journal-title":"Proceed. Nat. Acad. Sci."},{"key":"2021113011150657100_B137","doi-asserted-by":"publisher","first-page":"12848","DOI":"10.1074\/jbc.275.17.12848","article-title":"SOCS3 exerts its inhibitory function on interleukin-6 signal transduction through the SHP2 recruitment site of gp130","volume":"275","author":"Schmitz","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2021113011150657100_B138","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1016\/j.jmb.2008.06.038","article-title":"The SOCS box domain of SOCS3: structure and interaction with the elonginBC-cullin5 ubiquitin ligase","volume":"381","author":"Babon","year":"2008","journal-title":"J. Mol. Biol."},{"key":"2021113011150657100_B139","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.jmb.2009.01.024","article-title":"The SOCS box encodes a hierarchy of affinities for Cullin5: implications for ubiquitin ligase formation and cytokine signalling suppression","volume":"387","author":"Babon","year":"2009","journal-title":"J. Mol. Biol."},{"key":"2021113011150657100_B140","doi-asserted-by":"publisher","first-page":"12530","DOI":"10.1074\/jbc.M010074200","article-title":"The SOCS box of SOCS-1 accelerates ubiquitin-dependent proteolysis of TEL-JAK2","volume":"276","author":"Kamizono","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2021113011150657100_B141","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/nsmb.2519","article-title":"SOCS3 binds specific receptor-JAK complexes to control cytokine signaling by direct kinase inhibition","volume":"20","author":"Kershaw","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2021113011150657100_B142","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1073\/pnas.96.5.2071","article-title":"The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation","volume":"96","author":"Zhang","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011150657100_B143","doi-asserted-by":"publisher","first-page":"13261","DOI":"10.1073\/pnas.231486498","article-title":"The SOCS box of suppressor of cytokine signaling-1 is important for inhibition of cytokine action in vivo","volume":"98","author":"Zhang","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011150657100_B144","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/08977194.2013.877005","article-title":"Reconstruction of an active SOCS3-based E3 ubiquitin ligase complex in vitro: identification of the active components and JAK2 and gp130 as substrates","volume":"32","author":"Kershaw","year":"2014","journal-title":"Growth Factors (Chur, Switzerland)."},{"key":"2021113011150657100_B145","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.immuni.2011.12.015","article-title":"Suppression of cytokine signaling by SOCS3: characterization of the mode of inhibition and the basis of its specificity","volume":"36","author":"Babon","year":"2012","journal-title":"Immunity"},{"key":"2021113011150657100_B146","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1046\/j.1365-2443.1999.00263.x","article-title":"Cytokine-inducible SH2 protein-3 (CIS3\/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain","volume":"4","author":"Sasaki","year":"1999","journal-title":"Genes Cells"},{"key":"2021113011150657100_B147","first-page":"e25045","article-title":"SOCS3: An essential physiological inhibitor of signaling by interleukin-6 and G-CSF family cytokines","volume":"2","author":"White","year":"2013","journal-title":"JAKSTAT"},{"key":"2021113011150657100_B148","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1093\/emboj\/18.5.1309","article-title":"The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop","volume":"18","author":"Yasukawa","year":"1999","journal-title":"EMBO J."},{"key":"2021113011150657100_B149","doi-asserted-by":"publisher","first-page":"2535","DOI":"10.4049\/jimmunol.165.5.2535","article-title":"Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation","volume":"165","author":"Anhuf","year":"2000","journal-title":"J. Immunol."},{"key":"2021113011150657100_B150","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/j.trecan.2017.10.004","article-title":"Targeting Oncogenic Transcription Factors: Therapeutic Implications of Endogenous STAT Inhibitors","volume":"3","author":"Heppler","year":"2017","journal-title":"Trends Cancer"},{"key":"2021113011150657100_B151","doi-asserted-by":"publisher","first-page":"4957","DOI":"10.2147\/CMAR.S206175","article-title":"Negative regulators of STAT3 signaling pathway in cancers","volume":"11","author":"Wu","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"2021113011150657100_B152","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1093\/jjco\/28.1.12","article-title":"Elevated Serum Interleukin-6 Levels in Patients with Pancreatic Cancer","volume":"28","author":"Okada","year":"1998","journal-title":"Japanese J. Clin. Oncol."},{"key":"2021113011150657100_B153","first-page":"881","article-title":"Cytokine regulation of constitutive production of interleukin-8 and -6 by human pancreatic cancer cell lines and serum cytokine concentrations in patients with pancreatic cancer","volume":"21","author":"Wigmore","year":"2002","journal-title":"Int. J. Oncol."},{"key":"2021113011150657100_B154","doi-asserted-by":"publisher","first-page":"e97613","DOI":"10.1371\/journal.pone.0097613","article-title":"Selected cytokines in patients with pancreatic cancer: a preliminary report","volume":"9","author":"B\u0142ogowski","year":"2014","journal-title":"PLoS ONE"},{"key":"2021113011150657100_B155","first-page":"183","article-title":"Proinflammatory cytokines: an insight into pancreatic oncogenesis","volume":"69","author":"Miron","year":"2010","journal-title":"Roum. Arch. Microbiol. Immunol."},{"key":"2021113011150657100_B156","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1042\/cs0960083","article-title":"Relationship of serum levels of interleukin-6, soluble interleukin-6 receptor and tumour necrosis factor receptors to the acute-phase protein response in advanced pancreatic cancer","volume":"96","author":"Barber","year":"1999","journal-title":"Clin. Sci. (Lond.)"},{"key":"2021113011150657100_B157","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1002\/jcla.20395","article-title":"Diagnostic usefulness of serum interleukin 6 (IL-6) and C-reactive protein (CRP) in the differentiation between pancreatic cancer and chronic pancreatitis","volume":"24","author":"Mroczko","year":"2010","journal-title":"J. Clin. Lab. Anal."},{"key":"2021113011150657100_B158","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1007\/s10620-008-0390-z","article-title":"Clinical significance of interleukin-6 (IL-6) gene polymorphism and IL-6 serum level in pancreatic adenocarcinoma and chronic pancreatitis","volume":"54","author":"Talar-Wojnarowska","year":"2009","journal-title":"Dig. Dis. Sci."},{"key":"2021113011150657100_B159","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1097\/MPA.0000000000000335","article-title":"Characterization of patients with advanced pancreatic cancer and high serum interleukin-6 levels","volume":"44","author":"Miura","year":"2015","journal-title":"Pancreas"},{"key":"2021113011150657100_B160","doi-asserted-by":"publisher","first-page":"e5926","DOI":"10.1097\/MD.0000000000005926","article-title":"Serum interleukin-6 is associated with pancreatic ductal adenocarcinoma progression pattern","volume":"96","author":"Kim","year":"2017","journal-title":"Medicine"},{"key":"2021113011150657100_B161","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.pan.2018.11.002","article-title":"Circulating interleukin-6 is associated with disease progression, but not cachexia in pancreatic cancer","volume":"19","author":"Ramsey","year":"2019","journal-title":"Pancreatology"},{"key":"2021113011150657100_B162","doi-asserted-by":"crossref","first-page":"247","DOI":"10.20452\/pamw.144","article-title":"Clinical significance of interleukin-6 (IL-6) as a prognostic factor of cancer disease","volume":"117","author":"Lukaszewicz","year":"2007","journal-title":"Pol. Arch. Med. Wewn."},{"key":"2021113011150657100_B163","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw363.34","article-title":"Serum interleukin-6 as a prognostic biomarker for survival in patients with unresectable pancreatic cancer","volume":"27","author":"Chen","year":"2016","journal-title":"Annals Oncol."},{"key":"2021113011150657100_B164","doi-asserted-by":"publisher","first-page":"5228","DOI":"10.1177\/0300060518800588","article-title":"Serum levels of IL-6, IL-8, and IL-10 are indicators of prognosis in pancreatic cancer","volume":"46","author":"Feng","year":"2018","journal-title":"J. Int. Med. Res."},{"key":"2021113011150657100_B165","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1007\/s00262-005-0047-0","article-title":"Cytokine expression profile in human pancreatic carcinoma cells and in surgical specimens: implications for survival","volume":"55","author":"Bellone","year":"2006","journal-title":"Cancer Immunol. Immunother."},{"key":"2021113011150657100_B166","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s004230050233","article-title":"Tumor size and lymph-node status in pancreatic carcinoma -is there a correlation to the preoperative immune function?","volume":"384","author":"Wenger","year":"1999","journal-title":"Langenbecks Arch. Surg."},{"key":"2021113011150657100_B167","doi-asserted-by":"publisher","first-page":"5802","DOI":"10.1158\/1078-0432.CCR-05-0185","article-title":"Role of mononuclear cells and inflammatory cytokines in pancreatic cancer-related cachexia","volume":"11","author":"Martignoni","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"2021113011150657100_B168","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1158\/1078-0432.CCR-15-1732","article-title":"Systemic Immune Activity Predicts Overall Survival in Treatment-Na\u00efve Patients with Metastatic Pancreatic Cancer","volume":"22","author":"Farren","year":"2016","journal-title":"Clin. Cancer Res.: An Official J. Am. Assoc. for Cancer Res."},{"key":"2021113011150657100_B169","doi-asserted-by":"publisher","first-page":"3195025","DOI":"10.1155\/2018\/3195025","article-title":"Suppression of IL-6 Gene by shRNA Augments Gemcitabine Chemosensitization in Pancreatic Adenocarcinoma Cells","volume":"2018","author":"Xing","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"2021113011150657100_B170","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41586-019-1130-6","article-title":"Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring","volume":"569","author":"Shi","year":"2019","journal-title":"Nature"},{"key":"2021113011150657100_B171","doi-asserted-by":"publisher","first-page":"65982","DOI":"10.18632\/oncotarget.11786","article-title":"Pancreatic stellate cell secreted IL-6 stimulates STAT3 dependent invasiveness of pancreatic intraepithelial neoplasia and cancer cells","volume":"7","author":"Nagathihalli","year":"2016","journal-title":"Oncotarget"},{"key":"2021113011150657100_B172","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.ccr.2011.03.009","article-title":"Stat3\/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer","volume":"19","author":"Lesina","year":"2011","journal-title":"Cancer Cell"},{"key":"2021113011150657100_B173","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.4161\/cbt.6.7.4328","article-title":"IL-6 stimulates Th2 type cytokine secretion and upregulates VEGF and NRP-1 expression in pancreatic cancer cells","volume":"6","author":"Feurino","year":"2007","journal-title":"Cancer Biol. Ther."},{"key":"2021113011150657100_B174","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1002\/ijc.29445","article-title":"Inhibition of IL-6 signaling significantly reduces primary tumor growth and recurrencies in orthotopic xenograft models of pancreatic cancer","volume":"137","author":"Goumas","year":"2015","journal-title":"Int. J. Cancer"},{"key":"2021113011150657100_B175","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1007\/s10620-015-4001-5","article-title":"IL-6\/STAT3 Plays a Regulatory Role in the Interaction Between Pancreatic Stellate Cells and Cancer Cells","volume":"61","author":"Hamada","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"2021113011150657100_B176","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1158\/2159-8290.CD-18-0710","article-title":"IL1-Induced JAK\/STAT Signaling Is Antagonized by TGF\u03b2 to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma","volume":"9","author":"Biffi","year":"2019","journal-title":"Cancer Discover."},{"key":"2021113011150657100_B177","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1126\/science.1198443","article-title":"CD40 Agonists Alter Tumor Stroma and Show Efficacy Against Pancreatic Carcinoma in Mice and Humans","volume":"331","author":"Gregory","year":"2011","journal-title":"Science"},{"key":"2021113011150657100_B178","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/1756-9966-29-51","article-title":"Effects of IL-6 and AG490 on regulation of Stat3 signaling pathway and invasion of human pancreatic cancer cells in vitro","volume":"29","author":"Huang","year":"2010","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"2021113011150657100_B179","first-page":"2029","article-title":"LLL12 inhibits endogenous and exogenous interleukin-6-induced STAT3 phosphorylation in human pancreatic cancer cells","volume":"31","author":"Liu","year":"2011","journal-title":"Anticancer Res."},{"key":"2021113011150657100_B180","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/S1499-3872(14)60259-9","article-title":"Interleukin-6: a villain in the drama of pancreatic cancer development and progression","volume":"13","author":"Holmer","year":"2014","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"2021113011150657100_B181","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.smim.2014.01.002","article-title":"Interleukin-6 in inflammatory and malignant diseases of the pancreas","volume":"26","author":"Lesina","year":"2014","journal-title":"Semin. Immunol."},{"key":"2021113011150657100_B182","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.imlet.2016.11.010","article-title":"IL-6 roles -Molecular pathway and clinical implication in pancreatic cancer -A systemic review","volume":"181","author":"Pop","year":"2017","journal-title":"Immunol. Lett."},{"key":"2021113011150657100_B183","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1002\/ijc.27715","article-title":"Persistent activation of pancreatic stellate cells creates a microenvironment favorable for the malignant behavior of pancreatic ductal adenocarcinoma","volume":"132","author":"Tang","year":"2013","journal-title":"Int. J. Cancer"},{"key":"2021113011150657100_B184","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.2174\/13816128112092395","article-title":"Therapeutic potential of perineural invasion, hypoxia and desmoplasia in pancreatic cancer","volume":"18","author":"Liu","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"2021113011150657100_B185","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1101\/gad.1549407","article-title":"Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis","volume":"21","author":"Ancrile","year":"2007","journal-title":"Genes Dev."},{"key":"2021113011150657100_B186","doi-asserted-by":"publisher","first-page":"e50165","DOI":"10.1371\/journal.pone.0050165","article-title":"Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment","volume":"7","author":"Bao","year":"2012","journal-title":"PLoS ONE"},{"key":"2021113011150657100_B187","first-page":"2449","article-title":"Interleukin-6 inhibits radiation induced apoptosis in pancreatic cancer cells","volume":"21","author":"Miyamoto","year":"2001","journal-title":"Anticancer Res."},{"key":"2021113011150657100_B188","first-page":"460","article-title":"Interleukin-1alpha, 6 regulate the secretion of vascular endothelial growth factor A, C in pancreatic cancer","volume":"4","author":"Tang","year":"2005","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"2021113011150657100_B189","first-page":"4093","article-title":"Expression of IL-6 receptor in pancreatic cancer: involvement in VEGF induction","volume":"22","author":"Masui","year":"2002","journal-title":"Anticancer Res."},{"key":"2021113011150657100_B190","doi-asserted-by":"publisher","first-page":"5479","DOI":"10.1158\/0008-5472.CAN-06-3963","article-title":"Elevated interleukin-6 and G-CSF in human pancreatic cancer cell conditioned medium suppress dendritic cell differentiation and activation","volume":"67","author":"Bharadwaj","year":"2007","journal-title":"Cancer Res."},{"key":"2021113011150657100_B191","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190673","article-title":"Type 1 conventional dendritic cells are systemically dysregulated early in pancreatic carcinogenesis","volume":"217","author":"Lin","year":"2020","journal-title":"J. Exp. Med."},{"key":"2021113011150657100_B192","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.cmet.2016.10.010","article-title":"Tumor-Induced IL-6 Reprograms Host Metabolism to Suppress Anti-tumor Immunity","volume":"24","author":"Flint","year":"2016","journal-title":"Cell Metab."},{"key":"2021113011150657100_B193","doi-asserted-by":"publisher","first-page":"396","DOI":"10.4149\/neo_2011_05_396","article-title":"The effects and mechanisms of blockage of STAT3 signaling pathway on IL-6 inducing EMT in human pancreatic cancer cells in vitro","volume":"58","author":"Huang","year":"2011","journal-title":"Neoplasma"},{"key":"2021113011150657100_B194","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.bbagen.2016.10.006","article-title":"Paracrine IL-6 signaling mediates the effects of pancreatic stellate cells on epithelial-mesenchymal transition via Stat3\/Nrf2 pathway in pancreatic cancer cells","volume":"1861","author":"Wu","year":"2017","journal-title":"Biochimica et Biophysica Acta (BBA) -General Subjects"},{"key":"2021113011150657100_B195","doi-asserted-by":"publisher","first-page":"11143","DOI":"10.1074\/jbc.RA118.003276","article-title":"Interleukin-6 promotes pancreatic cancer cell migration by rapidly activating the small GTPase CDC42","volume":"293","author":"Razidlo","year":"2018","journal-title":"J. Biol. Chem."},{"key":"2021113011150657100_B196","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1136\/gutjnl-2016-311585","article-title":"IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer","volume":"67","author":"Mace","year":"2018","journal-title":"Gut"},{"key":"2021113011150657100_B197","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1046\/j.1432-1327.2001.01867.x","article-title":"Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses","volume":"268","author":"Jostock","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"2021113011150657100_B198"},{"key":"2021113011150657100_B199","doi-asserted-by":"publisher","first-page":"11467","DOI":"10.1007\/s13277-014-2459-y","article-title":"Plasma interleukin-11 (IL-11) levels have diagnostic and prognostic roles in patients with pancreatic cancer","volume":"35","author":"Ren","year":"2014","journal-title":"Tumor Biol."},{"key":"2021113011150657100_B200","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1093\/carcin\/bgs297","article-title":"Transcriptional regulation of the interleukin-11 gene by oncogenic Ras","volume":"33","author":"Shin","year":"2012","journal-title":"Carcinogenesis"},{"key":"2021113011150657100_B201","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.ccr.2013.06.017","article-title":"Interleukin-11 Is the Dominant IL-6 Family Cytokine during Gastrointestinal Tumorigenesis and Can Be Targeted Therapeutically","volume":"24","author":"Putoczki","year":"2013","journal-title":"Cancer Cell"},{"key":"2021113011150657100_B202","doi-asserted-by":"publisher","first-page":"194","DOI":"10.4143\/crt.2018.031","article-title":"Cancer-Associated Fibroblasts Promote the Chemo-resistance in Gastric Cancer through Secreting IL-11 Targeting JAK\/STAT3\/Bcl2 Pathway","volume":"51","author":"Ma","year":"2019","journal-title":"Cancer Res. Treat."},{"key":"2021113011150657100_B203","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.cytogfr.2015.07.015","article-title":"Emerging roles for IL-11 signaling in cancer development and progression: Focus on breast cancer","volume":"26","author":"Johnstone","year":"2015","journal-title":"Cytokine & Growth Factor Rev."},{"key":"2021113011150657100_B204","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1158\/0008-5472.CAN-15-2790","article-title":"LIF Drives Neural Remodeling in Pancreatic Cancer and Offers a New Candidate Biomarker","volume":"78","author":"Bressy","year":"2018","journal-title":"Cancer Res."},{"key":"2021113011150657100_B205","first-page":"90","article-title":"Expression and significance of leukemia inhibitory factor in human pancreatic cancer","volume":"94","author":"Peng","year":"2014","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"2021113011150657100_B206","first-page":"977","article-title":"Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: Involvement of regulation of LIF and its receptor expression","volume":"30","author":"Kamohara","year":"2007","journal-title":"Int. J. Oncol."},{"key":"2021113011150657100_B207","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.1038\/s41467-019-11044-9","article-title":"Blockade of leukemia inhibitory factor as a therapeutic approach to KRAS driven pancreatic cancer","volume":"10","author":"Wang","year":"2019","journal-title":"Nat. Commun."},{"key":"2021113011150657100_B208","first-page":"627","article-title":"Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-alpha and leukemia inhibitory factor in pancreatic carcinoma cells: Impact of CXCL-8 as an autocrine growth factor","volume":"31","author":"Kamohara","year":"2007","journal-title":"Int. J. Oncol."},{"key":"2021113011150657100_B209","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.3748\/wjg.v18.i10.1123","article-title":"Interleukin-8, a promising predictor for prognosis of pancreatic cancer","volume":"18","author":"Chen","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"2021113011150657100_B210","doi-asserted-by":"publisher","first-page":"827","DOI":"10.3892\/or.2016.4865","article-title":"Leukemia inhibitory factor receptor negatively regulates the metastasis of pancreatic cancer cells in vitro and in vivo","volume":"36","author":"Ma","year":"2016","journal-title":"Oncol. Rep."},{"key":"2021113011150657100_B211","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1097\/MPA.0000000000000155","article-title":"Serum cytokine profile in patients with pancreatic cancer","volume":"43","author":"Torres","year":"2014","journal-title":"Pancreas"},{"key":"2021113011150657100_B212","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1111\/j.1349-7006.2005.00064.x","article-title":"Experimental trial for diagnosis of pancreatic ductal carcinoma based on gene expression profiles of pancreatic ductal cells","volume":"96","author":"Ishikawa","year":"2005","journal-title":"Cancer Sci."},{"key":"2021113011150657100_B213","first-page":"2016","article-title":"Combined gene expression analysis of whole-tissue and microdissected pancreatic ductal adenocarcinoma identifies genes specifically overexpressed in tumor epithelia","volume":"55","author":"Badea","year":"2008","journal-title":"Hepato-Gastroenterol."},{"key":"2021113011150657100_B214","first-page":"2649","article-title":"Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer","volume":"63","author":"Logsdon","year":"2003","journal-title":"Cancer Res."},{"key":"2021113011150657100_B215","doi-asserted-by":"publisher","first-page":"3587","DOI":"10.1158\/1078-0432.CCR-04-1813","article-title":"Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia","volume":"11","author":"Segara","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"2021113011150657100_B216","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1158\/1541-7786.MCR-16-0337","article-title":"Potent EMT and CSC Phenotypes Are Induced By Oncostatin-M in Pancreatic Cancer","volume":"15","author":"Smigiel","year":"2017","journal-title":"Mol. Cancer Res."},{"key":"2021113011150657100_B217","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1097\/MPA.0000000000000020","article-title":"Evidence for the importance of personalized molecular profiling in pancreatic cancer","volume":"43","author":"Lili","year":"2014","journal-title":"Pancreas"},{"key":"2021113011150657100_B218","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1158\/1078-0432.CCR-08-1778","article-title":"Unique Methylation Pattern of Oncostatin M Receptor Gene in Cancers of Colorectum and Other Digestive Organs","volume":"15","author":"Deng","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"2021113011150657100_B219","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1074\/mcp.RA119.001779","article-title":"Upregulation of CD73 Confers Acquired Radioresistance and is Required for Maintaining Irradiation-selected Pancreatic Cancer Cells in a Mesenchymal State","volume":"19","author":"Nguyen","year":"2020","journal-title":"Mol. Cell. Proteomics"},{"key":"2021113011150657100_B220","doi-asserted-by":"publisher","first-page":"4001","DOI":"10.1038\/onc.2017.33","article-title":"Oncostatin M promotes cancer cell plasticity through cooperative STAT3-SMAD3 signaling","volume":"36","author":"Junk","year":"2017","journal-title":"Oncogene"},{"key":"2021113011150657100_B221","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1159\/000320179","article-title":"Cooperative Signaling between Oncostatin M, Hepatocyte Growth Factor and Transforming Growth Factor-\u03b2 Enhances Epithelial to Mesenchymal Transition in Lung and Pancreatic Tumor Models","volume":"193","author":"Argast","year":"2011","journal-title":"Cells Tissues Organs"},{"key":"2021113011150657100_B222","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1158\/0008-5472.CAN-06-2030","article-title":"Identification of pancreatic cancer stem cells","volume":"67","author":"Li","year":"2007","journal-title":"Cancer Res."},{"key":"2021113011150657100_B223","doi-asserted-by":"publisher","first-page":"R1067","DOI":"10.1152\/ajpregu.00320.2011","article-title":"Activation state of stromal inflammatory cells in murine metastatic pancreatic adenocarcinoma","volume":"302","author":"Benson","year":"2012","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2021113011150657100_B224","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/s12943-015-0479-x","article-title":"Enhanced therapeutic effect using sequential administration of antigenically distinct oncolytic viruses expressing oncostatin M in a Syrian hamster orthotopic pancreatic cancer model","volume":"14","author":"Nistal-Villan","year":"2015","journal-title":"Mol. Cancer"},{"key":"2021113011150657100_B225","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.4161\/onci.22504","article-title":"Cardiotrophin-1 determines liver engraftment of syngenic colon carcinoma cells through an immune system-mediated mechanism","volume":"1","author":"Bustos","year":"2012","journal-title":"Oncoimmunology"},{"key":"2021113011150657100_B226","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1038\/s41591-019-0612-2","article-title":"Antitumor activity of an engineered decoy receptor targeting CLCF1\u2013CNTFR signaling in lung adenocarcinoma","volume":"25","author":"Kim","year":"2019","journal-title":"Nat. Med."},{"key":"2021113011150657100_B227","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00969","article-title":"IL-27, IL-30, and IL-35: A Cytokine Triumvirate in Cancer","volume":"9","author":"Kourko","year":"2019","journal-title":"Front. Oncol."},{"key":"2021113011150657100_B228","doi-asserted-by":"publisher","first-page":"3958069","DOI":"10.1155\/2017\/3958069","article-title":"Dual Roles of IL-27 in Cancer Biology and Immunotherapy","volume":"2017","author":"Fabbi","year":"2017","journal-title":"Mediators Inflamm."},{"key":"2021113011150657100_B229","first-page":"634","article-title":"IL-27 promotes apoptosis of human pancreatic carcinoma Aspc1 cells","volume":"17","author":"Liu","year":"2010","journal-title":"Chinese J. Cancer Biother."},{"key":"2021113011150657100_B230","first-page":"1497","article-title":"Effects on apoptosis and cell cycle arrest contribute to the antitumor responses of interleukin-27 mediated by retrovirus in human pancreatic carcinoma cells","volume":"27","author":"Liu","year":"2012","journal-title":"Oncol. Rep."},{"key":"2021113011150657100_B231","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.cyto.2015.12.003","article-title":"Interleukin-27 inhibits malignant behaviors of pancreatic cancer cells by targeting M2 polarized tumor associated macrophages","volume":"89","author":"Yao","year":"2017","journal-title":"Cytokine"},{"key":"2021113011150657100_B232","doi-asserted-by":"publisher","first-page":"16430","DOI":"10.18632\/oncotarget.14857","article-title":"The antiangiogenic role of the pro-inflammatory cytokine interleukin-31","volume":"8","author":"Davidi","year":"2017","journal-title":"Oncotarget"},{"key":"2021113011150657100_B233","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/nm.4082","article-title":"Genotype tunes pancreatic ductal adenocarcinoma tissue tension to induce matricellular fibrosis and tumor progression","volume":"22","author":"Laklai","year":"2016","journal-title":"Nat. Med."},{"key":"2021113011150657100_B234","doi-asserted-by":"publisher","first-page":"180e112","DOI":"10.1053\/j.gastro.2016.03.010","article-title":"Loss of P53 Function Activates JAK2-STAT3 Signaling to Promote Pancreatic Tumor Growth, Stroma Modification, and Gemcitabine Resistance in Mice and Is Associated With Patient Survival","volume":"151","author":"Wormann","year":"2016","journal-title":"Gastroenterology."},{"key":"2021113011150657100_B235","doi-asserted-by":"publisher","first-page":"1932e1939","DOI":"10.1053\/j.gastro.2015.07.058","article-title":"Signal Transducer and Activator of Transcription 3, Mediated Remodeling of the Tumor Microenvironment Results in Enhanced Tumor Drug Delivery in a Mouse Model of Pancreatic Cancer","volume":"149","author":"Nagathihalli","year":"2015","journal-title":"Gastroenterology"},{"key":"2021113011150657100_B236","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1038\/nm.4099","article-title":"Regulation of pancreatic cancer aggressiveness by stromal stiffening","volume":"22","author":"Rath","year":"2016","journal-title":"Nat. Med."},{"key":"2021113011150657100_B237","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1007\/s11605-013-2168-7","article-title":"Activation of the IL-6R\/Jak\/Stat Pathway is Associated with a Poor Outcome in Resected Pancreatic Ductal Adenocarcinoma","volume":"17","author":"Denley","year":"2013","journal-title":"J Gastrointestinal Sur."},{"key":"2021113011150657100_B238","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1002\/jcp.24580","article-title":"Pancreatic Cancer-Induced Cachexia Is Jak2-Dependent in Mice","volume":"229","author":"Gilabert","year":"2014","journal-title":"J. Cellular Physiol."},{"key":"2021113011150657100_B239","first-page":"154","article-title":"Cancer anorexia -cachexia syndrome","volume":"44","author":"Muliawati","year":"2012","journal-title":"Acta Med. Indones"},{"key":"2021113011150657100_B240","doi-asserted-by":"publisher","first-page":"11708","DOI":"10.18632\/oncotarget.7336","article-title":"Overcoming chemo\/radio-resistance of pancreatic cancer by inhibiting STAT3 signaling","volume":"7","author":"Wu","year":"2016","journal-title":"Oncotarget"},{"key":"2021113011150657100_B241","doi-asserted-by":"publisher","first-page":"19863","DOI":"10.18632\/oncotarget.7887","article-title":"Prognostic role of STAT3 in solid tumors: a systematic review and meta-analysis","volume":"7","author":"Wu","year":"2016","journal-title":"Oncotarget"},{"key":"2021113011150657100_B242","doi-asserted-by":"publisher","first-page":"e25941","DOI":"10.1371\/journal.pone.0025941","article-title":"STAT3 knockdown reduces pancreatic cancer cell invasiveness and matrix metalloproteinase-7 expression in nude mice","volume":"6","author":"Li","year":"2011","journal-title":"PLoS ONE"},{"key":"2021113011150657100_B243","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1101\/gad.311852.118","article-title":"STAT3 is a master regulator of epithelial identity and KRAS-driven tumorigenesis","volume":"32","author":"D'Amico","year":"2018","journal-title":"Genes Dev."},{"key":"2021113011150657100_B244","doi-asserted-by":"publisher","first-page":"5020","DOI":"10.1158\/0008-5472.CAN-11-0908","article-title":"STAT3 plays a critical role in KRAS-induced pancreatic tumorigenesis","volume":"71","author":"Corcoran","year":"2011","journal-title":"Cancer Res."},{"key":"2021113011150657100_B245","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.omtn.2018.01.004","article-title":"miR-1266 Contributes to Pancreatic Cancer Progression and Chemoresistance by the STAT3 and NF-\u03baB Signaling Pathways","volume":"11","author":"Zhang","year":"2018","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"2021113011150657100_B246","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1038\/nrc3818","article-title":"Revisiting STAT3 signalling in cancer: new and unexpected biological functions","volume":"14","author":"Yu","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"2021113011150657100_B247","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1038\/nrc2734","article-title":"STATs in cancer inflammation and immunity: a leading role for STAT3","volume":"9","author":"Yu","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"2021113011150657100_B248","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1111\/j.1349-7006.2006.00340.x","article-title":"Inhibition of STAT3 activity with AG490 decreases the invasion of human pancreatic cancer cells in vitro","volume":"97","author":"Huang","year":"2006","journal-title":"Cancer Sci."},{"key":"2021113011150657100_B249","first-page":"2393","article-title":"WP1066, a potent inhibitor of Jak2\/STAT3 pathway inhibits pancreatic tumor growth both in vitro and in vivo","volume":"67","author":"Guha","year":"2007","journal-title":"Cancer Res."},{"key":"2021113011150657100_B250","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1093\/carcin\/bgt394","article-title":"Combined inhibition of Notch and JAK\/STAT is superior to monotherapies and impairs pancreatic cancer progression","volume":"35","author":"Palagani","year":"2014","journal-title":"Carcinogenesis"},{"key":"2021113011150657100_B251","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1038\/s41598-017-01973-0","article-title":"Inhibition of Jak\/STAT signaling reduces the activation of pancreatic stellate cells in vitro and limits caerulein-induced chronic pancreatitis in vivo","volume":"7","author":"Komar","year":"2017","journal-title":"Sci. Rep."},{"key":"2021113011150657100_B252","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.123281","article-title":"Tofacitinib enhances delivery of antibody-based therapeutics to tumor cells through modulation of inflammatory cells","volume":"4","author":"Simon","year":"2019","journal-title":"JCI Insight."},{"key":"2021113011150657100_B253","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.ejca.2007.08.028","article-title":"Mesothelin targeted cancer immunotherapy","volume":"44","author":"Hassan","year":"2008","journal-title":"European J. Cancer (Oxford, England: 1990)."},{"key":"2021113011150657100_B254","first-page":"3862","article-title":"Mesothelin is overexpressed in the vast majority of ductal adenocarcinomas of the pancreas: identification of a new pancreatic cancer marker by serial analysis of gene expression (SAGE)","volume":"7","author":"Argani","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"2021113011150657100_B255","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.3748\/wjg.v23.i9.1594","article-title":"miR-1181 inhibits invasion and proliferation via STAT3 in pancreatic cancer","volume":"23","author":"Wang","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"2021113011150657100_B256","doi-asserted-by":"publisher","first-page":"565","DOI":"10.2147\/CMAR.S159090","article-title":"L61H46 shows potent efficacy against human pancreatic cancer through inhibiting STAT3 pathway","volume":"10","author":"Bai","year":"2018","journal-title":"Cancer Manag. Res."},{"key":"2021113011150657100_B257","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1158\/0008-5472.CAN-09-2468","article-title":"Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells","volume":"70","author":"Lin","year":"2010","journal-title":"Cancer Res."},{"key":"2021113011150657100_B258","first-page":"1637","article-title":"STAT3-targeting RNA interference inhibits pancreatic cancer angiogenesis in vitro and in vivo","volume":"38","author":"Huang","year":"2011","journal-title":"Int. J. Oncol."},{"key":"2021113011150657100_B259","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1097\/MPA.0b013e318204ea7b","article-title":"Targeting STAT3 signaling in pancreatic cancer promotes antiapoptotic gene expression","volume":"40","author":"Glienke","year":"2011","journal-title":"Pancreas"},{"key":"2021113011150657100_B260","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.imlet.2019.10.003","article-title":"Impact of combination therapy with anti-PD-1 blockade and a STAT3 inhibitor on the tumor-infiltrating lymphocyte status","volume":"216","author":"Ashizawa","year":"2019","journal-title":"Immunol. Letters"},{"key":"2021113011150657100_B261","doi-asserted-by":"publisher","first-page":"4039","DOI":"10.1200\/JCO.2015.61.4578","article-title":"Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed","volume":"33","author":"Hurwitz","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"2021113011150657100_B262","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1007\/s10637-018-0580-2","article-title":"Ruxolitinib + capecitabine in advanced\/metastatic pancreatic cancer after disease progression\/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies","volume":"36","author":"Hurwitz","year":"2018","journal-title":"Invest. New Drugs"},{"key":"2021113011150657100_B263","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.2147\/OTT.S157331","article-title":"A Phase Ib study of ruxolitinib + gemcitabine +\/-nab-paclitaxel in patients with advanced solid tumors","volume":"11","author":"Bauer","year":"2018","journal-title":"Onco. Targets Ther"},{"key":"2021113011150657100_B264","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s10637-018-0650-5","article-title":"Phase 1 dose-escalation study of momelotinib, a Janus kinase 1\/2 inhibitor, combined with gemcitabine and nab-paclitaxel in patients with previously untreated metastatic pancreatic ductal adenocarcinoma","volume":"37","author":"Ng","year":"2019","journal-title":"Invest. New Drugs"},{"key":"2021113011150657100_B265","doi-asserted-by":"publisher","first-page":"4110","DOI":"10.1200\/JCO.2018.36.15_suppl.4110","article-title":"Phase 1b\/2 trial of cancer stemness inhibitor napabucasin (NAPA) + nab-paclitaxel (nPTX) and gemcitabine (Gem) in metastatic pancreatic adenocarcinoma (mPDAC)","volume":"36","author":"Bekaii-Saab","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"2021113011150657100_B266","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.2217\/fon-2018-0903","article-title":"CanStem111P trial: a Phase III study of napabucasin plus nab-paclitaxel with gemcitabine","volume":"15","author":"Sonbol","year":"2019","journal-title":"Future Oncol."},{"key":"2021113011150657100_B267","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/leu.2013.205","article-title":"Specificity and mechanism-of-action of the JAK2 tyrosine kinase inhibitors ruxolitinib and SAR302503 (TG101348)","volume":"28","author":"Zhou","year":"2014","journal-title":"Leukemia"},{"key":"2021113011150657100_B268","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/s13046-019-1289-6","article-title":"Napabucasin, a novel STAT3 inhibitor suppresses proliferation, invasion and stemness of glioblastoma cells","volume":"38","author":"Han","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"2021113011150657100_B269","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1080\/13543784.2017.1351941","article-title":"Do STAT3 inhibitors have potential in the future for cancer therapy?","volume":"26","author":"Wong","year":"2017","journal-title":"Exp. Opin. Investig. Drugs"},{"key":"2021113011150657100_B270","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1038\/sj.bjc.6605872","article-title":"A phase I\/II study of siltuximab (CNTO 328), an anti-interleukin-6 monoclonal antibody, in metastatic renal cell cancer","volume":"103","author":"Rossi","year":"2010","journal-title":"British J. Cancer"},{"key":"2021113011150657100_B271","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.clml.2012.12.010","article-title":"Complete remission achieved with single agent CNTO 328, an anti-IL-6 monoclonal antibody, in relapsed and refractory myeloma","volume":"13","author":"Chari","year":"2013","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"2021113011150657100_B272","doi-asserted-by":"publisher","DOI":"10.7717\/peerj-cs.67","article-title":"OncoLnc: linking TCGA survival data to mRNAs, miRNAs, and lncRNAs","volume":"2","author":"Anaya","year":"2016","journal-title":"PeerJ Computer Sci."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/134\/16\/2091\/891045\/cs-2019-1211c.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/134\/16\/2091\/891045\/cs-2019-1211c.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,11]],"date-time":"2024-08-11T19:48:52Z","timestamp":1723405732000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/134\/16\/2091\/226120\/Emerging-roles-for-the-IL-6-family-of-cytokines-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8]]},"references-count":272,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2020,8,28]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20191211","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,8]]},"published":{"date-parts":[[2020,8]]}}}