{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T03:44:18Z","timestamp":1789703058698,"version":"4.0.1"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:p>\n                    Clinical data have provided evidence that schistosomiasis can promote hepatocellular carcinogenesis. c\u2010Jun and STAT3 are critical regulators of liver cancer development and progression. The aim of the present study was to investigate the hepatocellular activation of c\u2010Jun and STAT3 by\n                    <jats:italic toggle=\"yes\">Schistosoma mansoni<\/jats:italic>\n                    infection. Expression and function of c\u2010Jun and STAT3 as well as proliferation and DNA repair were analyzed by western blotting, electrophoretic mobility\u2010shift assay, and immunohistochemistry in liver of\n                    <jats:italic toggle=\"yes\">S.\u00a0mansoni<\/jats:italic>\n                    \u2013infected hamsters, Huh7 cells, primary hepatocytes, and human liver biopsies. Hepatocellular activation of c\u2010Jun was demonstrated by nuclear translocation of c\u2010Jun, enhanced phosphorylation (Ser73), and AP\u20101\/DNA\u2010binding in response to\n                    <jats:italic toggle=\"yes\">S.\u00a0mansoni<\/jats:italic>\n                    infection. Nuclear c\u2010Jun staining pattern around lodged eggs without ambient immune reaction, and directionally from granuloma to the central veins, suggested that substances released from schistosome eggs were responsible for the observed effects. In addition, hepatocytes with c\u2010Jun activation show cell activation and DNA double\u2010strand breaks. These findings from the hamster model were confirmed by analyses of human biopsies from patients with schistosomiasis. Cell culture experiments finally demonstrated that activation of c\u2010Jun and STAT3 as well as DNA repair were induced by an extract from schistosome eggs (soluble egg antigens) and culture supernatants of live schistosome egg (egg\u2010conditioned medium), and in particular by IPSE\/alpha\u20101, the major component secreted by live schistosome eggs. The permanent activation of hepatocellular carcinoma\u2013associated proto\u2010oncogenes such as c\u2010Jun and associated transcription factors including STAT3 by substances released from tissue\u2010trapped schistosome eggs may be important factors contributing to the development of liver cancer in\n                    <jats:italic toggle=\"yes\">S.\u00a0mansoni<\/jats:italic>\n                    \u2013infected patients. Therefore, identification and therapeutic targeting of the underlying pathways is a useful strategy to prevent schistosomiasis\u2010associated carcinogenesis.\n                  <\/jats:p>","DOI":"10.1002\/hep.30192","type":"journal-article","created":{"date-parts":[[2018,7,27]],"date-time":"2018-07-27T13:04:42Z","timestamp":1532696682000},"page":"626-641","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":61,"title":["Schistosoma mansoni Egg\u2013Secreted Antigens Activate Hepatocellular Carcinoma\u2013Associated Transcription Factors c\u2010Jun and STAT3 in Hamster and Human Hepatocytes"],"prefix":"10.1097","volume":"72","author":[{"given":"Martin","family":"Roderfeld","sequence":"first","affiliation":[{"name":"Department of Gastroenterology,Justus\u2010Liebig\u2010University,Giessen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevinc","family":"Padem","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Justus\u2010Liebig\u2010University,Giessen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Lichtenberger","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Justus\u2010Liebig\u2010University,Giessen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Quack","sequence":"additional","affiliation":[{"name":"Institute of Parasitology,BFS, Justus\u2010Liebig\u2010University,Giessen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0931","authenticated-orcid":false,"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry,RWTH University Hospital Aachen,Aachen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Longerich","sequence":"additional","affiliation":[{"name":"Translational Gastrointestinal Pathology, Institute of Pathology,University Hospital Heidelberg,Heidelberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Schramm","sequence":"additional","affiliation":[{"name":"Experimental Pneumology, Priority Research Area Asthma & Allergy,Research Center Borstel,Parkallee, Borstel,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Churin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Justus\u2010Liebig\u2010University,Giessen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karuna","family":"Irungbam","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Justus\u2010Liebig\u2010University,Giessen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Tschuschner","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Justus\u2010Liebig\u2010University,Giessen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Windhorst","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics,Justus\u2010Liebig\u2010University,Giessen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph G.","family":"Grevelding","sequence":"additional","affiliation":[{"name":"Institute of Parasitology,BFS, Justus\u2010Liebig\u2010University,Giessen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Roeb","sequence":"additional","affiliation":[{"name":"Department of 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