{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T06:08:12Z","timestamp":1775887692125,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,5,8]],"date-time":"2017-05-08T00:00:00Z","timestamp":1494201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR60"],"award-info":[{"award-number":["TRR60"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672412"],"award-info":[{"award-number":["81672412"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81301865"],"award-info":[{"award-number":["81301865"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2017,7,15]]},"abstract":"<jats:p>Previous studies have shown that hepatocellular carcinoma (HCC) develops more frequently in hepatitis B virus surface antigen (HBsAg)\u2010transgenic mice (Alb\/HBs) than in wild\u2010type (WT) mice. However, the mechanism of this HCC model has not been well documented. Toll\u2010like receptor 4 (Tlr4) signaling probably links innate immunity and HCC progression. This study was designed to investigate the role of innate immunity in hepatocarcinogenesis in Alb\/HBs mice. Immunohistochemical analysis of liver specimens from Alb\/HBs mice (16 per group) showed that the oncogenes Bmi1 (16\/16, 100%) and Dkk1 (13\/16, 81.25%) were highly expressed in Alb\/HBs mice, whereas the other oncogenes evaluated were expressed in smaller percentages of mice (Afp, 9\/16, 56.2%; Ctnnb1, 5\/16, 31.3%; Epcam, 0\/16; 0%). Comparable results were obtained by quantitative PCR analysis. Hepatic gene expression of <jats:italic>Tlr2<\/jats:italic>, <jats:italic>Tlr4, Il6<\/jats:italic> and <jats:italic>Tnf<\/jats:italic> was additionally elevated in Alb\/HBs mice. Stimulation of primary murine hepatocytes with cell culture\u2010derived HBV particles or LPS increased the expression of oncogenes (<jats:italic>Bmi1<\/jats:italic>, <jats:italic>Dkk1<\/jats:italic>) and inflammatory factors (<jats:italic>Tnf, Il6, Tlr4<\/jats:italic>). Proliferation and colony formation of hepatoma cells were enhanced by treatment with HBV and LPS and were impaired by the suppression of <jats:italic>Bmi1<\/jats:italic> and <jats:italic>Dkk1<\/jats:italic> by small interfering RNAs. Substantial induction of BMI1 and DKK1 was found in liver biopsy samples from patients with HBV\u2010related HCC but not in HCC samples without HBV infection background. These findings suggest that innate immunity may link inflammation and tumor progression during chronic HBV infection, involving the oncogenes BMI1 and DKK1.<\/jats:p>","DOI":"10.1002\/ijc.30742","type":"journal-article","created":{"date-parts":[[2017,4,17]],"date-time":"2017-04-17T15:22:45Z","timestamp":1492442565000},"page":"354-363","source":"Crossref","is-referenced-by-count":18,"title":["Hepatic expression of oncogenes Bmi1 and Dkk1 is up\u2010regulated in hepatitis B virus surface antigen\u2013transgenic mice and can be induced by treatment with HBV particles or lipopolysaccharides <i>in vitro<\/i>"],"prefix":"10.1002","volume":"141","author":[{"given":"Rui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Essen, University Duisburg\u2010Essen  Germany"},{"name":"Department of Biliary\u2010Pancreatic Surgery Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine I.","family":"Real","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Essen, University Duisburg\u2010Essen  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biliary\u2010Pancreatic Surgery Sun Yat\u2010sen Memorial Hospital, Sun Yat\u2010sen University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo A.","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Pathology and Neuropathology University Hospital Essen, University Duisburg\u2010Essen  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Gerken","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Essen, University Duisburg\u2010Essen  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengji","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital Essen, University Duisburg\u2010Essen  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7125-3246","authenticated-orcid":false,"given":"Ruth","family":"Broering","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Essen, University Duisburg\u2010Essen  Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,5,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21513"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60207-5"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.04.061"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000343857"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26041"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-305785"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.19.6909"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90770-8"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.08.021"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24606"},{"key":"e_1_2_6_12_1","first-page":"78","article-title":"Hepatocellular carcinoma: current and prospective immunotherapeutic strategies","author":"Kikodze N","year":"2015","journal-title":"Georgian Med News"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i43.7500"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i11.1344"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12019"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3283"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22306"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2014.0039"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728221003642027"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2541"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210907"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/oncsis.2016.6"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.05.019"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22751"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22580"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.10.033"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802751200"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24529"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066457"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2003-37590"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.08.062"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21897"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-014-2347-5"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3317"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/286533a0"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7629"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70233-4"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.07.020"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.38"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420800"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26449"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.30742","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.30742","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T10:21:22Z","timestamp":1695550882000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.30742"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,8]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,7,15]]}},"alternative-id":["10.1002\/ijc.30742"],"URL":"https:\/\/doi.org\/10.1002\/ijc.30742","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,8]]}}}