{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:08:03Z","timestamp":1790744883313,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,12,18]],"date-time":"2011-12-18T00:00:00Z","timestamp":1324166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Multidrug resistance is a major reason for poor treatment results in advanced hepatoblastoma (<jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>). Several alternative treatment options are currently under investigation to improve the prognosis of affected patients<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>This study aimed to analyse the impact of sorafenib on the viability of HB cells and xenotransplanted <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content> tumours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cell viability and apoptosis were evaluated in two <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content> cell lines (<jats:styled-content style=\"fixed-case\">HUH<\/jats:styled-content>6 and <jats:styled-content style=\"fixed-case\">HepT<\/jats:styled-content>1) after treatment with sorafenib using <jats:styled-content style=\"fixed-case\">MTT<\/jats:styled-content> and Caspase 3 activation assay. Extracellular signal\u2010regulated kinase (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>) phosphorylation was investigated using <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>estern blot. In addition, sorafenib (30\u00a0mg\/kg) was administered orally to <jats:styled-content style=\"fixed-case\">NMRI<\/jats:styled-content> mice bearing subcutaneous <jats:styled-content style=\"fixed-case\">HUH<\/jats:styled-content>6 derived tumours. Tumour progression and viability were monitored by tumour volume and \u03b1\u2010fetoprotein (<jats:styled-content style=\"fixed-case\">AFP<\/jats:styled-content>) levels, and apoptosis was assessed using <jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content> assay. Tumour angiogenesis and mean vascular density (<jats:styled-content style=\"fixed-case\">MVD<\/jats:styled-content>) was determined using <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>31 staining, <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> phosphorylation was detected using indirect immunofluorescence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with sorafenib led to decreased <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> phosphorylation, reduced cell viability and induction of apoptosis in <jats:styled-content style=\"fixed-case\">HepT<\/jats:styled-content>1 and <jats:styled-content style=\"fixed-case\">HUH<\/jats:styled-content>6 cells. In <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content> xenografts, sorafenib significantly reduced tumour growth compared with control (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). <jats:styled-content style=\"fixed-case\">AFP<\/jats:styled-content> levels were lower in the sorafenib group (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.07). Relative apoptotic areas detected using <jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content> assay were increased (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.003). <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>31 staining revealed inhibition of angiogenesis, and mean vascular density was lower in the sorafenib group (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02). <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> phosphorylation was reduced in tumours tissues after sorafenib treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Treatment with sorafenib led to a potent inhibition of cell viability, tumour progression and angiogenesis. Sorafenib might therefore also be a promising treatment option for high risk or recurrent HB.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1478-3231.2011.02729.x","type":"journal-article","created":{"date-parts":[[2011,12,19]],"date-time":"2011-12-19T02:03:37Z","timestamp":1324260217000},"page":"574-581","source":"Crossref","is-referenced-by-count":17,"title":["Treatment effects of the multikinase inhibitor sorafenib on hepatoblastoma cell lines and xenografts in <scp>NMRI<\/scp>\u2010<scp>Foxn1<sup>nu<\/sup><\/scp> mice"],"prefix":"10.1111","volume":"32","author":[{"given":"Carmen","family":"Eicher","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery and Urology University Children's Hospital Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Dewerth","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Urology University Children's Hospital Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Kirchner","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Urology University Children's Hospital Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W.","family":"Warmann","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Urology University Children's Hospital Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Urology University Children's Hospital Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorin","family":"Armeanu\u2010Ebinger","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery and Urology University Children's Hospital Tuebingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,12,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.4857"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1443"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0013"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0708857"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.01.3441"},{"key":"e_1_2_7_7_1","first-page":"1","article-title":"Establishment of a cell line and its clonal sublines from a patient with hepatoblastoma","volume":"67","author":"Doi I","year":"1976","journal-title":"Gann"},{"key":"e_1_2_7_8_1","first-page":"809","article-title":"Characterization of the continuous cell line HepT1 derived from a human hepatoblastoma","volume":"74","author":"Pietsch T","year":"1996","journal-title":"Lab Invest"},{"key":"e_1_2_7_9_1","first-page":"4607","article-title":"P\u2010glycoprotein modulation improves in vitro chemosensitivity in malignant pediatric liver tumors","volume":"23","author":"Warmann S","year":"2003","journal-title":"Anticancer Res"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2006.04.002"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.11.002"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.12-4-426"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810613"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3468(95)90762-9"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10632"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.14.2665"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(00)00018-8"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/jpsu.2002.32886"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800908783497113"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.11-7-753"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2007.03.054"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207785"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1377"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208841"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0808"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.23295"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1478-3231.2011.02729.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1478-3231.2011.02729.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T03:19:27Z","timestamp":1698635967000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1478-3231.2011.02729.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,18]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012,4]]}},"alternative-id":["10.1111\/j.1478-3231.2011.02729.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1478-3231.2011.02729.x","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,18]]}}}