{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:46:00Z","timestamp":1791323160763,"version":"4.3.1"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2013,1,7]],"date-time":"2013-01-07T00:00:00Z","timestamp":1357516800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0052940","type":"journal-article","created":{"date-parts":[[2013,1,8]],"date-time":"2013-01-08T22:32:21Z","timestamp":1357684341000},"page":"e52940","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Synthesized Multiple Antigenic Polypeptide Vaccine Based on B-Cell Epitopes of Human Heparanase Could Elicit a Potent Antimetastatic Effect on Human Hepatocellular Carcinoma In Vivo"],"prefix":"10.1371","volume":"8","author":[{"given":"Jun","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-min","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-ju","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-qing","family":"Ru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai-ming","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2013,1,7]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1159\/000218339","article-title":"Hepatocellular carcinoma \u2013epidemiological trends and risk factors","volume":"27","author":"K Schutte","year":"2009","journal-title":"Dig Dis"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1002\/hep.22506","article-title":"Molecular targeted therapies in hepatocellular carcinoma","volume":"48","author":"JM Llovet","year":"2008","journal-title":"Hepatology"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/S0140-6736(03)14964-1","article-title":"Hepatocellular carcinoma","volume":"362","author":"JM Llovet","year":"2003","journal-title":"Lancet"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"4475","DOI":"10.1002\/cncr.25960","article-title":"Hepatocellular carcinoma with extrahepatic metastasis: clinical features and prognostic factors","volume":"117","author":"K Uchino","year":"2011","journal-title":"Cancer"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0092-8674(94)90187-2","article-title":"The implications of angiogenesis for the biology and therapy of cancer metastasis","volume":"79","author":"IJ Fidler","year":"1994","journal-title":"Cell"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1152\/ajpcell.2001.280.6.C1358","article-title":"Role of vascular endothelial growth factor in regulation of physiological angiogenesis","volume":"280","author":"N Ferrara","year":"2001","journal-title":"Am J Physiol Cell Physiol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/jb\/mvr060","article-title":"Critical role of c-Jun N-terminal kinase in regulating bFGF-induced angiogenesis in vitro","volume":"150","author":"S Kaikai","year":"2011","journal-title":"J Biochem"},{"key":"ref8","first-page":"9","article-title":"Intratumor microvessel density as a prognostic factor in cancer","volume":"147","author":"N Weidner","year":"1995","journal-title":"Am J Pathol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jss.2007.03.023","article-title":"Basement membrane proteins play an important role in the invasive processes of human pancreatic cancer cells","volume":"144","author":"H Sawai","year":"2008","journal-title":"J Surg Res"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.2174\/138161207781039742","article-title":"Heparanase: structure, biologica functions, and inhibition by heparin-derived mimetics of heparin sulfate","volume":"13","author":"I Vlodavsky","year":"2007","journal-title":"Curr Pharm Des"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/jcb.22005","article-title":"Cell surface heparan sulfate released by heparanase promotes melanoma cell migration and angiogenesis","volume":"106","author":"M Roy","year":"2009","journal-title":"J Cell Biochem"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1073\/pnas.0812846106","article-title":"Alternatively spliced Spalax heparanase inhibits extracellular matrix degradation, tumor growth, and metastasis","volume":"106","author":"NJ Nasser","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"8779","DOI":"10.1158\/0008-5472.CAN-06-1382","article-title":"Oligomannurarate sulfate, a novel heparanase inhibitor simultaneously targeting basicWbroblast growth factor, combats tumor angiogenesis and metastasis","volume":"66","author":"H Zhao","year":"2006","journal-title":"Cancer Res"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.2174\/092986706777935230","article-title":"Development of heparanase inhibitors for anti-cancer therapy","volume":"13","author":"HQ Miao","year":"2006","journal-title":"Curr Med Chem"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1080\/03008200802143281","article-title":"Heparanase: one molecule with multiple functions in cancer progression","volume":"49","author":"I Vlodavsky","year":"2008","journal-title":"Connect Tissue Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1055\/s-2007-982088","article-title":"PI-88 and novel heparin sulfate mimetics inhibit angiogenesis","volume":"33","author":"V Ferro","year":"2007","journal-title":"Semin Thromb Hemost"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1006\/scbi.2001.0420","article-title":"Mammalian heparanase: involvement in cancer metastasis, angiogenesis and normal development","volume":"12","author":"I Vlodavsky","year":"2002","journal-title":"Semin Cancer Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1007\/s00262-008-0651-x","article-title":"Screening and identification of novel B cell epitopes in human heparanase and their anti-invasion property for hepatocellular carcinoma","volume":"58","author":"JM Yang","year":"2009","journal-title":"Cancer Immunol Immunother"},{"key":"ref19","first-page":"869","article-title":"T-helper epitope peptide improves immunological effects of the B cell epitopes of human heparanase protein","volume":"28","author":"L Du","year":"2008","journal-title":"Chin J Microbiol Immunol"},{"key":"ref20","first-page":"455","article-title":"One Simple and Efficient Method for Purification of IgG Ab from Mice Ascites and Sera: Caprylic Acid\/Ammonium Sulfate Precipitation","volume":"30","author":"XB Liu","year":"1999","journal-title":"J WCUMS"},{"key":"ref21","first-page":"10","article-title":"Effects of anti-heparanase antibody on the growth and invasion of HCCLM6 human hepatocellular carcinoma cells","volume":"31","author":"XM Han","year":"2009","journal-title":"Chin J Oncology"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1097\/00008469-200308000-00006","article-title":"Twenty-year trends of primary liver cancer incidence rate in an urban Chinese population","volume":"12","author":"XS Hao","year":"2003","journal-title":"Eur J Can Prev"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/sj.bjp.0707182","article-title":"Heparanase: a target for drug discovery in cancer and inflammation","volume":"151","author":"EA McKenzie","year":"2007","journal-title":"Br J Pharmacol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1016\/j.biocel.2006.06.004","article-title":"Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis","volume":"12","author":"N Ilan","year":"2006","journal-title":"Int J Biochem Cell Biol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1002\/eji.201190035","article-title":"Cancer immunotherapy: Progress and challenges in the clinical setting","volume":"41","author":"HM Zarour","year":"2011","journal-title":"Eur J Immunol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"7716","DOI":"10.1158\/0008-5472.CAN-05-2363","article-title":"Heparanase: a new metastasis-associated antigen recognized in breast cancer patients by spontaneously induced memory T lymphocytes","volume":"66","author":"N Sommerfeldt","year":"2006","journal-title":"Cancer Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/sj.bjc.6690769","article-title":"New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis","volume":"81","author":"J Tian","year":"1999","journal-title":"Br J Cancer"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00432-003-0511-1","article-title":"A decade's studies on metastasis of hepatocellular carcinoma","volume":"130","author":"ZY Tang","year":"2004","journal-title":"J Cancer Res Clin Oncol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"630","DOI":"10.3748\/wjg.v7.i5.630","article-title":"Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97","volume":"5","author":"Y Li","year":"2001","journal-title":"World J Gastroenterol"},{"key":"ref30","first-page":"12264","article-title":"Research Progress in Animal Models of Liver Cancer","volume":"20","author":"FG Shen","year":"2011","journal-title":"Journal of Anhui Agri Sci"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1128\/IAI.31.3.1125-1131.1981","article-title":"Serological and Biological Activities of Anti-Haemophilus influenzae Ribosomal Serum","volume":"31","author":"M Katz","year":"1981","journal-title":"Infect Immun"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1093\/annonc\/mdl476","article-title":"A review of the use of trastuzumab (Herceptin) plus vinorelbine in metastatic breast cancer","volume":"18","author":"A Chan","year":"2007","journal-title":"Ann Oncol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"20457","DOI":"10.1074\/jbc.M414546200","article-title":"Identification and characterization of heparin\/heparan sulfate binding domains of the endoglycosidase heparanase","volume":"21","author":"F Levy-Adam","year":"2005","journal-title":"J Biol Chem"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s004320050025","article-title":"Expression of vascular endothelial growth factor in surgical specimens of hepatocellular carcinoma","volume":"126","author":"FQ An","year":"2000","journal-title":"J Cancer Res Clin Oncol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/00000658-200102000-00012","article-title":"Serum vascular endothelial growth factor predicts venous invasion in hepatocellular carcinoma: a prospective study","volume":"233","author":"RT Poon","year":"2011","journal-title":"Ann Surg"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s12020-011-9502-1","article-title":"Significance of heparanase-1 and vascular endothelial growth factor in adrenocortical carcinoma angiogenesis: potential for therapy","volume":"40","author":"YZ Xu","year":"2011","journal-title":"Endocrine"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"e2319","DOI":"10.1371\/journal.pone.0002319","article-title":"Heparanase facilitates cell adhesion and spreading by clustering of cell surface heparan sulfate proteoglycans","volume":"6","author":"F Levy-Adam","year":"2008","journal-title":"PLoS One"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0226124","type":"expression_of_concern","label":"Expression of concern","source":"retraction-watch","updated":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T00:00:00Z","timestamp":1575244800000},"record-id":"21715"},{"DOI":"10.1371\/journal.pone.0226124","type":"expression_of_concern","label":"Expression of concern","source":"publisher","updated":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T00:00:00Z","timestamp":1575244800000}}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0052940","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T02:03:11Z","timestamp":1595210591000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0052940"}},"subtitle":[],"editor":[{"given":"Irina V.","family":"Lebedeva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,1,7]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2013,1,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0052940","relation":{"expression_of_concern":[{"id-type":"doi","id":"10.1371\/journal.pone.0226124","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,7]]}}}