{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T04:36:25Z","timestamp":1783744585300,"version":"3.55.0"},"reference-count":53,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001501","name":"University Grants Commission","doi-asserted-by":"publisher","award":["7-32\/2007"],"award-info":[{"award-number":["7-32\/2007"]}],"id":[{"id":"10.13039\/501100001501","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","em-consulte.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomedicine & Pharmacotherapy"],"published-print":{"date-parts":[[2016,12]]},"DOI":"10.1016\/j.biopha.2016.10.078","type":"journal-article","created":{"date-parts":[[2016,11,4]],"date-time":"2016-11-04T23:01:49Z","timestamp":1478300509000},"page":"1679-1688","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":79,"special_numbering":"C","title":["\u201cHepatocellular carcinoma: A life-threatening disease\u201d"],"prefix":"10.1016","volume":"84","author":[{"given":"Shinu","family":"Chacko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subir","family":"Samanta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.biopha.2016.10.078_bib0005","series-title":"Modern Pharmacology with Clinical Applications","author":"Craig","year":"2004"},{"key":"10.1016\/j.biopha.2016.10.078_bib0010","series-title":"Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012","author":"Globocan","year":"2012"},{"issue":"12","key":"10.1016\/j.biopha.2016.10.078_bib0015","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/j.1753-4887.2007.tb00280.x","article-title":"Enhancing the efficacy of hepatocellular carcinoma chemotherapeutics with natural anticancer agents","volume":"65","author":"Alisi","year":"2007","journal-title":"Nutr. Rev."},{"issue":"3","key":"10.1016\/j.biopha.2016.10.078_bib0020","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1053\/jhep.2003.50093","article-title":"Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis","volume":"37","author":"Vel\u00e1zquez","year":"2003","journal-title":"Hepatology"},{"issue":"Suppl. 3","key":"10.1016\/j.biopha.2016.10.078_bib0025","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1016\/j.jceh.2014.05.013","article-title":"Epidemiology of hepatocellular carcinoma in India","volume":"4","author":"Acharya","year":"2014","journal-title":"J. Clin. Exp. Hepatol."},{"issue":"12","key":"10.1016\/j.biopha.2016.10.078_bib0030","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1056\/NEJMra1001683","article-title":"Hepatocellular carcinoma","volume":"365","author":"El-Serag","year":"2011","journal-title":"N. Engl. J. Med."},{"issue":"5","key":"10.1016\/j.biopha.2016.10.078_bib0035","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1053\/j.gastro.2004.09.014","article-title":"Hepatocellular carcinoma in cirrhosis: incidence and risk factors","volume":"127","author":"Fattovich","year":"2004","journal-title":"Gastroenterology"},{"issue":"4","key":"10.1016\/j.biopha.2016.10.078_bib0040","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/aje\/155.4.323","article-title":"Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women","volume":"155","author":"Donato","year":"2002","journal-title":"Am. J. Epidemiol."},{"issue":"5","key":"10.1016\/j.biopha.2016.10.078_bib0045","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1053\/jhep.2003.50193","article-title":"Nonalcoholic steatohepatitis: summary of an AASLD single topic conference","volume":"37","author":"Neuschwander-Tetri","year":"2003","journal-title":"Hepatology"},{"issue":"3","key":"10.1016\/j.biopha.2016.10.078_bib0050","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2174\/1573409911666151103114300","article-title":"Novel thiosemicarbazide hybrids with amino acids and peptides against hepatocellular carcinoma: a molecular designing approach towards multikinase inhibitor","volume":"11","author":"Chacko","year":"2015","journal-title":"Curr. Comp.-Aided Drug Des."},{"issue":"9","key":"10.1016\/j.biopha.2016.10.078_bib0055","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nrc1934","article-title":"Hepatocellular carcinoma pathogenesis: from genes to environment","volume":"6","author":"Farazi","year":"2006","journal-title":"Nat. Rev. Cancer"},{"issue":"02","key":"10.1016\/j.biopha.2016.10.078_bib0060","article-title":"Management of hepatocellular carcinoma: an update at the start of 2014","volume":"04","author":"Gaetano","year":"2014","journal-title":"J. Gastrointest. Dig. Syst."},{"issue":"9","key":"10.1016\/j.biopha.2016.10.078_bib0065","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1002\/cncr.29936","article-title":"Annual Report to the Nation on the Status of Cancer, 1975\u20102012, featuring the increasing incidence of liver cancer","volume":"122","author":"Ryerson","year":"2016","journal-title":"Cancer"},{"issue":"1","key":"10.1016\/j.biopha.2016.10.078_bib0070","first-page":"7","article-title":"Cancer statistics, 2016","volume":"66","author":"Siegel","year":"2016","journal-title":"CA: Cancer J. Clin."},{"issue":"5","key":"10.1016\/j.biopha.2016.10.078_bib0075","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1093\/annonc\/mdw027","article-title":"The global decrease in cancer mortality: trends and disparities","volume":"27","author":"Hashim","year":"2016","journal-title":"Ann. Oncol."},{"issue":"1","key":"10.1016\/j.biopha.2016.10.078_bib0080","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/hep.22312","article-title":"Trends in mortality from hepatocellular carcinoma in Europe 1980\u20132004","volume":"48","author":"Bosetti","year":"2008","journal-title":"Hepatology"},{"key":"10.1016\/j.biopha.2016.10.078_bib0085","unstructured":"About national cancer registry programme. http:\/\/www.ncrpindia.org\/About_NCRP.aspx, 2016 (Accessed 01 September 2016)."},{"key":"10.1016\/j.biopha.2016.10.078_bib0090","unstructured":"National cancer registry programme: Three-year report of population based cancer registries 2012\u20132014. http:\/\/ncrpindia.org\/Annual_Reports.aspx, 2016 (Accessed 01 September 2016)."},{"issue":"1","key":"10.1016\/j.biopha.2016.10.078_bib0095","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1080\/13651820410024058","article-title":"Staging systems in hepatocellular carcinoma","volume":"7","author":"Pons","year":"2005","journal-title":"HPB: Off. J. Int. Hepato Pancreato Biliary Assoc."},{"issue":"9399","key":"10.1016\/j.biopha.2016.10.078_bib0100","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/S0140-6736(03)14964-1","article-title":"Hepatocellular carcinoma","volume":"362","author":"Llovet","year":"2003","journal-title":"Lancet"},{"issue":"11","key":"10.1016\/j.biopha.2016.10.078_bib0105","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1056\/NEJM199603143341104","article-title":"Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis","volume":"334","author":"Mazzaferro","year":"1996","journal-title":"N. Engl. J. Med."},{"issue":"3","key":"10.1016\/j.biopha.2016.10.078_bib0110","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1053\/jhep.2002.32089","article-title":"Prognostic prediction and treatment strategy in hepatocellular carcinoma","volume":"35","author":"Bruix","year":"2002","journal-title":"Hepatology"},{"issue":"15","key":"10.1016\/j.biopha.2016.10.078_bib0115","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.3748\/wjg.v20.i15.4115","article-title":"Hepatocellular carcinoma review: current treatment, and evidence-based medicine","volume":"20","author":"Raza","year":"2014","journal-title":"World J. Gastroenterol.: WJG"},{"issue":"s2","key":"10.1016\/j.biopha.2016.10.078_bib0120","doi-asserted-by":"crossref","DOI":"10.1111\/j.1872-034X.2007.00189.x","article-title":"Japanese experience in ablation therapies for hepatocellular carcinoma","volume":"37","author":"Shiina","year":"2007","journal-title":"Hepatol. Res."},{"key":"10.1016\/j.biopha.2016.10.078_bib0125","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1102\/1470-7330.2008.0004","article-title":"Thermal ablation of hepatocellular carcinoma","volume":"8","author":"Crocetti","year":"2008","journal-title":"Cancer Imaging"},{"issue":"3","key":"10.1016\/j.biopha.2016.10.078_bib0130","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1148\/radiology.210.3.r99fe40655","article-title":"Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection","volume":"210","author":"Livraghi","year":"1999","journal-title":"Radiology"},{"issue":"1","key":"10.1016\/j.biopha.2016.10.078_bib0135","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1007\/BF00687096","article-title":"Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma\u2014a comparison of lipiodol-transcatheter arterial embolization with and without Adriamycin (first cooperative study)","volume":"31","author":"Kawai","year":"1992","journal-title":"Cancer Chemother. Pharmacol."},{"issue":"2","key":"10.1016\/j.biopha.2016.10.078_bib0140","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1053\/jhep.2003.50047","article-title":"Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival","volume":"37","author":"Llovet","year":"2003","journal-title":"Hepatology"},{"issue":"6","key":"10.1016\/j.biopha.2016.10.078_bib0145","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.jhep.2012.07.017","article-title":"Comparative study between doxorubicin-eluting beads and conventional transarterial chemoembolization for treatment of hepatocellular carcinoma","volume":"57","author":"Song","year":"2012","journal-title":"J. Hepatol."},{"issue":"5","key":"10.1016\/j.biopha.2016.10.078_bib0150","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1159\/000348325","article-title":"Treatment for hepatocellular carcinoma with portal vein tumor thrombosis: the emerging role for radioembolization using yttrium-90","volume":"84","author":"Lau","year":"2013","journal-title":"Oncology"},{"issue":"2","key":"10.1016\/j.biopha.2016.10.078_bib0155","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1053\/j.gastro.2010.10.049","article-title":"Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma","volume":"140","author":"Salem","year":"2011","journal-title":"Gastroenterology"},{"issue":"2","key":"10.1016\/j.biopha.2016.10.078_bib0160","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.jhep.2011.07.012","article-title":"Radioembolization for hepatocellular carcinoma","volume":"56","author":"Sangro","year":"2012","journal-title":"J. Hepatol."},{"issue":"1","key":"10.1016\/j.biopha.2016.10.078_bib0165","doi-asserted-by":"crossref","first-page":"48","DOI":"10.4161\/onci.1.1.18344","article-title":"Immunotherapy of hepatocellular carcinoma: unique challenges and clinical opportunities","volume":"1","author":"Pardee","year":"2012","journal-title":"Oncoimmunology"},{"issue":"7","key":"10.1016\/j.biopha.2016.10.078_bib0170","doi-asserted-by":"crossref","first-page":"980","DOI":"10.4254\/wjh.v7.i7.980","article-title":"Immunotherapy for hepatocellular carcinoma: from basic research to clinical use","volume":"7","author":"Hong","year":"2015","journal-title":"World J. Hepatol."},{"issue":"16","key":"10.1016\/j.biopha.2016.10.078_bib0175","first-page":"5902","article-title":"T-cell responses to HLA-A* 0201 immunodominant peptides derived from \u03b1-fetoprotein in patients with hepatocellular cancer","volume":"9","author":"Butterfield","year":"2003","journal-title":"Clin. Cancer Res."},{"issue":"9","key":"10.1016\/j.biopha.2016.10.078_bib0180","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1158\/1078-0432.CCR-05-2267","article-title":"Identification of HLA-A2-or HLA-A24-restricted CTL epitopes possibly useful for glypican-3-specific immunotherapy of hepatocellular carcinoma","volume":"12","author":"Komori","year":"2006","journal-title":"Clin. Cancer Res."},{"issue":"1","key":"10.1016\/j.biopha.2016.10.078_bib0185","doi-asserted-by":"crossref","first-page":"e0004","DOI":"10.5041\/RMMJ.10179","article-title":"Adoptive T cell immunotherapy for cancer","volume":"6","author":"Perica","year":"2015","journal-title":"Rambam Maimonides Med. J."},{"issue":"4","key":"10.1016\/j.biopha.2016.10.078_bib0190","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1056\/NEJMoa0708857","article-title":"Sorafenib in advanced hepatocellular carcinoma","volume":"359","author":"JM","year":"2008","journal-title":"N. Engl. J. Med."},{"issue":"10","key":"10.1016\/j.biopha.2016.10.078_bib0195","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.4155\/cli.11.116","article-title":"Personalized medicine in hepatocellular carcinoma: rationale and clinical data","volume":"1","author":"Pipa-Muniz","year":"2011","journal-title":"Clin. Investig."},{"issue":"2","key":"10.1016\/j.biopha.2016.10.078_bib0200","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/j.1365-2036.2011.04697.x","article-title":"The combination of sorafenib with transarterial chemoembolisation for hepatocellular carcinoma","volume":"34","author":"Cabrera","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"10.1016\/j.biopha.2016.10.078_bib0205","article-title":"Yttirum-90 resin microspheres as an adjunct to sorafenib in patients with unresectable HCC: A retrospective study for evaluation of survival benefit and adverse events","author":"Gadani","year":"2013","journal-title":"Soc. Interventional Radiol. Ann. Sci. Meeting"},{"issue":"12","key":"10.1016\/j.biopha.2016.10.078_bib0210","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1007\/s10822-014-9800-9","article-title":"Identification of novel inhibitors of human Chk1 using pharmacophore-based virtual screening and their evaluation as potential anti-cancer agents","volume":"28","author":"Kumar","year":"2014","journal-title":"J. Comput. Aided. Mol. Des."},{"issue":"4","key":"10.1016\/j.biopha.2016.10.078_bib0215","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1053\/j.seminoncol.2012.05.005","article-title":"Molecular targeted therapies in hepatocellular carcinoma","volume":"39","author":"Tanaka","year":"2012","journal-title":"Semin. Oncol."},{"issue":"6","key":"10.1016\/j.biopha.2016.10.078_bib0220","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1111\/cbdd.12036","article-title":"Discovery of novel vascular endothelial growth factor receptor 2 inhibitors: a virtual screening approach","volume":"80","author":"Zhang","year":"2012","journal-title":"Chem. Biol. Drug Des."},{"issue":"3","key":"10.1016\/j.biopha.2016.10.078_bib0225","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12032-014-0844-4","article-title":"Checkpoint kinase 1 is negatively regulated by miR-497 in hepatocellular carcinoma","volume":"31","author":"Xie","year":"2014","journal-title":"Med. Oncol."},{"issue":"5","key":"10.1016\/j.biopha.2016.10.078_bib0230","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.tips.2011.02.014","article-title":"Anticancer therapy with checkpoint inhibitors: what, where and when?","volume":"32","author":"Garrett","year":"2011","journal-title":"Trends Pharmacol. Sci."},{"issue":"6","key":"10.1016\/j.biopha.2016.10.078_bib0235","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.dld.2007.01.025","article-title":"Antisense integrin alphaV and beta3 gene therapy suppresses subcutaneously implanted hepatocellular carcinomas","volume":"39","author":"Li","year":"2007","journal-title":"Dig. Liver Dis."},{"issue":"1","key":"10.1016\/j.biopha.2016.10.078_bib0240","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/5289","article-title":"Cancer multidrug resistance","volume":"17","author":"Persidis","year":"2000","journal-title":"Nat. Biotechnol."},{"issue":"5","key":"10.1016\/j.biopha.2016.10.078_bib0245","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/S0169-409X(02)00045-5","article-title":"Poly (L-glutamic acid)\u2013anticancer drug conjugates","volume":"54","author":"Li","year":"2002","journal-title":"Adv. Drug. Deliv. Rev."},{"issue":"8","key":"10.1016\/j.biopha.2016.10.078_bib0250","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1021\/ol034032d","article-title":"Peptide heterocycle conjugates: a diverted edman degradation protocol for the synthesis of N-terminal 2-Iminohydantoins","volume":"5","author":"Evindar","year":"2003","journal-title":"Org. Lett."},{"issue":"1","key":"10.1016\/j.biopha.2016.10.078_bib0255","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1476-5381.1960.tb01216.x","article-title":"The structure\u2010activity relashionship of the antiviral chemotherapeutic activity of Isatin \u03b2-thiosemicarbazone","volume":"15","author":"Bauer","year":"1960","journal-title":"Br. J. Pharm. Chemother."},{"issue":"9","key":"10.1016\/j.biopha.2016.10.078_bib0260","doi-asserted-by":"crossref","first-page":"4702","DOI":"10.1016\/j.ejmech.2011.07.016","article-title":"Synthesis, molecular modeling and biological evaluation of chalcone thiosemicarbazide derivatives as novel anticancer agents","volume":"46","author":"Zhang","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.biopha.2016.10.078_bib0265","first-page":"309","article-title":"Anticancer agents: III synthesis and anticancer activity of some bisthiosemicarbazones and thiosemicarbazides","author":"Barry","year":"1966","journal-title":"Proceedings of the Royal Irish Academy Section B: Biological, Geological, and Chemical Science, JSTOR"}],"container-title":["Biomedicine & Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332216315803?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332216315803?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T22:42:18Z","timestamp":1773873738000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0753332216315803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12]]},"references-count":53,"alternative-id":["S0753332216315803"],"URL":"https:\/\/doi.org\/10.1016\/j.biopha.2016.10.078","relation":{},"ISSN":["0753-3322"],"issn-type":[{"value":"0753-3322","type":"print"}],"subject":[],"published":{"date-parts":[[2016,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"\u201cHepatocellular carcinoma: A life-threatening disease\u201d","name":"articletitle","label":"Article Title"},{"value":"Biomedicine & Pharmacotherapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biopha.2016.10.078","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}]}}