{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:12:18Z","timestamp":1793293938436,"version":"4.5.0"},"reference-count":405,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["18\/10953-9"],"award-info":[{"award-number":["18\/10953-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["16\/14420-0"],"award-info":[{"award-number":["16\/14420-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["16\/12015-0"],"award-info":[{"award-number":["16\/12015-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["310557\/2019-4"],"award-info":[{"award-number":["310557\/2019-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["Finance code 001"],"award-info":[{"award-number":["Finance code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FWO Vlaanderen","award":["G009514N and G010214N"],"award-info":[{"award-number":["G009514N and G010214N"]}]},{"name":"University Hospital of the Vrije Universiteit Brussel-Belgium","award":["Willy Gepts Fonds UZ-Brussel"],"award-info":[{"award-number":["Willy Gepts Fonds UZ-Brussel"]}]},{"name":"Center for Alternatives to Animal Testing (Johns Hopkins University)","award":["2018-13"],"award-info":[{"award-number":["2018-13"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related death globally. HCC is a complex multistep disease and usually emerges in the setting of chronic liver diseases. The molecular pathogenesis of HCC varies according to the etiology, mainly caused by chronic hepatitis B and C virus infections, chronic alcohol consumption, aflatoxin-contaminated food, and non-alcoholic fatty liver disease associated with metabolic syndrome or diabetes mellitus. The establishment of HCC models has become essential for both basic and translational research to improve our understanding of the pathophysiology and unravel new molecular drivers of this disease. The ideal model should recapitulate key events observed during hepatocarcinogenesis and HCC progression in view of establishing effective diagnostic and therapeutic strategies to be translated into clinical practice. Despite considerable efforts currently devoted to liver cancer research, only a few anti-HCC drugs are available, and patient prognosis and survival are still poor. The present paper provides a state-of-the-art overview of in vivo and in vitro models used for translational modeling of HCC with a specific focus on their key molecular hallmarks.<\/jats:p>","DOI":"10.3390\/cancers13215583","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T08:05:16Z","timestamp":1636358716000},"page":"5583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling"],"prefix":"10.3390","volume":"13","author":[{"given":"Guilherme Ribeiro","family":"Romualdo","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of S\u00e3o Paulo (USP), S\u00e3o Paulo 05508-270, Brazil"},{"name":"Department of Structural and Functional Biology, Biosciences Institute, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, Brazil"},{"name":"Department of Pathology, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaat","family":"Leroy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00edcero J\u00falio Silva","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of S\u00e3o Paulo (USP), S\u00e3o Paulo 05508-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3840-7749","authenticated-orcid":false,"given":"Gabriel Bacil","family":"Prata","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Biosciences Institute, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, Brazil"},{"name":"Department of Pathology, Botucatu Medical School, S\u00e3o Paulo State University (UNESP), Botucatu 18618-687, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Vanderborght","sequence":"additional","affiliation":[{"name":"Gut-Liver Immunopharmacology Unit, Basic and Applied Medical Sciences, Liver Research Center Ghent, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium"},{"name":"Hepatology Research Unit, Internal Medicine and Paediatrics, Liver Research Center Ghent, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tereza Cristina","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of S\u00e3o Paulo (USP), S\u00e3o Paulo 05508-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2180-1814","authenticated-orcid":false,"given":"Lu\u00eds Fernando","family":"Barbisan","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Biosciences Institute, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wellington","family":"Andraus","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Clinics Hospital, School of Medicine, University of S\u00e3o Paulo (HC-FMUSP), S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4862-9580","authenticated-orcid":false,"given":"Lindsey","family":"Devisscher","sequence":"additional","affiliation":[{"name":"Hepatology Research Unit, Internal Medicine and Paediatrics, Liver Research Center Ghent, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5436-1248","authenticated-orcid":false,"given":"Niels Olsen Saraiva","family":"C\u00e2mara","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences IV, University of S\u00e3o Paulo (USP), S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5115-8893","authenticated-orcid":false,"given":"Mathieu","family":"Vinken","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1388-7240","authenticated-orcid":false,"given":"Bruno","family":"Cogliati","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of S\u00e3o Paulo (USP), S\u00e3o Paulo 05508-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1038\/sj.bjc.6602590","article-title":"Survival rate in patients with hepatocellular carcinoma: A retrospective analysis of 389 patients","volume":"92","author":"Greten","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Op den Winkel, M., Nagel, D., Sappl, J., op den Winkel, P., Lamerz, R., Zech, C.J., Straub, G., Nickel, T., Rentsch, M., and Stieber, P. (2012). Prognosis of Patients with Hepatocellular Carcinoma. Validation and Ranking of Established Staging-Systems in a Large Western HCC-Cohort. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045066"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.cgh.2010.08.019","article-title":"Cirrhosis Is Present in Most Patients With Hepatitis B and Hepatocellular Carcinoma","volume":"9","author":"Yang","year":"2011","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/CEJ.0000000000000428","article-title":"Worldwide incidence of hepatocellular carcinoma cases attributable to major risk factors","volume":"27","author":"Baecker","year":"2018","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Makarova-rusher, O.V., Altekruse, S.F., Mcneel, T.S., Ulahannan, S., Duffy, A.G., Graubard, B.I., Greten, T.F., and Mcglynn, K.A. (2016). Population Attributable Fractions of Risk Factors for Hepatocellular Carcinoma in the United States. Cancer, 1757\u20131765.","DOI":"10.1002\/cncr.29971"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.cgh.2013.04.039","article-title":"Coffee Reduces Risk for Hepatocellular Carcinoma: An Updated Meta-analysis","volume":"11","author":"Bravi","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1097\/CEJ.0000000000000252","article-title":"Coffee and the risk of hepatocellular carcinoma and chronic liver disease: A systematic review and meta-analysis of prospective studies","volume":"26","author":"Bravi","year":"2017","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nrc4017","article-title":"Functional and genetic deconstruction of the cellular origin in liver cancer","volume":"15","author":"Marquardt","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"573","DOI":"10.2174\/1566524033479546","article-title":"Mechanisms of Human Hepatocarcinogenesis","volume":"3","author":"Coleman","year":"2003","journal-title":"Curr. Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1007\/s13238-014-0065-9","article-title":"The genetic and epigenetic alterations in human hepatocellular carcinoma: A recent update","volume":"5","author":"Liu","year":"2014","journal-title":"Protein Cell"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Llovet, J.M., Kelley, R.K., Villanueva, A., Singal, A.G., Pikarsky, E., Roayaie, S., Lencioni, R., Koike, K., Zucman-Rossi, J., and Finn, R.S. (2021). Hepatocellular carcinoma. Nat. Rev. Dis. Prim., 7.","DOI":"10.1038\/s41572-020-00240-3"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.cell.2017.05.046","article-title":"Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma","volume":"169","author":"Ally","year":"2017","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/s41575-018-0033-6","article-title":"Mouse models of hepatocellular carcinoma: An overview and highlights for immunotherapy research","volume":"15","author":"Brown","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nri2017","article-title":"Humanized mice in translational biomedical research","volume":"7","author":"Shultz","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"20160","DOI":"10.18632\/oncotarget.3969","article-title":"Genomic characterization of a large panel of patient-derived hepatocellular carcinoma xenograft tumor models for preclinical development","volume":"6","author":"Gu","year":"2015","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1136\/gutjnl-2017-315201","article-title":"Development of a new patient-derived xenograft humanised mouse model to study human-specific tumour microenvironment and immunotherapy","volume":"67","author":"Zhao","year":"2018","journal-title":"Gut"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/301527a0","article-title":"A severe combined immunodeficiency mutation in the mouse","volume":"301","author":"Bosma","year":"1983","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"180","DOI":"10.4049\/jimmunol.154.1.180","article-title":"Multiple defects in innate and adaptive immunologic function in NOD\/LtSz-scid mice","volume":"154","author":"Shultz","year":"1995","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/(SICI)1097-0215(19960410)66:2<239::AID-IJC17>3.0.CO;2-7","article-title":"Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues","volume":"66","author":"Sun","year":"1996","journal-title":"Int. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1002\/hep.510300420","article-title":"Cell motility mediated by rho and rho-associated protein kinase plays a critical role in intrahepatic metastasis of human hepatocellular carcinoma","volume":"30","author":"Genda","year":"1999","journal-title":"Hepatology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1002\/hep4.1365","article-title":"Hepatocellular Carcinoma Xenografts Established From Needle Biopsies Preserve the Characteristics of the Originating Tumors","volume":"3","author":"Blumer","year":"2019","journal-title":"Hepatol. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6477","DOI":"10.4049\/jimmunol.174.10.6477","article-title":"Human Lymphoid and Myeloid Cell Development in NOD\/LtSz- scid IL2R \u03b3 null Mice Engrafted with Mobilized Human Hemopoietic Stem Cells","volume":"174","author":"Shultz","year":"2005","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/S0928-4346(05)80004-0","article-title":"Establishment and characterization of liver metastatic model of human hepatoma in nude mice","volume":"1","author":"Aruga","year":"1993","journal-title":"Int. Hepatol. Commun."},{"key":"ref_27","first-page":"289","article-title":"Establishment of NOD\/SCID mouse models of human hepatocellular carcinoma via subcutaneous transplantation of histologically intact tumor tissue","volume":"25","author":"Yan","year":"2013","journal-title":"Chinese J. Cancer Res."},{"key":"ref_28","unstructured":"(2012). International Agency for Research on Cancer IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans: Chemical Agents and Related Occu-pations. IARC Monogr. Eval. Carcinog. Risks Chem. Man., 10F, 1\u2013628."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1080\/02652039209374046","article-title":"Review of the occurrence and formation of non-volatile N -nitroso compounds in foods","volume":"9","author":"Tricker","year":"1992","journal-title":"Food Addit. Contam."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S1383-5742(99)00015-0","article-title":"N-Nitroso compounds in the diet","volume":"443","author":"Lijinsky","year":"1999","journal-title":"Mutat. Res. Toxicol. Environ. Mutagen."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1093\/toxsci\/61.1.92","article-title":"DNA Damage Induced by Red Food Dyes Orally Administered to Pregnant and Male Mice","volume":"61","author":"Tsuda","year":"2001","journal-title":"Toxicol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.foodchem.2014.11.101","article-title":"Formation and mitigation of N-nitrosamines in nitrite preserved cooked sausages","volume":"174","author":"Herrmann","year":"2015","journal-title":"Food Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11141","DOI":"10.1158\/0008-5472.CAN-07-1369","article-title":"Role of CYP2E1 in Diethylnitrosamine-Induced Hepatocarcinogenesis in vivo","volume":"67","author":"Kang","year":"2007","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1124\/jpet.117.245555","article-title":"Higher CYP2E1 Activity Correlates with Hepatocarcinogenesis Induced by Diethylnitrosamine","volume":"365","author":"Gao","year":"2018","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0163-7258(96)00062-9","article-title":"N-Nitrosodiethylamine mechanistic data and risk assessment: Bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation","volume":"71","author":"Verna","year":"1996","journal-title":"Pharmacol. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1073\/pnas.81.6.1692","article-title":"O4-ethyldeoxythymidine, but not O6-ethyldeoxyguanosine, accumulates in hepatocyte DNA of rats exposed continuously to diethylnitrosamine","volume":"81","author":"Swenberg","year":"1984","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1002\/hep.24133","article-title":"Evolution of genomic instability in diethylnitrosamine-induced hepatocarcinogenesis in mice","volume":"53","author":"Aleksic","year":"2011","journal-title":"Hepatology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.jhep.2018.06.009","article-title":"Mutational landscape of a chemically-induced mouse model of liver cancer","volume":"69","author":"Connor","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1016\/j.bbapap.2013.08.005","article-title":"Comparative proteomic analysis of thiol proteins in the liver after oxidative stress induced by diethylnitrosamine","volume":"1834","year":"2013","journal-title":"Biochim. Biophys. Acta-Proteins Proteom."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/j.1440-1827.2009.02416.x","article-title":"Molecular pathology of early stage chemically induced hepatocarcinogenesis","volume":"59","author":"Ogawa","year":"2009","journal-title":"Pathol. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/carcin\/7.2.215","article-title":"Interstrain differences in susceptibility to liver carcinogenesis initiated by N-nitrosodiethylamine and its promotion by phenobarbital in C57BL\/6NCr, C3H\/HeNCr MTV- and DBA\/2NCr mice","volume":"7","author":"Diwan","year":"1986","journal-title":"Carcinogenesis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1007\/BF00390974","article-title":"Carcinogenicity of diethylnitrosamine in newborn, infant, and adult mice","volume":"108","author":"Vesselinovitch","year":"1984","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0304-3835(90)90268-3","article-title":"Liver tumor promoting ability of corn oil gavage in B6C3F1 male mice","volume":"50","author":"Klaunig","year":"1990","journal-title":"Cancer Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1177\/0192623311409596","article-title":"Dose-Related Induction of Hepatic Preneoplastic Lesions by Diethylnitrosamine in C57BL\/6 Mice","volume":"39","author":"Kushida","year":"2011","journal-title":"Toxicol. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1177\/019262338801600310","article-title":"Dose-Response Relationship of Diethylnitrosamine-Initiated Tumors in Neonatal Balb\/c Mice: Effect of Phenobarbital Promotion","volume":"16","author":"Klaunig","year":"1988","journal-title":"Toxicol. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1093\/carcin\/10.8.1409","article-title":"Strain differences in hepatic tumor promotion by phenobarbital in diethylnitrosamine- and dimethylnitrosamine-initiated infant male mice","volume":"10","author":"Weghorst","year":"1989","journal-title":"Carcinogenesis"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1080\/01926230252824770","article-title":"Quantitation of the Cancer Process in C57BL\/6J, B6C3F1 and C3H\/HeJ Mice","volume":"30","author":"Goldsworthy","year":"2002","journal-title":"Toxicol. Pathol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/toxsci\/kfs342","article-title":"Molecular Mechanisms of Fibrosis-Associated Promotion of Liver Carcinogenesis","volume":"132","author":"Uehara","year":"2013","journal-title":"Toxicol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Memon, A., Pyao, Y., Jung, Y., Lee, J.I., and Lee, W.K. (2020). A Modified Protocol of Diethylnitrosamine Administration in Mice to Model Hepatocellular Carcinoma. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155461"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/0304-3835(86)90183-7","article-title":"Dose-response relationship of phenobarbital promotion of diethylnitrosamine initiated tumors in rat liver","volume":"32","author":"Pereira","year":"1986","journal-title":"Cancer Lett."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0300-483X(01)00447-4","article-title":"Suppressive effect of irsogladine maleate on N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-initiated and glyoxal-promoted gastric carcinogenesis in rats","volume":"166","author":"Sugie","year":"2001","journal-title":"Toxicology"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Tan, Y., Yin, P., Tang, L., Xing, W., Huang, Q., Cao, D., Zhao, X., Wang, W., Lu, X., and Xu, Z. (2012). Metabolomics Study of Stepwise Hepatocarcinogenesis From the Model Rats to Patients: Potential Biomarkers Effective for Small Hepatocellular Carcinoma Diagnosis. Mol. Cell. Proteom., 11.","DOI":"10.1074\/mcp.M111.010694"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s00432-017-2364-z","article-title":"Hepatic inflammation-fibrosis-cancer axis in the rat hepatocellular carcinoma induced by diethylnitrosamine","volume":"143","author":"Ding","year":"2017","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/nm.1994","article-title":"Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice","volume":"15","author":"Liu","year":"2009","journal-title":"Nat. Med."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Romualdo, G.R., Prata, G.B., da Silva, T.C., Fernandes, A.A.H., Moreno, F.S., Cogliati, B., and Barbisan, L.F. (2018). Fibrosis-associated hepatocarcinogenesis revisited: Establishing standard medium-term chemically-induced male and female models. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0203879"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0304-3835(94)90055-8","article-title":"Decreased hepatocarcinogenic effect of diethylnitrosamine in experimentally induced liver cirrhosis in rat: Delay or inhibition?","volume":"79","author":"Zalatnai","year":"1994","journal-title":"Cancer Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.toxlet.2017.09.015","article-title":"An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular features","volume":"281","author":"Romualdo","year":"2017","journal-title":"Toxicol. Lett."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1002\/mc.1022","article-title":"Sequential changes in hepatocarcinogenesis induced by diethylnitrosamine plus thioacetamide in Fischer 344 rats: Induction of gankyrin expression in liver fibrosis, pRB degradation in cirrhosis, and methylation ofp16INK4A exon 1 in hepatocellular carcinom","volume":"30","author":"Park","year":"2001","journal-title":"Mol. Carcinog."},{"key":"ref_59","first-page":"188","article-title":"Promotion of liver cancer development by brief exposure to dietary 2-acetylaminofluorene plus partial hepatectomy or carbon tetrachloride","volume":"43","author":"Solt","year":"1983","journal-title":"Cancer Res."},{"key":"ref_60","first-page":"2774","article-title":"Histochemical characterization of focal hepatic lesions induced by single diethylnitrosamine treatment in infant mice","volume":"45","author":"Vesselinovitch","year":"1985","journal-title":"Cancer Res."},{"key":"ref_61","first-page":"G493","article-title":"Yes-associated protein is involved in proliferation and differentiation during postnatal liver development","volume":"302","author":"Septer","year":"2012","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1126\/science.1140485","article-title":"Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production","volume":"317","author":"Naugler","year":"2007","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.mrgentox.2008.11.004","article-title":"Dose-dependent alterations in gene expression in mouse liver induced by diethylnitrosamine and ethylnitrosourea and determined by quantitative real-time PCR","volume":"673","author":"Watanabe","year":"2009","journal-title":"Mutat. Res. Toxicol. Environ. Mutagen."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1023\/A:1022438528634","article-title":"Early bioenergetic changes in hepatocarcinogenesis: Preneoplastic phenotypes mimic responses to insulin and thyroid hormone","volume":"29","author":"Bannasch","year":"1997","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1080\/01926230309732","article-title":"Relevance of Hepatic Preneoplasia for Human Hepatocarcinogenesis","volume":"31","author":"Su","year":"2003","journal-title":"Toxicol. Pathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1054\/ghir.2002.0261","article-title":"Diethylnitrosamine induces long-lasting re-expression of insulin-like growth factor II during early stages of liver carcinogenesis in mice","volume":"12","author":"Lahm","year":"2002","journal-title":"Growth Horm. IGF Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/mc.2940060110","article-title":"Role of mutations at codon 61 of the c-Ha-ras gene during diethylnitrosamine-induced hepatocarcinogenesis in C3H\/He mice","volume":"6","author":"Klimek","year":"1992","journal-title":"Mol. Carcinog."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/mc.22510","article-title":"Role of the Braf V637E mutation in hepatocarcinogenesis induced by treatment with diethylnitrosamine in neonatal B6C3F1 mice","volume":"56","author":"Yamamoto","year":"2017","journal-title":"Mol. Carcinog."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1002\/hep.29677","article-title":"C\/EBP\u03b1-dependent preneoplastic tumor foci are the origin of hepatocellular carcinoma and aggressive pediatric liver cancer","volume":"67","author":"Cast","year":"2018","journal-title":"Hepatology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1002\/ijc.28610","article-title":"Genetic and epigenetic changes in fibrosis-associated hepatocarcinogenesis in mice","volume":"134","author":"Chappell","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1002\/mc.22323","article-title":"Differentially Expressed MicroRNAs Provide Mechanistic Insight into Fibrosis-Associated Liver Carcinogenesis in Mice","volume":"55","author":"Marrone","year":"2016","journal-title":"Mol. Carcinog."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1010428317737729","article-title":"Intravenous miR-144 inhibits tumor growth in diethylnitrosamine-induced hepatocellular carcinoma in mice","volume":"39","author":"He","year":"2017","journal-title":"Tumor Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"E9879","DOI":"10.1073\/pnas.1811029115","article-title":"Integrative genomic analysis of mouse and human hepatocellular carcinoma","volume":"115","author":"Dow","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1111\/cas.12700","article-title":"Differential reactivation of fetal\/neonatal genes in mouse liver tumors induced in cirrhotic and non-cirrhotic conditions","volume":"106","author":"Chen","year":"2015","journal-title":"Cancer Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1158\/1541-7786.MCR-18-0313","article-title":"Integrated Genomic Comparison of Mouse Models Reveals Their Clinical Resemblance to Human Liver Cancer","volume":"16","author":"Yim","year":"2018","journal-title":"Mol. Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1038\/ng1481","article-title":"Application of comparative functional genomics to identify best-fit mouse models to study human cancer","volume":"36","author":"Lee","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Liu, Y.-F., Zha, B.-S., Zhang, H.-L., Zhu, X.-J., Li, Y.-H., Zhu, J., Guan, X.-H., Feng, Z.-Q., and Zhang, J.-P. (2009). Characteristic gene expression profiles in the progression from liver cirrhosis to carcinoma induced by diethylnitrosamine in a rat model. J. Exp. Clin. Cancer Res., 28.","DOI":"10.1186\/1756-9966-28-107"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1093\/carcin\/12.10.1817","article-title":"Inhibitory effects of \u03b2-carotene on preneoplastic lesions induced in Wistar rats by the resistant hepatocyte model","volume":"12","author":"Moreno","year":"1991","journal-title":"Carcinogenesis"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.fct.2016.08.020","article-title":"Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis","volume":"96","author":"Romualdo","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Romualdo, G.R., Prata, G.B., da Silva, T.C., Evangelista, A.F., Reis, R.M., Vinken, M., Moreno, F.S., Cogliati, B., and Barbisan, L.F. (2020). The combination of coffee compounds attenuates early fibrosis-associated hepatocarcinogenesis in mice: Involvement of miRNA profile modulation. J. Nutr. Biochem., 85.","DOI":"10.1016\/j.jnutbio.2020.108479"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.cbi.2019.05.046","article-title":"\u03b2-ionone inhibits nonalcoholic fatty liver disease and its association with hepatocarcinogenesis in male Wistar rats","volume":"308","author":"Miranda","year":"2019","journal-title":"Chem. Biol. Interact."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"De Conti, A., Tryndyak, V., Heidor, R., Jimenez, L., Moreno, F.S., Beland, F.A., Rusyn, I., and Pogribny, I.P. (2020). Butyrate-containing structured lipids inhibit RAC1 and epithelial-to-mesenchymal transition markers: A chemopreventive mechanism against hepatocarcinogenesis. J. Nutr. Biochem., 86.","DOI":"10.1016\/j.jnutbio.2020.108496"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1080\/01635581.2020.1764067","article-title":"Protective Effects of Dietary Capsaicin on the Initiation Step of a Two-Stage Hepatocarcinogenesis Rat Model","volume":"73","author":"Romualdo","year":"2021","journal-title":"Nutr. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1080\/713611034","article-title":"Hepatotoxicity and Mechanism of Action of Haloalkanes: Carbon Tetrachloride as a Toxicological Model","volume":"33","author":"Weber","year":"2003","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Tsuchida, T., and Friedman, S.L. (2017). Mechanisms of hepatic stellate. Nat. Publ. Gr.","DOI":"10.1038\/nrgastro.2017.38"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0304-3835(93)90071-G","article-title":"Effects of carbon tetrachloride, ethanol and acetaldehyde on diethylnitrosamine-induced hepatocarcinogenesis in rats","volume":"70","author":"Cho","year":"1993","journal-title":"Cancer Lett."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1021\/tx3002719","article-title":"Metabolism and Toxicity of Thioacetamide and Thioacetamide S -Oxide in Rat Hepatocytes","volume":"25","author":"Hajovsky","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1177\/019262338701500107","article-title":"Placental Glutathione S-Transferase (GST-P) as a New Marker for Hepatocarcinogenesis: In Vivo Short-Term Screening for Hepatocarcinogens","volume":"15","author":"Tatematsu","year":"1987","journal-title":"Toxicol. Pathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1177\/019262339602400603","article-title":"Immunohistochemical Demonstration of the Gap Junctional Protein Connexin 32 and Proliferating Cell Nuclear Antigen in Glutathione S-Transferase Placental Form-Negative Lesions of Rat Liver Induced by Diethylnitrosamine and Clofibrate","volume":"24","author":"Ito","year":"1996","journal-title":"Toxicol. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.etp.2013.01.012","article-title":"Involvement of multiple cell cycle aberrations in early preneoplastic liver cell lesions by tumor promotion with thioacetamide in a two-stage rat hepatocarcinogenesis model","volume":"65","author":"Kimura","year":"2013","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.tox.2012.05.018","article-title":"Disruptive cell cycle regulation involving epigenetic downregulation of Cdkn2a (p16Ink4a) in early-stage liver tumor-promotion facilitating liver cell regeneration in rats","volume":"299","author":"Tsuchiya","year":"2012","journal-title":"Toxicology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.toxlet.2016.11.022","article-title":"Identification of epigenetically downregulated Tmem70 and Ube2e2 in rat liver after 28-day treatment with hepatocarcinogenic thioacetamide showing gene product downregulation in hepatocellular preneoplastic and neoplastic lesions produced by tumor promoti","volume":"266","author":"Mizukami","year":"2017","journal-title":"Toxicol. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.tox.2008.05.013","article-title":"A toxicogenomics approach for early assessment of potential non-genotoxic hepatocarcinogenicity of chemicals in rats","volume":"250","author":"Uehara","year":"2008","journal-title":"Toxicology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"785","DOI":"10.2131\/jts.39.785","article-title":"Detection of initiating potential of non-genotoxic carcinogens in a two-stage hepatocarcinogenesis study in rats","volume":"39","author":"Omura","year":"2014","journal-title":"J. Toxicol. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0304-3835(84)90157-5","article-title":"Inhibition by phenobarbital and lack of effect of amobarbital on the development of liver tumors induced by N-nitrosodiethylamine in juvenile B6C3F1 mice","volume":"23","author":"Diwan","year":"1984","journal-title":"Cancer Lett."},{"key":"ref_96","first-page":"475","article-title":"Hepatic foci of cellular and enzymatic alteration and nodules in rats treated with clofibrate or diethylnitrosamine followed by phenobarbital: Their rate of onset and their reversibility","volume":"76","author":"Greaves","year":"1986","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0304-3835(93)90102-F","article-title":"Alterations in populations of GST-p-immunoreactive single hepatocytes and hepatocellular foci after a single injection of N-nitrosodiethlyamine with or without phenobarbital promotion in male F344NCr rats","volume":"71","author":"Jang","year":"1993","journal-title":"Cancer Lett."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"7812","DOI":"10.1038\/sj.onc.1204982","article-title":"Selective pressure during tumor promotion by phenobarbital leads to clonal outgrowth of \u03b2-catenin-mutated mouse liver tumors","volume":"20","author":"Aydinlik","year":"2001","journal-title":"Oncogene"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1177\/019262330002800201","article-title":"Review Article: Paradoxical Effects of Phenobarbital on Mouse Hepatocarcinogenesis","volume":"28","author":"Lee","year":"2000","journal-title":"Toxicol. Pathol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1007\/s00204-016-1712-0","article-title":"Is the question of phenobarbital as potential liver cancer risk factor for humans really resolved?","volume":"90","author":"Braeuning","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.toxlet.2011.07.002","article-title":"N-Nitrosodiethylamine genotoxicity in primary rat hepatocytes: Effects of cytochrome P450 induction by phenobarbital","volume":"206","author":"Aiub","year":"2011","journal-title":"Toxicol. Lett."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"7197","DOI":"10.1158\/0008-5472.CAN-04-1459","article-title":"The Orphan Nuclear Receptor Constitutive Active\/Androstane Receptor Is Essential for Liver Tumor Promotion by Phenobarbital in Mice","volume":"64","author":"Yamamoto","year":"2004","journal-title":"Cancer Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/toxsci\/kfr166","article-title":"Gender-Specific Interplay of Signaling through \u03b2-Catenin and CAR in the Regulation of Xenobiotic-Induced Hepatocyte Proliferation","volume":"123","author":"Braeuning","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_104","first-page":"5087","article-title":"Lack of phenobarbital-mediated promotion of hepatocarcinogenesis in connexin32-null mice","volume":"60","author":"Moennikes","year":"2000","journal-title":"Cancer Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1093\/toxsci\/kfn043","article-title":"Tumor Promotion in Liver of Mice with a Conditional Cx26 Knockout","volume":"103","author":"Mahr","year":"2008","journal-title":"Toxicol. Sci."},{"key":"ref_106","first-page":"449","article-title":"Effect of Phenobarbital on the Development of Liver Tumors in Juvenile and Adult Mice","volume":"77","author":"Pereira","year":"1986","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1093\/carcin\/15.9.1791","article-title":"Rapid development of hepatic tumors in transforming growth factor \u03b1 transgenic mice associated with increased cell proliferation in precancerous hepatocellular lesions initiated by N -nitrosodiethylamine and promoted by phenobarbital","volume":"15","author":"Tamano","year":"1994","journal-title":"Carcinogenesis"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0304-3835(97)00415-1","article-title":"p53 point mutation enhanced by hepatic regeneration in aflatoxin B1-induced rat liver tumors and preneoplastic lesions","volume":"125","author":"Lee","year":"1998","journal-title":"Cancer Lett."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/mc.2940090307","article-title":"Alterations in the methylation status and expression of theraf oncogene in phenobarbital-induced and spontaneous B6C3F1 mouse liver tumors","volume":"9","author":"Ray","year":"1994","journal-title":"Mol. Carcinog."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/toxsci\/kfp050","article-title":"Phenobarbital Elicits Unique, Early Changes in the Expression of Hepatic Genes that Affect Critical Pathways in Tumor-Prone B6C3F1 Mice","volume":"109","author":"Phillips","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1080\/15287399109531574","article-title":"Hypomethylation of ras oncogenes in chemically induced and spontaneous b6c3f1 mouse liver tumors","volume":"34","author":"Vorce","year":"1991","journal-title":"J. Toxicol. Environ. Health"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1293\/tox.22.11","article-title":"Biological Basis of Differential Susceptibility to Hepatocarcinogenesis among Mouse Strains","volume":"22","author":"Maronpot","year":"2009","journal-title":"J. Toxicol. Pathol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/263701a0","article-title":"New principle for the analysis of chemical carcinogenesis","volume":"263","author":"Solt","year":"1976","journal-title":"Nature"},{"key":"ref_114","first-page":"595","article-title":"Rapid emergence of carcinogen-induced hyperplastic lesions in a new model for the sequential analysis of liver carcinogenesis","volume":"88","author":"Solt","year":"1977","journal-title":"Am. J. Pathol."},{"key":"ref_115","first-page":"1157","article-title":"Induction of resistant hepatocytes as a new principle for a possible short-term in vivo test for carcinogens","volume":"40","author":"Tsuda","year":"1980","journal-title":"Cancer Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1002\/ijc.2910400512","article-title":"Alternative methods of selecting rat hepatocellular noduli resistant to 2-acetylaminofluorene","volume":"40","author":"Hayes","year":"1987","journal-title":"Int. J. Cancer"},{"key":"ref_117","first-page":"186","article-title":"Experimental pathology of liver: Restoration of the liver of the white rat following partial surgical removal","volume":"12","author":"Higgins","year":"1931","journal-title":"Arch. Pathol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0955-2863(01)00187-5","article-title":"Effects of \u03b2-carotene and vitamin A on oval cell proliferation and connexin 43 expression during hepatic differentiation in the rat11This work was supported by grants from Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP\u2014process no. 1996\/7566\u2013","volume":"12","author":"Naves","year":"2001","journal-title":"J. Nutr. Biochem."},{"key":"ref_119","first-page":"2733","article-title":"Use of two sequential applications of initiators in the production of hepatomas in the rat: An examination of the Solt-Farber protocol","volume":"44","author":"Potter","year":"1984","journal-title":"Cancer Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1002\/jcb.21420","article-title":"Persistent and remodeling hepatic preneoplastic lesions present differences in cell proliferation and apoptosis, as well as in p53, Bcl-2 and NF-\u03baB pathways","volume":"103","author":"Mazzantini","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"ref_121","first-page":"1308","article-title":"Antigenic relationship between oval cells and a subpopulation of hepatic foci, nodules, and carcinomas induced by the \u201cresistant hepatocyte\u201d model system","volume":"51","author":"Faris","year":"1991","journal-title":"Cancer Res."},{"key":"ref_122","first-page":"1347","article-title":"Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma","volume":"134","author":"Sell","year":"1989","journal-title":"Am. J. Pathol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1002\/hep.23488","article-title":"Progenitor-derived hepatocellular carcinoma model in the rat","volume":"51","author":"Andersen","year":"2010","journal-title":"Hepatology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.jhep.2014.06.033","article-title":"YAP activation is an early event and a potential therapeutic target in liver cancer development","volume":"61","author":"Perra","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1002\/hep.26616","article-title":"MicroRNA\/gene profiling unveils early molecular changes and nuclear factor erythroid related factor 2 (NRF2) activation in a rat model recapitulating human hepatocellular carcinoma (HCC)","volume":"59","author":"Petrelli","year":"2014","journal-title":"Hepatology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/hep.27790","article-title":"Nrf2, but not \u03b2-catenin, mutation represents an early event in rat hepatocarcinogenesis","volume":"62","author":"Zavattari","year":"2015","journal-title":"Hepatology"},{"key":"ref_127","first-page":"770","article-title":"Sequential morphologic changes in aflatoxin B carcinogenesis in the rat","volume":"28","author":"Newberne","year":"1968","journal-title":"Cancer Res."},{"key":"ref_128","first-page":"2206","article-title":"Carcinogenesis in rats by aflatoxins B1, G1, and B2","volume":"29","author":"Butler","year":"1969","journal-title":"Cancer Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/0015-6264(74)90239-9","article-title":"Carcinogenic effects of low dietary levels of aflatoxin B1 in rats","volume":"12","author":"Wogan","year":"1974","journal-title":"Food Cosmet. Toxicol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1093\/jnci\/66.6.1159","article-title":"Carcinogenicity of Aflatoxlcol in Fischer 344 Rats2, 3, 4","volume":"66","author":"Nixon","year":"1981","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1093\/ajcn\/80.5.1106","article-title":"Human aflatoxicosis in developing countries: A review of toxicology, exposure, potential health consequences, and interventions","volume":"80","author":"Williams","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"8586","DOI":"10.1073\/pnas.90.18.8586","article-title":"Aflatoxin B1 induces the transversion of G-->T in codon 249 of the p53 tumor suppressor gene in human hepatocytes","volume":"90","author":"Aguilar","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_133","first-page":"9","article-title":"Aflatoxin B1-induced rat hepatic hyperplastic nodules do not exhibit a site-specific mutation within the p53 gene","volume":"53","author":"Hulla","year":"1993","journal-title":"Cancer Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1006\/taap.1994.1148","article-title":"Aflatoxin B1-Induced Lipid Peroxidation in Rat Liver","volume":"127","author":"Shen","year":"1994","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s11010-014-2306-x","article-title":"Activation of oxidative stress and inflammatory factors could account for histopathological progression of aflatoxin-B1 induced hepatocarcinogenesis in rat","volume":"401","author":"Singh","year":"2015","journal-title":"Mol. Cell. Biochem."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Shi, J., He, J., Lin, J., Sun, X., Sun, F., Ou, C., and Jiang, C. (2016). Distinct response of the hepatic transcriptome to Aflatoxin B1 induced hepatocellular carcinogenesis and resistance in rats. Sci. Rep., 6.","DOI":"10.1038\/srep31898"},{"key":"ref_137","first-page":"2079","article-title":"Requirement of cell proliferation for the initiation of liver carcinogenesis as assayed by three different procedures","volume":"41","author":"Columbano","year":"1981","journal-title":"Cancer Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1111\/j.1349-7006.2001.tb01055.x","article-title":"Differential Effects of Partial Hepatectomy and Carbon Tetrachloride Administration on Induction of Liver Cell Foci in a Model for Detection of Initiation Activity","volume":"92","author":"Sakai","year":"2001","journal-title":"Japanese J. Cancer Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.toxlet.2020.04.009","article-title":"Early molecular events associated with liver and colon sub-acute responses to 1,2-dimethylhydrazine: Potential implications on preneoplastic and neoplastic lesion development","volume":"329","author":"Barbisan","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1080\/01480545.2018.1464019","article-title":"Augmentation of diethylnitrosamine\u2013induced early stages of rat hepatocarcinogenesis by 1,2-dimethylhydrazine","volume":"42","author":"Punvittayagul","year":"2019","journal-title":"Drug Chem. Toxicol."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Pascale, R.M., Simile, M.M., Peitta, G., Seddaiu, M.A., Feo, F., and Calvisi, D.F. (2019). Experimental Models to Define the Genetic Predisposition to Liver Cancer. Cancers, 11.","DOI":"10.3390\/cancers11101450"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1534\/genetics.103.024521","article-title":"A Potent Modifier of Liver Cancer Risk on Distal Mouse Chromosome 1 This article is dedicated to the memory of our late colleague, Kristin M. Liss","volume":"167","author":"Bilger","year":"2004","journal-title":"Genetics"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3109\/03602539409029791","article-title":"Genetic Control of Hepatocarcinogenesis In C3H Mice","volume":"26","author":"Drinkwater","year":"1994","journal-title":"Drug Metab. Rev."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1093\/carcin\/9.6.885","article-title":"Rapid growth of preneoplastic lesions in hepatocarcinogen-Sensitive C3H\/HeJ male mice relative to C57BL\/6J male mice","volume":"9","author":"Hanigan","year":"1988","journal-title":"Carcinogenesis"},{"key":"ref_145","first-page":"209","article-title":"Chromosome mapping of murine susceptibility loci to liver carcinogenesis","volume":"53","author":"Gariboldi","year":"1993","journal-title":"Cancer Res."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/genetics\/139.1.387","article-title":"Identification of hepatocarcinogen-resistance genes in DBA\/2 mice","volume":"139","author":"Lee","year":"1995","journal-title":"Genetics"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/0378-4274(95)03505-2","article-title":"Genetics of liver tumor susceptibility in mice","volume":"82\u201383","author":"Dragani","year":"1995","journal-title":"Toxicol. Lett."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1006\/geno.1994.1466","article-title":"Multiple Loci Affect Genetic Predisposition to Hepatocarcinogenesis in Mice","volume":"23","author":"Manenti","year":"1994","journal-title":"Genomics"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/hep.22374","article-title":"Genetic control of resistance to hepatocarcinogenesis by the mouse Hpcr3 locus","volume":"48","author":"Manenti","year":"2008","journal-title":"Hepatology"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1002\/ijc.20225","article-title":"Polygenic control of hepatocarcinogenesis in Copenhagen \u00d7 F344 rats","volume":"111","author":"Pascale","year":"2004","journal-title":"Int. J. Cancer"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"10384","DOI":"10.1158\/0008-5472.CAN-06-2881","article-title":"Mapping a Sex Hormone\u2013Sensitive Gene Determining Female Resistance to Liver Carcinogenesis in a Congenic F344.BN- Hcs4 Rat","volume":"66","author":"Virdis","year":"2006","journal-title":"Cancer Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/carcin\/23.1.189","article-title":"Resistance of DRH strain rats to chemical carcinogenesis of liver: Genetic analysis of later progression stage","volume":"23","author":"Yan","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref_153","first-page":"373","article-title":"Genetic resistance to chemical hepatocarcinogenesis in the DRH rat strain","volume":"54","author":"Higashi","year":"2004","journal-title":"Comp. Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1128\/MCB.25.8.2957-2968.2005","article-title":"17\u03b2-Estradiol Inhibits Inflammatory Gene Expression by Controlling NF-\u03baB Intracellular Localization","volume":"25","author":"Ghisletti","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"40140","DOI":"10.1074\/jbc.M112.348763","article-title":"Estrogen represses hepatocellular carcinoma (HCC) Growth via Inhibiting Alternative Activation of Tumor-associated Macrophages (TAMs)","volume":"287","author":"Yang","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"17975","DOI":"10.1073\/pnas.1315319110","article-title":"Loss of estrogen-related receptor promotes hepatocarcinogenesis development via metabolic and inflammatory disturbances","volume":"110","author":"Hong","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Kalra, M., Mayes, J., Assefa, S., Kaul, A.K., and Kaul, R. (2008). Role of sex steroid receptors in pathobiology of hepatocellular carcinoma. World J. Gastroenterol., 14.","DOI":"10.3748\/wjg.14.5945"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1002\/hep.29715","article-title":"Significance and mechanism of androgen receptor overexpression and androgen receptor\/mechanistic target of rapamycin cross-talk in hepatocellular carcinoma","volume":"67","author":"Zhang","year":"2018","journal-title":"Hepatology"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1053\/j.gastro.2008.05.046","article-title":"Androgen Receptor Is a New Potential Therapeutic Target for the Treatment of Hepatocellular Carcinoma","volume":"135","author":"Ma","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cmet.2018.10.012","article-title":"Preclinical Models for Studying NASH-Driven HCC: How Useful Are They?","volume":"29","author":"Febbraio","year":"2019","journal-title":"Cell Metab."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.2337\/diabetes.53.12.3274","article-title":"Genetic Determinants of Energy Expenditure and Insulin Resistance in Diet-Induced Obesity in Mice","volume":"53","author":"Almind","year":"2004","journal-title":"Diabetes"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.jhep.2016.05.005","article-title":"A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer","volume":"65","author":"Asgharpour","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"7385","DOI":"10.1158\/0008-5472.CAN-09-1089","article-title":"Integrative Transcriptome Analysis Reveals Common Molecular Subclasses of Human Hepatocellular Carcinoma","volume":"69","author":"Hoshida","year":"2009","journal-title":"Cancer Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/j.ajpath.2014.01.034","article-title":"Development of Hepatocellular Carcinoma in a Murine Model of Nonalcoholic Steatohepatitis Induced by Use of a High-Fat\/Fructose Diet and Sedentary Lifestyle","volume":"184","author":"Dowman","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Tessitore, A., Cicciarelli, G., Del Vecchio, F., Gaggiano, A., Verzella, D., Fischietti, M., Mastroiaco, V., Vetuschi, A., Sferra, R., and Barnabei, R. (2016). MicroRNA expression analysis in high fat diet-induced NAFLD-NASH-HCC progression: Study on C57BL\/6J mice. BMC Cancer, 16.","DOI":"10.1186\/s12885-015-2007-1"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jhep.2018.03.011","article-title":"A simple diet- and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer","volume":"69","author":"Tsuchida","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.ccell.2014.09.003","article-title":"Metabolic Activation of Intrahepatic CD8+ T Cells and NKT Cells Causes Nonalcoholic Steatohepatitis and Liver Cancer via Cross-Talk with Hepatocytes","volume":"26","author":"Wolf","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/iep.12240","article-title":"Hepatocellular carcinoma in a mouse model fed a choline-deficient, L-amino acid-defined, high-fat diet","volume":"98","author":"Matsuo","year":"2017","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"De Minicis, S., Agostinelli, L., Rychlicki, C., Sorice, G.P., Saccomanno, S., Candelaresi, C., Giaccari, A., Trozzi, L., Pierantonelli, I., and Mingarelli, E. (2014). HCC Development Is Associated to Peripheral Insulin Resistance in a Mouse Model of NASH. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097136"},{"key":"ref_170","first-page":"4849","article-title":"Characterization of non-alcoholic steatohepatitis-derived hepatocellular carcinoma as a human stratification model in mice","volume":"34","author":"Takakura","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1172\/JCI20513","article-title":"Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas","volume":"113","author":"Horie","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ccr.2014.07.001","article-title":"ER Stress Cooperates with Hypernutrition to Trigger TNF-Dependent Spontaneous HCC Development","volume":"26","author":"Nakagawa","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s00795-013-0016-1","article-title":"A murine model for non-alcoholic steatohepatitis showing evidence of association between diabetes and hepatocellular carcinoma","volume":"46","author":"Fujii","year":"2013","journal-title":"Med. Mol. Morphol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"88517","DOI":"10.18632\/oncotarget.19774","article-title":"MicroRNA deregulation in nonalcoholic steatohepatitis-associated liver carcinogenesis","volume":"8","author":"Ortega","year":"2017","journal-title":"Oncotarget"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S1383-5742(02)00044-3","article-title":"Genotoxicity of Streptozotocin","volume":"512","author":"Bianchi","year":"2002","journal-title":"Mutat. Res. Mutat. Res."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Guo, S., Mao, X., Yan, Y., Zhang, Y., and Ming, L. (2020). Changes of liver transcriptome profiles following oxidative stress in streptozotocin-induced diabetes in mice. PeerJ, 8.","DOI":"10.7717\/peerj.8983"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"4722","DOI":"10.1158\/0008-5472.CAN-12-3797","article-title":"Proteomic and Lipidomic Signatures of Lipid Metabolism in NASH-Associated Hepatocellular Carcinoma","volume":"73","author":"Muir","year":"2013","journal-title":"Cancer Res."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0300-483X(94)02917-J","article-title":"The effects of long-term oral administration of ethanol on Sprague-Dawley rats \u2014 A condensed report","volume":"96","author":"Holmberg","year":"1995","journal-title":"Toxicology"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fct.2004.07.018","article-title":"Effect of ethanol on the tumorigenicity of urethane (ethyl carbamate) in B6C3F1 mice","volume":"43","author":"Beland","year":"2005","journal-title":"Food Chem. Toxicol."},{"key":"ref_180","first-page":"325","article-title":"Cessation of Long-term Alcohol Administration and Two-day Cycling of Exposure Respectively Promote and Inhibit Hepatocarcinogenesis in Rats","volume":"1","author":"Tanaka","year":"2000","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_181","first-page":"122","article-title":"Effects of cessation of alcohol exposure on rat hepatocarcinogenesis","volume":"7","author":"Wanibuchi","year":"2006","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.18632\/oncotarget.6511","article-title":"Connexin 32 dysfunction promotes ethanol-related hepatocarcinogenesis via activation of Dusp1-Erk axis","volume":"7","author":"Kato","year":"2016","journal-title":"Oncotarget"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1111\/j.1349-7006.2005.00110.x","article-title":"Dose-dependence of promotion of 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline-induced rat hepatocarcinogenesis by ethanol: Evidence for a threshold","volume":"96","author":"Kushida","year":"2005","journal-title":"Cancer Sci."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/j.1349-7006.2007.00677.x","article-title":"Chronic ethanol intake promotes double gluthatione S-transferase\/transforming growth factor-\u03b1-positive hepatocellular lesions in male Wistar rats","volume":"99","author":"Pires","year":"2008","journal-title":"Cancer Sci."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1158\/1940-6207.CAPR-13-0444-T","article-title":"Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis in Male Mice through Activation of the Wnt\/\u03b2-Catenin Signaling Pathway","volume":"7","author":"Mercer","year":"2014","journal-title":"Cancer Prev. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/j.1530-0277.2011.01660.x","article-title":"Chronic Ethanol Feeding Accelerates Hepatocellular Carcinoma Progression in a Sex-Dependent Manner in a Mouse Model of Hepatocarcinogenesis","volume":"36","author":"Walling","year":"2012","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.jhep.2019.12.016","article-title":"IL-17 signaling in steatotic hepatocytes and macrophages promotes hepatocellular carcinoma in alcohol-related liver disease","volume":"72","author":"Ma","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0304-3835(02)00685-7","article-title":"Enhancing risk of ethanol on MeIQx-induced rat hepatocarcinogenesis is accompanied with increased levels of cellular proliferation and oxidative stress","volume":"192","author":"Karim","year":"2003","journal-title":"Cancer Lett."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1080\/01926230600713632","article-title":"Existence of No Hepatocarcinogenic Effect Levels of 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline with or without Coadministration with Ethanol","volume":"34","author":"Wanibuchi","year":"2006","journal-title":"Toxicol. Pathol."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1002\/(SICI)1097-0215(19970611)71:6<1045::AID-IJC21>3.0.CO;2-B","article-title":"Enhancement by ethyl alcohol of experimental hepatocarcinogenesis induced by N-nitrosomorpholine","volume":"71","author":"Tatsuta","year":"1997","journal-title":"Int. J. Cancer"},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Yan, G., Wang, X., Sun, C., Zheng, X., Wei, H., Tian, Z., and Sun, R. (2017). Chronic Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis via Immune Disturbances. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-02887-7"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/ijc.11254","article-title":"Alterations of RB1, p53 and Wnt pathways in hepatocellular carcinomas associated with hepatitis C, hepatitis B and alcoholic liver cirrhosis","volume":"106","author":"Edamoto","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"14433","DOI":"10.18632\/aging.203059","article-title":"Chronic alcohol exposure promotes HCC stemness and metastasis through \u03b2-catenin\/miR-22-3p\/TET2 axis","volume":"13","author":"Chen","year":"2021","journal-title":"Aging"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/351317a0","article-title":"HBx gene of hepatitis B virus induces liver cancer in transgenic mice","volume":"351","author":"Kim","year":"1991","journal-title":"Nature"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0168-8278(99)80172-X","article-title":"Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein","volume":"31","author":"Yu","year":"1999","journal-title":"J. Hepatol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"5056","DOI":"10.1002\/pmic.200800779","article-title":"Proteomic analysis of liver tissue from HBx -transgenic mice at early stages of hepatocarcinogenesis","volume":"9","author":"Kim","year":"2009","journal-title":"Proteomics"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"4978","DOI":"10.1128\/jvi.70.8.4978-4985.1996","article-title":"Hepatitis B virus HBx protein induces transcription factor AP-1 by activation of extracellular signal-regulated and c-Jun N-terminal mitogen-activated protein kinases","volume":"70","author":"Benn","year":"1996","journal-title":"J. Virol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"5548","DOI":"10.1128\/JVI.79.9.5548-5556.2005","article-title":"The Transcriptional Transactivation Function of HBx Protein Is Important for Its Augmentation Role in Hepatitis B Virus Replication","volume":"79","author":"Tang","year":"2005","journal-title":"J. Virol."},{"key":"ref_199","first-page":"3400","article-title":"V Hepatocarcinogenesis due to chronic liver cell injury in hepatitis B virus transgenic mice","volume":"50","author":"Dunsford","year":"1990","journal-title":"Cancer Res."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1002\/hep.1840200510","article-title":"Hepatic preneoplasia in hepatitis B virus transgenic mice","volume":"20","author":"Toshkov","year":"1994","journal-title":"Hepatology"},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Lai, M.-W., Liang, K.-H., Lin, W.-R., Huang, Y.-H., Huang, S.-F., Chen, T.-C., and Yeh, C.-T. (2016). Hepatocarcinogenesis in transgenic mice carrying hepatitis B virus pre-S\/S gene with the sW172* mutation. Oncogenesis, 5.","DOI":"10.1038\/oncsis.2016.77"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/2053","article-title":"The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice","volume":"4","author":"Moriya","year":"1998","journal-title":"Nat. Med."},{"key":"ref_203","first-page":"407","article-title":"Evolution of neoplastic development in the liver of transgenic mice co-expressing c-myc and transforming growth factor-alpha","volume":"149","author":"Nagy","year":"1996","journal-title":"Am. J. Pathol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1046\/j.1365-2125.1996.03748.x","article-title":"Transgenic mouse models in carcinogenesis: Interaction of c- myc with transforming growth factor \u03b1 and hepatocyte growth factor in hepatocarcinogenesis","volume":"42","author":"Thorgeirsson","year":"1996","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1053\/j.gastro.2004.02.014","article-title":"Disruption of \u03b2-catenin pathway or genomic instability define two distinct categories of liver cancer in transgenic mice","volume":"126","author":"Calvisi","year":"2004","journal-title":"Gastroenterology"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"5054","DOI":"10.1038\/sj.onc.1203885","article-title":"Dual functions of E2F-1 in a transgenic mouse model of liver carcinogenesis","volume":"19","author":"Conner","year":"2000","journal-title":"Oncogene"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"17216","DOI":"10.1073\/pnas.0404761101","article-title":"Liver-targeted disruption of Apc in mice activates -catenin signaling and leads to hepatocellular carcinomas","volume":"101","author":"Colnot","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1158\/0008-5472.CAN-03-2123","article-title":"Hepatocarcinogenesis in Mice with \u03b2-Catenin and Ha-Ras Gene Mutations","volume":"64","author":"Harada","year":"2004","journal-title":"Cancer Res."},{"key":"ref_209","doi-asserted-by":"crossref","unstructured":"Chung, S.I., Moon, H., Kim, D.Y., Cho, K.J., Ju, H., Kim, D.Y., Ahn, S.H., Han, K., and Ro, S.W. (2016). Development of a transgenic mouse model of hepatocellular carcinoma with a liver fibrosis background. BMC Gastroenterol., 1\u20139.","DOI":"10.1186\/s12876-016-0423-6"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"6909","DOI":"10.1073\/pnas.84.19.6909","article-title":"Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice","volume":"84","author":"Chisari","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"115","DOI":"10.2119\/2006-00015.Barone","article-title":"Gene Expression Analysis in HBV Transgenic Mouse Liver: A Model to Study Early Events Related to Hepatocarcinogenesis","volume":"12","author":"Barone","year":"2006","journal-title":"Mol. Med."},{"key":"ref_212","first-page":"1278","article-title":"V Synergy between hepatitis B virus expression and chemical hepatocarcinogens in transgenic mice","volume":"51","author":"Sell","year":"1991","journal-title":"Cancer Res."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1177\/135965350901400216","article-title":"Identification of nonsense mutations in hepatitis B virus S gene in patients with hepatocellular carcinoma developed after lamivudine therapy","volume":"14","author":"Lai","year":"2009","journal-title":"Antivir. Ther."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1021\/pr070094c","article-title":"A Proteomics Method Revealing Disease-Related Proteins in Livers of Hepatitis-Infected Mouse Model","volume":"6","author":"Ichibangase","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/hep.20621","article-title":"Hepatitis C virus acts as a tumor accelerator by blocking apoptosis in a mouse model of hepatocarcinogenesis","volume":"41","author":"Kamegaya","year":"2005","journal-title":"Hepatology"},{"key":"ref_216","first-page":"715","article-title":"Oncogene-induced liver neoplasia in transgenic mice","volume":"4","author":"Sandgren","year":"1989","journal-title":"Oncogene"},{"key":"ref_217","first-page":"727","article-title":"Liver-specific expression and high oncogenic efficiency of a c-myc transgene activated by woodchuck hepatitis virus insertion","volume":"9","author":"Etiemble","year":"1994","journal-title":"Oncogene"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1002\/hep.510250415","article-title":"Hepatocarcinogenesis in woodchuck hepatitis virus\/c-myc mice: Sustained cell proliferation and biphasic activation of insulin-like growth factor II","volume":"25","author":"Liu","year":"1997","journal-title":"Hepatology"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"8847","DOI":"10.1073\/pnas.95.15.8847","article-title":"Somatic mutations of the -catenin gene are frequent in mouse and human hepatocellular carcinomas","volume":"95","author":"Coste","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1053\/j.gastro.2020.08.015","article-title":"Cooperation Between Distinct Cancer Driver Genes Underlies Intertumor Heterogeneity in Hepatocellular Carcinoma","volume":"159","author":"Yao","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1126\/science.aay8276","article-title":"Identifying strategies to target the metabolic flexibility of tumours","volume":"2","author":"Lin","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"4355","DOI":"10.1158\/0008-5472.CAN-17-0498","article-title":"Glucose Catabolism in Liver Tumors Induced by c-MYC Can Be Sustained by Various PKM1\/PKM2 Ratios and Pyruvate Kinase Activities","volume":"77","author":"Li","year":"2017","journal-title":"Cancer Res."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1002\/hep.30556","article-title":"Axis inhibition protein 1 (Axin1) Deletion\u2013Induced Hepatocarcinogenesis Requires Intact \u03b2-Catenin but Not Notch Cascade in Mice","volume":"70","author":"Qiao","year":"2019","journal-title":"Hepatology"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1016\/j.ajpath.2017.07.022","article-title":"Oncogenic Determination of a Broad Spectrum of Phenotypes of Hepatocyte-Derived Mouse Liver Tumors","volume":"187","author":"Yamamoto","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1038\/onc.2017.114","article-title":"Critical role of Myc activation in mouse hepatocarcinogenesis induced by the activation of AKT and RAS pathways","volume":"36","author":"Xin","year":"2017","journal-title":"Oncogene"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3727\/105221618X15174108894682","article-title":"The Effect of Selective c-MET Inhibitor on Hepatocellular Carcinoma in the MET-Active, \u03b2-Catenin-Mutated Mouse Model","volume":"18","author":"Zhan","year":"2018","journal-title":"Gene Expr."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1002\/hep.28601","article-title":"Modeling a human hepatocellular carcinoma subset in mice through coexpression of met and point-mutant \u03b2-catenin","volume":"64","author":"Tao","year":"2016","journal-title":"Hepatology"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1158\/0008-5472.CAN-10-2705","article-title":"Coactivation of AKT and \u03b2-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors","volume":"71","author":"Stauffer","year":"2011","journal-title":"Cancer Res."},{"key":"ref_229","first-page":"1","article-title":"Co-activation of AKT and c-Met triggers rapid hepatocellular carcinoma development via the mTORC1\/FASN pathway in mice","volume":"6","author":"Hu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_230","first-page":"1719","article-title":"Transgenic mouse model for synergistic effects of nuclear oncogenes and growth factors in tumorigenesis: Interaction of c-myc and transforming growth factor alpha in hepatic oncogenesis","volume":"53","author":"Murakami","year":"1993","journal-title":"Cancer Res."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature13589","article-title":"CRISPR-mediated direct mutation of cancer genes in the mouse liver","volume":"514","author":"Xue","year":"2014","journal-title":"Nature"},{"key":"ref_232","first-page":"1","article-title":"CRISPR\/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_233","doi-asserted-by":"crossref","unstructured":"Sachdeva, M. (2015). Immunology of hepatocellular carcinoma. World J. Hepatol., 7.","DOI":"10.4254\/wjh.v7.i17.2080"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.3748\/wjg.v25.i24.2977","article-title":"Immunotherapy for hepatocellular carcinoma: Current and future","volume":"25","author":"Johnston","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Kole, C., Charalampakis, N., Tsakatikas, S., Vailas, M., Moris, D., Gkotsis, E., Kykalos, S., Karamouzis, M.V., and Schizas, D. (2020). Immunotherapy for Hepatocellular Carcinoma: A 2021 Update. Cancers, 12.","DOI":"10.3390\/cancers12102859"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.4049\/jimmunol.172.5.2731","article-title":"Of Mice and Not Men: Differences between Mouse and Human Immunology","volume":"172","author":"Mestas","year":"2004","journal-title":"J. Immunol."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2014.00140","article-title":"Antigen Cross-Presentation of Immune Complexes","volume":"5","author":"Platzer","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_238","doi-asserted-by":"crossref","unstructured":"Macek Jilkova, Z., Kurma, K., and Decaens, T. (2019). Animal Models of Hepatocellular Carcinoma: The Role of Immune System and Tumor Microenvironment. Cancers, 11.","DOI":"10.3390\/cancers11101487"},{"key":"ref_239","doi-asserted-by":"crossref","unstructured":"Li, E., Lin, L., Chen, C.-W., and Ou, D.-L. (2019). Mouse Models for Immunotherapy in Hepatocellular Carcinoma. Cancers, 11.","DOI":"10.3390\/cancers11111800"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cpph.77","article-title":"Establishment of Humanized Mice from Peripheral Blood Mononuclear Cells or Cord Blood CD34+ Hematopoietic Stem Cells for Immune-Oncology Studies Evaluating New Therapeutic Agents","volume":"89","author":"Verma","year":"2020","journal-title":"Curr. Protoc. Pharmacol."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/0471142735.im1521s81","article-title":"Creation of \u201cHumanized\u201d Mice to Study Human Immunity","volume":"81","author":"Pearson","year":"2008","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"5329","DOI":"10.21873\/anticanres.14540","article-title":"The Development of Next-generation PBMC Humanized Mice for Preclinical Investigation of Cancer Immunotherapeutic Agents","volume":"40","author":"Morillon","year":"2020","journal-title":"Anticancer Res."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1096\/fj.201800636R","article-title":"Lack of acute xenogeneic graft- versus -host disease, but retention of T-cell function following engraftment of human peripheral blood mononuclear cells in NSG mice deficient in MHC class I and II expression","volume":"33","author":"Brehm","year":"2019","journal-title":"FASEB J."},{"key":"ref_244","doi-asserted-by":"crossref","unstructured":"Yao, L.-C., Cheng, M., Shultz, L.D., and Keck, J.G. (2020, January 27\u201328). Abstract 5619: PBMC humanized NSG-(K b D b ) null (IA) null mouse model to evaluate immune-oncology drug efficacy. Proceedings of the AACR Annual Meeting 2020, American Association for Cancer Research, Philadelphia, PA, USA.","DOI":"10.1158\/1538-7445.AM2020-5619"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.7314\/APJCP.2013.14.5.3109","article-title":"Anti-tumor Efficacy of a Hepatocellular Carcinoma Vaccine Based on Dendritic Cells Combined with Tumor-derived Autophagosomes in Murine Models","volume":"14","author":"Su","year":"2013","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1016\/j.ymthe.2019.07.019","article-title":"Recombinant Adenovirus Expressing a Soluble Fusion Protein PD-1\/CD137L Subverts the Suppression of CD8+ T Cells in HCC","volume":"27","author":"Zhang","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.it.2018.07.001","article-title":"Humanized Mice for the Study of Immuno-Oncology","volume":"39","author":"Decaudin","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2018.00054","article-title":"Modeling Human Antitumor Responses In Vivo Using Umbilical Cord Blood-Engrafted Mice","volume":"9","author":"Zumwalde","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"13022","DOI":"10.1073\/pnas.1000475107","article-title":"Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD\/SCID\/IL2r null humanized mice","volume":"107","author":"Shultz","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1146\/annurev-pathol-052016-100332","article-title":"Humanized Mouse Models of Clinical Disease","volume":"12","author":"Walsh","year":"2017","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.4049\/jimmunol.1400412","article-title":"Human Hematopoietic Reconstitution and HLA-Restricted Responses in Nonpermissive Alymphoid Mice","volume":"193","author":"Bourgine","year":"2014","journal-title":"J. Immunol."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1124\/dmd.31.8.1035","article-title":"Comparison of primary human hepatocytes and hepatoma cell line hepg2 with regard to their biotransformation properties","volume":"31","author":"Wilkening","year":"2003","journal-title":"Drug. Metab. DIspos."},{"key":"ref_253","first-page":"505","article-title":"In Vitro Models of the Liver: Disease Modeling, Drug Discovery and Clinical Applications","volume":"Volume 38","year":"2019","journal-title":"Tijdschrift voor Geneeskunde"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/10937404.2019.1692744","article-title":"Genetic toxicity assessment using liver cell models: Past, present, and future","volume":"23","author":"Guo","year":"2020","journal-title":"J. Toxicol. Environ. Health Part B"},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.apha.2018.08.001","article-title":"Primary hepatocytes and their cultures for the testing of drug-induced liver injury","volume":"85","author":"Cooreman","year":"2019","journal-title":"Adv. Pharmacol."},{"key":"ref_256","unstructured":"Muriel, P. (2017). In Vitro Models of HCC. Liver Pathophysiology, Elsevier."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/1043-6618(90)90746-Z","article-title":"Human hepatocytes in genotoxicity assays","volume":"22","author":"Brambilla","year":"1990","journal-title":"Pharmacol. Res."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.tox.2008.10.017","article-title":"Changes in gene expression and assessment of DNA methylation in primary human hepatocytes and HepG2 cells exposed to the environmental contaminants\u2014Hexabromocyclododecane and 17-\u03b2 oestradiol","volume":"256","author":"Aniagu","year":"2009","journal-title":"Toxicology"},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1177\/1091581811422453","article-title":"Effect of Aflatoxin B1 on Nuclear Receptors PXR, CAR, and AhR and Their Target Cytochromes P450 mRNA Expression in Primary Cultures of Human Hepatocytes","volume":"31","author":"Pascussi","year":"2012","journal-title":"Int. J. Toxicol."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3109\/01480545.2011.592194","article-title":"The mycotoxin, patulin, increases the expression of PXR and AhR and their target cytochrome P450s in primary cultured human hepatocytes","volume":"35","author":"Pascussi","year":"2012","journal-title":"Drug Chem. Toxicol."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3109\/01480545.2011.589438","article-title":"Ochratoxin A induces CYP3A4, 2B6, 3A5, 2C9, 1A1, and CYP1A2 gene expression in primary cultured human hepatocytes: A possible activation of nuclear receptors","volume":"35","author":"Pascussi","year":"2012","journal-title":"Drug Chem. Toxicol."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.tox.2016.05.002","article-title":"Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma","volume":"350\u2013352","author":"Rieswijk","year":"2016","journal-title":"Toxicology"},{"key":"ref_263","doi-asserted-by":"crossref","unstructured":"Pez, F., Gifu, P., Degli-Esposti, D., Fares, N., Lopez, A., Lefran\u00e7ois, L., Michelet, M., Rivoire, M., Bancel, B., and Sylla, B.S. (2019). In vitro transformation of primary human hepatocytes: Epigenetic changes and stemness properties. Exp. Cell Res., 384.","DOI":"10.1016\/j.yexcr.2019.111643"},{"key":"ref_264","doi-asserted-by":"crossref","unstructured":"Kiamehr, M., Heiskanen, L., Laufer, T., D\u00fcsterloh, A., Kahraman, M., K\u00e4kel\u00e4, R., Laaksonen, R., and Aalto-Set\u00e4l\u00e4, K. (2019). Dedifferentiation of Primary Hepatocytes is Accompanied with Reorganization of Lipid Metabolism Indicated by Altered Molecular Lipid and miRNA Profiles. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20122910"},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"629","DOI":"10.2174\/138920006778017759","article-title":"Molecular Mechanisms Underlying the Dedifferentiation Process of Isolated Hepatocytes and Their Cultures","volume":"7","author":"Elaut","year":"2006","journal-title":"Curr. Drug Metab."},{"key":"ref_266","first-page":"99","article-title":"Establishment of Sandwich Cultures of Primary Human Hepatocytes","volume":"Volume 1981","author":"Gijbels","year":"2019","journal-title":"Experimental Cholestasis Research"},{"key":"ref_267","doi-asserted-by":"crossref","unstructured":"Bell, C.C., Hendriks, D.F.G., Moro, S.M.L., Ellis, E., Walsh, J., Renblom, A., Fredriksson Puigvert, L., Dankers, A.C.A., Jacobs, F., and Snoeys, J. (2016). Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease. Sci. Rep., 6.","DOI":"10.1038\/srep25187"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1124\/dmd.116.074369","article-title":"Transcriptional, Functional, and Mechanistic Comparisons of Stem Cell\u2013Derived Hepatocytes, HepaRG Cells, and Three-Dimensional Human Hepatocyte Spheroids as Predictive In Vitro Systems for Drug-Induced Liver Injury","volume":"45","author":"Bell","year":"2017","journal-title":"Drug Metab. Dispos."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1093\/toxsci\/kfx289","article-title":"Comparison of Hepatic 2D Sandwich Cultures and 3D Spheroids for Long-term Toxicity Applications: A Multicenter Study","volume":"162","author":"Bell","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1093\/toxsci\/kfp206","article-title":"Modulation of Aflatoxin B1\u2013Mediated Genotoxicity in Primary Cultures of Human Hepatocytes by Diindolylmethane, Curcumin, and Xanthohumols","volume":"112","author":"Stapleton","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref_271","first-page":"1","article-title":"Studying non-alcoholic fatty liver disease: The ins and outs of in vivo, ex vivo and in vitro human models","volume":"41","author":"Green","year":"2018","journal-title":"Horm. Mol. Biol. Clin. Investig."},{"key":"ref_272","doi-asserted-by":"crossref","unstructured":"Saraswati, S., Alhaider, A., Abdelgadir, A.M., Tanwer, P., and Korashy, H.M. (2019). Phloretin attenuates STAT-3 activity and overcomes sorafenib resistance targeting SHP-1\u2013mediated inhibition of STAT3 and Akt\/VEGFR2 pathway in hepatocellular carcinoma. Cell Commun. Signal., 17.","DOI":"10.1186\/s12964-019-0430-7"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1053\/j.gastro.2020.02.011","article-title":"Persistent Polyfunctional Chimeric Antigen Receptor T Cells That Target Glypican 3 Eliminate Orthotopic Hepatocellular Carcinomas in Mice","volume":"158","author":"Li","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1177\/1535370216657448","article-title":"Cell sources for in vitro human liver cell culture models","volume":"241","author":"Zeilinger","year":"2016","journal-title":"Exp. Biol. Med."},{"key":"ref_275","doi-asserted-by":"crossref","unstructured":"Czauderna, C., Palestino-Dominguez, M., Castven, D., Becker, D., Zanon-Rodriguez, L., Hajduk, J., Mahn, F.L., Herr, M., Strand, D., and Strand, S. (2018). Ginkgo biloba induces different gene expression signatures and oncogenic pathways in malignant and non-malignant cells of the liver. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0209067"},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"18805","DOI":"10.1002\/jcb.29196","article-title":"MicroRNA-450b-3p inhibits cell growth by targeting phosphoglycerate kinase 1 in hepatocellular carcinoma","volume":"120","author":"Chen","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_277","doi-asserted-by":"crossref","unstructured":"Hirschfield, H., Bian, C.B., Higashi, T., Nakagawa, S., Zeleke, T.Z., Nair, V.D., Fuchs, B.C., and Hoshida, Y. (2018). In vitro modeling of hepatocellular carcinoma molecular subtypes for anti-cancer drug assessment. Exp. Mol. Med., 50.","DOI":"10.1038\/emm.2017.164"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"3372","DOI":"10.1158\/1078-0432.CCR-15-1638","article-title":"SIRT6 Overexpression Potentiates Apoptosis Evasion in Hepatocellular Carcinoma via BCL2-Associated X Protein\u2013Dependent Apoptotic Pathway","volume":"22","author":"Ran","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1093\/jnci\/djt007","article-title":"The Clinical Relevance of Cancer Cell Lines","volume":"105","author":"Gillet","year":"2013","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_280","doi-asserted-by":"crossref","unstructured":"Zanoni, M., Cortesi, M., Zamagni, A., Arienti, C., Pignatta, S., and Tesei, A. (2020). Modeling neoplastic disease with spheroids and organoids. J. Hematol. Oncol., 13.","DOI":"10.1186\/s13045-020-00931-0"},{"key":"ref_281","doi-asserted-by":"crossref","unstructured":"Feng, P.-C., Ke, X.-F., Kuang, H.-L., Pan, L.-L., Ye, Q., and Wu, J.-B. (2019). BMP2 secretion from hepatocellular carcinoma cell HepG2 enhances angiogenesis and tumor growth in endothelial cells via activation of the MAPK\/p38 signaling pathway. Stem Cell Res. Ther., 10.","DOI":"10.1186\/s13287-019-1301-2"},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1111\/cas.14262","article-title":"STMN1 upregulation mediates hepatocellular carcinoma and hepatic stellate cell crosstalk to aggravate cancer by triggering the MET pathway","volume":"111","author":"Zhang","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.31557\/APJCP.2019.20.12.3797","article-title":"Natural Killer Cell Expansion with Autologous Feeder Layer and Anti-CD3 Antibody for Immune Cell Therapy of Hepatocellular Carcinoma","volume":"20","author":"Hosseinzadeh","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_284","doi-asserted-by":"crossref","unstructured":"Sun, L., Wang, Y., Wang, L., Yao, B., Chen, T., Li, Q., Liu, Z., Liu, R., Niu, Y., and Song, T. (2019). Resolvin D1 prevents epithelial-mesenchymal transition and reduces the stemness features of hepatocellular carcinoma by inhibiting paracrine of cancer-associated fibroblast-derived COMP. J. Exp. Clin. Cancer Res., 38.","DOI":"10.1186\/s13046-019-1163-6"},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1002\/hep.30630","article-title":"A Positive Feedback Loop Between Cancer Stem-Like Cells and Tumor-Associated Neutrophils Controls Hepatocellular Carcinoma Progression","volume":"70","author":"Zhou","year":"2019","journal-title":"Hepatology"},{"key":"ref_286","doi-asserted-by":"crossref","unstructured":"Wuputra, K., Lin, C.-S., Tsai, M.-H., Ku, C.-C., Lin, W.-H., Yang, Y.-H., Kuo, K.-K., and Yokoyama, K.K. (2017). Cancer cell reprogramming to identify the genes competent for generating liver cancer stem cells. Inflamm. Regen., 37.","DOI":"10.1186\/s41232-017-0041-x"},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.jhep.2010.05.003","article-title":"Epigenetic regulation of cancer stem cells in liver cancer: Current concepts and clinical implications","volume":"53","author":"Marquardt","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_288","doi-asserted-by":"crossref","unstructured":"Gehart, H., and Clevers, H. (2020). Stem Cell-Derived Liver Cells. The Liver, Wiley.","DOI":"10.1002\/9781119436812.ch77"},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1080\/15476278.2017.1322243","article-title":"Microenvironment of a tumor-organoid system enhances hepatocellular carcinoma malignancy-related hallmarks","volume":"13","author":"Wang","year":"2017","journal-title":"Organogenesis"},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.1007\/s00204-019-02576-6","article-title":"Development of in vitro 3D cell model from hepatocellular carcinoma (HepG2) cell line and its application for genotoxicity testing","volume":"93","author":"Tomc","year":"2019","journal-title":"Arch. Toxicol."},{"key":"ref_291","doi-asserted-by":"crossref","unstructured":"Mi\u0161\u00edk, M., Nersesyan, A., Ropek, N., Huber, W.W., Haslinger, E., and Knasmueller, S. (2019). Use of human derived liver cells for the detection of genotoxins in comet assays. Mutat. Res. Toxicol. Environ. Mutagen., 845.","DOI":"10.1016\/j.mrgentox.2018.12.003"},{"key":"ref_292","doi-asserted-by":"crossref","unstructured":"Liu, C., Liu, Y., Xu, X., Guo, X., Sun, G., and Ma, X. (2016). Mesenchymal stem cells enhance the metastasis of 3D-cultured hepatocellular carcinoma cells. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2595-4"},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.mrgentox.2017.12.005","article-title":"A three-dimensional in vitro HepG2 cells liver spheroid model for genotoxicity studies","volume":"825","author":"Shah","year":"2018","journal-title":"Mutat. Res. Toxicol. Environ. Mutagen."},{"key":"ref_294","doi-asserted-by":"crossref","unstructured":"Eilenberger, C., Rothbauer, M., Ehmoser, E.-K., Ertl, P., and K\u00fcpc\u00fc, S. (2019). Effect of Spheroidal Age on Sorafenib Diffusivity and Toxicity in a 3D HepG2 Spheroid Model. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-41273-3"},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1002\/bit.26297","article-title":"Bioengineered three-dimensional co-culture of cancer cells and endothelial cells: A model system for dual analysis of tumor growth and angiogenesis","volume":"114","author":"Chiew","year":"2017","journal-title":"Biotechnol. Bioeng."},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12885-018-4871-y","article-title":"Co-culture of dendritic cells and cytokine-induced killer cells effectively suppresses liver cancer stem cell growth by inhibiting pathways in the immune system","volume":"18","author":"Yang","year":"2018","journal-title":"BMC Cancer"},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.cell.2016.05.082","article-title":"Modeling Development and Disease with Organoids","volume":"165","author":"Clevers","year":"2016","journal-title":"Cell"},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/ncb3312","article-title":"Organoids as an in vitro model of human development and disease","volume":"18","author":"Fatehullah","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_299","doi-asserted-by":"crossref","unstructured":"Van Tienderen, G.S., Groot Koerkamp, B., IJzermans, J.N.M., van der Laan, L.J.W., and Verstegen an Tienderen, M.M.A. (2019). Recreating Tumour Complexity in a Dish: Organoid Models to Study Liver Cancer Cells and their Extracellular Environment. Cancers, 11.","DOI":"10.3390\/cancers11111706"},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/3831213","article-title":"Remodelling and Improvements in Organoid Technology to Study Liver Carcinogenesis in a Dish","volume":"2019","author":"Tharehalli","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_301","doi-asserted-by":"crossref","unstructured":"Torresi, J., Tran, B.M., Christiansen, D., Earnest-Silveira, L., Schwab, R.H.M., and Vincan, E. (2019). HBV-related hepatocarcinogenesis: The role of signalling pathways and innovative ex vivo research models. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5916-6"},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.celrep.2018.07.001","article-title":"Organoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies","volume":"24","author":"Nuciforo","year":"2018","journal-title":"Cell Rep."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1172\/jci.insight.121490","article-title":"Human primary liver cancer organoids reveal intratumor and interpatient drug response heterogeneity","volume":"4","author":"Li","year":"2019","journal-title":"JCI Insight"},{"key":"ref_304","first-page":"1202","article-title":"Differential maintenance of cytochrome P450 enzymes in cultured precision-cut human liver slices","volume":"28","author":"Renwick","year":"2020","journal-title":"Drug Metab. Dispos."},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jim.2018.01.012","article-title":"Precision-cut human liver slice cultures as an immunological platform","volume":"455","author":"Wu","year":"2018","journal-title":"J. Immunol. Methods"},{"key":"ref_306","doi-asserted-by":"crossref","unstructured":"Janssen, A.W.F., Betzel, B., Stoopen, G., Berends, F.J., Janssen, I.M., Peijnenburg, A.A., and Kersten, S. (2015). The impact of PPAR\u03b1 activation on whole genome gene expression in human precision cut liver slices. BMC Genom., 16.","DOI":"10.1186\/s12864-015-1969-3"},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.tiv.2007.09.009","article-title":"Antigenotoxic effect of Xanthohumol in rat liver slices","volume":"22","author":"Plazar","year":"2008","journal-title":"Toxicol. Vitr."},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1093\/toxsci\/kfg064","article-title":"Gene expression in two hepatic cell lines, cultured primary hepatocytes, and liver slices compared to the in vivo liver gene expression in rats: Possible implications for toxicogenomics use of in vitro systems","volume":"73","author":"Boess","year":"2003","journal-title":"Toxicol. Sci."},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.addr.2017.07.004","article-title":"3D in vitro models of liver fibrosis","volume":"121","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_310","doi-asserted-by":"crossref","unstructured":"Prins, G., Luangmonkong, T., Oosterhuis, D., Mutsaers, H., Dekker, F., and Olinga, P. (2019). A Pathophysiological Model of Non-Alcoholic Fatty Liver Disease Using Precision-Cut Liver Slices. Nutrients, 11.","DOI":"10.3390\/nu11030507"},{"key":"ref_311","doi-asserted-by":"crossref","unstructured":"Gore, E., Bigaeva, E., Oldenburger, A., Kim, Y.O., Rippmann, J.F., Schuppan, D., Boersema, M., and Olinga, P. (2019). PI3K inhibition reduces murine and human liver fibrogenesis in precision-cut liver slices. Biochem. Pharmacol., 169.","DOI":"10.1016\/j.bcp.2019.113633"},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s00204-015-1543-4","article-title":"Experimental models of liver fibrosis","volume":"90","author":"Cogliati","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_313","first-page":"1247","article-title":"Human precision-cut liver tumor slices as a tumor patient-individual predictive test system for oncolytic measles vaccine viruses","volume":"34","author":"Zimmermann","year":"2009","journal-title":"Int. J. Oncol."},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s12072-018-9913-7","article-title":"Precision-cut liver slices: A versatile tool to advance liver research","volume":"13","author":"Palma","year":"2019","journal-title":"Hepatol. Int."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.tiv.2017.05.001","article-title":"Maintenance of high quality rat precision cut liver slices during culture to study hepatotoxic responses: Acetaminophen as a model compound","volume":"42","author":"Granitzny","year":"2017","journal-title":"Toxicol. Vitr."},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1002\/hep.30651","article-title":"A Bioreactor Technology for Modeling Fibrosis in Human and Rodent Precision-Cut Liver Slices","volume":"70","author":"Paish","year":"2019","journal-title":"Hepatology"},{"key":"ref_317","doi-asserted-by":"crossref","unstructured":"Vinken, M., and Rogiers, V. (2015). Immortalized Human Hepatic Cell Lines for In Vitro Testing and Research Purposes. Protocols in In Vitro Hepatocyte Research, Springer.","DOI":"10.1007\/978-1-4939-2074-7"},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1002\/ptr.5135","article-title":"Anticancer Effects of Baicalein on Hepatocellular Carcinoma Cells","volume":"28","author":"Zheng","year":"2014","journal-title":"Phyther. Res."},{"key":"ref_319","doi-asserted-by":"crossref","unstructured":"Zhou, T., Ye, L., Bai, Y., Sun, A., Cox, B., Liu, D., Li, Y., Liotta, D., Snyder, J.P., and Fu, H. (2014). Autophagy and Apoptosis in Hepatocellular Carcinoma Induced by EF25-(GSH)2: A Novel Curcumin Analog. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107876"},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.biocel.2017.07.010","article-title":"A computational integrative approach based on alternative splicing analysis to compare immortalized and primary cancer cells","volume":"91","author":"Tripathi","year":"2017","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/9175215","article-title":"Promoter Hypomethylation Is Responsible for Upregulated Expression of HAI-1 in Hepatocellular Carcinoma","volume":"2019","author":"Du","year":"2019","journal-title":"Dis. Markers"},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1093\/carcin\/bgv081","article-title":"Hepatocellular carcinoma-derived exosomes promote motility of immortalized hepatocyte through transfer of oncogenic proteins and RNAs","volume":"36","author":"He","year":"2015","journal-title":"Carcinogenesis"},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.bbrc.2018.10.144","article-title":"Regulation of periostin expression by Notch signaling in hepatocytes and liver cancer cell lines","volume":"506","author":"Kongkavitoon","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1053\/j.gastro.2019.05.001","article-title":"Analysis of Liver Cancer Cell Lines Identifies Agents With Likely Efficacy Against Hepatocellular Carcinoma and Markers of Response","volume":"157","author":"Caruso","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"5973","DOI":"10.21873\/anticanres.13802","article-title":"Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo","volume":"39","author":"Ogasawara","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1136\/gutjnl-2019-318506","article-title":"CDK12 inhibition mediates DNA damage and is synergistic with sorafenib treatment in hepatocellular carcinoma","volume":"69","author":"Wang","year":"2020","journal-title":"Gut"},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"14711","DOI":"10.1007\/s13277-016-5336-z","article-title":"Hint1 suppresses migration and invasion of hepatocellular carcinoma cells in vitro by modulating girdin activity","volume":"37","author":"Wu","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_328","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.ebiom.2019.09.007","article-title":"SWELL1 promotes cell growth and metastasis of hepatocellular carcinoma in vitro and in vivo","volume":"48","author":"Lu","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_329","first-page":"21","article-title":"CCL2\/CCR2 axis induces hepatocellular carcinoma invasion and epithelial-mesenchymal transition in\u00ef\u00bf\u00bdvitro through activation of the Hedgehog pathway","volume":"39","author":"Zhuang","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_330","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1097\/ALN.0000000000001528","article-title":"Lidocaine Induces Apoptosis and Suppresses Tumor Growth in Human Hepatocellular Carcinoma Cells In Vitro and in a Xenograft Model In Vivo","volume":"126","author":"Xing","year":"2017","journal-title":"Anesthesiology"},{"key":"ref_331","first-page":"2507","article-title":"In vitro effect of the Histone deacetylase inhibitor valproic acid on viability and apoptosis of the PLC\/PRF5 human hepatocellular carcinoma cell line","volume":"19","author":"Sanaei","year":"2018","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_332","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.mrgentox.2011.10.014","article-title":"Reduction of misleading (\u201cfalse\u201d) positive results in mammalian cell genotoxicity assays. I. Choice of cell type","volume":"742","author":"Fowler","year":"2012","journal-title":"Mutat. Res. Toxicol. Environ. Mutagen."},{"key":"ref_333","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.cbi.2006.12.003","article-title":"The human hepatoma HepaRG cells: A highly differentiated model for studies of liver metabolism and toxicity of xenobiotics","volume":"168","author":"Guillouzo","year":"2007","journal-title":"Chem. Biol. Interact."},{"key":"ref_334","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1248\/bpb.b17-00913","article-title":"Comparison of Drug Metabolism and Its Related Hepatotoxic Effects in HepaRG, Cryopreserved Human Hepatocytes, and HepG2 Cell Cultures","volume":"41","author":"Yokoyama","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"ref_335","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1007\/s00204-019-02406-9","article-title":"Quantitative comparison of in vitro genotoxicity between metabolically competent HepaRG cells and HepG2 cells using the high-throughput high-content CometChip assay","volume":"93","author":"Seo","year":"2019","journal-title":"Arch. Toxicol."},{"key":"ref_336","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1093\/carcin\/bgt054","article-title":"Transcriptomic responses generated by hepatocarcinogens in a battery of liver-based in vitro models","volume":"34","author":"Doktorova","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_337","doi-asserted-by":"crossref","first-page":"25","DOI":"10.7171\/jbt.18-2902-002","article-title":"The Cellosaurus, a Cell-Line Knowledge Resource","volume":"29","author":"Bairoch","year":"2018","journal-title":"J. Biomol. Tech."},{"key":"ref_338","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.humpath.2009.07.003","article-title":"Hep G2 is a hepatoblastoma-derived cell line","volume":"40","author":"Cheung","year":"2009","journal-title":"Hum. Pathol."},{"key":"ref_339","first-page":"470","article-title":"[Expressions of the metastasis-associated factors of a new human hepatocellular carcinoma cell line with highly metastatic potential]","volume":"79","author":"Tian","year":"1999","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref_340","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/BF02631017","article-title":"SK HEP-1: A human cell line of endothelial origin","volume":"28","author":"Heffelfinger","year":"1992","journal-title":"Vitr. Cell. Dev. Biol.-Anim."},{"key":"ref_341","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1124\/jpet.103.061713","article-title":"Induction of Drug Metabolism Enzymes and MDR1 Using a Novel Human Hepatocyte Cell Line","volume":"309","author":"Mills","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_342","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s11626-009-9219-0","article-title":"Establishment of a human neonatal hepatocyte cell line","volume":"45","author":"Reid","year":"2009","journal-title":"Vitr. Cell. Dev. Biol.-Anim."},{"key":"ref_343","doi-asserted-by":"crossref","first-page":"5123","DOI":"10.1073\/pnas.90.11.5123","article-title":"Simian virus 40 large tumor antigen-immortalized normal human liver epithelial cells express hepatocyte characteristics and metabolize chemical carcinogens","volume":"90","author":"Pfeifer","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_344","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/BF02723678","article-title":"Cell lines from non-neoplastic liver and hepatocellular carcinoma tissue from a single patient","volume":"32","author":"Noguchi","year":"1996","journal-title":"Vitr. Cell. Dev. Biol.-Anim."},{"key":"ref_345","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/cphy.c120011","article-title":"Liver Immunology","volume":"2","author":"Bogdanos","year":"2013","journal-title":"Compr Physiol."},{"key":"ref_346","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.1074\/mcp.M116.060145","article-title":"A Cell-type-resolved Liver Proteome","volume":"15","author":"Ding","year":"2016","journal-title":"Mol. Cell. Proteom."},{"key":"ref_347","doi-asserted-by":"crossref","unstructured":"Doumba, P.P., Nikolopoulou, M., Gomatos, I.P., Konstadoulakis, M.M., and Koskinas, J. (2013). Co-culture of primary human tumor hepatocytes from patients with hepatocellular carcinoma with autologous peripheral blood mononuclear cells: Study of their in vitro immunological interactions. BMC Gastroenterol., 13.","DOI":"10.1186\/1471-230X-13-17"},{"key":"ref_348","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1089\/ten.tec.2018.0134","article-title":"Three-Dimensional Spheroid Primary Human Hepatocytes in Monoculture and Coculture with Nonparenchymal Cells","volume":"24","author":"Baze","year":"2018","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_349","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3892\/ol.2016.5454","article-title":"Cell death in a co-culture of hepatocellular carcinoma cells and human umbilical vascular endothelial cells in a medium lacking glucose and arginine","volume":"13","author":"Tomizawa","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_350","doi-asserted-by":"crossref","unstructured":"Lin, J., Cao, S., Wang, Y., Hu, Y., Liu, H., Li, J., Chen, J., Li, P., Liu, J., and Wang, Q. (2018). Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1\/2\/HIF-1\u03b1\/VEGFA signalling in hepatocellular carcinoma. J. Exp. Clin. Cancer Res., 37.","DOI":"10.1186\/s13046-018-0727-1"},{"key":"ref_351","doi-asserted-by":"crossref","first-page":"567","DOI":"10.3748\/wjg.v25.i5.567","article-title":"Effect of adipose-derived mesenchymal stem cells on hepatocellular carcinoma: In vitro inhibition of carcinogenesis","volume":"25","author":"Serhal","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_352","doi-asserted-by":"crossref","first-page":"9419","DOI":"10.1002\/jcb.27259","article-title":"IL-6\/STAT3 pathway intermediates M1\/M2 macrophage polarization during the development of hepatocellular carcinoma","volume":"119","author":"Yin","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_353","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jhep.2014.10.029","article-title":"Alternatively activated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma","volume":"62","author":"Yeung","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_354","doi-asserted-by":"crossref","unstructured":"Schulte, L.-A., L\u00f3pez-Gil, J.C., Sainz, B., and Hermann, P.C. (2020). The Cancer Stem Cell in Hepatocellular Carcinoma. Cancers, 12.","DOI":"10.3390\/cancers12030684"},{"key":"ref_355","doi-asserted-by":"crossref","unstructured":"Zheng, Y.-W. (2013). Cellular reprogramming and hepatocellular carcinoma development. World J. Gastroenterol., 19.","DOI":"10.3748\/wjg.v19.i47.8850"},{"key":"ref_356","doi-asserted-by":"crossref","first-page":"261","DOI":"10.5009\/gnl15389","article-title":"Establishment of Hepatocellular Cancer Induced Pluripotent Stem Cells Using a Reprogramming Technique","volume":"11","author":"Kim","year":"2017","journal-title":"Gut Liver"},{"key":"ref_357","doi-asserted-by":"crossref","unstructured":"Gao, X., Sheng, Y., Yang, J., Wang, C., Zhang, R., Zhu, Y., Zhang, Z., Zhang, K., Yan, S., and Sun, H. (2018). Osteopontin alters DNA methylation through up-regulating DNMT1 and sensitizes CD133+\/CD44+ cancer stem cells to 5 azacytidine in hepatocellular carcinoma. J. Exp. Clin. Cancer Res., 37.","DOI":"10.1186\/s13046-018-0832-1"},{"key":"ref_358","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1002\/hep.23423","article-title":"An Identification of Novel Therapy for Human Hepatocellular Carcinoma by Using Human Induced Pluripotent Stem Cells","volume":"51","author":"Moriguchi","year":"2010","journal-title":"Hepatology"},{"key":"ref_359","doi-asserted-by":"crossref","unstructured":"Moriguchi, H., and Madson, J. (2013). The reprogramming therapy for a patient with advanced hepatocellular carcinoma by using human-induced pluripotent stem (iPS) cells technology. Case Reports, 2013.","DOI":"10.1136\/bcr-2013-008950"},{"key":"ref_360","doi-asserted-by":"crossref","first-page":"6103","DOI":"10.1073\/pnas.1912146117","article-title":"A hepatocyte differentiation model reveals two subtypes of liver cancer with different oncofetal properties and therapeutic targets","volume":"117","author":"Liu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_361","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1080\/15376516.2020.1800881","article-title":"Ready to go 3D? A semi-automated protocol for microwell spheroid arrays to increase scalability and throughput of 3D cell culture testing","volume":"30","author":"Basu","year":"2020","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_362","doi-asserted-by":"crossref","unstructured":"Kim, S.M., Han, J.M., Le, T.T., Sohng, J.K., and Jung, H.J. (2020). Anticancer and Antiangiogenic Activities of Novel \u03b1-Mangostin Glycosides in Human Hepatocellular Carcinoma Cells via Downregulation of c-Met and HIF-1\u03b1. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21114043"},{"key":"ref_363","doi-asserted-by":"crossref","unstructured":"Ceballos, M.P., Angel, A., Delprato, C.B., Livore, V.I., Ferretti, A.C., Lucci, A., Comanzo, C.G., de Lujan Alvarez, M., Quiroga, A.D., and Mottino, A.D. (2021). Sirtuin 1 and 2 inhibitors enhance the inhibitory effect of sorafenib in hepatocellular carcinoma cells. Eur. J. Pharmacol., 892.","DOI":"10.1016\/j.ejphar.2020.173736"},{"key":"ref_364","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1080\/1061186X.2020.1853743","article-title":"Erlotinib entrapped in cholesterol-depleting cyclodextrin nanoparticles shows improved antitumoral efficacy in 3D spheroid tumors of the lung and the liver","volume":"29","author":"Varan","year":"2021","journal-title":"J. Drug Target."},{"key":"ref_365","doi-asserted-by":"crossref","unstructured":"Song, Y., Lee, S.-Y., Kim, S., Choi, I., Kim, S.-H., Shum, D., Heo, J., Kim, A.-R., Kim, K.M., and Seo, H.R. (2020). Inhibitors of Na+\/K+ ATPase exhibit antitumor effects on multicellular tumor spheroids of hepatocellular carcinoma. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-62134-4"},{"key":"ref_366","doi-asserted-by":"crossref","unstructured":"Song, Y., Kim, J.-S., Kim, S.-H., Park, Y.K., Yu, E., Kim, K.-H., Seo, E.-J., Oh, H.-B., Lee, H.C., and Kim, K.M. (2018). Patient-derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinoma. J. Exp. Clin. Cancer Res., 37.","DOI":"10.1186\/s13046-018-0752-0"},{"key":"ref_367","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.addr.2014.02.006","article-title":"Drug discovery through stem cell-based organoid models","volume":"69\u201370","author":"Ranga","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_368","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1136\/gutjnl-2019-319256","article-title":"Liver organoids: From basic research to therapeutic applications","volume":"68","author":"Prior","year":"2019","journal-title":"Gut"},{"key":"ref_369","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.stem.2015.12.005","article-title":"Engineering Stem Cell Organoids","volume":"18","author":"Yin","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_370","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/8472712","article-title":"Development of Collagen-Based 3D Matrix for Gastrointestinal Tract-Derived Organoid Culture","volume":"2019","author":"Jee","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_371","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature12271","article-title":"Vascularized and functional human liver from an iPSC-derived organ bud transplant","volume":"499","author":"Takebe","year":"2013","journal-title":"Nature"},{"key":"ref_372","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/s41556-019-0359-5","article-title":"Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes","volume":"21","author":"Sun","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_373","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/j.1478-3231.2006.01268.x","article-title":"Ex vivo analysis of antineoplastic agents in precision-cut tissue slices of human origin: Effects of cyclooxygenase-2 inhibition in hepatocellular carcinoma","volume":"26","author":"Kern","year":"2006","journal-title":"Liver Int."},{"key":"ref_374","doi-asserted-by":"crossref","first-page":"8352","DOI":"10.1073\/pnas.0907676107","article-title":"Preclinical model of organotypic culture for pharmacodynamic profiling of human tumors","volume":"107","author":"Vaira","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_375","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0140-6736(18)30010-2","article-title":"Hepatocellular carcinoma","volume":"391","author":"Forner","year":"2018","journal-title":"Lancet"},{"key":"ref_376","doi-asserted-by":"crossref","first-page":"550.e1","DOI":"10.1016\/j.ccr.2014.04.002","article-title":"SnapShot: Hepatocellular Carcinoma","volume":"25","author":"Marquardt","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_377","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1056\/NEJMoa0708857","article-title":"Sorafenib in Advanced Hepatocellular Carcinoma","volume":"359","author":"Llovet","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_378","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.jhep.2016.01.012","article-title":"Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial","volume":"64","author":"Lencioni","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_379","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/hep.27290","article-title":"Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized phase III trial","volume":"60","author":"Kudo","year":"2014","journal-title":"Hepatology"},{"key":"ref_380","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1080\/0284186X.2018.1479070","article-title":"Are we SHARP enough? The importance of adequate patient selection in sorafenib treatment for hepatocellular carcinoma","volume":"57","author":"Labeur","year":"2018","journal-title":"Acta Oncol."},{"key":"ref_381","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/S0140-6736(18)30207-1","article-title":"Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial","volume":"391","author":"Kudo","year":"2018","journal-title":"Lancet"},{"key":"ref_382","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0140-6736(16)32453-9","article-title":"Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"389","author":"Bruix","year":"2017","journal-title":"Lancet"},{"key":"ref_383","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1056\/NEJMoa1717002","article-title":"Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma","volume":"379","author":"Meyer","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_384","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_385","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1002\/ijc.29113","article-title":"Sorafenib synergizes with metformin in NSCLC through AMPK pathway activation","volume":"136","author":"Groenendijk","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_386","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1016\/j.jcmgh.2020.12.009","article-title":"Predicting HCC Response to Multikinase Inhibitors With In Vivo Cirrhotic Mouse Model for Personalized Therapy","volume":"11","author":"Huang","year":"2021","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_387","doi-asserted-by":"crossref","unstructured":"Shen, J., Cai, W., Ma, Y., Xu, R., Huo, Z., Song, L., Qiu, X., Zhang, Y., Li, A., and Cao, W. (2020). hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling Pathway. Nanoscale Res. Lett., 15.","DOI":"10.1186\/s11671-020-03451-5"},{"key":"ref_388","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez, M.M., Onorato, A., Cantero, M.J., Dom\u00ednguez, L., Bayo, J., Fiore, E., Garc\u00eda, M., Atorrasagasti, C., Canbay, A., and Malvicini, M. (2021). 4-methylumbelliferone-mediated polarization of M1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-85491-0"},{"key":"ref_389","doi-asserted-by":"crossref","first-page":"7773","DOI":"10.2147\/OTT.S222097","article-title":"Intratumoral IL-12 Gene Therapy Inhibits Tumor Growth In A HCC-Hu-PBL-NOD\/SCID Murine Model","volume":"12","author":"Zhou","year":"2019","journal-title":"Onco. Targets. Ther."},{"key":"ref_390","doi-asserted-by":"crossref","first-page":"52866","DOI":"10.18632\/oncotarget.17905","article-title":"Treatment of hepatocellular carcinoma with a GPC3-targeted bispecific T cell engager","volume":"8","author":"Bi","year":"2017","journal-title":"Oncotarget"},{"key":"ref_391","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jcmgh.2018.08.008","article-title":"Dipeptidyl Peptidase 4 Inhibitors Reduce Hepatocellular Carcinoma by Activating Lymphocyte Chemotaxis in Mice","volume":"7","author":"Nishina","year":"2019","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_392","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1097\/CAD.0000000000000791","article-title":"Antitumor and immunomodulatory effects of a novel multitarget inhibitor, CS2164, in mouse hepatocellular carcinoma models","volume":"30","author":"Zhou","year":"2019","journal-title":"Anticancer. Drugs"},{"key":"ref_393","doi-asserted-by":"crossref","first-page":"11145","DOI":"10.18632\/oncotarget.24298","article-title":"Combination of AKT inhibitor ARQ 092 and sorafenib potentiates inhibition of tumor progression in cirrhotic rat model of hepatocellular carcinoma","volume":"9","author":"Jilkova","year":"2018","journal-title":"Oncotarget"},{"key":"ref_394","doi-asserted-by":"crossref","first-page":"23265","DOI":"10.18632\/oncotarget.15575","article-title":"Synergistic anti-tumor efficacy of sorafenib and fluvastatin in hepatocellular carcinoma","volume":"8","author":"Cheng","year":"2017","journal-title":"Oncotarget"},{"key":"ref_395","doi-asserted-by":"crossref","first-page":"5575","DOI":"10.2147\/OTT.S250233","article-title":"HDAC1\/2 Inhibitor Romidepsin Suppresses DEN-Induced Hepatocellular Carcinogenesis in Mice","volume":"13","author":"Afaloniati","year":"2020","journal-title":"Onco. Targets. Ther."},{"key":"ref_396","doi-asserted-by":"crossref","first-page":"894","DOI":"10.7150\/thno.21168","article-title":"Combined delivery of sorafenib and a MEK inhibitor using CXCR4-targeted nanoparticles reduces hepatic fibrosis and prevents tumor development","volume":"8","author":"Sung","year":"2018","journal-title":"Theranostics"},{"key":"ref_397","doi-asserted-by":"crossref","unstructured":"Wang, Q., Bin, C., Xue, Q., Gao, Q., Huang, A., Wang, K., and Tang, N. (2021). GSTZ1 sensitizes hepatocellular carcinoma cells to sorafenib-induced ferroptosis via inhibition of NRF2\/GPX4 axis. Cell Death Dis., 12.","DOI":"10.1038\/s41419-021-03718-4"},{"key":"ref_398","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1158\/1940-6207.CAPR-20-0200","article-title":"Immune Checkpoint Inhibition is Safe and Effective for Liver Cancer Prevention in a Mouse Model of Hepatocellular Carcinoma","volume":"13","author":"Chung","year":"2020","journal-title":"Cancer Prev. Res."},{"key":"ref_399","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fonc.2020.00645","article-title":"Protective Role of Decorin in Primary Hepatocellular Carcinoma","volume":"10","author":"Reszegi","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_400","doi-asserted-by":"crossref","unstructured":"Kojima, M., Takahashi, H., Kuwashiro, T., Tanaka, K., Mori, H., Ozaki, I., Kitajima, Y., Matsuda, Y., Ashida, K., and Eguchi, Y. (2020). Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165722"},{"key":"ref_401","first-page":"2668","article-title":"Berberine prevents non-alcoholic steatohepatitis-derived hepatocellular carcinoma by inhibiting inflammation and angiogenesis in mice","volume":"11","author":"Luo","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_402","doi-asserted-by":"crossref","first-page":"589","DOI":"10.5306\/wjco.v11.i8.589","article-title":"Novel molecular targets in hepatocellular carcinoma","volume":"11","author":"Chow","year":"2020","journal-title":"World J. Clin. Oncol."},{"key":"ref_403","first-page":"2993","article-title":"Recent progress in treatment of hepatocellular carcinoma","volume":"10","author":"Chen","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"ref_404","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1053\/j.gastro.2015.12.033","article-title":"Variable Intra-Tumor Genomic Heterogeneity of Multiple Lesions in Patients With Hepatocellular Carcinoma","volume":"150","author":"Xue","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_405","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1634\/theoncologist.2014-0304","article-title":"Drug Development for Hepatocellular Carcinoma: Knowing the Past Helps to Understand the Future","volume":"19","author":"Chan","year":"2014","journal-title":"Oncologist"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/21\/5583\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:27:35Z","timestamp":1760167655000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/21\/5583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,8]]},"references-count":405,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["cancers13215583"],"URL":"https:\/\/doi.org\/10.3390\/cancers13215583","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,8]]}}}