{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:31:10Z","timestamp":1788363070705,"version":"build-2803163510"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.fr","clinicalkey.jp","clinicalkey.es","clinicalkey.com.au","clinicalkey.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.tox.2025.154127","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T03:30:47Z","timestamp":1742959847000},"page":"154127","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Investigating the functional role of BUB1B in aflatoxin B1-associated hepatocarcinogenesis"],"prefix":"10.1016","volume":"514","author":[{"given":"Hayam","family":"Hamdy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaa A.","family":"Aly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyad","family":"Elkord","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.tox.2025.154127_bib1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4314\/ajcem.v24i1.2","article-title":"The synergism of hepatitis B and aflatoxicosis in hepatocellular carcinoma development: a mini-review","volume":"24","author":"Alao","year":"2023","journal-title":"Afr. J. Clin. Exp. Microbiol."},{"key":"10.1016\/j.tox.2025.154127_bib2","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/j.1349-7006.2009.01457.x","article-title":"High expression of BUBR1 is one of the factors for inducing DNA aneuploidy and progression in gastric cancer","volume":"101","author":"Ando","year":"2010","journal-title":"Cancer Sci."},{"key":"10.1016\/j.tox.2025.154127_bib3","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12071971","article-title":"JAK-STAT signalling pathway in cancer","volume":"12","author":"Brooks","year":"2020","journal-title":"Cancers"},{"key":"10.1016\/j.tox.2025.154127_bib4","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1080\/15376516.2021.2021339","article-title":"Aflatoxin B1: metabolism, toxicology, and its involvement in oxidative stress and cancer development","volume":"23","author":"Cao","year":"2022","journal-title":"Toxicol. Mech. Methods"},{"key":"10.1016\/j.tox.2025.154127_bib5","doi-asserted-by":"crossref","first-page":"106","DOI":"10.18632\/genesandcancer.53","article-title":"Requirement for BUB1B\/BUBR1 in tumor progression of lung adenocarcinoma","volume":"6","author":"Chen","year":"2015","journal-title":"Genes Cancer"},{"key":"10.1016\/j.tox.2025.154127_bib6","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/nature01355","article-title":"Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain","volume":"421","author":"Cua","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.tox.2025.154127_bib7","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1158\/2159-8290.CD-12-0353","article-title":"Cancer-specific requirement for BUB1B\/BUBR1 in human brain tumor isolates and genetically transformed cells","volume":"3","author":"Ding","year":"2013","journal-title":"Cancer Discov."},{"key":"10.1016\/j.tox.2025.154127_bib8","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1001\/archinte.167.18.1983","article-title":"Epidemiology of hepatocellular carcinoma in Hispanics in the United States","volume":"167","author":"El-Serag","year":"2007","journal-title":"Arch. Intern Med"},{"key":"10.1016\/j.tox.2025.154127_bib9","doi-asserted-by":"crossref","DOI":"10.1002\/gcc.22385","article-title":"Prevalence of germline mutations in the spindle assembly checkpoint gene BUB1B in individuals with early-onset colorectal cancer","volume":"55","author":"Hahn","year":"2016","journal-title":"Genes, Chromosomes Cancer"},{"key":"10.1016\/j.tox.2025.154127_bib10","first-page":"7","article-title":"JAK\/STAT signaling in hepatocellular carcinoma","author":"Hin Tang","year":"2020","journal-title":"Hepatic Oncol."},{"key":"10.1016\/j.tox.2025.154127_bib11","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The JAK\/STAT signaling pathway: from bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduct. Target Ther."},{"key":"10.1016\/j.tox.2025.154127_bib12","doi-asserted-by":"crossref","first-page":"1023177","DOI":"10.3389\/fonc.2022.1023177","article-title":"The role of IL-6\/JAK2\/STAT3 signaling pathway in cancers","volume":"12","author":"Huang","year":"2022","journal-title":"Front Oncol."},{"key":"10.1016\/j.tox.2025.154127_bib13","doi-asserted-by":"crossref","first-page":"62","DOI":"10.17998\/jlc.2024.03.13","article-title":"Changing etiology and epidemiology of hepatocellular carcinoma: asia and worldwide","volume":"24","author":"Kim","year":"2024","journal-title":"J. Liver Cancer"},{"key":"10.1016\/j.tox.2025.154127_bib14","doi-asserted-by":"crossref","first-page":"R966","DOI":"10.1016\/j.cub.2012.10.006","article-title":"The spindle assembly checkpoint","volume":"22","author":"Lara-Gonzalez","year":"2012","journal-title":"Curr. Biol. CB"},{"key":"10.1016\/j.tox.2025.154127_bib15","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1146\/annurev.immunol.16.1.293","article-title":"JAKS AND STATS: biological implications*","volume":"16","author":"Leonard","year":"1998","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.tox.2025.154127_bib16","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S1074-7613(00)80413-6","article-title":"IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses","volume":"4","author":"Magram","year":"1996","journal-title":"Immunity"},{"key":"10.1016\/j.tox.2025.154127_bib17","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.immuni.2008.03.001","article-title":"Th17 cell differentiation: the long and winding road","volume":"28","author":"McGeachy","year":"2008","journal-title":"Immunity"},{"key":"10.1016\/j.tox.2025.154127_bib18","first-page":"6","article-title":"STAT4 is expressed in neutrophils and promotes antimicrobial immunity","author":"Mehrpouya-Bahrami","year":"2021","journal-title":"JCI Insight"},{"key":"10.1016\/j.tox.2025.154127_bib19","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241210115","article-title":"Immunomodulatory role of interferons in viral and bacterial infections","volume":"24","author":"Mertowska","year":"2023","journal-title":"Int J. Mol. Sci."},{"key":"10.1016\/j.tox.2025.154127_bib20","first-page":"385","article-title":"The role of BUB and CDC proteins in low-grade breast cancers","author":"Mukherjee","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.tox.2025.154127_bib21","doi-asserted-by":"crossref","first-page":"4388","DOI":"10.4049\/jimmunol.169.8.4388","article-title":"Activated STAT4 has an essential role in Th1 differentiation and proliferation that is independent of its role in the maintenance of IL-12R beta 2 chain expression and signaling","volume":"169","author":"Nishikomori","year":"2022","journal-title":"J. Immunol."},{"key":"10.1016\/j.tox.2025.154127_bib22","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1083\/jcb.201210099","article-title":"Loss of BubR1 acetylation causes defects in spindle assembly checkpoint signaling and promotes tumor formation","volume":"202","author":"Park","year":"2013","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.tox.2025.154127_bib23","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241813764","article-title":"Exploring the JAK\/STAT signaling pathway in Hepatocellular Carcinoma: unraveling signaling complexity and therapeutic implications","volume":"24","author":"Park","year":"2023","journal-title":"Int J. Mol. Sci."},{"key":"10.1016\/j.tox.2025.154127_bib24","doi-asserted-by":"crossref","first-page":"1491394","DOI":"10.3389\/fcell.2024.1491394","article-title":"Role of spindle assembly checkpoint proteins in gametogenesis and embryogenesis","volume":"12","author":"Pun","year":"2025","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.tox.2025.154127_bib25","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1056\/NEJMoa1006565","article-title":"Homozygous BUB1B mutation and susceptibility to gastrointestinal neoplasia","volume":"363","author":"Rio Frio","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.tox.2025.154127_bib26","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a028415","article-title":"Interleukin-6 family cytokines","volume":"10","author":"Rose-John","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"10.1016\/j.tox.2025.154127_bib27","first-page":"81","article-title":"Aflatoxin B1: a review on metabolism, toxicity, occurrence in food, occupational exposure, and detoxification methods","volume":"124","author":"Rushing","year":"2019","journal-title":"Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"10.1016\/j.tox.2025.154127_bib28","doi-asserted-by":"crossref","first-page":"10188","DOI":"10.1073\/pnas.90.21.10188","article-title":"Interleukin 12 acts directly on CD4+\u2009T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming","volume":"90","author":"Seder","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.tox.2025.154127_bib29","doi-asserted-by":"crossref","first-page":"6343","DOI":"10.1007\/s13277-015-4520-x","article-title":"Genetic variants in IL12 influence both hepatitis B virus clearance and HBV-related hepatocellular carcinoma development in a Chinese male population","volume":"3","author":"Tan","year":"2016","journal-title":"Tumour Biol. J. Int. Soc. Oncodev. Biol. Med."},{"key":"10.1016\/j.tox.2025.154127_bib30","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nri1001","article-title":"Interleukin-12 and the regulation of innate resistance and adaptive immunity","volume":"3","author":"Trinchieri","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.tox.2025.154127_bib31","doi-asserted-by":"crossref","first-page":"5889","DOI":"10.1158\/0008-5472.CAN-12-1991","article-title":"Identification of FoxM1\/Bub1b signaling pathway as a required component for growth and survival of rhabdomyosarcoma","volume":"72","author":"Wan","year":"2012","journal-title":"Cancer Res."},{"key":"10.1016\/j.tox.2025.154127_bib32","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1038\/leu.2012.96","article-title":"Using combination therapy to override stromal-mediated chemoresistance in mutant FLT3-positive AML: synergism between FLT3 inhibitors, dasatinib\/multi-targeted inhibitors and JAK inhibitors","volume":"26","author":"Weisberg","year":"2012","journal-title":"Leukemia"},{"key":"10.1016\/j.tox.2025.154127_bib33","article-title":"Aflatoxins as risk factors for hepatocellular carcinoma in humans","volume":"52","author":"Wogan","year":"1992","journal-title":"Cancer Res."},{"key":"10.1016\/j.tox.2025.154127_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2020.106210","article-title":"The role of JAK\/STAT signaling pathway and its inhibitors in diseases","volume":"80","author":"Xin","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.tox.2025.154127_bib35","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.cancergencyto.2006.11.012","article-title":"Overexpression of BUBR1 is associated with chromosomal instability in bladder cancer","volume":"174","author":"Yamamoto","year":"2007","journal-title":"Cancer Genet. Cytogenet."},{"key":"10.1016\/j.tox.2025.154127_bib36","first-page":"589","article-title":"A global view of hepatocellular carcinoma: trends, risk, prevention and management","volume":"16","author":"Yang","year":"2019","journal-title":"Gastroenterol. Hepatol."},{"key":"10.1016\/j.tox.2025.154127_bib37","doi-asserted-by":"crossref","DOI":"10.3390\/ani12213050","article-title":"The analysis of E-Cadherin, N-Cadherin, vimentin, HER-2, CEA, CA15-3 and SF expression in the diagnosis of canine mammary tumors","volume":"12","author":"Yu","year":"2022","journal-title":"Animals"},{"key":"10.1016\/j.tox.2025.154127_bib38","article-title":"Overexpression of BUB1B contributes to progression of prostate cancer and predicts poor outcome in patients with prostate cancer","author":"Zhong","year":"2016","journal-title":"OncoTargets Ther."},{"key":"10.1016\/j.tox.2025.154127_bib39","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1182\/blood-2008-05-078154","article-title":"CD4 T cells: fates, functions, and faults","volume":"112","author":"Zhu","year":"2008","journal-title":"Blood"}],"container-title":["Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X25000836?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X25000836?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T11:14:06Z","timestamp":1744370046000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0300483X25000836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":39,"alternative-id":["S0300483X25000836"],"URL":"https:\/\/doi.org\/10.1016\/j.tox.2025.154127","relation":{},"ISSN":["0300-483X"],"issn-type":[{"value":"0300-483X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Investigating the functional role of BUB1B in aflatoxin B1-associated hepatocarcinogenesis","name":"articletitle","label":"Article Title"},{"value":"Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tox.2025.154127","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"154127"}}