{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:30:14Z","timestamp":1791333014007,"version":"4.3.1"},"reference-count":48,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":3662,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["li.uscap.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Laboratory Investigation"],"published-print":{"date-parts":[[2013,1]]},"DOI":"10.1038\/labinvest.2012.144","type":"journal-article","created":{"date-parts":[[2012,10,29]],"date-time":"2012-10-29T10:57:13Z","timestamp":1351508233000},"page":"8-19","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":77,"title":["OPA1 downregulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma"],"prefix":"10.1016","volume":"93","author":[{"given":"Xiangxuan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhai","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M","family":"Puszyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olorunseun O","family":"Ogunwobi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengde","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roniel","family":"Cabrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1038\/labinvest.2012.144_bib1","first-page":"10","volume":"55","author":"Jemal","year":"2005","journal-title":"Cancer Statistics CA Cancer J Clin"},{"key":"10.1038\/labinvest.2012.144_bib2","doi-asserted-by":"crossref","first-page":"3843","DOI":"10.1016\/j.transproceed.2010.06.016","article-title":"Liver transplantation for metastasized extragastrointestinal stromal tumor: a case report and an overview of literature","volume":"42","author":"Frilling","year":"2010","journal-title":"Transplant Proc"},{"key":"10.1038\/labinvest.2012.144_bib3","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1158\/0008-5472.CAN-05-0808","article-title":"The Raf inhibitor BAY 43-9006 (Sorafenib) induces caspase-independent apoptosis in melanoma cells","volume":"66","author":"Panka","year":"2006","journal-title":"Cancer Res"},{"key":"10.1038\/labinvest.2012.144_bib4","doi-asserted-by":"crossref","first-page":"e270","DOI":"10.1016\/j.leukres.2010.04.011","article-title":"Sorafenib induces sustained molecular remission in FLT3-ITD positive AML with relapse after second allogeneic stem cell transplantation without exacerbation of acute GVHD: a case report","volume":"34","author":"Winkler","year":"2010","journal-title":"Leuk Res"},{"key":"10.1038\/labinvest.2012.144_bib5","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1158\/1078-0432.CCR-06-2667","article-title":"Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants","volume":"13","author":"Guida","year":"2007","journal-title":"Clin Cancer Res"},{"key":"10.1038\/labinvest.2012.144_bib6","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1111\/j.1442-2050.2007.00799.x","article-title":"Sorafenib inhibits MAPK-mediated proliferation in a Barrett's esophageal adenocarcinoma cell line","volume":"21","author":"Keswani","year":"2008","journal-title":"Dis Esophagus"},{"key":"10.1038\/labinvest.2012.144_bib7","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.ejca.2010.11.021","article-title":"Immunomodulatory effects of sorafenib on peripheral immune effector cells in metastatic renal cell carcinoma","volume":"47","author":"Busse","year":"2011","journal-title":"Eur J Cancer"},{"key":"10.1038\/labinvest.2012.144_bib8","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0076-6879(05)07047-3","article-title":"Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF\/MEK\/ERK pathway in tumor cells and tyrosine kinases VEGFR\/PDGFR in tumor vasculature","volume":"407","author":"Adnane","year":"2006","journal-title":"Methods Enzymol"},{"key":"10.1038\/labinvest.2012.144_bib9","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1158\/1535-7163.MCT-08-0013","article-title":"Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling","volume":"7","author":"Wilhelm","year":"2008","journal-title":"Mol Cancer Ther"},{"key":"10.1038\/labinvest.2012.144_bib10","doi-asserted-by":"crossref","first-page":"9309","DOI":"10.1158\/0008-5472.CAN-10-1033","article-title":"Induction of DNA damage-inducible gene GADD45beta contributes to sorafenib-induced apoptosis in hepatocellular carcinoma cells","volume":"70","author":"Ou","year":"2010","journal-title":"Cancer Res"},{"key":"10.1038\/labinvest.2012.144_bib11","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1002\/hep.23836","article-title":"The Bcl-xL inhibitor, ABT-737, efficiently induces apoptosis and suppresses growth of hepatoma cells in combination with sorafenib","volume":"52","author":"Ou","year":"2010","journal-title":"Hepatology"},{"key":"10.1038\/labinvest.2012.144_bib12","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.jhep.2009.12.024","article-title":"The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma","volume":"52","author":"Shimizu","year":"2010","journal-title":"J Hepatol"},{"key":"10.1038\/labinvest.2012.144_bib13","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1053\/j.gastro.2011.03.006","article-title":"Targeted therapies for hepatocellular carcinoma","volume":"140","author":"Villanueva","year":"2011","journal-title":"Gastroenterology"},{"key":"10.1038\/labinvest.2012.144_bib14","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1056\/NEJMe0802241","article-title":"Sorafenib in liver cancer\u2014just the beginning","volume":"359","author":"Roberts","year":"2008","journal-title":"N Engl J Med"},{"key":"10.1038\/labinvest.2012.144_bib15","first-page":"295","article-title":"What is the indication for sorafenib in hepatocellular carcinoma? A clinical challenge","volume":"25","author":"Kim","year":"2011","journal-title":"Oncology"},{"key":"10.1038\/labinvest.2012.144_bib16","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1053\/j.gastro.2007.09.017","article-title":"Hepatitis C triggers apoptosis of newly developed hepatoma cell line through anti-viral defense system","volume":"133","author":"Zhu","year":"2007","journal-title":"Gastroenterology"},{"key":"10.1038\/labinvest.2012.144_bib17","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1097\/00000658-197401000-00016","article-title":"Hepatic cellular responses to liver cancer: abnormalities in metabolism of mitochondria isolated from human liver involved with carcinoma","volume":"179","author":"Ozawa","year":"1974","journal-title":"Ann Surg"},{"key":"10.1038\/labinvest.2012.144_bib18","first-page":"101","article-title":"Nucleic acids and protein synthesis in cancer cell mitochondria. II. Amino acid incorporation into proteins of rat liver and hepatoma cell mitochondria","volume":"22","author":"Inaba","year":"1968","journal-title":"Acta Med Okayama"},{"key":"10.1038\/labinvest.2012.144_bib19","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.ejcb.2007.04.002","article-title":"Mitochondrial clustering induced by overexpression of the mitochondrial fusion protein Mfn2 causes mitochondrial dysfunction and cell death","volume":"86","author":"Huang","year":"2007","journal-title":"Eur J Cell Biol"},{"key":"10.1038\/labinvest.2012.144_bib20","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.drudis.2010.12.006","article-title":"Newly developed strategies for multifunctional mitochondria-targeted agents in cancer therapy","volume":"16","author":"Zhang","year":"2011","journal-title":"Drug Discov Today"},{"key":"10.1038\/labinvest.2012.144_bib21","doi-asserted-by":"crossref","first-page":"4061","DOI":"10.1038\/sj.emboj.7601276","article-title":"Dissociating the dual roles of apoptosis-inducing factor in maintaining mitochondrial structure and apoptosis","volume":"25","author":"Cheung","year":"2006","journal-title":"EMBO J"},{"key":"10.1038\/labinvest.2012.144_bib22","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.cell.2006.06.010","article-title":"Mitochondria: dynamic organelles in disease, aging, and development","volume":"125","author":"Chan","year":"2006","journal-title":"Cell"},{"key":"10.1038\/labinvest.2012.144_bib23","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.semcdb.2009.12.003","article-title":"Mitochondrial dynamics in model organisms: what yeasts, worms and flies have taught us about fusion and fission of mitochondria","volume":"21","author":"Westermann","year":"2010","journal-title":"Semin Cell Dev Biol"},{"key":"10.1038\/labinvest.2012.144_bib24","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/jcp.22788","article-title":"Targeting mitochondria as a therapeutic target in cancer","volume":"227","author":"Wenner","year":"2012","journal-title":"J Cell Physiol"},{"key":"10.1038\/labinvest.2012.144_bib25","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1158\/1535-7163.MCT-09-0947","article-title":"Sorafenib induces growth arrest and apoptosis of human glioblastoma cells through the dephosphorylation of signal transducers and activators of transcription 3","volume":"9","author":"Yang","year":"2010","journal-title":"Mol Cancer Ther"},{"key":"10.1038\/labinvest.2012.144_bib26","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1096\/fj.05-5665fje","article-title":"Gossypol induces Bax\/Bak-independent activation of apoptosis and cytochrome c release via a conformational change in Bcl-2","volume":"20","author":"Lei","year":"2006","journal-title":"FASEB J"},{"key":"10.1038\/labinvest.2012.144_bib27","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1111\/j.1471-4159.2007.05197.x","article-title":"HIV-infected macrophages mediate neuronal apoptosis through mitochondrial glutaminase","volume":"105","author":"Tian","year":"2008","journal-title":"J Neurochem"},{"key":"10.1038\/labinvest.2012.144_bib28","doi-asserted-by":"crossref","first-page":"e5546","DOI":"10.1371\/journal.pone.0005546","article-title":"Mitochondrial fragmentation is involved in methamphetamine-induced cell death in rat hippocampal neural progenitor cells","volume":"4","author":"Tian","year":"2009","journal-title":"PLoS One"},{"key":"10.1038\/labinvest.2012.144_bib29","doi-asserted-by":"crossref","first-page":"5506","DOI":"10.1093\/nar\/22.24.5506","article-title":"A rapid and simple method for the isolation of apoptotic DNA fragments","volume":"22","author":"Herrmann","year":"1994","journal-title":"Nucleic Acids Res"},{"key":"10.1038\/labinvest.2012.144_bib30","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.1038\/sj.onc.1208484","article-title":"Arsenic trioxide (As(2)O(3)) induces apoptosis through activation of Bax in hematopoietic cells","volume":"24","author":"Zheng","year":"2005","journal-title":"Oncogene"},{"key":"10.1038\/labinvest.2012.144_bib31","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1038\/onc.2009.403","article-title":"Sorafenib, a dual Raf kinase\/vascular endothelial growth factor receptor inhibitor has significant anti-myeloma activity and synergizes with common anti-myeloma drugs","volume":"29","author":"Ramakrishnan","year":"2010","journal-title":"Oncogene"},{"key":"10.1038\/labinvest.2012.144_bib32","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1158\/1535-7163.MCT-06-0235","article-title":"Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways","volume":"5","author":"Yu","year":"2006","journal-title":"Mol Cancer Ther"},{"key":"10.1038\/labinvest.2012.144_bib33","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1023\/A:1025738712958","article-title":"Fusion, fragmentation, and fission of mitochondria","volume":"68","author":"Polyakov","year":"2003","journal-title":"Biochemistry (Mosc)"},{"key":"10.1038\/labinvest.2012.144_bib34","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.clinre.2010.12.007","article-title":"Liver transplantation in a patient treated by sorafenib for hepatocellular carcinoma","volume":"35","author":"Borentain","year":"2011","journal-title":"Clin Res Hepatol Gastroenterol"},{"key":"10.1038\/labinvest.2012.144_bib35","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1471-230X-11-4","article-title":"Complete response for advanced liver cancer during sorafenib therapy: case report","volume":"11","author":"Sacco","year":"2011","journal-title":"BMC Gastroenterol"},{"key":"10.1038\/labinvest.2012.144_bib36","doi-asserted-by":"crossref","first-page":"239","DOI":"10.4254\/wjh.v2.i6.239","article-title":"Long-term survival of a HCC-patient with severe liver dysfunction treated with sorafenib","volume":"2","author":"Roderburg","year":"2010","journal-title":"World J Hepatol"},{"key":"10.1038\/labinvest.2012.144_bib37","doi-asserted-by":"crossref","first-page":"6515","DOI":"10.1158\/0008-5472.CAN-09-1076","article-title":"Sorafenib inhibits non-small cell lung cancer cell growth by targeting B-RAF in KRAS wild-type cells and C-RAF in KRAS mutant cells","volume":"69","author":"Takezawa","year":"2009","journal-title":"Cancer Res"},{"key":"10.1038\/labinvest.2012.144_bib38","doi-asserted-by":"crossref","first-page":"2858","DOI":"10.1182\/blood-2010-06-291104","article-title":"Toxic effects of sorafenib when given early after allogeneic hematopoietic stem cell transplantation","volume":"116","author":"Yokoyama","year":"2010","journal-title":"Blood"},{"key":"10.1038\/labinvest.2012.144_bib39","first-page":"4951","article-title":"PI-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking Ras\/Raf\/MAPK and PI3K\/AKT\/mTOR pathways","volume":"30","author":"Gedaly","year":"2010","journal-title":"Anticancer Res"},{"key":"10.1038\/labinvest.2012.144_bib40","first-page":"408","article-title":"Sorafenib downregulates ERK\/Akt and STAT3 survival pathways and induces apoptosis in a human neuroblastoma cell line","volume":"3","author":"Chai","year":"2010","journal-title":"Int J Clin Exp Pathol"},{"key":"10.1038\/labinvest.2012.144_bib41","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jhep.2009.10.011","article-title":"Synergistic interactions between sorafenib and bortezomib in hepatocellular carcinoma involve PP2A-dependent Akt inactivation","volume":"52","author":"Chen","year":"2010","journal-title":"J Hepatol"},{"key":"10.1038\/labinvest.2012.144_bib42","doi-asserted-by":"crossref","first-page":"9490","DOI":"10.1158\/0008-5472.CAN-07-0598","article-title":"The multikinase inhibitor sorafenib potentiates TRAIL lethality in human leukemia cells in association with Mcl-1 and cFLIPL down-regulation","volume":"67","author":"Rosato","year":"2007","journal-title":"Cancer Res"},{"key":"10.1038\/labinvest.2012.144_bib43","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3324\/haematol.10692","article-title":"The ability of sorafenib to inhibit oncogenic PDGFRbeta and FLT3 mutants and overcome resistance to other small molecule inhibitors","volume":"92","author":"Lierman","year":"2007","journal-title":"Haematologica"},{"key":"10.1038\/labinvest.2012.144_bib44","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.chembiol.2011.01.001","article-title":"Prohibitin(g) cancer: aurilide and killing by OPA1-dependent cristae remodelling","volume":"18","author":"Semenzato","year":"2011","journal-title":"Chem Biol"},{"key":"10.1038\/labinvest.2012.144_bib45","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.4161\/cbt.8.17.9456","article-title":"Targeting bioenergetics to enhance cancer chemotherapy","volume":"8","author":"Kahatri","year":"2009","journal-title":"Cancer Biol Ther"},{"key":"10.1038\/labinvest.2012.144_bib46","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1101\/gad.460708","article-title":"Prohibitins control cell proliferation and apoptosis by regulating OPA1-dependent cristae morphogenesis in mitochondria","volume":"22","author":"Merkwirth","year":"2008","journal-title":"Genes Dev"},{"key":"10.1038\/labinvest.2012.144_bib47","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.cellsig.2009.01.020","article-title":"Regulation of OPA1-mediated mitochondrial fusion by leucine zipper\/EF-hand-containing transmembrane protein-1 plays a role in apoptosis","volume":"21","author":"Piao","year":"2009","journal-title":"Cell Signal"},{"key":"10.1038\/labinvest.2012.144_bib48","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1093\/cvr\/cvp181","article-title":"Mitochondrial OPA1, apoptosis, and heart failure","volume":"84","author":"Chen","year":"2009","journal-title":"Cardiovasc Res"}],"container-title":["Laboratory Investigation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/labinvest2012144.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/labinvest2012144","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0023683722013290?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0023683722013290?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/labinvest2012144.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T19:40:39Z","timestamp":1758397239000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0023683722013290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,1]]}},"alternative-id":["S0023683722013290"],"URL":"https:\/\/doi.org\/10.1038\/labinvest.2012.144","relation":{},"ISSN":["0023-6837"],"issn-type":[{"value":"0023-6837","type":"print"}],"subject":[],"published":{"date-parts":[[2013,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"OPA1 downregulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma","name":"articletitle","label":"Article Title"},{"value":"Laboratory Investigation","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1038\/labinvest.2012.144","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"https:\/\/doi.org\/10.1038\/labinvest.2012.169","name":"associatedlink","label":"CrossRef DOI link to the associated document"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2012 United States & Canadian Academy of Pathology.","name":"copyright","label":"Copyright"}]}}