{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:47:45Z","timestamp":1792669665436,"version":"4.5.0"},"reference-count":48,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T00:00:00Z","timestamp":1663545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","cmghjournal.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cellular and Molecular Gastroenterology and Hepatology"],"published-print":{"date-parts":[[2023]]},"DOI":"10.1016\/j.jcmgh.2022.09.009","type":"journal-article","created":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T04:26:16Z","timestamp":1663993576000},"page":"61-75","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":28,"title":["PFKFB3-mediated Pro-glycolytic Shift in Hepatocellular Carcinoma Proliferation"],"prefix":"10.1016","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2418-4858","authenticated-orcid":false,"given":"Qianhui","family":"Dou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron K.","family":"Grant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody","family":"Callahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Coutinho de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam L.","family":"Booth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imad","family":"Nasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan","family":"Moussa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneeb","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6941-7443","authenticated-orcid":false,"given":"Leo L.","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jcmgh.2022.09.009_bib1","first-page":"1","article-title":"Review of hepatocellular carcinoma: epidemiology, etiology, and carcinogenesis","volume":"16","author":"Ghouri","year":"2017","journal-title":"J\u00a0Carcinog"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib2","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/nrclinonc.2015.103","article-title":"Advances in targeted therapies for hepatocellular carcinoma in the genomic era","volume":"12","author":"Llovet","year":"2015","journal-title":"Nat Rev Clin Oncol"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib3","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.2353\/ajpath.2009.080596","article-title":"GLUT1 expression is increased in hepatocellular carcinoma and promotes tumorigenesis","volume":"174","author":"Amann","year":"2009","journal-title":"Am J Pathol"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib4","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1053\/j.gastro.2010.12.006","article-title":"Increased lipogenesis, induced by AKT-mTORC1-RPS6 signaling, promotes development of human hepatocellular carcinoma","volume":"140","author":"Calvisi","year":"2011","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib5","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/8813410","article-title":"Metabolic alteration in hepatocellular carcinoma: mechanism of lipid accumulation in well-differentiated hepatocellular carcinoma","volume":"2021","author":"Suzuki","year":"2021","journal-title":"Can J Gastroenterol Hepatol"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib6","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The emerging hallmarks of cancer metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/gastro\/goaa066","article-title":"Metabolic alterations and vulnerabilities in hepatocellular carcinoma","volume":"9","author":"Tenen","year":"2021","journal-title":"Gastroenterol Rep"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib8","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12943-015-0481-3","article-title":"Imaging metabolic heterogeneity in cancer","volume":"15","author":"Sengupta","year":"2016","journal-title":"Mol Cancer"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib9","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Science"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib10","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3389\/fimmu.2016.00052","article-title":"Lactate contribution to the tumor microenvironment: mechanisms, effects on immune cells and therapeutic relevance","volume":"7","author":"Romero-Garcia","year":"2016","journal-title":"Front Immunol"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib11","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.acra.2013.11.015","article-title":"The potential of hyperpolarized 13C MRI in assessing signaling pathways in cancer","volume":"21","author":"Zhang","year":"2014","journal-title":"Acad Radiol"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib12","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/nbm.1616","article-title":"In\u00a0vivo MRSI of hyperpolarized [1-13C]pyruvate metabolism in rat hepatocellular carcinoma","volume":"24","author":"Darpolor","year":"2011","journal-title":"NMR in Biomed"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib13","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/hep.30970","article-title":"Hyperpolarized metabolic imaging detects latent hepatocellular carcinoma domains surviving locoregional therapy","volume":"72","author":"Perkons","year":"2020","journal-title":"Hepatology"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib14","doi-asserted-by":"crossref","first-page":"8607","DOI":"10.1158\/0008-5472.CAN-08-0749","article-title":"Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading","volume":"68","author":"Albers","year":"2008","journal-title":"Cancer Res"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib15","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.cmet.2019.08.024","article-title":"Hyperpolarized MRI of human prostate cancer reveals increased lactate with tumor grade driven by monocarboxylate transporter 1","volume":"31","author":"Granlund","year":"2020","journal-title":"Cell Metab"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib16","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jamcollsurg.2008.01.020","article-title":"Risk factors and prognostic factors of local recurrence after radiofrequency ablation of hepatocellular carcinoma","volume":"207","author":"Lam","year":"2008","journal-title":"J\u00a0Am Coll Surg"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1148\/radiol.2015150080","article-title":"Hepatic radiofrequency ablation-induced stimulation of distant tumor growth is suppressed by c-Met inhibition","volume":"279","author":"Ahmed","year":"2016","journal-title":"Radiology"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib18","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1148\/radiol.2015141695","article-title":"Oncogenesis: an \u201coff-target\u201d effect of radiofrequency ablation","volume":"276","author":"Rozenblum","year":"2015","journal-title":"Radiology"},{"issue":"Suppl 3","key":"10.1016\/j.jcmgh.2022.09.009_bib19","doi-asserted-by":"crossref","first-page":"S436","DOI":"10.1245\/s10434-014-3575-z","article-title":"Expressions of hypoxia-inducible factor-1 and epithelial cell adhesion molecule are linked with aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation therapy","volume":"21","author":"Yamada","year":"2014","journal-title":"Ann Surg Oncol"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib20","first-page":"849","article-title":"Independent prognostic value of HIF-1[alpha] expression in radiofrequency ablation of lung cancer","volume":"19","author":"Wan","year":"2020","journal-title":"Oncol Lett"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib21","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.3892\/or.2015.4541","article-title":"Local recurrence of small cell lung cancer following radiofrequency ablation is induced by HIF-1\u03b1 expression in the transition zone","volume":"35","author":"Wan","year":"2016","journal-title":"Oncol Rep"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib22","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/nrc2468","article-title":"Hypoxia, HIF1 and glucose metabolism in the solid tumour","volume":"8","author":"Denko","year":"2008","journal-title":"Nat Rev Cancer"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib23","doi-asserted-by":"crossref","first-page":"6183","DOI":"10.1074\/jbc.M110978200","article-title":"Hypoxia-inducible factor-1-mediated expression of the 6-phosphofructo-2-kinase\/fructose-2,6-bisphosphatase-3 (PFKFB3) gene. Its possible role in the Warburg effect","volume":"277","author":"Minchenko","year":"2002","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib24","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/hepr.12705","article-title":"Pathophysiology of recurrent hepatocellular carcinoma after radiofrequency ablation","volume":"47","author":"Ikemoto","year":"2017","journal-title":"Hepatol Res"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib25","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s11605-007-0276-y","article-title":"Analysis of recurrence pattern and its influence on survival outcome after radiofrequency ablation of hepatocellular carcinoma","volume":"12","author":"Ng","year":"2008","journal-title":"J\u00a0Gastrointest Surg"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib26","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1148\/radiol.2016152241","article-title":"Hepatic thermal ablation: effect of device and heating parameters on local tissue reactions and distant tumor growth","volume":"281","author":"Velez","year":"2016","journal-title":"Radiology"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib27","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.1002\/cpbi.86","article-title":"Using MetaboAnalyst 4.0 for comprehensive and integrative metabolomics data analysis","volume":"68","author":"Chong","year":"2019","journal-title":"Curr Protoc Bioinformatics"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib28","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3390\/metabo10070285","article-title":"The pentose phosphate pathway dynamics in cancer and its dependency on intracellular pH","volume":"10","author":"Alfarouk","year":"2020","journal-title":"Metabolites"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib29","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.tibs.2014.06.005","article-title":"The pentose phosphate pathway and cancer","volume":"39","author":"Patra","year":"2014","journal-title":"Trends Biochem Sci"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib30","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1093\/neuonc\/now024","article-title":"Glycolysis and the pentose phosphate pathway are differentially associated with the dichotomous regulation of glioblastoma cell migration versus proliferation","volume":"18","author":"Kathagen-Buhmann","year":"2016","journal-title":"Neuro Oncol"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib31","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s00401-013-1173-y","article-title":"Hypoxia and oxygenation induce a metabolic switch between pentose phosphate pathway and glycolysis in glioma stem-like cells","volume":"126","author":"Kathagen","year":"2013","journal-title":"Acta Neuropathol"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib32","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1148\/radiol.15141918","article-title":"Radiofrequency ablation: inflammatory changes in the periablative zone can induce global organ effects, including liver regeneration","volume":"276","author":"Rozenblum","year":"2015","journal-title":"Radiology"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib33","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0163768","article-title":"PFK15, a small molecule inhibitor of PFKFB3, induces cell cycle arrest, apoptosis and inhibits invasion in gastric cancer","volume":"11","author":"Zhu","year":"2016","journal-title":"PLoS One"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib34","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1158\/1535-7163.MCT-13-0097","article-title":"Targeting 6-phosphofructo-2-kinase (PFKFB3) as a therapeutic strategy against cancer","volume":"12","author":"Clem","year":"2013","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib35","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1158\/1078-0432.CCR-19-1702","article-title":"Molecular imaging of extracellular tumor pH to reveal effects of locoregional therapy on liver cancer microenvironment","volume":"26","author":"Savic","year":"2020","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib36","first-page":"453","article-title":"Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release","volume":"39","author":"Goetze","year":"2011","journal-title":"Int J Oncol"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib37","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1158\/0008-5472.CAN-10-2828","article-title":"Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-B\/IL-8 pathway that drives tumor angiogenesis","volume":"71","author":"Vegran","year":"2011","journal-title":"Cancer Res"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41416-019-0667-3","article-title":"Metabolism and cancer: the future is now","volume":"122","author":"Frezza","year":"2020","journal-title":"Br J Cancer"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib39","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s41575-019-0217-8","article-title":"Metabolic rearrangements in primary liver cancers: cause and consequences","volume":"16","author":"Satriano","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib40","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1126\/science.1188015","article-title":"Evidence for an alternative glycolytic pathway in rapidly proliferating cells","volume":"329","author":"Vander Heiden","year":"2010","journal-title":"Science"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib41","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.1016\/j.febslet.2006.04.093","article-title":"PFKFB3 gene silencing decreases glycolysis, induces cell-cycle delay and inhibits anchorage-independent growth in HeLa cells","volume":"580","author":"Calvo","year":"2006","journal-title":"FEBS Lett"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib42","doi-asserted-by":"crossref","first-page":"5784","DOI":"10.1158\/1078-0432.CCR-05-0149","article-title":"Phosphorylation of the 6-phosphofructo-2-kinase\/fructose 2,6-bisphosphatase\/PFKFB3 family of glycolytic regulators in human cancer","volume":"11","author":"Bando","year":"2005","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib43","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s10549-016-3968-8","article-title":"Inhibition of 6-phosphofructo-2-kinase (PFKFB3) suppresses glucose metabolism and the growth of HER2+ breast cancer","volume":"160","author":"O\u2019Neal","year":"2016","journal-title":"Breast Cancer Res Treat"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib44","doi-asserted-by":"crossref","first-page":"3480","DOI":"10.1038\/ncomms4480","article-title":"Reduced methylation of PFKFB3 in cancer cells shunts glucose towards the pentose phosphate pathway","volume":"5","author":"Yamamoto","year":"2014","journal-title":"Nat Commun"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib45","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.cmet.2011.04.012","article-title":"13C-pyruvate imaging reveals alterations in glycolysis that precede c-Myc-induced tumor formation and regression","volume":"14","author":"Hu","year":"2011","journal-title":"Cell Metab"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib46","first-page":"114","article-title":"Highly malignant intra-hepatic metastatic hepatocellular carcinoma in rats","volume":"3","author":"Guo","year":"2010","journal-title":"Am J Transl Res"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib47","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0071996","article-title":"Model free approach to kinetic analysis of real-time hyperpolarized 13C magnetic resonance spectroscopy data","volume":"8","author":"Hill","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.jcmgh.2022.09.009_bib48","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1038\/nprot.2012.024","article-title":"A\u00a0positive\/negative ion\u2013switching, targeted mass spectrometry\u2013based metabolomics platform for bodily fluids, cells, and fresh and fixed tissue","volume":"7","author":"Yuan","year":"2012","journal-title":"Nat Protoc"}],"container-title":["Cellular and Molecular Gastroenterology and Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352345X22002016?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352345X22002016?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T18:32:58Z","timestamp":1762453978000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352345X22002016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023]]}},"alternative-id":["S2352345X22002016"],"URL":"https:\/\/doi.org\/10.1016\/j.jcmgh.2022.09.009","relation":{},"ISSN":["2352-345X"],"issn-type":[{"value":"2352-345X","type":"print"}],"subject":[],"published":{"date-parts":[[2023]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"PFKFB3-mediated Pro-glycolytic Shift in Hepatocellular Carcinoma Proliferation","name":"articletitle","label":"Article Title"},{"value":"Cellular and Molecular Gastroenterology and Hepatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jcmgh.2022.09.009","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier Inc. on behalf of the AGA Institute.","name":"copyright","label":"Copyright"}]}}