2020
Response to Epigenetic Disruption in Tumor Suppressor of Hepatocellular Carcinoma (HCC)
Luna A, Wu Q, Hlady R, Sathyanarayan A, Rustgi V, Guarrera J, Robertson K, Liu C. Response to Epigenetic Disruption in Tumor Suppressor of Hepatocellular Carcinoma (HCC). The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.08693.Peer-Reviewed Original ResearchHepatocellular carcinomaCancer risk detectionInhibitor 5-aza-2'-deoxycytidineHepatocellular carcinoma detectionHepatocellular carcinoma patientsEpigenetic changesHepatocellular carcinoma tumorsHuh7.5 cellsImproved treatment optionsHCC cell linesGene promoter sitesStressed cellsTreatment optionsTumor formationEpigenetic disruptionEffective treatmentGenetic mutationsLiver cancerEpigenetic dysregulationTumorMethylation inhibitorSuppressor of hepatocellular carcinomaTumor pathwaysWestern blot showEpigenetic events
2017
Hepatocellular Carcinoma Metastasis and Circulating Tumor Cells
Pham K, Delitto D, Liu C. Hepatocellular Carcinoma Metastasis and Circulating Tumor Cells. Molecular Pathology Library 2017, 153-173. DOI: 10.1007/978-3-319-68082-8_9.Peer-Reviewed Original ResearchHepatocellular carcinomaExtent of diseaseCancer cellsAggressive hepatocellular carcinomaHepatocellular carcinoma metastasisCirculating Tumor CellsCurative resectionSystemic treatmentMetastatic lesionsCarcinoma metastasisHCC microenvironmentSecondary tumorsDifferent malignanciesClinical practiceHost stromaHepatic microenvironmentPrimary siteHCC metastasisMetastasisMetastatic processCancer disseminationTumor cellsMetastatic cellsDistant sitesPhysiologic complexityEpigenetic Regulations in the Pathogenesis of HCC and the Clinical Application
Puszyk W, Robertson K, Liu C. Epigenetic Regulations in the Pathogenesis of HCC and the Clinical Application. 2017, 69-93. DOI: 10.1007/978-3-319-68082-8_5.Peer-Reviewed Original ResearchNonalcoholic fatty liver diseaseDevelopment of hepatocellular carcinomaHepatocellular carcinoma casesHepatocellular carcinomaHepatitis B virusHepatitis C virusRisk factorsChronic infectionNonalcoholic steatohepatitisViral hepatocellular carcinomaChronic cigarette smokingIndependent risk factorPathogenesis of hepatocellular carcinomaConsumption of excess caloriesLiver cancer casesFatty liver diseaseProgress to nonalcoholic steatohepatitisExposure to environmental factorsHCC casesLiver malignanciesConsumption of alcoholCancer casesB virusC virusLiver disease
2015
Effects of Alcohol metabolism on Hepatocellular carcinoma progression
Puszyk W, Hlady R, Tiedemann R, Robertson K, Liu C. Effects of Alcohol metabolism on Hepatocellular carcinoma progression. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.45.8.Peer-Reviewed Original ResearchHepatocellular carcinomaTumor progressionModel of HCCRisk of developmentHepatocellular carcinoma progressionEffects of alcoholCancer deathCommon causeAlcohol consumptionCell culture modelCarcinoma progressionCIMP cancersAlcohol metabolismEthanol metabolismTumor developmentProgressionCancerCulture modelPrimary tissuesDNA methylationMethylation abnormalitiesGene targetsMetabolismCarcinomaAbnormalities
2014
The combination of HTATIP2 expression and microvessel density predicts converse survival of hepatocellular carcinoma with or without sorafenib
Wang W, Liu L, Xu H, Sun H, Wu C, Zhu X, Zhang W, Xu J, Liu C, Long J, Ni Q, Tang Z, Yu X. The combination of HTATIP2 expression and microvessel density predicts converse survival of hepatocellular carcinoma with or without sorafenib. Oncotarget 2014, 5: 3895-3906. PMID: 25008315, PMCID: PMC4116529, DOI: 10.18632/oncotarget.2019.Peer-Reviewed Original ResearchConceptsSurvival of hepatocellular carcinomaMicrovessel densityHepatocellular carcinomaSorafenib treatmentDissemination of hepatocellular carcinomaAssociated with inhibition of angiogenesisAdvanced hepatocellular carcinomaMicrovessel density valuesCurative HCC resectionSuppressor of tumor growthInhibition of angiogenesisNegative prognostic indicatorAssociated with inhibitionSorafenib interventionHCC resectionSorafenib administrationOverall survivalDisease recurrencePrognostic factorsTissue microarrayPrognostic indicatorTumor growthSorafenibPersonalized treatmentPredictive valueIntegrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS‐MS
Fitian A, Nelson D, Liu C, Xu Y, Ararat M, Cabrera R. Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS‐MS. Liver International 2014, 34: 1428-1444. PMID: 24661807, PMCID: PMC4169337, DOI: 10.1111/liv.12541.Peer-Reviewed Original ResearchMeSH Keywords12-Hydroxy-5,8,10,14-eicosatetraenoic AcidAmino AcidsBile Acids and SaltsCarcinoma, HepatocellularChromatography, High Pressure LiquidDicarboxylic AcidsGas Chromatography-Mass SpectrometryHepatitis CHumansHydroxyeicosatetraenoic AcidsLiver CirrhosisLiver NeoplasmsMetabolomeMetabolomicsMultivariate AnalysisROC CurveSphingosineTandem Mass SpectrometryXanthineConceptsPresence of HCCHepatocellular carcinomaUPLC/MS-MSHCC patientsMetabolic alterationsHepatitis C cirrhosisBile acid metabolismHallmarks of HCCMetabolomic profilingAcid metabolismReceiver operator characteristic analysisOperator characteristic analysisGlobal metabolic alterationsMetabolic pathway disturbancesC cirrhosisHCV cirrhosisHepatitis CMetabolic disturbancesHCC developmentSerum metabolomeHealthy volunteersEicosanoid pathwayCirrhosisPathway disturbancesBile acidsEpigenetic regulation of OPA1 sensitizes hepatocellular carcinoma to sorafenib‐induced apoptosis (59.1)
Puszyk W, Dong H, Zhao F, Shisgal P, Cabrera R, Neslon D, Liu C. Epigenetic regulation of OPA1 sensitizes hepatocellular carcinoma to sorafenib‐induced apoptosis (59.1). The FASEB Journal 2014, 28 DOI: 10.1096/fasebj.28.1_supplement.59.1.Peer-Reviewed Original ResearchDNA methylationHepatocellular carcinomaEpigenetic regulationProtein OPA1HCC cellsMitochondrial fragmentationGene promoterC releaseEpigenetic analysisXenograft tumor growthEpigenetic markersSorafenib-induced apoptosisAkt pathwayOPA1HCC xenograft tumor growthHepatocellular carcinoma cellsNovel therapeutic targetExpression levelsTumorigenesis of HCCIdentification of patientsPathogenesis of HCCOPA1 knockdownApoptosisPrimary hepatocytesSensitivity of HCC
2013
Linking metabolism and epigenetic regulation in development of hepatocellular carcinoma
Puszyk W, Le Trinh T, Chapple S, Liu C. Linking metabolism and epigenetic regulation in development of hepatocellular carcinoma. Laboratory Investigation 2013, 93: 983-990. PMID: 23917878, PMCID: PMC4028619, DOI: 10.1038/labinvest.2013.94.Peer-Reviewed Original ResearchConceptsHepatocellular carcinomaLate-stage hepatocellular carcinomaDevelopment of HCCAltered liver metabolismHepatitis B virusMajor risk factorProgression of HCCHepatitis CLiver functionB virusMicro RNA expressionRisk factorsLiver metabolismMetabolic organSurvival rateCancerRNA expressionCommon formCarcinomaUnderlying metabolic processesLiverExogenous environmental factorsEnvironmental factorsExcessive consumptionExposureEpigenetic Upregulation of HGF and c-Met Drives Metastasis in Hepatocellular Carcinoma
Ogunwobi O, Puszyk W, Dong H, Liu C. Epigenetic Upregulation of HGF and c-Met Drives Metastasis in Hepatocellular Carcinoma. PLOS ONE 2013, 8: e63765. PMID: 23723997, PMCID: PMC3665785, DOI: 10.1371/journal.pone.0063765.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCarcinogenesisCarcinoma, HepatocellularCell Line, TumorDNA MethylationEpigenesis, GeneticEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHepatocyte Growth FactorHumansLiver NeoplasmsMesodermMiceMice, Inbred BALB CModels, BiologicalMolecular Sequence DataNeoplastic Cells, CirculatingPromoter Regions, GeneticProto-Oncogene Proteins c-metUp-RegulationConceptsEpithelial-mesenchymal transitionHepatocyte growth factorExpression of HGFHepatocellular carcinomaC-MetHematogenous disseminationTumor cellsRole of HGFOrthotopic syngeneic modelsMetastatic hepatocellular carcinomaMouse HCC modelC-Met expressionUpregulation of HGFPrimary tumor cellsPromoter demethylationNovel non-invasive approachPotential clinical applicationsPeripheral bloodSyngeneic modelHCC managementDrives metastasisEpigenetic upregulationHCC modelTumor progressionMetastatic potential
2012
Immune modulation of effector CD4+ and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma
Cabrera R, Ararat M, Xu Y, Brusko T, Wasserfall C, Atkinson M, Chang L, Liu C, Nelson D. Immune modulation of effector CD4+ and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma. Cancer Immunology, Immunotherapy 2012, 62: 737-746. PMID: 23223899, PMCID: PMC3863727, DOI: 10.1007/s00262-012-1380-8.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCarcinoma, HepatocellularCase-Control StudiesCD4-Positive T-LymphocytesCoculture TechniquesCytokinesDose-Response Relationship, ImmunologicEnzyme-Linked Immunosorbent AssayHumansInterleukin-2 Receptor alpha SubunitLiver NeoplasmsNiacinamidePhenylurea CompoundsSorafenibT-Lymphocytes, RegulatoryConceptsEffect of sorafenibHepatocellular carcinomaTeff activationT cellsLow dosesTeff responsesTumor immunityRegulatory T cell functionImpact of sorafenibEffector T cellsRegulatory T cellsTreg suppressive functionPeripheral mononuclear cellsCD25 surface expressionT cell functionNovel combination treatmentTreg suppressionEffector CD4Treg functionPharmacologic dosesTeff proliferationImmune reactivitySystemic drugsCD25 expressionMononuclear cellsOPA1 downregulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma
Zhao X, Tian C, Puszyk W, Ogunwobi O, Cao M, Wang T, Cabrera R, Nelson D, Liu C. OPA1 downregulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma. Laboratory Investigation 2012, 93: 8-19. PMID: 23108376, PMCID: PMC3860369, DOI: 10.1038/labinvest.2012.144.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCarcinoma, HepatocellularCell Line, TumorCytochromes cDown-RegulationGene Knockdown TechniquesGTP PhosphohydrolasesHumansLiverLiver NeoplasmsMiceMice, SCIDMitochondriaNiacinamidePhenylurea CompoundsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRaf KinasesRas ProteinsRNA, Small InterferingSignal TransductionSorafenibXenograft Model Antitumor AssaysConceptsHepatocellular carcinomaSorafenib-induced apoptosisHCC xenograft tumor growthOptic atrophy 1HCC cellsPatients' hepatocellular carcinomaNon-tumor tissue samplesAdvanced hepatocellular carcinomaPathogenesis of HCCNovel therapeutic targetTumorigenesis of HCCXenograft tumor growthTumor tissue analysisNormal human primary hepatocytesHuman primary hepatocytesCell growth inhibitionSorafenib treatmentHCC patientsTherapeutic targetExposure of cellsTumor growthMitochondrial injuryPatientsSorafenibOPA1 expressionIron Regulator Hepcidin Exhibits Antiviral Activity against Hepatitis C Virus
Liu H, Le Trinh T, Dong H, Keith R, Nelson D, Liu C. Iron Regulator Hepcidin Exhibits Antiviral Activity against Hepatitis C Virus. PLOS ONE 2012, 7: e46631. PMID: 23110054, PMCID: PMC3478283, DOI: 10.1371/journal.pone.0046631.Peer-Reviewed Original ResearchConceptsHCV infectionHepcidin expressionSerious chronic liver diseaseAntiviral activityHepatitis C viral infectionHepcidin expression levelsChronic HCV infectionChronic liver diseaseC viral infectionHepatitis C virusDirect antiviral activityIntracellular antiviral stateHepatocellular carcinoma progressionInnate antiviral defenseLiver diseaseC virusAntiviral effectHCV replicationIron overloadHepatocellular carcinomaExhibit antiviral activityHCVViral infectionSuppressive effectAmino acid peptideSerum levels of soluble CD25 as a marker for hepatocellular carcinoma
CABRERA R, FITIAN A, ARARAT M, XU Y, BRUSKO T, WASSERFALL C, ATKINSON M, LIU C, NELSON D. Serum levels of soluble CD25 as a marker for hepatocellular carcinoma. Oncology Letters 2012, 4: 840-846. PMID: 23205111, PMCID: PMC3506698, DOI: 10.3892/ol.2012.826.Peer-Reviewed Original ResearchSerum levelsEarly hepatocellular carcinomaHepatocellular carcinomaHCC presenceSoluble CD25Pg/Levels of sCD25Healthy control subjectsNovel predictive markerAdvanced cirrhosisPresent study studyAdvanced fibrosisTumor burdenTumor stageControl subjectsHCC patientsPredictive markerImmune factorsGlobal unmet needLarge cohortSCD25PatientsSmall seriesUnmet needSignificant positive correlationGlypican‐3 as a Potential Therapeutic Target for Hepatocellular Carcinoma Immunotherapy
Trinh T, Liu C. Glypican‐3 as a Potential Therapeutic Target for Hepatocellular Carcinoma Immunotherapy. The FASEB Journal 2012, 26: 405.1-405.1. DOI: 10.1096/fasebj.26.1_supplement.405.1.Peer-Reviewed Original ResearchHCC cell linesDifferent HCC cell linesGlypican-3Hepatocellular carcinomaTherapeutic targetCell linesNon-tumor liver tissuesHepatocellular Carcinoma ImmunotherapyCell proliferationNovel therapeutic targetPotential therapeutic targetCancer cell proliferationInhibited cell proliferationDose-dependent mannerAnti-GPC3 antibodiesHuman HCC tissuesNormal primary hepatocytesHCC immunotherapyCell surface heparinGPC3 expressionHCC tissuesLiver tissueImmunotherapyWestern blotHuman tumorsCyclooxygenase‐2 and Akt mediate multiple growth‐factor‐induced epithelial‐mesenchymal transition in human hepatocellular carcinoma
Ogunwobi O, Wang T, Zhang L, Liu C. Cyclooxygenase‐2 and Akt mediate multiple growth‐factor‐induced epithelial‐mesenchymal transition in human hepatocellular carcinoma. Journal Of Gastroenterology And Hepatology 2012, 27: 566-578. PMID: 22097969, PMCID: PMC3288221, DOI: 10.1111/j.1440-1746.2011.06980.x.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminsAlpha 1-AntitrypsinAnimalsCadherinsCarcinoma, HepatocellularCell MovementCell TransplantationCollagen Type ICyclooxygenase 2DinoprostoneEpidermal Growth FactorEpithelial-Mesenchymal TransitionFibroblast Growth Factor 2FibronectinsGene ExpressionHepatocyte Growth FactorHumansMiceOncogene Protein v-aktRNA, Small InterferingSignal TransductionTransforming Growth Factor beta1Tumor Cells, CulturedVimentinConceptsEpithelial-mesenchymal transitionCyclooxygenase-2Hepatocellular carcinomaBasic fibroblast growth factorGrowth factorProstaglandin E2Metastatic hepatocellular carcinomaProgression of HCCEffective therapeutic strategyExpression of vimentinHepatocyte growth factorGrowth factor βHuman hepatocellular carcinomaFibroblast growth factorAssociated hepatitisChemopreventive strategiesEpidermal growth factorMultiple growth factorsTherapeutic strategiesMesenchymal changesSignificant mortalityAkt pathwayMolecular targetingCancer invasionAkt
2011
Therapeutic and prognostic importance of epithelial–mesenchymal transition in liver cancers: Insights from experimental models
Ogunwobi O, Liu C. Therapeutic and prognostic importance of epithelial–mesenchymal transition in liver cancers: Insights from experimental models. Critical Reviews In Oncology/Hematology 2011, 83: 319-328. PMID: 22178416, DOI: 10.1016/j.critrevonc.2011.11.007.Peer-Reviewed Original ResearchConceptsEpithelial-mesenchymal transitionHepatocellular carcinomaHepatic metastasesPrognostic importanceExperimental modelColon cancerTreatment of patientsRole of EMTHuman cancer patientsPotential therapeutic targetHuman malignant diseaseSignificant morbidityCancer patientsMalignant diseaseMalignant conditionsLiver cancerTherapeutic targetBasic scientistsCancerFurther studiesPatientsCarcinomaMetastasisLiverHuman tissuesSurvivin Inhibition Is Critical for Bcl-2 Inhibitor-Induced Apoptosis in Hepatocellular Carcinoma Cells
Zhao X, Ogunwobi O, Liu C. Survivin Inhibition Is Critical for Bcl-2 Inhibitor-Induced Apoptosis in Hepatocellular Carcinoma Cells. PLOS ONE 2011, 6: e21980. PMID: 21829603, PMCID: PMC3148218, DOI: 10.1371/journal.pone.0021980.Peer-Reviewed Original ResearchConceptsBcl-2 inhibitorsCombination treatmentHCC cellsABT-263Survivin inhibitionHepatocellular carcinomaHuman liver cancer tissuesSingle treatmentFuture clinical trialsApoptotic effectsLiver cancer tissuesLiver cancer therapyERK activationHCC cell linesHepatocellular carcinoma cellsPreclinical dataClinical trialsTherapeutic effectLow doseNormal human hepatocytesCancer tissuesYM-155High dosesNovel Bcl-2 inhibitorABT-263-induced apoptosisHepatocyte growth factor upregulation promotes carcinogenesis and epithelial-mesenchymal transition in hepatocellular carcinoma via Akt and COX-2 pathways
Ogunwobi O, Liu C. Hepatocyte growth factor upregulation promotes carcinogenesis and epithelial-mesenchymal transition in hepatocellular carcinoma via Akt and COX-2 pathways. Clinical & Experimental Metastasis 2011, 28: 721-731. PMID: 21744257, PMCID: PMC3732749, DOI: 10.1007/s10585-011-9404-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCadherinsCarcinoma, HepatocellularCell AdhesionCell DifferentiationCell Line, TumorCell MovementCell ProliferationCyclooxygenase 2Enzyme-Linked Immunosorbent AssayEpithelial-Mesenchymal TransitionExtracellular Signal-Regulated MAP KinasesHepatocyte Growth FactorLiver Neoplasms, ExperimentalMiceMice, Inbred BALB CNeoplasm InvasivenessPhosphorylationProto-Oncogene Proteins c-aktReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSignal TransductionUp-RegulationVimentinConceptsEpithelial-mesenchymal transitionHepatocyte growth factorCyclooxygenase-2Hepatocellular carcinomaBNL cellsMarkers of EMTDevelopment of HCCAdvanced hepatocellular carcinomaCOX-2 pathwayMetastatic hepatocellular carcinomaUpregulation of HGFMesenchymal characteristicsGrowth factor upregulationE-cadherinCharacteristic epithelial morphologyCancer mortalitySubsequent metastasisEMT markersImportant causeMigratory capacityHCC cellsBNL CLCancer progressionCollagen 1Growth factorKinase inhibitor Sorafenib modulates immunosuppressive cell populations in a murine liver cancer model
Cao M, Xu Y, Youn J, Cabrera R, Zhang X, Gabrilovich D, Nelson D, Liu C. Kinase inhibitor Sorafenib modulates immunosuppressive cell populations in a murine liver cancer model. Laboratory Investigation 2011, 91: 598-608. PMID: 21321535, PMCID: PMC3711234, DOI: 10.1038/labinvest.2010.205.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzenesulfonatesBone Marrow CellsCarcinoma, HepatocellularCell DivisionCell Line, TumorDisease ProgressionImmunity, CellularLiver NeoplasmsMiceMice, Inbred BALB CMyeloid CellsNiacinamidePhenylurea CompoundsProtein Kinase InhibitorsPyridinesSorafenibSpleenT-Lymphocytes, RegulatoryConceptsMyeloid-derived suppressor cellsImmunosuppressive cell populationsAnti-tumor immunityTumor-bearing hostsImmune cell populationsLiver cancer modelMurine liver cancer modelHepatocellular carcinomaCell populationsCancer modelNovel multi-kinase inhibitorSuppressive immune cell populationBALB/c miceDepletion of TregsImpact of sorafenibRegulatory T cellsAdvanced hepatocellular carcinomaTreatment of sorafenibKinase inhibitor sorafenibMulti-kinase inhibitorHCC cell growthSuppressor cellsTumor burdenC miceCancer patientsDNA Methylation Suppresses Expression of the Urea Cycle Enzyme Carbamoyl Phosphate Synthetase 1 (CPS1) in Human Hepatocellular Carcinoma
Liu H, Dong H, Robertson K, Liu C. DNA Methylation Suppresses Expression of the Urea Cycle Enzyme Carbamoyl Phosphate Synthetase 1 (CPS1) in Human Hepatocellular Carcinoma. American Journal Of Pathology 2011, 178: 652-661. PMID: 21281797, PMCID: PMC3069978, DOI: 10.1016/j.ajpath.2010.10.023.Peer-Reviewed Original ResearchMeSH KeywordsCarbamoyl-Phosphate Synthase (Ammonia)Carcinoma, HepatocellularCell Line, TumorCpG IslandsDNA MethylationGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHepatocyte Nuclear Factor 3-betaHepatocytesHumansLiver NeoplasmsPromoter Regions, GeneticQuaternary Ammonium CompoundsRNA, MessengerUreaConceptsHCC cellsNoncancerous tissuesTumor tissueHepatocyte paraffin 1 antibodySurgical pathology practiceLiver cancer tissuesHuman HCC cellsCPS1 expressionHCC tumor tissuesLiver tumor tissuesHuman hepatocellular carcinomaHuman hepatocellular carcinoma cellsCultured human primary hepatocytesHuman primary hepatocytesHepatocellular carcinoma cellsHepatocellular carcinomaCPS1 geneRate-limiting enzymeLiver carcinogenesisCancer tissuesSynthetase 1Potential biomarkersCarbamoyl phosphate synthetase 1Pathology practiceCarcinoma cells