2023
Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation
Seike K, Kiledal A, Fujiwara H, Henig I, Burgos da Silva M, van den Brink M, Hein R, Hoostal M, Liu C, Oravecz-Wilson K, Lauder E, Li L, Sun Y, Schmidt T, Shah Y, Jenq R, Dick G, Reddy P. Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation. Immunity 2023, 56: 353-368.e6. PMID: 36736321, DOI: 10.1016/j.immuni.2023.01.007.Peer-Reviewed Original ResearchConceptsGraft-versus-host diseaseAmbient oxygen levelsGI graft-versus-host diseaseGut microbiome compositionMicrobiome-dependent mannerMicrobiome compositionMicrobial structureOxygen levelsIntestinal dysbiosisGraft-versus-host disease severityDysbiosisAllogeneic stem cell transplantationAnaerobic commensalsPathogenic T cellsStem cell transplantationIntestinal diseaseInflammatory bowel diseaseGastrointestinal (GI) diseasesCell transplantationIntestinal pathologyT cellsHostBowel diseaseHIF-1aIntestinal damage
2021
Fecal microbiota transplantation mitigates vaginal atrophy in ovariectomized mice
Huang J, Shan W, Li F, Wang Z, Cheng J, Lu F, Guo E, Beejadhursing R, Xiao R, Liu C, Yang B, Li X, Fu Y, Xi L, Wang S, Ma D, Chen G, Sun C. Fecal microbiota transplantation mitigates vaginal atrophy in ovariectomized mice. Aging 2021, 13: 7589-7607. PMID: 33658399, PMCID: PMC7993734, DOI: 10.18632/aging.202627.Peer-Reviewed Original ResearchConceptsVulvovaginal atrophyFecal microbiota transplantationOvarian functionFemale miceMicrobiota transplantationGut microbiotaVagina of miceMenopause-related symptomsVaginal atrophyEpithelial atrophyHormone therapyEstrogen deficiencyVaginal cellsOvariectomized miceOvariectomized onesVaginal healthFollow-upOld miceCancer patientsAlternative treatmentVaginaMiceModulating gut microbiotaOlder womenAtrophy
2019
T cell–derived interferon-γ programs stem cell death in immune-mediated intestinal damage
Takashima S, Martin M, Jansen S, Fu Y, Bos J, Chandra D, O'Connor M, Mertelsmann A, Vinci P, Kuttiyara J, Devlin S, Middendorp S, Calafiore M, Egorova A, Kleppe M, Lo Y, Shroyer N, Cheng E, Levine R, Liu C, Kolesnick R, Lindemans C, Hanash A. T cell–derived interferon-γ programs stem cell death in immune-mediated intestinal damage. Science Immunology 2019, 4 PMID: 31811055, PMCID: PMC7239329, DOI: 10.1126/sciimmunol.aay8556.Peer-Reviewed Original ResearchConceptsBone marrow transplantationIntestinal stem cellsDonor T cellsStem cell compartmentT cellsStem cell deathEpithelial culturesAllogeneic bone marrow transplantationDysregulated T cell activationT cell-mediated pathologyInhibition of JAK signalingStem cellsImmune-mediated damageActivated T cellsT cell activationCell compartmentCell deathTissue stem cellsPaneth cell nicheIFNg productionMarrow transplantationIntestinal immunopathologyInterferon-gHealthy miceStem cell colonies
2016
Critical role of oncogenic KRAS in pancreatic cancer (Review)
LIU J, JI S, LIANG C, QIN Y, JIN K, LIANG D, XU W, SHI S, ZHANG B, LIU L, LIU C, XU J, NI Q, YU X. Critical role of oncogenic KRAS in pancreatic cancer (Review). Molecular Medicine Reports 2016, 13: 4943-4949. PMID: 27121414, DOI: 10.3892/mmr.2016.5196.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaPancreatic cancerGenetically engineered mouse modelsPancreatic intraepithelial neoplasiaDevelopment of pancreatic ductal adenocarcinomaFormation of pancreatic intraepithelial neoplasiaProgression of pancreatic ductal adenocarcinomaIntraepithelial neoplasiaHigher mortality rateMutated KRASDuctal adenocarcinomaMouse modelHuman malignanciesKRASKRAS signalingPharmacological inhibitionOncogenic KRASPharmacological targetsMortality rateCancerTargeting KRASMolecular mechanismsProgressionALDOA functions as an oncogene in the highly metastatic pancreatic cancer
Ji S, Zhang B, Liu J, Qin Y, Liang C, Shi S, Jin K, Liang D, Xu W, Xu H, Wang W, Wu C, Liu L, Liu C, Xu J, Ni Q, Yu X. ALDOA functions as an oncogene in the highly metastatic pancreatic cancer. Cancer Letters 2016, 374: 127-135. PMID: 26854714, DOI: 10.1016/j.canlet.2016.01.054.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorCadherinsCarcinoma, Pancreatic DuctalCell Line, TumorFructose-Bisphosphate AldolaseGlycolysisHeterograftsHigh-Throughput Screening AssaysHumansMaleMiceMice, NudeNeoplasm InvasivenessNeoplasm MetastasisOncogenesPancreatic NeoplasmsReactive Oxygen SpeciesSignal TransductionConceptsHigh-throughput screening analysisAldolase APancreatic cancerRegulation of c-MycTGF-bE-cadherinAnalyzed gene expression signaturesRegulation of glycolysisResistant to conventional treatmentPancreatic cancer cell line PANC-1Cancer metabolic changesPrognosis of pancreatic cancerTransforming growth factor-bSubgroup of patientsCell line PANC-1Metastasis of pancreatic cancer cellsPoor prognosis of pancreatic cancerExpression regulationGene expression signaturesPancreatic cancer tissue samplesPancreatic cancer cellsGlycolytic genesGrowth factor BE-cadherin expressionCancer tissue samples
2015
Mature T cell responses are controlled by microRNA-142
Sun Y, Oravecz-Wilson K, Mathewson N, Wang Y, McEachin R, Liu C, Toubai T, Wu J, Rossi C, Braun T, Saunders T, Reddy P. Mature T cell responses are controlled by microRNA-142. Journal Of Clinical Investigation 2015, 125: 2825-2840. PMID: 26098216, PMCID: PMC4563679, DOI: 10.1172/jci78753.Peer-Reviewed Original ResearchConceptsCell cyclingE2F transcription factorsAtypical E2F transcription factorMature T cell responsesCell proliferationShort palindromic repeatsUpregulation of genesMiR-142T cell developmentTranscription factorsBioinformatics analysisTarget genesPalindromic repeatsMolecular approachesMolecular mechanismsCell developmentMolecular processesMicroRNA-142Targeted deletionWT T cellsGenesE2F8E2F7Multiple murine modelsT cell proliferationConnective tissue growth factor and integrin αvβ6: A new pair of regulators critical for ductular reaction and biliary fibrosis in mice
Pi L, Robinson P, Jorgensen M, Oh S, Brown A, Weinreb P, Le Trinh T, Yianni P, Liu C, Leask A, Violette S, Scott E, Schultz G, Petersen B. Connective tissue growth factor and integrin αvβ6: A new pair of regulators critical for ductular reaction and biliary fibrosis in mice. Hepatology 2015, 61: 678-691. PMID: 25203810, PMCID: PMC4303530, DOI: 10.1002/hep.27425.Peer-Reviewed Original ResearchMeSH KeywordsAdult Stem CellsAnimalsAntigens, NeoplasmBile Duct NeoplasmsBile Ducts, IntrahepaticCell AdhesionChemical and Drug Induced Liver InjuryCholangiocarcinomaConnective Tissue Growth FactorFemaleFibronectinsHumansIntegrinsLiver CirrhosisMaleMiceMice, KnockoutPyridinesRabbitsRatsTransforming Growth Factor beta1ConceptsConnective tissue growth factorDuctular reactionTissue growth factorIntegrin αvβ6Oval cell activationLiver injuryGrowth factorTamoxifen-inducible Cre-loxP systemCell activationRole of CTGFAlpha-smooth muscle actin stainingRelated liver diseasesSevere liver injuryGreen fluorescent protein reporter miceFibrosis-related genesMuscle actin stainingSirius red stainingPotential therapeutic targetHuman cirrhotic liversEpithelial cell adhesion moleculeDuctular epithelial cellsBiliary fibrosisCre-loxP systemLiver diseaseSerum markersHuman Mesenchymal Stromal Cells Attenuate Graft‐Versus‐Host Disease and Maintain Graft‐Versus‐Leukemia Activity Following Experimental Allogeneic Bone Marrow Transplantation
Auletta J, Eid S, Wuttisarnwattana P, Silva I, Metheny L, Keller M, Guardia‐Wolff R, Liu C, Wang F, Bowen T, Lee Z, Solchaga L, Ganguly S, Tyler M, Wilson D, Cooke K. Human Mesenchymal Stromal Cells Attenuate Graft‐Versus‐Host Disease and Maintain Graft‐Versus‐Leukemia Activity Following Experimental Allogeneic Bone Marrow Transplantation. Stem Cells 2015, 33: 601-614. PMID: 25336340, PMCID: PMC4304927, DOI: 10.1002/stem.1867.Peer-Reviewed Original ResearchConceptsT cell expansionT cell proliferationGraft-VersusHost diseaseLeukemia activityExperimental allogeneic bone marrow transplantationDonor T cell expansionAllogeneic bone marrow transplantationCytotoxic T cell activityAlloreactive T cell proliferationPotent GVL effectCyclo-oxygenase inhibitionT cell activityT cell suppressionBone marrow transplantationMarrow-derived mesenchymal stromal cellsSecondary lymphoid organsSplenic T cellsSplenic marginal zoneMixed leukocyte cultureMesenchymal stromal cellsBMT miceEP2 agonismGVL activityGVL effect
2014
A Small-Molecule c-Rel Inhibitor Reduces Alloactivation of T Cells without Compromising Antitumor Activity
Shono Y, Tuckett A, Ouk S, Liou H, Altan-Bonnet G, Tsai J, Oyler J, Smith O, West M, Singer N, Doubrovina E, Pankov D, Undhad C, Murphy G, Lezcano C, Liu C, O'Reilly R, van den Brink M, Zakrzewski J. A Small-Molecule c-Rel Inhibitor Reduces Alloactivation of T Cells without Compromising Antitumor Activity. Cancer Discovery 2014, 4: 578-591. PMID: 24550032, PMCID: PMC4011979, DOI: 10.1158/2159-8290.cd-13-0585.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFemaleGene Expression RegulationGraft vs Host DiseaseGraft vs Tumor EffectHematopoietic Stem Cell TransplantationHumansLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLProto-Oncogene Proteins c-relReceptors, Antigen, T-CellSmall Molecule LibrariesT-LymphocytesTransplantation, HomologousConceptsT cellsC-Rel activityAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationEffector T cellsRegulatory T cellsIL-2 levelsStem cell transplantationAntigen-specific cytotoxicityC-Rel-deficient T cellsC-RelHuman T cellsT cell receptor activationGut homingGVT activityImmunomodulatory therapyInhibitor administrationCell transplantationTumor activityImmune systemReceptor activationPharmaceutical inhibitionSmall molecule-based inhibitionAlloactivationBroad suppression
2013
Pharmacologic inhibition of PKCα and PKCθ prevents GVHD while preserving GVL activity in mice
Haarberg K, Li J, Heinrichs J, Wang D, Liu C, Bronk C, Kaosaard K, Owyang A, Holland S, Masuda E, Tso K, Blazar B, Anasetti C, Beg A, Yu X. Pharmacologic inhibition of PKCα and PKCθ prevents GVHD while preserving GVL activity in mice. Blood 2013, 122: 2500-2511. PMID: 23908466, PMCID: PMC3790515, DOI: 10.1182/blood-2012-12-471938.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell SeparationDisease Models, AnimalEnzyme InhibitorsFlow CytometryGraft vs Host DiseaseGraft vs Leukemia EffectHematopoietic Stem Cell TransplantationIsoenzymesLeukemiaLymphocyte ActivationLymphomaMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutProtein Kinase CProtein Kinase C-alphaProtein Kinase C-thetaT-LymphocytesConceptsHematopoietic cell transplantationDonor T cell proliferationAllogeneic hematopoietic cell transplantationT cell proliferationGVL activityGVL effectCytokine productionT cellsPharmacologic inhibitionChemokine/cytokine productionT-cell cytotoxicDonor T cellsPreclinical murine modelsPotential therapeutic targetT cell activationGVHD inductionGVHD preventionPrevents GVHDHost diseaseLeukemia effectSevere graftTherapeutic optionsCell transplantationEffective therapyPharmacologic approachesPLZF Confers Effector Functions to Donor T Cells That Preserve Graft-versus-Tumor Effects while Attenuating GVHD
Ghosh A, Holland A, Dogan Y, Yim N, Rao U, Young L, West M, Singer N, Lee H, Na I, Tsai J, Jenq R, Penack O, Hanash A, Lezcano C, Murphy G, Liu C, Sadelain M, Sauer M, Sant'Angelo D, van den Brink M. PLZF Confers Effector Functions to Donor T Cells That Preserve Graft-versus-Tumor Effects while Attenuating GVHD. Cancer Research 2013, 73: 4687-4696. PMID: 23733752, PMCID: PMC3732814, DOI: 10.1158/0008-5472.can-12-4699.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsBone Marrow TransplantationFlow CytometryGraft vs Host DiseaseGraft vs Tumor EffectKruppel-Like Transcription FactorsLymphocyte ActivationLymphocyte Culture Test, MixedMiceMice, Inbred BALB CMice, Inbred C57BLNeoplasms, ExperimentalPromyelocytic Leukemia Zinc Finger ProteinT-LymphocytesTransplantation, HomologousConceptsDonor T cellsT cellsPromyelocytic leukemia zinc fingerGVT effectInvariant natural killer T (iNKT) cellsAlloreactive donor T cellsAllogeneic bone marrow transplantationNatural killer T cellsTranscription factor promyelocytic leukemia zinc fingerKiller T cellsAlloreactive T cellsBone marrow transplantationConventional T cellsOverall improved outcomesLess GVHDLower GVHDPreserves graftTumor effectImproved survivalMarrow transplantationCytokine responsesImproved outcomesTumor relapseEffector functionsGVHDc‐Rel is an essential transcription factor for the development of acute graft‐versus‐host disease in mice
Yu Y, Wang D, Kaosaard K, Liu C, Fu J, Haarberg K, Anasetti C, Beg A, Yu X. c‐Rel is an essential transcription factor for the development of acute graft‐versus‐host disease in mice. European Journal Of Immunology 2013, 43: 2327-2337. PMID: 23716202, PMCID: PMC3940138, DOI: 10.1002/eji.201243282.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow TransplantationCell DifferentiationCell ProliferationForkhead Transcription FactorsGraft vs Host DiseaseImmune ToleranceLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutProto-Oncogene Proteins c-relTh1 CellsTh17 CellsT-Lymphocytes, RegulatoryTransplantation, HomologousConceptsT cellsAcute GVHDHost diseaseAllogeneic bone marrow transplantationAllogeneic hematopoietic cell transplantationC-RelGVHD target organsHematopoietic cell transplantationRegulatory T cellsBone marrow transplantationAcute graftLeukemia responseTransplant toleranceAllogeneic recipientsMarrow transplantationMinor histocompatibilityCell transplantationTh1 cellsLymphoid organsMurine modelTarget organsTherapeutic interventionsNF-κB familyGraftPotential targetPhosphatidylinositol 3-Kinase–Independent Signaling Pathways Contribute to ICOS-Mediated T Cell Costimulation in Acute Graft-Versus-Host Disease in Mice
Li J, Heinrichs J, Leconte J, Haarberg K, Semple K, Liu C, Gigoux M, Kornete M, Piccirillo C, Suh W, Yu X. Phosphatidylinositol 3-Kinase–Independent Signaling Pathways Contribute to ICOS-Mediated T Cell Costimulation in Acute Graft-Versus-Host Disease in Mice. The Journal Of Immunology 2013, 191: 200-207. PMID: 23729441, PMCID: PMC4318500, DOI: 10.4049/jimmunol.1203485.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsDisease Models, AnimalGene Knock-In TechniquesGraft vs Host DiseaseInducible T-Cell Co-Stimulator ProteinLymphocyte ActivationMiceMice, 129 StrainMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, TransgenicPhosphatidylinositol 3-KinaseSignal TransductionT-Lymphocyte SubsetsConceptsCD8 T cellsCD4 T cellsT cellsHost diseaseWild-type CD8 T cellsCD8 T cell compartmentAllogeneic bone marrow transplantationAcute Graft-VersusPathogenic potentialTotal T cellsAlloreactive T cellsBone marrow transplantationT cell compartmentWild-type T cellsIntracellular calcium mobilizationVivo pathogenic potentialT cell costimulationT cell activationKnockout T cellsAcute graftAcute GVHDGraft-VersusSevere GVHDGVHD modelMarrow transplantationEpigenetic 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 potentialAdoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity
Ghosh A, Dogan Y, Moroz M, Holland A, Yim N, Rao U, Young L, Tannenbaum D, Masih D, Velardi E, Tsai J, Jenq R, Penack O, Hanash A, Smith O, Piersanti K, Lezcano C, Murphy G, Liu C, Palomba M, Sauer M, Sadelain M, Ponomarev V, van den Brink M. Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity. Journal Of Clinical Investigation 2013, 123: 2654-2662. PMID: 23676461, PMCID: PMC3668849, DOI: 10.1172/jci66301.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntigen-Presenting CellsCell Line, TumorCytotoxicity, ImmunologicGraft RejectionGraft vs Host DiseaseHEK293 CellsHumansImmunotherapy, AdoptiveLeukemia, Lymphocytic, Chronic, B-CellMiceMice, Inbred BALB CMice, Inbred C57BLNeoplasm TransplantationT-LymphocytesTNF-Related Apoptosis-Inducing LigandConceptsGVT responseT cellsAllo-HSCTAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationCellular therapyAbsence of GVHDDR5-dependent mannerDonor T cellsAlloreactive T cellsStem cell transplantationChronic lymphocytic leukemia cellsPrecursor T cellsThird-party donorsLymphocytic leukemia cellsApoptosis-inducing ligandGVT activityHost diseaseCell transplantationCurative potentialTumor responseGVHDCertain malignanciesMouse modelHuman leukemia cell linesMicroRNA-34b inhibits pancreatic cancer metastasis through repressing Smad3.
Liu C, Cheng H, Shi S, Cui X, Yang J, Chen L, Cen P, Cai X, Lu Y, Wu C, Yao W, Qin Y, Liu L, Long J, Xu J, Li M, Yu X. MicroRNA-34b inhibits pancreatic cancer metastasis through repressing Smad3. 2013, 13: 467-78. PMID: 23305226, DOI: 10.2174/1566524011313040001.Peer-Reviewed Original ResearchConceptsMiR-34bTarget of miR-34bMicroRNA-34bTumor-suppressive microRNAMiR-34b expressionPancreatic cancer tissuesLuciferase assayProgression in vitroMicroRNAsCancer tissuesTumor-node-metastasisPancreatic cancerTumor metastasis suppressorTumor-node-metastasis (TNM) stageCancer progression in vitroMiRsLymph-node metastasisPancreatic cancer cellsPancreatic cancer metastasisER stress inducer thapsigarginHost-derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation
Toubai T, Sun Y, Luker G, Liu J, Luker K, Tawara I, Evers R, Liu C, Mathewson N, Malter C, Nieves E, Choi S, Murphy K, Reddy P. Host-derived CD8+ dendritic cells are required for induction of optimal graft-versus-tumor responses after experimental allogeneic bone marrow transplantation. Blood 2013, 121: 4231-4241. PMID: 23520337, PMCID: PMC3656455, DOI: 10.1182/blood-2012-05-432872.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsTumor-specific antigensGVT responseAllo-HCTAPC subsetsDendritic cellsExperimental allogeneic bone marrow transplantationHost-derived antigen-presenting cellsAllogeneic bone marrow transplantationAllogeneic hematopoietic cell transplantationAlloantigen-specific responsesHost-derived CD8Donor T cellsHematopoietic cell transplantationBone marrow transplantationRelevant murine modelStimulation of TLR3Host diseaseTumor effectMarrow transplantationCell transplantationTumor responseSerious toxicityT cellsOptimal graftLong-Term In Vivo Imaging of Multiple Organs at the Single Cell Level
Chen B, Jiao Y, Zhang P, Sun A, Pitt G, Deoliveira D, Drago N, Ye T, Liu C, Chao N. Long-Term In Vivo Imaging of Multiple Organs at the Single Cell Level. PLOS ONE 2013, 8: e52087. PMID: 23300962, PMCID: PMC3534688, DOI: 10.1371/journal.pone.0052087.Peer-Reviewed Original Research
2012
Guardian and Selective Killer: The Versatile Functions of TLR3 in Hepatocellular Carcinoma
Liu C. Guardian and Selective Killer: The Versatile Functions of TLR3 in Hepatocellular Carcinoma. Journal Of The National Cancer Institute 2012, 104: 1780-1782. PMID: 23197496, PMCID: PMC3514168, DOI: 10.1093/jnci/djs475.Peer-Reviewed Original ResearchOPA1 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 expression