2022
Interferon drives HCV scarring of the epigenome and creates targetable vulnerabilities following viral clearance
Hlady RA, Zhao X, Khoury L, Luna A, Pham K, Wu Q, Lee J, Pyrsopoulos NT, Liu C, Robertson KD. Interferon drives HCV scarring of the epigenome and creates targetable vulnerabilities following viral clearance. Hepatology 2022, 75: 983-996. PMID: 34387871, PMCID: PMC9416882, DOI: 10.1002/hep.32111.Peer-Reviewed Original ResearchConceptsDNA methylationHistone modificationsWide DNA methylationAberrant DNA methylationGene expression analysisDNA methyltransferase inhibitorOpen chromatinEpigenetic mechanismsEpigenetic targetsHuman patient samplesEpigenetic changesEpigenomeMethyltransferase inhibitorTargetable vulnerabilitiesMethylationHCC cell linesImmortalized hepatocytesCell linesFunctional effectsChronic HCV infectionChromatinHCV infectionImmune responsePatient samplesSynergizes
2019
Enhancement of sorafenib-mediated death of Hepatocellular carcinoma cells by Carnosic acid and Vitamin D2 analog combination
Wu Q, Wang X, Pham K, Luna A, Studzinski GP, Liu C. Enhancement of sorafenib-mediated death of Hepatocellular carcinoma cells by Carnosic acid and Vitamin D2 analog combination. The Journal Of Steroid Biochemistry And Molecular Biology 2019, 197: 105524. PMID: 31704246, PMCID: PMC7015782, DOI: 10.1016/j.jsbmb.2019.105524.Peer-Reviewed Original ResearchConceptsHepatocellular carcinomaVitamin DOral multi-kinase inhibitorTreatment of HCCAutophagy markers Beclin1Vitamin D insufficiencyCarnosic acidAdvanced hepatocellular carcinomaPromising therapeutic optionVitamin D analogsMulti-kinase inhibitorCell linesElevated protein levelsAnti-oxidant propertiesHCC cell linesHuman neoplastic cellsD insufficiencyGlobal cancer mortalityHepatocellular carcinoma cellsSystemic treatmentTherapeutic optionsCancer mortalityHCC cell deathPreclinical studiesLiver cancerIntegrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma
Hlady RA, Sathyanarayan A, Thompson JJ, Zhou D, Wu Q, Pham K, Lee J, Liu C, Robertson KD. Integrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma. Hepatology 2019, 69: 639-652. PMID: 30136421, PMCID: PMC6351162, DOI: 10.1002/hep.30211.Peer-Reviewed Original ResearchConceptsHistone modification profilesPromoter/enhancer functionGenome-wide assessmentTranscription of genesEpigenetic marksHistone modificationsEpigenome deregulationEpigenetic regulatorsBioinformatics strategyEpigenetic mechanismsModification profilesEpigenetic underpinningsLiver epigenomeEpigenetic profilesEnhancer functionEpigenetic parametersEpigenomeDecrease cell viabilityDriver lociSignificant deregulationCancer initiationTranscriptionHuman cancersCancer cell linesCell lines
2016
Isolation of Pancreatic Cancer Cells from a Patient-Derived Xenograft Model Allows for Practical Expansion and Preserved Heterogeneity in Culture
Pham K, Delitto D, Knowlton AE, Hartlage ER, Madhavan R, Gonzalo DH, Thomas RM, Behrns KE, George TJ, Hughes SJ, Wallet SM, Liu C, Trevino JG. Isolation of Pancreatic Cancer Cells from a Patient-Derived Xenograft Model Allows for Practical Expansion and Preserved Heterogeneity in Culture. American Journal Of Pathology 2016, 186: 1537-1546. PMID: 27102771, PMCID: PMC4901138, DOI: 10.1016/j.ajpath.2016.02.009.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsSubcutaneous injectionHuman leukocyte antigen class IICancer stem cell marker CD44Class I human leukocyte antigenHuman PC specimensHuman PC cellsPancreatic cancer cell linesDeath ligand 1Human leukocyte antigenStem cell marker CD44PC cell linesPancreatic cancer cellsCell linesCell marker CD44Epithelial cell adhesion moleculeLimited translational valueCancer cell linesLeukocyte antigenCell adhesion moleculePC cellsTherapeutic approachesFrequency of cellsXenograft modelCytokeratin 19
2015
Downstream mediators of the intratumoral interferon response suppress antitumor immunity, induce gemcitabine resistance and associate with poor survival in human pancreatic cancer
Delitto D, Perez C, Han S, Gonzalo DH, Pham K, Knowlton AE, Graves CL, Behrns KE, Moldawer LL, Thomas RM, Liu C, George TJ, Trevino JG, Wallet SM, Hughes SJ. Downstream mediators of the intratumoral interferon response suppress antitumor immunity, induce gemcitabine resistance and associate with poor survival in human pancreatic cancer. Cancer Immunology, Immunotherapy 2015, 64: 1553-1563. PMID: 26423423, PMCID: PMC5129167, DOI: 10.1007/s00262-015-1760-y.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityCell Line, TumorChemokine CXCL10DeoxycytidineDrug Resistance, NeoplasmEnzyme-Linked Immunosorbent AssayFlow CytometryGemcitabineGene Expression Regulation, NeoplasticHLA AntigensHumansInterferon-gammaInterferonsPancreatic NeoplasmsReceptors, CXCR3Tumor Cells, CulturedTumor MicroenvironmentConceptsPC cell linesPancreatic cancerAntitumor immunityPoor survivalPC microenvironmentHuman leukocyte antigen (HLA) class IMinimal inflammatory cell infiltrationEffective antitumor immunityImmune checkpoint ligandsUpregulation of PDL1Inflammatory cell infiltrationAntigen class IHuman pancreatic cancerAbsence of CD80Tumor-associated stromaCell linesCancer epithelial cellsCheckpoint ligandsCXCL10 concentrationsCell typesIFNγ responsesIndependent predictorsCD86 expressionChronic pancreatitisCell infiltrationVEGFR inhibitors upregulate CXCR4 in VEGF receptor-expressing glioblastoma in a TGFβR signaling-dependent manner
Pham K, Luo D, Siemann DW, Law BK, Reynolds BA, Hothi P, Foltz G, Harrison JK. VEGFR inhibitors upregulate CXCR4 in VEGF receptor-expressing glioblastoma in a TGFβR signaling-dependent manner. Cancer Letters 2015, 360: 60-67. PMID: 25676691, PMCID: PMC7294457, DOI: 10.1016/j.canlet.2015.02.005.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsAnimalsBenzylaminesBrain NeoplasmsCell Line, TumorCell MovementCyclamsFemaleGlioblastomaHeterocyclic CompoundsHumansInterleukin-2 Receptor alpha SubunitMaleMice, Inbred NODMice, KnockoutMice, SCIDMiddle AgedNeoplasm InvasivenessPiperidinesProtein Kinase InhibitorsQuinazolinesReceptor Cross-TalkReceptors, CXCR4Receptors, Transforming Growth Factor betaReceptors, Vascular Endothelial Growth FactorSignal TransductionTime FactorsUp-RegulationXenograft Model Antitumor AssaysConceptsTGFβ/TGFβRAnti-VEGF/VEGFR therapiesSignaling-dependent mannerMechanisms of crosstalkEnhanced invasive phenotypeVEGFR inhibitorsSurvival benefitHGF/METGBM cell linesInvasive phenotypeCXCL12/CXCR4 pathwayGreater survival benefitExpression of CXCR4VEGF/VEGFRMalignant phenotypeTumor-bearing animalsUpregulation of CXCR4Alternative therapeutic strategiesGBM progressionCell linesTGFβRRecurrent tumorsCXCR4 pathwayStandard treatmentCXCR4 antagonist
2013
Expression and Functional Heterogeneity of Chemokine Receptors CXCR4 and CXCR7 in Primary Patient-Derived Glioblastoma Cells
Liu C, Pham K, Luo D, Reynolds BA, Hothi P, Foltz G, Harrison JK. Expression and Functional Heterogeneity of Chemokine Receptors CXCR4 and CXCR7 in Primary Patient-Derived Glioblastoma Cells. PLOS ONE 2013, 8: e59750. PMID: 23555768, PMCID: PMC3605406, DOI: 10.1371/journal.pone.0059750.Peer-Reviewed Original ResearchConceptsFunction of CXCR4Chemokine receptor CXCR4CXCR4-CXCR7Receptor CXCR4Common primary brain tumorPrimary human GBM cellsPrimary brain tumorsPersonalized treatment approachesTube formationSurface expressionPatient-derived GBM cell linesNew therapeutic targetsCell linesHuman GBM cellsPatient-derived glioblastoma cellsGBM cell linesClinical benefitPoor prognosisSuccessful treatmentCell surface expressionCXCR7 axisCXCL12-CXCR4Intracranial tumorsGBM patientsBrain tumors