2020
Electronic Cigarettes Induce Mitochondrial DNA Damage and Trigger TLR9 (Toll-Like Receptor 9)-Mediated Atherosclerosis
Li J, Huynh L, Cornwell WD, Tang MS, Simborio H, Huang J, Kosmider B, Rogers TJ, Zhao H, Steinberg MB, Thu Thi Le L, Zhang L, Pham K, Liu C, Wang H. Electronic Cigarettes Induce Mitochondrial DNA Damage and Trigger TLR9 (Toll-Like Receptor 9)-Mediated Atherosclerosis. Arteriosclerosis Thrombosis And Vascular Biology 2020, 41: 839-853. PMID: 33380174, PMCID: PMC8608030, DOI: 10.1161/atvbaha.120.315556.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAtherosclerosisDisease Models, AnimalDNA DamageDNA, MitochondrialE-Cigarette VaporFemaleHumansInflammationInflammation MediatorsMacrophagesMaleMiceMice, Inbred C57BLMice, Knockout, ApoEMiddle AgedMitochondriaRAW 264.7 CellsSignal TransductionSmokersToll-Like Receptor 9VapingConceptsECV exposureTLR9 expressionInflammatory cytokinesClassical monocytesTLR9 activationAtherosclerotic plaquesEight-week-old ApoEUpregulation of TLR9Expression of TLR9Atherosclerotic lesion developmentOil Red O stainingToll-like receptorsDays/weekE-cig exposureMonocytes/macrophagesNormal laboratory dietRed O stainingPotential pharmacological targetElectronic cigarette useHours/dayProinflammatory cytokinesCig vaporPlasma levelsTLR9 antagonistTLR9 inhibitorE-cigarette promotes breast carcinoma progression and lung metastasis: Macrophage-tumor cells crosstalk and the role of CCL5 and VCAM-1
Pham K, Huynh D, Le L, Delitto D, Yang L, Huang J, Kang Y, Steinberg MB, Li J, Zhang L, Liu D, Tang MS, Liu C, Wang H. E-cigarette promotes breast carcinoma progression and lung metastasis: Macrophage-tumor cells crosstalk and the role of CCL5 and VCAM-1. Cancer Letters 2020, 491: 132-145. PMID: 32829009, PMCID: PMC9703643, DOI: 10.1016/j.canlet.2020.08.010.Peer-Reviewed Original ResearchConceptsBC cell growthCig exposureLung metastasesBreast cancerVCAM-1V-CAM-1Role of CCL5Upregulated protein expressionBC cell survivalE-cig exposurePro-tumorigenic factorsBC cell apoptosisBreast carcinoma progressionMetastatic lung colonizationCCR5 axisMFP tumorsTAMs infiltrationInfiltrated macrophagesCell growthCo-culture systemImmunohistochemical stainsCell crosstalkBC cellsBC growthProliferation indexThe role of survivin in the progression of pancreatic ductal adenocarcinoma (PDAC) and a novel survivin-targeted therapeutic for PDAC
Brown M, Zhang W, Yan D, Kenath R, Le L, Wang H, Delitto D, Ostrov D, Robertson K, Liu C, Pham K. The role of survivin in the progression of pancreatic ductal adenocarcinoma (PDAC) and a novel survivin-targeted therapeutic for PDAC. PLOS ONE 2020, 15: e0226917. PMID: 31929540, PMCID: PMC6957139, DOI: 10.1371/journal.pone.0226917.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaTypes of cancerDuctal adenocarcinomaSurvivin expressionSurvivin inhibitorClinical response rateNovel survivin inhibitorHalf of patientsElevated survivin expressionLower patient survivalPancreatic tumor microenvironmentPotential therapeutic targetExpression of survivinRole of survivinField of oncologyPancreatic cancer linesImmunotherapeutic approachesPatient survivalUntreated cohortTherapeutic responseInhibitor of survivinTreatment resistancePDAC progressionEffective treatmentTumor cell migration
2019
A Novel Small Molecule Inhibits Intrahepatocellular Accumulation of Z-Variant Alpha 1-Antitrypsin In Vitro and In Vivo
Zhang X, Pham K, Li D, Schutte RJ, Gonzalo DH, Zhang P, Oshins R, Tan W, Brantly M, Liu C, Ostrov DA. A Novel Small Molecule Inhibits Intrahepatocellular Accumulation of Z-Variant Alpha 1-Antitrypsin In Vitro and In Vivo. Cells 2019, 8: 1586. PMID: 31817705, PMCID: PMC6953066, DOI: 10.3390/cells8121586.Peer-Reviewed Original ResearchConceptsLiver diseaseAssociated liver injuryChronic liver diseaseMutant alpha 1Common genetic causePiZ miceCurative therapyLiver injuryLiver fibrosisNovel small moleculesAnimal modelsAlpha 1Genetic causeDiseaseIntracellular accumulationAlphaCandidate compoundsHuman alphaMutant alphaCell modelAATDFibrosisInjuryTherapySmall moleculesTumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer
Sivaram N, McLaughlin PA, Han HV, Petrenko O, Jiang YP, Ballou LM, Pham K, Liu C, van der Velden A, Lin RZ. Tumor-intrinsic PIK3CA represses tumor immunogenecity in a model of pancreatic cancer. Journal Of Clinical Investigation 2019, 129: 3264-3276. PMID: 31112530, PMCID: PMC6668699, DOI: 10.1172/jci123540.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsB7-1 AntigenCell Line, TumorClass I Phosphatidylinositol 3-KinasesHistocompatibility Antigens Class IHumansLymphocytes, Tumor-InfiltratingMiceMice, KnockoutMice, SCIDNeoplasms, ExperimentalPancreatic NeoplasmsProto-Oncogene Proteins c-aktSignal TransductionT-LymphocytesXenograft Model Antitumor AssaysConceptsPancreatic cancerT cellsT cell-deficient miceTumor-infiltrating T cellsAntigen-experienced T cellsCell-deficient miceFavorable patient outcomesOrthotopic implantation modelComplete tumor regressionMost pancreatic cancersT cell surveillanceT cell recognitionPancreatic cancer cellsMHC class IAvailable immunotherapiesAdoptive transferEffective immunotherapyTumor immunogenicityTumor regressionPancreatic tumorsPatient outcomesHost miceImmunodeficient miceCell surveillanceTumors
2018
RET rearrangements are actionable alterations in breast cancer
Paratala BS, Chung JH, Williams CB, Yilmazel B, Petrosky W, Williams K, Schrock AB, Gay LM, Lee E, Dolfi SC, Pham K, Lin S, Yao M, Kulkarni A, DiClemente F, Liu C, Rodriguez-Rodriguez L, Ganesan S, Ross JS, Ali SM, Leyland-Jones B, Hirshfield KM. RET rearrangements are actionable alterations in breast cancer. Nature Communications 2018, 9: 4821. PMID: 30446652, PMCID: PMC6240119, DOI: 10.1038/s41467-018-07341-4.Peer-Reviewed Original ResearchMeSH KeywordsAnilidesAnimalsAntineoplastic AgentsBreast NeoplasmsCell Line, TumorCell Transformation, NeoplasticFemaleGene Expression Regulation, NeoplasticHumansMCF-7 CellsMiceMice, NudeMitogen-Activated Protein KinasesNIH 3T3 CellsNuclear Receptor CoactivatorsOncogene Proteins, FusionPhosphatidylinositol 3-KinasesPiperidinesProto-Oncogene Proteins c-retPyridinesQuinazolinesRas Guanine Nucleotide Exchange FactorsReceptor, ErbB-2Signal TransductionXenograft Model Antitumor AssaysConceptsBreast cancerRET amplificationRET gene alterationsMetastatic breast cancerNCOA4-RET fusionXenograft tumor formationPI3K pathwayRadiographic responseActionable alterationsLung cancerRET fusionsRET alterationsRET inhibitionIndex caseTherapeutic targetRET rearrangementsCancerGenomic profilingGene alterationsK pathwayTumor formationGene RETNon-tumorigenic cellsSubsequent treatmentOncogenic potential
2017
A Novel Vaccine Targeting Glypican-3 as a Treatment for Hepatocellular Carcinoma
Wu Q, Pi L, Le Trinh T, Zuo C, Xia M, Jiao Y, Hou Z, Jo S, Puszyk W, Pham K, Nelson DR, Robertson K, Ostrov D, Rameshwar P, Xia CQ, Liu C. A Novel Vaccine Targeting Glypican-3 as a Treatment for Hepatocellular Carcinoma. Molecular Therapy 2017, 25: 2299-2308. PMID: 28865999, PMCID: PMC5628867, DOI: 10.1016/j.ymthe.2017.08.005.Peer-Reviewed Original ResearchConceptsC57/B6 miceHepatocellular carcinomaGlypican-3B6 miceIntravenous infusionImmune responseTumor-specific cytotoxic T lymphocyte responsesCytotoxic T lymphocyte responsesBALB/c miceTumor necrosis factor alphaFirst preclinical evidenceLocal immune responseT lymphocyte responsesLimited treatment optionsDurable tumor regressionNecrosis factor alphaAnti-HCC effectsCultured HCC cellsCTL responsesLymphocyte responsesPreclinical evidenceAntibody therapyMost HCC tissuesHigh morbidityTreatment options
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
Patient-Derived Xenograft Models for Pancreatic Adenocarcinoma Demonstrate Retention of Tumor Morphology through Incorporation of Murine Stromal Elements
Delitto D, Pham K, Vlada AC, Sarosi GA, Thomas RM, Behrns KE, Liu C, Hughes SJ, Wallet SM, Trevino JG. Patient-Derived Xenograft Models for Pancreatic Adenocarcinoma Demonstrate Retention of Tumor Morphology through Incorporation of Murine Stromal Elements. American Journal Of Pathology 2015, 185: 1297-1303. PMID: 25770474, PMCID: PMC4419203, DOI: 10.1016/j.ajpath.2015.01.016.Peer-Reviewed Original ResearchConceptsPancreatic adenocarcinoma specimensStromal elementsTumor morphologyAdenocarcinoma specimensSuccessful engraftmentXenograft modelPatient-derived xenograft modelsCancer cellsPatient-derived xenograftsPancreatic adenocarcinoma xenograftsAdenocarcinoma xenograft modelTumor-stromal interactionsPatient demographicsClinicopathologic factorsPatient survivalNonobese diabeticPancreatic adenocarcinomaSurgical specimensImmunodeficiency miceInitial implantationPathological analysisPreclinical platformAdenocarcinoma xenograftsXenograft microenvironmentTumor growth
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
2012
An in vivo model of epithelial to mesenchymal transition reveals a mitogenic switch
Jahn SC, Law ME, Corsino PE, Parker NN, Pham K, Davis BJ, Lu J, Law BK. An in vivo model of epithelial to mesenchymal transition reveals a mitogenic switch. Cancer Letters 2012, 326: 183-190. PMID: 22906417, PMCID: PMC3705571, DOI: 10.1016/j.canlet.2012.08.013.Peer-Reviewed Original ResearchConceptsCancer cellsPre-EMT cellsNumber of genesMesenchymal transitionDNA microarray analysisEpithelial cell transitionPost-EMT cellsMitogenic signalingMicroarray analysisCell transitionMesenchymal phenotypeBreast cancer cellsERK phosphorylationLPA receptorsVivo modelMEK inhibitorsTissue architectureGrowth inhibitory effectsEpithelial cellsC-MetInhibitors/antagonistsPDGFCellsPhenotypeEMTGlucocorticoids and histone deacetylase inhibitors cooperate to block the invasiveness of basal-like breast cancer cells through novel mechanisms
Law ME, Corsino PE, Jahn SC, Davis BJ, Chen S, Patel B, Pham K, Lu J, Sheppard B, Nørgaard P, Hong J, Higgins P, Kim JS, Luesch H, Law BK. Glucocorticoids and histone deacetylase inhibitors cooperate to block the invasiveness of basal-like breast cancer cells through novel mechanisms. Oncogene 2012, 32: 1316-1329. PMID: 22543582, PMCID: PMC3773700, DOI: 10.1038/onc.2012.138.Peer-Reviewed Original ResearchConceptsE-cadherin localizationE-cadherinPlasma membraneCytoplasmic vesiclesWild-type E-cadherinBreast cancer cellsSerine protease inhibitor plasminogen activator inhibitor-1HDAC inhibitorsCancer cellsBasal-like breast cancer cellsPro-invasive activityGreen fluorescent proteinFull-length formCDCP1 cleavageAnti-invasive functionInhibitor plasminogen activator inhibitor-1MDA-MB-231 cellsHistone deacetylase inhibitorsTriple-negative breast cancerE-cadherin levelsCellular invasionE-cadherin expressionFluorescent proteinCDCP1 proteinOrthotopic xenograft tumorsCCL5, CCR1 and CCR5 in murine glioblastoma: Immune cell infiltration and survival rates are not dependent on individual expression of either CCR1 or CCR5
Pham K, Luo D, Liu C, Harrison JK. CCL5, CCR1 and CCR5 in murine glioblastoma: Immune cell infiltration and survival rates are not dependent on individual expression of either CCR1 or CCR5. Journal Of Neuroimmunology 2012, 246: 10-17. PMID: 22425022, PMCID: PMC3335967, DOI: 10.1016/j.jneuroim.2012.02.009.Peer-Reviewed Original ResearchConceptsMicroglia/macrophagesGlioblastoma multiformeImmune cell infiltrationMalignant brain tumorsTumor bearing miceHuman glioblastoma multiformeMet-CCL5Cell infiltrationMurine glioblastomaCCR5 antagonistsBearing miceBrain tumorsCCR5Survival rateGlioblastoma microenvironmentTumor progressionCCR1CCL5MacrophagesGlioblastomaLymphocytesAntagonistMultiformeTumorsMice