2020
The 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
Tumor-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
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
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 ResearchMeSH KeywordsAnimalsCell Line, TumorEpithelial-Mesenchymal TransitionHumansMiceMitogensModels, BiologicalOligonucleotide Array Sequence AnalysisConceptsCancer 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 tumors