2024
BSLM-10 MOLECULAR AND HISTOLOGICAL CHARACTERIZATION OF NSCLC PROGRESSION TO LEPTOMENINGEAL METASTASIS WITH COMORBID INTRAPARENCHYMAL DISEASE
Kandigian S, Chande S, Dolezal D, Tang T, Wang D, Arnal-Estapé A, Cheok S, McGuone D, Liu Y, Goldberg S, Blondin N, Chiang V, Nguyen D. BSLM-10 MOLECULAR AND HISTOLOGICAL CHARACTERIZATION OF NSCLC PROGRESSION TO LEPTOMENINGEAL METASTASIS WITH COMORBID INTRAPARENCHYMAL DISEASE. Neuro-Oncology Advances 2024, 6: i7-i7. PMCID: PMC11296776, DOI: 10.1093/noajnl/vdae090.020.Peer-Reviewed Original ResearchNon-small cell lung cancerLeptomeningeal diseaseCentral nervous systemLeptomeningeal metastasesParenchymal metastasesCerebrospinal fluidTumor cellsTyrosine kinase inhibitor treatmentCell lung cancerKinase inhibitor treatmentCerebrospinal fluid of patientsCell linesCerebral lateral ventriclesIntra-arterial injectionTGF-b signalingIn vivo passageIntraparenchymal diseaseMechanisms of progressionTumor microenvironmentMultiplex immunofluorescenceAggressive treatmentLeptomeningeal infiltrationPerivascular invasionIntraparenchymal metastasesMurine model154 Elucidating the Immune Landscape of Radiation Necrosis Through Single Cell Analysis of Recurrent Brain Lesions in Patients After Stereotactic Radio Surgery
Robert S, Kiziltug E, Lu B, Arnal-Estape A, Nguyen D, Chiang V. 154 Elucidating the Immune Landscape of Radiation Necrosis Through Single Cell Analysis of Recurrent Brain Lesions in Patients After Stereotactic Radio Surgery. Neurosurgery 2024, 70: 35-36. DOI: 10.1227/neu.0000000000002809_154.Peer-Reviewed Original ResearchRadiation necrosisFluorescence-activated cell sortingInterferon-stimulated genesStereotactic radiosurgeryNatural killerMyeloid cellsImmune cellsRadiosurgical treatment of brain metastasesTreatment of brain metastasesCD4+ T cellsExpression of immune cellsMorbid side effectsTreatment of RNSubpopulations of myeloid cellsStereotactic radio surgeryMetastatic brain tumorsInvasive brain biopsyCellular immune profilesInflammatory immune responseCSF of patientsRN patientsBrain metastasesCD8+Immunotherapy optionsMetastatic tumorsASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts.
Hu B, Wiesehöfer M, de Miguel F, Liu Z, Chan L, Choi J, Melnick M, Arnal Estape A, Walther Z, Zhao D, Lopez-Giraldez F, Wurtz A, Cai G, Fan R, Gettinger S, Xiao A, Yan Q, Homer R, Nguyen D, Politi K. ASCL1 Drives Tolerance to Osimertinib in EGFR Mutant Lung Cancer in Permissive Cellular Contexts. Cancer Research 2024, 84: 1303-1319. PMID: 38359163, PMCID: PMC11142404, DOI: 10.1158/0008-5472.can-23-0438.Peer-Reviewed Original ResearchTyrosine kinase inhibitorsPatient-derived xenograftsEGFR mutant lung cancerMutant lung cancerPre-treatment tumorsResidual diseaseDrug toleranceLung cancerResidual tumor cells in vivoEGFR mutant lung adenocarcinomaTyrosine kinase inhibitor osimertinibEGFR tyrosine kinase inhibitorsTyrosine kinase inhibitor treatmentTumor cells in vivoMutant lung adenocarcinomaMaximal tumor regressionTranscription factor Ascl1Drug-tolerant cellsTime of maximal responseEvidence of cellsCells in vivoOsimertinib treatmentTumor regressionSingle cell transcriptional profilingTumor cells
2023
BSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS
Lu B, Lucca L, DiStasio M, Liu Y, Pham G, Buitrago-Pocasangre N, Arnal-Estape A, Moliterno J, Chiang V, Omuro A, Hafler D. BSBM-18 SINGLE-CELL PROFILING TUMOR-INFILTRATING IMMUNE CELLS REVEALS CXCL13+ FOLLICULAR HELPER-LIKE CD4+ T CELLS IN HUMAN BRAIN TUMORS. Neuro-Oncology Advances 2023, 5: iii4-iii4. PMCID: PMC10402449, DOI: 10.1093/noajnl/vdad070.014.Peer-Reviewed Original ResearchT cell populationsT cell functionT cellsHigh-grade gliomasBrain metastasesHuman brain tumorsImmune cellsBrain tumorsNon-small cell lung cancer brain metastasesB cellsAnti-PD-1 therapy responseCell lung cancer brain metastasesLung cancer brain metastasesProductive antitumor immune responsesFollicular helper T cellsT-cell receptor sequencingTumor-infiltrating T cellsAntitumor T-cell functionCancer brain metastasesCo-inhibitory receptorsAntitumor immune responseCell receptor sequencingLonger overall survivalCell functionTertiary lymphoid structures465 Defining the Immune Profile of Radiation Necrosis Through Single-cell Analysis of Intracranial Lesions
Robert S, Lu B, Arnal-Estape A, Nguyen D, Chiang V. 465 Defining the Immune Profile of Radiation Necrosis Through Single-cell Analysis of Intracranial Lesions. Neurosurgery 2023, 69: 97-98. DOI: 10.1227/neu.0000000000002375_465.Peer-Reviewed Original ResearchRadiation necrosisFluorescence-activated cell sortingImmune profileNatural killer (NK) cellsIncidence of radiation necrosisManagement of brain metastasesMetastatic brain tumor patientsMorbid side effectsTreatment of RNRecurrent metastatic diseaseExpression of Foxp3Cytotoxic T cellsInvasive brain biopsyCellular immune profilesInterleukin-7 receptorBrain tumor patientsBrain metastasesMetastatic diseaseMetastatic tumorsImmune landscapeIntraoperative samplesPatient survivalT cellsBrain biopsyIntracranial lesions
2022
Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer
Adua S, Arnal-Estapé A, Zhao M, Qi B, Liu Z, Kravitz C, Hulme H, Strittmatter N, López-Giráldez F, Chande S, Albert A, Melnick M, Hu B, Politi K, Chiang V, Colclough N, Goodwin R, Cross D, Smith P, Nguyen D. Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer. Nature Communications 2022, 13: 7690. PMID: 36509758, PMCID: PMC9744876, DOI: 10.1038/s41467-022-34889-z.Peer-Reviewed Original ResearchConceptsGene expression programsRas homolog family member ACancer cellsFamily member AEpidermal growth factor receptorExpression programsMetastatic cancer cellsSRF signalingGrowth factor receptorTumor microenvironmentLung cancerFunctional linkExtracellular lamininDrug-resistant cancer cellsMutant non-small cell lung cancerNon-small cell lung cancerCentral nervous system relapseMolecular studiesMember AEGFR-mutant lung cancerFactor receptorNervous system relapseCell lung cancerDisseminated tumor cellsBrain tumor microenvironmentHuman WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation
Cai WL, Chen JF, Chen H, Wingrove E, Kurley SJ, Chan LH, Zhang M, Arnal-Estape A, Zhao M, Balabaki A, Li W, Yu X, Krop ED, Dou Y, Liu Y, Jin J, Westbrook TF, Nguyen DX, Yan Q. Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation. ELife 2022, 11: e78163. PMID: 36043466, PMCID: PMC9584608, DOI: 10.7554/elife.78163.Peer-Reviewed Original ResearchConceptsBreast cancer cellsMetastatic breast cancerBreast cancerRibosomal gene expressionCancer cellsKnockdown of WDR5Vivo genetic screenReversible epigenetic mechanismsGenetic screenTranslation regulationTriple-negative breast cancerEpigenetic regulatorsEpigenetic mechanismsBreast cancer growthCancer-related deathTranslation efficiencyWDR5Novel therapeutic strategiesTranslation rateGene expressionCell growthAdvanced diseaseEffective therapyMetastatic capabilityPotent suppression513 Surveilling Cerebrospinal Fluid Protein Biomarkers in Brain Metastasis
Cheok S, Arnal-Estape A, Wei W, Nguyen D, Chiang V. 513 Surveilling Cerebrospinal Fluid Protein Biomarkers in Brain Metastasis. Neurosurgery 2022, 68: 129-129. DOI: 10.1227/neu.0000000000001880_513.Peer-Reviewed Original ResearchBrain metastasesCerebrospinal fluidIntraparenchymal diseaseCentral nervous system pathologyCerebrospinal fluid (CSF) protein biomarkersIntraparenchymal brain metastasesManagement of patientsNormal pressure hydrocephalusNervous system pathologyCurrent diagnostic standardNon-malignant samplesWarrants further explorationCSF profilePressure hydrocephalusRadiation necrosisLung cancerSimilar pathogenesisBrain parenchymaInflammatory diseasesIntracranial diseaseBreast cancerClinical dataCSF leakTreatment responsePatients
2021
Preclinical Models for the Study of Lung Cancer Pathogenesis and Therapy Development
Arnal-Estapé A, Foggetti G, Starrett JH, Nguyen DX, Politi K. Preclinical Models for the Study of Lung Cancer Pathogenesis and Therapy Development. Cold Spring Harbor Perspectives In Medicine 2021, 11: a037820. PMID: 34518338, PMCID: PMC8634791, DOI: 10.1101/cshperspect.a037820.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPatient-derived xenograftsPreclinical modelsLung cancer translational researchExperimental preclinical modelsLung cancer pathogenesisLung cancer cell linesNumerous preclinical modelsLung cancer subtypesLung cancer researchCancer translational researchCancer cell linesMouse modelNew therapeutic vulnerabilitiesCancer subtypesTumor progressionCancer pathogenesisTherapeutic vulnerabilitiesTranslational researchTherapy developmentCell linesCancer researchThree-dimensional culture systemCulture systemPathogenesisXenograftsTumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF
Cheok SK, Narayan A, Arnal-Estape A, Gettinger S, Goldberg SB, Kluger HM, Nguyen D, Patel A, Chiang V. Tumor DNA Mutations From Intraparenchymal Brain Metastases Are Detectable in CSF. JCO Precision Oncology 2021, 5: 163-172. PMID: 34250381, PMCID: PMC8232069, DOI: 10.1200/po.20.00292.Peer-Reviewed Original ResearchConceptsIntraparenchymal brain metastasesBrain metastasesCell-free DNAExtracranial tumorsBrain metastasis tissuesProgressive brain metastasesThird of patientsNormal pressure hydrocephalusTumor DNA mutationsPrimary cancer typeAnalysis of CSFSamples of CSFLeptomeningeal diseaseEffective surrogate markerBrain biopsyPressure hydrocephalusLumbar punctureSurrogate markerCancer-associated genesMetastasis tissuesPatientsMetastasisDiscordant responsesRenal cellsGenomic profiling
2020
35. EVALUATING CSF CIRCULATING TUMOR DNA IN INTRAPARENCHYMAL BRAIN METASTASIS
Cheok S, Narayan A, Arnal-Estape A, Patel A, Nguyen D, Chiang V. 35. EVALUATING CSF CIRCULATING TUMOR DNA IN INTRAPARENCHYMAL BRAIN METASTASIS. Neuro-Oncology Advances 2020, 2: ii6-ii6. PMCID: PMC7401400, DOI: 10.1093/noajnl/vdaa073.023.Peer-Reviewed Original ResearchIntraparenchymal brain metastasesBrain metastasis tissuesNormal pressure hydrocephalusBrain metastasesCerebrospinal fluidLeptomeningeal diseaseCell-free DNACSF ctDNAMetastasis tissuesTumor DNASamples of CSFStudy 12 patientsPrimary cancer typeAnalysis of CSFIntraparenchymal diseaseFurther therapySystemic metastasesPlasma ctDNASixteen patientsIntraparenchymal tumorsPressure hydrocephalusColorectal cancerLumbar punctureDetection of novelCancer-associated genesTumor progression and chromatin landscape of lung cancer are regulated by the lineage factor GATA6
Arnal-Estapé A, Cai WL, Albert AE, Zhao M, Stevens LE, López-Giráldez F, Patel KD, Tyagi S, Schmitt EM, Westbrook TF, Nguyen DX. Tumor progression and chromatin landscape of lung cancer are regulated by the lineage factor GATA6. Oncogene 2020, 39: 3726-3737. PMID: 32157212, PMCID: PMC7190573, DOI: 10.1038/s41388-020-1246-z.Peer-Reviewed Original ResearchConceptsChromatin landscapeTranscription factorsBone morphogenetic protein (BMP) signalingDiverse transcriptional programsAlters chromatin accessibilityMultiple genomic lociMorphogenetic protein signalingDistal enhancer elementsSelective transcription factorsEpithelial cell typesSurfactant protein CChromatin accessibilityGenomic lociTranscriptional programsLung adenocarcinoma progressionTumor progressionEpigenetic mechanismsProtein signalingBiological functionsLUAD progressionLUAD cellsEnhancer elementsLineage dependencyTumor suppressionLung cancer cellsSpecific chromatin landscapes and transcription factors couple breast cancer subtype with metastatic relapse to lung or brain
Cai WL, Greer CB, Chen JF, Arnal-Estapé A, Cao J, Yan Q, Nguyen DX. Specific chromatin landscapes and transcription factors couple breast cancer subtype with metastatic relapse to lung or brain. BMC Medical Genomics 2020, 13: 33. PMID: 32143622, PMCID: PMC7060551, DOI: 10.1186/s12920-020-0695-0.Peer-Reviewed Original ResearchConceptsOpen chromatin signaturesTranscription factorsChromatin landscapeChromosome conformation captureOpen chromatin landscapeSpecific chromatin landscapesHomophilic cell adhesionTransposase-accessible chromatinEnhancer-promoter interactionsSpecific transcription factorsActive chromatin sitesATAC-seq dataMetastatic cellsGene expression dataChromatin signaturesConformation captureChromatin sitesActive chromatinATAC-seqEpigenomic propertiesChIP-seqChromatin immunoprecipitationEndothelial cell migrationEpigenomic analysisTranscriptomic differences
2019
Adaptive Protein Translation by the Integrated Stress Response Maintains the Proliferative and Migratory Capacity of Lung Adenocarcinoma Cells
Albert AE, Adua SJ, Cai WL, Arnal-Estapé A, Cline GW, Liu Z, Zhao M, Cao PD, Mariappan M, Nguyen DX. Adaptive Protein Translation by the Integrated Stress Response Maintains the Proliferative and Migratory Capacity of Lung Adenocarcinoma Cells. Molecular Cancer Research 2019, 17: 2343-2355. PMID: 31551255, PMCID: PMC6938689, DOI: 10.1158/1541-7786.mcr-19-0245.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 4Adenocarcinoma of LungAmino AcidsCarbon-Nitrogen Ligases with Glutamine as Amide-N-DonorCell Line, TumorCell ProliferationCyclin B1Eukaryotic Initiation Factor-2Gene Expression Regulation, NeoplasticHumansNF-E2-Related Factor 2Oxidative StressPhosphatidylinositol 3-KinasesProtein BiosynthesisProteostasisSignal TransductionStress, PhysiologicalTOR Serine-Threonine KinasesConceptsIntegrated stress responseProtein translationCell cycle progressionLung adenocarcinoma cellsLung cancer cellsNew regulatory layerCertain oncogenic mutationsAmino acid limitationNovel regulatory mechanismControl of proteostasisCancer cellsDifferent biological consequencesEIF2α-dependent mannerAmino acid metabolismAdenocarcinoma cellsNrf2 protein levelsPI3K pathwayConserved pathwayRegulatory layerISR pathwayATF4 branchCell cycle regulator cyclin B1MTOR/PI3K pathwaySelect proteinsAsparagine synthetaseCerebrospinal Fluid Biomarkers of Brain Metastasis
Cheok S, Arnal-Estape A, Narayan A, Zakaria M, Goldberg S, Patel A, Nguyen D, Chiang V. Cerebrospinal Fluid Biomarkers of Brain Metastasis. Neurosurgery 2019, 66: 310-631. DOI: 10.1093/neuros/nyz310_631.Peer-Reviewed Original ResearchNestin+NG2+ Cells Form a Reserve Stem Cell Population in the Mouse Prostate
Hanoun M, Arnal-Estapé A, Maryanovich M, Zahalka AH, Bergren SK, Chua CW, Leftin A, Brodin PN, Shen MM, Guha C, Frenette PS. Nestin+NG2+ Cells Form a Reserve Stem Cell Population in the Mouse Prostate. Stem Cell Reports 2019, 12: 1201-1211. PMID: 31130357, PMCID: PMC6565923, DOI: 10.1016/j.stemcr.2019.04.019.Peer-Reviewed Original ResearchConceptsReserve stem cell populationLineage-tracing analysisStem cell populationStem cell activityProstate stem cellsEpithelial cellsBipotential capacityProstate epithelial cellsTissue maintenanceLuminal epithelial cellsMesenchymal cellsStem cellsCell populationsOrgan damageProstate organoidsNG2 expressionRegenerative capacityRare subsetMouse prostateProstate epitheliumTransgenic miceTissue graftCell activityClonal levelCellsTranscriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis
Wingrove E, Liu ZZ, Patel KD, Arnal-Estapé A, Cai WL, Melnick MA, Politi K, Monteiro C, Zhu L, Valiente M, Kluger HM, Chiang VL, Nguyen DX. Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis. Cell Reports 2019, 27: 1277-1292.e7. PMID: 31018140, PMCID: PMC6592283, DOI: 10.1016/j.celrep.2019.03.085.Peer-Reviewed Original ResearchConceptsBrain metastasesBrain tumor microenvironmentLineage programTumor microenvironmentTumor plasticityStromal gene expressionTranscriptomic hallmarksGene expressionTranscriptional hallmarksMultiple tumor typesMolecular landscapeStromal interactionsMajor siteIntact tissueNeuroinflammatory responseSyngeneic modelPatient biopsiesTumor typesMetastasisMalignant cellsDifferent subtypesTumor cellsHallmarkTranscriptomeCellsTranscriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis
Wingrove E, Liu Z, Patel K, Arnal‐Estape A, Melnick M, Politi K, Monteiro C, Zhu L, Valiente M, Kluger H, Chiang V, Nguyen D. Transcriptomic Hallmarks of Tumor Plasticity and Stromal Interactions in Brain Metastasis. The FASEB Journal 2019, 33: 368.8-368.8. DOI: 10.1096/fasebj.2019.33.1_supplement.368.8.Peer-Reviewed Original ResearchBrain tumor microenvironmentBrain metastasesTumor microenvironmentTumor cellsLung adenocarcinomaTumor lesionsBrain metastatic tumor cellsBreast cancer brain metastasesHuman tumorsExpression of TIM3Cancer brain metastasesMetastatic brain tumorsExpression of astrocytesIntra-arterial injectionTumor-associated macrophagesSyngeneic model systemModels of melanomaFull-text articlesMetastatic tumor cellsCNS metastasesNeuroinflammatory responseBrain lesionsLung tumorsT cellsAthymic mice
2018
Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment.
Stevens LE, Arnal-Estapé A, Nguyen DX. Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment. Journal Of Visualized Experiments 2018 PMID: 30010648, PMCID: PMC6102009, DOI: 10.3791/56650.Peer-Reviewed Original ResearchConceptsCancer cell engraftmentAirways of miceLung cancer cellsCell engraftmentLung cancerTumor cellsTumorigenic capacityNew orthotopic modelNon-physiological sitesTumor cell injectionCancer cellsLung tumor incidenceTreatment-refractory diseaseFull clinical spectrumLung cancer subtypesLung adenocarcinoma subtypesAdditional animal modelsStrains of miceFlanks of miceRefractory diseaseThoracic malignanciesAdenocarcinoma subtypeClinical spectrumOrthotopic transplantationTumor incidencePre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment
Stevens L, Arnal-Estapé A, Nguyen D. Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment. Journal Of Visualized Experiments 2018 DOI: 10.3791/56650-v.Peer-Reviewed Original Research