2024
Chemotherapy drives tertiary lymphoid structures that correlate with ICI-responsive TCF1+CD8+ T cells in metastatic ovarian cancer
Lanickova T, Hensler M, Kasikova L, Vosahlikova S, Angelidou A, Pasulka J, Griebler H, Drozenova J, Mojzisova K, Vankerckhoven A, Laco J, Ryška A, Dundr P, Kocian R, Cibula D, Brtnicky T, Skapa P, Jacob F, Kovar M, Praznovec I, McNeish I, Halaska M, Rob L, Coosemans A, Orsulic S, Galluzzi L, Spisek R, Fucikova J. Chemotherapy drives tertiary lymphoid structures that correlate with ICI-responsive TCF1+CD8+ T cells in metastatic ovarian cancer. Clinical Cancer Research 2024, 31: 164-180. PMID: 39163092, PMCID: PMC11701433, DOI: 10.1158/1078-0432.ccr-24-1594.Peer-Reviewed Original ResearchHigh-grade serous ovarian carcinomaImmune checkpoint inhibitorsTertiary lymphoid structuresT cellsLymphoid structuresRecruitment of immune effector cellsMature tertiary lymphoid structuresCD8+ T cellsMetastatic ovarian cancerT-cell phenotypeFollicular T cellsSerous ovarian carcinomaSignificant survival benefitNeo-adjuvant chemotherapyImmune effector cellsIndependent patient cohortTargeted anticancer agentsCombinatorial partnersTesting chemotherapyCheckpoint inhibitorsTfh cellsCalreticulin exposureOvarian carcinomaPaclitaxel-carboplatinSyngeneic model
2023
MODL-02. DEVELOPMENT OF RODENT GLIOBLASTOMA MODELS OF MGMT-MEDIATED TEMOZOLOMIDE RESISTANCE
Lee T, Bhatt D, Sundaram R, Saltzman W, Bindra R, Vasquez J. MODL-02. DEVELOPMENT OF RODENT GLIOBLASTOMA MODELS OF MGMT-MEDIATED TEMOZOLOMIDE RESISTANCE. Neuro-Oncology 2023, 25: v298-v298. PMCID: PMC10640218, DOI: 10.1093/neuonc/noad179.1153.Peer-Reviewed Original ResearchMouse glioma modelPotential therapeutic targetMGMT overexpressionGlioma modelTherapeutic targetTumor growthDaily x 5 daysMGMT expressionMGMT inhibitorsUseful preclinical toolTumor immune microenvironmentImportant prognostic biomarkerFischer 344 ratsHuman GBM cell linesDelays tumor growthHigh MGMT expressionMouse glioma cellsRodent glioblastoma modelsSyngeneic Fischer 344 ratsGBM cell linesAlkylator therapyO6-methylguanine-DNA methyltransferaseChemoimmunotherapy combinationImmune microenvironmentSyngeneic model
2020
Potent BRD4 inhibitor suppresses cancer cell-macrophage interaction
Yin M, Guo Y, Hu R, Cai WL, Li Y, Pei S, Sun H, Peng C, Li J, Ye R, Yang Q, Wang N, Tao Y, Chen X, Yan Q. Potent BRD4 inhibitor suppresses cancer cell-macrophage interaction. Nature Communications 2020, 11: 1833. PMID: 32286255, PMCID: PMC7156724, DOI: 10.1038/s41467-020-15290-0.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnimalsCell CommunicationCell Cycle ProteinsCell Line, TumorCell ProliferationDisease Models, AnimalDown-RegulationDrug DesignFemaleHumansHypoxia-Inducible Factor 1, alpha SubunitMacrophage Colony-Stimulating FactorMacrophagesMice, Inbred BALB CMice, NudeNeoplasmsPhosphorylationProto-Oncogene Proteins c-mycReceptors, Granulocyte-Macrophage Colony-Stimulating FactorSignal TransductionTranscription FactorsTreatment OutcomeConceptsTumor growthMajor clinical stagesBET inhibitorsProliferation of tumorsExtraterminal domain (BET) family proteinsTumor cell proliferationClinical stageTumor shrinkageSyngeneic modelPotent BRD4 inhibitorsSmall molecule inhibitorsSolid tumorsBRD4 inhibitionTumor cellsOral bioavailabilityCancer treatmentCell proliferationBRD4 inhibitorsMolecule inhibitorsMultiple mechanismsC-MycTumorsInhibitorsShort-term starvation reduces IGF-1 levels to sensitize lung tumors to PD-1 immune checkpoint blockade
Ajona D, Ortiz-Espinosa S, Lozano T, Exposito F, Calvo A, Valencia K, Redrado M, Remírez A, Lecanda F, Alignani D, Lasarte J, Macaya I, Senent Y, Bértolo C, Sainz C, Gil-Bazo I, Eguren-Santamaría I, Lopez-Picazo J, Gonzalez A, Perez-Gracia J, de Andrea C, Vicent S, Sanmamed M, Montuenga L, Pio R. Short-term starvation reduces IGF-1 levels to sensitize lung tumors to PD-1 immune checkpoint blockade. Nature Cancer 2020, 1: 75-85. PMID: 35121837, DOI: 10.1038/s43018-019-0007-9.Peer-Reviewed Original ResearchConceptsPD-1 blockadeCell death protein 1 (PD-1) pathwayPD-1 immune checkpoint blockadeCD8/Treg ratioHigh IGF-1R expressionInsulin-like growth factor-1Cell lung cancer treatmentIGF-1 levelsPD-1 inhibitionImmune checkpoint blockadeTumor-specific immunityCell lung cancerIGF-1R expressionHigher plasma levelsLung cancer progressionLung cancer treatmentIGF-1 receptorGrowth factor-1Protein 1 pathwayTreg ratioCD8 cellsCheckpoint blockadePD-1Syngeneic modelLung cancer
2019
Transcriptomic 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 cellsHallmarkTranscriptomeCells
2013
Epigenetic 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 potential
2009
Antibody-mediated FOXP3 protein therapy induces apoptosis in cancer cells in vitro and inhibits metastasis in vivo.
Heinze E, Baldwin S, Chan G, Hansen J, Song J, Clements D, Aragon R, Nishimura R, Reeves M, Weisbart R. Antibody-mediated FOXP3 protein therapy induces apoptosis in cancer cells in vitro and inhibits metastasis in vivo. International Journal Of Oncology 2009, 35: 167-73. PMID: 19513564, DOI: 10.3892/ijo_00000325.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalApoptosisBreast NeoplasmsCaspase 3Cell Line, TumorCell SurvivalColorectal NeoplasmsDose-Response Relationship, DrugFemaleForkhead Transcription FactorsHumansImmunoconjugatesImmunoglobulin FragmentsLiver NeoplasmsMiceMice, Inbred BALB COvarian NeoplasmsRecombinant Fusion ProteinsTransfectionConceptsColon cancer metastasisCancer cellsCancer metastasisColon cancer cellsBALB/c miceProtein therapyImmune suppressive functionCell deathDose-dependent cell deathRegulatory cellsTumor burdenClinical efficacySyngeneic modelC miceNuclear transcription factorMouse modelSuppressive functionInhibits metastasisMetastasisZ-VAD-FMKClinical potentialTherapyCaspase-3Foxp3Cell killing
1999
An Essential Role for Macrophage Migration Inhibitory Factor (MIF) in Angiogenesis and the Growth of a Murine Lymphoma
Chesney J, Metz C, Bacher M, Peng T, Meinhardt A, Bucala R. An Essential Role for Macrophage Migration Inhibitory Factor (MIF) in Angiogenesis and the Growth of a Murine Lymphoma. Molecular Medicine 1999, 5: 181-191. PMID: 10404515, PMCID: PMC2230298, DOI: 10.1007/bf03402061.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesCell DivisionCollagenDisease Models, AnimalDrug CombinationsEndothelium, VascularHumansImmunohistochemistryLamininLymphoma, B-CellMacrophage Migration-Inhibitory FactorsMiceMice, Inbred StrainsNeovascularization, PathologicOligonucleotides, AntisenseProteoglycansTumor Cells, CulturedConceptsMacrophage migration inhibitory factorRole of MIFAnti-MIF monoclonal antibodyMigration inhibitory factorB-cell lymphomaMonoclonal antibodiesCell lymphomaEffect of MIFBackgroundMacrophage migration inhibitory factorInhibitory factorC3H/HeN miceTumor-associated neovasculatureActivation of macrophagesAutocrine growth factorMicrovascular endothelial cellsCultured microvascular endothelial cellsAnti-neoplastic agentsNew blood vessel formationSolid tumor biologyEndothelial cell proliferationMIF expressionHeN miceSyngeneic modelMIF proteinTumor response
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