2019
Suppressing miR-21 activity in tumor-associated macrophages promotes an antitumor immune response
Sahraei M, Chaube B, Liu Y, Sun J, Kaplan A, Price NL, Ding W, Oyaghire S, García-Milian R, Mehta S, Reshetnyak YK, Bahal R, Fiorina P, Glazer PM, Rimm DL, Fernández-Hernando C, Suárez Y. Suppressing miR-21 activity in tumor-associated macrophages promotes an antitumor immune response. Journal Of Clinical Investigation 2019, 129: 5518-5536. PMID: 31710308, PMCID: PMC6877327, DOI: 10.1172/jci127125.Peer-Reviewed Original ResearchConceptsTumor-associated macrophagesMiR-21 expressionTumor growthMiR-21Immune responseCytotoxic T cell responsesC motif chemokine 10Antitumor immune responseT cell responsesAntitumoral immune responseTumor immune infiltratesInduction of cytokinesPotential therapeutic implicationsMiR-21 inhibitionStages of carcinogenesisAngiostatic phenotypeTumor cell deathIL-12Immune infiltratesTherapeutic implicationsSolid tumorsTumor neovascularizationTumor progressionTumor microenvironmentTumor pathogenesisSiglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy
Wang J, Sun J, Liu LN, Flies DB, Nie X, Toki M, Zhang J, Song C, Zarr M, Zhou X, Han X, Archer KA, O’Neill T, Herbst RS, Boto AN, Sanmamed MF, Langermann S, Rimm DL, Chen L. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nature Medicine 2019, 25: 656-666. PMID: 30833750, PMCID: PMC7175920, DOI: 10.1038/s41591-019-0374-x.Peer-Reviewed Original ResearchConceptsNormalization cancer immunotherapyTumor microenvironmentSiglec-15Antibody blockadeCancer immunotherapyImmune suppressorMyeloid cellsAntigen-specific T cell responsesB7-H1/PDTumor-infiltrating myeloid cellsB7-H1 moleculesAnti-tumor immunityT cell responsesPotential targetImmune evasion mechanismsInhibits tumor growthMacrophage colony-stimulating factorColony-stimulating factorB7-H1Evasion mechanismsMouse modelHuman cancer cellsTumor growthCell responsesGenetic ablation
2016
Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo
Cocco E, Lopez S, Black J, Bellone S, Bonazzoli E, Predolini F, Ferrari F, Schwab CL, Menderes G, Zammataro L, Buza N, Hui P, Wong S, Zhao S, Bai Y, Rimm DL, Ratner E, Litkouhi B, Silasi DA, Azodi M, Schwartz PE, Santin AD. Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo. British Journal Of Cancer 2016, 115: 303-311. PMID: 27351214, PMCID: PMC4973158, DOI: 10.1038/bjc.2016.198.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorClass I Phosphatidylinositol 3-KinasesCyclin EDNA Copy Number VariationsFemaleGene Knockdown TechniquesHeterograftsHumansIn Situ Hybridization, FluorescenceIn Vitro TechniquesMiceMutationOncogene ProteinsPhosphatidylinositol 3-KinasesRNA, MessengerTissue Array AnalysisUterine NeoplasmsConceptsUterine serous carcinomaSerous carcinomaTumor growthCyclin E1 (CCNE1) gene amplificationRecurrent uterine serous carcinomaPrimary USC cell linesNovel therapeutic optionsSingle-agent treatmentIdeal therapeutic targetUSC cell linesCyclin E1 expressionUSC patientsUSC xenograftsInhibited cell growthCell cycle analysisAggressive variantTherapeutic optionsCCNE1 amplificationEndometrial tumorsCYC065Therapeutic targetClinical optionPIK3CA driver mutationsDriver mutationsXenograftsTriple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence
Balko JM, Schwarz LJ, Luo N, Estrada MV, Giltnane JM, Dávila-González D, Wang K, Sánchez V, Dean PT, Combs SE, Hicks D, Pinto JA, Landis MD, Doimi FD, Yelensky R, Miller VA, Stephens PJ, Rimm DL, Gómez H, Chang JC, Sanders ME, Cook RS, Arteaga CL. Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence. Science Translational Medicine 2016, 8: 334ra53. PMID: 27075627, PMCID: PMC5256931, DOI: 10.1126/scitranslmed.aad3001.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCell Line, TumorCell ProliferationChromosomes, Human, Pair 9Cohort StudiesFemaleGene AmplificationGene Knockdown TechniquesGenetic LociHumansJanus Kinase 2Middle AgedSignal TransductionSpheroids, CellularSTAT3 Transcription FactorSTAT6 Transcription FactorTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerJAK2 amplificationBreast cancerUntreated triple-negative breast cancerEventual metastatic spreadBasal-like cancersBreast cancer subtypesTNBC cell linesAmplification of JAK2Janus kinase 2 (JAK2) geneNeoadjuvant chemotherapyOverall survivalTNBC xenograftsJAK1/2 inhibitorClinical trialsMetastatic spreadKinase 2 geneJAK2-specific inhibitorTumor growthCancer subtypesMammosphere formationPatientsPotential biomarkersTumor progressionJAK2 inhibitorsmiR-34a Silences c-SRC to Attenuate Tumor Growth in Triple-Negative Breast Cancer
Adams BD, Wali VB, Cheng CJ, Inukai S, Booth CJ, Agarwal S, Rimm DL, Győrffy B, Santarpia L, Pusztai L, Saltzman WM, Slack FJ. miR-34a Silences c-SRC to Attenuate Tumor Growth in Triple-Negative Breast Cancer. Cancer Research 2016, 76: 927-939. PMID: 26676753, PMCID: PMC4755913, DOI: 10.1158/0008-5472.can-15-2321.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerBreast cancerTumor growthMiR-34a replacement therapyTNBC cell linesDifferent TNBC subtypesPromising therapeutic strategyAttenuates tumor growthHuman clinical trialsMiRNA-profiling studiesMiR-34a levelsCell linesPotent antitumorigenic effectsMiR-34a targetsHuman tumor specimensC-SrcReplacement therapyTNBC subtypesAggressive subtypeTreatment optionsClinical trialsDisease progressionEffective therapyPatient outcomesC-Src inhibitor
2005
Automated Quantitative Analysis of Activator Protein-2α Subcellular Expression in Melanoma Tissue Microarrays Correlates with Survival Prediction
Berger AJ, Davis DW, Tellez C, Prieto VG, Gershenwald JE, Johnson MM, Rimm DL, Bar-Eli M. Automated Quantitative Analysis of Activator Protein-2α Subcellular Expression in Melanoma Tissue Microarrays Correlates with Survival Prediction. Cancer Research 2005, 65: 11185-11192. PMID: 16322269, DOI: 10.1158/0008-5472.can-05-2300.Peer-Reviewed Original ResearchConceptsAP-2 expressionM.D. Anderson Cancer CenterCytoplasmic expression levelsAnderson Cancer CenterAP-2 levelsProgression of melanomaMelanoma tissue microarrayClinicopathologic factorsRetrospective cohortMetastatic groupPrognostic significanceBreslow depthCancer CenterNevi groupPoor prognosisMetastatic melanomaPrimary tumorPrimary melanomaDiagnosis groupsTissue microarrayTumor growthMelanoma specimensMalignant transformationHuman melanomaMelanoma progression