2023
High-grade B-cell lymphoma, not otherwise specified: a multi-institutional retrospective study
Zayac A, Landsburg D, Hughes M, Bock A, Nowakowski G, Ayers E, Girton M, Hu M, Beckman A, Li S, Medeiros L, Chang J, Stepanovic A, Kurt H, Sandoval-Sus J, Ansari-Lari M, Kothari S, Kress A, Xu M, Torka P, Sundaram S, Smith S, Naresh K, Karimi Y, Epperla N, Bond D, Farooq U, Saad M, Evens A, Pandya K, Naik S, Kamdar M, Haverkos B, Karmali R, Oh T, Vose J, Nutsch H, Rubinstein P, Chaudhry A, Olszewski A. High-grade B-cell lymphoma, not otherwise specified: a multi-institutional retrospective study. Blood Advances 2023, 7: 6381-6394. PMID: 37171397, PMCID: PMC10598493, DOI: 10.1182/bloodadvances.2023009731.Peer-Reviewed Original ResearchConceptsProgression-free survivalMulti-institutional retrospective studyHigh-grade B-cell lymphomaOverall survivalB-cell lymphomaComplete responseMYC rearrangementRetrospective studyBCL6 rearrangementsGerminal center B-cell immunophenotypeHigh serum lactate dehydrogenaseHigh-risk clinical factorsBetter progression-free survivalIntensive chemotherapy programsPoor performance statusStage IV diseaseFirst-line regimensMain prognostic factorsDose-intense chemotherapyHigh-grade morphologic featuresSerum lactate dehydrogenaseB-cell immunophenotypeDA-EPOCHR-CHOPMost patientsElevated glucose metabolism driving pro-inflammatory response in B cells contributes to the progression of type 1 diabetes
Li Z, Zhao M, Li J, Luo W, Huang J, Huang G, Xie Z, Xiao Y, Huang J, Li X, Zhao B, Zhou Z. Elevated glucose metabolism driving pro-inflammatory response in B cells contributes to the progression of type 1 diabetes. Clinical Immunology 2023, 255: 109729. PMID: 37562723, DOI: 10.1016/j.clim.2023.109729.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCross-Sectional StudiesCytokinesDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1GlucoseHumansMiceMice, Inbred NODProto-Oncogene Proteins c-mycSignal TransductionConceptsType 1 diabetesPro-inflammatory responseB cellsGlucose metabolismCytokine productionAberrant B cell responsesNon-obese diabetic (NOD) micePro-inflammatory cytokine productionHigh blood glucose levelsOnset of diabetesInflammatory cytokine productionAdaptive immune responsesB cell responsesCross-sectional cohortImmune system failureDiabetic mouse modelB cell functionBlood glucose levelsB cell populationsB cell metabolismPancreatic beta cellsB cell proliferationElevated glucose metabolismInsulitis developmentNOD miceEpigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1‐EEF1A1 Axis
Li M, Yang L, Chan A, Pokharel S, Liu Q, Mattson N, Xu X, Chang W, Miyashita K, Singh P, Zhang L, Li M, Wu J, Wang J, Chen B, Chan L, Lee J, Zhang X, Rosen S, Müschen M, Qi J, Chen J, Hiom K, Bishop A, Chen C. Epigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1‐EEF1A1 Axis. Advanced Science 2023, 10: 2206584. PMID: 37075745, PMCID: PMC10265057, DOI: 10.1002/advs.202206584.Peer-Reviewed Original ResearchConceptsProtein translation machineryHistone H4 acetylationOncogenic transcription factorNuA4 histoneChromatin remodelersGene bodiesEpigenetic networksTranslation machineryATPase componentEpigenetic controlTumor progressionCRISPR screensTranscription factorsH4 acetylationEpigenetic dysregulationRUVBL1Oncogenic signalingProtein synthesisPatient-derived samplesMYCPharmacological inhibitionEEF1A1 expressionMultiple cancersNovel opportunitiesDynamic interplay
2021
The p53 transcriptional response across tumor types reveals core and senescence-specific signatures modulated by long noncoding RNAs
Tesfaye E, Martinez-Terroba E, Bendor J, Winkler L, Olivero C, Chen K, Feldser DM, Zamudio JR, Dimitrova N. The p53 transcriptional response across tumor types reveals core and senescence-specific signatures modulated by long noncoding RNAs. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2025539118. PMID: 34326251, PMCID: PMC8346867, DOI: 10.1073/pnas.2025539118.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisCell Line, TumorCell ProliferationCellular SenescenceDNA DamageE2F Transcription FactorsGene Expression Regulation, NeoplasticGenome-Wide Association StudyMiceNeoplasmsProto-Oncogene Proteins c-mycRNA, Long NoncodingSignal TransductionStress, PhysiologicalTumor Suppressor Protein p53ConceptsOncogenic contextPermanent cell cycle arrestP53-induced lncRNAsP53 transcriptional responseMYC target genesTumor suppressor mechanismRepression of E2FP53-binding siteP53-dependent senescenceTumor-type specificCell cycle arrestTranscriptional responseProliferative arrestTarget genesMurine cancer cell linesTranscriptional signatureRegulatory axisTumor typesCycle arrestP53 functionDistinct tumor typesFunctional investigationDownstream mediatorP53 pathwayCancer cell linesIntegrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma
Bakouny Z, Braun DA, Shukla SA, Pan W, Gao X, Hou Y, Flaifel A, Tang S, Bosma-Moody A, He MX, Vokes N, Nyman J, Xie W, Nassar AH, Abou Alaiwi S, Flippot R, Bouchard G, Steinharter JA, Nuzzo PV, Ficial M, Sant’Angelo M, Forman J, Berchuck JE, Dudani S, Bi K, Park J, Camp S, Sticco-Ivins M, Hirsch L, Baca SC, Wind-Rotolo M, Ross-Macdonald P, Sun M, Lee GM, Chang SL, Wei XX, McGregor BA, Harshman LC, Genovese G, Ellis L, Pomerantz M, Hirsch MS, Freedman ML, Atkins MB, Wu CJ, Ho TH, Linehan WM, McDermott DF, Heng DYC, Viswanathan SR, Signoretti S, Van Allen EM, Choueiri TK. Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma. Nature Communications 2021, 12: 808. PMID: 33547292, PMCID: PMC7865061, DOI: 10.1038/s41467-021-21068-9.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalB7-H1 AntigenCarcinoma, Renal CellCTLA-4 AntigenCyclin-Dependent Kinase Inhibitor p16Gene Expression ProfilingGene Expression Regulation, NeoplasticHigh-Throughput Nucleotide SequencingHumansImmune Checkpoint InhibitorsImmune Checkpoint ProteinsKidney NeoplasmsMutationProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins c-mycRetrospective StudiesRhabdoid TumorSignal TransductionSurvival AnalysisTranscription, GeneticTumor Suppressor ProteinsUbiquitin ThiolesteraseConceptsRhabdoid renal cell carcinomaImmune checkpoint inhibitorsRenal cell carcinomaCell carcinomaImmune-inflamed phenotypeIntegrative molecular characterizationPD-L1 expressionReal-world cohortMultiple clinical trialsMYC transcriptional programsMolecular featuresCheckpoint inhibitorsClinical outcomesImmune activationImmunologic characteristicsAggressive tumorsImmune infiltrationClinical trialsClinical characterizationRCC tumorsBAP1 mutationsDistinctive molecular featuresTumorsCDKN2A deletionMolecular drivers
2020
p62-dependent autophagy in airway smooth muscle cells regulates metabolic reprogramming and promotes airway remodeling
Yu H, Cheng Y, Zhang G, Wang X, Gu W, Guo X. p62-dependent autophagy in airway smooth muscle cells regulates metabolic reprogramming and promotes airway remodeling. Life Sciences 2020, 266: 118884. PMID: 33310038, DOI: 10.1016/j.lfs.2020.118884.Peer-Reviewed Original ResearchConceptsKnockdown of p62Mechanism of p62Bronchial smooth muscle cellsP62-dependent autophagyIncreased p62 expressionP62 expressionAirway remodelingGlucose consumptionAutophagy fluxAutophagic fluxCCK8 assayP62 overexpressionTranswell methodP62Glycolytic genesGlycolytic proteinsLactate productionMetabolic reprogrammingMigration in vitroHuman bronchial smooth muscle cellsBSMC proliferationCell migrationSmooth muscle cellsAirway remodeling processPromote airway remodelingBayesian copy number detection and association in large-scale studies
Cristiano S, McKean D, Carey J, Bracci P, Brennan P, Chou M, Du M, Gallinger S, Goggins MG, Hassan MM, Hung RJ, Kurtz RC, Li D, Lu L, Neale R, Olson S, Petersen G, Rabe KG, Fu J, Risch H, Rosner GL, Ruczinski I, Klein AP, Scharpf RB. Bayesian copy number detection and association in large-scale studies. BMC Cancer 2020, 20: 856. PMID: 32894098, PMCID: PMC7487704, DOI: 10.1186/s12885-020-07304-3.Peer-Reviewed Original ResearchSignalling input from divergent pathways subverts B cell transformation
Chan LN, Murakami MA, Robinson ME, Caeser R, Sadras T, Lee J, Cosgun KN, Kume K, Khairnar V, Xiao G, Ahmed MA, Aghania E, Deb G, Hurtz C, Shojaee S, Hong C, Pölönen P, Nix MA, Chen Z, Chen CW, Chen J, Vogt A, Heinäniemi M, Lohi O, Wiita AP, Izraeli S, Geng H, Weinstock DM, Müschen M. Signalling input from divergent pathways subverts B cell transformation. Nature 2020, 583: 845-851. PMID: 32699415, PMCID: PMC7394729, DOI: 10.1038/s41586-020-2513-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCell Line, TumorCell Transformation, NeoplasticEnzyme ActivationExtracellular Signal-Regulated MAP KinasesFemaleHumansLeukemia, B-CellMiceProtein Tyrosine Phosphatase, Non-Receptor Type 6Proto-Oncogene Proteins c-bcl-6Proto-Oncogene Proteins c-mycSignal TransductionSTAT5 Transcription FactorConceptsPre-B cell receptorPrincipal oncogenic driverDivergent pathwaysSignal transduction proteinsPro-B cell stageSingle-cell mutationTranscription factor MYCOncogenic driversDivergent signaling pathwaysSingle oncogenic pathwayCentral oncogenic driverMore mature cellsGenetic reactivationTranscriptional programsB-cell transformationProtein kinasePathway componentsERK activationIndividual mutationsOncogenic STAT5Signaling pathwaysCell transformationCytokine receptorsGenetic lesionsDivergent circuitsDerangements in HUWE1/c-MYC pathway confer sensitivity to the BET bromodomain inhibitor GS-626510 in uterine cervical carcinoma
Bonazzoli E, Bellone S, Zammataro L, Gnutti B, Guglielmi A, Pelligra S, Nagarkatti N, Manara P, Tymon-Rosario J, Zeybek B, Altwerger G, Menderes G, Han C, Ratner E, Silasi DA, Huang GS, Andikyan V, Azodi M, Schwartz PE, Santin AD. Derangements in HUWE1/c-MYC pathway confer sensitivity to the BET bromodomain inhibitor GS-626510 in uterine cervical carcinoma. Gynecologic Oncology 2020, 158: 769-775. PMID: 32600791, PMCID: PMC8253557, DOI: 10.1016/j.ygyno.2020.06.484.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsCell Line, TumorFemaleHumansImidazolesIn Situ Hybridization, FluorescenceIsoxazolesMiceMiddle AgedProteinsProto-Oncogene Proteins c-mycSignal TransductionTumor Suppressor ProteinsUbiquitin-Protein LigasesUterine Cervical NeoplasmsXenograft Model Antitumor AssaysYoung AdultConceptsC-myc expressionC-Myc pathwayTwice-daily oral dosesC-MycWestern blotChemotherapy-resistant diseaseUterine cervical carcinomaPotential therapeutic targetEffective therapeutic agentDose-response decreaseCC xenograftsCell line growthOral dosesCervical carcinomaPrimary tumorDeletion/mutationClinical studiesTherapeutic targetTherapeutic agentsNormal tissuesBET inhibitorsVivo activityQRT-PCRCell proliferationGene deletion/mutationABL1, Overexpressed in Hepatocellular Carcinomas, Regulates Expression of NOTCH1 and Promotes Development of Liver Tumors in Mice
Wang F, Hou W, Chitsike L, Xu Y, Bettler C, Perera A, Bank T, Cotler SJ, Dhanarajan A, Denning MF, Ding X, Breslin P, Qiang W, Li J, Koleske AJ, Qiu W. ABL1, Overexpressed in Hepatocellular Carcinomas, Regulates Expression of NOTCH1 and Promotes Development of Liver Tumors in Mice. Gastroenterology 2020, 159: 289-305.e16. PMID: 32171747, PMCID: PMC7387191, DOI: 10.1053/j.gastro.2020.03.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, HepatocellularCell Line, TumorDatasets as TopicDisease Models, AnimalFemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansKaplan-Meier EstimateLiverLiver NeoplasmsMaleMicePhosphorylationPrognosisProto-Oncogene MasProto-Oncogene Proteins c-ablProto-Oncogene Proteins c-mycPyrimidinesReceptor, Notch1Xenograft Model Antitumor AssaysConceptsShorter survival timeLiver tumorsExpression of Notch1Hepatocellular carcinomaHuman HCC cellsHCC cellsXenograft tumorsSurvival timeExpression of MYCLiver tissueTreatment of HCCAlbumin-Cre miceNon-tumor liver tissuesABL proto-oncogene 1Nontumor liver tissuesHuman HCC specimensHuh7 HCC cellsHepatocyte-specific disruptionHCC tissue microarrayProto-oncogene 1HCC cell linesShort hairpin RNACancer Genome AtlasKnockdown of Notch1Tumor levelsPotent 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-MycTumorsInhibitorsp53 Activates the Long Noncoding RNA Pvt1b to Inhibit Myc and Suppress Tumorigenesis
Olivero CE, Martínez-Terroba E, Zimmer J, Liao C, Tesfaye E, Hooshdaran N, Schofield JA, Bendor J, Fang D, Simon MD, Zamudio JR, Dimitrova N. p53 Activates the Long Noncoding RNA Pvt1b to Inhibit Myc and Suppress Tumorigenesis. Molecular Cell 2020, 77: 761-774.e8. PMID: 31973890, PMCID: PMC7184554, DOI: 10.1016/j.molcel.2019.12.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisCell LineCell ProliferationCells, CulturedChromatinEnhancer Elements, GeneticGene Expression RegulationHumansLung NeoplasmsMiceMice, Inbred C57BLPromoter Regions, GeneticProto-Oncogene MasProto-Oncogene Proteins c-mycRNA, Long NoncodingStress, PhysiologicalTumor Suppressor Protein p53ConceptsMYC transcriptional networkLong noncoding RNA PVT1Cellular proliferationTumor suppressor p53Chromatin organizationTranscriptional networksTarget genesMYC transcriptionTranscriptional activityKb downstreamMYC levelsOncogenic signalingSuppressor p53Suppress tumorigenesisDNA damageRNA PVT1Autochthonous mouse modelMYCTranscriptionP53Anti-proliferative activityTumor progressionTumor growthLung cancerMouse model
2019
Prognostic impact of somatic mutations in diffuse large B-cell lymphoma and relationship to cell-of-origin: data from the phase III GOYA study
Bolen C, Klanova M, Trneny M, Sehn L, He J, Tong J, Paulson J, Kim E, Vitolo U, Di Rocco A, Fingerle-Rowson G, Nielsen T, Lenz G, Oestergaard M. Prognostic impact of somatic mutations in diffuse large B-cell lymphoma and relationship to cell-of-origin: data from the phase III GOYA study. Haematologica 2019, 105: 2298-2307. PMID: 33054054, PMCID: PMC7556630, DOI: 10.3324/haematol.2019.227892.Peer-Reviewed Original ResearchConceptsDiffuse large B-cell lymphomaLarge B-cell lymphomaB-cell lymphomaPrognostic impact of somatic mutationsCell-of-origin subtypesBCL2 alterationsCell of originPrognostic impactImpact of somatic mutationsMolecular heterogeneity of diffuse large B-cell lymphomaGerminal center B-cell-like diffuse large B-cell lymphomaHeterogeneity of diffuse large B-cell lymphomaTargeted DNA next-generation sequencingAssociated with shorter progression-free survivalShorter progression-free survivalSomatic mutationsDNA next-generation sequencingParaffin-embedded tissue biopsiesProgression-free survivalMultivariate Cox regressionBCL2 translocationsUntreated patientsPotential treatment targetPrognostic differencesPrognostic effectEpstein-Barr-Virus-Induced One-Carbon Metabolism Drives B Cell Transformation
Wang LW, Shen H, Nobre L, Ersing I, Paulo JA, Trudeau S, Wang Z, Smith NA, Ma Y, Reinstadler B, Nomburg J, Sommermann T, Cahir-McFarland E, Gygi SP, Mootha VK, Weekes MP, Gewurz BE. Epstein-Barr-Virus-Induced One-Carbon Metabolism Drives B Cell Transformation. Cell Metabolism 2019, 30: 539-555.e11. PMID: 31257153, PMCID: PMC6720460, DOI: 10.1016/j.cmet.2019.06.003.Peer-Reviewed Original ResearchMeSH KeywordsAminohydrolasesB-LymphocytesCell Transformation, ViralEpstein-Barr Virus InfectionsEpstein-Barr Virus Nuclear AntigensFemaleFolic AcidGlycolysisHEK293 CellsHerpesvirus 4, HumanHumansLymphocyte ActivationMethylenetetrahydrofolate Dehydrogenase (NADP)MitochondriaMultifunctional EnzymesNADPOxidation-ReductionProteomeProto-Oncogene Proteins c-mycSerineConceptsEpstein-Barr virusOne-carbon metabolismSynthesis of serinePost-transplant B cell lymphomasB-cell transformationPrimary human B cellsMitochondrial remodelingTargets MYCRedox defenseNADPH productionB-cell outgrowthCell transformationMetabolic pathwaysB-cell lymphomaPotential therapeutic targetB cell growthMitochondrial NADPHViral proteinsB cell proliferationCell growthNADPH levelsHuman B cellsCell proliferationMTHFD2Infected cellsp53 Is a Master Regulator of Proteostasis in SMARCB1-Deficient Malignant Rhabdoid Tumors
Carugo A, Minelli R, Sapio L, Soeung M, Carbone F, Robinson F, Tepper J, Chen Z, Lovisa S, Svelto M, Amin S, Srinivasan S, Del Poggetto E, Loponte S, Puca F, Dey P, Malouf G, Su X, Li L, Lopez-Terrada D, Rakheja D, Lazar A, Netto G, Rao P, Sgambato A, Maitra A, Tripathi D, Walker C, Karam J, Heffernan T, Viale A, Roberts C, Msaouel P, Tannir N, Draetta G, Genovese G. p53 Is a Master Regulator of Proteostasis in SMARCB1-Deficient Malignant Rhabdoid Tumors. Cancer Cell 2019, 35: 204-220.e9. PMID: 30753823, PMCID: PMC7876656, DOI: 10.1016/j.ccell.2019.01.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAutophagyCell Line, TumorCyclin-Dependent Kinase Inhibitor p16Endoplasmic Reticulum StressFemaleGene Expression Regulation, NeoplasticHumansMaleMice, 129 StrainMice, Inbred C57BLMice, KnockoutProteasome InhibitorsProteostasisProto-Oncogene Proteins c-mycRhabdoid TumorSignal TransductionSMARCB1 ProteinTumor Cells, CulturedTumor Suppressor Protein p53Unfolded Protein ResponseConceptsMalignant rhabdoid tumorRhabdoid tumorUnfolded protein responseClinical pathological featuresAggressive pediatric malignancyCombination of agentsPediatric malignanciesMouse modelP53 axisMosaic mouse modelChromatin remodeling genesER stress responseTumorsHuman oncogenesisBiallelic inactivationMalignancyProtein responseDramatic activationHuman diseasesMaster regulatorExquisite sensitivityAutophagic machineryAgentsDiseaseStress responseSin1/mTORC2 regulate B cell growth and metabolism by activating mTORC1 and Myc
Li M, Lazorchak AS, Ouyang X, Zhang H, Liu H, Arojo OA, Yan L, Jin J, Han Y, Qu G, Fu Y, Xu X, Liu X, Zhang W, Yang Z, Ruan C, Wang Q, Liu D, Huang C, Lu L, Jiang S, Li F, Su B. Sin1/mTORC2 regulate B cell growth and metabolism by activating mTORC1 and Myc. Cellular & Molecular Immunology 2019, 16: 757-769. PMID: 30705387, PMCID: PMC6804816, DOI: 10.1038/s41423-018-0185-x.Peer-Reviewed Original ResearchConceptsCell growthActivation of mTORC2MTOR complex 2B cell growthAkt-dependent inactivationC-myc proteinMolecular mechanismsSIN1Molecular levelGenetic ablationB cell-mediated immunitySpecific roleCell sizeMetabolismB cell proliferationComplexes 2GrowthAnti-viral immunityMTORC2GSK3B cellsMYCKey componentProteinTransitional stageSynergistic activity of BET inhibitor MK-8628 and PLK inhibitor Volasertib in preclinical models of medulloblastoma
Han Y, Lindner S, Bei Y, Garcia H, Timme N, Althoff K, Odersky A, Schramm A, Lissat A, Künkele A, Deubzer H, Eggert A, Schulte J, Henssen A. Synergistic activity of BET inhibitor MK-8628 and PLK inhibitor Volasertib in preclinical models of medulloblastoma. Cancer Letters 2019, 445: 24-33. PMID: 30611741, DOI: 10.1016/j.canlet.2018.12.012.Peer-Reviewed Original ResearchConceptsModel of medulloblastomaMYC-amplified medulloblastomaMK-8628Preclinical models of medulloblastomaAnti-tumor effectsPreclinical modelsTherapeutic efficacyCentral nervous system tumorsAggressive clinical courseHigh-risk medulloblastomaTherapy-related morbidityCurrent treatment regimensNervous system tumorsTargeted treatment approachesBET protein BRD4MYC protein stabilityIn vivo modelsMYC amplificationMedulloblastoma modelApoptotic cell deathCell cycle arrestClinical courseTreatment regimensSystem tumorsTarget of Plk1
2018
Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors
Li C, Bonazzoli E, Bellone S, Choi J, Dong W, Menderes G, Altwerger G, Han C, Manzano A, Bianchi A, Pettinella F, Manara P, Lopez S, Yadav G, Riccio F, Zammataro L, Zeybek B, Yang-Hartwich Y, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Zizioli V, Odicino F, Pecorelli S, Ardighieri L, Silasi DA, Litkouhi B, Ratner E, Azodi M, Huang GS, Schwartz PE, Lifton RP, Schlessinger J, Santin AD. Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 116: 619-624. PMID: 30584090, PMCID: PMC6329978, DOI: 10.1073/pnas.1814027116.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAzepinesBRCA1 ProteinBRCA2 ProteinCell Line, TumorClass I Phosphatidylinositol 3-KinasesFemaleHumansMiceMutationNeoplasm MetastasisNeoplasm Recurrence, LocalOvarian NeoplasmsProteinsProto-Oncogene Proteins c-mycTriazolesTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsOvarian cancerWhole-exome sequencingC-myc amplificationRecurrent tumorsPrimary tumorBET inhibitorsChemotherapy-resistant diseaseRecurrent ovarian cancerLethal gynecologic malignancyBilateral ovarian cancerChemotherapy-resistant tumorsPrimary metastatic tumorsMutational landscapeSomatic mutationsFresh-frozen tumorsGynecologic malignanciesMetastatic tumorsPrimary cell linesC-MYC gainPIK3CA amplificationTranscoelomic metastasisTherapeutic targetPatientsMetastatic abilityTumorsThe Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification
Lu YC, Sanada C, Xavier-Ferrucio J, Wang L, Zhang PX, Grimes HL, Venkatasubramanian M, Chetal K, Aronow B, Salomonis N, Krause DS. The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification. Cell Reports 2018, 25: 2083-2093.e4. PMID: 30463007, PMCID: PMC6336197, DOI: 10.1016/j.celrep.2018.10.084.Peer-Reviewed Original ResearchMeSH KeywordsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCell CycleCell LineageGene Expression RegulationGene Regulatory NetworksHEK293 CellsHigh-Throughput Nucleotide SequencingHumansMegakaryocyte-Erythroid Progenitor CellsProto-Oncogene Proteins c-mycReproducibility of ResultsSignal TransductionTranscription, GeneticTumor Suppressor Protein p53ConceptsMegakaryocytic-erythroid progenitorsCommon myeloid progenitorsTranscription factorsCell cycleSingle-cell RNA sequencingRegulatory transcription factorsMegakaryocyte-erythroid progenitorsCell cycle regulatorsCell cycle activationFate specificationLineage specificationE lineageMalignant disease statesGenetic manipulationRNA sequencingE progenitorsErythroid maturationCycle regulatorsDifferential expressionHuman cellsHealthy human cellsCycle activationMegakaryocyte progenitorsMolecular signaturesMyeloid progenitorsInhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer
Bonazzoli E, Predolini F, Cocco E, Bellone S, Altwerger G, Menderes G, Zammataro L, Bianchi A, Pettinella F, Riccio F, Han C, Yadav G, Lopez S, Manzano A, Manara P, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Schlessinger J, Santin AD. Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer. Clinical Cancer Research 2018, 24: 4845-4853. PMID: 29941483, PMCID: PMC6168417, DOI: 10.1158/1078-0432.ccr-18-0864.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntineoplastic AgentsApoptosisAurora Kinase AAurora Kinase BAzepinesCell Line, TumorCell ProliferationCystadenocarcinoma, SerousDose-Response Relationship, DrugEndometrial NeoplasmsExome SequencingFemaleGene Expression Regulation, NeoplasticHumansMiceMiddle AgedPhosphorylationPrimary Cell CultureProteinsProto-Oncogene Proteins c-mycTriazolesUterine NeoplasmsXenograft Model Antitumor AssaysConceptsUterine serous carcinomaPrimary USC cell linesUSC cell linesC-myc expressionCell linesC-MycChemotherapy-resistant diseaseQRT-PCRHigh c-myc expressionDose-dependent decreaseDose-dependent increasePotential therapeutic targetEffective therapeutic agentMouse xenograft modelClin Cancer ResFresh frozen tumor tissueC-myc gene amplificationUSC xenograftsEndometrial cancerAggressive variantSerous carcinomaWhole-exome sequencing studiesClinical studiesConcentrations/dosesXenograft model
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