2021
Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer
Mirzapoiazova T, Xiao G, Mambetsariev B, Nasser MW, Miaou E, Singhal SS, Srivastava S, Mambetsariev I, Nelson MS, Nam A, Behal A, Arvanitis LD, Atri P, Muschen M, Tissot FLH, Miser J, Kovach JS, Sattler M, Batra SK, Kulkarni P, Salgia R. Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer. Molecular Cancer Therapeutics 2021, 20: 1820-1835. PMID: 34253596, PMCID: PMC8722383, DOI: 10.1158/1535-7163.mct-21-0013.Peer-Reviewed Original ResearchConceptsProtein phosphatase 2APhosphatase 2ASerine/threonine phosphataseDNA damage responseRegulation of apoptosisSmall molecule inhibitorsGlycolytic ATP productionThreonine phosphataseTwo-dimensional cultureLB100ATP productionMolecule inhibitorsPP2AThree-dimensional spheroid modelEndothelial cell monolayersGlucose uptakeCell viabilitySCLC cellsTherapeutic targetApoptosisCell monolayersMass spectrometrySpheroid modelTumor spheroidsCells
2017
Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia
Takao S, Chien W, Madan V, Lin D, Ding L, Sun Q, Mayakonda A, Sudo M, Xu L, Chen Y, Jiang Y, Gery S, Lill M, Park E, Senapedis W, Baloglu E, Müschen M, Koeffler H. Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia. Leukemia 2017, 32: 616-625. PMID: 28904384, DOI: 10.1038/leu.2017.281.Peer-Reviewed Original ResearchMeSH KeywordsAcrylamidesAminopyridinesAnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell ProliferationCell SurvivalCytokinesDisease Models, AnimalFemaleHumansMaleMiceNADNicotinamide PhosphoribosyltransferaseP21-Activated KinasesPrecursor B-Cell Lymphoblastic Leukemia-LymphomaSignal TransductionXenograft Model Antitumor AssaysConceptsB-cell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaP21-activated kinase 4Nicotinamide phosphoribosyltransferaseLymphoblastic leukemiaNAMPT inhibitionPatient-derived xenograft murine modelsPrognosis of patientsNicotinamide adenine dinucleotideNovel therapeutic strategiesNicotinic acid supplementationNovel dual inhibitorXenograft murine modelCell growth inhibitionAcid supplementationMurine modelTherapeutic strategiesRate-limiting enzymeCytogenetic abnormalitiesVivo efficacyPatientsNAMPT inhibitorsInhibitory effectDual inhibitorKinase 4
2016
Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation
McCracken A, McMonigle R, Tessier J, Fransson R, Perryman M, Chen B, Keebaugh A, Selwan E, Barr S, Kim S, Roy S, Liu G, Fallegger D, Sernissi L, Brandt C, Moitessier N, Snider A, Clare S, Müschen M, Huwiler A, Kleinman M, Hanessian S, Edinger A. Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation. Leukemia 2016, 31: 669-677. PMID: 27573555, PMCID: PMC5332311, DOI: 10.1038/leu.2016.244.Peer-Reviewed Original ResearchConceptsS1P receptor activationAnti-leukemic actionProtein phosphatase 2APro-apoptotic targetsPhosphatase 2ASphingosine kinase 2Efficient phosphorylationGenetic approachesReceptor activationKinase 2Nutrient accessChemical biologyPhosphorylationTight inverse correlationDistinct mechanismsS1P receptorsAnti-leukemic activityNovel therapeutic approachesLeukemia progressionReceptor activityMRNA expressionAnti-leukemic agentsActivationEnhanced potencyBiology
2010
Development of resistance to dasatinib in Bcr/Abl-positive acute lymphoblastic leukemia
Fei F, Stoddart S, Müschen M, Kim Y, Groffen J, Heisterkamp N. Development of resistance to dasatinib in Bcr/Abl-positive acute lymphoblastic leukemia. Leukemia 2010, 24: 813-820. PMID: 20111071, PMCID: PMC3038787, DOI: 10.1038/leu.2009.302.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBlotting, WesternCells, CulturedDasatinibDrug Resistance, NeoplasmEmbryo, MammalianFibroblastsFusion Proteins, bcr-ablHumansLeukemia, ExperimentalMiceMice, Inbred NODMice, KnockoutMice, SCIDPhosphorylationPrecursor Cell Lymphoblastic Leukemia-LymphomaProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrimidinesReceptors, CXCR4Src-Family KinasesStromal CellsThiazolesConceptsLong-term treatmentBcr/Abl-positive acute lymphoblastic leukemiaPhiladelphia chromosome-positive leukemiaAcute lymphoblastic leukemia cellsLeukemia cellsTreatment of miceAcute lymphoblastic leukemiaEffects of dasatinibLymphoblastic leukemia cellsTyrosine kinase inhibitionDrug-resistant cellsHigh-dose pulseBCR/ABLDasatinib monotherapyDaily doseDevelopment of resistanceDasatinib treatmentLymphoblastic leukemiaB lineage cellsCell surface expressionCXCR4 inhibitorsEnhanced cell deathLow doseLow dosesDasatinib
2001
Resistance to CD95‐mediated apoptosis in breast cancer is not due to somatic mutation of the CD95 gene
Müschen M, Re D, Betz B, Moers C, Wolf J, Niederacher D, Diehl V, Beckmann M. Resistance to CD95‐mediated apoptosis in breast cancer is not due to somatic mutation of the CD95 gene. International Journal Of Cancer 2001, 92: 309-310. PMID: 11291062, DOI: 10.1002/1097-0215(200102)9999:9999<::aid-ijc1188>3.0.co;2-5.Peer-Reviewed Original Research
2000
Somatic Mutation of the Cd95 Gene in Human B Cells as a Side-Effect of the Germinal Center Reaction
Müschen M, Re D, Jungnickel B, Diehl V, Rajewsky K, Küppers R. Somatic Mutation of the Cd95 Gene in Human B Cells as a Side-Effect of the Germinal Center Reaction. Journal Of Experimental Medicine 2000, 192: 1833-1840. PMID: 11120779, PMCID: PMC2213498, DOI: 10.1084/jem.192.12.1833.Peer-Reviewed Original ResearchConceptsDeath domainCD95 geneSomatic mutationsNegative selectionNon-Ig genesHuman B cellsSomatic hypermutation machineryApoptosis-resistant cellsTumor suppressor geneDD mutationsLast exonHypermutation machinerySuppressor geneApoptosis resistanceGenesB cellsImmunoglobulin genesGerminal center B cellsSomatic hypermutationMutationsCD95 pathwayGC B-cell lymphomasGC B cellsCellsGerminal center reactionSomatic mutations of the CD95 gene in Hodgkin and Reed-Sternberg cells.
Müschen M, Re D, Bräuninger A, Wolf J, Hansmann M, Diehl V, Küppers R, Rajewsky K. Somatic mutations of the CD95 gene in Hodgkin and Reed-Sternberg cells. Cancer Research 2000, 60: 5640-3. PMID: 11059754.Peer-Reviewed Original ResearchDefining CD95 as a tumor suppressor gene
Müschen M, Warskulat U, Beckmann M. Defining CD95 as a tumor suppressor gene. Journal Of Molecular Medicine 2000, 78: 312-325. PMID: 11001528, DOI: 10.1007/s001090000112.Peer-Reviewed Original ResearchConceptsTumor suppressor geneSuppressor geneCD95L expressionReceptor-ligand systemCD95L-mediated apoptosisKey regulatorDe novo expressionMalignant cellsGenesSomatic mutationsCD95 geneLymphocyte homeostasisBystander cellsCD95ApoptosisNatural ligandMalignant progressionNonmalignant counterpartsNovo expressionTumor progressionExpressionCellsTumor cellsGermlineAntitumor immunityCD95 ligand expression as a mechanism of immune escape in breast cancer
Müschen M, Moers C, Warskulat U, Even J, Niederacher D, Beckmann M. CD95 ligand expression as a mechanism of immune escape in breast cancer. Immunology 2000, 99: 69-77. PMID: 10651943, PMCID: PMC2327134, DOI: 10.1046/j.1365-2567.2000.00921.x.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisBreast NeoplasmsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesEnzyme-Linked Immunosorbent AssayFas Ligand ProteinFas ReceptorFemaleFlow CytometryHumansImmunohistochemistryJurkat CellsLymphocyte CountMembrane GlycoproteinsProtein IsoformsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerConceptsBreast cancer cellsT cellsBreast cancerCD95L expressionImmune escapeIFN-gammaCancer cellsJurkat T cellsTumor-infiltrating T cellsCD95L mRNA levelsDepletion of CD4Cultured breast cancer cellsBreast cancer patientsPeripheral blood lymphocytesCD95/CD95L systemBreast cancer cell linesNon-malignant mammary tissuesActivated T cellsCD95 ligand expressionRate of apoptosisBreast cancer sectionsCancer cell linesInteraction of CD95Systemic immunosuppressionCancer patients
1999
CD95 ligand expression in dedifferentiated breast cancer
Müschen M, Moers C, Warskulat U, Niederacher D, Betz B, Even J, Lim A, Josien R, Beckmann M, Häussinger D. CD95 ligand expression in dedifferentiated breast cancer. The Journal Of Pathology 1999, 189: 378-386. PMID: 10547600, DOI: 10.1002/(sici)1096-9896(199911)189:3<378::aid-path439>3.0.co;2-d.Peer-Reviewed Original ResearchConceptsReverse transcriptase-polymerase chain reactionBreast cancerCD95 ligand expressionMRNA levelsLigand expressionGrade III breast cancerMammary tissueCD95L mRNA levelsTumor-infiltrating lymphocytesCD95 ligandHigh-grade carcinomaQuantitative reverse transcriptase-polymerase chain reactionBenign mammary tissuesTissue sectionsBreast cancer tissuesNon-malignant mammary tissuesTranscriptase-polymerase chain reactionBreast cancer tissue sectionsBreast cancer sectionsCancer tissue sectionsGrade IGrade IIHistopathological gradingReceptor expressionCancer tissuesInvolvement of Soluble CD95 in Churg-Strauss Syndrome
Müschen M, Warskulat U, Perniok A, Even J, Moers C, Kismet B, Temizkan N, Simon D, Schneider M, Häussinger D. Involvement of Soluble CD95 in Churg-Strauss Syndrome. American Journal Of Pathology 1999, 155: 915-925. PMID: 10487849, PMCID: PMC1866905, DOI: 10.1016/s0002-9440(10)65191-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedApoptosisCell SurvivalCells, CulturedChurg-Strauss SyndromeClone CellsCulture Media, ConditionedEnzyme-Linked Immunosorbent AssayEosinophilsFas Ligand ProteinFas ReceptorFemaleGenes, T-Cell Receptor betaHumansImmunosuppressive AgentsMaleMembrane GlycoproteinsMiddle AgedMultigene FamilyReceptors, Tumor Necrosis FactorReverse Transcriptase Polymerase Chain ReactionRNA, MessengerT-LymphocytesConceptsChurg-Strauss syndromeSoluble CD95CSS patientsOligoclonal T cell expansionTCR Vbeta gene usageAutoimmune lymphoproliferative disordersVbeta gene usageRole of eosinophilsT cell expansionPeripheral blood lymphocytesT cell clonesSoluble splice variantCD95L-mediated apoptosisCD95 receptor expressionImmunosuppressive therapyClinical improvementCDR3 motifsEffector cellsLymphoproliferative disordersCS patientsBlood lymphocytesReceptor expressionHealthy individualsVbeta genesEosinophilsRegulation of CD95 (APO‐1/ FAS) ligand and receptor expression in squamous‐cell carcinoma by interferon‐γ and cisplatin
Moers C, Warskulat U, Müschen M, Even J, Niederacher D, Josien R, Koldovsky U, Beckmann M, Häussinger D. Regulation of CD95 (APO‐1/ FAS) ligand and receptor expression in squamous‐cell carcinoma by interferon‐γ and cisplatin. International Journal Of Cancer 1999, 80: 564-572. PMID: 9935158, DOI: 10.1002/(sici)1097-0215(19990209)80:4<564::aid-ijc14>3.0.co;2-x.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaExpression of CD95LPrimary cell linesPrimary squamous cell carcinomaStroma cellsCD95L expressionAddition of CDDPCD95L mRNA levelsTumor-associated immunosuppressionHuman primary cell linesMRNA levelsEffect of cisplatinCell linesCD95 ligand expressionInvasive tumor tissuesAutologous lymphocytesCell carcinomaReceptor expressionSCC cellsSoluble receptorLigand expressionTumor tissueTumor samplesReceptor isoformsInvasion factors
1998
Fas LIGAND, TUMOR NECROSIS FACTOR-α EXPRESSION, AND APOPTOSIS DURING ALLOGRAFT REJECTION AND TOLERANCE
Josien R, Müschen M, Gilbert E, Douillard P, Heslan J, Soulillou J, Cuturi M. Fas LIGAND, TUMOR NECROSIS FACTOR-α EXPRESSION, AND APOPTOSIS DURING ALLOGRAFT REJECTION AND TOLERANCE. Transplantation 1998, 66: 887-893. PMID: 9798699, DOI: 10.1097/00007890-199810150-00013.Peer-Reviewed Original ResearchConceptsAllograft rejectionTNF-alphaDonor-specific blood transfusionApoptotic cellsNecrosis factor α expressionRole of CD95LAcute allograft rejectionDonor-specific transfusionGraft-infiltrating cellsHeterotopic cardiac allograftsCytotoxic T cellsTarget cell lysisTNF-alpha expressionTumor necrosis factorExpression of CD95LCD95/CD95LExpression of FasAcute rejectionCardiac allograftsBlood transfusionIntragraft expressionNecrosis factorT cellsCD95 antigenAllograftsRegulation of CD95 (APO‐1/Fas) receptor and ligand expression by lipopolysaccharide and dexamethasone in parenchymal and nonparenchymal rat liver cells
Müschen M, Warskulat U, Douillard P, Gilbert E, Häussinger D. Regulation of CD95 (APO‐1/Fas) receptor and ligand expression by lipopolysaccharide and dexamethasone in parenchymal and nonparenchymal rat liver cells. Hepatology 1998, 27: 200-208. PMID: 9425938, DOI: 10.1002/hep.510270131.Peer-Reviewed Original ResearchConceptsSinusoidal endothelial cellsNumber of KCsCD95L mRNA levelsKupffer cellsParenchymal cellsMRNA levelsNonparenchymal rat liver cellsNonparenchymal cellsCD95L expressionEffects of lipopolysaccharideMeans of immunocytochemistryLiver Kupffer cellsAddition of supernatantsPresence of lipopolysaccharideLiver cell populationsRat liver Kupffer cellsMessenger RNA levelsCD95 receptorLPS treatmentRat liver cellsThymic lymphocytesCD95 expressionLigand expressionLPS additionPrimary hepatocyte culturesRegulation of CD95 (Apo-1/Fas) Ligand and Receptor Expression in Human Embryonal Carcinoma Cells by Interferon γ and all-trans Retinoic Acid
Müschen M, Warskulat U, Schmidt B, Schulz W, Häussinger D. Regulation of CD95 (Apo-1/Fas) Ligand and Receptor Expression in Human Embryonal Carcinoma Cells by Interferon γ and all-trans Retinoic Acid. Biological Chemistry 1998, 379: 1083-1092. PMID: 9792441, DOI: 10.1515/bchm.1998.379.8-9.1083.Peer-Reviewed Original ResearchConceptsTrans retinoic acidTera-2 cellsTera-2 embryonal carcinoma cellsEmbryonal carcinoma cellsRetinoic acidT lymphocytesCarcinoma cellsJurkat T lymphocytesCD95 ligandReceptor isoformsCD95 receptorCD95 ligand expressionHuman embryonal carcinoma cellsAntitumor immunityControl conditionReceptor expressionInterferon γInterferon gammaLigand expressionProtein levelsDifferential regulationCD95 ligationIFNgammaLymphocytesApoptosis