2023
Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221.
Chen C, Zirpoli G, Barlow W, Budd G, McKiver B, Pusztai L, Hortobagyi G, Albain K, Damaj M, Godwin A, Thompson A, Henry N, Ambrosone C, Stringer K, Hertz D. Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221. Journal Of The National Comprehensive Cancer Network 2023, 21: 1172-1180.e3. PMID: 37935109, PMCID: PMC10976748, DOI: 10.6004/jnccn.2023.7062.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyVitamin D insufficiencyD insufficiencyVitamin DPaclitaxel scheduleMechanical hypersensitivityPeripheral neuropathyRisk factorsDeficient dietPaclitaxel-Induced Peripheral NeuropathyEarly-stage breast cancerPaclitaxel-containing chemotherapyVitamin D supplementationSufficient vitamin DVitamin D deficiencyBody mass indexMultiple logistic regressionSelf-reported raceD supplementationD deficiencySensitized miceProspective trialFemale patientsMass indexPredictive biomarkers
2022
CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression
Zhang M, Liu ZZ, Aoshima K, Cai WL, Sun H, Xu T, Zhang Y, An Y, Chen JF, Chan LH, Aoshima A, Lang SM, Tang Z, Che X, Li Y, Rutter SJ, Bossuyt V, Chen X, Morrow JS, Pusztai L, Rimm DL, Yin M, Yan Q. CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression. Science Translational Medicine 2022, 14: eabf5473. PMID: 35108062, PMCID: PMC9003667, DOI: 10.1126/scitranslmed.abf5473.Peer-Reviewed Original ResearchConceptsBreast cancer metastasisReticuloendotheliosis viral oncogene homolog ACancer metastasisImmune suppressionM2 macrophagesWorse metastasis-free survivalMetastatic breast cancerMetastasis-free survivalV-rel avian reticuloendotheliosis viral oncogene homolog ACancer-related deathPrimary breast tumorsMultiple mouse modelsNF-κB signalingImmunocompetent settingNuclear factor-κB family membersMetastasis-promoting genesDistant metastasisMetastatic sitesPrimary tumorEffective therapyBreast cancerMetastasis treatmentMouse modelBreast tumorsMetastasis
2019
CD36-Mediated Metabolic Rewiring of Breast Cancer Cells Promotes Resistance to HER2-Targeted Therapies
Feng WW, Wilkins O, Bang S, Ung M, Li J, An J, del Genio C, Canfield K, DiRenzo J, Wells W, Gaur A, Robey RB, Guo JY, Powles RL, Sotiriou C, Pusztai L, Febbraio M, Cheng C, Kinlaw WB, Kurokawa M. CD36-Mediated Metabolic Rewiring of Breast Cancer Cells Promotes Resistance to HER2-Targeted Therapies. Cell Reports 2019, 29: 3405-3420.e5. PMID: 31825825, PMCID: PMC6938262, DOI: 10.1016/j.celrep.2019.11.008.Peer-Reviewed Original ResearchConceptsFA uptakeHER2-positive breast cancerFA transporter CD36Anti-HER2 therapyBreast cancer patientsMetabolic rewiringHER2 inhibitor lapatinibMMTV-neu miceDeletion of CD36Breast cancer cellsAcquisition of resistancePoor prognosisCancer patientsHER2 inhibitionBreast cancerInhibitor lapatinibCDNA microarray analysisPharmacological inhibitionMammary tissueDe novo FA synthesisCD36Promotes ResistanceResistant cellsCancer cellsExpression increasesIdentification and Validation of a Novel Biologics Target in Triple Negative Breast Cancer
Wali VB, Patwardhan GA, Pelekanou V, Karn T, Cao J, Ocana A, Yan Q, Nelson B, Hatzis C, Pusztai L. Identification and Validation of a Novel Biologics Target in Triple Negative Breast Cancer. Scientific Reports 2019, 9: 14934. PMID: 31624295, PMCID: PMC6797726, DOI: 10.1038/s41598-019-51453-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBreastCell Line, TumorCell MembraneCell ProliferationDatasets as TopicDrug DevelopmentFemaleGABA-A Receptor AntagonistsGene Expression ProfilingGene Knockdown TechniquesHumansImmunoconjugatesImmunoglobulin Fab FragmentsMaytansineMiceMolecular Targeted TherapyReceptors, GABA-ATriple Negative Breast NeoplasmsXenograft Model Antitumor AssaysConceptsTriple-negative breast cancerNegative breast cancerTNBC cell growthBreast cancerMDA-MB-468 xenograftsPotential novel therapeutic targetNovel biologic targetsNovel therapeutic targetBreast cancer tissuesReceptors/cellAntibody-drug conjugate (ADC) developmentMost normal tissuesTreatment optionsCell growthTherapeutic targetBiologic targetsNude miceCancer tissuesVivo functional assaysLow expressionNormal tissuesNovel targetCancerSignificant anticancer activityADC development
2017
Structural insights into POT1-TPP1 interaction and POT1 C-terminal mutations in human cancer
Chen C, Gu P, Wu J, Chen X, Niu S, Sun H, Wu L, Li N, Peng J, Shi S, Fan C, Huang M, Wong CC, Gong Q, Kumar-Sinha C, Zhang R, Pusztai L, Rai R, Chang S, Lei M. Structural insights into POT1-TPP1 interaction and POT1 C-terminal mutations in human cancer. Nature Communications 2017, 8: 14929. PMID: 28393832, PMCID: PMC5394241, DOI: 10.1038/ncomms14929.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsConserved SequenceDNA DamageDNA Mutational AnalysisDNA RepairGenomic InstabilityHumansMiceModels, MolecularMolecular ChaperonesMutationNeoplasmsPhosphoproteinsProstaglandin-E SynthasesProtein BindingProtein Structure, SecondaryScattering, Small AngleShelterin ComplexStructure-Activity RelationshipTelomere-Binding ProteinsX-Ray DiffractionConceptsTelomerase-mediated telomere extensionHuman cancersDNA damage responseC-terminal mutationsOB foldsHuman POT1Chromosome endsGenome instabilityPOT1-TPP1Telomere extensionDamage responseStable heterodimerA-NHEJStructural insightsC-terminusInappropriate repairTPP1POT1Heart-shaped structureMissense mutationsTerminal portionMutationsDomainMutantsTelomeres
2016
miR-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
2014
Effects of Obesity on Transcriptomic Changes and Cancer Hallmarks in Estrogen Receptor–Positive Breast Cancer
Fuentes-Mattei E, Velazquez-Torres G, Phan L, Zhang F, Chou PC, Shin JH, Choi HH, Chen JS, Zhao R, Chen J, Gully C, Carlock C, Qi Y, Zhang Y, Wu Y, Esteva FJ, Luo Y, McKeehan WL, Ensor J, Hortobagyi GN, Pusztai L, Symmans W, Lee MH, Yeung SC. Effects of Obesity on Transcriptomic Changes and Cancer Hallmarks in Estrogen Receptor–Positive Breast Cancer. Journal Of The National Cancer Institute 2014, 106: dju158. PMID: 24957076, PMCID: PMC4110474, DOI: 10.1093/jnci/dju158.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipokinesAgedAnimalsAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsCell ProliferationDisease Models, AnimalEverolimusFemaleHumansKaplan-Meier EstimateMetforminMiceMice, TransgenicMiddle AgedObesityPostmenopauseProspective StudiesProto-Oncogene Proteins c-aktReceptors, EstrogenSignal TransductionSirolimusTOR Serine-Threonine KinasesTranscriptomeConceptsEstrogen receptor-positive breast cancerReceptor-positive breast cancerBreast cancer cell proliferationEffect of obesityBreast cancer patientsObese mouse modelAdipocyte-secreted adipokineCancer cell proliferationCancer patientsBreast cancerMouse modelCell proliferationAssociation of obesityAkt/mTOR activationMammary tumor growthEpithelial-mesenchymal transition genesAKT/mTOR pathwayBreast cancer aggressivenessBreast tumor formationCancer hallmarksPostmenopausal womenPretreatment biopsiesProspective cohortAdipokine secretionCancer death
2013
TIG1 Promotes the Development and Progression of Inflammatory Breast Cancer through Activation of Axl Kinase
Wang X, Saso H, Iwamoto T, Xia W, Gong Y, Pusztai L, Woodward WA, Reuben JM, Warner SL, Bearss DJ, Hortobagyi GN, Hung MC, Ueno NT. TIG1 Promotes the Development and Progression of Inflammatory Breast Cancer through Activation of Axl Kinase. Cancer Research 2013, 73: 6516-6525. PMID: 24014597, PMCID: PMC6135947, DOI: 10.1158/0008-5472.can-13-0967.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAxl Receptor Tyrosine KinaseBlotting, WesternCell AdhesionCell CycleCell MovementCell ProliferationDisease ProgressionFemaleFluorescent Antibody TechniqueHumansImmunoprecipitationInflammatory Breast NeoplasmsMediator ComplexMiceNeoplasm InvasivenessProto-Oncogene ProteinsReal-Time Polymerase Chain ReactionReceptor Protein-Tyrosine KinasesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingSignal TransductionTumor Cells, CulturedConceptsInflammatory breast cancerBreast cancerAxl expressionMalignant propertiesHigh tumoral expressionIBC cell proliferationMatrix metalloproteinase-9Inhibited tumor growthIBC specimensIBC cellsShorter survivalTumoral expressionProteasome-dependent degradationMetalloproteinase-9TIG1 expressionNF-κBTherapeutic targetTumor growthReceptor tyrosine kinasesAxl functionLethal formAxlIBC treatmentCancerAggressive propertiesInk4a/Arf−/− and HRAS(G12V) transform mouse mammary cells into triple-negative breast cancer containing tumorigenic CD49f− quiescent cells
Kai K, Iwamoto T, Kobayashi T, Arima Y, Takamoto Y, Ohnishi N, Bartholomeusz C, Horii R, Akiyama F, Hortobagyi GN, Pusztai L, Saya H, Ueno NT. Ink4a/Arf−/− and HRAS(G12V) transform mouse mammary cells into triple-negative breast cancer containing tumorigenic CD49f− quiescent cells. Oncogene 2013, 33: 440-448. PMID: 23376849, PMCID: PMC3957346, DOI: 10.1038/onc.2012.609.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Transformation, NeoplasticCyclin-Dependent Kinase Inhibitor p16FemaleFlow CytometryImmunohistochemistryIntegrin alpha6Mammary Neoplasms, ExperimentalMiceMice, Inbred C57BLMice, KnockoutNeoplastic Stem CellsOligonucleotide Array Sequence AnalysisProto-Oncogene Proteins p21(ras)Real-Time Polymerase Chain ReactionTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerHuman triple-negative breast cancerBreast cancerTumor-initiating potentialIntratumoral heterogeneityInk4a/Claudin-low breast cancerMouse mammary tumor modelNon-mammary tumorsHigh tumor-initiating potentialMouse mammary fat padMammary cellsMammary fat padMammary tumor modelIndividual breast tumorsTumor precursor cellsQuiescent cellsTumor-initiating cellsPathological featuresProgesterone receptorMammary tumorsEstrogen receptorAnimal modelsFat padBreast tumors
2012
Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα− breast cancer
Liu JC, Voisin V, Bader GD, Deng T, Pusztai L, Symmans WF, Esteva FJ, Egan SE, Zacksenhaus E. Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα− breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5832-5837. PMID: 22460789, PMCID: PMC3326451, DOI: 10.1073/pnas.1201105109.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsCalcium-Binding ProteinsCD24 AntigenCell DifferentiationCell DivisionEstrogen Receptor alphaFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmHumansIntercellular Signaling Peptides and ProteinsJagged-1 ProteinMembrane ProteinsMiceNeoadjuvant TherapyNeoplastic Stem CellsPrognosisReceptor, ErbB-2Serrate-Jagged ProteinsSignal TransductionTrastuzumabTreatment OutcomeConceptsTumor-initiating cellsMammary tumor-initiating cellsBreast cancerClinical outcomesPrognostic signatureHuman epidermal growth factor receptorAnti-HER2 drugsAnti-HER2 therapyHigh-risk patientsHigh-risk subgroupsEpidermal growth factor receptorGrowth factor receptorBC cohortRisk patientsAggressive diseaseBC patientsRetrospective analysisImmune responsePrognostic powerTumor growthPatientsChemotherapyFactor receptorCancerFraction of cells
2010
The role of tumor initiating cells in drug resistance of breast cancer: Implications for future therapeutic approaches
Lacerda L, Pusztai L, Woodward WA. The role of tumor initiating cells in drug resistance of breast cancer: Implications for future therapeutic approaches. Drug Resistance Updates 2010, 13: 99-108. PMID: 20739212, DOI: 10.1016/j.drup.2010.08.001.Peer-Reviewed Original ResearchConceptsTumor initiating cellsInitiating cellsCancer cellsLong-term outcomesBreast cancer recurrenceFuture therapeutic approachesTumor-stromal interactionsBreast cancer cellsHedgehog inhibitor cyclopamineNeoadjuvant chemotherapyResidual diseaseEffective therapyCancer recurrenceBreast cancerTherapeutic approachesInhibitor lapatinibInhibitor cyclopamineTherapy resistanceRegulation of tumorChemical library screenDrug resistanceChemotherapy-resistant subpopulationMultidrug resistanceNovel targetResistant subpopulations
2009
Inhibition of Lipocalin 2 Impairs Breast Tumorigenesis and Metastasis
Leng X, Ding T, Lin H, Wang Y, Hu L, Hu J, Feig B, Zhang W, Pusztai L, Symmans WF, Wu Y, Arlinghaus RB. Inhibition of Lipocalin 2 Impairs Breast Tumorigenesis and Metastasis. Cancer Research 2009, 69: 8579-8584. PMID: 19887608, DOI: 10.1158/0008-5472.can-09-1934.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAnimalsBlotting, WesternBreast NeoplasmsCell Line, TumorFemaleFlow CytometryGene Expression Regulation, NeoplasticHumansImmunohistochemistryLipocalin-2LipocalinsMatrix Metalloproteinase 9MiceMice, KnockoutNeoplasm InvasivenessNF-kappa BOncogene ProteinsReceptor, ErbB-2Reverse Transcriptase Polymerase Chain ReactionSignal TransductionConceptsLCN2 expressionBreast cancerBreast tumorigenesisMatrix metalloproteinase-9 activityTumor formationMammary tumor mouse modelMammary tumor formationMetalloproteinase-9 activityMatrix metalloproteinase-9Breast cancer therapyTumor mouse modelBreast tumor formationAkt/NFBreast cancer cellsMurine breast tumorsInhibitory monoclonal antibodiesLCN2 functionsLung metastasesLipocalin-2Metalloproteinase-9Mouse modelAggressive typeBreast tumorsKappaB pathwayMetastasis
1999
Relative cytotoxic activity of immunotoxins reactive with different epitopes on the extracellular domain of the c‐erbB‐2 (HER‐2/neu) gene product p185
Boyer C, Pusztai L, Wiener J, Xu F, Dean G, Bast B, O'Briant K, Greenwald M, DeSombre K, Bast R. Relative cytotoxic activity of immunotoxins reactive with different epitopes on the extracellular domain of the c‐erbB‐2 (HER‐2/neu) gene product p185. International Journal Of Cancer 1999, 82: 525-531. PMID: 10404066, DOI: 10.1002/(sici)1097-0215(19990812)82:4<525::aid-ijc10>3.0.co;2-j.Peer-Reviewed Original ResearchConceptsDifferent epitopesHER-2 receptorBreast cancer cell linesHER-2/neu geneRelative cytotoxic activityCytotoxic activityCancer cell linesEpitope targetsImmunotoxin therapyC-erbBImmunoglobulin isotypesUnconjugated antibodyEffective immunotoxinsExtracellular domainClonogenic assayImmunotoxinEpitope expressionNeu geneCompetitive binding assaysAntibodiesEpitopesAntibody bindingCell linesReceptorsBinding assays
1998
Cell surface density of p185(c-erbB-2) determines susceptibility to anti-p185(c-erbB-2)-ricin A chain (RTA) immunotoxin therapy alone and in combination with anti-p170(EGFR)-RTA in ovarian cancer cells.
Dean G, Pusztai L, Xu F, O'Briant K, DeSombre K, Conaway M, Boyer C, Mendelsohn J, Bast R. Cell surface density of p185(c-erbB-2) determines susceptibility to anti-p185(c-erbB-2)-ricin A chain (RTA) immunotoxin therapy alone and in combination with anti-p170(EGFR)-RTA in ovarian cancer cells. Clinical Cancer Research 1998, 4: 2545-50. PMID: 9796989.Peer-Reviewed Original ResearchConceptsOvarian cancer cellsReceptors/cellCancer cellsC-erbBSynergistic cytotoxicityCopies/cellTumor cellsSKOV3 human ovarian cancer cellsHuman ovarian cancer cellsClonogenic tumor cellsCell surface densityBreast cancerRTA immunotoxinsNude miceSame immunotoxinFirst treatmentAnchorage-independent growthAnchorage-dependent growthVivo growthClonogenic cellsImmunotoxinExpression levelsSignificant correlationCell linesNormal cells