2023
Cellular protection from H2O2 toxicity by Fv-Hsp70: protection via catalase and gamma-glutamyl-cysteine synthase
Hino C, Chan G, Jordaan G, Chang S, Saunders J, Bashir M, Hansen J, Gera J, Weisbart R, Nishimura R. Cellular protection from H2O2 toxicity by Fv-Hsp70: protection via catalase and gamma-glutamyl-cysteine synthase. Cell Stress And Chaperones 2023, 28: 429-439. PMID: 37171750, PMCID: PMC10352194, DOI: 10.1007/s12192-023-01349-6.Peer-Reviewed Original ResearchConceptsHeat shock proteinsGamma-glutamylcysteine synthaseCellular protectionAcute oxidative stressLid domainProtein-binding domainsATPase domainCysteine synthaseOxidative stressCellular stressRecombinant proteinsSH-SY5Y cellsEndogenous heat shock proteinsShock proteinsCell deathProteinProtein catalaseHSP70H2O2 toxicityCellsSynthaseΜM concentrationsDomainCatalaseDirect response
2021
Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of Self Antigen–Specific Clones
Glauzy S, Olson B, May CK, Parisi D, Massad C, Hansen JE, Ryu C, Herzog EL, Meffre E. Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of Self Antigen–Specific Clones. Arthritis & Rheumatology 2021, 74: 307-317. PMID: 34279059, PMCID: PMC8766600, DOI: 10.1002/art.41927.Peer-Reviewed Original ResearchConceptsB cell tolerance checkpointsEarly B cell tolerance checkpointsPeripheral B cell tolerance checkpointsNaive B cellsMature naive B cellsSystemic sclerosisTransitional B cellsTolerance checkpointsB cellsHealthy donorsAutoreactive mature naive B cellsAutoreactive naive B cellsAntigen-specific B cellsCentral B cell toleranceB cell toleranceB cell productionAntigen-specific clonesReactivity of antibodiesSingle B cellsSSc patientsSerum autoantibodiesAutoimmune diseasesImmune complexesPatientsCell toleranceENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody
Rattray Z, Deng G, Zhang S, Shirali A, May CK, Chen X, Cuffari BJ, Liu J, Zou P, Rattray N, Johnson CH, Dubljevic V, Campbell JA, Huttner A, Baehring JM, Zhou J, Hansen JE. ENT2 facilitates brain endothelial cell penetration and blood-brain barrier transport by a tumor-targeting anti-DNA autoantibody. JCI Insight 2021, 6: e145875. PMID: 34128837, PMCID: PMC8410084, DOI: 10.1172/jci.insight.145875.Peer-Reviewed Original ResearchConceptsBlood-brain barrierAnti-DNA autoantibodiesBrain tumorsBreast cancer brain metastasesBlood-brain barrier transportBrain tumor immunotherapyCancer brain metastasesBrain endothelial cellsEndothelial cell penetrationCNS lupusNeurotoxic autoantibodiesBrain metastasesTumor immunotherapyBarrier transportAntibody-based approachesCNS penetrationAutoantibodiesEfficacy studiesOrthotopic glioblastomaEndothelial cellsTumorsCancer cellsNucleoside fluxesActionable mechanismsKey transporters
2020
LRRC31 inhibits DNA repair and sensitizes breast cancer brain metastasis to radiation therapy
Chen Y, Jiang T, Zhang H, Gou X, Han C, Wang J, Chen AT, Ma J, Liu J, Chen Z, Jing X, Lei H, Wang Z, Bao Y, Baqri M, Zhu Y, Bindra RS, Hansen JE, Dou J, Huang C, Zhou J. LRRC31 inhibits DNA repair and sensitizes breast cancer brain metastasis to radiation therapy. Nature Cell Biology 2020, 22: 1276-1285. PMID: 33005030, PMCID: PMC7962994, DOI: 10.1038/s41556-020-00586-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAtaxia Telangiectasia Mutated ProteinsBrain NeoplasmsBreast NeoplasmsCell ProliferationDNA DamageDNA RepairFemaleGamma RaysHumansMiceMice, Inbred BALB CMice, NudeMutS Homolog 2 ProteinNuclear ProteinsPhosphorylationRadiation-Sensitizing AgentsSignal TransductionTumor Cells, CulturedXenograft Model Antitumor Assays
2018
Incidence of radiographically occult nodal metastases in HPV+ oropharyngeal carcinoma: Implications for reducing elective nodal coverage
Loganadane G, Kelly JR, Lee NC, Kann BH, Mahajan A, Hansen JE, Belkacémi Y, Yarbrough W, Husain ZA. Incidence of radiographically occult nodal metastases in HPV+ oropharyngeal carcinoma: Implications for reducing elective nodal coverage. Practical Radiation Oncology 2018, 8: 397-403. PMID: 29730282, DOI: 10.1016/j.prro.2018.03.009.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overCarcinoma, Squamous CellFemaleFollow-Up StudiesHumansImage Processing, Computer-AssistedLymphatic MetastasisMaleMiddle AgedNeoplasm StagingOropharyngeal NeoplasmsPapillomaviridaePapillomavirus InfectionsPositron Emission Tomography Computed TomographyPrognosisRadiotherapy DosageRadiotherapy Planning, Computer-AssistedRadiotherapy, Intensity-ModulatedRetrospective StudiesConceptsRadiation field designPreoperative imagingPathologic involvementN stageOropharyngeal squamous cell carcinomaElective nodal coverageLevel II diseasePercent of patientsPositive lymph nodesOccult nodal metastasisClinical N stageRadiation therapy doseRecords of patientsNodal levelPathologic N stageSquamous cell carcinomaHuman papilloma virusTreatment deescalationNeoadjuvant therapyNodal diseaseNeck dissectionNodal involvementOropharyngeal carcinomaProspective trialSystemic agentsSmoking Is the Most Significant Modifiable Lung Cancer Risk Factor in Systemic Lupus Erythematosus.
Bernatsky S, Ramsey-Goldman R, Petri M, Urowitz MB, Gladman DD, Fortin PR, Yelin EH, Ginzler E, Hanly JG, Peschken C, Gordon C, Nived O, Aranow C, Bae SC, Isenberg D, Rahman A, Hansen JE, Pierre Y, Clarke AE. Smoking Is the Most Significant Modifiable Lung Cancer Risk Factor in Systemic Lupus Erythematosus. The Journal Of Rheumatology 2018, 45: 393-396. PMID: 29335347, PMCID: PMC5834350, DOI: 10.3899/jrheum.170652.Peer-Reviewed Original ResearchConceptsLung cancer risk factorsSystemic lupus erythematosusCancer risk factorsLung cancer casesLung cancer riskLung cancerRisk factorsSLE cohortDisease activityLupus erythematosusDrug exposureCancer casesCancer riskMcGill University Health CentreCumulative disease activityIncident lung cancerUniversity Health CentreCancer risk studiesInstitutional review boardHigher SLEDAIMedication exposureSLE controlsAdjusted effectHealth centersAdjusted model
2016
Breast cancer in systemic lupus
Bernatsky S, Ramsey-Goldman R, Petri M, Urowitz MB, Gladman DD, Fortin P, Ginzler E, Romero-Diaz J, Peschken C, Jacobsen S, Hanly JG, Gordon C, Nived O, Yelin EH, Isenberg D, Rahman A, Bae SC, Joseph L, Witte T, Ruiz-Irastorza G, Aranow C, Kamen D, Sturfeldt G, Foulkes WD, Hansen JE, St Pierre Y, Raymer PC, Tessier-Cloutier B, Clarke AE. Breast cancer in systemic lupus. Lupus 2016, 26: 311-315. PMID: 27687028, PMCID: PMC5250552, DOI: 10.1177/0961203316664595.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusBreast cancer riskAnti-dsDNA positivityBreast cancer casesBreast cancerCancer riskDisease activitySLE patientsHazard ratioCancer casesSLE samplesBreast cancer hazard ratioCancer hazard ratioCumulative disease activityFemale SLE patientsCase-cohort analysisCancer-free controlsCohort entrySLE durationClinical characteristicsSystemic lupusClinical factorsLupus erythematosusDrug exposureFamily historyA lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors
Chen Z, Patel JM, Noble PW, Garcia C, Hong Z, Hansen JE, Zhou J. A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of nanoparticles to tumors. Oncotarget 2016, 7: 59965-59975. PMID: 27494868, PMCID: PMC5312362, DOI: 10.18632/oncotarget.11015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, AntinuclearAntibodies, CatalyticBreast NeoplasmsCell Line, TumorDNADoxorubicinDrug Delivery SystemsFemaleHumansLactic AcidLupus Coagulation InhibitorMammary Neoplasms, AnimalMiceMice, Inbred BALB CNanoparticlesPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerTumor MicroenvironmentConceptsDelivery of nanoparticlesDOX-loaded nanoparticlesTumor-targeting mechanismDrug delivery mechanismsAmount of moleculesNanoparticle deliveryLupus anti-DNA autoantibodiesNanoparticlesProof of conceptRelease of DNASurface modificationBind moleculesAutocatalytic effectDelivery mechanismTumor neovasculatureMoleculesDeliveryDoxorubicinTumor microenviromentMajor limitationEfficiencyLigandsSubsequent treatmentToxic agentsDNADNA-damaging autoantibodies and cancer: the lupus butterfly theory
Noble PW, Bernatsky S, Clarke AE, Isenberg DA, Ramsey-Goldman R, Hansen JE. DNA-damaging autoantibodies and cancer: the lupus butterfly theory. Nature Reviews Rheumatology 2016, 12: 429-434. PMID: 27009542, DOI: 10.1038/nrrheum.2016.23.Peer-Reviewed Original Research
2015
DNA-dependent targeting of cell nuclei by a lupus autoantibody
Weisbart RH, Chan G, Jordaan G, Noble PW, Liu Y, Glazer PM, Nishimura RN, Hansen JE. DNA-dependent targeting of cell nuclei by a lupus autoantibody. Scientific Reports 2015, 5: 12022. PMID: 26156563, PMCID: PMC4496662, DOI: 10.1038/srep12022.Peer-Reviewed Original ResearchConceptsLupus anti-DNA autoantibodiesAnti-DNA autoantibodiesTumor cell nucleiSingle-chain variable fragmentPotential therapeutic applicationsLupus autoantibodiesTherapeutic approachesIschemic conditionsCertain cancer cellsChain variable fragmentCancer cellsCell nucleiAutoantibodiesNecrotic regionsVariable fragmentTherapeutic applicationsDNA damageNuclear uptakeScFvMalignancyGreater understandingTumorsStrokeDiseaseOptimizing a Lupus Autoantibody for Targeted Cancer Therapy
Noble PW, Chan G, Young MR, Weisbart RH, Hansen JE. Optimizing a Lupus Autoantibody for Targeted Cancer Therapy. Cancer Research 2015, 75: 2285-2291. PMID: 25832653, DOI: 10.1158/0008-5472.can-14-2278.Peer-Reviewed Original Research
2014
A nucleolytic lupus autoantibody is toxic to BRCA2-deficient cancer cells
Noble PW, Young MR, Bernatsky S, Weisbart RH, Hansen JE. A nucleolytic lupus autoantibody is toxic to BRCA2-deficient cancer cells. Scientific Reports 2014, 4: 5958. PMID: 25091037, PMCID: PMC5380011, DOI: 10.1038/srep05958.Peer-Reviewed Original ResearchConceptsLupus autoantibodiesTherapeutic agentsCancer cellsSystemic lupus erythematosusBRCA2-deficient cellsLupus erythematosusBRCA2-deficient cancer cellsDLD1 colon cancer cellsColon cancer cellsSuch antibodiesLower riskAutoantibodiesSpecific cancersAntibodiesMalignancyDifferential effectsToxic effectsPotential utilityCellsAgentsFurther supportDNA-damaging agentsErythematosusTherapyCancerSystemic Lupus Erythematosus and Malignancies A Review Article
Tessier-Cloutier B, Clarke AE, Ramsey-Goldman R, Gordon C, Hansen JE, Bernatsky S. Systemic Lupus Erythematosus and Malignancies A Review Article. Rheumatic Disease Clinics Of North America 2014, 40: 497-506. PMID: 25034158, DOI: 10.1016/j.rdc.2014.04.005.Commentaries, Editorials and LettersConceptsSystemic lupus erythematosus populationRisk of lymphomaSystemic lupus erythematosusCancer risk profileHormone-sensitive cancersLung cancer riskRisk of cancerImmunosuppressive medicationsCervical dysplasiaLupus erythematosusDecreased riskSimilar pathophysiologyCancer riskHepatic carcinomaSLERisk profileRecent dataRiskHigh rateCancerReview articleErythematosusMedicationsLupusCarcinoma
2013
Breast Cancer in Systemic Lupus Erythematosus
Cloutier B, Clarke AE, Ramsey-Goldman R, Wang Y, Foulkes W, Gordon C, Hansen JE, Yelin E, Urowitz MB, Gladman D, Fortin PR, Wallace DJ, Petri M, Manzi S, Ginzler EM, Labrecque J, Edworthy S, Dooley MA, Senécal JL, Peschken CA, Bae SC, Isenberg D, Rahman A, Ruiz-Irastorza G, Hanly JG, Jacobsen S, Nived O, Witte T, Criswell LA, Barr SG, Dreyer L, Sturfelt G, Bernatsky S. Breast Cancer in Systemic Lupus Erythematosus. Oncology 2013, 85: 117-121. PMID: 23887245, PMCID: PMC3934367, DOI: 10.1159/000353138.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusSLE durationHistological typeBreast cancerDuctal carcinomaSLE cohortLupus erythematosusMultivariate logistic regression analysisDuctal histological typeIndependent risk factorCommon histological typeBreast cancer riskLogistic regression analysisRegression analysisLobular adenocarcinomaIndependent predictorsMixed histologyCancer RegistryRisk factorsHistological statusCancer riskCarcinomaHistology informationCancerCancer dates
2012
Targeting Cancer with a Lupus Autoantibody
Hansen JE, Chan G, Liu Y, Hegan DC, Dalal S, Dray E, Kwon Y, Xu Y, Xu X, Peterson-Roth E, Geiger E, Liu Y, Gera J, Sweasy JB, Sung P, Rockwell S, Nishimura RN, Weisbart RH, Glazer PM. Targeting Cancer with a Lupus Autoantibody. Science Translational Medicine 2012, 4: 157ra142. PMID: 23100628, PMCID: PMC3713477, DOI: 10.1126/scitranslmed.3004385.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusAnti-DNA antibodiesLupus autoantibodiesProstate cancerCancer therapyLupus anti-DNA antibodiesHuman tumor xenograftsDNA-damaging therapiesCultured tumor cellsSLE patientsLupus erythematosusSLE pathophysiologyAutoimmune diseasesDose doxorubicinTumor xenograftsAutoantibodiesHuman cancer cellsTherapyTherapeutic agentsTumor cellsCancerCancer cellsLupusMalignancyPrecise roleA Cell-Penetrating Bispecific Antibody for Therapeutic Regulation of Intracellular Targets
Weisbart RH, Gera JF, Chan G, Hansen JE, Li E, Cloninger C, Levine AJ, Nishimura RN. A Cell-Penetrating Bispecific Antibody for Therapeutic Regulation of Intracellular Targets. Molecular Cancer Therapeutics 2012, 11: 2169-2173. PMID: 22863609, DOI: 10.1158/1535-7163.mct-12-0476-t.Peer-Reviewed Original ResearchConceptsBispecific antibodiesBispecific single-chain Fv fragmentsMonoclonal antibody 3G5Cancer therapyDelivery of antibodiesIntracellular targetsMolecular therapyTherapeutic useTherapeutic regulationMonoclonal antibodiesTherapyAntibodiesMAb 3E10Single-chain Fv fragmentInhibits growthP53 levelsImportant targetMDM2Limited accessFv fragmentTargetTumors
2010
Recombinant Fv-Hsp70 Protein Mediates Neuroprotection After Focal Cerebral Ischemia in Rats
Zhan X, Ander BP, Liao IH, Hansen JE, Kim C, Clements D, Weisbart RH, Nishimura RN, Sharp FR. Recombinant Fv-Hsp70 Protein Mediates Neuroprotection After Focal Cerebral Ischemia in Rats. Stroke 2010, 41: 538-543. PMID: 20075343, PMCID: PMC2957177, DOI: 10.1161/strokeaha.109.572537.Peer-Reviewed Original ResearchConceptsFocal cerebral ischemiaCerebral ischemiaInfarction volumeSensorimotor functionSaline-treated control groupIntraluminal suture techniqueExperimental ischemic strokeExperimental stroke modelsMiddle cerebral arteryOnset of ischemiaInfarct volumeIschemic brainIschemic strokeCerebral arteryFocal ischemiaControl brainsStroke modelTail veinIschemiaControl groupSuture techniqueWestern blotEndogenous Hsp70RatsBrain
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
2008
p21-activated Kinase-aberrant Activation and Translocation in Alzheimer Disease Pathogenesis*
Ma QL, Yang F, Calon F, Ubeda OJ, Hansen JE, Weisbart RH, Beech W, Frautschy SA, Cole GM. p21-activated Kinase-aberrant Activation and Translocation in Alzheimer Disease Pathogenesis*. Journal Of Biological Chemistry 2008, 283: 14132-14143. PMID: 18347024, PMCID: PMC2376243, DOI: 10.1074/jbc.m708034200.Peer-Reviewed Original ResearchConceptsCultured hippocampal neuronsAlzheimer's diseaseHippocampal neuronsDendritic spinesTransgenic miceAlzheimer's disease brainAlzheimer's amyloid pathologyAlzheimer's disease (AD) pathogenesisBeta-amyloid oligomersOligomer treatmentSrc family tyrosine kinase inhibitor PP2P-NR2BSynaptic deficitsAmyloid pathologyDisease brainTyrosine kinase inhibitor PP2Disease pathogenesisCognitive deficitsMental retardation syndromeProtein drebrinKinase inhibitor PP2DiseaseNeuronsRetardation syndromeMice
2007
Intranuclear Protein Transduction through a Nucleoside Salvage Pathway*
Hansen JE, Tse CM, Chan G, Heinze ER, Nishimura RN, Weisbart RH. Intranuclear Protein Transduction through a Nucleoside Salvage Pathway*. Journal Of Biological Chemistry 2007, 282: 20790-20793. PMID: 17525162, DOI: 10.1074/jbc.c700090200.Peer-Reviewed Original ResearchConceptsNucleoside salvage pathwaySalvage pathwaySpecific nuclear localizationCargo proteinsGene regulationMolecular delivery vehiclesProtein transportProtein transductionTranscription factorsNuclear localizationGene expressionNuclear membraneHuman diseasesLiving cellsCell nucleiCell membraneNew molecular therapiesNumerous diseasesPathwayTransductionCellsRegulationMolecular therapyFirst demonstrationNew avenues