2024
Cathepsin B Nuclear Flux in a DNA-Guided “Antinuclear Missile” Cancer Therapy
Cao F, Tang C, Chen X, Tu Z, Jin Y, Turk O, Nishimura R, Ebens A, Dubljevic V, Campbell J, Zhou J, Hansen J. Cathepsin B Nuclear Flux in a DNA-Guided “Antinuclear Missile” Cancer Therapy. ACS Central Science 2024 DOI: 10.1021/acscentsci.4c00559.Peer-Reviewed Original ResearchAntinuclear antibodiesCancer therapyTumor-specific surface antigenLysosomal protease cathepsin BAntibody-drug conjugatesNecrotic tumorTumor environmentExtracellular nucleic acidsSurface antigensProtease cathepsin BCancer cellsTumorNucleoside salvage pathwayDrug linkersNucleoside salvageTherapyCross membrane barriersMembrane barrierCathepsin BLiving cancer cellsDNA guidesAntinuclearSalvage pathwayCathepsinNuclear penetrationNuclear-penetrating scleroderma autoantibody inhibits topoisomerase 1 cleavage complex formation
May C, Noble P, Herzog E, Meffre E, Hansen J. Nuclear-penetrating scleroderma autoantibody inhibits topoisomerase 1 cleavage complex formation. Biochemical And Biophysical Research Communications 2024, 720: 150123. PMID: 38759301, DOI: 10.1016/j.bbrc.2024.150123.Peer-Reviewed Original ResearchDiffuse cutaneous systemic sclerosisCutaneous systemic sclerosisAnti-topoisomerase 1Systemic lupus erythematosusDiscovery of autoantibodiesMechanisms of autoimmunityInhibit DNA repairScleroderma autoantibodiesScleroderma subtypeSystemic sclerosisLupus erythematosusAutoantibodiesCancer therapyPathophysiologyReagent resourcesCellular dysfunctionAntibodiesCell nucleiDNA repair
2023
Selected-Lesion Stereotactic Radiosurgery in Treatment of Patients with Multiple Brain Metastases: A Single Institution Retrospective Study
Mange A, Singh C, Theriault B, Hansen J, An Y, Aneja S, Chiang V. Selected-Lesion Stereotactic Radiosurgery in Treatment of Patients with Multiple Brain Metastases: A Single Institution Retrospective Study. International Journal Of Radiation Oncology • Biology • Physics 2023, 117: e135. DOI: 10.1016/j.ijrobp.2023.06.939.Peer-Reviewed Original ResearchMultiple brain metastasesBrain metastasesStereotactic radiosurgeryMedian KPSCommon indicationTumor characteristicsClinical trialsSRS treatmentSingle-institution retrospective studySubsequent-line treatmentMethods Clinical dataPatient selection criteriaTreatment of patientsSubset of lesionsNumber of lesionsDiagnosis of melanomaCNS progressionCNS radiationPrior WBRTOverall survivalPalliative treatmentPatient characteristicsProgressive diseaseImmunotherapy trialsSurvival groupCellular 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
2022
Inhibition of NETosis by a Nuclear-Penetrating Anti-DNA Autoantibody
Chen X, Cuffari BJ, Dubljevic V, Shirali A, Zhou J, Campbell JA, Suits SC, O'Sullivan KM, Hansen JE. Inhibition of NETosis by a Nuclear-Penetrating Anti-DNA Autoantibody. ImmunoHorizons 2022, 6: 356-365. PMID: 35697479, DOI: 10.4049/immunohorizons.2100091.Peer-Reviewed Original ResearchConceptsNeutrophil extracellular trapsAnti-DNA autoantibodiesRelease of NETsInhibition of NETosisOncology clinical trialsDifferentiated PLB-985 cellsMechanisms of NETosisCalcium ionophore ionomycinPLB-985 cellsIndependent NETosisC57BL/6 miceClinical trialsExtracellular trapsSuch AbsAutoantibodiesNeutrophil biologyDNA damage responseTherapeutic potentialNETosisHistone citrullinationIonophore ionomycinWestern blotSignificant inhibitionMultiple diseasesNeutrophils
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 toleranceRecognition and Management of Adverse Radiation Effects
Cheok S, Hansen J, Chiang V. Recognition and Management of Adverse Radiation Effects. 2021, 391-404. DOI: 10.1201/9781003167464-36.ChaptersAdverse radiation effectsRadiation necrosisStereotactic radiosurgeryRole of SRSImmune-mediated componentLaser interstitial thermotherapyMore brain lesionsBrain metastasesSystemic therapyIntracranial pathologyMalignant pathologyBrain lesionsNecrosisInterstitial thermotherapyPathologyContemporary evidenceBevacizumabCraniotomyMetastasisTherapyLesionsRadiosurgerySteroidsENT2 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 transportersChapter 48 Malignancies in systemic lupus erythematosus
Ladouceur A, Tissera H, Clarke A, Ramsey-Goldman R, Gordon C, Hansen J, Bernatsky S. Chapter 48 Malignancies in systemic lupus erythematosus. 2021, 461-467. DOI: 10.1016/b978-0-12-814551-7.00048-9.ChaptersSystemic lupus erythematosusSLE patientsLupus erythematosusGeneral populationOverall cancer incidence ratesHormone-sensitive cancersCancer incidence ratesRisk of breastDrug exposureIncidence rateProstate cancerHormonal changesHigh riskCancer profilePatientsCancerGenetic factorsErythematosusRiskPotential reasonsLymphomaMalignancyPathophysiologyPopulationBreastImpact of tissue heterogeneity correction on Gamma Knife stereotactic radiosurgery of acoustic neuromas.
Peters GW, Tien CJ, Chiang V, Yu J, Hansen JE, Aneja S. Impact of tissue heterogeneity correction on Gamma Knife stereotactic radiosurgery of acoustic neuromas. Journal Of Radiosurgery And SBRT 2021, 7: 207-212. PMID: 33898084, PMCID: PMC8055239.Peer-Reviewed Original Research
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 AssaysMulti-institutional retrospective review of stereotactic radiosurgery for brain metastasis in patients with small cell lung cancer without prior brain-directed radiotherapy.
Miccio JA, Barsky A, Gao S, Verma V, Noticewala SS, Jairam V, Johnson SB, Yu JB, Hansen JE, Aneja S, An Y, Decker RH, Bulent Omay S, Li J, Kurtz GA, Alonso-Basanta M, Lee JYK, Chiang VL, Park HS. Multi-institutional retrospective review of stereotactic radiosurgery for brain metastasis in patients with small cell lung cancer without prior brain-directed radiotherapy. Journal Of Radiosurgery And SBRT 2020, 7: 19-27. PMID: 32802575, PMCID: PMC7406345.Peer-Reviewed Original ResearchWhole brain radiotherapyBrain metastasesOverall survivalNeurologic deathSmall-cell lung cancer (SCLC) brain metastasesCell lung cancer brain metastasesLung cancer brain metastasesSalvage whole brain radiotherapyMulti-institutional retrospective reviewSmall cell lung cancerMost SCLC patientsSCLC brain metastasesTime of SRSMedian overall survivalCancer brain metastasesCell lung cancerIntracranial progressionSCLC patientsUpfront radiosurgeryBrain radiationBrain radiotherapySelect patientsRetrospective reviewLung cancerStereotactic radiosurgery
2019
Upfront Stereotactic Radiosurgery in the Treatment of Brain Metastasis from Small Cell Lung Cancer
Miccio J, Johnson S, Jairam V, Yu J, Hansen J, Aneja S, An Y, Decker R, Omay S, Chiang V, Park H. Upfront Stereotactic Radiosurgery in the Treatment of Brain Metastasis from Small Cell Lung Cancer. International Journal Of Radiation Oncology • Biology • Physics 2019, 105: e81-e82. DOI: 10.1016/j.ijrobp.2019.06.2348.Peer-Reviewed Original ResearchResults of a pilot/phase II study of gamma knife radiosurgery for brain metastases and implications for future prospective clinical trials
Yu J, Singh C, Bindra R, Contessa J, Husain Z, Hansen J, Park H, Roberts K, Bond J, Tien C, Guo F, Colaco R, Housri N, Magnuson W, Mahajan A, Omay S, Chiang V. Results of a pilot/phase II study of gamma knife radiosurgery for brain metastases and implications for future prospective clinical trials. Journal Of Radiation Oncology 2019, 8: 39-46. DOI: 10.1007/s13566-018-0370-7.Peer-Reviewed Original ResearchYale-New Haven HospitalPhase II studyBrain metastasesClinical trialsII studyKnife radiosurgeryLocal controlPre-defined primary endpointWhole-brain radiation treatmentFuture prospective clinical trialsEvaluable brain metastasesSymptomatic radiation necrosisMedian patient ageLocal control ratePhase 2 studyGood local controlProspective clinical trialsNumber of metastasesLarge clinical trialsProportional hazards regressionFuture clinical trialsGamma knife radiosurgeryImportant clinical variablesStandard clinical practiceNew Haven Hospital
2018
Incidence of Radiographically Occult Nodal Metastases in HPV-Driven Oropharyngeal Carcinoma: Implications for Reducing Elective Nodal Coverage
Kelly J, Loganadane G, Lee N, Kann B, Mahajan A, Hansen J, Belkacemi Y, Yarbrough W, Husain Z. Incidence of Radiographically Occult Nodal Metastases in HPV-Driven Oropharyngeal Carcinoma: Implications for Reducing Elective Nodal Coverage. International Journal Of Radiation Oncology • Biology • Physics 2018, 102: s197-s198. DOI: 10.1016/j.ijrobp.2018.07.095.Peer-Reviewed Original ResearchA Pilot/Phase II Study of Stereotactic Radiosurgery for Brain Metastases Using Rational Dose Selection
Yu J, Singh C, Bindra R, Contessa J, Husain Z, Hansen J, Park H, Roberts K, Bond J, Tien C, Guo F, Colaco R, Housri N, Magnuson W, Omay B, Chiang V. A Pilot/Phase II Study of Stereotactic Radiosurgery for Brain Metastases Using Rational Dose Selection. International Journal Of Radiation Oncology • Biology • Physics 2018, 102: e372-e373. DOI: 10.1016/j.ijrobp.2018.07.1113.Peer-Reviewed Original ResearchIncidence 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 agentsRe-engineering and evaluation of anti-DNA autoantibody 3E10 for therapeutic applications
Rattray Z, Dubljevic V, Rattray NJW, Greenwood DL, Johnson CH, Campbell JA, Hansen JE. Re-engineering and evaluation of anti-DNA autoantibody 3E10 for therapeutic applications. Biochemical And Biophysical Research Communications 2018, 496: 858-864. PMID: 29374508, DOI: 10.1016/j.bbrc.2018.01.139.Peer-Reviewed Original ResearchSmoking 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
2017
Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids
Johnson CH, Santidrian AF, LeBoeuf SE, Kurczy ME, Rattray NJW, Rattray Z, Warth B, Ritland M, Hoang LT, Loriot C, Higa J, Hansen JE, Felding BH, Siuzdak G. Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids. Cancer & Metabolism 2017, 5: 9. PMID: 29093815, PMCID: PMC5663111, DOI: 10.1186/s40170-017-0171-2.Peer-Reviewed Original ResearchLung metastasesMFP tumorsMammary fat pad tumorsCholesterol sulfateCancer cellsPrimary mammary fat pad tumorSpontaneous tumor metastasisMouse xenograft modelPathway analysisDistant organ sitesPrimary cancerNormal lungMouse modelXenograft modelOrgan sitesMetastasisMetastatic nicheDNA/RNA synthesisTumor cellsCancer metastasisNormal tissuesTumor metastasisTumorsDistant sitesMetabolic characteristics