2023
Application of novel PACS-based informatics platform to identify imaging based predictors of CDKN2A allelic status in glioblastomas
Tillmanns N, Lost J, Tabor J, Vasandani S, Vetsa S, Marianayagam N, Yalcin K, Erson-Omay E, von Reppert M, Jekel L, Merkaj S, Ramakrishnan D, Avesta A, de Oliveira Santo I, Jin L, Huttner A, Bousabarah K, Ikuta I, Lin M, Aneja S, Turowski B, Aboian M, Moliterno J. Application of novel PACS-based informatics platform to identify imaging based predictors of CDKN2A allelic status in glioblastomas. Scientific Reports 2023, 13: 22942. PMID: 38135704, PMCID: PMC10746716, DOI: 10.1038/s41598-023-48918-4.Peer-Reviewed Original ResearchConceptsInformatics platformDeep learning algorithmsImaging featuresCDKN2A alterationsLearning algorithmHeterozygous lossHomozygous deletionLarge datasetsDeep white matter invasionGBM molecular subtypesNew informaticsQualitative imaging biomarkersWhole-exome sequencingQualitative imaging featuresGBM resectionRadiographic evidenceWorse prognosisPACSMolecular subtypesPial invasionImaging biomarkersCDKN2A mutationsAllele statusNoninvasive identificationMagnetic resonance imagesAnti-seed PNAs targeting multiple oncomiRs for brain tumor therapy
Wang Y, Malik S, Suh H, Xiao Y, Deng Y, Fan R, Huttner A, Bindra R, Singh V, Saltzman W, Bahal R. Anti-seed PNAs targeting multiple oncomiRs for brain tumor therapy. Science Advances 2023, 9: eabq7459. PMID: 36753549, PMCID: PMC9908025, DOI: 10.1126/sciadv.abq7459.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainBrain NeoplasmsCell Line, TumorGlioblastomaMiceNanoparticlesPeptide Nucleic AcidsTemozolomideConceptsConvection-enhanced deliveryHigh recurrence rateOrthotopic mouse modelBrain tumor therapyTreatment of glioblastomaRecurrence ratePoor survivalLethal malignancyMouse modelGBM progressionTumor cellsGlioblastomaTumor therapyBioadhesive nanoparticlesOncomiRSurvivalTreatmentSeed regionMalignancyTemozolomideTherapy
2022
Spectrum of qualitative and quantitative imaging of pilomyxoid, intermediate pilomyxoid and pilocytic astrocytomas in relation to their genetic alterations
Fadel SA, von Reppert M, Kazarian E, Omay EZE, Marks A, Linder N, Hoffmann KT, Darbinyan A, Huttner A, Aboian MS. Spectrum of qualitative and quantitative imaging of pilomyxoid, intermediate pilomyxoid and pilocytic astrocytomas in relation to their genetic alterations. Neuroradiology 2022, 65: 195-205. PMID: 35984480, DOI: 10.1007/s00234-022-03027-3.Peer-Reviewed Original ResearchMeSH KeywordsAstrocytomaBrain NeoplasmsChildHumansMutationProto-Oncogene Proteins B-rafRetrospective StudiesConceptsPilocytic astrocytomaImaging characteristicsADC valuesAggressive imaging characteristicsSuprasellar pilocytic astrocytomaRecurrence/progressionPediatric brain tumorsFrontal white matterWhole-exome sequencingPilomyxoid astrocytomaIntraventricular extensionSuprasellar regionThird ventriclePosterior fossaAtypical locationBrain tumorsWhite matterGrade 1TumorsAstrocytomasDriver mutationsExome sequencingGenetic alterationsPatientsHippocampusCross-platform analysis reveals cellular and molecular landscape of glioblastoma invasion
Chen AT, Xiao Y, Tang X, Baqri M, Gao X, Reschke M, Sheu WC, Long G, Zhou Y, Deng G, Zhang S, Deng Y, Bai Z, Kim D, Huttner A, Kunes R, Günel M, Moliterno J, Saltzman WM, Fan R, Zhou J. Cross-platform analysis reveals cellular and molecular landscape of glioblastoma invasion. Neuro-Oncology 2022, 25: 482-494. PMID: 35901838, PMCID: PMC10013636, DOI: 10.1093/neuonc/noac186.Peer-Reviewed Original ResearchConceptsCrystallin alpha BTumor invasionGBM invasionHistology samplesMolecular landscapeTreatment of glioblastomaPostoperative recurrenceGBM patientsInvasive glioblastomaResection modelGlioblastomaNon-invasive counterpartsGBM samplesGlioblastoma invasionCD44PatientsInvasionAlpha BCellular levelTranscriptomic featuresRNA sequencing dataRecurrenceHistology stainsLevelsDisease
2021
Surgical strategies for older patients with glioblastoma
Barak T, Vetsa S, Nadar A, Jin L, Gupte TP, Fomchenko EI, Miyagishima DF, Yalcin K, Vasandani S, Gorelick E, Zhao AY, Antonios J, Theriault BC, Lifton N, Marianayagam N, Omay B, Omay ZE, Huttner A, McGuone D, Blondin NA, Corbin Z, Fulbright RK, Moliterno J. Surgical strategies for older patients with glioblastoma. Journal Of Neuro-Oncology 2021, 155: 255-264. PMID: 34626296, PMCID: PMC8651607, DOI: 10.1007/s11060-021-03862-z.Peer-Reviewed Original ResearchConceptsKarnofsky performance scoreLength of surgeryOlder patientsOverall survivalPostoperative complicationsSurgical resectionSurgical strategyLow preoperative KPS scorePoor Karnofsky performance scoreLow Karnofsky performance scoreYale-New Haven HospitalPostoperative adjuvant treatmentPreoperative KPS scoreAdjuvant treatment regimensExtent of resectionNew Haven HospitalUse of ioMRIAdjuvant treatmentHospital stayKPS scoreMethodsClinical dataConsecutive patientsPrognostic factorsTreatment regimensExperienced handsENT2 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 transportersHemorrhage Into a Subependymal Giant Cell Astrocytoma in an Adult With Tuberous Sclerosis
Barbiero FJ, Huttner AJ, Fulbright RK, Baehring JM. Hemorrhage Into a Subependymal Giant Cell Astrocytoma in an Adult With Tuberous Sclerosis. The Neurologist 2021, 26: 122-124. PMID: 34190204, DOI: 10.1097/nrl.0000000000000338.Peer-Reviewed Original ResearchMeSH KeywordsAdultAstrocytomaBrain NeoplasmsDelayed DiagnosisHemorrhageHumansMagnetic Resonance ImagingMaleTuberous SclerosisYoung AdultConceptsIntracranial hemorrhageMagnetic resonance imaging (MRI) brainSubependymal giant cell astrocytomaCentral nervous system tumorsYoung adultsLife-threatening complicationsGiant cell astrocytomaNervous system tumorsTuberous sclerosis complexForamen of MonroRare genetic disorderGerm-line mutationsUncommon causeHematoma evacuationDiagnostic delaySpontaneous hemorrhageUnusual causeSubependymal nodulesSurveillance imagingSkin changesTumor resectionSystem tumorsAdenoma sebaceumTuberous sclerosisSkin lesionsNanoparticle-mediated convection-enhanced delivery of a DNA intercalator to gliomas circumvents temozolomide resistance
Wang Y, Jiang Y, Wei D, Singh P, Yu Y, Lee T, Zhang L, Mandl HK, Piotrowski-Daspit AS, Chen X, Li F, Li X, Cheng Y, Josowitz A, Yang F, Zhao Y, Wang F, Zhao Z, Huttner A, Bindra RS, Xiao H, Mark Saltzman W. Nanoparticle-mediated convection-enhanced delivery of a DNA intercalator to gliomas circumvents temozolomide resistance. Nature Biomedical Engineering 2021, 5: 1048-1058. PMID: 34045730, PMCID: PMC8497438, DOI: 10.1038/s41551-021-00728-7.Peer-Reviewed Original ResearchConceptsConvection-enhanced deliveryPatient-derived xenograftsTMZ-resistant gliomasTMZ-resistant cellsGlioma cell linesSurvival benefitTemozolomide resistanceChemotherapeutic temozolomideDetectable toxicityTemozolomideOxaliplatin prodrugHuman glioblastomaGenome-wide RNA profilingTranslational strategiesDrugsCell linesGliomasAnticancer drugsMetabolomic analysisGlioblastomaDeliveryDistinct mechanismsRNA profilingMetabolic pathwaysPatientsDual activating FGFR1 mutations in pediatric pilomyxoid astrocytoma
Fomchenko EI, Reeves BC, Sullivan W, Marks AM, Huttner A, Kahle KT, Erson‐Omay E. Dual activating FGFR1 mutations in pediatric pilomyxoid astrocytoma. Molecular Genetics & Genomic Medicine 2021, 9: e1597. PMID: 33448156, PMCID: PMC8077124, DOI: 10.1002/mgg3.1597.Peer-Reviewed Original ResearchMeSH KeywordsAstrocytomaBrain NeoplasmsHumansInfantMaleMutation, MissenseReceptor, Fibroblast Growth Factor, Type 1ConceptsPilomyxoid astrocytomaPediatric patientsVariant allele frequencyHypothalamic/chiasmatic regionPathologic tissue diagnosisTreatment-related morbidityHigh recurrence ratePI3K/mTOR inhibitionYears of ageExome sequencing resultsSimilar time pointsWhole exome sequencing resultsHypothalamic dysfunctionClinical presentationSurgical managementRecurrence rateShorter survivalAggressive subtypeVision lossChiasmatic regionTissue diagnosisPatient tumorsRadiation therapyFGFR inhibitorsFGFR1 mutations
2020
Genomic alterations in Turcot syndrome: Insights from whole exome sequencing
Karschnia P, Erson-Omay EZ, Huttner AJ, Kaulen LD, Duran D, Fulbright RK, Günel M, Baehring JM. Genomic alterations in Turcot syndrome: Insights from whole exome sequencing. Journal Of The Neurological Sciences 2020, 417: 117056. PMID: 32739502, DOI: 10.1016/j.jns.2020.117056.Peer-Reviewed Original ResearchA Rare Case of a Pediatric Medullary Intracranial Germinoma
Seifert K, Huttner A, Malhotra A. A Rare Case of a Pediatric Medullary Intracranial Germinoma. World Neurosurgery 2020, 138: 137-140. PMID: 32147555, DOI: 10.1016/j.wneu.2020.02.147.Peer-Reviewed Original Research[11C]Methionine and [11C]PBR28 as PET Imaging Tracers to Differentiate Metastatic Tumor Recurrence or Radiation Necrosis
Tran TT, Gallezot JD, Jilaveanu LB, Zito C, Turcu G, Lim K, Nabulsi N, Huang H, Huttner A, Kluger HM, Chiang VL, Carson R. [11C]Methionine and [11C]PBR28 as PET Imaging Tracers to Differentiate Metastatic Tumor Recurrence or Radiation Necrosis. Molecular Imaging 2020, 19: 1536012120968669. PMID: 33147119, PMCID: PMC7649862, DOI: 10.1177/1536012120968669.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsHumansMethionineNecrosisNeoplasm Recurrence, LocalPositron-Emission TomographyRadiation InjuriesReceptors, GABAConceptsRadiation necrosisTumor regrowthStereotactic radiosurgeryBrain metastasesPET tracersHigh amino acid uptakeMetastatic tumor recurrenceLung cancer cellsSpecific PET tracersPET imaging tracerTumor recurrenceAmino acid uptakeImaging tracerReliable markerDiagnostic imagingLack of specificityAcid uptakeCancer cellsSpecific markersMethionine levelsTranslocator proteinSequential imagingInflammationMetastasisDual tracer
2019
Somatic PRKAR1A mutation in sporadic atrial myxoma with cerebral parenchymal metastases: a case report
Roque A, Kimbrough T, Traner C, Baehring JM, Huttner A, Adams J, Canosa S, Sklar J, Madri JA. Somatic PRKAR1A mutation in sporadic atrial myxoma with cerebral parenchymal metastases: a case report. Journal Of Medical Case Reports 2019, 13: 389. PMID: 31874650, PMCID: PMC6930684, DOI: 10.1186/s13256-019-2317-z.Peer-Reviewed Original ResearchMeSH KeywordsBrain NeoplasmsCarney ComplexChemoradiotherapyCyclic AMP-Dependent Protein Kinase RIalpha SubunitDopamine AgentsExome SequencingFemaleGene Expression Regulation, NeoplasticGenes, Tumor SuppressorGerm-Line MutationHeart NeoplasmsHumansIntracranial HemorrhagesMemantineMiddle AgedMyxomaTreatment OutcomeConceptsAtrial myxomaSporadic tumorsExtra-cardiac complicationsMetastatic cardiac myxomaMajority of tumorsDissemination of tumorsIntracranial hemorrhagic lesionsWhole-exome sequencingAutosomal dominant conditionConclusionsOur patientsSporadic myxomasInvasive tumor cellsParenchymal metastasesCardiac myxomaCase reportClinical behaviorHemorrhagic lesionsAneurysm formationBenign neoplasmsMyxomaSporadic lesionsVascular wallCarney complexTumorsGermline mutationsComplications associated with immunotherapy for brain metastases.
Tran TT, Jilaveanu LB, Omuro A, Chiang VL, Huttner A, Kluger HM. Complications associated with immunotherapy for brain metastases. Current Opinion In Neurology 2019, 32: 907-916. PMID: 31577604, PMCID: PMC7398556, DOI: 10.1097/wco.0000000000000756.Peer-Reviewed Original ResearchConceptsBrain metastasesNeurologic toxicityImmune therapyPhase 2 clinical trialCheckpoint inhibitor therapyImmune checkpoint inhibitorsMultiple phase 2 clinical trialsTreatment-related morbidityBrain metastatic diseaseSymptomatic edemaCheckpoint inhibitorsAdverse eventsDurable responsesMedian survivalMetastatic diseaseInhibitor therapyMore patientsIntracranial activityPatient groupRadiation necrosisClinical trialsTherapy trialsMultidisciplinary teamMetastasisPatientsDNMT3A co-mutation in an IDH1-mutant glioblastoma
Fomchenko EI, Erson-Omay EZ, Zhao A, Bindra RS, Huttner A, Fulbright RK, Moliterno J. DNMT3A co-mutation in an IDH1-mutant glioblastoma. Molecular Case Studies 2019, 5: a004119. PMID: 31371348, PMCID: PMC6672028, DOI: 10.1101/mcs.a004119.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkers, TumorBrain NeoplasmsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3ADNA Modification MethylasesEpigenesis, GeneticGene Expression ProfilingGene Expression Regulation, NeoplasticGlioblastomaGliomaHumansIsocitrate DehydrogenaseMaleMutationMutation, MissensePromoter Regions, GeneticConceptsIDH1-mutant glioblastomaEpigenetic controlHistone modificationsTranscriptional regulationDNA methylationExpression profilesGlioblastoma biologySomatic mutationsDe novoMutationsMutant glioblastomasTumor landscapeMutational profileTargeted therapeutic approachesGlioblastomaImportant roleMethylationDNMT3ABiologyGliomagenesisMissenseRegulationNovoPrimary brain tumorsTherapeutic approaches
2018
Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib
Marks AM, Bindra RS, DiLuna ML, Huttner A, Jairam V, Kahle KT, Kieran MW. Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib. Pediatric Blood & Cancer 2018, 65: e26969. PMID: 29380516, DOI: 10.1002/pbc.26969.Peer-Reviewed Original ResearchConceptsAnaplastic gangliogliomaBRAF/MEK inhibitor combinationsBRAF V600ESubsequent tumor responseDabrafenib/trametinibLarge clinical trialsSquamous cell carcinomaMEK inhibitor combinationsSignificant side effectsSignificant skin reactionsCell carcinomaCase reportSkin reactionsTumor responseClinical trialsBrain tumorsInhibitor combinationsSide effectsAdolescent femalesGangliogliomaTrametinibPrevious reactionsV600EMonotherapyRash
2017
Leiomyosarcoma of the infratemporal fossa with perineurial spread along the right mandibular nerve: a case report
Barbiero FJ, Huttner AJ, Judson BL, Baehring JM. Leiomyosarcoma of the infratemporal fossa with perineurial spread along the right mandibular nerve: a case report. CNS Oncology 2017, 06: 281-285. PMID: 28990793, PMCID: PMC6004886, DOI: 10.2217/cns-2017-0004.Peer-Reviewed Original ResearchConceptsMandibular nerveRight mandibular nerveRight cavernous sinusSmooth muscle differentiationNerve biopsyCase reportMass lesionNeck cancerCavernous sinusMalignant tumorsGI tractInfratemporal fossaMedical literatureLeiomyosarcomaSkin appendagesSimilar casesNerveTumorsMuscle differentiationPeculiar patternDiplopiaHeadacheBiopsyPatientsMyometriumSOX2 immunity and tissue resident memory in children and young adults with glioma
Vasquez JC, Huttner A, Zhang L, Marks A, Chan A, Baehring JM, Kahle KT, Dhodapkar KM. SOX2 immunity and tissue resident memory in children and young adults with glioma. Journal Of Neuro-Oncology 2017, 134: 41-53. PMID: 28620836, PMCID: PMC7906294, DOI: 10.1007/s11060-017-2515-8.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAge FactorsAntigen-Presenting CellsB7-H1 AntigenBrain NeoplasmsCell ProliferationChildChild, PreschoolCytokinesFemaleFlow CytometryGliomaHumansInfantMaleMyeloid CellsProgrammed Cell Death 1 ReceptorReceptors, ImmunologicRNA, Small InterferingSOXB1 Transcription FactorsT-LymphocytesTransfectionYoung AdultConceptsPediatric glial tumorsGlial tumorsT cellsExpression of SOX2Inhibitory checkpointsCD8/CD4 T cellsTissue-resident memory phenotypeTumor-infiltrating immune cellsTumor-infiltrating T cellsTumor cellsYoung adultsResident memory phenotypeTissue-resident memoryAnti-tumor immunityT cell immunityCD4 T cellsNatural killer cellsGlial tumor cellsNew antigenic targetsSingle-cell mass cytometryHigh mutation burdenStem cell antigenGlioma initiating cellsImmune checkpointsPD-1Surface chemistry governs cellular tropism of nanoparticles in the brain
Song E, Gaudin A, King AR, Seo YE, Suh HW, Deng Y, Cui J, Tietjen GT, Huttner A, Saltzman WM. Surface chemistry governs cellular tropism of nanoparticles in the brain. Nature Communications 2017, 8: 15322. PMID: 28524852, PMCID: PMC5454541, DOI: 10.1038/ncomms15322.Peer-Reviewed Original ResearchConceptsSurface chemistryDifferent surface chemistriesDrug deliveryNanoparticlesNanoparticle designChemistryTherapeutic efficacyAssociation rateFunctionalizationCentral nervous systemConvection-enhanced deliverySignificant uptakeBrain interstitiumOrthotopic modelNervous systemNeurological diseasesAdverse toxicityCellular tropismExtent of internalizationCellular depositionBrainCell populationsDepositionPropertiesGlioblastoma
2016
Distribution of polymer nanoparticles by convection-enhanced delivery to brain tumors
Saucier-Sawyer JK, Seo YE, Gaudin A, Quijano E, Song E, Sawyer AJ, Deng Y, Huttner A, Saltzman WM. Distribution of polymer nanoparticles by convection-enhanced delivery to brain tumors. Journal Of Controlled Release 2016, 232: 103-112. PMID: 27063424, PMCID: PMC4893898, DOI: 10.1016/j.jconrel.2016.04.006.Peer-Reviewed Original ResearchConceptsConvection-enhanced deliveryBlood-brain barrierBrain-penetrating nanoparticlesIntracranial tumorsBrain tumorsGlioblastoma multiformeHealthy brainMain tumor massFatal brain tumorPresence of tumorBrain tumor treatmentLocal recurrenceInfusion sitePeritumoral tissuesTumor massCED infusionIndividual tumorsTumorsNecrotic regionsTumor treatmentLocal administrationHeterogeneous distribution patternAdministrationBrainCell targeting