2024
Tertiary amine modification enables triterpene nanoparticles to target the mitochondria and treat glioblastoma via pyroptosis induction
Gao X, Tang X, Tu Z, Yu J, Bao Y, Long G, Sheu W, Wu H, Liu J, Zhou J. Tertiary amine modification enables triterpene nanoparticles to target the mitochondria and treat glioblastoma via pyroptosis induction. Biomaterials 2024, 317: 123035. PMID: 39731842, PMCID: PMC11827167, DOI: 10.1016/j.biomaterials.2024.123035.Peer-Reviewed Original ResearchConceptsSurvival of tumor-bearing miceBrain tumorsEffective treatmentPenetrate brain tumorsEffective treatment of glioblastomaTumor-bearing micePrimary brain tumorTreatment of glioblastomaMitochondria-targeted effectsTreating glioblastomaCancer treatmentGlioblastomaEffective killingTherapeutic targetHexokinase inhibitorGBM cellsPyroptosis inductionMitochondriaTumorGlycyrrhetinic acidTargeting effectTreatmentThe novel DNA cross-linking agent KL-50 is active against patient-derived models of new and recurrent post-temozolomide mismatch repair-deficient glioblastoma
McCord M, Sears T, Wang W, Chaliparambil R, An S, Sarkaria J, James C, Ruggeri B, Gueble S, Bindra R, Horbinski C. The novel DNA cross-linking agent KL-50 is active against patient-derived models of new and recurrent post-temozolomide mismatch repair-deficient glioblastoma. Neuro-Oncology 2024, 27: 644-651. PMID: 39658092, PMCID: PMC11889708, DOI: 10.1093/neuonc/noae257.Peer-Reviewed Original ResearchMedian survival of miceSurvival of miceMedian survivalIDH wild-type glioblastomaO-6-methylguanine-DNA methyltransferaseExposure to temozolomideAcquired resistance to TMZWild-type glioblastomaPatient-derived xenograftsSensitivity to temozolomidePatient-derived modelsResistance to temozolomideLN229 glioma cellsPatient-derived glioblastomaRecurrent tumorsMGMT deficiencyFractionated RTTemozolomideLow dosesImprove outcomesGlioblastomaEnzyme deficiencyMismatch repairGlioma cellsGBM12EPCO-34. DECIPHERING THE LONGITUDINAL TRAJECTORIES OF GLIOBLASTOMA BY INTEGRATIVE SINGLE-CELL GENOMICS
Spitzer A, Johnson K, Nomura M, Garofano L, Nehar-belaid D, Darnell N, Greenwald A, Bussema L, Oh Y, Varn F, D’Angelo F, Gritsch S, Anderson K, Migliozzi S, Castro L, Chowdhury T, Robine N, Reeves C, Park J, Lipsa A, Hertel F, Golebiewska A, Niclou S, Nusrat L, Kellet S, Das S, Moon H, Paek S, Bielle F, Laurenge A, Di Stefano A, Mathon B, Picca A, Sanson M, Tanaka S, Saito N, Ashley D, Keir S, Huse J, Yung W, Lasorella A, Iavarone A, Verhaak R, Tirosh I, Suvà M. EPCO-34. DECIPHERING THE LONGITUDINAL TRAJECTORIES OF GLIOBLASTOMA BY INTEGRATIVE SINGLE-CELL GENOMICS. Neuro-Oncology 2024, 26: viii9-viii9. PMCID: PMC11553653, DOI: 10.1093/neuonc/noae165.0033.Peer-Reviewed Original ResearchMalignant cellsStandard-of-care therapyCell typesMalignant cell fractionIDH-wildtype glioblastomaTumor DNA sequencingRecurrent GBM specimensMesenchymal-like cellsAssociated with specific changesMGMT methylationCell statesTreatment responseSingle-cell genomicsComposition of cell typesSingle-nucleus RNA sequencingMalignant stateDistribution of cell typesRecurrent samplesGBM specimensLongitudinal cohortGlioblastomaDNA sequencesClinical annotationDeletion phenotypeCell fractionFeeding the wrath with myelin
Ghosh S, Rothlin C. Feeding the wrath with myelin. Trends In Immunology 2024, 45: 729-731. PMID: 39341708, PMCID: PMC11471388, DOI: 10.1016/j.it.2024.09.004.Peer-Reviewed Original ResearchCASCADES, a novel SOX2 super‐enhancer‐associated long noncoding RNA, regulates cancer stem cell specification and differentiation in glioblastoma
Shahzad U, Nikolopoulos M, Li C, Johnston M, Wang J, Sabha N, Varn F, Riemenschneider A, Krumholtz S, Krishnamurthy P, Smith C, Karamchandani J, Watts J, Verhaak R, Gallo M, Rutka J, Das S. CASCADES, a novel SOX2 super‐enhancer‐associated long noncoding RNA, regulates cancer stem cell specification and differentiation in glioblastoma. Molecular Oncology 2024, 19: 764-784. PMID: 39323013, PMCID: PMC11887672, DOI: 10.1002/1878-0261.13735.Peer-Reviewed Original ResearchCancer stem cellsGlioma CSCsPresence of cancer stem cellsCancer stem cell compartmentPrimary malignant brain tumorGlioma cancer stem cellsMalignant brain tumorsCancer-specific mannerMedian survivalTumor recurrenceTreatment resistanceStem cell specificationRegulation of stemnessTumor developmentRegulation of Sox2Brain tumorsNeuronal lineageStem cellsGlioblastomaTherapeutic targetSOX2Cell RepositoryCell-specificTumorLong noncoding RNAsAutocatalytic, Brain Tumor‐Targeting Delivery of Bardoxolone Methyl Self‐Assembled Nanoparticles for Glioblastoma Treatment
Ye Z, Sheu W, Qu H, Peng B, Liu J, Zhang L, Yuan F, Wei Y, Zhou J, Chen Q, Xiao X, Zhang S. Autocatalytic, Brain Tumor‐Targeting Delivery of Bardoxolone Methyl Self‐Assembled Nanoparticles for Glioblastoma Treatment. Small Science 2024, 4 DOI: 10.1002/smsc.202470027.Peer-Reviewed Original ResearchCell-specific cross-talk proteomics reveals cathepsin B signaling as a driver of glioblastoma malignancy near the subventricular zone
Norton E, Whaley L, Jones V, Brooks M, Russo M, Morderer D, Jessen E, Schiapparelli P, Ramos-Fresnedo A, Zarco N, Carrano A, Rossoll W, Asmann Y, Lam T, Chaichana K, Anastasiadis P, Quiñones-Hinojosa A, Guerrero-Cázares H. Cell-specific cross-talk proteomics reveals cathepsin B signaling as a driver of glioblastoma malignancy near the subventricular zone. Science Advances 2024, 10: eadn1607. PMID: 39110807, PMCID: PMC11305394, DOI: 10.1126/sciadv.adn1607.Peer-Reviewed Original ResearchConceptsBrain tumor-initiating cellsLateral ventricleNeuronal maturationMalignancy-associated phenotypesSubventricular zone contactIncreased expression of cathepsin BMalignant primary brain tumorTumor-initiating cellsAggressive malignant primary brain tumorPrimary brain tumorTumor microenvironment researchExpression of cathepsin BNeural stem/progenitor cellsCathepsin BInduction of senescenceStem/progenitor cellsCell-intrinsicSubventricular zoneCross-talkTherapeutic strategiesBrain tumorsIncreased expressionGBM biologyLentiviral knockdownGlioblastomaAutocatalytic, Brain Tumor‐Targeting Delivery of Bardoxolone Methyl Self‐Assembled Nanoparticles for Glioblastoma Treatment
Ye Z, Sheu W, Qu H, Peng B, Liu J, Zhang L, Yuan F, Wei Y, Zhou J, Chen Q, Xiao X, Zhang S. Autocatalytic, Brain Tumor‐Targeting Delivery of Bardoxolone Methyl Self‐Assembled Nanoparticles for Glioblastoma Treatment. Small Science 2024, 4: 2400081. PMID: 40212541, PMCID: PMC11935168, DOI: 10.1002/smsc.202400081.Peer-Reviewed Original ResearchBlood-brain barrierBardoxolone methylGlioblastoma multiformeBrain tumorsSurvival of miceSelf-assembled nanoparticlesInhibited GBM tumor growthEnhance drug penetrationGlioblastoma multiforme treatmentKill GBM cellsLack of effective drugsTumor growthDrug penetrationIntravenous administrationP28 peptideEffective drugsGlioblastoma treatmentTumorClinical applicationGBM cellsPeptide-conjugatesTreatmentBrainBardoxoloneGlioblastomaPractical guidance for direct oral anticoagulant use in the treatment of venous thromboembolism in primary and metastatic brain tumor patients
Ranjan S, Leung D, Ghiaseddin A, Taylor J, Lobbous M, Dhawan A, Budhu J, Coffee E, Melnick K, Chowdhary S, Lu‐Emerson C, Kurz S, Burke J, Lam K, Patel M, Dunbar E, Mohile N, Peters K. Practical guidance for direct oral anticoagulant use in the treatment of venous thromboembolism in primary and metastatic brain tumor patients. Cancer 2024, 130: 1577-1589. PMID: 38288941, DOI: 10.1002/cncr.35220.Peer-Reviewed Original ResearchConceptsDirect oral anticoagulantsLow-molecular-weight heparinVenous thromboembolismIntracranial hemorrhageBrain tumorsEfficacy of direct oral anticoagulantsMetastatic brain tumor patientsRisk of intracranial hemorrhageTreatment of venous thromboembolismManagement of venous thromboembolismMetastatic brain tumorsOral anticoagulant useTreat venous thromboembolismOff-label useBrain tumor patientsBrain metastasesOral anticoagulantsAnticoagulant useTumor patientsClinical trialsPatientsClinical guidanceThromboembolismGlioblastomaHeparinGlioblastom – aktuelle Therapiekonzepte
Rieger D, Renovanz M, Kurz S, Bombach P, Paulsen F, Roder C, Tatagiba M, Niyazi M, Tabatabai G. Glioblastom – aktuelle Therapiekonzepte. Die Onkologie 2024, 30: 145-156. DOI: 10.1007/s00761-024-01473-7.Peer-Reviewed Original ResearchClinical trialsWorld Health Organization classificationCombination of radiotherapyFirst-line therapyDiagnosis of glioblastomaPatterns of disease progressionTherapeutic clinical trialsTumor Treating FieldsCurrent treatment conceptsCentral nervous systemNeuro-oncology careTemozolomide chemotherapyFirst-linePostoperative therapyPrimary neoplasmsOrganization classificationUnfavorable prognosisTumor progressionClinical statusDisease progressionTreatment conceptTreatment recommendationsBiomarker-basedNervous systemGlioblastoma
2023
EPCO-37. DISSECTING GBM EVOLUTION FOLLOWING STANDARD-OF-CARE BY LARGE-SCALE LONGITUDINAL SINGLE NUCLEUS RNA-SEQUENCING
Nomura M, Spitzer A, Johnson K, Garofano L, Nehar-Belaid D, Oh Y, Anderson K, Najac R, Bussema L, Varn F, D’Angelo F, Chowdhury T, Migliozzi S, Park J, Ermini L, Golebiewska A, Niclou S, Das S, Paek S, Moon H, Mathon B, Di Stefano A, Bielle F, Laurenge A, Sanson M, Tanaka S, Saito N, Keir S, Ashley D, Huse J, Yung W, Lasorella A, Iavarone A, Verhaak R, Suva M, Tirosh I. EPCO-37. DISSECTING GBM EVOLUTION FOLLOWING STANDARD-OF-CARE BY LARGE-SCALE LONGITUDINAL SINGLE NUCLEUS RNA-SEQUENCING. Neuro-Oncology 2023, 25: v132-v132. PMCID: PMC10639295, DOI: 10.1093/neuonc/noad179.0499.Peer-Reviewed Original ResearchSingle-nucleus RNA sequencingLarge-scale longitudinal cohortTME compositionRecurrent samplesGood clinical courseInitial tumor resectionMajority of patientsTumor microenvironment cellsPrimary tumor samplesMGMT methylation statusTME changesClinical courseRNA sequencingTherapy failureLikely respondersTumor resectionDisease progressionNucleus RNA sequencingLongitudinal cohortReciprocal increaseTumor samplesMicroenvironment cellsMalignant cell fractionGlioblastomaRecurrenceTMIC-20. A SPATIALLY RESOLVED HUMAN GLIOBLASTOMA ATLAS REVEALS DISTINCT CELLULAR AND MOLECULAR PATTERNS OF ANATOMICAL NICHES
Shah N, Park H, Sonpatki P, Han K, Yu H, Kim S, Chowdhury T, Byun Y, Kang H, Lee J, Lee S, Won J, Kim T, Choi S, Shin Y, Ku J, Lee S, Yun H, Park S, Park C, Park W. TMIC-20. A SPATIALLY RESOLVED HUMAN GLIOBLASTOMA ATLAS REVEALS DISTINCT CELLULAR AND MOLECULAR PATTERNS OF ANATOMICAL NICHES. Neuro-Oncology 2023, 25: v282-v282. PMCID: PMC10639919, DOI: 10.1093/neuonc/noad179.1086.Peer-Reviewed Original ResearchCellular componentsBulk RNA-seq dataAnatomical nichesSingle-cell atlasSingle-cell RNARNA-seq dataMulti-omics profilingDifferent cellular componentsInteraction networksSpatial transcriptomeCellular heterogeneitySpatial interaction networkDistinct cellularMolecular patternsCellular architectureNicheUnrecognized subtypesSpatial organizationAbstract GlioblastomaValuable resourceGlioma samplesStromal cellsEffective combinatorial therapiesComprehensive insightGlioblastomaToward Precision Oncology in Glioblastoma with a Personalized Cancer Genome Reporting Tool and Genetic Changes Identified by Whole Exome Sequencing
Erdogan O, Özkaya Ş, Erzik C, Bilguvar K, Arga K, Bayraklı F. Toward Precision Oncology in Glioblastoma with a Personalized Cancer Genome Reporting Tool and Genetic Changes Identified by Whole Exome Sequencing. OMICS A Journal Of Integrative Biology 2023, 27: 426-433. PMID: 37669106, DOI: 10.1089/omi.2023.0117.Peer-Reviewed Original ResearchConceptsTreatment optionsWhole-exome sequencingPrecision/personalized medicineExome sequencingLimited treatment optionsGenetic alterationsPersonalized medicinePotential therapeutic targetAggressive brain tumorTumor tissue samplesPoor prognosisGBM patientsTargetable pathwaysBrain tumorsTherapeutic targetLarger studyMolecular findingsNeurosurgical oncologyGenomic profilingPatientsPersonalized therapyMolecular profilingAkt/GlioblastomaPrecision oncologyCorrecting the drug development paradigm for glioblastoma requires serial tissue sampling
Singh K, Hotchkiss K, Parney I, De Groot J, Sahebjam S, Sanai N, Platten M, Galanis E, Lim M, Wen P, Minniti G, Colman H, Cloughesy T, Mehta M, Geurts M, Arrillaga-Romany I, Desjardins A, Tanner K, Short S, Arons D, Duke E, Wick W, Bagley S, Ashley D, Kumthekar P, Verhaak R, Chalmers A, Patel A, Watts C, Fecci P, Batchelor T, Weller M, Vogelbaum M, Preusser M, Berger M, Khasraw M. Correcting the drug development paradigm for glioblastoma requires serial tissue sampling. Nature Medicine 2023, 29: 2402-2405. PMID: 37488293, PMCID: PMC11983287, DOI: 10.1038/s41591-023-02464-8.Peer-Reviewed Original ResearchAn expanded safety/feasibility study of the EMulate Therapeutics Voyager™ System in patients with recurrent glioblastoma
Barkhoudarian G, Badruddoja M, Blondin N, Chowdhary S, Cobbs C, Duic J, Flores J, Fonkem E, McClay E, Nabors L, Salacz M, Taylor L, Vaillant B, Gill J, Kesari S. An expanded safety/feasibility study of the EMulate Therapeutics Voyager™ System in patients with recurrent glioblastoma. CNS Oncology 2023, 12: cns102. PMID: 37462385, PMCID: PMC10410686, DOI: 10.2217/cns-2022-0016.Peer-Reviewed Original ResearchConceptsMedian overall survivalProgression-free survivalOverall survivalRecurrent glioblastomaAdverse eventsTherapy groupMedian progression-free survivalDevice-related adverse eventsSafety/feasibilitySerious adverse eventsFurther prospective studiesConcurrent therapyInvestigator's discretionStandard chemotherapyProspective studyTRIAL REGISTRATIONPatientsMonthsTreatmentHome-use deviceGlioblastomaWeeksSurvivalTotalGroupPatient-derived glioblastoma cell lines with conserved genome profiles of the original tissue
Kim S, Cho Y, Shin Y, Yu H, Chowdhury T, Kim S, Yi K, Choi C, Cha S, Park C, Ku J. Patient-derived glioblastoma cell lines with conserved genome profiles of the original tissue. Scientific Data 2023, 10: 448. PMID: 37438387, PMCID: PMC10338444, DOI: 10.1038/s41597-023-02365-y.Peer-Reviewed Original ResearchConceptsCell linesPatient-derived glioblastoma cell linesPatient-derived cell linesWhole exome sequencing datasetsExome sequencing datasetsGBM cell linesGlioblastoma cell linesSequence dataGenomic featuresLethal intracranial tumorSequencing technologiesSequencing datasetsMolecular markersWES datasetsGenome profilesMutational signaturesDruggable targetsNumber alterationsBiological credibilityGenomic profilesBiological platformMolecular characteristicsOriginal tissueTumor tissueGlioblastomaThe SNP rs755622 is associated with immune activation in glioblastoma
Alban T, Grabowski M, Otvos B, Bayik D, Wang W, Zalavadia A, Makarav V, Troike K, McGraw M, Rabljenovic A, Lauko A, Neumann C, Roversi G, Waite K, Cioffi G, Patil N, Tran T, McCortney K, Steffens A, Diaz-Montero C, Brown J, Egan K, Horbinski C, Barnholtz-Sloan J, Rajappa P, Vogelbaum M, Bucala R, Chan T, Ahluwalia M, Lathia J. The SNP rs755622 is associated with immune activation in glioblastoma. JCI Insight 2023, 8: e160024. PMID: 37252795, PMCID: PMC10371339, DOI: 10.1172/jci.insight.160024.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorImmune activationCytokine macrophage migration inhibitory factorMigration inhibitory factorLactotransferrin (LTF) expressionLeukocyte infiltrationHallmark of glioblastomaImmune microenvironmentTreatment responseRs755622Inhibitory factorDrug resistanceGermline mutationsIntratumoral heterogeneityTumoral microenvironmentGermline SNPsGlioblastomaAnti-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 ResearchConceptsConvection-enhanced deliveryHigh recurrence rateOrthotopic mouse modelBrain tumor therapyTreatment of glioblastomaRecurrence ratePoor survivalLethal malignancyMouse modelGBM progressionTumor cellsGlioblastomaTumor therapyBioadhesive nanoparticlesOncomiRSurvivalTreatmentSeed regionMalignancyTemozolomideTherapy
2022
Deciphering the Clinical Trials of Immunotherapy in Glioblastoma: What a Neuroradiologist Needs to Know
Varzaneh F, Merkaj S, Petersen G, Bahar R, Jekel L, Pala A, Malhotra A, Ivanidze J, Aboian M. Deciphering the Clinical Trials of Immunotherapy in Glioblastoma: What a Neuroradiologist Needs to Know. Neurographics 2022, 12: 176-187. DOI: 10.3174/ng.2100055.Peer-Reviewed Original ResearchTreatment of glioblastomaClinical trialsTrial failuresImmune checkpoint inhibitorsMechanisms of immunotherapyPrimary intracranial neoplasmsCheckpoint inhibitorsSurgical resectionImmunotherapeutic approachesSurvival outcomesIntracranial neoplasmsRadiation therapyImmunotherapyGlioblastoma treatmentGlioblastomaMultidisciplinary approachTrialsTreatmentNeuroradiologistsPresent studyFuture directionsResectionChemotherapyFailurePrognosisSingle cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma
Coy S, Wang S, Stopka S, Lin J, Yapp C, Ritch C, Salhi L, Baker G, Rashid R, Baquer G, Regan M, Khadka P, Cole K, Hwang J, Wen P, Bandopadhayay P, Santi M, De Raedt T, Ligon K, Agar N, Sorger P, Touat M, Santagata S. Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma. Nature Communications 2022, 13: 4814. PMID: 35973991, PMCID: PMC9381513, DOI: 10.1038/s41467-022-32430-w.Peer-Reviewed Original ResearchConceptsPediatric high-grade gliomasHigh-grade gliomasDiffuse midline gliomaH3K27M-mutant diffuse midline gliomaAstrocyte-like differentiationPoor outcomeInflammatory microenvironmentClinical significanceMidline gliomaTherapeutic targetingMyeloid cellsPurinergic signalingImmune adaptationEGFR amplificationTumor cellsGliomasExtracellular purinergicPurinergicGlioblastomaCD39CD73Functional stateMicroenvironmentMicrogliaCells
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