2023
Trial in Progress: An Open-Label Expansion Trial Evaluating the Safety, PK/PD, and Clinical Activity of Emavusertib (CA-4948) + Ibrutinib in R/R Primary CNS Lymphoma
Grommes C, Nowakowski G, Rosenthal A, Lunning M, Ramchandren R, Regales L, Fowle M, Lane M, Wang C, Omuro A, Leslie L, Soussain C, Dabrowska-Iwanicka A, Ferreri A, Tun H. Trial in Progress: An Open-Label Expansion Trial Evaluating the Safety, PK/PD, and Clinical Activity of Emavusertib (CA-4948) + Ibrutinib in R/R Primary CNS Lymphoma. Blood 2023, 142: 3143. DOI: 10.1182/blood-2023-190391.Peer-Reviewed Original ResearchPrimary central nervous system lymphomaInterleukin-1 receptor-associated kinase 4FMS-like tyrosine kinase 3Toll-like receptorsExpansion cohortPCNSL patientsDisease progressionRefractory primary central nervous system lymphomaDiagnosis of PCNSLCentral nervous system lymphomaPathogenesis of PCNSLSafety/tolerabilityOpen-label trialBlood-brain barrier penetrationPrimary CNS lymphomaSufficient blood-brain barrier penetrationNervous system lymphomaInitial clinical dataKey inclusion criteriaPotent oral inhibitorCentral nervous systemBrain barrier penetrationPK/PDTyrosine kinase 3Further preclinical studies
2022
Reduced blood-brain barrier penetration of acne vulgaris antibiotic sarecycline compared to minocycline corresponds with lower lipophilicity
Grada A, Del Rosso J, Moore A, Gold L, Harper J, Damiani G, Shaw K, Obagi S, Salem R, Tanaka S, Bunick C. Reduced blood-brain barrier penetration of acne vulgaris antibiotic sarecycline compared to minocycline corresponds with lower lipophilicity. Frontiers In Medicine 2022, 9: 1033980. PMID: 36569144, PMCID: PMC9773825, DOI: 10.3389/fmed.2022.1033980.Peer-Reviewed Original ResearchAdverse eventsClinical trialsVestibular side effectsBlood-brain barrier penetrationSecond-generation tetracyclineNon-clinical studiesLower ratesH postdosingAcne vulgarisSide effectsMinocyclineBrain samplesPotential associationSarecyclineBarrier penetrationDoxycyclineTrialsLow lipophilicityPenetranceTetracyclineDizzinessVertigoPostdosingRosaceaAcne
2017
Local DNA Repair Inhibition for Sustained Radiosensitization of High-Grade Gliomas
King AR, Corso CD, Chen EM, Song E, Bongiorni P, Chen Z, Sundaram RK, Bindra RS, Saltzman WM. Local DNA Repair Inhibition for Sustained Radiosensitization of High-Grade Gliomas. Molecular Cancer Therapeutics 2017, 16: 1456-1469. PMID: 28566437, PMCID: PMC5545124, DOI: 10.1158/1535-7163.mct-16-0788.Peer-Reviewed Original ResearchConceptsHigh-grade gliomasPoor blood-brain barrier penetrationLocal disease progressionBlood-brain barrier penetrationEffect of radiotherapyIntrinsic pontine gliomaTreatment of glioblastomaMol Cancer TherCranial radiationDosing schedulesMultimodal treatmentIntracranial gliomasDisease progressionExtracranial tumorsPontine gliomaAggressive phenotypeRadiotherapy approachesGliomasMinimal toxicityRadiotherapyGlioblastomaBarrier penetrationTreatmentRadiosensitizerChemotherapy
2016
Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial
Xu R, Shimizu F, Hovinga K, Beal K, Karimi S, Droms L, Peck KK, Gutin P, Iorgulescu JB, Kaley T, DeAngelis L, Pentsova E, Nolan C, Grommes C, Chan T, Bobrow D, Hormigo A, Cross JR, Wu N, Takebe N, Panageas K, Ivy P, Supko JG, Tabar V, Omuro A. Molecular and Clinical Effects of Notch Inhibition in Glioma Patients: A Phase 0/I Trial. Clinical Cancer Research 2016, 22: 4786-4796. PMID: 27154916, PMCID: PMC5050072, DOI: 10.1158/1078-0432.ccr-16-0048.Peer-Reviewed Original ResearchConceptsRecurrent tumorsCancer-initiating cell populationGamma secretase inhibitor RO4929097Blood-brain barrier disruptionBlood-brain barrier penetrationDose-limiting toxicityNotch intracellular domainPotential therapeutic optionSignificant decreaseRelative plasma volumeHigh-grade gliomasTumor explant culturesNotch pathwayI trialDismal prognosisTherapeutic optionsBarrier disruptionDrug exposureAnaplastic astrocytomaAngiogenic factorsTumor tissueAntiangiogenic roleTarget modulationDrug penetrationPerfusion MRI
1986
Review: Recent Advances in the Pathogenesis and Pathophysiology of Bacterial Meningitis
Quagliarello V, Scheld W. Review: Recent Advances in the Pathogenesis and Pathophysiology of Bacterial Meningitis. The American Journal Of The Medical Sciences 1986, 292: 306-309. PMID: 3535498, DOI: 10.1097/00000441-198611000-00010.Peer-Reviewed Original ResearchConceptsBacterial meningitisHost defenseBactericidal antibiotic therapyInterstitial brain edemaIrreversible neuronal injuryBlood-brain barrier penetrationImpaired host defenseExperimental animal modelsVirulence factorsBrain barrier penetrationSurface virulence factorsBacterial virulence factorsMeningitis developmentPathophysiologic sequelaeMeningeal pathogensNeuronal injuryAntibiotic therapyBrain edemaWorldwide morbidityPathogenetic sequencePathogenetic stepsAnimal modelsMucosal colonizationMeningitisMorbidity
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