grant
Targeted drug delivery system to overcome blood-brain barrier and therapeutic resistance to current standard of care in Glioblastoma
Organization WAYNE STATE UNIVERSITYLocation DETROIT, UNITED STATESPosted 1 Apr 2023Deadline 31 Mar 2028
NIHUS FederalResearch GrantFY202520S Catalytic Proteasome20S Core Proteasome20S Proteasome20S ProteosomeAPF-1ATP-Dependent Proteolysis Factor 1AddressAffinityAlcohol Chemical ClassAlcoholsAlkylating AgentsAlkylationAlkylatorsAmino AcidsAnimalsAntabuseApoptoticBindingBioavailabilityBiodistributionBiological AvailabilityBiological MarkersBloodBlood - brain barrier anatomyBlood Reticuloendothelial SystemBlood-Brain BarrierBody TissuesBrainBrain NeoplasiaBrain NeoplasmsBrain Nervous SystemBrain TumorsC-jun Amino-Terminal KinaseC-jun Kinase-1C-jun N-Terminal Kinase 1Cancer TreatmentCarbonCarcinogen-DNA AdductsCell BodyCell Culture TechniquesCellsChemicalsChemoresistanceChlorotoxinClinical ResearchClinical StudyCombined Modality TherapyCombretastatin A-4ComplexCopperCoupledCu elementCurcuminCysteineDDTCDIECADNADNA AdductsDNA Damage RepairDNA Double Strand BreakDNA RepairDNA Repair EnzymesDNA-6-O-Methylguanine[protein]-L-Cysteine S-MethyltransferaseDeoxyribonucleic AcidDevelopmentDiagnosisDiethylcarbamodithioic AcidDiethyldioneDiethyldithiocarbamic AcidDiethyldithiocarbaminic AcidDiethyldithioneDiferuloylmethaneDisulfidesDisulfiramDitiocarbDoseDrug DeliveryDrug Delivery SystemsDrug TargetingDrugsEC 2.1.1EC 2.1.1.63EffectivenessEncapsulatedEncephalonEngineeringEnvironmentEnzyme GeneEnzymesFDA approvedFormulationFractionated radiotherapyGeneral Prognostic FactorGlial Cell TumorsGlial NeoplasmGlial TumorGlioblastomaGliomaGoalsGrade IV Astrocytic NeoplasmGrade IV Astrocytic TumorGrade IV AstrocytomaGuanine-O(6)-AlkyltransferaseHMG-20Half-CystineHemato-Encephalic BarrierHematologyHeterogeneityHeterograftHeterologous TransplantationHigh Mobility Protein 20Hydrogen OxideImmunoblottingImmunohistochemistryImmunohistochemistry Cell/TissueImmunohistochemistry Staining MethodIn VitroIntratumoral heterogeneityIntravenousJN KinaseJNKJNK Mitogen-Activated Protein KinasesJNK1JNK1 KinaseJNK1 proteinJNK1A2JNK21B1/2L-CysteineLigandsLytotoxicityMAP Kinase 8MAP Kinase 8 GeneMAPK8MAPK8 Mitogen-Activated Protein KinaseMAPK8 geneMGMTMGMT geneMR ImagingMR TomographyMRIMRIsMacropainMacroxyproteinaseMagnetic Resonance ImagingMalignant CellMalignant Glial NeoplasmMalignant Glial TumorMalignant GliomaMalignant Neoplasm TherapyMalignant Neoplasm TreatmentMalignant Neuroglial NeoplasmMalignant Neuroglial TumorMediatingMedical Imaging, Magnetic Resonance / Nuclear Magnetic ResonanceMedicationMethodsMethylated-DNA Protein-Cysteine MethyltransferaseMethylated-DNA-Protein-Cysteine S-MethyltransferaseMethylguanine-DNA Methyltransferase GeneMethyltransferaseMitogen-Activated Protein Kinase 8ModelingMolecularMolecular InteractionMonitorMorphologyMulticatalytic ProteinaseMultimodal TherapyMultimodal TreatmentNMR ImagingNMR TomographyNeuroglial NeoplasmNeuroglial TumorNuclear Magnetic Resonance ImagingO(6)-AGTO(6)-Alkylguanine-DNA AlkyltransferaseO(6)-MeG-DNA MethyltransferaseO(6)-Methylguanine DNA TransmethylaseO(6)-Methylguanine MethyltransferaseO(6)-Methylguanine-DNA MethyltransferaseO6-Alkylguanine DNA AlkyltransferaseOralOral AdministrationOral Drug AdministrationPRKM8Pathway interactionsPatientsPeptidesPharmaceutical PreparationsPhase 2 Clinical TrialsPhase II Clinical TrialsPhysiologicPhysiologic AvailabilityPhysiologicalPlayPolymersPrognosisPrognostic FactorPrognostic/Survival FactorProsomeProteasomeProteasome Endopeptidase ComplexProtein MethylasesProtein MethyltransferasesProteinsProteosomeR-Series Research ProjectsR01 MechanismR01 ProgramRT-PCRRadiation therapyRadioresistanceRadiotherapeuticsRadiotherapyReceptor ProteinRecurrent diseaseRelapsed DiseaseReportingResearchResearch GrantsResearch Project GrantsResearch ProjectsResistanceReverse Transcriptase Polymerase Chain ReactionRoleSAP Kinase-1SAPK/JNKSAPK1 Mitogen-Activated Protein KinaseSAPK1/JNKSafetySerum ProteinsSolubilitySpecificityStomachStress-Activated Protein Kinase JNK1Stress-Activated Protein Kinase gammaSystemTemodalTemodarTestingTetraethylthiuram DisulfideThiocarbTissuesToxic effectToxicitiesTreatment EfficacyTumor BurdenTumor CellTumor LoadTurmeric YellowUbiquitinUnscheduled DNA SynthesisWaterWestern BlottingWestern ImmunoblottingWorkXenograftXenograft ModelXenograft procedureXenotransplantationZeugmatographyalkylguanine DNA alkyltransferaseaminoacidanti-cancer therapybeta-hydroxypropylcyclodextrinbio-markersbiologic markerbiomarkerbloodbrain barrierc-jun N-Terminal Kinasecancer cellcancer therapycancer-directed therapycell culturecell cultureschelationchemoresistantchemotherapy resistancechemotherapy resistantclinical applicabilityclinical applicationcombination therapycombined modality treatmentcombined treatmentcombretastatin A4cytotoxiccytotoxicitydetermine efficacydevelopmentaldiethyl-carbamodithioic aciddrug/agentefficacy analysisefficacy assessmentefficacy determinationefficacy evaluationefficacy examinationevaluate efficacyexamine efficacyextracellularfractionated radiationgastricglial-derived tumorglioblastoma multiformeheterogeneity in tumorshydroxypropyl-beta-cyclodextrinimprovedin vivoinhibitorintervention efficacyintra-tumoral heterogeneityintraoral drug deliveryintratumor heterogeneityjun-NH2-Terminal Kinasemethazolastonemethylasemethylguanine DNA methyltransferasemulti-modal therapymulti-modal treatmentmulticatalytic endopeptidase complexnano particle deliverynanoparticle deliverednanoparticle deliveryneoplastic cellneuroglia neoplasmneuroglia tumornoveloverexpressoverexpressionpathwayphase 2 trialphase II protocolphase II trialpolymerpolymericpre-clinicalpre-clinical studypreclinicalpreclinical studyprotein blottingradiation resistanceradiation treatmentradio resistancereal time monitoringrealtime monitoringreceptorrepairrepairedresistance to therapyresistantresistant to therapyresponse to therapyresponse to treatmentreverse transcriptase PCRsite targeted deliverysocial rolespongioblastoma multiformestandard of carestress-activated protein kinase 1successtargeted agenttargeted deliverytemozolomidetherapeutic efficacytherapeutic resistancetherapeutic responsetherapy efficacytherapy resistanttherapy responsetransmethylasetreatment resistancetreatment responsetreatment responsivenesstreatment with radiationtumortumor heterogeneitytumors in the brainwater solubilityxeno-transplantxeno-transplantationxenograft transplant modelxenotransplant model
Description preview
Project Summary/Abstract: The uniform lethality of glioblastoma (GBM) with a survival of less than 2
years despite best available therapy is attributed to treatment resistance due to DNA repair mechanisms that
drive disease relapse and tumor heterogeneity. One prognostic factor identified as a reliable biomarker for GBM
sensitivity to temozolomide…
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