Stem cell, tumor and bone marrow microenvironment cross-talk in vivo
体内干细胞、肿瘤和骨髓微环境的串扰
基本信息
- 批准号:7430502
- 负责人:
- 金额:$ 230.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-09-30 至 2012-08-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAcylationAddressAdhesivesAffectAffinityAnatomyAnimal ModelAnimalsAntibodiesAntigen-Presenting CellsAntigensApoptosisApoptoticArchitectureAreaArgonArtsAscaridilAspirate substanceAvidinAwardB-LymphocytesBehaviorBenignBibliographyBindingBiological AssayBiological AvailabilityBiologyBiotechnologyBiotinBloodBlood CellsBlood Component RemovalBlood VesselsBlood specimenBone MarrowBone Marrow NeoplasmsBone Marrow Stem CellBone Marrow TransplantationBone marrow biopsyCD19 geneCD3 AntigensCD34 geneCSF3 geneCXCR4 ReceptorsCXCR4 geneCalcium-Sensing ReceptorsCalvariaCancer BiologyCancerousCell AdhesionCell Adhesion MoleculesCell CommunicationCell LineCell SurvivalCell TherapyCell divisionCell membraneCell physiologyCell surfaceCellsCharacteristicsChargeChemistryChemokine, OtherChicagoClassClinicalClinical ResearchCoculture TechniquesCollaborationsCommunicationCommunitiesComplexConfocal MicroscopyCountCulture MediaDNADana-Farber Cancer InstituteDataDeath RateDendritic CellsDependenceDepthDetectionDevelopmentDextransDimensionsDisciplineDiseaseDockingDoseDrug Delivery SystemsDrug MonitoringDyesE-SelectinElementsEncapsulatedEnd PointEndothelial CellsEngineeringEngraftmentEnvironmentErythroid CellsEthylene GlycolsEventExhibitsExperimental Animal ModelExperimental ModelsExposure toExtracellular MatrixExtracellular Matrix ProteinsFilmFlow CytometryFluorescenceFluorescent Antibody TechniqueFosteringFutureGaliumGasesGeneral HospitalsGoalsGreen Fluorescent ProteinsGrowthGrowth FactorHalf-LifeHarvestHematologic NeoplasmsHematologyHematopoiesisHematopoieticHematopoietic stem cellsHeterogeneityHistologyHome environmentHomeostasisHomingHomologous GeneHourHumanHybridsITGAM geneITGAX geneImageImage AnalysisImaging TechniquesImmersion Investigative TechniqueImmuneImmunocompromised HostImmunofluorescence ImmunologicImmunohistochemistryImmunologyImmunomagnetic SeparationIn VitroIncubatedIndividualInflammatoryInjection of therapeutic agentInstitutionIntegrin alpha4beta1Integrin alpha5beta1Interphase CellInvasiveInvestigationJournalsKnowledgeKryptonLabelLaboratoriesLaboratory ResearchLasersLateralLeadLearningLegal patentLettersLeukemic CellLeukemic Hematopoietic Stem CellLifeLigandsLipidsLiposomesLiteratureLocalizedLocationLongitudinal StudiesLymphoidMagnetic Resonance ImagingMagnetismMaintenanceMalignant - descriptorMalignant NeoplasmsManualsManufacturer NameMarrowMassachusettsMeasuresMediatingMediator of activation proteinMedicalMedicineMembraneMembrane FluidityMetastatic Neoplasm to the Bone MarrowMethodsMicroscopeMicroscopyMicrospheresMinorityModelingMolecularMolecular ProbesMolecular ProfilingMolecular TargetMolecular and Cellular BiologyMusMutationMyelogenousN-CadherinNanotechnologyNatural regenerationNatureNeoplasm MetastasisNeoplastic Endothelial CellNeuronsNormal CellNumbersOccupationsOncologyOrganic solvent productOsteoblastsOutcomeP-SelectinPathologicPathologyPatientsPatternPerivascular NeoplasmPharmaceutical PreparationsPhosphorylcholinePhotonsPhysical ChemistryPhysicsPhysiologicalPlayPolyethylene GlycolsPolymer ChemistryPolymerase Chain ReactionPopulationPositioning AttributePre-B Acute Lymphoblastic LeukemiaProbabilityProcessPropertyProto-Oncogene Protein c-kitProtocols documentationRNARadiology SpecialtyRangeRateReactionReceptor CellRecording of previous eventsRegulationResearchResearch DesignResearch Ethics CommitteesResearch PersonnelResistanceResolutionResourcesReticular CellReverse Transcriptase Polymerase Chain ReactionRiskRoleRunningSCID MiceSalineSamplingSapphireScanningScienceScientistScreening procedureSensitivity and SpecificitySerumShapesSignal TransductionSignal Transduction PathwaySiteSmall Interfering RNASolutionsSorting - Cell MovementSpeedSpleenStagingStandards of Weights and MeasuresStem Cell DevelopmentStem cell transplantSterilityStimulusStressStromal Cell-Derived Factor 1Stromal CellsStudentsSurfaceSystemT-LymphocyteTailTechniquesTechnologyTestingTherapeuticThinkingTimeTissue BanksTissuesTitaniumTitrationsTrainingTranslational ResearchTransplantationTreatment ProtocolsTumor AngiogenesisTumor BiologyTumor Cell InvasionTumor Stem CellsUniversitiesVascular Cell Adhesion Molecule-1Vascular Endothelial CellVascular Endothelial Growth FactorsVeinsVisible RadiationWaterWeekWorkXenograft ModelXenograft procedureabstractingangiogenesisantibody conjugateaqueousbasebody systembonecancer cellcancer stem cellcancer therapycareercell behaviorcell growthcell motilitycell typecellular imagingchemokinechemokine receptorchemotherapyclinical applicationclinically significantcraniumcyaninecyanine dyecytokinecytotoxicdaydesigndesiredetectordextrandisorder controlethylene glycolexperiencefluorophoreforgingfunctional grouphuman diseaseimprovedin vivoinhibitor/antagonistinnovationinsightinterestintravital fluorescence microscopyintravital microscopyirradiationlensleukemiamacrophagemagnetic cell separationmanmicrocalorimetrymigrationmolecular dynamicsmolecular imagingmouse modelnanoparticleneoplastic cellneovascularizationnew technologynotch proteinnovelnovel strategiesnovel therapeuticsoutcome forecastparticleperipheral bloodpre-clinicalpreventprogenitorprogramsprototypereceptorresearch studyresponseresponse to injuryself-renewalsizeskillssmall moleculestemstem cellssuccesstargeted deliverytherapeutic targettooltraffickingtumortumor eradicationtumor growthtwo-photonuptakezeta potential
项目摘要
A growing body of evidence suggests that the host microenvironment plays an important role in the
regulation of both normal and malignant stem cell self-renewal and differentiation. The specific locations,
cellular components and molecular details of these stem cell niches are, however, little understood. Using in
vivo confocal and multiphoton molecular imaging techniques to study cell interactions in the intact murine bone
marrow (BM), we have defined a novel perivascular tumor and hematopoietic stem/progenitor cell (HSPC)
niche. We have identified the molecules used by leukemic cells to access this niche, however the mechanisms
governing HSC transit to these areas have not yet been defined. Moreover, the role of this niche in
maintaining normal HSCs or coordinating specific HSC cell functions is unknown. Given the importance of
HSC-based transplantation therapies as well as the clinical significance of tumor metastasis to the BM, there is
great therapeutic potential in understanding these cellular interactions. The long-term goals of our research
are, therefore, to define the molecular architecture and functional significance of this tumor and HSC niche
using state-of-the-art in vivo imaging techniques combined with cell and molecular biology approaches.
Specifically, we will 1) examine the mechanisms governing HSC transit and engraftment in these niches, 2)
determine how tumor growth impacts the niche and whether tumor and benign HSCs compete within the niche,
and 3) develop targeted nanoparticles to release encapsulated compounds in precise regions of the vascular
niche. These nanoparticles will serve as a unique tool to elucidate the critical molecules that mediate HSC and
tumor proliferation in the niche and as a prototype for a targeted drug delivery agent. Ultimately, we aim to use
the knowledge from these studies to design specific anti-tumor treatments that spare normal hematopoiesis
and to define factors that improve the efficacy of stem cell-based therapies.
越来越多的证据表明,宿主微环境在细胞凋亡过程中起着重要作用
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Dorothy A Sipkins其他文献
Dorothy A Sipkins的其他文献
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{{ truncateString('Dorothy A Sipkins', 18)}}的其他基金
Identifying and exploiting therapeutic vulnerabilities of tumor-host interactions that drive bone-to-meninges breast cancer metastasis
识别和利用导致骨到脑膜乳腺癌转移的肿瘤与宿主相互作用的治疗脆弱性
- 批准号:
10826488 - 财政年份:2023
- 资助金额:
$ 230.25万 - 项目类别:
Novel use of PI3K inhibition to prevent recurrence of B-cell acute lymphoblastic leukemia
PI3K 抑制预防 B 细胞急性淋巴细胞白血病复发的新用途
- 批准号:
10455633 - 财政年份:2021
- 资助金额:
$ 230.25万 - 项目类别:
Novel use of PI3K inhibition to prevent recurrence of B-cell acute lymphoblastic leukemia
PI3K 抑制预防 B 细胞急性淋巴细胞白血病复发的新用途
- 批准号:
10289183 - 财政年份:2021
- 资助金额:
$ 230.25万 - 项目类别:
Defining and targeting a novel pathway for central nervous system leptomeningeal metastasis
定义和靶向中枢神经系统软脑膜转移的新途径
- 批准号:
10322127 - 财政年份:2020
- 资助金额:
$ 230.25万 - 项目类别:
Defining and targeting a novel pathway for central nervous system leptomeningeal metastasis
定义和针对中枢神经系统软脑膜转移的新途径
- 批准号:
10553654 - 财政年份:2020
- 资助金额:
$ 230.25万 - 项目类别:
Defining and targeting a novel pathway for central nervous system leptomeningeal metastasis
定义和靶向中枢神经系统软脑膜转移的新途径
- 批准号:
9888134 - 财政年份:2020
- 资助金额:
$ 230.25万 - 项目类别:
Defining and targeting a novel pathway for central nervous system leptomeningeal metastasis
定义和针对中枢神经系统软脑膜转移的新途径
- 批准号:
10079480 - 财政年份:2020
- 资助金额:
$ 230.25万 - 项目类别:
Defining the Rules of Breast Cancer Cell Traffic Through Bone
定义乳腺癌细胞通过骨运输的规则
- 批准号:
10368923 - 财政年份:2017
- 资助金额:
$ 230.25万 - 项目类别:
Defining the Rules of Breast Cancer Cell Traffic Through Bone
定义乳腺癌细胞通过骨运输的规则
- 批准号:
10066311 - 财政年份:2017
- 资助金额:
$ 230.25万 - 项目类别:
Defining the Rules of Breast Cancer Cell Traffic Through Bone
定义乳腺癌细胞通过骨运输的规则
- 批准号:
9239952 - 财政年份:2017
- 资助金额:
$ 230.25万 - 项目类别:
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