Characterization of the cellular mechanisms of radiation induced brain necrosis for clinical intervention
放射性脑坏死细胞机制的表征用于临床干预
基本信息
- 批准号:10661007
- 负责人:
- 金额:$ 17.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-02 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAdultAdverse effectsAnimal ModelAnimalsApoptosisAreaBiologicalBiological FactorsBiological MarkersBrainBrain InjuriesBrain NeoplasmsCancerousCell DeathCellsCerebrumCessation of lifeCharacteristicsChildhoodChildhood EpendymomaClinicalClinical DataCoculture TechniquesCognitiveCognitive deficitsCranial IrradiationDataDependenceDisease modelDistalDoseEducational workshopEffectivenessExposure toGliomaHumanImageIn VitroIncidenceInflammatoryIntensity modulated proton therapyInterventionInvestigationKnowledgeLaboratoriesLaboratory StudyLinear Energy TransferLinkMagnetic Resonance ImagingMalignant Childhood NeoplasmMissionModalityModelingMolecularNational Cancer InstituteNecrosisNecrosis InductionNormal tissue morphologyOrganoidsOutcomeParalysedPathway interactionsPatientsPhotonsPlanning TechniquesPreparationPreventionProcessProtonsPublic HealthRadiationRadiation InjuriesRadiation necrosisRadiation therapyRelative Biological EffectivenessResearchResearch SupportReverse engineeringRodentRoentgen RaysRoleScanningSignal TransductionSurvivorsTechniquesTissuesTransgenic AnimalsTreatment Side EffectsUncertaintybrain cellbrain tissuecancer cellcancer rehabilitationcancer therapycell injurycell typeclinical practiceclinically relevantcombatdesigndisorder controlhigh riskimaging platformimprovedin vivoin vivo Modelinduced pluripotent stem cellinsightirradiationmedulloblastomanovelpediatric patientspharmacologicpre-clinicalpredictive modelingproton beamproton therapyradiation effectradiation responseradiation riskresponseside effecttreatment planningtreatment responsetumor
项目摘要
Project Summary/Abstract
Cure rates for childhood cancers have improved. Unfortunately, many survivors now live with life-long side
effects from treatment itself. Radiation therapy, used for brain tumors, is particularly damaging. The most
serious side effect is necrosis which can result in weakness, paralysis or even death. Proton therapy is an
increasingly popular radiation modality. Proton therapy reduces exposure to normal tissues and the reby
may decrease the incidence of cognitive deficits following radiation. However, recent studies, including our
own suggest that certain areas of proton beams may be more damaging to brain tissue than others
potentially leading to higher rates of necrosis. Here we will develop high accuracy models to correlate
necrosis with the physical parameters of proton beams. These models will include multi-cell type human
brain “organoids” as well as rodent animal models. Using these models as well as clinical data, we will
identify the physical factors of proton therapy which may lead to necrosis. This is significant in that this data
may be used to design safer proton therapy treatments in which the most biologically effective portions of
beams are solely placed within the tumor. This should reduce necrosis and improve disease control. In a
second component of our study, we will examine the molecular mechanisms of necrosis. Rather than being
simple dis-organized death, we will determine if radiation induces an orderly programmed cell death
pathway. We will conduct the following aims; (1) relate the physical factors of proton beams with biological
response, (2) explore the cellular and molecular mechanisms of radiation induced brain damage and (3)
validate the clinical consequences of variability in the effectiveness of proton beams. The knowledge gained
will quickly influence the treatment of brain tumor patients and expedite the clinical introduction of agents
and approaches to combat the negative effects of radiation on the brain.
项目总结/摘要
儿童癌症的治愈率有所提高。不幸的是,许多幸存者现在生活与终身的一面
治疗本身的影响。放射治疗,用于脑肿瘤,是特别有害的。最
严重的副作用是坏死,可导致虚弱、瘫痪甚至死亡。质子治疗是一种
越来越流行的放射疗法质子治疗减少了对正常组织的暴露,
可以降低辐射后认知缺陷的发生率。然而,最近的研究,包括我们
他自己的研究表明,质子束的某些区域对脑组织的损害可能比其他区域更大
可能导致更高的坏死率。在这里,我们将开发高准确度模型来进行关联
质子束物理参数造成的坏死这些模型将包括多细胞类型的人类
脑“类器官”以及啮齿动物模型。使用这些模型以及临床数据,我们将
确定质子治疗可能导致坏死的物理因素。这一数据的重要性在于,
可用于设计更安全的质子治疗,其中,
光束仅放置在肿瘤内。这将减少坏死并改善疾病控制。中
我们研究的第二个组成部分,我们将研究坏死的分子机制。而不是
简单的无序死亡,我们将确定辐射是否会诱导有序的程序性细胞死亡
通路我们将进行以下工作:(1)将质子束的物理因素与生物学特性联系起来,
反应,(2)探索放射性脑损伤的细胞和分子机制,(3)
验证质子束有效性变化的临床后果。获得的知识
将迅速影响脑肿瘤患者的治疗,并加快药物的临床引入,
以及对抗辐射对大脑的负面影响的方法。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cognitive and Imaging Differences After Proton and Photon Whole Brain Irradiation in a Preclinical Model.
- DOI:10.1016/j.ijrobp.2021.09.005
- 发表时间:2022-02-01
- 期刊:
- 影响因子:0
- 作者:Tang TT;Zawaski JA;Kesler S;Beamish CA;Inoue T;Perez EC;Bronk L;Poenisch F;Briere TM;Sabek OM;Grosshans DR;Waleed Gaber M
- 通讯作者:Waleed Gaber M
Cranial irradiation induces axon initial segment dysfunction and neuronal injury in the prefrontal cortex and impairs hippocampal coupling.
颅脑照射会引起轴突起始段功能障碍和前额皮质神经元损伤,并损害海马耦合。
- DOI:10.1093/noajnl/vdaa058
- 发表时间:2020
- 期刊:
- 影响因子:0
- 作者:Zhang,Die;Zhou,Wei;Lam,ThanhThai;Li,Yan;Duman,JosephG;Dougherty,PatrickM;Grosshans,DavidR
- 通讯作者:Grosshans,DavidR
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{{ truncateString('DAVID R GROSSHANS', 18)}}的其他基金
Determining the optimal ion and fractionation scheme for the treatment of GBM in a comprehensive human organoid model
在综合人体类器官模型中确定治疗 GBM 的最佳离子和分级方案
- 批准号:
10360627 - 财政年份:2021
- 资助金额:
$ 17.49万 - 项目类别:
Project 3: Enhanced Sensitivity of Tumors to Proton Beam Therapy: Mechanisms and Biomarkers.
项目 3:增强肿瘤对质子束治疗的敏感性:机制和生物标志物。
- 批准号:
10491858 - 财政年份:2021
- 资助金额:
$ 17.49万 - 项目类别:
Characterization of the cellular mechanisms of radiation induced brain necrosis for clinical intervention
放射性脑坏死细胞机制的表征用于临床干预
- 批准号:
10273297 - 财政年份:2021
- 资助金额:
$ 17.49万 - 项目类别:
Project 3: Enhanced Sensitivity of Tumors to Proton Beam Therapy: Mechanisms and Biomarkers.
项目 3:增强肿瘤对质子束治疗的敏感性:机制和生物标志物。
- 批准号:
10270307 - 财政年份:2021
- 资助金额:
$ 17.49万 - 项目类别:
Determining the optimal ion and fractionation scheme for the treatment of GBM in a comprehensive human organoid model
在综合人体类器官模型中确定治疗 GBM 的最佳离子和分级方案
- 批准号:
10570305 - 财政年份:2021
- 资助金额:
$ 17.49万 - 项目类别:
Characterization of the cellular mechanisms of radiation induced brain necrosis for clinical intervention
放射性脑坏死细胞机制的表征用于临床干预
- 批准号:
10460578 - 财政年份:2021
- 资助金额:
$ 17.49万 - 项目类别:
(PQ 9) Synaptic basis of deficits in attention and executive function following cranial radiation
(PQ 9) 颅脑辐射后注意力和执行功能缺陷的突触基础
- 批准号:
9763496 - 财政年份:2016
- 资助金额:
$ 17.49万 - 项目类别:
(PQ 9) Synaptic basis of deficits in attention and executive function following cranial radiation
(PQ 9) 颅脑辐射后注意力和执行功能缺陷的突触基础
- 批准号:
9172110 - 财政年份:2016
- 资助金额:
$ 17.49万 - 项目类别:
Mapping Proton RBE Variability Using Automated Biology and Monte Carlo Techniques
使用自动化生物学和蒙特卡罗技术绘制质子 RBE 变异性
- 批准号:
8754187 - 财政年份:2014
- 资助金额:
$ 17.49万 - 项目类别:
Mapping Proton RBE Variability Using Automated Biology and Monte Carlo Techniques
使用自动化生物学和蒙特卡罗技术绘制质子 RBE 变异性
- 批准号:
8887318 - 财政年份:2014
- 资助金额:
$ 17.49万 - 项目类别:
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