Efficacy and toxicity of TRAIL against gliomas
TRAIL对抗胶质瘤的功效和毒性
基本信息
- 批准号:7340756
- 负责人:
- 金额:$ 18.17万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-01-05 至 2010-12-31
- 项目状态:已结题
- 来源:
- 关键词:AdenovirusesAnimal ModelApoptosisApoptoticAstrocytesBIRC4 geneBrainBrain NeoplasmsBystander EffectCaspaseCell LineCell surfaceCellsCessation of lifeChemicalsClinical TrialsDataDisease regressionDominant-Negative MutationDown-RegulationFamily memberGliomaHumanIn VitroInduction of ApoptosisLifeLigandsLocal TherapyMalignant - descriptorMalignant GliomaMalignant NeoplasmsMediatingModelingMorbidity - disease rateMusNonmetastaticNormal CellNormal tissue morphologyNude MiceOperative Surgical ProceduresOrganPathway interactionsPrimatesRNA InterferenceRadiation therapyRecurrenceRelative (related person)Research PersonnelResistanceRodentRodent ModelRoleSliceStandards of Weights and MeasuresTNFSF10 geneTestingTherapeuticTissuesToxic effectTumor Necrosis Factor-alphaTumor Necrosis FactorsXenograft ModelXenograft procedureanalogbasebrain cellchemotherapyhuman TNF proteinimprovedin vivoinhibitor/antagonistinterestmortalityneoplastic cellnovelprogramsreceptorresistance mechanismresponsesurvivintumor
项目摘要
Malignant gliomas are associated with high morbidity and mortality. Standard therapies such as surgery, radiation
therapy and chemotherapy do not offer effective options and local recurrence is the norm. However, being locally
malignant nonmetastatic tumors, they may be amenable to control using effective tumor-targeted local therapies. TNF-
related apoptosis inducing ligand (TRAIL/Apo2L) induces apoptosis in gliomas in vitro and prolongs survival in
xenograft rodent models. It is nontoxic to normal organs in animal models including primates. However, the efficacy of
local intracranial delivery of TRAIL, its toxicity to brain-adjacent-to-tumor and selectivity towards gliomas in humans
remain to be fully explored. In this study, we will test the efficacy and toxicity of TRAIL in a living human glioma & brain
slice model and in xenograft models. Our preliminary data suggests that soluble TRAIL is active against gliomas in vitro
and in vivo and that its activity is modulated by the Akt pathway. We hypothesize that: a) soluble untagged TRAIL will
be effective against human glioma and nontoxic to normal brain 2) Inhibition of Akt can sensitize human gliomas to
TRAIL and increase survival in a glioma model 3) resistance to TRAIL is mediated by differing mechanisms in normal
and tumor cells permitting selective targeting of resistance mechanisms in tumors. To test these hypotheses, we
propose the following specific aims 1) determine the efficacy and toxicity of soluble untagged TRAIL expressed by an
adenovirus in a mouse intracranial xenograft and an ex-vivo living human glioma slice model. 2) determine the in vivo
effect and relevance of Akt inhibition to TRAIL-induced apoptosis in gliomas. 3) determine the mechanisms of TRAIL
resistance in normal brain and resistant glioma cells in human living tumor/ brain slice model and the effects of
modulating these mechanisms on TRAIL sensitivity. The combined use of human living brain slices and intracranial
xenograft models are aimed at providing direct and highly relevant data on the efficacy of TRAIL against human gliomas
and its toxicity against the brain . The results of this study could also potentially provide a basis for clinical trials using
TRAIL or analogues against gliomas and allow rational selection of agents to modulate the tumor resistance to TRAIL.
恶性神经胶质瘤具有高发病率和高死亡率。标准疗法,比如手术,放疗
项目成果
期刊论文数量(0)
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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VINAY K PUDUVALLI其他文献
VINAY K PUDUVALLI的其他文献
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{{ truncateString('VINAY K PUDUVALLI', 18)}}的其他基金
A Novel Hsp90 Inhibitor as a Chemo and Radiosensitizer in Adults with Glioblastoma
一种新型 Hsp90 抑制剂作为成人胶质母细胞瘤的化疗和放射增敏剂
- 批准号:
10480888 - 财政年份:2019
- 资助金额:
$ 18.17万 - 项目类别:
A Novel Hsp90 Inhibitor as a Chemo and Radiosensitizer in Adults with Glioblastoma
一种新型 Hsp90 抑制剂作为成人胶质母细胞瘤的化疗和放射增敏剂
- 批准号:
10397791 - 财政年份:2019
- 资助金额:
$ 18.17万 - 项目类别:
A Novel Hsp90 Inhibitor as a Chemo and Radiosensitizer in Adults with Glioblastoma
一种新型 Hsp90 抑制剂作为成人胶质母细胞瘤的化疗和放射增敏剂
- 批准号:
10687871 - 财政年份:2019
- 资助金额:
$ 18.17万 - 项目类别:
Patient Oriented Research Program in Neuro-oncology
以患者为中心的神经肿瘤学研究计划
- 批准号:
8731813 - 财政年份:2012
- 资助金额:
$ 18.17万 - 项目类别:
Patient Oriented Research Program in Neuro-oncology
以患者为中心的神经肿瘤学研究计划
- 批准号:
8846550 - 财政年份:2012
- 资助金额:
$ 18.17万 - 项目类别:
Patient Oriented Research Program in Neuro-oncology
以患者为中心的神经肿瘤学研究计划
- 批准号:
8459885 - 财政年份:2012
- 资助金额:
$ 18.17万 - 项目类别:
Patient Oriented Research Program in Neuro-oncology
以患者为中心的神经肿瘤学研究计划
- 批准号:
8300649 - 财政年份:2012
- 资助金额:
$ 18.17万 - 项目类别:
Efficacy and toxicity of TRAIL against gliomas
TRAIL对抗胶质瘤的功效和毒性
- 批准号:
7167160 - 财政年份:2006
- 资助金额:
$ 18.17万 - 项目类别:
Efficacy and toxicity of TRAIL against gliomas
TRAIL对抗胶质瘤的功效和毒性
- 批准号:
7749939 - 财政年份:2006
- 资助金额:
$ 18.17万 - 项目类别:
Efficacy and toxicity of TRAIL against gliomas
TRAIL对抗胶质瘤的功效和毒性
- 批准号:
7033212 - 财政年份:2006
- 资助金额:
$ 18.17万 - 项目类别:
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