Role of NKCC1 on Brain Tumor Stem Cell Migration After EGF and Slit-2 Stimulation
EGF 和 Slit-2 刺激后 NKCC1 对脑肿瘤干细胞迁移的作用
基本信息
- 批准号:7865447
- 负责人:
- 金额:$ 49.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-06-15 至 2015-02-28
- 项目状态:已结题
- 来源:
- 关键词:AccountingAffectAnionsBehaviorBrainBrain NeoplasmsCell VolumesCellsCharacteristicsChloride IonChloridesDiffuseDiseaseDrosophila sli proteinEpidermal Growth FactorEpidermal Growth Factor ReceptorExcisionGlioblastomaGliomaGoalsGrowthGrowth FactorHumanIn VitroIncidenceIndividualInfiltrationIon CotransportKnowledgeLinkMalignant GliomaMalignant Intracranial NeoplasmMalignant NeoplasmsMeasuresMediatingMethylationMigration AssayMolecularNeoplasm MetastasisOperative Surgical ProceduresPathway interactionsPatientsPatternPlayPopulationPrimary Brain NeoplasmsPrimary NeoplasmProcessQuinonesRadiation therapyRecurrenceRegulationResearchRoleSignal PathwaySignal TransductionStem cellsSurvival RateSystemTestingTherapeuticTumor AngiogenesisTumor Cell InvasionTumor Stem CellsWorkaxonal guidancecancer cellcell motilitychemotherapychloride-cotransporter potassiumglioma cell linein vivomedulloblastomamigrationneoplastic cellnerve stem cellnew therapeutic targetoutcome forecastoverexpressionpreventprotein expressionpublic health relevanceresponsesodium-potassium-chloride cotransporter 1 proteintumor
项目摘要
DESCRIPTION (provided by applicant): Glioblastoma multiforme (GBM), the most common and devastating intracranial malignant tumor accounts for 20% of all primary brain tumors and has a median survival rate of only 14 months. Cancer cells often disseminate far from primary tumors and individual glioma cells migrate from the gross tumor into the surrounding parenchyma, making complete surgical resection nearly impossible. This migratory capacity of malignant gliomas represents the greatest challenge to any potential therapy in spite of advances in surgery, chemotherapy and radiotherapy and growth of the remaining invasive cells leads to a recurrence incidence of 99%. What exactly regulates the migratory capacity of brain tumor cells is not fully understood and need to be studied. The main goal of this proposal is to understand the link between known pro- migratory signals such as epidermal growth factor (EGF) and Slit proteins with cell volume regulation. EGF and Slit proteins may play an important role in the modulation of invasive and migratory ability of GBM derived stem cells through Akt pathway that in turn regulates the activation of ion cotransport NKCC1. We propose to study invasive patterns and cell volume changes resulting in the extension of a leading process of a migrating cell, using various cell migration assays and measuring intracellular anion concentration. The results obtained from this work will help us understand the downstream signaling pathways involved in the activation of cascade mechanism responsible for brain tumor cell migration. Further, such knowledge will undoubtedly result in better therapeutic alternatives to current sub-optimal treatments for this devastating disease.
PUBLIC HEALTH RELEVANCE: Glioblastoma multiforme (GBM) is the most common and devastating primary malignant tumor. Our project aims to study the migration of GBM-derived Brain Tumor Stem Cells (BTSCs). BTSCs are thought to be responsible for maintaining the bulk of the tumor and to induce recurrence after surgical resection, nevertheless the molecular mechanisms that regulate their migration are not known. In this study, we propose to understand the role of pro-migratory signals in brain tumor invasion in order to increase the available targets to prevent brain tumor dispersal.
描述(申请人提供):多形性胶质母细胞瘤(GBM)是最常见和最具破坏性的颅内恶性肿瘤,占所有原发脑肿瘤的20%,中位生存期仅为14个月。癌细胞通常扩散到远离原发肿瘤的地方,个别胶质瘤细胞从肉眼肿瘤转移到周围的实质,使得完全手术切除几乎是不可能的。恶性胶质瘤的这种迁移能力是对任何潜在治疗方法的最大挑战,尽管手术、化疗和放射治疗取得了进展,剩余的侵袭细胞的生长导致了99%的复发率。究竟是什么调节了脑瘤细胞的迁移能力,目前还不完全清楚,还需要研究。这项建议的主要目的是了解已知的促迁移信号,如表皮生长因子(EGF)和Sit蛋白与细胞体积调节之间的联系。EGF和Sit蛋白可能通过Akt途径调节GBM来源干细胞的侵袭和迁移能力,进而调节离子共转运蛋白NKCC1的激活。我们建议使用各种细胞迁移分析和测量细胞内阴离子浓度来研究导致迁移细胞主导过程延长的侵袭模式和细胞体积变化。这项工作的结果将有助于我们了解参与激活脑瘤细胞迁移的级联机制的下游信号通路。此外,这些知识无疑将导致更好的治疗方案,而不是目前这种毁灭性疾病的次佳治疗方案。
公共卫生相关性:多形性胶质母细胞瘤(GBM)是最常见和破坏性最大的原发恶性肿瘤。本课题旨在研究GBM来源的脑肿瘤干细胞(BTSC)的迁移。BTSCs被认为是维持大部分肿瘤并导致手术切除后复发的原因,然而,调控其迁移的分子机制尚不清楚。在这项研究中,我们建议了解亲迁移信号在脑肿瘤侵袭中的作用,以增加有效的靶点来防止脑肿瘤的扩散。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
ALFREDO QUINONES-HINOJOSA其他文献
ALFREDO QUINONES-HINOJOSA的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('ALFREDO QUINONES-HINOJOSA', 18)}}的其他基金
A Bioprinted Volumetric Model of Vascularized Glioblastoma
血管化胶质母细胞瘤的生物打印体积模型
- 批准号:
10717766 - 财政年份:2023
- 资助金额:
$ 49.74万 - 项目类别:
BMP4 Engineered Mesenchymal Stem Cell Therapy for Glioblastoma
BMP4 工程间充质干细胞治疗胶质母细胞瘤
- 批准号:
9188284 - 财政年份:2015
- 资助金额:
$ 49.74万 - 项目类别:
BMP4 Engineered Mesenchymal Stem Cell Therapy for Glioblastoma
BMP4 工程间充质干细胞治疗胶质母细胞瘤
- 批准号:
9065529 - 财政年份:2015
- 资助金额:
$ 49.74万 - 项目类别:
Role of NKCC1 on Brain Tumor Stem Cell Migration After EGF and Slit-2 Stimulation
EGF 和 Slit-2 刺激后 NKCC1 对脑肿瘤干细胞迁移的作用
- 批准号:
8660402 - 财政年份:2013
- 资助金额:
$ 49.74万 - 项目类别:
Role of NKCC1 on Brain Tumor Stem Cell Migration After EGF and Slit-2 Stimulation
EGF 和 Slit-2 刺激后 NKCC1 对脑肿瘤干细胞迁移的作用
- 批准号:
8436280 - 财政年份:2010
- 资助金额:
$ 49.74万 - 项目类别:
Role of NKCC1 on Brain Tumor Stem Cell Migration After EGF and Slit-2 Stimulation
EGF 和 Slit-2 刺激后 NKCC1 对脑肿瘤干细胞迁移的作用
- 批准号:
8625346 - 财政年份:2010
- 资助金额:
$ 49.74万 - 项目类别:
Role of NKCC1 on Brain Tumor Stem Cell Migration After EGF and Slit-2 Stimulation
EGF 和 Slit-2 刺激后 NKCC1 对脑肿瘤干细胞迁移的作用
- 批准号:
8257549 - 财政年份:2010
- 资助金额:
$ 49.74万 - 项目类别:
Role of NKCC1 on Brain Tumor Stem Cell Migration After EGF and Slit-2 Stimulation
EGF 和 Slit-2 刺激后 NKCC1 对脑肿瘤干细胞迁移的作用
- 批准号:
8088160 - 财政年份:2010
- 资助金额:
$ 49.74万 - 项目类别:
Migration of Human Neural Stem Cells In Vitro and In Vivo
人类神经干细胞的体外和体内迁移
- 批准号:
7907627 - 财政年份:2006
- 资助金额:
$ 49.74万 - 项目类别:
Migration of Human Neural Stem Cells In Vitro and In Vivo
人类神经干细胞的体外和体内迁移
- 批准号:
7131997 - 财政年份:2006
- 资助金额:
$ 49.74万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 49.74万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 49.74万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 49.74万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 49.74万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 49.74万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 49.74万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 49.74万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 49.74万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 49.74万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 49.74万 - 项目类别:
Studentship