权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Regulation and function of the vascular niche in glioma recurrance

神经胶质瘤复发中血管生态位的调节和功能

基本信息

批准号：
8741084
负责人：
WILLIAM A WEISS
金额：
$ 8.41万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-26 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8741084
关键词：
Adult Affect Astrocytoma Automobile Driving Blood Vessels Brain Neoplasms Cells Coculture Techniques Conditioned Culture Media Data Diffuse Diffusion Magnetic Resonance Imaging ES01 ES05 Endothelial Cells Extracellular Matrix Gene Expression Gene Expression Profiling Genes Genetic Engineering Glioblastoma Glioma Human Immune In Vitro Infiltration Integrins Malignant Glioma Measures Mechanics Mediating Mesenchymal Microglia Modeling Molecular Molecular Target Monitor Mus Natural regeneration Oligodendroglia Oligodendroglioma-Astrocytoma Patients Property Radiation Radiation therapy Radiation-Induced Change Recurrence Regulation Relapse Signal Transduction Signal Transduction Pathway Stem cells Stream Subgroup TGFB1 gene Testing Time Tissues Transgenic Mice Transgenic Model Transplantation Tumor Tissue Vascularization Xenograft Model brain cell cellular targeting chemotherapy cytokine human NCOR1 protein insight interstitial irradiation malignant breast neoplasm mouse model neoplastic cell nerve stem cell notch protein oligodendroglioma outcome forecast progenitor radiation resistance regenerative response stem cell niche tumor tumor microenvironment viscoelasticity white matter

项目摘要

A.2. Gene expression analysis of gliomas, the most common brain tumor in adults, identifies subtypes enriched for progenitor and NSC genes. Diffuse gliomas are divided into astrocytomas, oligodendrogliomas, and oligoastrocytomas. Among malignant gliomas, (oligodendroglioma grade 3, astrocytoma grade 3-4), oligodendroglioma shows the most favorable prognosis Gene expression studies demonstrate four subtypes of grade 4 glioma (glioblastoma multiforme or GBM). Oligodendrogliomas and a subgroup of proneural GBMs express oligodendrocyte progenitor cell (OPC)-related genes. In contrast, mesenchymal GBMs display genes associated with NSCs, and a microenvironment rich in vascular and immune cells. GBM subclasses show distinct signal transduction pathways. Proneural and mesenchymal GBM subtypes also persist in vitro, where mesenchymal GBMs are associated with TGFB-, integrin- and endothelial-signaling. In genetically engineered murine astrocytoma models, tumors can originate from SVZ NSCs. We and others have recently demonstrated that oligodendroglioma, the most proneural glioma, is derived from OPCs in white matter, partly explaining the favorable prognosis and response to chemotherapy. We propose that the cell of origin for glioma subtypes also influences response to therapy and composition of the tumor microenvironment.

A.2.神经胶质瘤是成人中最常见的脑肿瘤，其基因表达分析鉴定了富含祖细胞和NSC基因的亚型。弥漫性胶质瘤分为星形细胞瘤、少突胶质细胞瘤和少突星形细胞瘤。在恶性胶质瘤（少突胶质细胞瘤3级，星形细胞瘤3-4级）中，少突胶质细胞瘤显示出最有利的预后。基因表达研究证实了4级胶质瘤的四种亚型（多形性胶质母细胞瘤或GBM）。少突胶质细胞瘤和前神经GBM亚群表达少突胶质细胞祖细胞（OPC）相关基因。相反，间充质GBM显示与NSC相关的基因，以及富含血管和免疫细胞的微环境。GBM亚类显示不同的信号转导途径。前神经和间充质GBM亚型在体外也持续存在，其中间充质GBM与TGFB、整合素和内皮信号传导相关。在基因工程改造的鼠星形细胞瘤模型中，肿瘤可以起源于SVZ NSC。我们和其他人最近证实，少突胶质细胞瘤是最常见的神经胶质瘤，来源于白色物质中的OPCs，部分解释了其良好的预后和对化疗的反应。我们提出胶质瘤亚型的起源细胞也影响对治疗的反应和肿瘤微环境的组成。