Normal & Neoplastic Growth in the Brain

普通的

基本信息

批准号：
8396597
负责人：
SUZANNE J BAKER
金额：
$ 2.31万
依托单位：
ST. JUDE CHILDREN'S RESEARCH HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8396597
关键词：
Accounting Address Adult Adverse effects Automobile Driving Bioinformatics Biological Biological Models Biological Process Biology Biopsy Biotechnology Brain Brain Neoplasms Brain Stem Cell physiology Cells Central Nervous System Neoplasms Cerebellum Child Childhood Childhood Brain Neoplasm Childhood Central Nervous System Neoplasm Childhood Glioma Childhood Medulloblastomas Choroid Plexus Carcinoma Chromosome abnormality Clinical Investigator Clinical Research Clinical Trials Collaborations Collection Communities DNA Damage DNA Repair Data Development Developmental Process Diagnosis Diffuse Disease Disease model Frequencies Funding Gene Expression Genes Genome Genomics Glioma Goals Growth Growth and Development function Histopathology Human Incidence Individual Infant Institution Knowledge Lead Life Long-Term Survivors Magnetic Resonance Imaging Maintenance Malignant Childhood Neoplasm Malignant Neoplasms Malignant neoplasm of brain Mean Survival Times MicroRNAs Modeling Molecular Molecular Abnormality Molecular Target Morbidity - disease rate Mutation National Cancer Institute Nature Neoplasms Nervous system structure New Agents Oncogenic Operative Surgical Procedures Pathogenesis Pathway interactions Patients Preclinical Testing Primary Neoplasm Process Publications Publishing Radiation Reagent Regimen Regulation Research Research Personnel Research Project Grants Resources Rhabdoid Tumor Risk Sampling Series Signal Pathway Signal Transduction Signal Transduction Pathway Solid Stem cells Structure Subgroup Survival Rate System Techniques Tern Therapeutic Therapeutic Agents Therapeutic Intervention Time Tissues Transduction Gene Translating Translational Research Tumor Biology United States Work aggressive therapy cancer stem cell clinical material effective therapy experience fight against forging gene function genome wide association study improved inhibitor/antagonist insight interest medulloblastoma mortality mouse model neoplastic cell neuropathology new therapeutic target novel novel therapeutics outcome forecast patient population peer pressure programs prospective response skills small molecule smoothened signaling pathway success tool tumor tumorigenesis

项目摘要

DESCRIPTION (provided by Project Leader): Brain tumors are the most common group of solid malignancies in children, causing devastating mortality and morbidity in a very understudied patient population. The goal of this program project is to improve understanding and treatment of pediatric brain tumors. During the first funding period, Project leaders worked together to develop novel mouse models that provided key biological insights into cerebellar growth regulation and medulloblastoma development, used these models for relevant preclinical testing of new therapeutic agents, and translated research results into clinical trials. The current application expands the focus of the program to encompass additional pediatric brain tumors. Five interactive projects plan directed studies of growth regulation in the brain using human tumors and mouse models to study signal transduction, gene expression and function in the context of pediatric brain tumors and brain development. An Administrative Core, a Bioinformatics and Biotechnology Core and a Neuropathology Core provide essential support to all projects. In Project 1, S. Baker investigates the molecular pathogenesis of pediatric high-grade glioma taking advantage of a large collection of primary tumors and novel mouse models for glioma that she developed. In Project 2, T. Curran investigates the mechanism of action of a small molecule inhibitor of Hedgehog signaling that he showed ablated medulloblastoma in his model systems. In Project 3, R. Gilbertson will define molecular subgroups of medulloblastoma through analysis of human tumors and development of mouse models, and will characterize cancer stem cells and their niches in subclasses of medulloblastoma. In Project 4, P. McKinnon will further his analysis of defective DNA damage response underlying brain tumor development and will determine the effects of DNA repair inhibitors as a therapeutic approach for brain tumors. In Project 5, M. Roussel and C. Sherr will explore mechanisms of oncogenic transformation in medulloblastoma, and will define microRNAs that modulate gene expression in cerebellar development and medulloblastoma. Integrated analyses within the group will identify common and unique signal transduction pathways in pediatric brain tumorigenesis.

描述（由项目负责人提供）：脑肿瘤是儿童中最常见的固体恶性肿瘤群体，导致毁灭性的死亡率和发病率在非常研究的患者人群中。该计划项目的目的是改善对小儿脑肿瘤的理解和治疗。在第一个资金期间，项目负责人共同开发了新型的小鼠模型，这些模型为小脑生长调节和髓母细胞瘤的发展提供了关键的生物学见解，使用这些模型对新的治疗剂进行了相关的临床前测试，并将研究结果转化为临床试验。当前的应用程序扩大了该程序的重点，以涵盖其他小儿脑肿瘤。五个互动项目计划使用人类肿瘤和小鼠模型对大脑中生长调节的指示研究，以研究小儿脑肿瘤和脑发育的背景下的信号转导，基因表达和功能。行政核心，生物信息学和生物技术核心以及神经病理学核心为所有项目提供了基本的支持。在项目1中，贝克（S. Baker）研究了她开发的大量原发性肿瘤和新型小鼠模型的小儿高级神经胶质瘤的分子发病机理。在项目2中，T。Curran研究了刺猬信号的小分子抑制剂的作用机理，他在模型系统中显示出消融的髓母细胞瘤。在项目3中，吉尔伯逊（R. Gilbertson）将通过分析人类肿瘤和小鼠模型的发展来定义髓母细胞瘤的分子亚组，并将表征癌干细胞及其壁ni，中髓母细胞瘤的亚类。在项目4中，P。McKinnon将进一步分析他对脑瘤发育的有缺陷DNA损伤反应的分析，并将确定DNA修复抑制剂作为脑肿瘤的治疗方法的影响。在项目5中，M。Roussel和C. Sherr将探索髓母细胞瘤中致癌转化的机制，并将定义在小脑发育和髓母细胞瘤中调节基因表达的microRNA。该组内的综合分析将确定小儿脑肿瘤发生中常见和独特的信号转导途径。