The role of microglia and macrophages in the development of brain tumors

小胶质细胞和巨噬细胞在脑肿瘤发生中的作用

• 批准号: 7877736
• 负责人: Joanna Phillips
• 金额: $ 16.14万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7877736
• 关键词: Address; Advisory Committees; Blood; Blood Vessels; Brain; Brain Neoplasms; Brain imaging; Breast; Carcinoma; Cell Proliferation; Cells; Characteristics; Coculture Techniques; Color; Commit; Development; Diagnosis; Diagnostic Neoplasm Staging; Diffuse; Disease; Drug Delivery Systems; Epithelial; Epithelial Neoplasms; Excision; Exhibits; Flow Cytometry; Genetic; Glioblastoma; Glioma; Goals; Growth Factor; Harvest; Human; Imaging technology; Immigration; Immune; Immune response; Immunohistochemistry; Individual; Infiltration; Interleukin-10; Laboratories; Lead; Lesion; Lung; Macrophage Activation; Malignant Glioma; Malignant Neoplasms; Malignant neoplasm of brain; Matrix Metalloproteinases; Methods; Microglia; Microscope; Modality; Modeling; Molecular; Molecular Profiling; Monitor; Mus; Neoplasm Metastasis; Neuraxis; Neurologic; Operative Surgical Procedures; Pathology; Pattern; Peptide Hydrolases; Peripheral; Phenotype; Physicians; Play; Population; Prevalence; Primary Brain Neoplasms; Principal Investigator; Production; Radiation therapy; Regulatory T-Lymphocyte; Research; Research Ethics; Research Personnel; Research Training; Resistance; Role; Scientist; Site; Skin; Slice; Stem cells; Stimulus; Techniques; Testing; Therapeutic; Time; Training; Tumor Biology; Tumor Promotion; Tumor Tissue; Tumor stage; United States; Wild Type Mouse; career development; chemokine; cytokine; design; human data; immunoregulation; improved; in vivo; insight; macrophage; member; migration; mouse model; neoplastic cell; novel; programs; research study; response; self-renewal; tumor; tumor growth; tumor immunology; tumor progression; tumorigenesis

DESCRIPTION (provided by applicant): Project Summary: This proposal describes a 5-year-long career development program whose goal is to prepare Dr. Phillips for the role of an independent academic investigator. The project sponsor, Dr. Zena Werb, will provide the principle guidance. Dr. Werb is an internationally recognized expert on the tumor microenvironment and has a distinguished record of training independent scientists. The project co-sponsor, Dr. David Rowitch, is an internationally recognized expert on brain tumor development with a demonstrated commitment to training clinician-scientists. In addition to Drs. Werb and Rowitch, the members of the advisory committee will provide additional scientific and career development related guidance. The research program will address the hypothesis that microglia and macrophages accelerate brain tumor progression and infiltration. Microglia and macrophages are a significant component of the brain tumor microenvironment; however, their activation phenotype and function are unclear. In this project, the role of microglia and macrophages in the development of infiltrating glial tumors will be assessed in three specific aims. First, I will examine the activation patterns of microglia and macrophages in infiltrating glial tumors over time. Studies will be performed using a robust murine model for infiltrating glioma and the results will be confirmed in human tumor tissue. Second, I will determine whether microglia and macrophages promote tumor cell infiltration. Using novel imaging technology I will monitor the dynamic interactions of immune cells and tumor cells. Third, I will determine the in vivo significance of the microglial and macrophage response to brain tumor by depleting it or modifying it. The research training will also include a formal didactic program in research ethics, tumor biology, advanced molecular techniques, and tumor immunology. The UCSF Pathology Department is fully committed to Dr. Phillips' career development and UCSF provides an ideal setting for the training of independent physician scientists. Relevance: In 2007, it is estimated that 20,500 individuals will be diagnosed with cancer of the brain and nervous system in the United States. Despite current therapies infiltrating gliomas, the most common type of primary brain tumor, continues to progress and is often fatal. The research proposed in this project will yield important insight into the factors in the microenvironment that contribute to brain tumor progression and infiltration and potentially may aid in the development of new therapies for glioma.

描述（由申请人提供）：项目摘要：该提案描述了一项为期5年的职业发展计划，其目标是为菲利普斯博士准备独立学术研究员的角色。项目发起人Zena Werb博士将提供主要指导。 Werb博士是肿瘤微环境的国际公认专家，并且具有训练独立科学家的杰出记录。该项目的共同提案国David Rowitch博士是国际公认的脑肿瘤发展专家，并表现出对培训临床医生的承诺。除了Drs。咨询委员会成员Werb和Rowitch将提供与科学和职业发展有关的其他指导。该研究计划将解决以下假设：小胶质细胞和巨噬细胞加速脑肿瘤的进展和浸润。小胶质细胞和巨噬细胞是脑肿瘤微环境的重要组成部分。但是，它们的激活表型和功能尚不清楚。在该项目中，将在三个特定目标中评估小胶质细胞和巨噬细胞在浸润神经胶质肿瘤发展中的作用。首先，我将随着时间的流逝研究浸润神经胶质肿瘤中小胶质细胞和巨噬细胞的激活模式。研究将使用强大的鼠模型进行浸润神经胶质瘤进行，并将在人类肿瘤组织中确认结果。其次，我将确定小胶质细胞和巨噬细胞是否促进肿瘤细胞浸润。使用新型成像技术，我将监测免疫细胞和肿瘤细胞的动态相互作用。第三，我将通过耗尽或修改小胶质细胞和巨噬细胞对脑肿瘤的体内意义。研究培训还将包括一项关于研究伦理学，肿瘤生物学，晚期分子技术和肿瘤免疫学方面的形式教学计划。 UCSF病理学系完全致力于菲利普斯博士的职业发展，UCSF为培训独立医师科学家提供了理想的环境。相关性：2007年，据估计，在美国，将有20,500名患有大脑和神经系统癌的人。尽管当前的疗法渗透了神经胶质瘤，但最常见的原发性脑肿瘤类型仍在继续前进，而且通常是致命的。该项目中提出的研究将对微环境中的因素产生重要的见解，这些因素有助于脑肿瘤进展和浸润，并可能有助于开发新的神经胶质瘤疗法。