Molecular Therapeutics for Anaplastic Gliomas

间变性胶质瘤的分子治疗

• 批准号: 7454560
• 负责人: G. YANCEY GILLESPIE
• 金额: $ 107.3万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-05 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7454560
• 关键词: Address; Angiogenesis Inhibitors; Animals; Biology; Biometry; Brain Neoplasms; Cancer Center; Clinical Protocols; Clinical Research Protocols; Clinical Trials; Core Facility; Cytokine Signaling; Cytomegalovirus; Development; Enzymes; Gelatinase B; Gene Expression; Glioma; Human; Interferons; Invasive; Ion Channel; Laboratories; Lead; Malignant Glioma; Malignant neoplasm of brain; Malignant neoplasm of central nervous system; Mediating; Modality; Molecular; Pathogenesis; Patients; Program Development; Protein Fragment; Purpose; Reproduction spores; Research; Research Personnel; Research Project Grants; Role; Scientist; Signal Transduction Pathway; Therapeutic; Thrombospondin 1; Translating; Translational Research; Tumor Tissue; Universities; Viral; Viral Genes; Viral Vector; antiangiogenesis therapy; base; career; chemotherapy; gene therapy; novel; outcome forecast; programs; virology

In spite of over thirty years of effort, the prognosis for patients afflicted with malignant gliomas remains dismal. It is the purpose of this Brain Cancer SPORE to have a positive impact on this unacceptable situation by translating the laboratory-based efforts of five groups of scientists into clinical protocols that address the needs for more effective treatments. The themes that will be investigated in this SPORE include: Pathogenesis, Anti-Invasion Strategies, Glioma-Host Interactions, Viral and Gene Therapy, and Anti-Angiogenesis Strategies. Five research projects are proposed, each of which has a translational component that has or is expected to lead to a clinical research protocol. These include: 1) "The role of Human Cytomegalovirus in Human Malignant Glioma Pathogenesis" which will examine an intriguing finding that suggests that cytomegalovirus promotes the development and progression of gliomas; 2) "Interferon-Mediated Suppression of MMP-9 Gene Expression and Function in Gliomas" which will examine the role of cytokines and signal transduction pathways in regulating secretion of a pro-invasive enzyme; 3) "Ion Channels and Transporters as Novel, Glioma-specific Targets", which will examine how abnormal functioning of glioma ion channels can be potentially manipulated to develop new treatment modalities, 4) "Viral and Molecular Chemotherapy of Malignant CNS Tumors", which will utilize the extensive expertise in virology available at UAB to development new gene and viral vector therapies for gliomas, and 5) "The Role of TSP-1 and -2 in the Biology of Gliomas", which will investigate how to utilize fragments of the protein thrombospondin as anti-angiogenic agents. These projects will be supported by Four Cores: 1) Human Brain Tumor Tissue, 2) Clinical Trials; 3) Brain Tumor Animal Core Facility; and 4) Biostatistics. In addition, the SPORE will have a Career Development Program directed at developing the careers of young investigators in brain tumor translational research and a Developmental/Pilot Research Program. This SPORE has strong institutional commitments from both the University and its Cancer Center, and we fully expect to develop active collaborative interactions with both our institutional SPOREs as well as with other SPOREs nationally.

尽管经过三十多年的努力，恶性神经胶质瘤患者的预后仍然令人沮丧。该脑癌孢子的目的是通过将五组科学家基于实验室的努力转化为满足更有效治疗需求的临床方案，对这种不可接受的情况产生积极影响。本次 SPORE 将研究的主题包括：发病机制、抗入侵策略、神经胶质瘤-宿主相互作用、病毒和基因治疗以及抗血管生成策略。提出了五个研究项目，每个项目都有一个已经或有望形成临床研究方案的转化部分。其中包括：1）“人类巨细胞病毒在人类恶性胶质瘤发病机制中的作用”，该研究将研究一项有趣的发现，表明巨细胞病毒促进胶质瘤的发生和进展； 2）“干扰素介导的神经胶质瘤中MMP-9基因表达和功能的抑制”将检查细胞因子和信号转导途径在调节促侵袭酶分泌中的作用； 3)“离子通道和转运蛋白作为新的神经胶质瘤特异性靶标”，将研究如何潜在地操纵神经胶质瘤离子通道的异常功能来开发新的治疗方式，4)“恶性中枢神经系统肿瘤的病毒和分子化疗”，其中将利用 UAB 提供的广泛的病毒学专业知识来开发针对神经胶质瘤的新基因和病毒载体疗法，以及 5)“TSP-1 和 -2 在神经胶质瘤生物学”，它将研究如何利用血小板反应蛋白片段作为抗血管生成剂。这些项目将得到四个核心的支持：1）人脑肿瘤组织，2）临床试验； 3）脑肿瘤动物核心设施； 4) 生物统计学。此外，SPORE还将有一个职业发展计划，旨在发展脑肿瘤转化研究领域的年轻研究人员的职业生涯，以及一个发展/试点研究计划。该 SPORE 得到了大学及其癌症中心的强有力的机构承诺，我们完全期望与我们的机构 SPORE 以及全国其他 SPORE 建立积极的合作互动。