Molecular Therapeutics for Anaplastic Gliomas

尽管经过30多年的努力，恶性胶质瘤患者的预后仍然令人沮丧。这种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临床方案，解决对更有效治疗的需求，从而对这一不可接受的情况产生积极影响。本次研究的主题包括：发病机制，抗侵袭策略，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，每个项目都有一个翻译部分，已经或预计会导致临床研究方案。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》，它将检验一项有趣的发现，表明巨细胞病毒促进胶质瘤的发展和进展；2)《干扰素介导的对胶质瘤中基质金属蛋白酶-9基因表达和功能的抑制》，它将研究细胞因子和信号转导通路在调节一种前侵袭性酶的分泌中的作用；3)“离子通道和转运体作为新的胶质瘤特异性靶点”，它将研究如何潜在地操纵胶质瘤离子通道的异常功能，以开发新的治疗方法；4)“恶性中枢神经系统肿瘤的病毒和分子化疗”，它将利用UAB在病毒学方面的广泛专业知识，开发新的胶质瘤基因和病毒载体疗法；以及5)“TSP-1和-2在胶质瘤生物学中的作用”，它将研究如何将血栓螺旋蛋白的片段用作抗血管生成剂。这些项目将得到四个核心的支持：1)人类脑瘤组织，2)临床试验，3)脑瘤动物核心设施，以及4)生物统计学。此外，孢子还将有一个职业发展计划，旨在发展年轻研究人员在脑瘤翻译研究方面的职业生涯，以及一个开发/先导研究计划。这一孢子有来自大学及其癌症中心的强有力的机构承诺，我们完全期待与我们的机构孢子以及与全国其他孢子发展积极的合作互动。

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.