RECEPTOR-TARGETED PROTEIN TOXINS FOR BRAIN TUMOR THERAPY

用于脑肿瘤治疗的受体靶向蛋白毒素

• 批准号: 2100835
• 负责人: Nathan A. Berger
• 金额: $ 15.56万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2100835
• 关键词: brain neoplasms; growth factor receptors; neoplasm /cancer chemotherapy; toxin

This proposal is to develop a Brain Tumor Research Center at Case Western Reserve University and University Hospitals of Cleveland whose central focus will be the development application of membrane targeted, peptide toxins to improve therapy for malignant brain tumors. The proposal constitutes a synergistic, interdisciplinary, interaction of the clinical, scientific and organizational expertise of physicians and scientists from the Departments of Neurosurgery, Neurology, Neurosciences, Molecular Biology, Medicine, Pediatrics and the Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University. Project 1 will examine the fundamental role of the epidermal growth factor receptor (EGF-R) and the associated signal transduction processes in establishing and maintaining the transformed state in gliomas. Project 2 will examine the role of neurotrophins and the trk family of protooncogenes for their role in growth promotion and establishment of the malignant state in primitive neuroectodermal tumors and astrocytomas. Project 3 will analyze human brain tumors for activation of a specific series of oncogenes including PDGF, Gli and acidic and basic FGF, postulated to be involved in promoting glial cell proliferation. This project will also establish brain tumor derived, human cell lines and test representative samples to evaluate the growth regulating effect of interfering with function and/or expression of these oncogenes. Project 4 will examine the in vitro and in vivo cytotoxic effects of a series of fusion protein constructs, composed of epidermal growth factor (EGF) fused with bacterial exotoxins, on human brain tumors bearing the EGF receptor. Project 5 will develop and test monoclonal antibodies with specificity for malignant astrocyte determinants for their cytotoxic effects on brain tumors. The program will promote the multidisciplinary clinical management of patients with brain tumors and will serve to foster technology transfer from research lab to clinical trials.

这个建议是在凯斯西海岸建立一个脑肿瘤研究中心 克利夫兰储备大学和大学医院， 重点将是膜靶向肽的开发应用， 毒素来改善恶性脑肿瘤的治疗。 该提案 构成了一个协同的，跨学科的，相互作用的， 医生的临床、科学和组织专门知识， 来自神经外科，神经病学， 神经科学、分子生物学、医学、儿科学和爱尔兰 克利夫兰大学医院和凯斯西方癌症中心 储备大学。 项目1将审查 表皮生长因子受体（EGF-R）及其相关信号 在建立和维持转化的 神经胶质瘤的状态。 项目2将研究神经营养因子的作用， 原癌基因的trk家族在生长促进中的作用， 原始神经外胚叶肿瘤恶性状态的确立 和星形细胞瘤 项目3将分析人类脑肿瘤， 激活一系列特定的癌基因，包括PDGF、Gli和 酸性和碱性成纤维细胞生长因子，假定参与促进神经胶质细胞 增殖 该项目还将建立脑肿瘤衍生， 人细胞系和试验代表性样品，以评价生长 干扰这些分子的功能和/或表达的调节作用 致癌基因 项目4将检查体外和体内细胞毒性 一系列融合蛋白构建体的作用，由表皮细胞组成， 生长因子（EGF）融合细菌外毒素，对人脑肿瘤 EGF受体 项目5将开发和测试单克隆 恶性星形胶质细胞决定簇特异性抗体 它们对脑肿瘤的细胞毒性作用。 该计划将促进 脑肿瘤患者的多学科临床管理， 将有助于促进从研究实验室到临床的技术转移 审判