GROWTH FACTORS IN PRIMARY CENTRAL NERVOUS SYSTEM NEOPLASMS

原发性中枢神经系统肿瘤的生长因子

• 批准号: 3774179
• 负责人: TIMOTHY B MAPSTONE
• 金额: --
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3774179
• 关键词: antisense nucleic acid; central nervous system neoplasms; gel electrophoresis; gene expression; growth factor; messenger RNA; oligonucleotides; oncogenes; platelet derived growth factor; thymidine; tritium

Recent data concerning tumor initiation and progression in colon cancer suggests a multistep phenomena. Screening studies of primary CNS tumors for oncogene activity have likewise shown a number of different genes inappropriately activated suggesting that this tumor may also result from a multifactorial process. This project proposes to screen CNS tumor explants for activity of four putative oncogenes - PDGF, Gli, bfgf and a FGF. Expression will be characterized according to cell type and level of malignancy (e.g., astrocytoma vs. glioblastoma, medulloblastoma with astrocytic differentiation vs. PNET). Representative tumor explants will be propagated and used to test therapeutic regimens thus allowing for monitoring of oncogene level changes with respect to effective therapy. This model system will allow novel therapeutic regimens to be developed to directly attack the aberrant gene either by identifying and neutralizing the protein product of the gene or by introducing antisense DNA or other blocking agents to inhibit expression of the putative oncogene. Interference with gene expression will result in either cell death or cellular differentiation ad quiescence. This project will provide insight into the molecular mechanisms of CNS neoplasms by evaluating the hypothesis that specific genes provide a specific phenotypic characteristic of neoplastic cells and that by modifying their expression the neoplastic phenotype be modulated to a more benign form.

关于结肠癌肿瘤发生和进展的最新数据 表明是多步骤现象 原发性中枢神经系统肿瘤的筛查研究 同样显示了许多不同的基因 不适当的激活，这表明这种肿瘤也可能是由于 多因素的过程 本项目拟筛选中枢神经系统肿瘤 用于四种推定的癌基因-PDGF、Gli、bfgf和 a成基金。 表达将根据细胞类型和水平进行表征 恶性肿瘤（例如，星形细胞瘤与胶质母细胞瘤、髓母细胞瘤 星形胶质细胞分化与PNET）。 代表性肿瘤外植体将 被传播并用于测试治疗方案，从而允许 监测癌基因水平变化与有效治疗的关系。 该模型系统将允许开发新的治疗方案 直接攻击异常基因， 中和该基因的蛋白质产物或通过引入反义 DNA或其他阻断剂，以抑制推定的 癌基因 干扰基因表达会导致细胞 死亡或细胞分化停滞。 该项目将 通过以下方式深入了解CNS肿瘤的分子机制： 评估特定基因提供特定的 肿瘤细胞的表型特征，以及通过修饰它们的 表达肿瘤表型被调节为更良性的形式。