GROWTH FACTORS IN PRIMARY CENTRAL NERVOUS SYSTEM NEOPLASMS

关于结肠癌发生和发展的最新数据 暗示了一种多步骤现象。原发中枢神经系统肿瘤的筛查研究 因为癌基因的活性同样显示出许多不同的基因 不适当的激活表明这种肿瘤也可能是 一个多因素的过程。本项目建议对中枢神经系统肿瘤进行筛查 四种可能的癌基因--PDGF、Gli、bFGF和 A成纤维细胞生长因子。表达将根据细胞类型和水平进行表征 恶性程度(例如，星形细胞瘤与胶质母细胞瘤、髓母细胞瘤与 星形细胞分化与PNET)。有代表性的肿瘤植入者将 被传播并用于测试治疗方案，从而允许 监测癌基因水平的变化，以进行有效的治疗。 这一模型系统将使新的治疗方案得以开发。 通过识别和识别来直接攻击异常基因 中和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 致癌基因。对基因表达的干扰将导致任一细胞 死亡或细胞分化和静止。这个项目将 通过以下方式深入了解中枢神经系统肿瘤的分子机制 评估特定基因提供特定基因的假设 肿瘤细胞的表型特征及其修饰方法的研究 表达肿瘤的表型被调整为更良性的形式。

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.