GROWTH FACTORS IN PRIMARY CENTRAL NERVOUS SYSTEM NEOPLASMS

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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.