This is a request for funding for a Feasibility Grant to enable us to develop a Brain Tumor Research Center. Five research Projects and 2 Core units are proposed. Our initial goal is to explore the molecular biological determinants of tumorigenesis in primary brain tumors emphasizing a comparison between pediatric and adult conditions. The proposed research, utilizing our unique pediatric brain tumor tissue resource, may allow us to identify the earliest events that promote malignant transformation. Project 1 will determine whether germinal mutations of the tumor suppressor gene p53 are implicated in the pathogenesis of brain tumors in 3 genetically high risk patient groups - familial cancer, multiple primary neoplasms and congenital tumors. Project 2 will explore the role of mutations of dominant and recessive regulators of Myc expression in tumorigenesis and malignant transformation. Project 3 will correlate growth factor and growth factor receptor expression with clinical parameters in astrocytomas and PNET's. Project 4 will relate the expression of cell surface molecules (cell adhesion, extracellular matrix and glycolipids) with patterns of metastasis (intra-axial vs. leptomeningeal) and survival in astrocytomas and PNET's. Project 5 will examine methods of augmenting host cellular immune function and increasing tumor antigenicity to extend the promising IL-2/LAK clinical brain tumor trials at NYU. The 2 Core Units, 9001 Patient Registry and Data Base, and 9002 Tumor Bank will promote the clinical applications of the Projects. Our long term goal is to establish a Center which facilitates clinical and basic science interactions to improve methods of diagnosis and treatment of patients with primary brain and spinal cord tumors.
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