This proposal has been extensively revised taking into account all of the criticisms and suggestions of the reviewers. It is still based on the results of our comprehensive glycolipid analyses of human glioma tissues that revealed specific glycolipid patterns correlating with: a) astrocytoma and oligodendroglioma phenotypes; b) astrocytoma grade; and c) patient survival. In this project we will build upon these findings by conducting three series of experiments in collaboration with other investigators on this Program Project. The main goal of the first series is to elucidate the biological significance of these glycolipid alterations; the second investigates the molecular basis for these abnormalities; the third evaluates the diagnostic and prognostic relevance of critical glycolipid changes in human gliomas. In brief, these are as follows: 1. To elucidate the biological significance of these glycolipid alterations we will transfect two glioma cell lines with genes encoding specific glycosyltransferases to determine if this modulates their glycolipid compositions, growth properties, or phenotypic characteristics. These will be studied both in vitro and as implants in nude mice. 2. To determine if changes in glycolipid compositions of gliomas are associated with alterations in expression (mRNA levels) of the genes encoding glycosyltransferases. 3. To determine the diagnostic and prognostic value of immunohistochemical assays for specific glycolipids in a prospective, programmatically interactive group study. These experiments involve collaborations with investigators in all three of the other projects, and rely upon services in all components of the Scientific Resources Core. Results should yield considerable insight into the biological significance of the glycolipid changes in gliomas, and determine if these changes have diagnostic and prognostic clinical value.
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