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The goal of the proposed project is to use gelatinase-binding peptides for development of experimental therapeutic agents against human gliomas. Gelatinases A and B (MMP-2 and MMP-9) are expressed by neovascularizing endothelial cells and invasive tumor cells of many different tumor types. In the current proposal, we shall target several glioma cell lines generated in our lab with gelatinase-binding peptide and its derivatives (conjugates to proapoptotic peptides and and/or synthetic drugs). Effectiveness of peptides/derivatives will be assessed in in vitro viability and invasion assays. The compounds proven efficient in inhibition of glioma cell migration and tumor cell killing will be evaluated in glioma xenografts in vivo. The proposed project is expected to contribute to the field of brain tumor research by fine dissection of the role of gelatinases in glioma biology in vitro and in vivo as well as by validation of gelatinase-directed experimental therapy. |