The study of the pathophysiology of malignant glioma and development of treatment strategies

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Malignant gliomas are inevitably fatal, despite concerted, interdisciplinary efforts to improve the prognosis of patients with these tumors. The biological characteristics of malignant gliomas are their fast growth, neovascularization, and invasiveness into the surrounding brain. A great variety of molecules play important roles in these events. We studied the pathophysiology of malignant gliomas in Nan effort to develop novel treatment strategies to combat these malignant neoplasms.We previously purified MCP-1 (monocyte chemoattractant protein-1) from glioma cells and confirmed that this protein participates significantly in the invasion of macrophages into glioma tissue. Therefore, we posited that control of malignant glioma growth may be possible via the regulation of molecules whose activities result in the characteristic features of malignant gliomas.We subsequently established that MCP-1 and thrombin derived from glioma cells are involved in the neovascularization characteristic of these tumors. Using a conformation-epitope-recognizing mAb and a phase-display library, we succeeded in the cloning and functional characterization of the MCP-1 receptor gene and produced a peptide that mimics MCP-1 and expresses antagonistic activity. We also developed highly efficient electro-gene therapy for solid tumors arid suggest that our gratifying results will lead to the development of clinically applicable treatment strategies against malignant tumors.