Development of new strategies for cancer treatment based in system biological-analysis of cancer system abnormality

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The purpose of this research is to develop the new strategies of cancer treatment based on systems biological analysis of cancer system abnormality. New genomic aberrations were found in glioblastoma cells by microarray-based comparative genomic hybridization. The first attempts to apply detrended fluctuation analysis to copy number profiles by considering the reading direction as the time axis demonstrated that higher long-term fractal scaling exponents correlated well with longer survival of glioblastoma patients. Proteomic technique using both SELDI-TOF MS(surface enhanced laser desorption/ionization time-of-flight mass spectrometry) and MALDI(matrix assisted laser desorption/ionization) TOF MS identified pleiotrophin as a specific growth factor of neural stem cells and transthyretin as a brain ischemia-specific protein. Petri-Net simulation demonstrated that trimer formation of soluble FasL is essential to enhance apoptotic enhancing activity. The four molecular mechanisms of biological robustness such as redundancy, diversity, feedback, modularity and decoupling were found in glioblastoma biomolecular system. Molecular connection network established by PathwayAssist software had the characteristics of scale-free networks such as existence of hub, obligation of power law, so-called small world and bow-tie structure. The intentional attack to hub protein/subsystem seems to easily destroy the scale-free network of cancer.