Genetic and biologic progression in astrocytomas and their relation to angiogenic dysregulation.

摘要: Infiltrative astrocytic neoplasms are the most common malignancies of central nervous system. They remain clinically problematic because their involvement brain structures critical to proper cognitive, behavioral, and motor function; widely invasive properties, which make them difficult resect totally; nearly inevitable biologic progression in spite adjuvant therapy. Glioblastoma multiforme (GBM, World Health Organization grade IV), malignant form infiltrating astrocytoma, can present as a high-grade lesion from outset (so-called de novo GBM) or evolve lower precursor (secondary GBM). Molecular genetic investigations suggest that GBM is best regarded clinicopathologic entity composed multiple molecular subsets. alterations associated with define subsets include epidermal growth factor receptor amplifications, p53 mutations, retinoblastoma pathway [most commonly, p16(CDKN2A) losses], chromosome 10 alterations, including PTEN mutations. Despite wide range events ultimately lead GBM, vascular changes remarkably similar. Microvascular hyperplasia spatially temporally pseudopalisading necrosis believed be driven by hypoxia-induced expression proangiogenic cytokines such endothelial factor. In addition, thought contribute directly indirectly angiogenic dysregulation. Both mutations losses on may tip balance toward an phenotype through upregulation factors and/or downregulation angiogenesis inhibitors. Understanding relation regulation eventually therapies specifically directed at molecularly defined these diseases.