Immunohistopathological and neuroimaging characterization of murine orthotopic xenograft models of glioblastoma multiforme recapitulating the most salient features of human disease.

作者: R Alzani , E Scanziani , E Radaelli , A Degrassi , E Pesenti

DOI: 10.14670/HH-24.879

关键词: Pathologyp14arfPI3K/AKT/mTOR pathwayImmunohistochemistryMedicineMdm2AngiogenesisProtein kinase BCarcinogenesisPTEN

摘要: Tumorigenesis in human glioblastoma multiforme (GBM) is driven by several genetic abnormalities with disruption of important molecular pathways, such as p53/MDM2/p14ARF and EGFR/PTEN/Akt/mTOR. The malignant progression GBM also primarily associated a peculiar multistep pathophysiological process characterized intratumoral ischemic necrosis (i.e. pseudopalisading necrosis) activation the hypoxia-inducible factor (HIF)-1alpha pathway consequent peritumoral microvascular proliferation infiltrative behaviour. Predictable preclinical animal models should recapitulate main pathobiological hallmarks disease. In this study we describe two murine orthotopic xenograft using U87MG U251 cell lines. Ten Balb/c nude male mice were orthotopically implanted either (5 mice) or Intracranial tumor growth was monitored through Magnetic Resonance Imaging (MRI). Immunohistopathological examination whole cranium performed 30 days after implantation. xenografts recapitulated salient features described for GBM, including invasive behaviour, wide areas necrosis, florid peripheral angiogenesis, GFAP vimentin expression, nonfunctional p53 striking active-caspase-3 HIF-1alpha expression along pseudopalisades. proved to be very dissimilar from showing expansile growth, occasional necrotic foci without pseudopalisades, lacunar pattern lack functional inconsistent expression. Expression pAkt upregulated both models. results obtained suggest that model may proposed predictive reliable tool studies since it recapitulates most reported GBM.

参考文章(0)