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Abstract
BackgroundGlioblastoma (GBM) is the most common primary brain tumor and the most aggressive glial tumor. This tumor is highly heterogeneous, angiogenic, and insensitive to radio- and chemotherapy. Here we have investigated the progression of GBM produced by the injection of human GBM cells into the brain parenchyma of immunocompetent mice.MethodsXenotransplanted animals were submitted to magnetic resonance imaging (MRI) and histopathological analyses.ResultsOur data show that two weeks after injection, the produced tumor presents histopathological characteristics recommended by World Health Organization for the diagnosis of GBM in humans. The tumor was able to produce reactive gliosis in the adjacent parenchyma, angiogenesis, an intense recruitment of macrophage and microglial cells, and presence of necrosis regions. Besides, MRI showed that tumor mass had enhanced contrast, suggesting a blood–brain barrier disruption.ConclusionsThis study demonstrated that the xenografted tumor in mouse brain parenchyma develops in a very similar manner to those found in patients affected by GBM and can be used to better understand the biology of GBM as well as testing potential therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-923) contains supplementary material, which is available to authorized users.
Highlights
Glioblastoma (GBM) is the most common primary brain tumor and the most aggressive glial tumor
Two weeks after GBM cell injection, the magnetic resonance imaging (MRI) revealed hemorrhage and necrosis in the core of the tumor mass, which was confirmed by later histological analyses
Histological analyses showed that the xenografted tumor infiltrates the brain parenchyma, forming a solid tumor mass (Figure 2A), and presents all microscopic histopathological features required for the diagnosis of GBM according to the World Health Organization (WHO) classification [1,4,20], namely cellular atypia, presence of mitotic figures, endothelial vascular proliferation including formation of glomeruloid vessels, and/or necrosis (Figures 2A–C)
Summary
Glioblastoma (GBM) is the most common primary brain tumor and the most aggressive glial tumor. This tumor is highly heterogeneous, angiogenic, and insensitive to radio- and chemotherapy. Glioblastoma (GBM) represents the most common primary brain tumor and the most aggressive glial tumor, leading to poor prognosis for patients in whom the average survival is 12 to 14 months after diagnosis, according to the World Health Organization (WHO). Because most GBM symptoms are non-specific, GBM diagnosis may be suggested by MRI exams, but can only be confirmed by histopathological analysis [4,5,6], which in most cases is done when patients are already in advanced stages of the disease. There is a growing body of evidence suggesting that the brain microenvironment as a whole favors GBM growth and spread [2,13]
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