1,720,970 research outputs found
A library of engineered microRNA to find new tumor suppressors genes involved in glioblastoma formation.
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Noninvasive Monitoring of Glioma Growth in the Mouse
No full textMalignant gliomas are the most common and deadly primary malignant brain tumors. In vivo orthotopic models could doubtless represent an appropriate tool to test novel treatment for gliomas. However, methods commonly used to monitor the growth of glioma inside the mouse brain are time consuming and invasive. We tested the reliability of a minimally invasive procedure, based on a secreted luciferase (Gaussia luciferase), to frequently monitor the changes of glioma size. Gluc activity was evaluated from blood samples collected from the tail tip of mice twice a week, allowing to make a growth curve for the tumors. We validated the correlation between Gluc activity and tumor size by analysing the tumor after brain dissection. We found that this method is reliable for monitoring human glioma transplanted in immunodeficient mice, but it has strong limitation in immunocompetent models, where an immune response against the luciferase is developed during the first weeks after transplant
Six3 controls the neural progenitor status in the murine CNS
No full textSix3, a homeodomain-containing transcriptional regulator belonging to the Six/so family, shows a defined spatiotemporal expression pattern in the developing murine telencephalon, suggesting that it may control the development of specific subsets of neural progenitors. We find that retrovirus-mediated misexpression of Six3 causes clonal expansion of isolated cortical progenitor cells by shortening their cell cycle and by prolonging their amplification period, while maintaining them in an immature precursor state. Our results show that the observed effects exerted by Six3 overexpression in mammalian brain depend strictly on the integrity of its DNA-binding domain, suggesting that Six3 action likely relies exclusively on its transcriptional activity. In vivo upregulation of Six3 expression in single progenitor cells of the embryonic telencephalon keeps them in an undifferentiated state. Our observations point to a role of Six3 in the control of the subtle equilibrium between proliferation and differentiation of defined precursor populations during mammalian neurogenesis. © The Author 2007. Published by Oxford University Press. All rights reserved
Progression from low-to high-grade in a glioblastoma model reveals the pivotal role of immunoediting
No full textThe mutual reshape of tumor and immune system cells during tumor progression is a widely accepted notion in different cancers including gliomas. The importance of this phenomenon in shaping glioma progression and the mechanisms governing it, however, are not fully elucidated. Taking advantage of a well-characterized in vivo glioma model we performed an analysis of glioma cells transcriptomes at different stages of progression and unveiled the reorganization of glioma-immune system interactions. Specifically, we show that the inability of low-grade glioma cells to orthotopically graft in syngeneic immunocompetent mice, positively correlates with the abundance of infiltrating lymphocytes in donor tumors and with a highly immunostimulatory transcriptional profile. Notably, during tumor progression glioma cells downregulate these genes and the immune infiltrate shifts towards a pro-tumorigenic phenotype. Challenging low-grade gliomas with grafting into immunodeficient hosts revealed the crucial role of the adaptive immune system in constraining glioma progression. Finally, we observed that although progression still takes place in immunodeficient mice, it is slower, likely due to a milder selection thus reinforcing the view of a pivotal role for the immune system in regulating glioma progression
Platelet derived growth factor B gene expression in the Xenopus laevis developing central nervous system
Full text linkPlatelet-derived growth factor B (PDGF-B) belongs to the mitogen and growth factor family and like the other members it has many roles in cell differentiation, proliferation and migration during development, adult life and in pathological conditions. Among them it has been observed that aberrant PDGF signalling is frequently linked to glioma development and progression, and Pdgf-b over-expression in mouse neural progenitors leads to the formation of gliomas. Despite this evidence, the mechanisms underlying PDGF-B driven tumorigenesis and its role during brain development are not fully understood. In order to contribute to clarifying possible new roles of pdgf-b signalling, we present here the embryonic gene expression pattern of pdgf-b, so far unknown in early vertebrate development. By using Xenopus laevis as a model system we performed qRT-PCR and whole mount in situ hybridization. Pdgf-b mRNA is expressed in discrete regions of the developing central nervous system, in the cranial nerve placodes and in the notochord. We also compared the gene expression of pdgf-b with that of its receptor pdgfr-a suggesting so far unsuspected roles for this signalling pathway during the development of specific embryonic structures
Experimental Models of Glioma
No full textThe development and refinement of animal models of gliomagenesis has been fundamental to test hypotheses concerning the aetiology of gliomas and their molecular and cellular pathogenesis. During the last few decades, modeling has gained in complexity and is nowadays mostly relying on the cell type-specific modulation of the expression of candidate oncogenes and oncosup-pressors. Despite such technological advances, the recent appreciation of the molecular heterogeneity underlying human high-grade glioma variability re-vealed the need for a deeper characterization of the available models. It is now clear that most of the existing animal systems mimic one of the human molecular classes, known as "proneural", leaving the other groups un-derrepresented. While there is thus the need for an expansion of the range of available models, existing ones have already proven useful as translational research platforms, allowing preliminary assessment of the efficacy of classi-cal and innovative therapeutic approaches. In this contribution, we provide a general view of the field and synthesize our understanding of the biology of the most thoroughly studied model family, that of PDGF-induced gliomas
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