Browsing by Subject "Gliomas"

Now showing 1 - 5 of 5
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    Immune profiling of gliomas reveals a connection with IDH1/2 mutations, Tau function and the vascular phenotype
    (MDPI, 2020-11-02) Cejalvo, Teresa; Gargani, Ricardo; Segura Collar, Berta; Mata Martínez, Pablo; Herránz, Beatriz; Cantero, Diana; Ruano, Yoland; García Pérez, Daniel; Pérez Núñez, Ángel; Ramos, Ana; Hernández Laín, Aurelio; Martín Soberón, María Cruz; Sepúlveda Sánchez, Juan M.; Farmacología; Facultades de la UMU::Facultad de Medicina
    Background: Gliomas remain refractory to all attempted treatments, including those using immune checkpoint inhibitors. The characterization of the tumor (immune) microenvironment has been recognized as an important challenge to explain this lack of response and to improve the therapy of glial tumors. Methods: We designed a prospective analysis of the immune cells of gliomas by flow cytometry. Tumors with or without isocitrate dehydrogenase 1/2 (IDH1/2) mutations were included in the study. The genetic profile and the presence of different molecular and cellular features of the gliomas were analyzed in parallel. The findings were validated in syngeneic mouse models. Results: We observed that few immune cells infiltrate mutant IDH1/2 gliomas whereas the immune content of IDH1/2 wild-type tumors was more heterogeneous. Some of them contained an important immune infiltrate, particularly enriched in myeloid cells with immunosuppressive features, but others were more similar to mutant IDH1/2 gliomas, with few immune cells and a less immunosuppressive profile. Notably, we observed a direct correlation between the percentage of leukocytes and the presence of vascular alterations, which were associated with a reduced expression of Tau, a microtubule-binding protein that controls the formation of tumor vessels in gliomas. Furthermore, overexpression of Tau was able to reduce the immune content in orthotopic allografts of GL261 cells, delaying tumor growth. Conclusions: We have confirmed the reduced infiltration of immune cells in IDH1/2 mutant gliomas. By contrast, in IDH1/2 wild-type gliomas, we have found a direct correlation between the presence of vascular alterations and the entrance of leukocytes into the tumors. Interestingly, high levels of Tau inversely correlated with the vascular and the immune content of gliomas. Altogether, our results could be exploited for the design of more successful clinical trials with immunomodulatory molecules.
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    Lectins as differentiation markers of human gliomas
    (Murcia : F. Hernández, 1991) Figols, J.; Cervós-Navarro, J.; Madrid Cuevas, Juan Francisco
    The lectins Concanavalin A (Con A). Ricinus communis agglutinin (RCA-1), Peanut agglutinin (PNA) and Wheat germ agglutinin (WGA) as well as the irnmunomarkers for glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) were used in a series of 21 glial turnors (4 pylocytic astrocytornas, 5 grade 11 astrocytornas, 3 anaplastic astrocytornas, 4 glioblastornas and 5 oligodendrogliornas). ConA binds to al1 tumoral astrocytes in low grade astrocytomas, as well as to well differentiated tumoral astrocytes in anaplastic astrocytomas and glioblastornas. RCA-1 has a similar behaviour. PNA, and to a lesser degree WGA, binds selectively to the oligodendroglial plasma membrane in well differentiated oligodendrogliomas. The results suggest that these lectins are markers of differentiation in gliomas rather than of malignancy.
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    Microvascular adaptive changes in experimental endogenous brain gliomas
    (Murcia : F. Hernández, 2009) Bulnes, Susana; Bilbao, Juan; Lafuente, José Vicente
    Glioma growth depends on microvascular adaptation and angiogenesis. Our study focused on the structural changes that occur in the microvasculature to adapt to glioma growth. Vascular morphology, morphometry and permeability studies were performed in induced rat gliomas. Tumours were identified by magnetic resonance imaging and histopathology. Blood brain barrier integrity was examined by EBA and GluT-1 immunostaining and correlated with vascular permeability for gadolinium and intravital dyes. VEGF165 immunoexpression was also analyzed. Tumours were grouped in microtumours (6.69±0.99 mm3) displaying a homogeneous T2-w hyperintense signal corresponding to low-grade gliomas, and macrotumours (900.79±332.39 mm3) showing gadolinium contrast enhancement, intravital dye extravasation and histopathological features of highgrade gliomas. Results show that the microvascular network becomes aberrant as we move from micro to macrotumours. Vessel density decreases, whereas the relative area occupied by the vascular network increases. Microtumours display homogeneous angioarchitecture composed of simple and mildly dilated vessels similar to normal tissue. Macrotumours show different patterns, following a gradient from the neoangiogenic border to the hypoxic core. The tumour core contains scarce, huge, dilated vessels with some profiles co-expressing GluT-1 and VEGF165, the peripheral tissue shows light dilated vessels co-expressing EBA and GluT-1, and the border area displays glomeruloid vessels strongly positive for VEGF. Glucose uptake was maintained for some vascular endothelial sections in areas where BBB function was lost. In conclusion, during development of gliomas the microvasculature becomes aberrant, undergoing a sequence of adaptive changes which involve the distribution and permeability of vessels. This explains the disturbances of blood flow and the increased permeability.
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    Molecular biology of glioma tumorigenesis
    (Murcia : F. Hernández, 2003) Ware, M.L.; Berger, M.S.; Binder, D.K.
    Gliomas are the most common intracranial malignant tumors in humans, and high-grade gliomas in particular pose a unique challenge due to their propensity for proliferation and tissue invasion. Our understanding of glioma oncogenesis, proliferation, and invasion has been greatly advanced in the past 10 years as researchers have gained a better understanding of the molecular biology of these tumors. This article highlights glioma histopathology, as well as cytogenetic and molecular alterations associated with the pathogenesis of human gliomas. It is hoped that better understanding of the molecular pathogenesis of gliomas will improve tumor classification as well as lead to novel targets for therapy and prognostic markers.
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    Toward a molecular classification of the gliomas: histopathology, molecular genetics, and gene expression profiling
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2000) Caskey, L. S.; Fuller, G. N.; Bruner, J. M.; Yung, W.K.A; Sawaya, R. E.; Holland, E. C.; Zhang, W.
    As many as 100 ,000 new cases of brain tumor are diagnosed each year in the United States. About half of these are primary gliomas and the remaining half are metastatic tumors and non-glial primary tumors. Currently, gliomas are classified based on phenotypic characteristics. Recent progress in the elucidation of genetic alterations found in gliomas have raised the exciting possibility of using genetic and molecular analyses to resolve some of the problematic issues currently associated with the histological approach to glioma classification. Recently , immunohistochemical studies using novel proliferation markers have significantly advanced the assessment of tumor growth potential and the grading criteria of some tumor subtypes. Preliminary studies using cDNA array technologies suggest that the profiling of gene expression patterns may provide a novel and meaningful approach to glioma classification and subclassification. Furthermore, cDNA array technologies may also be used to identify candidate genes involved in glioma tumor development, invasion, and progression. This review summarizes current glioma classification schemes that are based on histopathological characteristics and discusses the potential for using cDNA array technology in the molecular classification of gliomas.