Human Gliomas (human + glioma)

Distribution by Scientific Domains
Distribution within Medical Sciences

Terms modified by Human Gliomas

  • human glioma cell
  • human glioma cell line

  • Selected Abstracts


    Buckland M
    No abstract is available for this article. [source]

    Expression of T-type calcium channel splice variants in human glioma

    GLIA, Issue 2 2004
    Isabelle Latour
    Abstract In humans, three isoforms of the T-type (Cav3.1) calcium-channel ,1 subunit have been reported as a result of alternate splicing of exons 25 and 26 in the III,IV linker region (Cav3.1a, Cav3.1b or Cav3.1bc). In the present study, we report that human glioma express Cav3.1 channels in situ, that splicing of these exons is uniquely regulated and that there is expression of a glioma-specific novel T-type variant (Cav3.1ac). Seven human glioma samples were collected at surgery, RNA was extracted, and cDNA was produced for RT-PCR analysis. In addition, three glioma cell lines (U87, U563, and U251N), primary cultures of human fetal astrocytes, as well as adult and fetal human brain cDNA were used. Previously described Cav3.1 splice variants were present in glioma samples, cultured cells and whole brain. Consistent with the literature, our results reveal that in the normal adult brain, Cav3.1a transcripts predominate, while Cav3.1b is mostly fetal-specific. RT-PCR results on glioma and glioma cell lines showed that Cav3.1 expression in tumor cells resemble fetal brain expression pattern as Cav3.1bc is predominantly expressed. In addition, we identified a novel splice variant, Cav3.1ac, expressed in three glioma biopsies and one glioma cell line, but not in normal brain or fetal astrocytes. Transient expression of this variant demonstrates that Cav3.1ac displays similar current-voltage and steady-state inactivation properties compared with Cav3.1b, but a slower recovery from inactivation. Taken together, our data suggest glioma-specific Cav3.1 gene regulation, which could possibly contribute to tumor pathogenesis. 2004 Wiley-Liss, Inc. [source]

    MMP-7 (matrilysin) expression in human brain tumors

    Claire Rome
    Abstract Matrix metalloproteinases (MMP) which degrades protein components of the extra-cellular matrix and basement membrane seems to be largely involved in cancer invasiveness. MMP proteolitic activity essentially comes from stromal cells but matrilysin (MMP-7) is produced by the tumor itself. Thus, MMP-7 is investigated to address the particular invasive behavior of human glioma. Both MMP-7 mRNA and protein were clearly identified in human glioma. MMP-7 mRNA expression was highly variable within our glioma population. When analyzing MMP-7 mRNA expression in different primary brain tumors, we found highly variable levels of expression not related to their invasive behavior. In successive biopsies obtained in the same patients with glioblastoma, MMP-7 mRNA was quantified and appeared variable, but intra-individual variations were lower than inter-individual differences. With a xenograft model of U87 human tumors in RAG2/,c immune-deficient mice, the strict tumor origin of MMP-7 was shown. Additionally, MMP-7 expression by U87 cells which is low in culture was stimulated by these cells while forming tumors and the level of expression was higher when the tumor cells were implanted within the brain. These data provide some consistent information about cross-talk occurring between the tumor and the surrounding stroma to regulate MMP-7 expression. 2007 Wiley-Liss, Inc. [source]

    Characterization and gene expression profiling in glioma cell lines with deletion of chromosome 19 before and after microcell-mediated restoration of normal human chromosome 19

    Kristen L. Drucker
    Nearly 10% of human gliomas are oligodendrogliomas. Deletion of chromosome arm 19q, often in conjunction with deletion of 1p, has been observed in 65,80% of these tumors. This has suggested the presence of a tumor suppressor gene located on the 19q arm. Chromosome 19 deletion is also of interest due to the better prognosis of patients with deletion, including longer survival and better response to chemotherapy, compared with patients without deletion. Two glioma cell lines with deletion of 19q were used for chromosome 19 microcell-mediated transfer, to assess the effect of replacing the deleted segment. Complementation with chromosome 19 significantly reduced the growth rate of the hybrid cells compared with the parental cell lines. Affymetrix U133 Plus 2.0 Gene Chip analysis was performed to measure and compare the expression of the chromosome 19 genes in the chromosome 19 hybrid cell lines to the parental cell line. Probes were considered significantly different when a P value <0.01 was seen in all of the cell line comparisons. Of 345 probes within the commonly deleted 19q region, seven genes (APOE, RCN3, FLJ10781, SAE1, STRN4, CCDC8, and BCL2L12) were identified as potential candidate genes. RT-PCR analysis of primary tumor specimens showed that several genes had significant differences when stratified by tumor morphology or deletion status. This suggests that one or more of these candidates may play a role in glioma formation or progression. 2009 Wiley-Liss, Inc. [source]

    Cooperative expression of junctional adhesion molecule-C and -B supports growth and invasion of glioma

    GLIA, Issue 5 2010
    Mirna Tenan
    Abstract Brain invasion is a biological hallmark of glioma that contributes to its aggressiveness and limits the potential of surgery and irradiation. Deregulated expression of adhesion molecules on glioma cells is thought to contribute to this process. Junctional adhesion molecules (JAMs) include several IgSF members involved in leukocyte trafficking, angiogenesis, and cell polarity. They are expressed mainly by endothelial cells, white blood cells, and platelets. Here, we report JAM-C expression by human gliomas, but not by their normal cellular counterpart. This expression correlates with the expression of genes involved in cytoskeleton remodeling and cell migration. These genes, identified by a transcriptomic approach, include poliovirus receptor and cystein-rich 61, both known to promote glioma invasion, as well as actin filament associated protein, a c-Src binding partner. Gliomas also aberrantly express JAM-B, a high affinity JAM-C ligand. Their interaction activates the c-Src proto-oncogene, a central upstream molecule in the pathways regulating cell migration and invasion. In the tumor microenvironment, this co-expression may thus promote glioma invasion through paracrine stimuli from both tumor cells and endothelial cells. Accordingly, JAM-C/B blocking antibodies impair in vivo glioma growth and invasion, highlighting the potential of JAM-C and JAM-B as new targets for the treatment of human gliomas. 2009 Wiley-Liss, Inc. [source]

    HSP27 mediates SPARC-induced changes in glioma morphology, migration, and invasion

    GLIA, Issue 10 2008
    William A. Golembieski
    Abstract Secreted protein acidic and rich in cysteine (SPARC) regulates cell,extracellular matrix interactions that influence cell adhesion and migration. We have demonstrated that SPARC is highly expressed in human gliomas, and it promotes brain tumor invasion in vitro and in vivo. To further our understanding regarding SPARC function in glioma migration, we transfected SPARC-green fluorescent protein (GFP) and control GFP vectors into U87MG cells, and assessed the effects of SPARC on cell morphology, migration, and invasion after 24 h. The expression of SPARC was associated with elongated cell morphology, and increased migration and invasion. The effects of SPARC on downstream signaling were assessed from 0 to 6 h and 24 h. SPARC increased the levels of total and phosphorylated HSP27; the latter was preceded by activation of p38 MAPK and inhibited by the p38 MAPK inhibitor SB203580. Augmented expression of SPARC was correlated with increased levels of HSP27 mRNA. In a panel of glioma cell lines, increasing levels of SPARC correlated with increasing total and phosphorylated HSP27. SPARC and HSP27 were colocalized to invading cells in vivo. Inhibition of HSP27 mRNA reversed the SPARC-induced changes in cell morphology, migration, and invasion in vitro. These data indicate that HSP27, a protein that regulates actin polymerization, cell contraction, and migration, is a novel downstream effector of SPARC-regulated cell morphology and migration. As such, it is a potential therapeutic target to inhibit SPARC-induced glioma invasion. 2008 Wiley-Liss, Inc. [source]

    High cerebral blood volume in human gliomas predicts deletion of chromosome 1p: Preliminary results of molecular studies in gliomas with elevated perfusion

    Meng Law MD
    Abstract Purpose To determine if increased perfusion using dynamic susceptibility contrast perfusion MRI (DSC MRI) in gliomas may be predictive of 1p19q deletions. Loss of heterozygosity of chromosomes 1p and 19q confers responsiveness to chemotherapy improving survival in gliomas. Materials and Methods We retrospectively reviewed 16 patients who had DSC MRI and molecular studies of their excised gliomas for 1p19q deletions. Allelic status was assessed by loss of heterozygosity using polymerase chain reaction (PCR). DNA was extracted from paraffin curls of brain tumor sections and nail clippings. Relative cerebral blood volume (rCBV) measurements were then statistically compared with the presence of 1p and 19q deletions. Results Patients with 1p19q deletions (N = 7) demonstrated rCBV values of 10.54 2.93. Patients without 1p deletions (N = 9) had rCBV values of 4.84 2.4 (P = 0.012). Logistic regression demonstrated that rCBV was able to predict the presence of a 1p deletion to significance levels of 0.038 and 0.044, adjusted and not adjusted for age and sex, respectively. The kappa coefficient for the agreement between predicted deletion status using rCBV and the truedeletion status was 0.746 (P = 0.0028). Deletions of 19q alone, or together with 1p deletions, were not associated with high rCBV. Conclusion Histopathologic, molecular, and imaging evidence supports increased neovascularity in gliomas with 1p deletions in this preliminary study. We propose a diagnostic algorithm to obtain molecular studies in gliomas demonstrating high rCBV. J. Magn. Reson. Imaging 2007;25:1113,1119. 2007 Wiley-Liss, Inc. [source]

    A comparison of Ktrans measurements obtained with conventional and first pass pharmacokinetic models in human gliomas

    Hamied A. Haroon MSc
    Abstract Purpose To compare in a group of patients with cerebral gliomas the estimates of Ktrans between a conventionally established pharmacokinetic model and a recently developed first pass method. Materials and Methods Glioma patients (23) were studied using T1 -weighted dynamic contrast-enhanced magnetic resonance imaging (MRI), and two alternative pharmacokinetic models were used for analysis to derive the volume transfer constant Ktrans. These were a modified version of the established model (yielding KTK) and a recently published method based on first pass leakage profile (FP) of contrast bolus (yielding Kfp). Results We found a strong correlation between intra-tumoral median KTK and Kfp (rho = 0.650, P < 0.01), but the values from the conventional model were consistently and significantly higher (mean of inter-tumoral Kfp and KTK medians were 0.018 minute,1 and 0.284 minute,1, respectively, P < 0.001). The spatial distribution of KTK and Kfp showed poor correlation in the presence of large vascular structures and good correlation elsewhere. Conclusion KTK and Kfp produce similar biologic information within voxels not dominated by vascular tissue. The FP method avoids erroneous overestimation of Ktrans in areas of significant intravascular contrast. Findings are in keeping with the predictions of previous mathematical simulations. J. Magn. Reson. Imaging 2004;19:527,536. 2004 Wiley-Liss, Inc. [source]

    Pleiotrophin, an angiogenic and mitogenic growth factor, is expressed in human gliomas

    Rolf Mentlein
    Abstract Pleiotrophin (PTN) is a mitogenic/angiogenic, 15.3 kDa heparin-binding peptide that is found in embryonic or early postnatal, but rarely in adult, tissues. Since developmentally regulated factors often re-appear in malignant cells, we examined PTN expression in human glioma cell lines, cell cultures derived from solid gliomas and glioma sections. PTN mRNA or protein was detected by reverse transcriptase-polymerase chain reaction, immunohistochemistry, western blot or enzyme-linked immunoassay in all WHO III and IV grade gliomas and cells analyzed in vitro or in situ. One WHO II grade glioma investigated was PTN negative. In vitro, PTN was synthesized in perinuclear regions of glioma cells, secreted into the cultivation medium, but its production varied considerably between glioma cells cultivated from different solid gliomas or glioma cell lines. In situ, PTN expression was restricted to distinct parts/cells of the tumour. PTN did not influence the proliferation of glioma cells themselves, but stimulated [3H]thymidine incorporation into DNA of microglial cells. Furthermore, in Boyden chamber assays, PTN showed a strong chemotactic effect on murine BV-2 microglial cells. PTN is supposed to be a paracrine growth/angiogenic factor that is produced by gliomas and contributes to their malignancy by targeting endothelial and microglial cells. [source]

    The value and correlation between PRL-3 expression and matrix metalloproteinase activity and expression in human gliomas

    NEUROPATHOLOGY, Issue 6 2007
    Lingfei Kong
    Local invasion of tumor cells is characteristic of most human glioma invasions. It is associated with increased motility and a potential to degrade the extracellular matrix. Matrix metalloproteinases (MMPs) have been proved to be a main process in local invasion of brain tumor. PRL-3 is a new protein tyrosine phosphatase which would also degrade the extracellular matrix and has been proved to be expressed in liver metastases derived from colorectal cancer. In this study, we sought to investigate the expression of PRL-3 in glioma tissues and investigate the relationship between MMPs (MMP2, MMP9, membrane-type matrix metalloproteinase 1 [MT1-MMP]) activity and expression in gliomas. The modifications of in situ hybridization of mRNA phosphatase of regenerating liver-3 (PRL-3) methods are preformed in the study of paraffin-embedded slides. The immunohistochemistry and gelatin zymography are used to detect the expression of PRL-3 and activity of MMPs. The results show that PRL-3 mRNA and antibody of PRL-3 are detected in glioma tissues mainly in grades IV and III, only a little in grade II, but not in normal brain tissue and glioma grade I. MMP2 and MMP9 are observed mainly in glioma tissues of grades IV and III in activity and expression. MT1-MMP protein is located in glioma tissues and vessel endothelial cells. This is the first report of detecting PRL-3 expression in gliomas, especially in grades III and IV, which may play an important role in progression of gliomas. PRL-3, MMP2 and MT1-MMP cooperatively contribute to gliomas invasion. Intermediate MMP2 (MT1-MMP, TIMP-2, MMP2 trimeric complex) is detected in high grades of glioma tissues by gelatin zymography and may be a marker indicating latent malignance of gliomas. [source]

    Vesicle amine transport protein-1 (VAT-1) is upregulated in glioblastomas and promotes migration

    S. Mertsch
    Aim:,Diffuse invasion of single-glioma cells is the main obstacle to successful therapy of these tumours. After identifying vesicle amine transport protein-1 (VAT-1) as being upregulated in invasive human gliomas, we study its possible function in glioblastoma cell migration. Methods:,Based on data obtained from previous oligonucleotide arrays, we investigated expression of VAT-1 in glioblastoma tissue and cell lines on mRNA levels using reverse transcriptase PCR. Furthermore, we examined the amount and localization of VAT-1 protein using immunoblotting and immunohistochemistry. Using small interfering RNA technology we repressed VAT-1 expression in human glioma cell lines and analysed their migration using wound healing and transwell migration assays. Results:,Increased VAT-1 mRNA and protein levels were found in glioblastoma tissues and cell lines compared with normal human brain. Small interfering RNA-mediated VAT-1 knockdown led to significantly reduced migration of human glioma cells. Conclusions:,VAT-1 is overexpressed in glioblastomas and functionally involved in glioma cell migration, representing a new component involved in glioma invasion. [source]

    Histomorphometry of brain tumours

    R. Nafe
    In this review, the results of previous histomorphometric studies of brain tumours are summarized and discussed with respect to their potential value for diagnostic purposes and for tumour research. In the majority of these studies, human gliomas were investigated. In a few studies, human meningiomas and other human or experimental tumour types were investigated. A computerized image analysis system was used for the morphometric analyses in most studies. The three main histologic structures examined were tumour cell nuclei, nucleolar organizer regions and tumour vessels. The current state of knowledge provides evidence that a diagnostic benefit could be provided by histomorphometric investigations of brain tumours, especially for grading of gliomas and with respect to independent prognostic information. Additional studies are necessary to delineate the spectrum of histomorphometric parameters and the investigation of their prognostic significance for cases with the same tumour type and tumour grade. Together with many recently published observations in this field, this review shows that histomorphometry is an important approach towards the investigation of brain tumour biology. [source]

    Differential protein expression in human gliomas and molecular insights

    Vaibhav C. Chumbalkar
    Abstract Gliomas are the most common of the primary intracranial tumors with astrocytomas constituting about 40%. Using clinically and histologically assessed astrocytomas, we have studied their protein profiles using a two-dimensional gel electrophoresis-mass spectrometry approach and identified differentially expressed proteins which may be useful molecular indicators to understand these tumors. Examination of the protein profiles of 27,astrocytoma samples of different grades revealed 72,distinct, differentially expressed proteins belonging to various functional groups such as cytoskeleton and intermediate filament proteins, heat shock proteins (HSPs), enzymes and regulatory proteins. Based on the consistency of their differential expression, 29,distinct proteins could be short-listed and may have a role in the pathology of astrocytomas. Some were found to be differentially expressed in both Grade,III and IV astrocytomas while others were associated with a particular grade. A notable observation was underexpression of Prohibitin, a potential tumor suppressor protein, Rho-GDP dissociation inhibitor, Rho-GDI, a regulator of Rho GTPases and HSPs as well as destabilization of glial fibrillary acidic protein, GFAP, major protein of the glial filaments, in Grade,III malignant tumors. We attempt to explain glioma malignancy and progression in terms of their combined role. [source]

    Galectins Are Differentially Expressed in Supratentorial Pilocytic Astrocytomas, Astrocytomas, Anaplastic Astrocytomas and Glioblastomas, and Significantly Modulate Tumor Astrocyte Migration

    BRAIN PATHOLOGY, Issue 1 2001
    Isabelle Camby
    Galectins, a family of mammalian lectins with specificity to ,-galactosides, are involved in growth-regulatory mechanisms and cell adhesion. A relationship is assumed to exist between the levels of expression of galectins and the level of malignancy in human gliomas. A comparative study of this aspect in the same series of clinical samples is required to prove this hypothesis. Using computer-assisted microscopy, we quantitatively characterized by immunohistochemistry the levels of expression of galectins-1, -3 and-8 in 116 human astrocytic tumors of grades I to IV. Extent of transcription of galectins-1, -3, and -8 genes was investigated in 8 human glioblastoma cell lines by means of RT-PCR techniques. Three of these cell lines were grafted into the brains of nude mice in order to characterize in vivo the galectins-1, -3 and -8 expression in relation to the patterns of the tumor invasion of the brain. The role of galectin-1, -3 and -8 in tumor astrocyte migration was quantitatively determined in vitro by means of computer-assisted phase-contrast videomicroscopy. The data indicate that the levels of galectin-1 and galectin-3 expression significantly change during the progression of malignancy in human astrocytic tumors, while that of galectin-8 remains unchanged. These three galectins are involved in tumor astrocyte invasion of the brain parenchyma since their levels of expression are higher in the invasive parts of xenografted glioblastomas than in their less invasive parts. Galectin-3, galectin-1, and to a lesser extent galectin-8, markedly stimulate glioblastoma cell migration in vitro. Since bands for the transcripts of human galectins-2, -4 and -9 were apparently less frequent and intense in the 8 human glioblastoma cell lines, this system provides an excellent model to assign defined roles to individual galectins and delineate overlapping and distinct functional aspects. [source]