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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Long term in vitro cultures of six human malignant gliomas were established to obtain permanent lines and to assess, under conditions of prolonged culture, changes in morphology and phenotype of neoplastic cells and the extent of these modifications. We analyzed expression of the following markers by immunocytochemistry: glioma-specific antigens (GE2 and CG12), fibronectin, intermediate filaments (GFAP, vimentin, neurofilaments), class I and II histocompatibility antigens (HLA-ABC and HLA-DR), growth factor and receptor (alpha TGF and EGF-receptor), proliferation-associated antigen (Ki-67). Strong and stable staining with the two antiglioma monoclonal antibodies (GE2 and CG12) was seen, with coexpression of GFAP and fibronectin in five of six cell lines (after 20 passages) and presence of vimentin and neurofilaments. HLA-DR expression was heterogeneous, with a peculiar intracellular compartmentation in four of six cell lines. Cells showed clear cytoplasmic positivity for alpha TGF and strong membrane staining for EGF-receptor. In previous studies we showed that these cell lines have increased copies of chromosome 7; therefore we speculate that an autocrine pathway of stimulation may maintain the neoplastic growth. The percentage of Ki-67 positive proliferating cells ranged from 40 to greater than 60%, depending on cell line and passage. A slight decrease in the positivity of some markers (GFAP, vimentin and HLA-DR in 2/6 cell lines) was observed after prolonged in vitro culture (greater than 12 months), but morphophenotypic modifications, established within a few passages after explanation, were maintained with time. A clonogenic assay showed values of plating efficiency (PE) higher than corresponding values of other similar cell lines with a tendency to increase in the late passages. PE and Ki-67 positivity were not associated with tumorigenicity into nude mice (except the Hu 197 cell line). These results indicate that, in culture, all six cell lines acquired stable morphology, a well defined antigenic phenotype and high growth rate. Further studies will be performed on these permanent cell lines to clarify differentiation steps of malignant gliomas.
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PMID:Morphological heterogeneity and phenotype modifications during long term in vitro cultures of six new human glioblastoma cell lines. 233 Jun 9

A 50-year-old female patient died of an untreatable glioma apoplecticum. At autopsy a strongly vascularized glial tumour was found. The criteria for malignancy according to the WHO classification were only partially fulfilled by this tumour which displayed morphological features of an astrocytoma but could not be further subclassified. By light microscopy, angioma-like vascular proliferations, large cells with brightly eosinophilic cytoplasm, and small cells with hyperchromatic nuclei were found. Most large cells had vesicular, excentrically placed nuclei and contained fibrillary whorls or amorphous, irregular cytoplasmic inclusions. By immunohistochemical staining, using antibodies to glial fibrillary acidic protein (GFAP) the fibrillary whorls were identified as aggregates of glial filaments. The amorphous inclusions lacked GFAP immunoreactivity and appeared in the electron microscope as electron dense material surrounded by a dense network of glial filaments. The abnormal perikaryal inclusions of these atypical astrocytoma cells appeared to be peculiar alterations of Rosenthal fibres closely mimicing Mallory bodies.
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PMID:Peculiar changes in Rosenthal fibres in an atypical astrocytoma. 234

Recent studies have suggested that astrocytes share with the macrophages several properties in vitro, among which is the ability to express MHC Class II molecules and to present some antigens to syngeneic primed lymphocytes (MHC-restricted presentation). It has been claimed in the literature that astrocytes cannot start the presentation and cannot express the related MHC Class II molecules if not previously stimulated with gamma IFN. In this paper we report that 2 human GFAP + glioma cell lines, incubated in culture with various soluble antigens for at least 24 h, were able, in the absence of gamma IFN or of activated lymphocytes, to express the MHC Class II and to expose the antigens on their surfaces. Moreover, when a lysosomotropic agent such as chloroquine was added during the incubation, no MHC Class II expression was observed. This last datum suggests that in astrocytes, as is already known in macrophages, the processing of antigens and their assembling with MHC Class II molecules probably involves the lysosomal apparatus.
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PMID:MHC class II expression by human glioma cells after in vitro incubation with soluble antigens. 235 71

The protein kinase-C (PKC) second messenger system contributes to regulation of cell growth and differentiation. This study was undertaken to examine the effects of modulators of the PKC enzyme system on the state of differentiation and proliferation rates of human gliomas in vitro. The administration of the PKC-activating phorbol esters 4-beta-phorbol-12,13-dibutyrate (PDB) and phorbol-12-myristate-13-acetate (PMA) resulted in a dose-related inhibition of growth of human glioma cell lines in vitro as measured by 3H-thymidine uptake. The synthetic nonphorbol PKC activator (SC-9) produced an even more pronounced decrease of 3H-thymidine uptake. Diacylglycerol, an endogenous activator of the system, applied externally, transiently decreased the proliferation, in concordance with its short-lived existence in vivo. Conversely, the administration of 4-alpha-phorbol-12,13-didecanoate (alpha-PDD), a phorbol ester that binds but does not activate the enzyme, had no effect on the proliferation rate. At the dosages that maximally decreased proliferation, there was no evidence of direct glioma cell lysis induced by these agents as measured by a chromium-release assay. Immunocytochemical analysis and cytofluorometric measurement of glial fibrillary acidic protein (GFAP) staining in the treated cultures revealed an increase in GFAP staining over control cultures. In contrast to the response of glioma cells, nonmalignant human adult astrocytes treated with the PKC activators responded by increasing their proliferation rate. The authors postulate that the diametrically opposed effects of PKC activators on nonmalignant astrocytes versus glioma growth may be due to a high intrinsic PKC activity in glioma cells, with resultant down-regulation of enzyme activity following the administration of the pharmacological activators.
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PMID:Inhibition of growth of established human glioma cell lines by modulators of the protein kinase-C system. 200 88

A panel of nine monoclonal antibodies raised against human hemopoietic cells was used for immunohistological labeling of frozen sections of human nervous tissues and tumors. Three antibodies showed a remarkably consistent labeling pattern when tested on 18 samples of normal or reactive tissue, on 31 neurogenic and 17 non-neurogenic tumors in an indirect immunofluorescence technique. VIM C6, an antibody recognizing cells of the granulocyte series, showed surface labeling of normal and reactive glial cells and of all types of glioma regardless of the grade of malignancy. VIT 13, an antibody recognizing activated T-cells, labeled the processes of normal, reactive, and neoplastic glia in a manner very similar to but not identical with glial fibrillary acidic protein (GFAP). VIB C5, an antibody recognizing B cells and granulocytes, showed surface labeling restricted to malignant cells (malignant gliomas and primitive neuroectodermal tumors) and fetal brain, thus recognizing, within the nervous system, an oncofetal antigen. Due to this operational specificity within the nervous system, some of the antibodies described here might have a role as diagnostic markers for CNS tumors. This study confirms and expands previous data that sharing of antigenic determinants by hemopoietic cells and nervous tissue or neurogenic tumors is common. However, the significance of such cross-recognition is still obscure. It is tempting to speculate that cross-reacting auto-antibodies might contribute to tissue damage in some immune-mediated neurologic diseases (myasthenia gravis, multiple sclerosis, CNS involvement in systemic lupus erythematosus) or to impairment of immunoregulation in multiple sclerosis or glioma patients. Furthermore, sharing of surface determinants might be responsible for the dual tissue tropism of some viruses, including the lymphotrophic virus (HTLV) in the encephalopathy of the acquired immune deficiency syndrome (AIDS).
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PMID:Shared antigenic determinants between human hemopoietic cells and nervous tissues and tumors. 241 Oct 97

We have used cytofluorometry to examine the formaldehyde sensitivity of the binding of a monoclonal antibody (MAB) to its epitope on glial fibrillary acidic protein in human malignant glioma cells in culture. When acetone-extracted whole cells or cytoskeletons, made by extracting with Triton in stabilizing buffer (Tsb), are fixed with formaldehyde, binding of the MAB Tp-GFAP1 to GFAP is abolished or greatly reduced. Fixation with the bifunctional protein crosslinking reagent dithiobis (succinimidyl propionate) (DTSP) has the same negative effect as formaldehyde. If cytoskeletons are further extracted with Tsb containing 250 mM ammonium sulfate (Thsb), fixation with formaldehyde or DTSP has reduced or no effect on the binding of Tp-GFAP1. The data are consistent with the hypothesis that aldehyde sensitivity of Tp-GFAP1 is caused by the crosslinking of a second protein to GFAP that blocks the binding of the MAB to its epitope. This putative blocking protein is part of the Triton-insoluble cytoskeleton, but it begins to be solubilized in 50 mM ammonium sulfate and it is largely removed in 250 mM ammonium sulfate (Thsb). SDS-PAGE shows that extraction with Thsb also removes a large number of proteins from the cytoskeleton, one of which could be the blocking protein. A second antibody to GFAP, designated Tp-GFAP3, was raised against cytoskeletons which had been fixed with DTSP and in which the epitope recognized by Tp-GFAP1 was presumably blocked. Tp-GFAP3 is not sensitive to fixation by either formaldehyde or DTSP.
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PMID:Formaldehyde sensitivity of a GFAP epitope, removed by extraction of the cytoskeleton with high salt. 244 10

The peroxidase anti-peroxidase technique was used for localization of glial fibrillary acidic protein (GFAP) and vimentin (VM) in 19 ependymal tumors in order to determine if a unique pattern of intermediate filament (IF) expression could be demonstrated. Cytokeratin (CK) immunoreactivity was examined in a subgroup of 7 tumors with papillary pattern. Nineteen non-ependymal neuroectodermal tumors were used as controls. Ependymomas, subependymomas and astrocytomas were positive for both IF. Oligodendrogliomas, oligodendroglial portions of mixed gliomas and the majority of medulloblastomas were negative for GFAP and VM. Areas of poor differentiation in all tumors demonstrated little expression of any IF. A composite ependymoma/choroid plexus papilloma showed the presence of GFAP, VM and CK in the papillomatous portion only. Four papillary ependymomas were negative for CK. This study emphasizes the parallel distribution of GFAP and VM in well differentiated ependymomas and other glial tumors and casts doubt upon the concept of VM as a marker for de-differentiation in neuroectodermal neoplasia.
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PMID:Immunocytochemical analysis of intermediate filaments in human ependymal tumors. 245 16

Intermediate filament proteins are cytoskeletal components in most vertebrate eukaryotic cells and some of these proteins are recognized markers of cell differentiation. To investigate the expression of intermediate filament proteins of the S-phase cells in human glial tumors, we have examined fourteen patients with benign and malignant gliomas by immunohistochemical study using in vivo labeling with bromodeoxyuridine (BrdU). Five glioblastoma multiforme, five anaplastic astrocytoma, three fibrillary astrocytoma and one gemistocytic astrocytoma were studied. All patients were given intravenous infusion of BrdU (10 mg/kg) one hour before craniotomy for labeling the S-phase cells of the tumors. Surgical specimens were immersed in 70% ethanol, and embedded in paraffin. Four micron sections were immunostained with anti-BrdU monoclonal antibody (Mab) and anti-vimentin Mab by avidin-biotin complex (ABC) method, and anti-glial fibrillary acidic protein (GFAP) serum by peroxidase-antiperoxidase (PAP) method. All sections (except for case 4) were double-labeled with anti-BrdU Mab and anti-GFAP serum, or with anti-BrdU Mab and anti-vimentin Mab. The population of BrdU-labeled cells (i.e. S-phase cells), and double-labeled cells were analyzed. The proportions of BrdU-labeled cells ranged from 6.1% to 17.0% (average 11.1%) in glioblastoma multiforme, from 3.5% to 15.6% (average 8.8%) in anaplastic astrocytoma, and from 2.0% to 2.8% (average 2.5%) in fibrillary astrocytomas. One gemistocytic astrocytoma showed S-phase fraction of 1.7%. Two recurrent cases of anaplastic astrocytoma showed higher S-phase fractions than other non-recurrent cases of anaplastic astrocytoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunohistochemical study of S-phase cells in human gliomas]. 246 Jan 17

Extracellular matrix (ECM) components of two glial fibrillary acidic protein positive (GFAP+) glioma lines U251 and UM6 were studied by silver stain, morphometry, immunofluorescence, enzyme-linked immunosorbent assay, and biosynthetic labeling. Both GFAP+ lines expressed the following qualitative features in common with previously studied GFAP-negative gliomas: (a) laminin, (b) type IV collagen, (c) extracellular fibrils of silver-reducing collagen (d) pattern of reactivity with lectins. Quantitative differences in GFAP+ glioma proteins included less collagen and more laminin than GFAP-negative gliomas. Sparse collagen of GFAP+ gliomas aggregated as extracellular masses. Individual cells of UM6 simultaneously expressed GFAP and mesenchymal ECM components. Results show qualitative similarities of ECM expression among GFAP+ and negative gliomas suggesting a common lineage of these two glioma cell types and universal expression of two epithelial components of ECM, laminin and type IV collagen, among cultured gliomas. Moreover, there is a diversity of quantity and type of ECM proteins of GFAP+ gliomas with the U251 line most restricted in its expression of ECM components and with UM6 manifesting markers of epithelial and mesenchymal lineage. This diversity suggests a capacity for regulation of phenotypic expression of ECM beyond that explained simply by the presence of two cell types of different lineage.
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PMID:Products of cells cultured from gliomas. VII. Extracellular matrix proteins of gliomas which contain glial fibrillary acidic protein. 246 18

We have obtained a cDNA fragment to human glial fibrillary acidic protein (GFAP) by immunoscreening a lambda gt11 human brain cDNA library with antibody to bovine GFAP. The highly homologous nucleotide sequence of this clone with that of the mouse GFAP enabled the identification of this cDNA as one encoding GFAP. As this cDNA hybridized with a single major RNA species in Northern blots of RNA from human and mouse brain tissues and gave one or two bands in Southern blots of human genomic DNA, it was considered to be specific for GFAP. Using this cDNA as a probe we investigated the levels of GFAP expression in ten human glioma cell lines. A 3.5-kb GFAP mRNA was detected in five of the ten glioma cell lines, one of which was U-251 MG cell line and the other four were clones derived from the same tumor (CL1, 2, 3, and 4). There was a difference in the amount of GFAP mRNA among U-251 MG and the four clonal cell lines. Quantitative evaluation of this difference by RNA dot blot analysis revealed that the amount of GFAP mRNA expressed in CL3 was about 1/5 and in CL4 about 1/10 the amount expressed in U-251 MG, CL1, and CL2. Semiquantitative Western blot analysis showed that GFAP levels corresponded to the GFAP mRNA levels in these cell lines. By Southern blot analysis of genomic DNA the GFAP gene was similarly detected in all of these cell lines regardless of the level of GFAP expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential expression of glial fibrillary acidic protein in human glioma cell lines. 247 40


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