Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gangliosides in human gliomas were investigated and found to have an altered composition and concentration as compared to normal grey and white matter of brain. The major gangliosides GM1, GD1a, and GT1b were markedly reduced in the tumour tissue and in contrast there was an increase of gangliosides GM3 and GD3, which often appeared as the dominating ones. Moreover, the tumours contained gangliosides, both mono- and oligosialylated, which could not be detected in the normal brain. The concentration of gangliosides, 0.7 +/- 0.4 mumol sialic acid/g, was significantly lower as compared to normal brain grey (p less than 0.001) and white matter (p less than 0.01), which contained 3.5 +/- 0.3 and 1.2 +/- 0.3 mumol sialic acid/g respectively. The tumour tissue concentration of phospholipids was 14 +/- 8 and of cholesterol 19 +/- 12 mumol/g. The appearance in glioma tissue of gangliosides that are not found in normal brain tissue suggests that these are tumour associated and might serve as surface antigens detectable by specific monoclonal antibodies.
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PMID:Potential ganglioside antigens associated with human gliomas. 287 7

Malignant transformation is characterized by the uncontrolled proliferation of cells. And changes in the composition of glycolipids, cell surface component which may be involved in regulation of cell growth, were often observed in the malignant transformation. In this study, cholesterol, lipid-bound phosphorus, cerebroside, sulfatide and ganglioside were quantitated in the tissue of 20 human malignant brain tumors (malignant glioma, 8; low grade glioma, 4; metastatic tumor, 7; malignant meningioma, 1). As compared with normal brain, all tumor tissue contained lower cholesterol, sialic acid, cerebroside and sulfatide. Metastatic brain tumor or glioma showed characteristic patterns in the content of ganglioside, cerebroside and sulfatide respectively. The ganglioside patterns of metastatic tumor or glioma contained a greater proportion of structurally simpler gangliosides than normal brain. And in metastatic tumor, GM3 was a major ganglioside. On the contrary, glioma had increased proportion of GM3 and GD3 gangliosides. High grade glioma such as Grade 3-4 contained higher proportion of GM3 and GD3, whereas low grade glioma (Grade 1-2) contained less proportion of GM3 and GD3.
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PMID:[Lipid composition of human malignant brain tumors]. 303 15

In this study, MAbs to the 'conventional' gangliosides expressed by human gliomas were generated and used to detect ganglioside species previously unisolated or defined in normal adult CNS tissue. Despite the marked phenotypic and genotypic heterogeneity shown by glioma cell lines (Bigner et al., 1981), the ganglioside phenotype of these cell lines is remarkably consistent qualitatively, if not quantitatively, in the ganglioside species expressed (Table V). The majority of cell lines and tumor samples express GM2, GD2 and GD3; this does not provide a diagnostic advantage (Vick et al., 1992). Nevertheless, as the relative amounts of these gangliosides in tumor as compared with normal adult CNS tissue is considerable, such reagents might be considered in compartmental immunotherapeutic approaches. Since GD2 and GD3 have been determined to mediate tumoricidal activity with human effector cells via specific antiganglioside epitope MAbs (Thurin et al., 1987; Kushner and Cheung, 1991; Barker et al., 1991; Reisfeld, 1993), cell-mediated approaches, as well as targeted immunoglobulin therapies, are also possible. The prospect of a more targeted approach with little or no effect on normal CNS tissue is now possible via the 'oncofetal' epitopes characteristic of 3'-isoLM1 and 3',6'-isoLD1. Several factors recommend the use of these moieties for compartmental immunotherapy; the inability to detect them within the adult CNS; the relatively high frequency of expression of 3'-isoLM1 and 3',6'-isoLD1, especially in human tumor samples (50-100%, depending upon the series and assay); and the existence of specific MAbs reactive with these epitopes. Current technology is being applied to these MAbs to transfer the specific recognition capacity of existing murine MAbs into various human framework structures of any desired immunoglobulin class, and thereby, biologic function. The variety of effector functions, the stability in affinity, labeling capacity, and the exquisite sensitivity of these MAbs for these glioma-distinctive epitopes is an exciting and promising approach for immunotherapy of human CNS tumors.
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PMID:Detection of glioma-associated gangliosides GM2, GD2, GD3, 3'-isoLM1 3',6'-isoLD1 in central nervous system tumors in vitro and in vivo using epitope-defined monoclonal antibodies. 751 92

Adhesion of eight cell lines, derived from human gliomas of different histological types, to fibronectin, collagen I, vitronectin, and laminin was investigated in vitro. The glioma cell lines were found to attach to these substrates to different extents. Interestingly, all cell lines strongly attached to laminin. In addition, glioma cell adhesion was found to be dose dependent. Moreover, adhesion of three cell lines to fibronectin and collagen I was partially inhibited and to vitronectin completely prevented by GRGDTP peptide, indicating the involvement of integrin receptors in glioma cell adhesion. We have demonstrated, recently, that gangliosides play an important role in promoting glioma cell invasion of the reconstituted basement membrane, Matrigel, in vitro. In order to study the mechanism of action of gangliosides in this process, the role of six gangliosides (GM1, GM3, GD3, GD1a, GD1b, and GT1b) in cell adhesion to the four proteins was investigated in three cell lines. Although all gangliosides, with the exception of GM3, were found to enhance cell adhesion to these proteins to different extents, GD3 proved to be the most effective adhesion-promoting ganglioside in all three cell lines. GM3 was found to inhibit cell adhesion to the four proteins in one cell line but enhanced cell adhesion in two other cell lines. The three cell lines were found to express both GD3 and gangliosides recognised by the A2B5 antibody. Furthermore, adhesion of the three cell lines to fibronectin, vitronectin, laminin, and collagen I was inhibited by incubation with A2B5, demonstrating the involvement of intrinsic cell membrane gangliosides in adhesion of glioma cells to these proteins. Taken together with the observation that gangliosides modulate integrin receptor function, these data suggest that gangliosides may play a central role in the control of the adhesive and invasive properties of human glioma cells.
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PMID:Adhesion of human glioma cell lines to fibronectin, laminin, vitronectin and collagen I is modulated by gangliosides in vitro. 774 20

In order to evaluate the proliferation and differentiation potentials of ethylnitrosourea (ENU)-induced rat glioma cells, the authors attempted to obtain a cell line that maintains glial features in long-term culture. One of five cell lines cultivated from ENU-induced rat gliomas merited particular interest because of the differentiation of its neoplastic glia. This cell line, designated as HITS glioma, had a polygonal cell body and formed a monolayer with pile-up foci in vitro, in contrast to the other cell lines, which displayed a mesenchymal change through passages. GFAP-positive cells, found in the primary culture, disappeared in the late passages of HITS glioma, as they did in the other cell lines. Galactocerebroside (GC), GD3 ganglioside, and Leu7 were not expressed in the cell lines during culture. Subcutaneous inoculation of HITS glioma into neonatal rats induced tumors with histopathological components mimicking the histopathological appearance of ENU-induced gliomas. The components also had a fraction of GFAP-positive cells. Such findings indicate that HITS glioma cells may be composed of immature glial cells which are able to differentiate into astrocytic cells under certain conditions. Several growth factors which play a role in gliogenesis were used to evaluate the mechanism(s) of proliferation and/or differentiation of HITS glioma. These growth factors did not induce the expression of GFAP and other antigenic expression in HITS glioma, even though some promoted the proliferation of HITS glioma. Although the mechanism involving the astrocytic differentiation of HITS glioma is unknown, HITS glioma may serve as an effective tool in research to evaluate the mechanisms of proliferation and differentiation of neoplastic glia.
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PMID:GFAP expression in the subcutaneous tumors of immature glial cell line (HITS glioma) derived from ENU-induced rat glioma. 816 56

We previously showed that gangliosides inhibit DNA synthesis in Swiss 3T3 cells stimulated with platelet-derived growth factor (PDGF) in a dose-responsive manner. This correlated with the inhibitory effects of several gangliosides (except GM3) on tyrosine phosphorylation of the PDGF receptor (PDGFR). [35S]Methionine-labeled Swiss 3T3 cells were incubated either with or without gangliosides and stimulated with PDGF, and proteins were cross-linked with bis(sulfosuccinimidyl) suberate. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that two protein bands (170 and 350 kDa) were specifically immunoprecipitated with an anti-PDGFR antibody. Using both Swiss 3T3 and human glioma U-1242MG cells, western blots with anti-PDGFR and anti-phosphotyrosine antibodies confirmed that these bands were the PDGFR monomer and dimer, respectively, and that phosphotyrosine was present in these bands only after cells were stimulated with PDGF. Of the gangliosides tested, GM1, GM2, GD1a, GD1b, GD3, and GT1b, but not GM3, inhibited the formation of the 350-kDa band. These results demonstrate that all gangliosides tested, except GM3, probably inhibit PDGF-mediated growth by preventing dimerization of PDGFR monomers. Loss of more complex gangliosides in human gliomas would permit unregulated activation of the PDGFR, contributing to uncontrolled growth stimulation. We propose that ganglioside inhibition of receptor dimerization is a novel mechanism for regulating and coordinating several trophic factor-mediated cell functions.
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PMID:Gangliosides inhibit platelet-derived growth factor-stimulated receptor dimerization in human glioma U-1242MG and Swiss 3T3 cells. 851 85

Vascular endothelial growth factor (VEGF) is an angiogenic factor which is known to be expressed in several malignancies including glioma. The effect of transforming growth factor-beta (TGF-beta) isoforms as well as gangliosides on VEGF production was investigated in human glioma cell lines. TGF-beta isoforms and gangliosides were found to differentially stimulate VEGF production by these cells. The ganglioside GD3 enhanced this release to the greatest extent and the stimulation was more marked in a glioblastoma cell line than in the two other anaplastic astrocytoma cell lines. These results suggest that both TGF-betas and gangliosides may act as indirect angiogenic factors by stimulating VEGF secretion.
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PMID:Vascular endothelial growth factor production is stimulated by gangliosides and TGF-beta isoforms in human glioma cells in vitro. 860 72

A major hallmark of gliomas is their intense neovascularisation. Ganglioside GD3, is one of the major gangliosides which has been implicated in tumour angiogenesis. Recently we reported that GD3 was a potent stimulator of vascular endothelial growth factor release in human glioma cell lines. In the present study we were able to detect GD3-immunoreactivity in 10 out of 10 cases of glioblastoma multiforme and 7 out of 10 cases of anaplastic astrocytoma while low grade tumours were negative. Interestingly, GD3 was intensively expressed in hypervascularised areas of high grade gliomas. These data support the involvement of this ganglioside in brain tumour angiogenesis.
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PMID:Vascular and perivascular GD3 expression in human glioma. 864 Jul 53

Matrix metalloproteinases (MMPs) are zinc-dependent peptidases and are amongst those enzymes responsible for extracellular matrix (ECM) degradation during tumour-cell migration. Gangliosides are a family of acidic membrane glycolipids thought to play a role during cell development, differentiation and oncogenic transformation. In this descriptive study, we investigated the effects of six exogenous gangliosides (GM1, GM3, GD1a, GD1b, GD3 and GT1b) on the secretion of MMP-2 (72 kDa gelatinase or gelatinase-A) and MMP-9 (92 kDa gelatinase or gelatinase-B). Cell-conditioned media from eight human glioma-derived cell-lines served as the source of MMPs and were investigated using SDS-PAGE zymography. Six of the cell lines showed upregulation of secretion of both enzymes by all six gangliosides. Of the remaining two cell lines, one showed inhibition of MMP secretion by all gangliosides and the other had a small but differential response to the range of gangliosides investigated. These results suggest that gangliosides may stimulate glioma cell invasiveness by promoting MMP expression.
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PMID:The effect of exogenous gangliosides on matrix metalloproteinase secretion by human glioma cells in vitro. 908 68

Glioma-associated gangliosides, in particular the expression of foetal gangliosides 3'-isoLM1 and 3'6'-isoLD1, have been investigated in biopsies from 44 patients with astrocytoma grade II, anaplastic astrocytoma, anaplastic oligodendrogliomas, oligodendrogliomas, and glioblastoma multiforme. The total ganglioside content decreased in proportion to the estimated number of tumour cells present in the biopsy. Ganglioside GD3 was increased in 17 of the tumour tissues and in 6 of the surrounding area specimens. In agreement with our previous studies, tumour specimens contained the lactoseries ganglioside 3'-isoLM1 and, as demonstrated for the first time, the disialylated form of the ganglioside, 3'6'-isoLD1. These gangliosides are in normal brain tissue restricted to the developmental period. Most frequent was the expression of ganglioside 3'-isoLM1 which was detected in 92% of the tumour specimens in concentrations varying between just detectable amounts to 13 nmol/g wet weight. In the area surrounding the macroscopic tumour tissue 78% of the specimens expressed 3'-isoLM1 and the values varied between just detectable amounts to 24 nmol/g wet weight. Ganglioside 3'6'-isoLD1 was found in 47% of the tumour biopsies and in only 17% of the specimens taken outside macroscopic tumour tissue. The values varied between non-detectable amounts to 40 nmol/g wet weight of tissue. The expression of 3'-isoLM1 correlated significantly (p < 0.01) to malignancy grade. For 3'6'-isoLD1 a significant (p < 0.05) difference was found between tumour and surrounding tissue. Likewise, 3'6'-isoLD1 correlated significantly (p < 0.05) to malignancy grade. The correlation between 3'-isoLM1 and 3'6'-isoLD1 to malignancy grade and the frequent expression of these gangliosides both in the tumour itself and in its surrounding area should encourage additional studies concerning their biological role in tumour disease.
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PMID:The presence of foetal ganglioside antigens 3'-isoLM1 and 3'6'-isoLD1 in both glioma tissue and surrounding areas from human brain. 908 72


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