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)

Loss of genetic information from a number of specific regions of the genome has been documented in primary human gliomas. Recently loss of heterozygosity or nullizygosity of the IFN beta 1 gene has been found in glioblastomas. We used Restriction Fragment Length Polymorphism (RFLP) analysis in order to screen the frequency of the loss of this genes in glial tumors of malignancy grades I-IV. Nullizygosity for IFN beta 1 was detected in 8/30 (27%) of glioblastomas (malignancy grade IV) and loss of heterozygosity in a further two cases (7%). In total, 33% of these tumors lost least one copy of the IFN beta 1 gene. Among the 10 anaplastic gliomas (grade III), 2 (20%) showed loss of one copy of the gene which none of the 7 low grade gliomas (grades I or II) showed any evidence of loss of IFN beta 1 alleles. The loss of the IFN beta 1 gene would appear to be a late event associated with the development of an increasingly malignant phenotype in human gliomas and to be confined to gliomas of malignancy grade III or IV.
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PMID:Frequency of IFN beta 1 gene loss in 47 primary human gliomas. 810 98

Basement membrane invasion precedes meningeal dissemination and systemic metastasis of glioma cells. In order to investigate the invasive ability of glioblastomas and the functional role of extracellular matrix receptors, the authors performed in vitro invasion assays where the number of cells was determined from freshly resected tumors (primary cultures and fifth passages) and from cell lines (U-138 MG, U-373 MG, and GaMg) that had migrated through a filter coated with a reconstituted basement membrane (Matrigel). The involvement of integrin adhesion molecules was examined by preincubation of glioma cells with blocking antibodies to specific integrin chains. Cells from all of the glioblastomas had migrated through the Matrigel after 4 to 24 hours; the number of invasive cells was highest in the cell lines. Invasion of U-138 MG cells was reduced with antibodies to alpha 7, alpha v, beta 1, and beta 3 integrin chains and markedly increased by anti-alpha 5, while invasion of U-373 MG cells was reduced by antibodies to alpha 3, alpha v, beta 1, and beta 3 and increased by anti-alpha 6. It is concluded that: 1) glioma cells are able to penetrate Matrigel, indicating that the basement membrane is not a resistant barrier for infiltrating cells; and 2) basement membrane invasion is mediated by integrins in a complex manner. Some integrins promote while others inhibit basement membrane invasion. Furthermore, the integrins involved may differ between various glioma cells.
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PMID:Basement membrane invasion of glioma cells mediated by integrin receptors. 811 64

Malignant gliomas are associated with a state of systemic immunosuppression which appears to be partially mediated by transforming growth factor beta (TGF-beta) secreted from glioma cells. In a recently described animal model of malignant glioma, massive activation of local microglial cells and formation of microglia-derived macrophages has been observed in the absence of detectable tumour regression. We have investigated the in situ expression of TGF-beta in rat glioma as a possible cause of ineffective tumour destruction. Two weeks following unilateral injection of glioma cells, large tumours were observed in the affected hemisphere. In situ hybridization for TGF-beta 1 mRNA revealed an intense signal over the entire tumour area. In the peritumoural area, at sites of glial activation, a lower signal was obtained over cellular profiles containing nuclei typical for microglia, as well as other unidentified cellular profiles. No signal was obtained over the contralateral unaffected hemisphere. Northern blot analysis revealed a strong expression of TGF-beta 1 mRNA in tumour tissue, a lesser signal in the peritumoural reactive brain tissue and virtually no signal in normal tissue. Our data indicate that the experimental rat glioma has the potential to secrete TGF-beta in vivo which might render the microglial infiltration ineffective. TGF-beta expressed by activated microglial cells themselves might further inhibit their tumoricidal potential, thus contributing further to unrestrained tumour growth.
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PMID:In situ detection of transforming growth factor-beta mRNA in experimental rat glioma and reactive glial cells. 817 93

A human blood group B-active glycosphingolipid, belonging to the ganglio-series, was isolated from rat glioma cell line RG2 subcutaneous isografts. The oligosaccharide structure of the glycosphingolipid was completely characterized as Gal alpha 1-3(Fuc alpha 1-2)Gal beta 1-3GalNAc beta 1-4Gal beta 1-4Glc beta 1- 1'ceramide by NMR spectrometry, negative fast atom bombardment-mass spectrometry, sequential degradation by glycosidases and methylation analysis. Human blood group B antigenicity and the activity of this glycosphingolipid were confirmed by immunostaining on thin-layer chromatography and the inhibition of hemagglutination, respectively. Although the lipid has been detected in rat granuloma, bone marrow cells, spleen, thymus, ascites hepatoma cells and gastric mucosa, this is the first report of the occurrence of the B-active lipid in glioma.
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PMID:Human blood group B-active ganglio-glycosphingolipid in rat glioma. 839 23

Two monoclonal antibodies, DMAb-21 and DMAb-22, directed against the lactotetraose series ganglioside-associated epitope IV3NeuAc,III6-NeuAcLcOse4Cer (3',6'-isoLD1), were found to define the minimum binding epitope NeuAc(or NeuGc)alpha 2-3Gal beta 1-3(NeuAc or NeuGc)alpha 2-6GlcNAc. The distribution of 3',6'-isoLD1 in cultured cell lines and derived xenografts of primary tumors of the human central nervous system and of embryonal or neuroectodermal tumor derivation was determined. Only 4 of 26 cell lines, 3 teratomas and 1 pancreatic adenocarcinoma, expressed detectable 3',6'-isoLD1 when cultured in vitro; none of 14 tested glioma lines, including 2 that expressed the monosialo-precursor IV3NeuAcLcOse4Cer in vitro, expressed detectable levels. Expression of 3',6'-isoLD1 was more frequent when neoplastic cells were grown in xenograft form in athymic mice; 4 of 10 glioma and 2 of 2 teratoma xenograft ganglioside extracts were positive for 3',6'-isoLD1. The absence of 3',6'-isoLD1 in cultured tumor cells of the central nervous system and its proportional increased presence in tumor cells of the same origin grown in vivo further supports previous studies suggesting that ganglioside expression may be modified by environmental forces. The expression of lacto series gangliosides both in vitro and in vivo by teratoma and pancreatic adenocarcinoma cells, as opposed to only in vivo expression by glioma cells, suggests that tissue-specific forces may also exist. Immunohistochemical localization of 3',6'-isoLD1 in frozen sections of primary central nervous system neoplasms including those of glial and nonglial origin was performed; 20 of 30 (67%) of glial tumors were positive. Among nonglial tumors, 21 of 34 (62%) of epithelial cancers were reactive with anti-3',6'-isoLD1 monoclonal antibodies; notably negative were carcinomas of the ovary and lung carcinomas of all subtypes. Lymphomas and infiltrative lymphocytes were uniformly negative. The restriction of 3',6'-isoLD1 expression within the human central nervous system to periods of fetal-neonatal astroglial proliferation, to intense reactive astrocytosis, and to primary neoplasms, and the production of specific monoclonal antibodies to this epitope provide a specific complex for immunolocalization and, eventually, immunotherapy.
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PMID:Lactotetraose series ganglioside 3',6'-isoLD1 in tumors of central nervous and other systems in vitro and in vivo. 841 36

Transforming growth factors-beta 1 and -beta 2 (TGF-beta 1 and -beta 2) are important growth-regulatory proteins for astroglial neoplasms. We analyzed their role in tumor-cell proliferation in 12 glioma cell lines, employing phosphorothioate antisense oligodeoxynucleotides (S-ODNs, 14 mer), specifically targeted against the coding sequences of TGF-beta 1-mRNA and TGF-beta 2-mRNA. TGF-beta 1-S-ODNs inhibited cell proliferation in 5 of 12 gliomas, whereas TGF-beta 2-S-ODNs reduced the cell proliferation in all glioma cell lines, compared to nonsense-S-ODN-treated and S-ODN-untreated cells as controls. The efficacy and specificity of antisense effects was validated by Northern-blot analysis and determination of protein concentrations in culture supernatants (ELISA). Exogenous hrTGF-beta 1 either stimulated or inhibited the cell lines, whereas pnTGF-beta 2 stimulated the proliferation of most glioma cells. Blocking the extracellular pathway of TGF-beta by neutralizing antibodies only slightly inhibited those cell lines, which were markedly stimulated by TGF-betas. As the effects of TGF-beta 2-S-ODNs were much stronger than those of TGF-beta neutralizing antibodies, we postulate that the endogenously produced TGF-beta 2 control glioma-cell proliferation, in part by an intracellular loop.
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PMID:Transforming growth factor-beta-mediated autocrine growth regulation of gliomas as detected with phosphorothioate antisense oligonucleotides. 857 54

The C6 glioma cell line, which expresses beta 1- and beta 2-adrenoceptors at a ratio of 80:20, was used to investigate the durations of action of formoterol at beta 1-adrenoceptors and of salmeterol at both beta 1- and beta 2-adrenoceptors in an attempt to determine whether the sustained duration of action of salmeterol was unique to beta 2-adrenoceptors or, as with formoterol, resulted from its lipophilic nature and partitioning into the bulk lipid of the plasma membrane. In this cell line, formoterol, like the nonselective beta-adrenoceptor agonist isoprenaline, behaved as a potent, full agonist at beta 1-adrenoceptors and did not seem to exhibit a high degree of selectivity for beta 2-adrenoceptors. Salmeterol seemed to stimulate cAMP accumulation in C6 cells predominantly via activation of the subpopulation of beta 2-adrenoceptors. However, at high (micromolar) agonist concentrations, salmeterol also activated beta 1-adrenoceptors, albeit with low potency and efficacy. At high concentrations (30 microM), salmeterol attenuated cAMP responses mediated by activation of beta 1-adrenoceptors by isoprenaline (Kp = 1.6 microM), indicating that salmeterol exhibited a low affinity for beta 1-adrenoceptors in C6 cells. In multiple washout experiments, cAMP responses to isoprenaline and formoterol waned with increasing numbers of washing processes. Therefore, it seemed that formoterol relied on its moderately lipophilic nature to partition into bulk lipid of the plasma membrane to produce sustained activity, particularly at high agonist concentrations. Salmeterol was found to persist at beta 2-adrenoceptors in C6 cells despite washing cell monolayers up to four times. To determine the duration of action of salmeterol at beta 1-adrenoceptors expressed on the same cells, use was made of full/partial agonist interactions. In cells exposed to a single washout of agonist-containing medium, salmeterol (30 microM) lost its ability to attenuate responses to the more efficacious agonist, isoprenaline. This observation provided convincing evidence to support the hypothesis that salmeterol exhibits sustained agonist activity at beta 2-adrenoceptors, but not beta 1-adrenoceptors, expressed on the same cells. Therefore, the sustained activity of salmeterol at beta 2-adrenoceptors seems to be unique and does not result solely from its partitioning into bulk lipid of the plasma membrane.
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PMID:Comparison of duration of agonist action at beta 1- and beta 2- adrenoceptors in C6 glioma cells: evidence that the long duration of action of salmeterol is specific to the beta 2-adrenoceptor. 862 43

We have investigated the effect of integrin antibodies to a well-characterized alpha 5 beta 1 (fibronectin receptor) and to a multi-specific alpha 3 beta 1 (laminin, collagen, and fibronectin receptor), on the expression of matrix metalloproteases and the invasion ability of two human glioblastoma cell lines, SNB19 and U251. Cell adhesion assays indicated that both cell lines adhere to fibronectin, type IV collagen and laminin. Adhesion of cells to fibronectin was inhibited by a RGD peptide. Cells treated with anti-alpha 3 beta 1 or anti-alpha 5 beta 1 antibodies expressed increased levels of MMP-2. An in vitro matrigel assay also showed that the alpha 3 beta 1 antibody-treated cells had greater invasive ability than the controls. Immunofluorescence data showed that glioma cells treated with either anti-alpha 3 beta 1 or anti-alpha 5 beta 1 antibodies expressed diminished alpha 3 beta-1 and alpha 5 beta 1 integrins relative to the controls. The data show that treatment of cells with alpha 3 beta 1 antibody diminishes the integrin expression on the cell surface and increases the MMP-2 activity and invasiveness.
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PMID:Modulation of matrix metalloprotease-2 and invasion in human glioma cells by alpha 3 beta 1 integrin. 863 58

We examined the role of beta 1- and beta 2-adrenergic receptor (AR) density and ratio in catecholamine-stimulated cAMP responses in rat C6 glioma cells. These cells, which normally express both subtypes, were stably transfected with an isopropylthio-beta-D-galactoside-inducible vector containing either beta 1AR or beta 2AR coding sequences, and receptor expression was controlled by the time and concentration of isopropylthio-beta-D-galactoside exposure. Induction of the dominant beta 1AR subtype increased the potencies of isoproterenol (ISO) and other agonists in stimulating cAMP accumulation by 20-40-fold without changing maximal response. Induction of beta 2AR expression caused 7-13-fold increases in the potency of ISO, epinephrine, and zinterol, but not of norepinephrine, and a 20-40% loss in maximal response to all agonists. Selective antagonists showed that both subtypes contributed in a nonadditive manner in the response to ISO under different conditions. After beta 2AR induction, the effects of ISO were not blocked by the beta 1-selective antagonist CGP 20712A but were shifted 100-fold to the right by the beta 2-selective antagonist ICI 118,551. However, in the presence of ICI 118,551, CGP 20712A caused an additional 100-fold decrease in ISO potency, and Schild analysis revealed complex interactions between the two subtypes. Each antagonist alone caused smaller shifts to the right in the dose-response curve to NE and, when present simultaneously, completely abolished the NE response. We conclude that beta 1ARs and beta 2ARs have different efficiencies in activating cAMP accumulation in C6 glioma cells. Activation of coexisting subtypes results in complex and sometimes synergistic interactions between the two subtypes, which vary with agonist concentration, selectivity, subtype density, and ratio.
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PMID:Inducible expression of beta 1- and beta 2-adrenergic receptors in rat C6 glioma cells: functional interactions between closely related subtypes. 870 Jan 11

The expression of CMP-NeuAc: Gal beta 1,4GlcNAc alpha 2,6 sialyltransferase (alpha 2,6-ST) [EC 2.4.99.1] and glycoproteins bearing alpha 2,6-linked sialic acids were examined in primary human brain tumours and cell lines. 79% (19/24) of the meningiomas expressed alpha 2,6-ST mRNA, 42% (10/24) of which showed very high expression. alpha 2,6-ST mRNA expression was undetectable in normal brain tissue. In contrast, only 1/13 of the gliomas examined expressed detectable alpha 2,6-ST mRNA. Metastases to the brain did not express measurable amounts of alpha 2,6-ST mRNA. Less expression was found in malignant (i.e. anaplastic) compared to benign (i.e. meningothelial) meningiomas. Two-dimensional SDS-PAGE of glioma and meningioma proteins, followed by Sambucus nigra lectin staining, revealed the presence of a glycoprotein bearing alpha 2,6-linked sialic acids, M(r) = 53 kDa and a pI = 7.0 (MEN-1) that appeared in all seven of the meningiomas examined, but was expressed at barely detectable levels, if at all, in seven out of the seven glioblastomas examined. Thus, decreased alpha 2,6-ST expression may play a role in the aggressive nature of anaplastic meningiomas, but appears to be virtually absent in all tumours of glial origin.
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PMID:The expression of CMP-NeuAc: Gal beta 1,4GlcNAc alpha 2,6 sialyltransferase [EC 2.4.99.1] and glycoproteins bearing alpha 2,6-linked sialic acids in human brain tumours. 874 63


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