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)

Viral infection results in enhancement of HLA-class I expression in a number of cell types, including glial cells, which normally do not express these molecules. This enhancement may occur through a direct interaction between a viral component and the HLA-class I gene or indirectly through virus-induced soluble factors produced by infected cells. These include cytokines such as IFN-gamma, IFN-alpha/beta, and TNF-alpha, known to enhance class I expression. Measles virus (MV) infection of a human glioma cell line (U-105 MG) and of primary human umbilical vein endothelial cells enhances the expression of HLA-class I molecules on these cells. The enhancement of HLA-class I is dependent on infectious virus, as antibody-neutralized MV has no effect on class I expression. In this study, we demonstrate the presence of an HLA-class I-enhancing factor in supernatants from MV-infected cells. The supernatant class I-enhancing factor is not IFN-gamma, IFN-alpha, or TNF-alpha because MV-infected cells did not produce measurable levels of these cytokines as detected by immunoassay or polymerase chain reaction. In contrast, IFN-beta is produced by the infected cells and the supernatant class I-enhancing factor could be entirely neutralized by antibodies to IFN-beta, but not antibodies to IFN-alpha, TNF-alpha, or non-immune sera. Furthermore, preincubation of cells with neutralizing antibodies to IFN-beta prior to infection blocked MV enhancement of HLA-class I completely in the U-105 MG cells and by as much as 74% in the umbilical vein endothelial cells. The results of these experiments provide direct evidence that enhanced HLA-class I expression in MV-infected cells is mediated primarily by IFN-beta.
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PMID:Direct evidence that interferon-beta mediates enhanced HLA-class I expression in measles virus-infected cells. 824 64

Southern blot analyses of the 9p-localized type I interferon (IFN) genes in DNAs obtained from malignant glioma cell lines and glial tumor tissue have indicated that homozygous deletions of the IFN-alpha and IFN-beta genes often occur during the development of the highly malignant central nervous system neoplasm, glioblastoma. We have applied a set of markers that span the IFN region on 9p to the analysis of DNAs from 30 human glioma cell lines in order to define the region of homozygous deletion associated with this cancer more precisely. Fourteen of the cell lines revealed either complete (12 cases) or partial (2 cases) homozygous deletions of the IFN-alpha gene cluster; no instances of homozygous deletions were observed that did not involve the IFN-alpha region. Genomic DNA identified by the markers nearest to and flanking the IFN-alpha genes were retained in 5 of the cases with homozygous deletions. Consequently, these results limit the extent of homozygous deletions in glioma cell lines to a small region of 9p21-p22 that includes most of the type I IFN locus.
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PMID:Localization of chromosome 9p homozygous deletions in glioma cell lines with markers constituting a continuous linkage group. 833 74

Human interferon beta (IFN-beta) has been used for the treatment of patients with benign and malignant astrocytomas. The effect of IFN-beta on pituitary function, however, has not been precisely evaluated before. In this study the serum levels of various anterior pituitary hormones including GH, PRL, ACTH, and TSH were measured to determine the effects of IFN-beta on pituitary endocrine function in 19 consecutive glioma patients receiving IFN-beta. Daily doses of 3 x 10(6) U of IFN-beta were administered as a 30-min intravenous drip infusion beginning at 0800 h every morning during the first week and then 4 times a week for additional 6 weeks. Blood samples were taken on the day prior to administration as controls (0900 h and 1500 h), and on the first day of administration (0900 h and 1500 h) and after 7 days of administration (0900 h) in order to determine the acute and chronic or integrated effects of IFN-beta on the above pituitary hormones. No significant change in serum concentrations of any of the pituitary hormones examined was observed, suggesting that human natural IFN-beta used for the treatment of gliomas has no significant effect on the secretion of these hormones from the pituitary in these patients.
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PMID:A study of anterior pituitary hormones secretion in patients with glioma receiving interferon-beta treatment. 888 29

The growth inhibitory effect of IFN-beta was evaluated in 5 human glioma cell lines (AO2V4, GJC, GJR, NN and NNR) and in normal astrocyte cultures (SC and TM). All 5 glioma cell lines showed an anti-proliferative response to IFN-beta whereas normal glial cells were non-responsive. IFN-beta at 10, 100 and 500 U/ml lead to a 30%, 70% and 80% relative decrease in cell number after 12 days, respectively in AO2V4 cells. GJC and GJR cell lines also responded significantly to the lowest concentration of IFN-beta tested and at 500 U/ml the relative cell number decreased 55%. The NN and NNR cells were the least responsive to IFN-beta with maximum growth inhibition of 30% at 500 U IFN-beta/ml. Following treatment with IFN-beta, AO2V4, GJC, GJR and normal astrocytes all expressed mRNA encoding the anti-viral protein, 2-5A synthetase demonstrating that IFN-beta bound to receptors on all four cell lines and activated signal transduction pathways required for induction of an anti-viral protein. A determination of the relative number of viable cells showed that none of these cells exhibited a significant decrease in cell viability. Since the antiproliferative response to IFN-beta was not primarily due to cell death, the effect of IFN-beta on cell cycle progression was evaluated by flow cytometry. All treated glioma cell lines showed a relative increase in proportion of cells in S phase. AO2V4 cells had a 50%-80% increase in the percentage of cells in S phase, whereas GJC, GJR and NNR had percentage increases of 20%-40%. IFN-beta treatment of normal astrocytes did not significantly alter their cell cycle profile. These data suggest that IFN-beta exerts its antiproliferative effect on glioma cells by arresting the ordered progression through S phase or decreasing entry into G2/M phase of the cell cycle.
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PMID:Interferon-beta inhibits proliferation and progression through S phase of the cell cycle in five glioma cell lines. 894 96

Rat interferon beta (IFN beta) was cloned from a part of rat genomic DNA by the polymerase chain reaction (PCR) with reference to the nucleotide sequence data of a mouse IFN beta. The sequence result showed that the clone had 555 bp of open reading frame (ORF) which encoded a 184-amino acid polypeptide. Comparison of our data with those of mouse and human IFN beta revealed 86.7 and 67.6% homology at the nucleotide level, and 76.2 and 48.9% homology at the amino acid level, respectively. This ORF was inserted into an expression vector, pCAGGS, and COS-1 cells were then transfected with the plasmid encapsulated in cationic multilamellar liposomes. From the results of reverse transcription-PCR and cytopathic activity assay, this ORF expressed IFN beta in COS-1 cells. When the cultured cells of rat glioma cell line T9 were transfected with the plasmid, their growth was markedly suppressed due to the expression of rat IFN beta.
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PMID:Isolation and expression of rat interferon beta gene and growth-inhibitory effect of its expression on rat glioma cells. 912 38

Systemic interferon-beta-Ib (IFN-beta-Ib) reduces the frequency of clinical exacerbations and the number of magnetic resonance imaging (MRI)-defined lesions in patients with relapsing-remitting MS. The basis for this clinical effect is not understood. While IFN-beta-Ib has been demonstrated to have antiproliferative and immunomodulatory effects on the systemic immune system, its actions on neural cells could also contribute to its therapeutic efficacy. In this study, we have examined possible immune and non-immune effects of IFN-beta-Ib on CNS-derived primary human cells. With respect to immune-related effects, application of IFN-beta-Ib did not decrease basal expression of HLA-DR on astrocytes or microglia, and it reduced the IFN-gamma-enhanced HLA-DR expression on adult human astrocytes only at high concentrations (1000 IU ml-1); IFN-beta-Ib at all concentrations tested did not reduce the IFN-gamma-enhanced HLA-DR expression by fetal astrocytes or adult microglial cells. In contrast, but in correspondence with the literature, the IFN-gamma-enhanced HLA-DR expression on a glioma cell line was attenuated by IFN-beta-Ib in a dose-dependent manner. With respect to non-immune effects, the number of adult human oligodendrocytes and their state of morphological differentiation were not affected by IFN-beta-Ib. Proliferation of the mitotically active fetal human astrocytes, however, was reduced by IFN-beta-Ib treatment. Lactate dehydrogenase assays revealed that IFN-beta-Ib was not toxic to neural cells, including adult oligodendrocytes and fetal human neurons. We conclude that IFN-beta-Ib lacks efficacy in down-regulating HLA-DR expression by primary human neural cells and that regulation of MHC class II antigens is unlikely to be a mechanism for its beneficial effect in MS. Finally, the lack of toxicity of IFN-beta-Ib on human neural cells is important for a drug that will probably be used widely.
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PMID:Immune and non-immune actions of interferon-beta-Ib on primary human neural cells. 934 64

1. Human medulloblastoma (ONS-76), a central nervous system (CNS)-derived undifferentiated cell line, was found to possess glial characteristics as defined by responses in the interferon (IFN) system; ONS-76 cells produced as much IFN-beta as human fibroblast and glioma cells by viral infection and poly(I):poly(C) induction. 2. Major histocompatibility complex (MHC) class I antigens were also induced under IFN-beta stimulation. ONS-76 cells expressed neurofilament protein, as shown by Northern blot analysis, and morphological differentiation was induced by dibutyryl cyclic AMP (dcAMP). 3. Expression of IFN-beta and MHC class I antigens was suppressed in ONS-76 cells during the dcAMP-induced differentiation. 4. These results showed that ONS-76 cells possessed a glial property in IFN system responses and a neuronal property in cytoskeleton protein, suggesting that the precursors of medulloblastoma may be characterized as bipotent neuronal and glial progenitors in CNS.
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PMID:Interferon yield and MHC antigen expression of human medulloblastoma cells and its suppression during dibutyryl cyclic AMP-induced differentiation: do medulloblastoma cells derive from bipotent neuronal and glial progenitors? 977 50

In this study, we examined the clinical course and prognosis of 32 patients with malignant glioma (17 patients with anaplastic astrocytoma, 15 patients with glioblastoma) treated with the MIC regimen (radiation, MCNU, carboplatin and IFN-beta) or MICE regimen (radiation, MCNU, carboplatin, etoposide and IFN-beta). Ten patients were treated with the MIC regimen and 22 patients with the MICE regimen. The patients treated with the MIC and MICE regimens exhibited no significant difference in clinical background factors. The response rate was 50.0% among the 8 evaluable patients treated with the MIC regimen, and 40.0% among the 20 evaluable patients treated with the MICE regimen. The first- and second-year survival rates for the MIC regimen were 40.0% and 30.0%, and those for the MICE regimen were 68.2% and 36.4%. The overall first- and second-year survivals were 59.4% and 33.9%, respectively. The 50% survival time was 8.6 months for the MIC regimen, 14.9 months for the MICE regimen, and 13.4 months overall. There was no significant difference in response rate or survival period between the group treated with the MIC regimen and that treated with the MICE regimen. Age, histological grade of malignancy, radicality of surgery and total dose of irradiation did not affect length of survival. The only factors significantly related to length of survival were response to the induction therapy and performance of maintenance therapy. These results did not demonstrate the superiority of either the MIC or MICE regimen to other regimens previously reported for the treatment of glioma. In addition, etoposide was found not to improve the efficacy of this type of combined chemoradiation therapy.
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PMID:[A clinical evaluation of combination therapy with radiation, MCNU, carboplatin and IFN-beta or with radiation, MCNU, carboplatin, etoposide and IFN-beta for malignant gliomas]. 983 7

We investigated the immunological responses induced by human interferon beta (IFNbeta) gene transfer in human gliomas produced in the brains of nude mice. A suspension of human glioma U251-SP cells was injected into the brains of nude mice. The IFNbeta gene was transferred by intratumoral injection with cationic liposomes or cationic liposomes associated with anti-glioma monoclonal antibody (immunoliposomes). When intratumoral injection of liposomes or immunoliposomes containing the human IFNbeta gene was performed every second day for a total of six injections, starting 7 days after tumor transplantation, complete disappearance of the tumor was observed in six of seven mice that had received liposomes and in all seven mice receiving immunoliposomes. In addition, experimental gliomas injected with immunoliposomes were much smaller than those injected with ordinary liposomes following delayed injections beginning 14 days after transplantation. An immunohistochemical study of the treated nude mouse brains revealed a remarkable induction of natural killer (NK) cells expressing asialoGM1 antigen. To investigate the significance of NK cells in the antitumor effect, we injected liposomes or immunoliposomes containing the human IFNbeta gene into tumors in nude mice depleted of NK cells by irradiation and anti-asialoGM1 antibody administration. The antitumor effect of the liposomes or immunoliposomes was abolished. Subsequent subcutaneous glioma challenge of the nude mice after intracerebral tumor implantation and gene transfer resulted in no subcutaneous tumor growth. These results suggest that the induction of NK cells is important in the cytocidal effect of liposomes or immunoliposomes containing the human IFNbeta gene upon experimental gliomas.
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PMID:Effect of human interferon beta gene transfer upon human glioma, transplanted into nude mouse brain, involves induced natural killer cells. 987 76

The 2',5'-oligoadenylate synthetases are key enzymes that mediate antiviral actions of interferon (IFN). The mRNAs for the intermediate isoforms (p69) of human 2',5'-oligoadenylate synthetase are rapidly induced 10- to 20-fold in HT1080 glioma cells by IFN-beta and induced 3-fold at 24 h by IFN-gamma. Induction is mediated by three regulatory elements, an IFN-stimulated response element and two identical sites resembling interferon response factor binding sites that are located within 300 bp of the transcriptional start site. Maximal induction requires all three elements, yet mutation in the most distal IRF-1-like site diminishes transcription only slightly. Mutation in the ISRE substantially decreases constitutive expression but does not abrogate the response to IFNs. Simultaneous mutation in all three elements abolishes responsiveness to both IFN-beta and IFN-gamma. Both constitutive and IFN-beta-induced expression from the p69 promoter is blocked in mutant cell lines deficient in components of the transcription factor, interferon-stimulated gene factor 3, suggesting that it is the primary factor controlling IFN-beta induced expression of this gene.
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PMID:Transcriptional induction of the p69 isoform of 2',5'-oligoadenylate synthetase by interferon-beta and interferon-gamma involves three regulatory elements and interferon-stimulated gene factor 3. 988 23


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