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)

This paper describes the determination of the effect of IFN-beta on U-251 MG cells using the bromodeoxyuridine (BrdU/DNA) analysis technique. The cell cycle perturbation of exponentially growing cells was estimated by a newly developed two-dimensional analysis of sequential BrdU/DNA distributions measured at 4-hr intervals after IFN-beta administration. The U-251 MG cell line was sensitive to IFN-beta, and cell proliferation was inhibited by 50.0% at 48 hr. Analysis of DNA histograms indicated that IFN-beta accumulated the cells in the S-phase, from 16 to 48 hr after treatment. In the two-dimensional analysis, labeled cells treated with IFN-beta moved from the S-phase through the G2M-phase and then entered the G1-phase within 12 hr after the initial treatment, in a pattern similar to labeled cells untreated with IFN-beta. After 16 hr, labeled cells treated with IFN-beta began to accumulate in the S-phase and remained there even after 48 hr. These results imply that IFN-beta may have an effect on the G1-phase, thereby inducing S-phase accumulation of human glioma cell line U-251 MG.
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PMID:Effect of interferon-beta on the cell cycle of human glioma cell line U-251 MG: flow cytometric two-dimensional (BrdU/DNA) analysis. 322 Dec 57

In order to analyze the efficacy of combination therapy with Hu-IFN-beta, ACNU and radiation (IAR), nine patients with malignant glioma were treated as a control study. They received 100 X 10(4) IU Hu-IFN-beta daily for seven days intravenously or intratumorally, 3 mg/kg ACNU on day 2 and 5,000-6,000 rads of radiation from day 3. Four out of nine patients showed complete response and one partial response with this IAR therapy. Case 1 was a 64-year-old man who had glioblastoma in the left frontal lobe. Postoperative residual tumors disappeared completely with this therapy. Case 3 was a 8-year-old girl who had an enhanced high-density lesion in the medulla oblongata and pons. After IAR therapy, the high-density lesion was completely vanished and her clinical manifestations of multiple cranial nerve palsy and pyramidal sign were improved remarkably. The major side effects of IAR therapy were mild or moderate myelosuppression, and some patients also showed hepatic dysfunction, mild fever and gastrointestinal toxicities. However, all these side effects were mild and transient and soon recovered to normal levels. These results suggest that IAR therapy is effective and will prolong the survival time of patients with malignant glioma.
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PMID:[Combination therapy with IFN-beta, ACNU and radiation (IAR) in malignant brain tumors]. 345 40

Augmentation of cytotoxicity against malignant glioma using a combination of Hu IFN-beta and ACNU was analyzed in vitro from the points of cell growth inhibition and alteration of the DNA histogram. Cytotoxicity was tested by exposing 13 human glioma cell lines to ACNU at a concentration of 5 micrograms/ml and/or Hu IFN-beta at a concentration of 10(3) IU/microliters. These concentrations were considered to be clinical doses. Additive or synergistic effects of the combination of the two agents were observed in all cell lines tested. The cytotoxic effect of two log kill was seen in two cell lines given ACNU treatment alone, one cell line treated with Hu IFN-beta alone, and nine treated with the combination. Flow-cytometry studies of the DNA histogram showed accumulation in the G2+M phase with ACNU and in the S phase with Hu IFN-beta. On the other hand, marked accumulation using the combination in the S phase followed by the G2+M phase was observed and this accumulation lasted for over a week. The present results show an augmentation of antitumor activity and suggest the effectiveness of combined Hu IFN-beta/ACNU therapy in the treatment of patients with malignant glioma.
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PMID:[Combination therapy with HU IFN-beta and ACNU against malignant brain tumors, Part 1. Experimental study in vitro]. 385 55

The purpose of this investigation is to elucidate antitumor activity of human interferon-beta (Hu IFN-beta) against nervous system tumors. The study of growth inhibition in vitro with IFN against a variety of human glioma and neuroblastoma cell lines showed a significant response with sensitive cell lines at the concentration of 1 X 10(3) IU/ml in the medium. With resistant cell lines, however, tumor cells were proliferated as control even at the concentration of 10(4) IU/ml. The activation of lymphocyte-mediated cytotoxicity was also studied. The microcytotoxicity test with AJ glioma cells as target was used to evaluate it. In this system, percentage of cytotoxicity was 33 +/- 10.0% by lymphocytes obtained from six healthy adult men and four patients with malignant glioma, and it was increased to 71 and 72% seven days after intravenous administration of IFN (daily dose 3 X 10(6) IU) for the treatment of gliomas. The results indicate that human IFN-beta is considered effective in the treatment of malignant gliomas.
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PMID:[Effect of interferon on malignant brain tumor]. 718 55

Antineoplaston (Ap), a new antitumor agent, was clinically tested for effects on malignant brain tumors. The materials were 3 cases of glioblastoma (G,B), 2 cases of anaplastic astrocytoma, 1 case of pontine glioma, 2 cases of metastatic brain tumor and 1 case of medulloblastoma. All patients underwent radiochemotherapy and surgical resection of the tumors except the cases of pontine glioma, metastatic brain tumor and anaplastic astrocytoma. For gliomas, radiochemotherapy was used with Hu-IFN-beta. Ap was administered at a dose of 7-10 g/day in combination with remission maintenance therapy of gliomas. Complete response was obtained in one anaplastic astrocytoma. Partial response was obtained in 2 cases, a pontine glioma and a metastatic brain tumor. No change was observed in 2 cases, an anaplastic astrocytoma and a multiple brain metastasis. Progression of the disease was observed in 4 cases, 3 glioblastomas and 1 medulloblastoma, which showed continuous increase in tumor size. The effects of Ap on malignant brain tumors were considered due to synergy, since it was administered with other drugs and acceleration of tumor cellular differentiation. Ap is useful as an approach to remission maintenance therapy for brain tumors.
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PMID:The effect of Antineoplaston, a new antitumor agent on malignant brain tumors. 747 50

Adult neurons normally lack the expression of MHC class I molecules, which has implications on virus clearance from the central nervous system. The author previously demonstrated that HLA class I up-regulation in measles virus (MV)-infected glial cells is primarily mediated by IFN-beta. In contrast, this study demonstrates that MV-infection of the neuronal cell lines IMR-32 and CHP-126 fails to up-regulate HLA class I expression, which was associated with an inability of MV to induce IFN-beta in the neuronal cell lines. However, treatment with IFN-beta on coculture of the IMR-32 neuronal cell line with MV-infected glioma cells resulted in the up-regulation of HLA class I on the former, which could be neutralized by anti-IFN-beta Ab. The inability of MV to up-regulate HLA class I expression on the neuronal cell line IMR-32 was not virus specific because similar findings were observed with mumps virus or stimulation with the synthetic dsRNA polyinosinic polycytidylic acid (PIPC). Induction of IFN-beta gene expression by virus requires binding of NF-kappa B to the positive regulatory domain II element of the IFN-beta promoter. Our studies indicate that MV, TNF-alpha, or PIPC induces NF-kappa B (p50 and p65 subunits) binding to positive regulatory domain II in the glioma cell line. In contrast, such activity was induced by TNF-alpha but not MV or PIPC in the neuronal cell line IMR-32. This indicated that HLA class I expression is differentially regulated in glial and neuronal cell lines in response to MV, which correlates with differential binding of NF-kappa B to the IFN-beta promoter and induction of IFN-beta gene expression.
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PMID:Differential up-regulation of HLA class I molecules on neuronal and glial cell lines by virus infection correlates with differential induction of IFN-beta. 763 59

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

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

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


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