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)

The effect of measles virus (MV) infection on mRNA expression and protein synthesis of cytokines in human malignant glioma cell lines (D-54 and U-251) was investigated. Primary MV infections led in both cell lines to the induction of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interferon-beta (IFN-beta), and tumor necrosis factor-alpha (TNF-alpha). In contrast, persistently infected astrocytoma lines continually produced IL-6 (two out of 12 lines high levels) and IFN-beta, whereas only 1 out of 12 lines synthesized TNF-alpha and none IL-1 beta. The pathways for induction of IL-1 beta and TNF-alpha expression were not suppressed by the persistent MV infection, since IL-1 beta and TNF-alpha could be induced by external stimuli like diacylglycerol analog plus calcium ionophore. Interestingly, persistently infected astrocytoma cells synthesized considerably higher levels of IL-1 beta and TNF-alpha than uninfected cells after additional external induction. These results suggest that in the central nervous system (CNS) of SSPE patients a percentage of persistently infected astrocytes may continually synthesize IL-6 and IFN-beta, and in the presence of additional external stimuli, as possibly provided by activated lymphocytes, might overexpress the inflammatory cytokines IL-1 beta and TNF-alpha. This may be of pathogenetic significance in CNS diseases associated with persistent MV infections.
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PMID:Differential induction of cytokines by primary and persistent measles virus infections in human glial cells. 768 10

In our previous study on liposome-mediated transfection of the human interferon-beta (HuIFN-beta) gene into subcutaneously implanted human gliomas in nude mice, we found that HuIFN-beta was produced and secreted by the tumor cells and that the growth of solid tumors was completely inhibited. The present study investigated the growth-inhibitory effect of liposomes containing the HuIFN-beta gene inserted into a vector (pSV2IFN-beta) on T9 rat glioma implanted into the brains of rats. Tumor cells and liposomes containing pSV2IFN-beta or other additives were simultaneously injected into the brains of rats. HuIFN-beta was detected in solid gliomas growing in the brains of rats injected with liposomes and magnetic resonance imaging (MRI) showed that tumor growth was inhibited. In addition, the latent period until the appearance of neurological symptoms was significantly prolonged in rats treated with liposomes containing pSV2IFN-beta. However, the survival time of the treated rats was not significantly increased.
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PMID:Growth inhibition of intracerebral rat glioma by transfection-induced human interferon-beta. 777 50

We have been devoting our efforts to develop the useful liposomes that have high potentials of gene transfer and we aim human gene therapy for malignant glioma with cytokine genes. In our previous study, we prepared our original reverse-phase evaporation vesicles (REV) by an improved procedure of reverse-phase evaporation method. However, this procedure was very complicate. In this paper, a simple procedure for the preparation of cationic multilamellar vesicles (MLV) was introduced, and efficient expression and growth-inhibitory effect of MLV with entrapped human interferon-beta gene to glioma cells was comparable to that obtained with REV. Considering the present experiments, MLV seem to be more preferable for clinical application.
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PMID:Efficient transfection of human interferon-beta gene to human glioma cells by means of cationic multilamellar liposomes coupled with a monoclonal antibody [corrected]. 780 78

The cytocidal effect of endogenously produced human interferon-beta was tested on glioma transplanted into the brain of nude mice by intracranial injection of a cell suspension of human glioma cell line U251-SP. When plasmid pSV2IFN-beta, bearing the human interferon-beta gene, was encapsulated into cationic multilamellar liposomes composed of N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride, dilauroyl phosphatidylcholine, and dioleoyl phosphatidylethanolamine in a molar ratio of 1:2:2 and injected intratumorally, human interferon-beta was produced in the tumor. The tumor completely disappeared if the injection was done shortly after the transplantation. Even when the tumor did not disappear, survival of the tumor-bearing nude mice was markedly prolonged. In control experiments made with normal brain having no glioma, interferon-beta was not detected.
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PMID:Interferon-beta endogenously produced by intratumoral injection of cationic liposome-encapsulated gene: cytocidal effect on glioma transplanted into nude mouse brain. 801 82

In order to study the dynamic relationship in glioma cells between O6-alkylguanine-DNA alkyltransferase (AGT) activity and resistance to the cytotoxic effect of chloroethylnitrosoureas (CENUs), we investigated the changes in sensitivity to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) after modulation of AGT activity. In ACNU-resistant rat glioma cell lines (9LR1, 9LR3, and 9LR12) and a human glioma cell (HNG-1), O6-methylguanine enhanced cytotoxicity to ACNU following a depletion of AGT activity. But no enhancement of cytotoxicity was seen in an ACNU-sensitive rat glioma cell line (9L). In the 9L and 9LR12 cells, equivalently sublethal doses of ACNU similarly depleted AGT activity but the regeneration rates of this repair protein were different. In the case of a 7-day pretreatment with human recombinant interferon-beta (HuIFN-beta), although it could modulate AGT activity in HNG-1 cells, no definite influence on cellular sensitivity to CENUs was observed. However, a 50-day pretreatment with HuIFN-beta conferred resistance to CENUs on them despite its effect to reduce AGT activity. Thus, diversity was seen in the relation between AGT activity and resistance to CENUs when AGT activity was modulated by HuIFN-beta. The results of this study suggest that AGT activity is one of factors affecting cellular sensitivity to CENUs but that alternative mechanisms of tolerance may be induced depending upon some environmental effects.
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PMID:Interrelationship between O6-alkylguanine-DNA alkyltransferase activity and susceptibility to chloroethylnitrosoureas in several glioma cell lines. 812 May 66

Mouse glioma-26 (G-26) cell line established in this laboratory was used in the study. The in vitro effect of ascorbyl esters, viz., ascorbyl-palmitate (As-P), -stearate (As-S) and mouse interferon-alpha/beta (MulFN-alpha/beta) on the glioma cell viability, proliferation and glutathione S-transferase (GST) activity was investigated. Cell viability and proliferation were examined by colorimetric MTT assay and [3H]-thymidine incorporation, respectively. Incubation (24h) of G-26 cells with As-S, As-P or MulFN-alpha/beta, resulted in a dose dependent decrease in cell viability (IC50 = 125 microM As-S; 175 microM As-P and 3.6 x 10(4) U/ml MulFN-alpha/beta) and proliferation (IC50 = 157 microM As-S; 185 microM As-P and 3.6 x 10(4) U/ml MulFN-alpha/beta). A combined exposure to 175 microM As-S and 800 U/ml of MulFN-alpha/beta resulted in a greater than an additive effect on cell viability and proliferation. The inhibition of cell proliferation/viability by interferon was species specific and was observed only with homologous MulFN-alpha/beta, but not with human interferon-alpha lymphoblastoid or human interferon-beta. Ascorbyl esters inhibited cytosolic GST activity (1-50 = 15.0 microM As-S and 28.5 microM As-P) towards 1-chloro-2,4-dinitrobenzene in a dose dependent manner. The apparent Ki values for affinity purified GST, deduced from Dixon plots were 0.95 microM and 2.0 microM for As-S and As-P, respectively. Significant inhibition of GST was also observed in the cytosol isolated from G-26 cells exposed to 300 microM As-S or 800 U/ml MulFN-alpha/beta.
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PMID:Inhibition of cell proliferation and glutathione S-transferase by ascorbyl esters and interferon in mouse glioma. 841 Jan 36

Superinduction of human interferon-beta (HuIFN-beta) from human glioma cells has greater cytotoxicity than purified HuIFN-beta derived from fibroblasts. However, superinduction requires several reagents like polyI:polyC, cycloheximide, and actinomycin D, which may contaminate the conditioned medium and obscure the effect of superinduced HuIFN-beta. The present study used minimum doses of polyI:polyC and cycloheximide without actinomycin D to superinduce HuIFN-beta. The superinduced HuIFN-beta was purified by passing the medium through molecular sieve column chromatography. Fractionation of the eluate provided semipurified superinduced HuIFN-beta which demonstrated a growth inhibitory effect against both the U251-MG autologous human glioma cell line and the SK-MG-1 homologous glioma cell line. This effect was neutralized by addition of anti-HuIFN-beta monoclonal antibody (YSB-1). In a separate experiment, combinations of superinduction reagents were found not to have growth inhibitory effects because all inhibition in superinduced medium was completely neutralized by YSB-1. Superinduced HuIFN-beta has a pure growth inhibitory effect on both autologous and homologous glioma cells, so may affect autocrine secretion of cytokines.
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PMID:Growth inhibition of human glioma cells by superinduced human interferon-beta. 853 25

The mortality and morbidity of patients with malignant glioma is not satisfactory, although the survival time is prolonged by several adjuvant therapies. In order to increase the survival time, various studies have been undertaken. In the present article, at first we discuss the effectiveness of the single and/or combined therapy of interferon-beta. Although a synergistic effects with radiation is noted in nitrosoureas and interferon-beta, and it is the most effective treatment for malignant glioma at present, it is still necessary to continue to search for an effective strategy to prolong survival of the patients. To improve the interferon-beta cytokine therapy, we have studied liposome mediated transfection of cytokine genes to control glioma cells. For this purpose, human beta-interferon gene entrapped in liposome was transfected into glioma cells and the growth inhibitory effect was observed. Successful secretion of interferon-beta and remarkable suppression effect to the glioma cells was demonstrated and this effect was enhanced by conjugating with monoclonal antibody G-22 on the surface of liposome. These results suggest that interferon-beta gene transfection by the use of liposome coupled with monoclonal antibody might become a useful technique for gene therapy of malignant glioma.
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PMID:[The effectiveness of interferon-beta against glioma cells and its augmentation of growth inhibitory effect by transfection of its gene]. 865 52

Between 1988 and 1993, 71 patients with glioblastoma or anaplastic astrocytoma were treated either with accelerated hyperfractionation radiotherapy (1.5 Gy twice daily to a total dose of 69 Gy, n = 35) or with conventional fractionation radiotherapy (1.8 Gy daily to 64.8 Gy, n = 36). Two patients in each group did not complete radiotherapy, leaving 67 evaluable. All patients received the chemotherapeutic regime ACNU intraarterially (50 mg/m2) or intravenously (100 mg/m2) prior to and after radiotherapy. Between 1990 and 1992, 19 patients also received intravenous interferon-beta (3 x 10(6) U, three times weekly) during radiotherapy. The median survival time was 14.5 months for the accelerated hyperfractionation group and 14 months for the conventional fractionation group. The median time to progression was 12 months for the accelerated hyperfractionation group and 9.5 months for the conventional fractionation group. There was no significant difference in either survival (P = 0.89) or progression-free survival (P = 0.25) between the accelerated hyperfractionation and conventional fractionation groups. Interferon therapy was associated with poorer survival. Brain necrosis developed in four out of 10 patients receiving accelerated hyperfractionation radiotherapy plus interferon-beta, but in none of nine patients receiving conventional fractionation radiotherapy plus interferon (P = 0.033). In conclusion, our study failed to demonstrate any possible benefit of accelerated hyperfractionation radiotherapy for malignant glioma. The incidence of brain necrosis may be increased by combining accelerated hyperfractionation radiotherapy and interferon-beta.
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PMID:Comparison of accelerated hyperfractionated radiotherapy and conventional radiotherapy for supratentorial malignant glioma. 907 Mar 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


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