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 human glioma cell lines U251 and HP591 were chosen as "in vitro" models for functional astrocytes. When cultured in the presence of IL-1 beta these cell lines demonstrated a marked increase in interleukin-6 production and in [3H]-thymidine uptake. The addition of dbcAMP could mimic the first effect of IL-1 beta but at the same time suppressed cell proliferation. These results suggest that IL-1 beta possibly exerts one of its biological effects (IL-6 synthesis) by means of the cyclic AMP pathway.
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PMID:"In vitro" effect of interleukin-1 beta on human glioma cell lines: regulation of cell proliferation and IL-6 production. 133 65

Glioma cell lines express proteins of the complement alternative pathway, namely C3, factor B, factor H, and factor I. Secretion of these proteins was shown by a sensitive and specific ELISA. C3 and factor H were rapidly secreted by glioma cell line CB193 and reached a concentration of 140 ng/ml/10(6) cells after 72 h of culture. Factor B and factor I were secreted at a lower rate and reached concentrations of 25 and 15 ng/ml/10(6) cells, respectively. Western blot and immunoprecipitation experiments showed that secreted proteins were identical to the corresponding plasma proteins. For factor H, besides the well known 150-kDa species, an additional polypeptide of 45 kDa with factor H immunoreactivity was observed. This species corresponded to the N-terminal truncated form found in plasma. In preliminary experiments, we observed control of these syntheses by cytokines. IL-1 beta significantly increased C3 secretion, with no effect on factor H. Secretion of factor H was enhanced by IFN-gamma. These results show that a glioma cell line could be a useful tool to study complement biosynthesis by glial cells in humans.
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PMID:Expression of complement components of the alternative pathway by glioma cell lines. 138 64

Biological effects of human natural tumor necrosis factor-alpha (TNF) on glioblastoma cells in vitro and on glioma patients were investigated. TNF treatment on glioblastoma cells, even at a high dose (256 U/ml), exhibited no remarkable cytocidal activity in MTT assay, but at lower doses significantly inhibited colony forming and DNA synthesis. TNF at a low dose (10 U/ml) stimulated production of prostaglandin E2, Mn-superoxide dismutase, interleukin (IL)-6 and IL-8 by glioblastoma cells. These results indicated that the direct effect of TNF on human glioblastoma cells is rather antiproliferative than cytotoxic and is to modulate their metabolic pathways. In an early Phase I clinical trial, TNF was administered intracranially to six patients bearing glioblastoma. In this trial, the author studied in vivo immunological responses in the cerebrospinal fluid and regional fluid after the regional TNF injections. TNF in these body fluids were detected with a half life of several hours. There occurred a substantial number of leukocyte migration after the TNF administration. Neutrophils appeared first peaking at 8 to 12 hours, and then CD4+CD8-T cells and CD11b+CD13+CD14+ monocytes followed. IL-8 activity in the cerebrospinal fluid simultaneously corresponded to peak of the neutrophil migration. Increases in IL-6, IL-1 beta and prostaglandin E2 levels in the cerebrospinal fluid, regional fluid or both occurred peaking at 8 to 12 hours after TNA infection. Neither IL-2 nor interferons was detected. In conclusion, TNF may act as an antineoplastic agent by its direct cytostatic effects and indirectly through immune modulatory effects.
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PMID:[In vitro and in vivo immunobiological responses of glioblastoma to human natural tumor necrosis factor-alpha]. 142 94

We investigated the effects of daily subcutaneous (SC) injections of 100, 200, or 400 micrograms/kg murine recombinant interleukin-1 beta (rIL-1 beta) or its excipient on normal Fischer 344 rats and ones harboring a malignant RT-2 glioma. The tumor model has a predictable course with animals dying on days 14-17 following an intracerebral inoculation of 10(4) RT-2 glioma cells. Treatments with rIL-1 beta or excipient began on day seven post-tumor inoculation and continued for 7 days. We observed no significant effect on core body temperatures although there was a significant (p less than 0.05) decrease in body weight in all rIL-1 beta treated animals. When tumor-bearing animals became moribund, they received an intraperitoneal injection of bromodeoxyuridine (BUdr) and were sacrificed two hours later. Blood samples were obtained prior to their sacrifice by transcardiac perfusion with a buffered aldehyde solution. Recombinant IL-1 beta affected blood differentials; causing neutrophilia, lymphopenia, and slight thrombocythemia. The BUdr labeling index of glioma cells did not significantly differ between treatment groups, although tumors differed histologically at the time of necropsy. Tumors of rIL-1 beta treated animals had more extensive necrosis and a greater degree of leukocyte infiltration. Survival studies were conducted in which rats were given continuous daily SC injections of rIL-1 beta until day of death. Overall survival between the two groups differed significantly in studies using 100 micrograms/kg/d (p less than 0.05); rIL-1 beta treated rats had a mean survival time of 22 (+/- 3.0) days while excipient controls had a mean survival time of 17 (+/- 0.5) days. Similarly, at a dose of 200 micrograms rIL-1 beta/kg/d, mean survival was significantly (p less than 0.05) increased as compared to excipient controls (18.75 +/- 1.5 vs. 15.25 +/- 1.7 days, respectively). Daily injections of 400 micrograms/kg did not significantly increase the survival of glioma bearing animals, possibly as a consequence of rIL-1 beta toxicity at this dose.
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PMID:Systemic treatment with murine recombinant interleukin-1 beta inhibits the growth and progression of malignant glioma in the rat. 161 37

Expression of the lymphokine genes in human astroglial cell lineage was studied. Primers for 9 different human lymphokines, from IL-1 alpha to IL-8, were used to analyze RNA transcripts in 5 cultured human astrocytoma, one neuroblastoma cell line and 4 fresh brain specimens by polymerase chain reaction (PCR). mRNA transcripts of neither IL-1 nor IL-3, the biological activities of which were observed in rat primary cultured astrocytes, could be detected within these cell lines. Two out of 5 unstimulated astrocytomas, U138 and U373, expressed IL-6 genes. IL-8 gene was detected within U87, U138, U251, U373 glioma cells. After stimulation with IL-1 beta, all astrocytoma and one neuroblastoma cell line expressed IL-6 and IL-8 genes. In addition to the cultured cells, we examined IL-6 and IL-8 gene expression within human malignant astrocytoma specimens. The result shows that three out of four glioma specimens expressed IL-6 and IL-8 genes. From these results, it is suspected that astroglial cell-derived IL-6 or IL-8 may participate in local immune reactions accompanying infection, degeneration and malignancies in the central nervous system.
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PMID:[An analysis of lymphokine gene expression within astrocytoma]. 163 May 67

Cells that produce tumor necrosis factor-alpha (TNF-alpha) require the presence of signaling molecules since this cytokine is not normally expressed in a constitutive manner. It has been demonstrated that glial cells can produce TNF-alpha; however, the specific inducing molecules and their mechanism(s) of action have not been clearly defined. In this study, we examined the effect of human recombinant interleukin-1 beta (IL-1 beta) on the expression of TNF-alpha by CH235-MG human malignant glioma cells. CH235-MG cells do not constitutively express TNF-alpha mRNA or protein; however, upon stimulation with IL-1 beta, these cells synthesize and secrete biologically active TNF-alpha. IL-1 beta induces the expression of a 1.9 kb TNF-alpha mRNA species. Kinetic analysis demonstrated optimum TNF-alpha mRNA expression after a 4 h exposure to IL-1 beta, and peak TNF-alpha protein production at 18 h. Cycloheximide (CHX), an inhibitor of protein synthesis, markedly increased expression of TNF-alpha mRNA in IL-1 beta stimulated CH235-MG cells, indicating that de novo protein synthesis is not required for astroglioma TNF-alpha gene expression. Nuclear run-off analysis demonstrates that IL-1 beta causes transcriptional activation of the TNF-alpha gene, and CHX enhances IL-1 beta-induced TNF-alpha transcription. Studies of TNF-alpha mRNA stability using actinomycin D show that IL-1 beta-induced TNF-alpha mRNA has a half-life of approximately 30 min, and CHX increases the half-life of IL-1 beta-induced TNF-alpha mRNA to approximately 210 min. These results indicate that IL-1 beta, a cytokine present in the central nervous system during some pathological disease states, is a potent inducer of TNF-alpha in human malignant glioma cells.
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PMID:Interleukin-1 beta induction of tumor necrosis factor-alpha gene expression in human astroglioma cells. 173 80

Expression of the Cytokine genes in human astroglial cell lineage was studied. Primers for 5 different human cytokine, TNF-alpha, -beta, IFN-gamma, G-CSF and GM-CSF, were used to analyze messenger RNA transcripts in 5 cultured human astrocytoma, one neuroblastoma cell lines and fresh brain specimens by polymerase chain reaction (PCR). Three out of 5 unstimulated astrocytomas, U138, U251, U373 MG and IMR32 neuroblastoma cells expressed TNF-alpha genes. After stimulation with IL-1 beta (1000 U/ml) all these cell lines expressed TNF-alpha genes. TNF-beta genes could not be detected in these cell lines even in the presence of any cytokine stimuli. We were able to detect expression of IFN-gamma genes within 2 astrocytoma cell lines (U87MG and A172), which interestingly did not show TNF-alpha activity. Constitutive expression of mRNA transcripts of GM -CSF could be detected in all astrocytoma and two out of 5 unstimulated astrocytomas, U87MG and U138MG, expressed G-CSF genes. After stimulation with IL-1 beta, all cell lines expressed G-CSF. In addition, we also examined gene expression of these cytokines within 4 human malignant astrocytoma specimens, 2 peritumoral brain and 2 autopsied normal brains. The results show that tumor and surrounding lesions express TNF-alpha (4 of 6), TNF-beta (1/6), IFN-gamma (4/6), G-CSF (3/6) and GM-CSF (5/6) but not normal brains. One tumor specimen also expresses TNF-beta as well as TNF-alpha genes (case 2). From these results, it is suspected that astroglial cell-derived cytokines may participate in local immune reactions accompanying glioma in the brain.
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PMID:[Expression of cytokine genes within astrocytoma cell lines and brain specimens]. 179 21

The therapeutic potential of interleukin 1 (IL-1) in the treatment of malignant glioma was investigated. The direct effect of recombinant human IL-1 beta (rHuIL-1 beta) on cultured U-373 MG glioma cell was evaluated in vitro by BrdU uptake assay, and these effects were compared with those of human interferon beta (HuIFN-beta). Though a growth inhibition and an increase of the percentage of process bearing cells were observed with rHuIL-1 beta at a concentration of 100 ng/ml, these in vitro effects of rHuIL-1 beta were less than those of HuIFN-beta at the same concentrations. Prevention of and enhanced recovery from myelosuppression caused by ACNU by rHuIL-1 beta were evaluated in BALB/c mice. Intravenous injection of ACNU at a dose of 60 mg/kg caused marked decreases in the number of leukocytes, neutrophils, reticulocytes and thrombocytes after seven days. Pretreatment with 1 microgram/mouse of rHuIL-1 beta as a single i.p. injection had a significant preventive effect on these myelosuppression including thrombocytopenia. Enhanced recovery by rHuIL-1 beta administrated seven days after injection of ACNU was also observed. Experimental combination immunochemotherapy with ACNU and rHuIL-1 beta was performed in nude mice inoculated with human glioblastoma subcutaneously. More than 60 mg/kg of ACNU given intraperitoneally inhibited the growth of human glioblastoma in nude mice, but had no effect on survival time of nude mice. The antitumor effect of ACNU was significantly augmented by coadministration of 1 microgram/mouse rHuIL-1 beta. The elongation of the survival time of the tumor bearing nude mice was also observed in combined use of ACNU with rHuIL-1 beta. These results suggest that the combined use of IL-1 with chemotherapeutic agents seems to be desirable for clinical application in the treatment of patient with malignant gliomas from the viewpoints of the direct anti-tumor effect, the enhancement of the host immunity, and the prevention of myelosuppression caused by those agents.
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PMID:[Application of interleukin 1 in the treatment of malignant gliomas with special reference to the experimental combination therapy with ACNU]. 235 Jan 91

Interleukin 1 is a monokine produced by macrophage and has an ability to activate thymocytes. In addition to the immunological regulatory effect, interleukin 1 has attracted a great deal of investigators as a new peptide hormone that was secreted by many cells and has a various physiological activities. In central nervous systems, interleukin 1 promotes the glial cells proliferations on the injured brain and the fetal brain. The cell sources of interleukin 1 in central nervous systems are considered to the microglial cells. On gliomas, Lachmann and Dinarello reported growth promoting effect of IL-1 on U-373 MG human glioblastoma cell. The authors investigated the roles and effects of IL-1 on the growth of gliomas using recombinant human IL-1 beta and anti-HuIL-1 beta monoclonal antibody. On Immunohistochemistry, paraffin sections of 10 cases of gliomas were stained with immunoperoxidase method using anti-human IL-1 beta and anti-GFAP mouse monoclonal antibody. All astrocytomas examined and 2 of 4 glioblastomas were stained by anti-IL-1 beta. The origin of IL-1 that was stained by immunoperoxidase staining is unknown. The authors think it that IL-1 existed in glioma cells were secreted by microglial cells or that the glioma cells themselves secreted IL-1. In either case, IL-1 must be related to the growth of glioma in situ. On immunocytochemistry, U-373 MG human glioblastoma cells purchased from ATCC were incubated on cover-slip with 0 and 10 U/ml of rHuIL-1 beta for 3 or 7 days. The cells were stained with immunoperoxidase method using anti-GFAP monoclonal antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Interleukin 1 and gliomas: immunohistochemical and immunocytochemical examinations]. 284 Jan 6

The effects of irradiation on cytokine production in glioma cell lines, NP1, NP2 and NP3, were studied. Culture supernatants were collected after 6, 24, 48 or 72 hours and the concentrations of interleukin (IL)-6 and IL-8 measured by enzyme-linked immunosorbent assay. Spontaneous and IL-1 beta-stimulated productions were analyzed. Some cells were given a single dose of Lineac irradiation (10 or 20 Gy). Production of IL-6 (with or without IL-1 beta stimulation) increased gradually to a maximum after 72 hours, more in the 20 Gy-irradiated cells than 10 Gy cells (p < 0.01). Production of IL-8 increased gradually to a maximum after 48 or 72 hours. Spontaneous production of IL-8 increased more in 20 Gy-irradiated cells than 10 Gy cells after 6 and 24 hours (p < 0.01), but increased more in 10 Gy cells than 20 Gy cells after 48 and 72 hours (p < 0.01). The production of IL-8 stimulated by IL-1 beta increased more in 10 Gy cells than 20 Gy cells 24 hours later (p < 0.01). IL-6 and IL-8 production differed in the response to irradiation. Our data suggest that bidirectional communication between the immune system and glioma cells changes after radiotherapy.
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PMID:Effects of irradiation on cytokine production in glioma cell lines. 750 9


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