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)

A close association between human T-lymphotropic virus type I (HTLV-I) infection and a group of chronic myelopathies of unknown etiology has recently been established and the name "HTLV-I associated myelopathy" (HAM) has been coined. Although the mechanism of neural tissue damage in HAM remains virtually unknown, several lines of evidence suggest the involvement of a soluble factor(s) including cytokines and viral proteins in the disease process. In this study, we examined cytopathic effects of the supernatants from 6 HTLV-I carrier human T lymphocyte cell lines on 4 human and one murine neuroblastoma cell lines, and 2 human glioma cell lines. Among 6 lymphocyte cell culture supernatants, only 1 from MT-2 cell culture repeatedly exerted cytopathic effects on human neuroblastoma cells, particularly on IMR-32 cells: marked retraction of neurites leading to cellular clumping. This activity was neither abolished by treatment of the medium at 80 degrees C for 30 min or by UV-irradiation, nor was it neutralized by anti-HTLV-I antibodies. The MT-2 supernatant also induced mild cytopathic changes in 2 other human neuroblastoma cell lines and 2 human glioma cell lines. This activity was abolished by treatment of the medium at 80 degrees C for 30 min but not at 56 degrees C for 30 min. Myelinated murine cerebellum explants and other cell lines showed no morphological changes when incubated with the MT-2 supernatant. In addition, the growth of THP-1 cells, a monocyte/macrophage lineage cell line, was remarkably suppressed when maintained in the MT-2 conditioned medium, accompanied by enhancement of phagocytic activity. The THP-1 conditioned medium, on the other hand, suppressed tumor necrosis factor (TNF) activity detected in the MT-2 culture. These observations suggest that HTLV-I induced cytokines may directly act on neural cells, but their action appears to be regulated by the intricate interactions of lymphocytic and monocytic cells.
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PMID:Neurotoxic activity in HTLV-I carrier lymphocyte culture. 268 38

To determine whether tumor necrosis factor is of potential value for the treatment of human malignant gliomas, we studied the effects of human recombinant tumor necrosis factor (rTNF-alpha) on the morphology, incorporation of tritiated thymidine, and proliferation of 5 established cell lines derived from human malignant gliomas and 3 normal human brain cell cultures. A radioreceptor analysis for rTNF-alpha was performed on all cell lines and cultures. Two of the 5 human glioma cell lines (SF-188 and U 343 MG-A) demonstrated a marked decrease (60% or less of untreated controls) in the uptake of tritiated thymidine when treated with rTNF-alpha at a concentration of 40 U/ml; rTNF-alpha at 100 U/ml had antiproliferative and cytotoxic effects on both cell lines. The growth and proliferation of cell lines SF-126 and U 251 MG were not affected by rTNF-alpha even at high concentrations (5,000 U/ml). The growth and proliferation of SF-539 were affected to an intermediate degree. A colony-forming efficiency assay corroborated the results of the proliferation studies: SF-126 was relatively resistant (surviving fraction of 0.9 at 500 U/ml) and SF-188 was relatively sensitive (surviving fraction of 0.08 at 500 U/ml) to the cytotoxic effects of rTNF-alpha. Time-sequence electron microscopy showed that rTNF-alpha at a concentration of 500 U/ml caused ultrastructural changes in SF-188, including increased intracytoplasmic vesiculation, swelling and degeneration of mitochondria, loss of cell:cell junctional complexes, and fragmentation of the plasma membrane. Studies with 125I-rTNF-alpha showed a variable degree of binding in all cell lines and cultures. SF-188, a highly sensitive cell line, demonstrated the strongest binding of 125I-rTNF-alpha (3,400 receptors/cell with high affinity; kd = 0.27 nM), while SF-126, a highly resistant cell line, had the weakest binding (809 receptors/cell; kd = 0.25 nM). We conclude that there is a spectrum of antiproliferative and cytotoxic activity among glioma-derived tumor cell lines exposed to rTNF-alpha. An increased number of rTNF-alpha receptors appears to be a necessary but insufficient condition to explain the antiproliferative effects observed in some glioma-derived cell lines.
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PMID:The effects of human recombinant tumor necrosis factor on glioma-derived cell lines: cellular proliferation, cytotoxicity, morphological and radioreceptor studies. 283 52

We studied the effects of cytokines on cultured microvascular endothelial cells derived from gerbil brain. Microvascular endothelial cells were derived from the endothelial cells of gerbil brain. First, effects of tumor necrosis factor (TNF) or [3H] thymidine up-take by the endothelial cells and human smooth muscle cells were studied. After 4 days exposure to TNF, 50 microCi/ml of [3H] thymidine were added to these cells. [3H] thymidine up-take by the endothelial cells were suppressed by adding TNF dose-dependently. Especially, [3H] thymidine up-take by endothelial cells cultured with 1000 U/ml TNF for 4 days were 25 to 62% of the control values. These cells exposed to 1000 U/ml TNF, furthermore, became spindlelike in appearance and over up each other. But, TNF had no effect on human smooth muscle cells. Second, instead of TNF, interferon-gamma (gamma IFN) were studied in the same way. But, [3H] thymidine up-take by the endothelial cells were not effected by adding gamma IFN. Third, the supernatant of the cultured glioma cells were studied in the same way. The supernatants of 6 glioma cells in 8 cases showed TNF like activity to the endothelial cells of gerbil brain. These supernatants, that is, suppressed [3H] thymidine up-take by the endothelial cells over 50%. These suppression were, furthermore, released by adding 50 microliter anti-TNF antibodies. So, we found the cytotoxic effects of TNF on the endothelial cells of gerbil brain. The supernatants of glioma cells, also, showed TNF like activity to the endothelial cells.
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PMID:[Effects of cytokines on cultured microvascular endothelial cells derived from gerbil brain]. 315 Feb 87

Type beta transforming growth factor (beta-TGF) is a potent regulator of cell growth and differentiation. The human glioblastoma cell line, T-MGI, was growth inhibited by beta-TGF under anchorage independent conditions. The antiproliferative effect of beta-TGF was potentiated to nearly total arrest by low doses of retinoic acid (RA) or tumor necrosis factor (TNF), while epidermal growth factor, platelet-derived growth factor, interleukin-2, and gamma interferon did not have this potentiating effect. The potentiation of the beta-TGF effect by RA and TNF could not be explained by modulation of the epidermal growth factor receptor, the beta-TGF receptor, or the TNF receptor. beta-TGF alone and in combination with RA or TNF were further tested on primary cultures from freshly resected human glioma biopsies (n = 13). There was great individual variation in sensitivity to beta-TGF, RA, or TNF. The astrocytoma and oligodendroglioma cells were inhibited to various degrees by beta-TGF or TNF, while most of the glioblastomas were not sensitive to these agents. Most of the biopsies were stimulated by RA. RA or TNF did not potentiate the growth inhibitory effect of beta-TGF on biopsy cells. We therefore think it unlikely that beta-TGF in combination with RA or TNF will be effective agents in the treatment of gliomas.
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PMID:Effects of type beta transforming growth factor in combination with retinoic acid or tumor necrosis factor on proliferation of a human glioblastoma cell line and clonogenic cells from freshly resected human brain tumors. 316 58

Growth of cultured human glioblastoma cells was profoundly inhibited by concentrated lymphokines prepared from mitogen-activated blood mononuclear cells of normal donors. Cloning efficiency of glioma cells and their absolute number were decreased as well. Partially purified leukoregulin, free of lymphotoxin, tumor necrosis factor and gamma-interferon, similarly suppressed DNA synthesis and clonogenicity. The decrease in absolute numbers of tumor target cells indicated that leukoregulin was directly cytolytic as well as cytostatic for human glioblastoma cells. Our data indicate that leukoregulin is at least one of the factors produced by activated lymphocytes which inhibits the proliferation of human glioblastoma in vitro.
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PMID:Leukoregulin inhibits the growth of human glioblastoma in vitro. 376 Jan 59

We examined whether oligodendrocytes, neurons, and astroglia derived from the human central nervous system differ in susceptibility to injury mediated by tumor necrosis factor (TNF)-alpha and by activated CD4+ T cells acting via a TNF-independent mechanism. Injury was assessed either as cell membrane-directed (lysis), measured by 51chromium (Cr) or lactate dehydrogenase (LDH) release, or nucleus-directed (apoptosis), measured by morphologic features based on propidium iodide (PI) staining and by DNA fragmentation measured by a terminal transferase (TdT)-mediated dUTP biotin nick end labeling technique (TUNEL). TNF did not induce 51Cr or LDH release in any cell targets, but did induce nuclear (66 +/- 2% of cells) and DNA (68 +/- 2% of cells) fragmentation selectively in the oligodendrocytes over 96 hr. At this time, there was no significant loss of oligodendrocyte cell number. Nuclear injury could be induced in neurons by serum deprivation and in malignant astrocytes by the combination of TNF and low serum. CD4+ T cells activated with phytohemagglutin (pha) or anti-CD3 plus interleukin-2 induced significant 51Cr and LDH release in all target cells tested; only pha-activated CD4+ T-cell cocultures showed reduced target cell numbers. Significant nuclear fragmentation was observed only for glioma cells (22 +/- 1% of cells). Differences in susceptibility to different immune effector mechanisms and in the nature of the injury response to the same effector mediator among human CNS-derived neural cells will need to be considered in design of therapeutic strategies aimed at protecting or limiting target cell injury consequent to disease or trauma.
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PMID:Differential susceptibility of human CNS-derived cell populations to TNF-dependent and independent immune-mediated injury. 747 83

We have examined the induction of nitric oxide synthase (NOS) activity in the rat astrocyte-derived C6 glioma cell line. In contrast to the previous results with primary astrocyte cultures, incubation of C6 cells with bacterial endotoxin lipopolysaccharide (LPS; 1 microgram/ml for 24 h) did not stimulate NO2 production. However, addition of either tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma), cytokines that by themselves had no effect on NOS activity, imparted LPS responsiveness onto these cells in a dose-dependent manner (EC50 values of 39 ng/ml of TNF-alpha and 9.4 U/ml of IFN-gamma), and the effect of TNF-alpha could be further potentiated (twofold) by the presence of interleukin-1 beta. The simultaneous presence of TNF-alpha and IFN-gamma yielded a greater response than either cytokine alone; however, the respective EC50 values were not affected. A cytoplasmic extract from induced C6 cells catalyzed the Ca(2+)-independent conversion of L-arginine to L-citrulline, with an apparent Km of 51.2 microM, and this activity could be blocked by L-arginine analogues in the potency order amino > methyl > nitroarginine. Immunoblot analysis revealed an apparent molecular mass of 125 kDa for the NOS protein induced in C6 cells. These results indicate that the combination of LPS plus cytokines can induce NOS activity in C6 glioma cells with properties similar to those of the enzyme expressed in primary astrocyte cultures.
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PMID:Induction of nitric oxide synthase in rat C6 glioma cells. 750 14

Granulocyte-macrophage colony-stimulating factor (GM-CSF) production and receptor expression by human glioblastomas was studied. Enzyme-linked immunosorbent assay showed four of 10 glioblastoma cell lines spontaneously released GM-CSF (2.9-9.2 pg GM-CSF protein/ml culture medium), which was enhanced by stimulation with tumor necrosis factor-alpha (TNF) (10 U/ml) up to 410 pg/ml. TNF also induced secretion of GM-CSF by another cell line. Northern blot analysis identified increasing GM-CSF gene expression by cells following TNF stimulation. However, no GM-CSF protein was detectable in the cerebrospinal fluid of three malignant glioma patients. Intratumoral administration of TNF in the patients also failed to stimulate GM-CSF levels in the cerebrospinal fluid. A binding assay using flow cytometry with biotinylated GM-CSF and Scatchard analysis using 125I-labeled GM-CSF failed to demonstrate GM-CSF receptor expression on the 13 cell lines. Exogenous GM-CSF stimulation had no effect on production of prostaglandin E2, interleukin-6, or interleukin-8 by glioma cells. Human glioblastoma cells secrete GM-CSF without expressing the receptor in vitro, but there was no evidence of GM-CSF production in vivo.
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PMID:Human glioblastoma cells produce granulocyte-macrophage colony-stimulating factor in vitro, but not in vivo, without expressing its receptor. 750 98

The effects of tumor necrosis factor-alpha (TNF) on proliferation and cell cycle alterations in human malignant glioma cell lines, SF-188 and LN-382, were investigated by flow cytometry with the bromodeoxyuridine-propidium iodide dual staining technique. Low concentrations of TNF (1-100 U/ml) suppressed the growth of SF-188 assessed by cell count, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and thymidine incorporation assay, but not that of LN-382. After TNF treatment, the percentage of SF-188 cells in the G0/G1 phase increased, while the percentage of cells in the S phase decreased. LN-382 cells did not show any marked change in cell kinetics. TNF arrests certain human glioma cells in the G0/G1 phase resulting in reduction of deoxyribonucleic acid synthesis in the subsequent S phase, suppressing the proliferation pathway.
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PMID:Antiproliferative effect of tumor necrosis factor-alpha on human glioblastoma cells linked with cell cycle arrest in G1 phase. 751 47

In this study, we investigated the expression of granulocyte colony-stimulating factor (G-CSF), G-CSF mRNA, G-CSF receptor mRNA in glioma cell lines, G-CSF in glioma cyst fluids, and the effect of recombinant G-CSF on the proliferation of glioma cells. First, to determine whether G-CSF is produced by glioma cells, we analyzed for the presence of G-CSF by ELISA in supernatants from glioma cell lines. G-CSF was detected in six of fourteen glioma cell lines constitutively, and, after stimulation with tumor necrosis factor-alpha (TNF-alpha), G-CSF was detected in four of eight cell lines which did not produce G-CSF constitutively. Then, we analyzed the expression of G-CSF mRNA by reverse-transcriptase polymerase chain reaction (RT-PCR) in six cell line, of which two produced G-CSF constitutively and three produced G-CSF only after stimulation with TNF-alpha. G-CSF mRNA was detected in all cell lines studied. To determine whether G-CSF was produced in vivo, we analyzed the presence of G-CSF by ELISA in five glioma cyst fluids, but G-CSF was not detected in any. We also analyzed the effect of G-CSF on the proliferation of glioma cells. The growth of glioma cells alone was not different from that of glioma cells incubated with recombinant G-CSF. In addition, we analyzed the presence of G-CSF receptor mRNA in glioma cells by RT-PCR; G-CSF receptor mRNA was not detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The expression of granulocyte colony-stimulating factor in malignant gliomas]. 753 27


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