Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Leukoregulin inhibits the growth of human glioblastoma in vitro. 376 Jan 59

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.
 ...
PMID:Human glioblastoma cells produce granulocyte-macrophage colony-stimulating factor in vitro, but not in vivo, without expressing its receptor. 750 98

To elucidate which cytokine receptors may be expressed by human glioblastoma and normal astrocytic cells, the presence of messenger ribonucleic acid (RNA) for a number of cytokine receptors was examined in 16 glioblastoma cell lines and adult and fetal astrocytes. A complementary deoxyribonucleic acid copy of total RNA was synthesized and amplified with specific primers using the polymerase chain reaction method. The receptors studied were interleukin (IL)-1 receptor type I (IL-1RI) and type II (IL-1RII), p75 and p55 tumor necrosis factor (TNF) receptors (p75TNFR and p55TNFR), interferon (IFN)-alpha/beta and -gamma receptors (IFN-alpha/beta R and IFN-gamma R), granulocyte-macrophage (GM) colony-stimulating factors receptor alpha subunit (GM-CSFR), G-CSF receptor (G-CSFR), M-CSF receptor (c-fms, M-CSFR), stem cell factor receptor (c-kit, SCFR), IL-6 receptor (IL-6R), and IL-8 receptor (IL-8R). Transcripts for IL-1RI, p55TNFR, IFN-alpha/beta R, and IFN-gamma R were present in all cell lines. The presence of IL-1RII, p75TNFR, GM-CSFR, M-CSFR, SCFR, IL-6R, and IL-8R was identified in 13, eight, seven, eight, 14, three, and one cell lines, respectively. Normal astrocytes were positive for IL-1RI, p75TNFR, p55TNFR, IFN-alpha/beta R, IFN-gamma R, M-CSFR, and SCFR, showing a similarity to glioblastoma cells. Expression of IL-1RII was observed in adult astrocytes but not in fetal astrocytes. Furthermore, gene expression was assessed in normal brain tissue and 11 glioblastoma tissue specimens. The normal brain tissue expressed IL-1RI, IL-1RII, IFN-alpha/beta R, M-CSFR, and SCFR. Of the 11 glioblastoma tissue specimens, IL-1RI was positive in 11, IL-1RII in 10, p75TNFR in nine, p55TNFR in nine, IFN-alpha/beta R in 10, IFN-gamma R in 10, GM-CSFR in two, G-CSFR in three, IL-8R in eight, and M-CSFR and SCFR in 11. These expressions were consistent with those in the cell lines, except for IL-8R. It is concluded that glioblastoma cells and normal astrocytes express a similar set of cytokine receptor genes in vitro and in vivo. Possible autocrine loops are suggested for IL-1 alpha/IL-1RI, TNF-alpha/p55TNFR, IFN-beta/IFN-alpha/beta R, M-CSF/M-CSFR, and SCF/SCFR in glioblastomas.
 ...
PMID:Analysis of cytokine receptor messenger RNA expression in human glioblastoma cells and normal astrocytes by reverse-transcription polymerase chain reaction. 751 61

Expression of the two types of tumor necrosis factor (TNF) receptor, p55 and p75, in 12 human glioblastoma cell lines was studied. Reverse-transcription polymerase chain reaction detected messenger ribonucleic acid (mRNA) transcripts of p55 TNF receptor in all 12 cell lines tested, but p75 TNF receptor mRNA in only four cell lines. Flow cytometric analysis with anti-p55 and anti-p75 TNF receptor monoclonal antibodies demonstrated both p55 and p75 proteins in these four cell lines, but the level of expression of p75 molecule was very low. Correlation of p55 and p75 TNF receptor expression with TNF-induced growth suppression and production of bioactive molecules (interleukin-6, interleukin-8, manganase-superoxide dismutase, prostaglandin E2) showed that p55 TNF receptor mediates these TNF actions, but none of the responses were influenced by the presence of the p75 TNF receptor, which apparently has no specific role.
 ...
PMID:p55 and p75 tumor necrosis factor receptor expression on human glioblastoma cells. 756 86

Tumor necrosis factor-alpha is a pluripotent cytokine that is reportedly mitogenic to astrocytes. We examined expression of the astrocyte intermediate filament component glial fibrillary acidic protein in astrocyte cultures and the U373 glioblastoma cell line after treatment with tumor necrosis factor-alpha. Treatment with tumor necrosis factor-alpha for 72 h resulted in a decrease in content of glial fibrillary acidic protein and its encoding mRNA. At the same time, tumor necrosis factor-alpha treatment increased the expression of the cytokine interleukin-6 by astrocytes. The decrease in glial fibrillary acidic protein expression was greater when cells were subconfluent than when they were confluent. Thymidine uptake studies demonstrated that U373 cells proliferated in response to tumor necrosis factor-alpha, but primary neonatal astrocytes did not. However, in both U373 cells and primary astrocytes tumor necrosis factor-alpha induced an increase in total cellular protein content. Treatment of astrocytes and U373 cells for 72 h with the mitogenic cytokine basic fibroblast growth factor also induced a decrease in glial fibrillary acidic protein content and an increase in total protein level, demonstrating that this effect is not specific for tumor necrosis factor-alpha. The decrease in content of glial fibrillary acidic protein detected after tumor necrosis factor-alpha treatment is most likely due to dilution by other proteins that are synthesized rapidly in response to cytokine stimulation.
 ...
PMID:Tumor necrosis factor-alpha and basic fibroblast growth factor decrease glial fibrillary acidic protein and its encoding mRNA in astrocyte cultures and glioblastoma cells. 759 70

Although tumor necrosis factor-alpha (TNF) has been applied to early clinical trials for patients with malignant glioma, majority of human glioma cells has been reported to be resistant to TNF cytocidal effect in vitro. This study investigated antiproliferative effect of the TNF associated with induction of differentiation and expression of two distinct TNF receptors on human glioblastoma cell lines. The expression of p55 and p75 TNF receptors on 12 human glioblastoma cell lines was assessed by polymerase chain reaction and flow cytometry. p55 TNF receptor was detected in all cell lines, and only 4 cell lines concomitantly expressed p75 TNF receptor. Twelve human glioblastoma cell lines were treated with low-dose TNF, up to 256 U/ml for 7 days. TNF did not exhibit its cytocidal effect, but showed antiproliferative effects with inhibition of DNA synthesis in majority of cell lines tested. Flow cytometry with the bromodeoxyuridine-propidium iodide dual staining technique demonstrated that this antiproliferative effect of TNF was attributed to accumulation of glioblastoma cells in G0/G1 phase, suppressing the proliferative pathway. Furthermore the TNF stimulation increased glial fibrillary acidic protein and production of bioactive molecules including interleukin(IL)-6, IL-8, granulocyte-macrophage colony stimulating factor, prostaglandin E2 and manganous superoxide dismutase. In conclusion, human glioblastoma cells had p55 TNF receptor as a functional receptor and well responded to low-dose TNF stimulation, but not susceptible TNF cytocydal effect. The effect of TNF on glioblastoma cells appeared to modulate cell differentiation. TNF may be utilized as an agent for a differentiation therapy for human glioblastomas.
 ...
PMID:[Antiproliferative effect of tumor necrosis factor-alpha on human glioblastoma cells]. 777 79

The purpose of our study was to investigate the susceptibility of human glioblastoma multiforme (GBM) cells to lysis by human peripheral-blood monocytes following activation with biological response modifiers (BRM) and to lysis by various BRMs directly. Cytotoxic effects were determined using a monocyte-/BRM-mediated tumor cytotoxicity assay. Human peripheral-blood monocytes from healthy donors were activated in vitro by incubation for 24 h with different BRMs such as gamma- and beta-interferon (gamma, beta-IFN), lipopolysaccharide (LPS), muramyldipeptide (MDP) and tumor necrosis factor-alpha (TNF-alpha) in varying concentrations and combinations. Seven human GBM cell lines as well as an adenocarcinoma brain metastasis cell line and a malignant melanoma cell line served as target cells. Radiolabeled target cells were cocultivated with activated monocytes or with BRMs directly. Cytotoxicity was calculated after 72 h of cocultivation. High levels of cytotoxicity were mediated by monocytes activated with beta-IFN in six out of eight brain tumor cell lines and with TNF-alpha in five cell lines. The combination of two BRMs, in particular the combination of gamma-IFN + beta-IFN and gamma-IFN + TNF-alpha, was associated with an enhanced monocyte mediated lysis exceeding LPS control, whereas the combination of gamma-IFN + MDP was very effective against the metastasis cell line. Monocyte-mediated cytotoxicity against tumor target cells was up to ten fold higher than direct cytotoxicity of soluble BRMs. Our data indicate that BRM-stimulated peripheral-blood monocytes exert cytotoxic properties against human glioblastoma cells in vitro, which exceed those of BRMs alone up to ten fold. The higher tumoricidal activities observed after stimulation with combined BRMs suggest mutual promoting mechanisms of BRMs acting on the stimulation of lyctic activity in human peripheral blood monocytes.
 ...
PMID:Activated monocytes kill malignant brain tumor cells in vitro. 780 82

The monocyte chemotactic protein-1 (MCP-1) is a 76 amino acid protein that specifically attracts monocytes. The expression of MCP-1 gene can be induced by lipopolysaccharides (LPS), phorbol esters (TPA) and several cytokines. However, how they regulate MCP-1 gene expression is not known. We tested whether the two putative TPA-responsive elements (TREs) and one kappa B enhancer-like region found in the MCP-1 promoter region, are involved in this regulation of MCP-1 gene expression. The 5' untranslated region of MCP-1 gene was linked to chloramphenicol acetyl transferase (CAT) reporter gene and transfected into human glioblastoma cells in which endogenous MCP gene expression was found to be stimulated by TPA and tumor necrosis factor-alpha (TNF-alpha). The 128 bp 5'-flanking region containing one TRE was adequate for basal promoter activity but the presence of both TREs in the MCP-1 promoter region were needed to give TPA responsive enhancement (2.5 fold) of expression of the marker gene. Mutations in either of the TRE's could abolish the TPA induction of CAT expression. Replacement of the kappa B enhancer-like element with a TRE-like sequence caused a 10-fold enhancement of CAT expression by TPA treatment. Random mutation of kappa B enhancer-like element did not affect CAT expression or its TPA induction. None of the MCP promoter constructs showed significant increase in CAT expression by treatment with tumor necrosis factor-alpha (TNF-alpha). This result suggested that the TNF regulation of MCP-1 gene involves other parts of the gene besides the proximal 5' flanking region.
 ...
PMID:Functional role of the cis-acting elements in human monocyte chemotactic protein-1 gene in the regulation of its expression by phorbol ester in human glioblastoma cells. 789 69

Transforming growth factor-beta (TGF-beta) has a variety of immunosuppressive properties. We investigated the effect of TGF-beta secreted by glioblastoma (T98G) cells on the secretion of tumor necrosis factor-alpha and -beta (TNFs) by lymphokine activated killer (LAK) cells stimulated with tumor cells. The supernatant from T98G cells was preincubated with anti-TGF-beta 1 and -beta 2 neutralizing antibodies or untreated, and added to a coculture of LAK and Daudi cells. The neutralizing antibodies were added to LAK/Daudi and LAK culture, and natural human TGF-beta 1 and recombinant human TGF-beta 2 were also added to the LAK/Daudi culture. LAK cells were also cultured with T98G cells, of which the supernatant contained both active and latent forms of TGF-beta 1 and TGF-beta 2, and the neutralizing antibodies were added to the coculture. TNFs activity in the supernatants from LAK/Daudi cultures was examined by a specific bioassay. Addition of the supernatant from T98G cells to LAK/Daudi culture resulted in the inhibition of TNFs secretion by LAK cells. The inhibition was abrogated by the pretreatment of the supernatants with the anti-TGF-beta antibodies. Addition of TGF-beta 1 and TGF-beta 2 to LAK/Daudi culture inhibited TNFs secretion by LAK cells in a dose-dependent manner. Addition of anti-TGF-beta antibodies to LAK culture resulted in an increase of TNFs secretion. These results suggest that, if tumor cells have the capacity to convert TGF-beta from a latent to an active form, the active TGF-beta suppresses TNFs secretion by LAK cells stimulated with the tumor cells, and that TGF-beta secreted and activated by glioblastoma cells suppresses the propagation of immune reaction by inhibiting TNFs secretion by activated lymphocytes adjacent to tumor cells.
 ...
PMID:Inhibition of tumor necrosis factor-alpha and -beta secretion by lymphokine activated killer cells by transforming growth factor-beta. 796 Nov 25

The effects of a recombinant human interleukin-1 (IL-1) receptor antagonist (IL-1ra) and a recombinant human soluble IL-1 receptor (sIL-1R) on cytokine-induced intercellular adhesion molecule-1 (ICAM-1) expression in a human glioblastoma cell line and a neuroblastoma cell line were determined. Cells were incubated with IL-1 beta, tumor necrosis factor (TNF) alpha and interferon (IFN) gamma. Cells were also tested under identical conditions with an IL-1 beta synthetic peptide fragment (IL-1 beta 208-240) previously shown to possess biological activity. IL-1 beta, TNF alpha and IFN gamma potentiated ICAM-1 expression in both cell lines in a dose-related manner. The IL-1 beta 208-240 fragments, corresponding to the rabbit, rat and human sequences, enhanced ICAM-1 expression in glioblastoma cells at high doses. ICAM-1 expression induced by IL-1 beta, rabbit IL-1 beta 208-240 and human IL-1 beta 208-240 was blocked by the IL-1ra, while TNF alpha- and IFN gamma-induced ICAM-1 expression were not. ICAM-1 expression induced by IL-1 beta and human IL-1 beta 208-240 was also blocked by the sIL-1R. Our findings suggest that IL1 beta 208-240 acts as an IL-1 beta agonist in enhancing ICAM-1 expression in vitro and that this effect is receptor-mediated.
 ...
PMID:Intercellular adhesion molecule-1 expression induced by interleukin (IL)-1 beta or an IL-1 beta fragment is blocked by an IL-1 receptor antagonist and a soluble IL-1 receptor. 809 61


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>