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 blood-brain barrier GLUT1 glucose transporter is localized in brain to the capillary endothelium, which makes up the blood-brain barrier (BBB) in vivo. However, its expression is markedly downregulated in cultured bovine brain capillary endothelium (ECL cells), possibly due to the absence of brain-derived or astrocyte trophic factors in the tissue culture medium. To examine this hypothesis, we studied the effect of a bovine brain homogenate (BBH), and conditioned media and plasma membranes obtained from the rat C6 glioma cell line, on the abundance of the GLUT1 transcript in ECL cells. BBH induced a significant increase in the abundance of both GLUT1 and actin mRNAs, and this effect was dose and time dependent. The increase in the GLUT1 mRNA levels correlated with an increase in the transcriptional rate of this gene measured by nuclear run-on experiments. C6 conditioned media and C6 plasma membranes had no effect on the abundance of either GLUT1 or actin mRNA. To determine whether known growth factors cause BBH-like induction of GLUT1 and actin mRNAs, a series of growth factors was also tested. EGF and PDGF had no effect on the levels of these mRNAs. Basic FGF had a moderate effect and TNF alpha partially mimicked the effect of BBH on both GLUT1 and actin transcripts. The present data suggests that brain-derived trophic factors present in BBH stimulate BBB-GLUT1 glucose transporter gene expression in ECL cells through a transcriptional mechanism. Although this effect was partially mimicked by TNF alpha, C6 cell membranes or C6 conditioned media were unable to induce changes in the abundance of GLUT1 mRNA. Therefore, BBH may be a useful model to study the characterization of soluble brain-derived trophic factors involved in the induction of BBB-GLUT1 gene expression.
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PMID:Enhanced expression of the blood-brain barrier GLUT1 glucose transporter gene by brain-derived factors. 801 84

We have shown that several human malignant glioma cell lines are stimulated by bacterial lipopolysaccharide (E. coli 0111:B4, 1 microgram/ml) to produce a high molecular weight (> 200 kD) growth activity for BALB 3T3, clone A31 cells. This glioma-derived growth factor (GDGF-2) acts like a 'competence' factor. Malignant glioma cell line D-54 MG constitutively produced GDGF-2, which we have partially characterized from serum-free conditioned culture medium. GDGF-2 is resistant to heat (100 degrees C, 5 min), acidic (pH 2, 2 hr) or reducing (0.5 M 2 ME, 30 min) conditions as well as exposure to RNases; however, it is sensitive to > 4 freeze-thaw cycles, alkaline (pH 11, 2 hr) conditions or pre-treatment with proteolytic enzymes. GDGF-2 had a pl of 6.8 determined by preparative isoelectric focusing, bound to DEAE, with elution at 35 and 185 mM NaCl and at 43% acetonitrile from a C4 reversed phase column. GDGF-2 activity was not neutralized by antibodies to TGF alpha, TGF beta, PDGF, VEGF or TNF alpha indicating that it is not immunochemically related to these growth factors. However GDGF-2 co-chromatographed on Superose 12 HPLC (250 x 9 mm; 5% isopropanol, 6 mM CHAPS in PBS) with a substance that suppressed growth of mink lung epithelial cells (Mv1Lu), but not BALB 3T3 cells, and could be neutralized by anti-TGF beta antibodies. GDGF-2 activity eluted from heparin columns in 0.6 M NaCl; thus, it is not a heparin binding growth factor. D-54 MG cell line produced alpha 2-macroglobulin (alpha 2M), which is known to bind TGF beta; however, immunoprecipitation of alpha 2M did not deplete TGF beta or GDGF-2 activity. Further, neither GDGF-2 or TGF beta can be dissociated into lower molecular weight active components by chromatography in high salt (2 M NaCl) or 2-ME (0.5 M). GDGF-2 may be a novel autocrine or paracrine mitogen, stimulating mitotic division or interfering with normal cell growth regulation.
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PMID:Partial characterization of glioma-derived growth factor 2: a novel mitogenic activity from human cell line D-54 MG. 814 64

Human T lymphotropic virus type I (HTLV-I) is linked to adult T cell leukemia as well as to HTLV-I-associated myelopathy/tropical spastic paraparesis. In this report, we studied the effects of HTLV-I-infected cell supernatants on HUVEC, fibroblasts, and glioma cells. The HTLV-I-infected cell supernatants (HUT102 and MT-2) strongly inhibited the proliferation of HUVEC, although they enhanced the proliferation of the fibroblasts. Regarding the glioma cells, only the MT-2 supernatant showed weak inhibitory effects on the proliferation. However, the HTLV-I-uninfected cell supernatants showed no effects on these target cells. The biologic activities of both HUT102 and MT-2 supernatants were found to be dose dependent and were reduced by heat treatment at 100 degrees C for 5 min, but not at 56 degrees C for 30 min. These activities were not dependent on the concentrations of HTLV-I viral particles and were only minimally affected by the presence of anti-HTLV-I Abs. A bioassay of various cytokines revealed that the activity of TNF was much higher in the HUT102 and MT-2 supernatants than in the HTLV-I-uninfected cell supernatants (MOLT-4, Jurkat, and K-562). rTNF-alpha and rTNF-beta also showed strong inhibitory effects on HUVEC as well as on the enhancement of the fibroblast growth. With the use of Sephadex G-100 column chromatography, we obtained the highest activities from the 60- through 70-kDa fractions of the HUT102 supernatant and some activities from the 20- through 30-kDa fractions. The biologic activities of both the whole HUT102 supernatant and its active fractions were completely blocked by anti-TNF-beta mAb, although they were not blocked by anti-TNF-alpha mAb. In a Western blot assay, the 25- and 27-kDa bands of TNF-beta were shown clearly in the HUT102 supernatant, although no TNF-alpha bands appeared. These findings suggest that TNF-beta is present in either its oligomeric or monomeric form in the HTLV-I-infected cell supernatants and is also mainly responsible for the supernatants' effects on HUVECs and fibroblasts.
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PMID:TNF-beta produced by human T lymphotropic virus type I-infected cells influences the proliferation of human endothelial cells and fibroblasts. 820 18

Tolerance to endotoxin (lipopolysaccharide, LPS) was shown to be mediated by an inhibition of cytokine production. We have studied the effect of 3-day pretreatment with LPS on production of IL-6 in response to a subsequent challenge with LPS in a mouse glioma. The results indicated that in this model, a complete blockage of IL-6 production is induced by LPS pretreatment. This is associated with a decrease of LPS-induced IL-6 mRNA levels. LPS-induced IL-6 production can be restored by PMA, as it was previously observed in vivo, suggesting that down-regulation of IL-6 response in LPS tolerance occurs at the transcriptional level, probably by down-regulating protein kinase C or some other PMA-activable signaling system. IL-6 production is also down-regulated by 3-day preincubation with IL-6 and, to a lesser extent, with IL-1 or TNF, indicating that IL-6 can down-regulate its own production.
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PMID:Suppression of interleukin-6 production in endotoxin tolerance in a mouse glioma cell line: reversal by phorbol ester. 845 31

Constitutive expression of the cellular proto-oncogenes c-fos and c-jun, and in a lesser extent ras, was demonstrated in the glioma cell line C-6 by flow cytometry analysis using specific mono and polyclonal antibodies. Basal expression of the products of the early response genes c-fos and c-jun were increased 66 and 50% when Theiler's murine encephalomyelitis virus (TMEV) infected these cells. No increase in ras transcription could be demonstrated after infection. This activation follows a kinetic reaching maximum values after 60 min and was proportional to the multiplicity of infection used. The described effect was completely abrogated by rabbit antibodies to TMEV but was not altered by normal rabbit serum. Furthermore, an intact infectious virion is needed to detect this effect. Fetal calf serum and lipopolysaccharide stimulation slightly increases c-fos and c-jun expression following a slower kinetics. Cytokine treatment (IL-1 alpha, IL-6, IFN-gamma and TNF alpha), did not induce oncogene over-expression. Therefore, this stimulation seems to be linked to the TMEV infectious process.
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PMID:Overexpression of basal c-fos and c-jun but not of ras oncogenes after Theiler's murine encephalomyelitis virus infection of glial cells. 879 9

Morphological and immunocytological changes of intermediate filaments of cultured human malignant glioma cells were studied by adding various growth factors or cytokines using stereoscopic high voltage electron microscopy operated at 1,000 kV. The gold-colloid immuno-cytochemical method was used to stain GFAP and vimentin. Growth rate of tumor cells increased when EGF, TGF-alpha, and PDGF administered and decreased when FGF, TNF, and CLN-IgG administered. Morphological changes of cells were not remarkable when EGF, PDGF, IL-1, and FGF were administered. The cytoplalsmic organellaes were damaged after administrating TNF and CLN-IgG to cells.
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PMID:Changes of intermediate filaments in cultured human glioma cells with various growth factors and cytokines using high voltage immunoelectron microscopy. 891 26

The pro-inflammatory and blood-brain barrier (BBB) effects of intratumoral (IT) injection of human recombinant tumor necrosis factor-alpha (rTNF-alpha) were studied in the Fischer rat RT-2 glioma model. Animals received a single stereotaxic injection of either 6 x 10(4) U rTNF-alpha or excipient (vehicle) into the center of an intracerebrally implanted glioma. In order to demonstrate any effects rTNF-alpha might have on the BBB, studies were conducted using endogenous IgG (150 kD) as a tracer. Forty-eight hours following injection of excipient, a margin of peritumoral IgG extravasation was observed while rats treated with 6 x 10(4) U rTNF-alpha showed a dense and extensive IgG extravasation involving both hemispheres. Histological examination revealed that an IT rTNF-alpha injection induced leukocytic adherence, neutrophilic cuffing and infiltration throughout the lesion from 12 to 72 h after injection. These histological observations were supported by quantification of cerebral myeloperoxidase (MPO) levels which indicated a significant increase in neutrophils over the excipient recipients at 4 and 12 h. These MPO levels contrasted with our earlier studies in normal rats which revealed no significant difference in tissue MPO levels following injection of excipient or rTNF-alpha. In addition, when MPO levels in tumor models and normal rats receiving TNF were compared, a significantly greater presence of neutrophils was seen in tumor models at 12 h post-TNF injection. We believe that the increased inflammatory response seen in a progressing glioma compared to normal brain may be the result of decreased resistance to leukocytic infiltration due to increased vascular surface area, the lack of infiltration-resistant perivascular basement membrane, and/or increased extracellular space.
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PMID:Effects of an intratumoral injection of human recombinant tumor necrosis factor-alpha on cerebrovascular permeability and leukocytic infiltration in a rat glioma model. 900 60

The antitumor activities of recombinant human tumor necrosis factor-alpha (rH-TNF alpha) and liposome-entrapped rH-TNF alpha were evaluated in various glioma cell lines and a rat brain T9 gliosarcoma model. rH-TNF alpha had a direct cytotoxic activity against various glioma cell lines in vitro, and indirect cytotoxic activity against gliosarcoma (T9) in vivo. Liposome-entrapped rH-TNF alpha had increased direct cytotoxic activity in vitro, and against experimentally induced brain tumors in vivo. The effects in vivo were probably due to vascular damage of the tumor vessels as shown by histological examination and activation of cytotoxic macrophages as shown in vitro. These results indicate that the general or local administration of liposome-entrapped rH-TNF alpha may become a useful adjunct treatment for malignant brain tumor.
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PMID:Antitumor activity of recombinant human tumor necrosis factor-alpha (rH-TNF alpha) and liposome-entrapped rH-TNF alpha. 936 33

Numerous in vivo methodologies have documented the invasive behavior of glioma cells through normal brain parenchyma. Glioma cell locomotion has also been assessed with a number of in vitro assays including the Boyden chamber and other chemotaxis assays, colloidal gold cell tracking, analysis of migration of cells tumor cells from spheroids, confrontation cultures of glioma cells with aggregates of non-neoplastic tissue, time-lapse video microscopy, electron microscopic examination of the cytomorphologic correlates of cell motility, the radial dish assay, and quantitative enzyme immunoassay of proteins associated with invasion (e.g. laminin). Several of these techniques have been specifically modified to assess the effects of cytokines on glioma cell motility in vitro. Cytokines studied utilizing these methods include: epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), the bb dimer of platelet-derived growth factor (PDGFbb), nerve growth factor (NGF), interleukin 2 (IL-2), transforming growth factors alpha and beta 1 (TGF alpha and TGFstraat1), and tumor necrosis factor alpha (TNF alpha). This review summarizes the investigational methods used to evaluate random and directional glioma cell motility and invasion in vivo and in vitro. The roles of specific mitogens as motogens, as evaluated with these methods are then presented.
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PMID:Mitogens as motogens. 944 23

We evaluated the antitumor effects of ionizing radiation and tumor necrosis factor-alpha (TNF-alpha) gene therapy in human malignant glioma (D54) xenografts. An adenoviral vector (Ad5) containing DNA sequences of the Egr-1 promoter was linked to a cDNA encoding the TNF-alpha gene (Ad. Egr-TNF). Athymic nude mice bearing D54 xenografts received intratumoral injections of Ad.Egr-TNF or the null vector (Ad.null), with and without fractionated radiation, 5 gray (Gy) per day for 6 days, a total dose of 30 Gy. Administration of Ad.Egr-TNF and 30 Gy resulted in complete tumor regression in 71% of xenografts compared with xenografts treated with radiation alone (7.4%, P = 0.006), Ad.Egr-TNF alone (0%, P = 0.012) or Ad.null with 30 Gy (0%, P = 0.002). Combined treatment with Ad.Egr-TNF and 30 Gy significantly reduced mean fractional tumor volumes compared with radiation alone (P = 0.002), Ad.Egr-TNF alone (P = 0.002) and Ad.null plus 30 Gy (P = 0.018). Histopathologic analyses of glioma xenografts treated with Ad.Egr-TNF and radiation revealed tumor vessel thrombosis by day 4 and necrosis by day 7. Thrombosis was not observed in tumors treated with Ad.Egr-TNF alone and was significantly reduced in all other treatment groups. These studies suggest that in the D54 glioma xenograft model, the antitumor effects of combining radiation and Ad.Egr-TNF are mediated, in part, by the destruction of the tumor microvasculature.
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PMID:Adenoviral TNF-alpha gene therapy and radiation damage tumor vasculature in a human malignant glioma xenograft. 961 48


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