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 new approach to the treatment of malignant glioma is cytokine gene therapy to produce growth inhibitors in cells. Previously, we showed that human glioma cells selectively transfected with the gene of interferon (IFN)-beta and/or IFN-gamma by our novel liposomes tagged with monoclonal antibody against a glioma-associated antigen achieved a remarkable growth inhibition effect. In the present experiment, we demonstrated the effectiveness of gene therapy against glioma cells using liposomes bearing a plasmid containing the gene for tumor necrosis factor (TNF)-alpha. We also found that the effect of endogenous TNF-alpha was enhanced by treatment of IFN-gamma prior to the transfection with the TNF-alpha gene.
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PMID:Growth inhibition of glioma cells by liposome-mediated cell transfection with tumor necrosis factor-alpha gene--its enhancement by prior gamma-interferon treatment. 128 76

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

We have studied the effect of tumor necrosis factor (TNF-alpha) on transformed neural and glial-derived cell lines. TNF-alpha at physiological doses was able to arrest the growth and inhibit DNA synthesis of N103 neuroblastoma cells. This phenomenon was accompanied by a morphological cell differentiation characterized by the outgrowth of neurites. By contrast, TNF-alpha induced an increase in the growth rate of C6 glioma cells and upon cytokine addition a higher number of C6 cells were found in the S + G2 phase of the cell cycle. C6 cells did not show morphological changes under this treatment. Analogous results were obtained with IFN-gamma. These neurotrophic and mitogenic effects of TNF-alpha suggest a putative role of this cytokine in the regeneration of brain tissue upon brain injury.
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PMID:Differential effects of tumor necrosis factor on the growth and differentiation of neuroblastoma and glioma cells. 190 93

Human malignant glioma cell lines and clones were incubated with various concentrations of recombinant human TNF-alpha, either alone or in combination with recombinant human IFN-gamma. The surface expression of HLA-ABC (class I) antigens and beta 2-microglobulin, was significantly enhanced by TNF-alpha alone on every cell line and clone tested. After incubation with both TNF-alpha and IFN-gamma, the surface expression of HLA-ABC antigens was only slightly higher than that observed with each cytokine alone. In contrast to IFN-gamma, TNF-alpha had no effect on the surface expression of HLA-DR (class II) antigens. Moreover, the surface expression of HLA-DR induced by IFN-gamma was unaffected by TNF-alpha. The increased expression of HLA-ABC antigens after treatment with TNF-alpha or IFN-gamma correlated with increased levels of HLA-ABC-specific mRNA. In addition, TNF-alpha, like IFN-gamma, selectively enhanced the surface expression of a tumor-associated antigen, Me14-D12, while it had no effect on the expression of various other surface antigens. In the absence of actinomycin D, TNF-alpha exhibited no direct cytotoxic/cytostatic effect on the glioma cell lines tested. These results indicate that TNF-alpha can enhance the surface expression of HLA-ABC antigens on human glioma cells in the absence of a direct cytotoxic/cytostatic effect.
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PMID:Effects of recombinant human tumor necrosis factor-alpha on the surface phenotype and the growth of human malignant glioma cell lines. 314

Lymphokine-activated killer (LAK) cells generated from peripheral blood lymphocytes incubated with recombinant interleukin-2 were transfected with the human gamma-interferon (HuIFN-gamma) gene by means of liposomes having a positive charge on their surface. The cells secreted significant amounts of HuIFN-gamma (reaching more than 5 U/ml) into the culture medium. The HuIFN-gamma produced by the cells induced intercellular adhesion molecule-1 (ICAM-1) and enhanced the expression of Fas antigen on the surface of human glioma cells. Also, LAK cells transfected with HuIFN-gamma gene exhibited reinforcement of cytotoxicity toward human glioma cell lines (U251-MG and SK-MG-1). Furthermore, the reinforcement was significantly quenched by anti-ICAM-1 and/or anti-TNF-alpha monoclonal antibody.
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PMID:Reinforced cytotoxicity of lymphokine-activated killer cells toward glioma cells by transfection of the killer cells with the gamma-interferon gene. 753 27

Besides surgery, the therapeutic possibilities for the treatment of human gliomas include adoptive cellular immunotherapy, radioimmunotherapy, immunotherapy mediated by chemoimmunoconjugates and, more recently, bispecific monoclonal antibodies (biMAbs). Anti-CD3 x anti-tenascin (TN) is the first reagent of a number of biMAbs under investigation for prospective use in vivo to maximize the cell-mediated cytolytic potential of glioma patients. This biMAb originated from the fusion of 2 parental hybridomas, made resistant by retrovirus-mediated infection to the different metabolic drugs, geneticin and methotrexate, respectively. The resulting hybrid hybridomas were selected on the basis of the double specificity for CD3 and TN, cloned several times and grown under continuous metabolic pressure. The different families of recombinant antibodies were then purified by high-pressure liquid chromatography on hydroxylapatite columns. Immunohistochemical studies on tumor specimens of different origin and histotype have shown that the selected biMAb presented a distribution pattern similar to that of the parental anti-TN MAb, maintaining the same staining homogeneity and intensity. Moreover, the mitogenic activity of anti-CD3 x anti-TN biMAb on peripheral blood mononuclear cells was similar to that featured by the parental anti-CD3 MAb. Furthermore, the hybrid molecule induced TNF-alpha gene expression in activated PBMC. Finally, the anti-CD3 x anti-TN featured the desired killer targeting ability, being able to induce a significantly increased cytotoxic activity against TN+ tumor cells.
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PMID:Bispecific monoclonal antibody anti-CD3 x anti-tenascin: an immunotherapeutic agent for human glioma. 753 78

Neovascularization is a prerequisite for glioma growth, so inhibition of angiogenesis may achieve control of glioma growth. We examined whether glioma cells induce angiogenesis and proliferation in microvascular endothelial cells from Fisher 344 rat brains by co-culture in a physical separation system with rat C6 glioma cells or rat T9 gliosarcoma cells. Endothelial cells cultured on type 1 collagen formed capillary-like structures. C6 glioma cells co-cultured with endothelial cells promoted the formation of these capillary-like structures. However, conditioned medium from C6 cells inhibited the proliferation of endothelial cells. T9 cells had little effect on the formation of capillary-like structures and no effect on the proliferation of endothelial cells. We also examined the effects of human tumor necrosis factor (TNF)-alpha on the formation of the capillary-like structures and on the proliferation of endothelial cells. Human TNF-alpha inhibited the formation of capillary-like structures induced by C6 glioma cells at a concentration of 100 U/ml, as well as the proliferation of endothelial cells at a concentration of 1000 U/ml. These results indicate that induction of angiogenesis varies with glioma cell lines and angiogenesis does not correspond with proliferation of endothelial cells. TNF-alpha can inhibit angiogenesis in gliomas in vitro.
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PMID:Angiogenesis in microvascular endothelial cells induced by glioma cells and inhibited by tumor necrosis factor in vitro. 754 Nov 18

Adult neurons normally lack the expression of MHC class I molecules, which has implications on virus clearance from the central nervous system. The author previously demonstrated that HLA class I up-regulation in measles virus (MV)-infected glial cells is primarily mediated by IFN-beta. In contrast, this study demonstrates that MV-infection of the neuronal cell lines IMR-32 and CHP-126 fails to up-regulate HLA class I expression, which was associated with an inability of MV to induce IFN-beta in the neuronal cell lines. However, treatment with IFN-beta on coculture of the IMR-32 neuronal cell line with MV-infected glioma cells resulted in the up-regulation of HLA class I on the former, which could be neutralized by anti-IFN-beta Ab. The inability of MV to up-regulate HLA class I expression on the neuronal cell line IMR-32 was not virus specific because similar findings were observed with mumps virus or stimulation with the synthetic dsRNA polyinosinic polycytidylic acid (PIPC). Induction of IFN-beta gene expression by virus requires binding of NF-kappa B to the positive regulatory domain II element of the IFN-beta promoter. Our studies indicate that MV, TNF-alpha, or PIPC induces NF-kappa B (p50 and p65 subunits) binding to positive regulatory domain II in the glioma cell line. In contrast, such activity was induced by TNF-alpha but not MV or PIPC in the neuronal cell line IMR-32. This indicated that HLA class I expression is differentially regulated in glial and neuronal cell lines in response to MV, which correlates with differential binding of NF-kappa B to the IFN-beta promoter and induction of IFN-beta gene expression.
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PMID:Differential up-regulation of HLA class I molecules on neuronal and glial cell lines by virus infection correlates with differential induction of IFN-beta. 763 59

The ability of a mannoprotein antigen from Candida albicans (MP) or interleukin-2 (IL-2) to induce cytokines in cultures of peripheral blood mononuclear cells (PBMC) of glioma patients and healthy controls was evaluated by mRNA expression and by protein secretion. The subjects studied were all responsive to both MP and IL-2, as assayed by lymphoproliferation of PBMC cultures. In control subjects, MP and IL-2 were strong inducers of IFN-gamma, IL-1 beta, TNF-alpha, and GM-CSF mRNA expression, but only MP was able to induce considerable levels of IL-6 and IL-2 mRNA expression. In MP-activated PBMC from glioma subjects, a highly defective IFN-gamma, together with a significant reduction in TNF-alpha and GM-CSF mRNA expression, was observed. This impairment was paralleled by a decreased accumulation of IL-6 and IL-2 mRNA. The pattern of cytokine mRNAs in IL-2-activated PBMC of glioma patients confirmed the impairment of IFN-gamma mRNA expression paralleled by a reduction in IL-6, TNF-alpha and GM-CSF mRNA, compared with healthy subjects. Coherently, in PBMC cultures from glioma patients, there was a clear-cut decrease in the secretion of IL-6 and TNF-alpha and especially of IFN-gamma compared with healthy controls. No or very low levels of IL-4, IL-10, and TGF-beta 2 mRNA expression were detected in PBMC cultures of both glioma and control populations, irrespective of the activation conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Defective expression of interferon-gamma, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and interleukin-6 in activated peripheral blood lymphocytes from glioma patients. 764 44

Expression of the cytokine genes in human glioma cell lines and specimens was studied. Primers for 7 different human cytokine, IL-1 beta, IL-6, IL-8, GM-CSF, TGF-beta 1, TNF-alpha and IFN-gamma were used to analyze messenger RNA transcripts by polymerase chain reaction (PCR). Messenger RNA encoding for IL-1 beta, IL-6, IL-8, GM-CSF and TGF-beta 1 was found to be expressed in some of glioma cell lines. And those showed a proliferative response to IL-1 beta. IL-8 mRNA was found in 2 of 5 low grade gliomas, in 8 of 9 high grade gliomas. TGF-beta 1 mRNA was found in all gliomas, in 1 of 2 normal brains. IL-1 beta mRNA was only found in normal brains. TNF-alpha and IFN-gamma were not found in glioma cell lines and specimens. IL-8 mRNA was apt to be found more frequently among high grade glioma specimens.
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PMID:Cytokine gene expression on glioma cell lines and specimens. 769 19


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