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 mannoprotein preparation (MP) from Candida albicans induced MHC-unrestricted cytotoxicity in peripheral blood mononuclear cells (PBMC) from healthy subjects, but not in those from glioma-bearing subjects. The two groups of subjects did not significantly differ in the number of cells bearing typical natural killer (NK) markers (both in resting and MP stimulated PBMC) and NK activity. However, interferon gamma (IFN-gamma) production was in tumour patients minimal or significantly reduced, as compared to healthy subjects, following PBMC stimulation by MP or phytohaemoagglutinin, respectively. In addition, minimal, if any, stimulation of interleukin-2 (IL-2) production was achieved in MP stimulated PBMC from glioma patients. Considering the pivotal role of the above cytokines in immune responses, particularly in those concerning generation of antitumour effectors, our results consistently suggest that defective cytokine production is one possible mechanism of immunological impairment in glioma patients. They also provide indirect support for a possible clinical use of IFN-gamma as an immunopotentiating agent in gliomatous subjects.
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PMID:Cell mediated cytotoxicity and cytokine production in peripheral blood mononuclear cells of glioma patients. 171 54

Recombinant tumor necrosis factor alpha (TNF-alpha) significantly enhanced epidermal growth factor receptor (EGF-R) expression in U373-MG glioma cell line as determined by binding of anti-EGF-R monoclonal antibody (MAb) 425. The optimal dose of TNF-alpha was 1000 U/ml of media. When TNF-alpha was combined with recombinant interferon gamma (IFN-gamma), further upregulation of EGF-R was observed. However, IFN-gamma itself did not show any EGF-R enhancement in this cell line. Scatchard analysis of receptor binding revealed that this enhancement of EGF-R expression was due to an increase in the EGF-R density. TNF-alpha did not affect expression of other brain tumor-associated antigens defined by MAb ASHE2, ASHG4 and ASAY1. Cultured fibroblasts showed no upregulation of EGF-R by TNF-alpha, suggesting a differential effect of TNF-alpha on EGF-R expression on glioma cells and normal cells. We investigated whether TNF-alpha treatment of glioma cells increased the tumoricidal effects of radiolabeled MAb 425 which correlate with MAb density on tumor cell surfaces. Growth inhibition of glioma cells in culture by 125I-labeled MAb 425 was significantly enhanced after treatment of the cells with TNF-alpha. In previous clinical trials, 125I-labeled MAb 425 has shown immunotherapeutic effects in glioma patients. The present study provides the basis for considerations of combined immunotherapy of glioma patients with 125I-labeled MAb 425 and cytokines.
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PMID:[Enhancement of epidermal growth factor receptor (EGF-R) expression on glioma cells by cytokines]. 174 26

Human glioblastoma cells secrete an inhibitory factor termed "glioblastoma-derived T-cell suppressor factor" (G-TsF). A member of the transforming growth factor beta (TGF beta) family, G-TsF is identical to TGF beta 2. The present study investigated the effect of G-TsF/TGF beta 2 on the proliferative and cytotoxic properties of tumor-infiltrating lymphocytes (TIL's) isolated from malignant gliomas after expansion in vitro with interleukin-2 (IL-2). The results demonstrate that the IL-2 (5 to 20 U/ml)-dependent proliferative response of glioma-derived TIL's was inhibited 70% to 85% by G-TsF/TGF beta 2 and that the inhibitory effect could be reduced by using increasing concentrations of IL-2 (100 to 200 U/ml). Tumor necrosis factor alpha (TNF alpha) enhanced the IL-2-dependent proliferation of TIL's cultured in low concentrations of IL-2 (10 U/ml); however, neither TNF alpha nor interferon gamma was able to reduce the inhibitory effect of TGF beta 2 on TIL proliferation. In addition, TGF beta 2 suppressed 60% to 100% the cytotoxic response of glioma-derived TIL's against several tumor targets, including autologous glioma cells, and the suppressive effect was shown to be reduced by increasing concentrations of IL-2.
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PMID:Inhibition of lymphocyte function by glioblastoma-derived transforming growth factor beta 2. 254 42

We have investigated the phenotype of seven human glioma cell lines established in vitro from primary tumour explants. Indirect immunofluorescence and flow cytofluorimetry revealed a heterogeneous distribution of surface GE 2 and CG 12 Tumour Associated Antigens (TAA). In one group of cell lines TAA were detected both at the cell surface and in the cytosol, whereas in a second group of glioma cell lines TAA were found only in the cytosol. We have also investigated the sensitivity of glioma-derived cell lines to antibody-toxin and ligand-toxin conjugates (Immunotoxins). Monoclonal antibodies anti GE 2 antigen linked to ricin toxin A subunit (RTA) showed poor cytotoxicity, which increased about 50 fold when the whole toxin was linked to anti GE 2 monoclonals. Treatment with human recombinant interferon gamma (IFN-gamma) greatly augmented the percentage of HLA-DR+ cells and the amount of HLA-DR antigens per cell. IFN-gamma treatment resulted in a net increase of sensitivity to anti HLA-DR Immunotoxins (IT). Human diferric transferrin linked to RTA exhibited a potent cytotoxic effect against human glioma-derived cells when used in the presence of the lysosomotropic carboxylic ionophore monensin.
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PMID:Human glioma cell lines: tumour associated antigens distribution and sensitivity to antibody-toxin or ligand-toxin conjugates. A preliminary report. 326 95

Immunobiology of the normal and tumoral astrocytes studies interactions between these cells and the immune system. Their antigenic characterization defines 3 classes of antigens: glial antigens, tumor associated antigens (neuroectodermal and gliomatous) and lymphoid differentiation antigens which can be modulated by gamma interferon and other cytokines. Glioma associated antibodies could be used for radiolocalization of tumours and for immunotherapy. The enhancement or induction of the Major Histocompatibility Complex antigen expression by interferon gamma could enhance tumour-antigen presentation by glioma cells to helper and cytotoxic T cells and thus activate the host's immune response. The presence of oncogenes and their products in glioma cells, mainly growth factor receptors, brings new potential therapies using oncogenes products as tumoral markers or as targets for monoclonal antibodies blocking their mitogenic activity. Normal and tumoral astrocytes produce lymphokines: interleukin 1, interleukin 3, prostaglandin E as well as a suppressor factor inhibiting interleukin 2 mediated effects and probably responsible for the suppression of glioma infiltrating T cells. The interaction of astrocytes with several humoral factors related to the immune system and their capacity to function as antigen presenting cells underline their importance for immune reactions within the central nervous system.
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PMID:[Immunobiology of the normal and tumor astrocyte]. 332 64

This study evaluates cerebral entry of mouse interferon alpha/beta (MuIFN alpha/beta) or mouse interferon gamma (MuIFN-gamma) following continuous (3 day), subcutaneous infusion of normal or glioma bearing mice. The intracerebral C57BL/6 mouse glioma-26 (G-26) model was used at days 10-14 post tumor implant, the advanced stage of glioma progression as defined by histology and the median survival time (27 +/- 3.8 days). The infusion of horseradish peroxidase (HRP) in vivo at day 10 or 11 post glioma implant showed strong staining in the tumor bed indicating compromised blood-brain barrier (BBB). In addition, histochemistry with Bandeiraea simplicifolia isolectin B4 demonstrated the accumulation and/or activation of macrophage/microglia. The 3 day infusion of mice (day 11-14 post tumor implant) via subcutaneous (sc) osmotic micro-pumps with MuIFN alpha/beta (8x10(5) - 1.7x10(6) international units [IU]/ml) or with recombinant mouse interferon gamma (rMuIFN-gamma) (1x10(6) IU/ml) resulted in a low but detectable (1-5 IU/ml) cerebral level of IFN. The IFN levels in the blood (20-40 IU/ml) and brain, measured by assay of inhibition of viral cytopathic effect (CPE) or ELISA assay for MuIFN-gamma, showed no difference between normal and glioma bearing mice. The lipoxygenase (LO) activity (dioxygenase) of glioma tissue and contralateral control was evaluated in non-treated and MuIFN alpha/beta continuously (3 day) treated mice. The LO activity in glioma tissue was significantly higher (p < 0.05) than the contralateral control in non-treated mice. However, following sc MuIFN alpha/beta infusion the LO activity of glioma decreased to control level.
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PMID:Interferon entry through the blood-brain barrier in glioma and its effect on lipoxygenase activity. 752 Nov 51

The effect of intratumoral recombinant interferon gamma (rIFN-gamma) as adjuvant to open cytoreduction and external irradiation of 60 Gy on survival in adults with a newly diagnosed high-grade cerebral glioma was studied. The patients were randomised during surgery into the rIFN-gamma group (n = 14) or the control group (n = 17), and the latter received a subcutaneous reservoir of rIFN-gamma injections. Intratumoral rIFN-gamma was given three times a week for 4 weeks until radiotherapy, escalating the dose from 5 micrograms to 50 micrograms. Both groups received external whole-brain irradiation of 40 Gy and a local boost of 20 Gy. After radiotherapy, rIFN-gamma was continued with 50 micrograms twice a week up to 9 weeks. The patients received no chemotherapy. Intratumoral rIFN-gamma was tolerated well with transient fever only. There were 12 glioblastomas (GBs) in the control group and nine in the rIFN-gamma group with completed irradiation. The patients were followed clinically and by computerised tomography (CT) every third month until death. Tumour responses were seen in three interferon-treated (one still alive 45 months after operation) and in two conventionally treated patients. The progression of the tumour volumes on CT did not differ between the IFN-treated and control groups. There were no differences in the survival times. Median survival of the rIFN-gamma-treated patients was 54 weeks (95% CI 35-68) and of the control patients 55 weeks (95% CI 41-77). Intratumoral rIFN-gamma given in the study doses does not seem to inhibit tumour growth or improve the prognosis of patients with high-grade glioma.
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PMID:Randomised, controlled study of intratumoral recombinant gamma-interferon treatment in newly diagnosed glioblastoma. 801 25

The ethyl-N-nitrosourea-induced rat glioma N32 was treated with the mutagenic compound N-methyl-N'-nitro-N-nitrosoguanidine and the surviving cells cloned by limited dilution. Out of 20 clones tested 8 did not produce tumors subcutaneously even after challenge doses 3 log units above the minimal tumor dose for N32. All of 5 clones grew in a retarded manner intracerebrally but produced tumors in some animals. Preimmunizations with three of the rejected clones (tum-) gave protection against subcutaneous and intracerebral isografts of the unmutated N32. This effect could be enhanced if the cells used for immunizations were pretreated with interferon gamma (IFN gamma) for 48 h. If immunizations were started subsequent to challenge, only immunization with one of two tested tum- clones pretreated with IFN gamma induced significant rejection against intracerebral N32 isografts. Both N32 and its tum- clones were MHC class I positive and MHC class II negative. IFN gamma treatment enhanced the MHC class I expression with 20%-90% on the tum- clones and with 40% on N32. MHC class II expression could be induced on N32 cells after 7 days of IFN gamma treatment but not on any of the tum- clones tested. We conclude that the enhancing effect of IFN gamma treatment on tumor isograft rejection may depend on up-regulation of MHC class I but not of MHC class II. This investigation demonstrates that it is possible to induce rejection of weakly immunogenic intracerebral brain tumors by immunization with selected highly immunogenic tumor cell mutants. In conjunction with relevant cytokines, the cross-protective effect of these tum- variants might be further enhanced and serve as a model for immunotherapy against malignant human brain tumors.
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PMID:Immunization with mutagen-treated (tum-) cells causes rejection of nonimmunogenic rat glioma isografts. 851 54

We studied the changes of tumor size after gene therapy treatment and its relationship with the changes of vascular volume as measured by dynamic contrast-enhanced magnetic resonance imaging (MRI), to investigate whether the vascular changes is predictive of tumor regression. The study was carried out using a spontaneously regressing rat tumor model (C6 Glioma grown subcutaneously in rats). Three rats were treated with recombinant adenoviruses expressing three genes, mouse interleukin 1-alpha (IL1-alpha), mouse interferon gamma (IFN-gamma), and human transforming growth factor beta (TGF-beta), one from each kind. Two rats were treated with saline as controls. Longitudinal studies were performed to monitor the changes of tumor volume (based on T(2)-weighted images) and the vascular volume (based on dynamic contrast enhanced images). In untreated animals, tumor regression was preceded by several days with a decrease in vascular volume. When the tumor growth was perturbed by expression of mouse IL-1alpha, the increase in vascular volume was correlated with the continuing growth in size, and the decrease in vascular volume was predictive of the onset of tumor regression. As new advances in immunotherapy in cancer treatment emerge, the ability to determine the efficacy of therapy as early as possible will enable optimization of treatment regiments. The vascularity changes measured by dynamic MRI may provide a means to serve for this purpose.
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PMID:Prediction of gene therapy-induced tumor size changes by the vascularity changes measured using dynamic contrast-enhanced MRI. 1074 41

Malignant gliomas are frequent and the prognosis is poor. The cytokine interferon gamma (IFN-gamma) enhances several immune phenomena and may be used in immunotherapy of tumours. Therefore we investigated the influence of IFN-gamma on human cell lines T98G, U87MG, 86HG39 and 85HG66, measuring cell viability (MTT-test) and proliferation (3H-thymidine uptake). IFN-gamma markedly decreased viability and proliferation of all investigated cell lines. Expression of CD44 and adhesion to hyaluronic acid (HA) are involved in glioma invasion. Influence of IFN-gamma on these two features has also been investigated. IFN-gamma markedly decreased HA-adhesion in all three investigated cell lines, whereas CD44 expression remained uninfluenced. To summarise, IFN-gamma strongly decreased cell growth and HA-adhesion of malignant glioma cell lines in vitro. We suggest further investigations to characterise better the role of IFN-gamma as a treatment opportunity for malignant gliomas.
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PMID:Interferon gamma inhibits proliferation and hyaluronic acid adhesion of human malignant glioma cells in vitro. 1080 25


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