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)

Transforming growth factor-beta (TGF-beta) is known to have a potent inhibitory influence on several immune functions. It has recently been demonstrated that TGF-beta 2 is identical to the glioblastoma-derived T cell suppressor factor (G-TsF). In the present study, human malignant glioma cell lines were incubated with various concentrations of TGF-beta 2. An optimal concentration of 1 ng/ml TGF-beta 2 produced a partial but significant decrease of HLA-DR (class II) surface antigen expression on glioma cells expressing this antigen, as well as decreased levels of HLA-DR-specific mRNA. The surface expression of other HLA-related molecules, such as HLA-ABC (class I) and beta 2-microglobulin, was not influenced by TGF-beta 2. The suppressive effect of TGF-beta 2 on HLA-DR expression, both at the surface antigenic and cytoplasmic mRNA levels, could be completely overcome by adding relatively high concentrations (500 U/ml) of interferon (IFN)-gamma to the culture system. However, TGF-beta 2 inhibited the enhancement of HLA-DR surface expression produced by low concentrations of IFN-gamma on some cells which initially did not express these antigens. These results show that TGF-beta 2 can act as a regulator of HLA-DR antigen expression on human glioma cells.
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PMID:Transforming growth factor-beta 2 down-regulates HLA-DR antigen expression on human malignant glioma cells. 314 81

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

The effects of interleukin 2 (IL2) and interferon (IFN) on the generation and lytic activation of syngeneic murine malignant glioma (a methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin, 203-glioma)-specific cytotoxic T-lymphocyte (G-CTL) were investigated. The surface marker analysis showed that G-CTLs from both intracranial and s.c. tumor-bearing mice were composed of thymectomy-resistant (mature) Lyt-1-.2.3+ and thymectomy-sensitive (immature) Lyt-1+.2.3+ CTLs, which markedly decreased concurrently with increased intracranial pressure. G-CTLs were confirmed to be activated with target specificity by both factors in a different way. The CTL activation by IL2 (20 units/ml) remained for a longer time, although a lag time of 5 days after initial culture was required. IL2 influenced Lyt-1+.2.3+ CTLs to proliferate and develop the lytic potential. In contrast, even a 3-h incubation with IFN (1000 units/ml) could enhance the cytotoxicity, but the augmenting effects were observed no longer than 5 days later. IFN activated Lyt-1-.2.3+ CTLs and increased their proportion of the total cell population with a simultaneous decrease of Lyt-1+.2.3+ CTLs. Therefore, it was suggested that IL2 may provide a growth of CTL populations and that IFN can accelerate recruitment of new effectors, causing activation of the lytic process.
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PMID:Immunoregulatory effects of interleukin 2 and interferon on syngeneic murine malignant glioma-specific cytotoxic T-lymphocytes. 325 57

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 investigation tested the hypothesis that the growth inhibiting effects of human beta-interferon on cultured human glioma cells involves changes in the ganglioside composition of these cells. Four cell lines derived from human malignant gliomas (12-18, U-251 MG, I29-A, 7-24) and two lines from human fetal brain (CHI, CHII) were cultured in the presence and in the absence of human beta-interferon (HuIFN-beta), 1,000 units per ml medium for three days before harvesting. Human beta-interferon had an inhibitory effect on growth of glioma but not fetal brain cells. Total ganglioside sialic acid for all cell lines ranged between 3.5 and 13.8 micrograms/10(7) cells (0.6-3.9 micrograms/mg protein). No distinct difference in the amount of total ganglioside per cell was observed between neoplastic and non-neoplastic cells, but the latter had more ganglioside per mg total protein. All cell lines displayed different patterns of gangliosides determined by high performance thin layer chromatography, but there was no distinct difference between glioma and fetal brain cells. Human beta-interferon increased the total amount of ganglioside per cell in one fetal brain and two glioma lines, but on a protein basis in only one glioma cell line (I29-A); HuIFN-beta had only minor effects on ganglioside patterns. There was a slight shift towards a greater proportion of structurally simpler gangliosides in both fetal brain and two glioma cell lines exposed to HuIFN-beta, but the reverse occurred in glioma U-251 MG. None of these changes strongly correlated with the degree of growth inhibition due to HuIFN-beta.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth inhibition of cultured human glioma cells by beta-interferon is not dependent on changes in ganglioside composition. 333 70

Case histories of 5 tumor patients treated with natural leukocyte interferon-alpha (IFN-alpha) are presented. One patient with juvenile laryngeal papillomatosis responded well to interferon treatment, but the disease recurred when therapy was withdrawn. Upon reinstitution of treatment, the patient once again responded well. Another patient with myelomatosis also responded well to interferon therapy and in this case, too, the tumor recurred when interferon treatment was withdrawn. Reinstitution of interferon therapy was, however, unsuccessful. One patient with generalized giant cell tumor of bone responded with regression after more than 5 years of interferon treatment. Another patient with pulmonary osteosarcoma metastases, having received irradiation and interferon combination therapy followed by sole interferon treatment, responded well with a lasting stationary radiogram after 6 years of interferon treatment. One patient with malignant glioma, showing signs of tumor growth during the first few months of interferon therapy, eventually responded, and became disease-free after 6 years. The latter 3 patients are continuously receiving interferon therapy although more than 5 years have elapsed since their interferon therapy was initiated. It is suggested that interferon therapy for malignant tumors be given for life (or to progression of disease) in responding patients. Such a concept entails biological implications for interferon therapy in general and for antitumor action of interferons in particular. Other possible clinical schedules should only be constructed within the framework of controlled clinical trials.
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PMID:Does successful interferon treatment of tumor patients require life-long treatment? 347 1

Three cell samples in different passages of the line U-343 MGa, derived from a human malignant glioma biopsy, gave rise to clones with different amounts of platelet-derived growth factor (PDGF)-like activity secreted to extracellular medium, and of 125I-labeled PDGF binding. Sixteen clones were completely karyotyped with the G-banding technique. The unique markers 1p-q+, 16p- found in all clones, as well as in the parallel uncloned line, U-343 MG, provided evidence of their common origin. The deduced early, possibly partly primary, deviations had the formula 44, XY, 1p-q+, -14, 16p-, -22, where loss of one chromosome 22 is in accordance with previous reports on early chromosomal deviations in gliomas. Two clones, the hypodiploid 26L and 5H, represented early progressional changes. The other clones followed two patterns of late progressional changes, probably starting from the karyotype of 5H, with additional markers and doubling of the stemlines. In late progressional line I 12q+ and in II +7 were the most characteristic findings. Northern blot analysis using complementary DNA clones for the A and B chains of PDGF showed that both PDGF chains were expressed in 26L and 5H indicating that activation of the PDGF genes could have been an early event in the development of this glioma. Clones with late progression pattern II had been subjected to the highest selective pressure in vitro, and they secreted the highest amount of PDGF-like activity to the extracellular medium. Among them were the most rapidly and tightly growing cells and some clones with high 125I-labeled epidermal growth factor binding. Possibly these findings reflect progressional changes including defective regulation of the growth factor/growth factor receptor genes, selected for in vitro, without involving gross rearrangements or amplifications of the genes. The possible significance of extra chromosomes 7, with the PDGF A chain and epidermal growth factor receptor genes, and of the 12q+ marker, located near the gamma interferon gene is discussed.
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PMID:Evidence for progressional changes in the human malignant glioma line U-343 MGa: analysis of karyotype and expression of genes encoding the subunit chains of platelet-derived growth factor. 349 14

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

The authors have established a murine malignant glioma-specific cytotoxic T lymphocyte clone (G-CTLL 1) by T cell growth factor (TCGF) using 203-glioma (a methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin). The cloned cells were found to release a large amount of gamma interferon (IFN) in response to glioma-associated antigen-specific stimulation. The authors have investigated whether the IFN produced can contribute to killing the target cells. Adding anti-mouse gamma IFN antibody to the mixed clone-target cell culture inhibited IFN production by the cloned cells but the toxicity of the cells was minimally diminished. Therefore, it is suggested that the endogenous gamma IFN produced by the TCGF-dependent cloned cytotoxic T lymphocyte line does not have direct cytotoxic action on the target cells. Furthermore, IFN production as well as cytotoxicity was blocked by anti-Lyt-2 monoclonal antibody in the absence of complement. This suggests that IFN plays a role in the process of antigen recognition of target cells because the Lyt-2 molecule is involved in an antigen-specific function on the cytotoxic T lymphocyte receptor. The role of TCGF in gamma IFN production was also investigated. The spontaneous production of gamma IFN by the cloned cells paralleled the amounts of exogenous TCGF added to the cultures, but TCGF had no synergistic effect on IFN production in the presence of mitogen or tumor antigen. Accordingly, it is possible that TCGF stimulates the cloned cells to proliferate, causing IFN release.
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PMID:Immunoregulatory role in gamma interferon production by a T cell growth factor-dependent experimental malignant glioma-specific cytotoxic T lymphocyte clone. 393 9

The direct antitumoral effect of interferon-alpha on human glioma was suggested in a study involving tissue culture, and scanning and transmission electron microscopy. Consequently, intratumoral local administration of interferon-alpha for four cases of human glioma was performed, and each survival period from the initiation of its application was seven, eight, three and two months. Slight direct antitumoral effect of interferon was observed in the findings of both CT scan and autopsy in our series, but the survival time was not as great as we had expected. One of the reasons for this was thought to be insufficient permeability of interferon-alpha into the residual infiltrating tumor tissue. Therefore, the use of systemic administration of interferon or another adjuvant therapy with local administration of interferon would be expected to produce better results.
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PMID:[A study on the direct antitumoral effect of interferon-alpha on human glioma]. 395 71


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