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 humoral interactions between three malignant glioma early-passage cell cultures and in vitro interleukin (IL)-1 alpha- and IL-2-activated autologous peripheral blood mononuclear cells (PBMC's) were investigated, employing standard and modified (separated by permeable membranes) mixed lymphocyte tumor cell (MLTC) cultures. In modified MLTC's, glioma cells clearly inhibit proliferation of PBMC's (up to 60%), whereas lymphokine-activated PBMC's enhance glioma cell growth up to 12-fold, as determined by 3H-thymidine incorporation assays. Glioma cells produce both stimulatory (IL-6) and inhibitory proteins (transforming growth factor-beta) for PBMC's. Lymphokine-activated PBMC's secrete IL-1 alpha, IL-2, IL-4, IL-6, interferon-gamma, and tumor necrosis factor-alpha, which may modulate glioma cell proliferation. None of these cytokines stimulated glioma cells as intensely as modified MLTC systems. These observations indicate that in vitro lymphokine-activated PBMC's, although suppressed by humoral glioma-derived factors, may enhance glioma cell proliferation with soluble factors secreted into the culture medium. The authors conclude that glioma-lymphocyte growth regulatory networks include stimulatory and inhibitory factors from both cell populations, which may modulate tumor progression. These observations may have relevance for adoptive immunotherapy in patients with gliomas.
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PMID:In vitro studies of cytokine-mediated interactions between malignant glioma and autologous peripheral blood mononuclear cells. 793 92

The transforming growth factor-beta (TGF-beta) superfamily plays a role in embryogenesis and regeneration. We have reported that osteogenic protein-1 (OP-1) promotes cell aggregation and induces the expression of the neural cell adhesion molecules N-CAM and L1 in proliferating neuroblastoma x glioma hybrid NG108-15 cells (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 10326-10330; Perides, G., Hu, G., Rueger, D. C., and Charness, M. E. (1993) J. Biol. Chem. 268, 25197-25205). Here we show that the structurally homologous bone morphogenetic proteins (BMP) BMP-2 and BMP-4 are 10-50-fold more potent in these actions than the subfamily comprising BMP-5, BMP-6, and OP-1 (BMP-7). In contrast, members of the TGF-beta subfamily, activin-A, inhibin-A, and 29 additional growth factors and cytokines did not induce N-CAM. The addition of serum to cells growing in serum-free medium caused a concentration-dependent increase in N-CAM and L1 expression; however, serum did not potentiate the induction of N-CAM and L1 by 40 ng/ml OP-1. These findings suggest the presence in NG108-15 cells of a BMP-2/BMP-4 receptor that discriminates subtle differences in structure among homologous members of the TGF-beta superfamily. An endogenous ligand for this receptor may be present in serum.
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PMID:Regulation of neural cell adhesion molecule and L1 by the transforming growth factor-beta superfamily. Selective effects of the bone morphogenetic proteins. 827 80

We examined transforming growth factor-beta (TGF-beta) activity in cerebrospinal fluid of 39 patients with various brain tumors, and found it in 10 glioma cases that had lesions related to subarachnoid space or ventricle. In one glioma case, TGF-beta detected on admission disappeared after radiation and chemotherapy. We confirmed that five glioma cell lines produced TGF-beta, and that four of them produced active form of TGF-beta directly. The active form of TGF-beta was also identified from cerebrospinal fluid before the acidification treatment in two cases. The calculated contents were 110 ng/ml and 18 ng/ml. These results indicate that active form of TGF-beta is directly produced by tumor cells in patients with glioma, and may contribute to immunodeficiency of the host.
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PMID:Detection of active form of transforming growth factor-beta in cerebrospinal fluid of patients with glioma. 832 Jan 72

Vascular endothelial growth factor (VEGF) is an angiogenic factor which is known to be expressed in several malignancies including glioma. The effect of transforming growth factor-beta (TGF-beta) isoforms as well as gangliosides on VEGF production was investigated in human glioma cell lines. TGF-beta isoforms and gangliosides were found to differentially stimulate VEGF production by these cells. The ganglioside GD3 enhanced this release to the greatest extent and the stimulation was more marked in a glioblastoma cell line than in the two other anaplastic astrocytoma cell lines. These results suggest that both TGF-betas and gangliosides may act as indirect angiogenic factors by stimulating VEGF secretion.
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PMID:Vascular endothelial growth factor production is stimulated by gangliosides and TGF-beta isoforms in human glioma cells in vitro. 860 72

In this study, we examined whether human glioma cells are angiogenic in a model using human microvascular endothelial cells, and also which factor is responsible for the glioma-dependent angiogenesis. Tubular morphogenesis in type I collagen gel by human microvascular endothelial cells was stimulated in the presence of 10 and 100 ng/ml of vascular endothelial growth factor (VEGF), 10 ng/ml basic fibroblast growth factor (bFGF) and 10 ng/ml of interleukin-8 (IL-8). Tube formation of the microvascular endothelial cells was assayed in the glioma cell lines IN157 and IN301, co-cultured using the double chamber method. IN301 cells had much higher levels of VEGF, bFGF and transforming growth factor-beta mRNA than IN157 cells, whereas the two had similar levels of transforming growth factor-alpha mRNA. By contrast, IN157 cells had much higher levels of IL-8 mRNA than IN301 cells. IN301-dependent tubular morphogenesis was inhibited by anti-VEGF or anti-bFGF antibody, and the inhibition was almost complete when anti-VEGF and anti-bFGF antibodies were present. On the other hand, IN157-dependent tubular morphogenesis was inhibited by anti-IL-8 antibody, but not by anti-VEGF or anti-bFGF antibodies. These findings demonstrated dual paracrine controls of tumor angiogenesis by human glioma cells. One is mediated through VEGF and/or bFGF, and the other, through IL-8.
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PMID:Dual pathways of tubular morphogenesis of vascular endothelial cells by human glioma cells: vascular endothelial growth factor/basic fibroblast growth factor and interleukin-8. 863 9

Human malignant gliomas are rather resistant to all current therapeutic approaches including surgery, radiotherapy and chemotherapy as well as antibody-guided or cellular immunotherapy. The immunotherapy of malignant glioma has attracted interest because of the immunosuppressed state of malignant glioma patients which resides mainly in the T-cell compartment. This T-cell suppression has been attributed to the release by the glioma cells of immunosuppressive factors like transforming growth factor-beta (TGF-beta) and prostaglandins. TGF-beta has multiple effects in the immune system, most of which are inhibitory. TGF-beta appears to control downstream elements of various cellular activation cascades and regulates the expression of genes that are essential for cell cycle progression and mitosis. Since TGF-beta-mediated growth arrest of T-cell lines results in their apoptosis in vitro, glioma-derived TGF-beta may prevent immune-mediated glioma cell elimination by inducing apoptosis of tumor-infiltrating lymphocytes in vivo. T-cell apoptosis in the brain may be augmented by the absence of professional antigen-presenting cells and of appropriate costimulating signals. Numerous in vitro studies predict that tumor-derived TGF-beta will incapacitate in vitro-expanded and locally administered lymphokine-activated killer cells (LAK-cells) or tumor-infiltrating lymphocytes. Thus, TGF-beta may be partly responsible for the failure of current adoptive cellular immunotherapy of malignant glioma. Recent experimental in vivo studies on non-glial tumors have corroborated that neutralization of tumor-derived TGF-beta activity may facilitate immune-mediated tumor rejection. Current efforts to improve the efficacy of immunotherapy for malignant glioma include various strategies to enhance the immunogenicity of glioma cells and the cytotoxic activity of immune effector cells, e.g., by cytokine gene transfer. Future strategies of cellular immunotherapy for malignant glioma will have to focus on rendering glioma cell-targeting immune cells resistent to local inactivation and apoptosis which may be induced by TGF-beta and other immunosuppressive molecules at the site of neoplastic growth. Cytotoxic effectors targeting Fas/APO-1, the receptor protein for perforin-independent cytotoxic T-cell killing, might be promising, since Fas/APO-1 is expressed by glioma cells but not by untransformed brain cells, and since Fas/APO-1-mediated killing in vitro is not inhibited by TGF-beta.
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PMID:The failure of current immunotherapy for malignant glioma. Tumor-derived TGF-beta, T-cell apoptosis, and the immune privilege of the brain. 886 71

Malignant glioma cells secrete transforming growth factor-beta (TGF-beta) which has potent immunosuppressive properties. We investigated the effect of interleukin-1 beta (IL-1 beta) on TGF-beta secretion from malignant glioma cells in vitro. T98G glioblastoma cells were treated with various doses of IL-1 beta and the TGF-beta activity in the supernatant was determined using a specific bioassay. Six other human malignant glioma cell lines were also treated with 1000 U/ml of IL-1 beta, and the TGF-beta activity in the supernatants was determined. The effect of IL-1 beta on the growth of tumor cells was also assessed by a bioassay using crystal violet which reflects the actual cell number in the plate wells. IL-1 beta treatment resulted in inhibition of TGF-beta secretion in two malignant glioma cell lines. TGF-beta secretion from T98G cells was suppressed by IL-1 beta in a dose-related manner. However, IL-1 beta treatment resulted in an obvious increase (> 20%) of TGF-beta secretion in two tumor lines, and a slight increase (< 20%) in three tumor lines. IL-1 beta did not affect the growth of four malignant glioma cell lines, and only slightly affected the growth of the other three cell lines. IL-1 beta modulates TGF-beta secretion from malignant glioma cells, but not in a consistent way.
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PMID:Modulation of transforming growth factor-beta secretion from malignant glioma cells by interleukin-1 beta. 886 49

Glia cell line-derived neurotrophic factor (GDNF), a recently cloned member of the transforming growth factor-beta (TGF-beta) superfamily, has been implicated in the survival, morphological and functional differentiation of midbrain dopaminergic neurons and motoneurons in vitro and in vivo. The factor may thus have utility in the treatment of various human neurodegenerative disorders. Mechanisms regulating expression of GDNF in normal and diseased brain as a possible means to increase the local availability of GDNF are only beginning to be explored. We have established and employed a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) to study and compare levels of expression of GDNF mRNA in several cell types and to investigate its regulation. GDNF expression was clearly evident in primary cultured astrocytes, the glioma B49 and C6 cell, but less pronounced in the Schwannoma RN22 cell lines. Little or no signal could be observed in neuroblastoma cell lines (IMR32, LAN-1) or the pheochromocytoma cell line PC12, emphasizing the glial character of this factor. Using the C6 cell line we found that fibroblast growth factor-2 (FGF-2; bFGF) can increase GDNF mRNA levels, whereas FGF-1, platelet-derived growth factor (PDGF), and vasoactive intestinal polypeptide (VIP) are apparently ineffective. Several other factors (forskolin, kainic acid, triiodothyronine dexamethasone, GDNF, TGF-beta 1, and interleukin-6) appear to have slightly negative effects on GDNF mRNA levels at the concentrations tested. To further explore the relationship between FGF-2 and GDNF, we also addressed the question whether GDNF, like FGF-2, may have an effect on C6 cell proliferation. We conclude that (1) glial and glial tumor cells, rather than neuronal cell lines, express GDNF, (2) that FGF-2 has a prominent inductive effect on GDNF expression and (3) that GDNF stimulates C6 cell proliferation. Finally, these data suggest that neurotrophic actions of FGF-2 in mixed glial-neuronal cell cultures might be mediated in part by GDNF.
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PMID:GDNF mRNA levels are induced by FGF-2 in rat C6 glioblastoma cells. 888 50

Expression of tenascin, an extracellular matrix glycoprotein, was measured in glioma cell lines using a newly established enzyme immunoassay. Secreted tenascin was found at concentrations greater than 800 ng/ml in eight of 14 glioma, three small cell lung carcinoma, two melanoma, and one sarcoma cell lines. The remaining six glioma and other carcinoma cell lines, and cell lines originating from normal tissues demonstrated low levels or no secretion into the supernatant. The glioma cell line, U-251-MG nu/nu, which has almost 100% transplantability in nude mice, had the highest expression level of tenascin among the glioma cell lines examined. Even low secretor glioma cell lines released high concentrations of tenascin, detectable by assaying the NP-40 solubilized cell lysates. Flow cytometric analysis revealed that tenascin was located on both the cell surface and primarily in the cytoplasm of glioma cells. When the glioma cell lines were exposed to tumor necrosis factor-alpha (TNF-alpha), levels of secreted tenascin increased between 36% and 380%, whereas transforming growth factor-beta induced only minimal changes. These results suggest that glioma cell lines may be classified according to the degree of tenascin secretion/expression: high secretor type, low secretor type, and non-expressing type. The increase in tenascin secretion by TNF-alpha suggests that the expression of tenascin in glioma growth and development may be mediated through a cytokine network.
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PMID:Enzyme immunoassay of glioma cell tenascin secretion and augmentation by tumor necrosis factor-alpha. 918 37

Glioblastoma cells secrete transforming growth factor-beta (TGF-beta), which has a variety of immunosuppressive properties. We investigated the effect of irradiation TGF-beta secretion by malignant glioma cells. Three malignant glioma cell lines (T98G, A172, KG-1-C) were cultured and irradiated using 10 and 50 Gy Linac radiation. After further culture for 36 hours in serum-free culture medium, the supernatants were collected. The TGF-beta activity in the culture supernatants was determined using a specific bioassay. The levels of the active form and total TGF-beta in the supernatants from irradiated malignant glioma cells decreased compared to those from un-irradiated cells. However, since irradiation inhibited the growth of tumor cells, the amount of TGF-beta secretion per cell in irradiated cells tended to increase after irradiation. These results suggest that malignant glioma cells can still secrete TGF-beta and activate latent TGF-beta even after large dose irradiation, despite the inhibition of tumor growth.
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PMID:Effect of irradiation on transforming growth factor-beta secretion by malignant glioma cells. 919 90


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