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)

Cells that produce tumor necrosis factor-alpha (TNF-alpha) require the presence of signaling molecules since this cytokine is not normally expressed in a constitutive manner. It has been demonstrated that glial cells can produce TNF-alpha; however, the specific inducing molecules and their mechanism(s) of action have not been clearly defined. In this study, we examined the effect of human recombinant interleukin-1 beta (IL-1 beta) on the expression of TNF-alpha by CH235-MG human malignant glioma cells. CH235-MG cells do not constitutively express TNF-alpha mRNA or protein; however, upon stimulation with IL-1 beta, these cells synthesize and secrete biologically active TNF-alpha. IL-1 beta induces the expression of a 1.9 kb TNF-alpha mRNA species. Kinetic analysis demonstrated optimum TNF-alpha mRNA expression after a 4 h exposure to IL-1 beta, and peak TNF-alpha protein production at 18 h. Cycloheximide (CHX), an inhibitor of protein synthesis, markedly increased expression of TNF-alpha mRNA in IL-1 beta stimulated CH235-MG cells, indicating that de novo protein synthesis is not required for astroglioma TNF-alpha gene expression. Nuclear run-off analysis demonstrates that IL-1 beta causes transcriptional activation of the TNF-alpha gene, and CHX enhances IL-1 beta-induced TNF-alpha transcription. Studies of TNF-alpha mRNA stability using actinomycin D show that IL-1 beta-induced TNF-alpha mRNA has a half-life of approximately 30 min, and CHX increases the half-life of IL-1 beta-induced TNF-alpha mRNA to approximately 210 min. These results indicate that IL-1 beta, a cytokine present in the central nervous system during some pathological disease states, is a potent inducer of TNF-alpha in human malignant glioma cells.
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PMID:Interleukin-1 beta induction of tumor necrosis factor-alpha gene expression in human astroglioma cells. 173 80

Human promonocyte cells chronically infected with human immunodeficiency virus type (HIV-1) (clone U1.1.5) were grown in the presence of media conditioned by human astrocytes and glioma cell lines U251 and 253. HIV-1 expression was assessed by measuring reverse transcriptase activity. All media conditioned by unstimulated and lipopolysaccharide (LPS) stimulated glial cells induced HIV-1 expression and contained detectable levels of interleukin-6 (IL-6) but not tumor necrosis factor-alpha (TNF-alpha). An antibody against IL-6, but not against TNF-alpha, reduced the induction of HIV-1 by the conditioned media in a concentration-dependent manner. The magnitude of HIV-1 induction by the conditioned media was proportional to the concentration of IL-6 in them. The data indicate that normal and transformed human astrocytes are capable of stimulating HIV-1 expression in chronically infected promonocytic cells by secreting IL-6. The results demonstrate that cytokines secreted by neural cells could play an important role in regulating HIV-1 expression in the brain.
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PMID:Human astrocytes stimulate HIV-1 expression in a chronically infected promonocyte clone via interleukin-6. 174 78

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

Lyme disease is a multisystemic disease caused by a tickborne spirochete, Borrelia burgdorferi. Neuroborreliosis is characterized by intrathecal production of antibodies specific for the spirochete. This suggests that spirochetal infection of the central nervous system produces conditions that support the maturation of B lymphocytes to immunoglobulin-secreting cells. Interleukin 6 (IL-6) stimulates B cell differentiation into antibody-secreting cells. The present study was undertaken to determine whether B. burgdorferi can stimulate cells of central nervous system origin to secrete IL-6. C6 rat glioma cells cultured with spirochetes induced secretion of IL-6 activity. Peak stimulation was achieved at 24 h with 25 spirochetes per glioma cell. Glioma cells were also stimulated to produce IL-6 by interleukin 1 and tumor necrosis factor. That very few spirochetes are found in Lyme disease patients suggests that biologic amplification factors derived from the organism or the host, or both, are responsible for the pathogenesis of this disease. IL-6 can now be added to the growing list of such factors.
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PMID:Cytokines and the pathogenesis of neuroborreliosis: Borrelia burgdorferi induces glioma cells to secrete interleukin-6. 190 2

We have studied serum concentrations of immunoassayable tumor necrosis factor-alpha (TNF alpha) and iodothyronines (T4, T3, and rT3) in normal subjects (n = 16) and patients with nonthyroidal illnesses (NTI; n = 13), hyperthyroidism (n = 10), and hypothyroidism (n = 9). The mean (+/- SEM; femtomoles per mL) serum concentration of TNF alpha was 45 +/- 4.3 in normal subjects, 84 +/- 38 in NTI, 54 +/- 6.0 in hyperthyroidism, and 50 +/- 10 in hypothyroidism; the various values did not differ significantly from one another. Serum TNF alpha was well within the normal range in all NTI patients, except one patient with a brain glioma and infection in whom it was elevated (540 fmol/mL). There was no significant correlation between serum TNF alpha and serum T4, T3, or rT3 levels in NTI patients. Similarly, there was no correlation between serum TNF alpha and serum thyroid hormone (T3 or T4) levels when data in normal subjects were combined with those in NTI patients. The dialyzable fraction of T3 and the free T3 concentration did not correlate with serum TNF alpha levels. However, there was a tendency toward a positive correlation between dialyzable fraction of T4 and the serum concentration of TNF alpha in NTI (r = 0.54; n = 11; 0.05 greater than P less than 0.1). The relationship between these two parameters became more clear when data in normal subjects and NTI patients were combined for statistical analysis (r = 0.59; n = 22; P less than 0.005). The free T4 concentration correlated positively with serum TNF alpha levels whether the data in NTI patients were analyzed alone (r = 0.93; P less than 0.001) or in combination with data from normal subjects (r = 0.85; P less than 0.001). Our data suggest that circulating TNF alpha may contribute to elevated free T4 in NTI. However, it is not a universal or common factor in the pathogenesis of other alterations in serum thyroid hormone levels in NTI (euthyroid sickness syndrome).
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PMID:A study of the serum concentration of tumor necrosis factor-alpha in thyroidal and nonthyroidal illnesses. 202 11

In this study, we tried to examine the efficacy of a cytotoxic factor which is induced by periodic, repeated local administration of OK-432 into the tumor cavity of malignant glioma patients. OK-432 was administered intratumorally via a tube to 4 malignant glioma patients on Days 1, 3, 5, 7 and 12 in doses of 0.5 KE, 1 KE, 2 KE, and 3 KE, respectively. Cerebrospinal fluid (CSF) was collected several times during the 24-hour period beginning immediately after the administration on Day 12. The CSF was added to the culture medium of rat glioma cells (GA-1 and C-6) in order to observe the cytotoxic effect morphologically. The clinical efficacy in the patients was evaluated from the changes in tumor size observed by CT. CSF collected from the tumor cavity of 3 patients was bloody. By adding this bloody CSF, a significant morphological cytotoxic effect was observed on both the GA-1 and C-6 glioma cells in culture. The level of cytotoxicity was higher with the bloody fluid collected at 4 to 24 hours after the final administration than with the bloody fluid collected immediately after the final administration. The cytotoxic effect of this fluid was stronger than that of rabbit TNF (tumor necrosis factor) serum induced with P. acnes and LPS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Antitumor effect of direct intra-tumor administration of OK-432 on malignant glioma: basic and clinical observations]. 203 13

Human malignant gliomas possess some of the same immune-related functions as astrocytes do. For instance, they are capable of secreting various immunoregulatory molecules and expressing HLA-DR antigens on their surface. The human malignant glioma cell line, D54-MG, was used to investigate the proliferative effects of tumor necrosis factor-alpha (TNF-alpha) and the expression of specific surface receptors for TNF-alpha. Additionally, we were interested in examining whether D54-MG cells are capable of synthesizing and secreting biologically active TNF-alpha. D54-MG cells responded in a mitogenic fashion upon incubation with TNF-alpha for 48 h under serum-free conditions. 125I-labeled TNF-alpha was used in this study to investigate the expression of receptors specific for TNF-alpha on D54-MG cells. Scatchard analysis of our receptor binding data produced curvilinear plots indicating there are two distinct receptor sites for TNF-alpha. From these data, we calculated that there are approximately 3500 high affinity and 24,666 low affinity binding sites per cell. Pretreating these cells with interferon-gamma (IFN-gamma) resulted in a 2-fold increase in the number of high affinity binding sites and a moderate increase in the number of low affinity binding sites, with no appreciable change in binding affinity (Kd) of either site. D54-MG cells were unable to constitutively secrete TNF-alpha; however, upon stimulation, these cells synthesize and secrete biologically active TNF-alpha. Polyclonal antisera reactive with human macrophage-derived TNF-alpha neutralized the cytotoxicity of D54-MG-derived TNF-alpha, demonstrating that the cytotoxic activity was in fact due to TNF-alpha. Our observations indicate that TNF-alpha could act in an autocrine fashion to induce the proliferation of this malignant glioma cell line and that TNF-alpha exerts its effect by binding to specific TNF-alpha receptors whose expression was enhanced by IFN-gamma.
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PMID:Tumor necrosis factor production and receptor expression by a human malignant glioma cell line, D54-MG. 217 2

In this study we tested the effect of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and a combination of these immunotherapeutics on clonogenic growth of cell lines and primary cultures of malignant human brain tumors. Out of 29 primary cultures studied, 5 were inhibited 50% or more by IFN-gamma (10 ng/ml), 6 were inhibited 50% or more by TNF-alpha (10 ng/ml) and 14 were inhibited 50% or more by a combination of IFN-gamma (10 ng/ml) and TNF-alpha (10 ng/ml). The doses of the immunotherapeutics used in this in vitro study are achievable in serum after intravenous administration of IFN-gamma and TNF-alpha without causing unacceptable side effects. We believe that some glioma patients and some patients with brain metastases will benefit from receiving treatment with IFN-gamma, TNF-alpha or a combination of these immunotherapeutics. The patients should be selected for treatment with these immunotherapeutics according to in vitro sensitivity results.
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PMID:Effects of interferon-gamma and tumor necrosis factor-alpha on clonogenic growth of cell lines and primary cultures from human gliomas and brain metastases. 250 Jan 40

Microvascular endothelial cells were isolated from gerbil brain and cultured. These cells retained an endothelial-specific marker, FVIII-related antigen. Alkaline phosphatase activity was also present in early passage. Two weeks after plating, these cells were attached to the culture dishes and had become like cobblestones in appearance. Then, the addition of tumor necrosis factor at a concentration of 1000 U/ml or more suppressed the DNA synthesis activity of endothelial cells by about 70% and induced morphological changes in the cells, which developed a spindle-like form and showed overlapping of cells, indicating loss of contact inhibition. The administration of interferon-tau induced no change. When a similar experiment was performed using culture supernatants of human glioma cells that had been cultured for a few days, DNA synthesis activity was suppressed by approximately 50% or more in 6 of 12 samples. The suppression of activity, however, was abolished by the addition of anti-tumor necrosis factor antibody in these 6 cases, suggesting the presence of activity resembling that of the tumor necrosis factor in the culture supernatants.
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PMID:Effects of cytokines on cultured microvascular endothelial cells derived from gerbil brain. 250 60

A cultured glioma cell line, SR-B10.A, which was derived from a brain tumor induced in an adult female B10.A mouse by Rous sarcoma virus (RSV), has been established. The morphological appearance of the tumor produced by s.c. inoculating SR-B10.A cells was analogous to an astrocytoma of human glioma. Glial fibrillary acidic protein as well as S-100 protein was positive in these SR-B10.A tumor cells. A population doubling time of the cultured cells was 18.5 hours. Chromosomal analysis revealed a defect in one of the sex chromosomes. Integration of RSV genome was proven to be positive in SR-B10.A cells. It was possible to generate cytotoxic effector cells in the syngeneic B10.A mouse against SR-B10.A. The tumor-bearing syngeneic hosts harbored a suppressor activity in the splenocytes. Although recombinant human tumor necrosis factor (rH-TNF) had no growth inhibitory effect on the SR-B10.A cells in vitro, the s.c. implanted and growing tumor regressed when rH-TNF was administered intratumorally several times. In addition, this anti-tumor effect was completely abrogated when the host mice were treated with wholebody x-ray irradiation prior to the tumor cells inoculation. In contrast, neither rH-TNF (i.v.) nor cyclophosphamide (i.p.) induced the regression of SR-B10.A, indicating that efficacy of the locally administered rH-TNF is dependent on the host immune mechanism. These results suggest that SR-B10.A is a potentially useful tumor model in evaluating efficacy of immunomodulators.
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PMID:Potential usefulness of a cultured glioma cell line induced by Rous sarcoma virus in B10.A mouse as an immunotherapy model. 255 17


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