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)

In phase-I clinical trials of adoptive immunotherapy using lymphokine-activated killer (LAK) cells plus recombinant interleukin-2 (rIL-2) (Cetus) for the treatment of malignant glioma, we observed that blood mononuclear cells (MNC) from patients dependent on dexamethasone for management of cerebral edema produced substantially less LAK activity as compared to MNC of normal blood donors or glioma patients not receiving steroid therapy. Therefore, we examined the in vitro effects, brought about by therapeutically attainable concentrations of various corticosteroids, on the proliferative response, production of gamma interferon (IFN-gamma), and induction of LAK activity from blood MNC of normal donors. Incubation in media containing rIL-2 (1000 U/ml) with either dexamethasone, hydrocortisone, methylprednisolone, or prednisolone profoundly affected all of these parameters. First, while 0.01 micrograms/ml of either dexamethasone or hydrocortisone caused a slight enhancement of the mitogenic response of lymphocytes to phytohemagglutinin, a dose-dependent decline occurred as concentrations increased to 10 micrograms/ml. The addition of prednisolone and methylprednisolone elicited a dose-dependent inhibition of lymphocyte proliferation over the entire concentration range tested. At 0.1 microgram/ml or higher, dexamethasone, hydrocortisone, methylprednisolone and prednisolone significantly (P less than 0.02) inhibited the production of IFN-gamma: respectively 18.9%, 4.4%, 2.2%, and 12.3% of the IFN-gamma produced by MNC in the absence of steroids. All four corticosteroids inhibited the induction of LAK activity. Compared to MNC that had been incubated with 1000 U/ml rIL-2 alone, MNC cultured with rIL-2 and 10 micrograms/ml either dexamethasone or prednisolone demonstrated significantly lower cytotoxicity (P less than 0.05) for the natural-killer-cell-resistant cell line, Daudi. Culturing MNC with hydrocortisone had a more dramatic result, causing a significant decline (P less than 0.01) in lytic activity at both 1.0 micrograms/ml and 10 micrograms/ml, while incubation with methylprednisolone produced a significant drop (P less than 0.02) in LAK-mediated cytotoxicity at 0.1 micrograms/ml as well as 1.0 micrograms/ml and 10 micrograms/ml. When cytotoxicity was expressed as lytic units per million effectors, a dose-response decline in lytic activity was once again apparent, with hydrocortisone, methylprednisolone and prednisolone showing significant inhibition (P less than 0.05) at both 1.0 micrograms/ml and 10 micrograms/ml and dexamethasone at 10 micrograms/ml (P less than 0.01). These results indicate that corticosteroids commonly used in the management of cere
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PMID:Corticosteroids inhibit the generation of lymphokine-activated killer activity in vitro. 249 21

The modulation of HLA-DR and HLA-A, -B, and -C by human recombinant immune interferon (IFN-gamma) was studied on 10 malignant glioma cell lines established in our laboratory, on 8 clones or subclones derived from these lines, and on a fetal astrocyte cell line. Comparative studies were performed with recombinant leukocyte interferon (IFN-alpha). The results not only confirmed the selective activity of IFN-gamma on the modulation of HLA-DR expression, as opposed to that of IFN-alpha, but also demonstrated a marked heterogeneity in the response of glioma cell lines and their clones to the two types of IFN tested. For example, all 3 clones of an inducible cell line could be modulated to express HLA-DR, whereas only 2 of 5 clones derived from a noninducible line were modulated. This heterogeneity did not seem to be due to the absence of the receptor for IFN-gamma on the surface of these cells, since almost all of the cell lines or clones tested (17 of 19) responded to IFN-gamma by the induction or enhancement of the expression for either HLA-DR or HLA-A, -B, and -C (or both). The heterogeneity of induction was also demonstrated between clones derived from a glioma line that did not express HLA-DR after IFN-gamma treatment. The production of HLA-DR by one of the clones was abundant enough to be confirmed by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis.
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PMID:Heterogeneity of the induction of HLA-DR expression by human immune interferon on glioma cell lines and their clones. 308 Jun 35

Treatment of partly purified large granular lymphocytes (LGL) with either IFN-alpha or IFN-gamma for 2 hr augmented their NK cell activity. This augmentation was completely inhibited by the addition of 10 micrograms/ml of cycloheximide. In contrast, when the effects of IFN-gamma on the synthesis of specific proteins in these cells was directly studied by use of two-dimensional gel electrophoresis, we found that IFN-gamma was unable to induce any of the earlier detected, IFN-alpha/IFN-beta-inducible proteins within 18 hr of incubation. No additional, IFN-gamma-induced proteins were detected in either the partly purified LGL or purified T cells. In contrast, the effects of the two factors were comparable in the glioma cell line 251 MG. This shows i) that the effects of IFN-alpha and IFN-gamma are dependent on the responder cell type, ii) that there exists at least one mechanism that can augment NK cell activity that is not dependent on the increased synthesis of the IFN-alpha-inducible proteins, and iii) that either the nine IFN-alpha-inducible proteins are not involved in any leukocyte function that is augmentable by both IFN-alpha and IFN-gamma, or that the two factors exert their actions in leukocyte through different mechanisms.
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PMID:The augmentation of human natural killer cell activity by interferon-gamma is not associated with the induction of the interferon-alpha-inducible proteins. 308 47

Several anti-human glioma cytotoxic conjugates were studied in vitro. Monoclonal antibodies (MAbs) to the GE2 glioma-associated antigen (anti-GE 2) and MAbs to HLA-DR antigens (D1/12) or human diferric transferrin (Tfn) were linked to the potent cytotoxin ricin (anti-GE 2-ricin) or to its A subunit (anti-GE 2-RTA, D1/12-RTA, Tfn-RTA). Anti-GE 2-RTA had low cytotoxic activity in both the absence and the presence of lysosomotropic substances inhibiting intracellular degradation. Anti-GE 2-ricin was about 1,000 times more toxic than RTA alone, but showed only 14-fold target specificity. D1/12-RTA was about 20 times more toxic than RTA and its cytotoxic effect increased about 6- to 7-fold when cell-surface HLA-DR antigen expression was enhanced by IFN-gamma treatment. Human diferric Tfn linked to RTA demonstrated the highest cytotoxic activity, being about 5,000 times more toxic than RTA alone for glioma cells and about 6,000 times more toxic for Jurkat cells in the presence of the carboxylic ionofore monensin. Ricin toxin was only about 5 times more toxic for Jurkat and glioma cells than Tfn-RTA-monensin. Tfn-RTA was over 100,000 times more potent than the chemotherapeutic agent BCNU in reducing glioma cell survival in vitro. Addition of 80% human pooled cerebrospinal fluid (CSF) reduced Tfn-RTA toxicity about 10-fold. Kinetics of Tfn-RTA cytotoxicity at non-saturating concentrations indicated that over 80% of target cells could be killed within 8-10 hr in the absence and within 10-12 hr in the presence of human pooled CSF.
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PMID:Sensitivity of human glioma cells to cytotoxic heteroconjugates. 313 94

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

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

Peripheral blood mononuclear cells (PBMC) of malignant glioma-bearing patients were stimulated in vitro with Interleukin-2 (IL-2) or a glucomannan-protein antigen of Candida albicans (GMP) then assayed for proliferation, production of IFN-gamma, and generation of cytotoxic effectors against either K562 tumor cell line or freshly-cultured allogenic glioma cells. PBMC of healthy, age and sex-matched subjects were the controls. PBMC of glioma-bearing patients did not differ, as a whole, from PBMC of healthy donors in IL-2 or GMP-induced proliferation. However, they showed a lesser ability to produce IFN as well as a substantial inability to generate cytotoxic effectors following GMP stimulation. PBMC of glioma patients were fully responsive to IL-2 in cytotoxicity generation, as were the PBMC from normal subjects. The results suggest that glioma patients may have a defective antigen-mediated activation of natural cytotoxic effectors. This hyporesponsiveness is not accompanied by depressed lymphoproliferation and does not apparently involve a reduced response to IL-2.
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PMID:Cell-mediated cytotoxicity in glioma-bearing patients: differential responses of peripheral blood mononuclear cells to stimulation with interleukin-2 and microbial antigen. 314 18

The expression of the intercellular adhesion molecule-1 (ICAM-1) and neural cell adhesion molecule (NCAM) by glioma cell lines was investigated. The effects of interferon (IFN)-gamma or irradiation on the expression was also assessed. Two glioma cell lines showed more than 75% NCAM-positive cells. After treatment with IFN-gamma or irradiation, another three cell lines were induced to show more than 50% positive cells. Three glioma cell lines showed more than 50% ICAM-1-positive cells. After treatment with IFN-gamma, another two cell lines were induced to show more than 50% positive cells. After treatment with irradiation, one more cell line was induced to show more than 50% positive cells. ICAM-1 and NCAM expression by glioma cell lines is susceptible to modulation by IFN-gamma or irradiation.
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PMID:Effects of irradiation on the expression of the adhesion molecules (NCAM, ICAM-1) by glioma cell lines. 750 10

Lipopolysaccharide (LPS) or a combination of interleukin (IL)-1 beta and interferon (IFN)-gamma cause transcriptional induction of a calcium-independent nitric oxide synthase (NOS) in astrocytes and C6 glioma cells. LPS induction of NOS in C6 cells was evidenced by a small amount of nitrite accumulation as compared with cells exposed to IL-1 beta/IFN-gamma, but the maximal NOS activity achieved (as revealed by cGMP formation) was the same. The NOS activity induced by LPS in C6 cells was maximal at 4 to 8 hr and then rapidly decreased, while NOS activity induced by IL-1 beta/IFN-gamma slowly decreased after 4 hr. In addition, the effects of re-presenting IL-1 beta/IFN-gamma to both astrocytes and C6 cells after maximal induction of activity of the inducible form of NOS were studied. The re-addition of cytokines prolonged both NOS mRNA expression and also enzyme activity, suggesting effects at either the transcriptional (further induction) or translational level (mRNA stability). These results imply that the time course of NO production by induced astrocytes depends both upon the nature of the inducing stimulus and the frequency of the cells' exposure to it.
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PMID:Duration of expression of inducible nitric oxide synthase in glial cells. 753 44

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


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