Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Globoid cell leukodystrophy (Krabbe disease) is characterized by the accumulation of a toxic metabolite, psychosine (galactosylsphingosine), which is a substrate for the deficient enzyme (galactocerebroside beta-galactosidase). This study underscores the possible role of psychosine in the effect of inducible nitric oxide synthase (iNOS) -derived NO in the pathophysiology of this demyelinating disease. For the first time, we provide evidence of the expression of iNOS in CNS of Krabbe patient and show that the iNOS-expressing cells in the CNS were astrocytes. Psychosine potentiated the LPS-induced production of proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) in primary rat astrocytes and regulated the cytokine-mediated production of NO in C6 glioma and primary rat astrocyte. Psychosine induced cytokine-mediated nuclear translocation of AP-1 and C/EBP by potentiating the expression of Fra-1 and C/EBP-delta proteins. This suggests that psychosine maintained or sustained the cytokine-primed expression of iNOS by further potentiating the nuclear translocation of AP-1 and C/EBP without modulating the cytokine-mediated transcription activity of NF-kappaB. This study hypothesizes that accumulated psychosine leads to production of cytokines and iNOS expression. The ensuing excessive production of NO and ONOO- may play a role in pathogenesis of Krabbe disease.
 ...
PMID:Galactosylsphingosine (psychosine)-induced expression of cytokine-mediated inducible nitric oxide synthases via AP-1 and C/EBP: implications for Krabbe disease. 1197 30

We compared the effects ofAlzheimer's peptide (Abeta1-42), a,-antichymotrypsin (ACT) and an ACT/Abeta1-42 mixture on human glioma DK-MG cells. The solution of Abeta (5 microM) formed by 2-h incubation at room temperature induced tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 levels by 55 and 45%, respectively, and increased gelatinase B activity by 67%, while exposure of cells to the ACT/Abeta1-42 mixture (1:10 molar ratio ACT: Abeta1-42) under the same experimental conditions showed no effect on IL-6 levels or gelatinase B activity, but strongly induced TNF-alpha (by 190%), compared to the controls. Stimulation of the cells with Abeta1-42 alone, but not with ACT, increased by about 20% low-density lipoprotein (LDL) uptake and mRNA levels for LDL receptor and HMG-CoA reductase, while the ACT/Abeta1-42 mixture significantly increased LDL uptake (by 50%), up-regulated mRNA levels for LDL receptor and HMG-CoA reductase by 48 and 63%, respectively, and increased lipid accumulation by about 20-fold. These data suggest a possible new role for Abeta in Alzheimer's disease through its interaction with the inflammatory reactant, ACT.
 ...
PMID:Glioma cell activation by Alzheimer's peptide Abeta1-42, alpha1-antichymotrypsin, and their mixture. 1247 84

Statins are known to exert a number of biological effects apart from reducing cholesterol synthesis. The results of recent studies indicate that patients treated with pravastatin have a lower prevalence of diagnosed Alzheimer's disease (AD). These observations prompted us to examine the effects of pravastatin on Alzheimer's peptide (Abeta(1-42))-induced pro-inflammatory activation in the human glioma cell line in vitro. Cells alone or cells pre-treated with pravastatin (0.1mg x ml(-1)) for 24h were stimulated with 5 microM of freshly dissolved Abeta(1-42) for the next 24h. The pre-treatment of cells with pravastatin diminished the capacity of Abeta to induce metalloproteinases, cytokine IL-6 and free radical levels. Although both pravastatin and Abeta(1-42) separately increased PPARgamma activity, the combination of Abeta(1-42) and pravastatin resulted in no effect on PPARgamma expression. These data indicate that soluble forms of Abeta(1-42), which are a potent stimulus of pro-inflammatory activation of glioma cells in vitro, could be a good target for pravastatin.
 ...
PMID:Pravastatin inhibits pro-inflammatory effects of Alzheimer's peptide Abeta(1-42) in glioma cell culture in vitro. 1254 59

Many tumor cells are resistant to Fas-mediated killing, which has been primarily used as a mechanism to evade immune attack. In this study, we found a new action of Fas on tumors where activation of the Fas signal may force tumor cells to produce survival factors for neutrophils. Human peripheral circulating neutrophils in coculture with glioma cells showed significant delays in spontaneous apoptosis. Interleukin (IL)-6 and IL-8 partially mediated the glioma cell-associated, protective effect on neutrophils. The Fas agonistic antibody CH-11 dose-dependently stimulated the expression of IL-6 and IL-8 in glioma cells. Accordingly, blocking the Fas/FasL interaction reduced IL-6 and IL-8 production in glioma cells and impaired their protective effect on neutrophils. Coculture with glioma cells also affected the expression of cytokines in neutrophils, including IL-8, interferon-gamma, and tumor necrosis factor alpha to various extents. Collectively, our results demonstrate bi-directional cross-talk between tumor and immune cells. Although Fas activation alone cannot induce apoptosis in tumor cells, it may potentially initiate an effective anti-tumor response through a circumvented mechanism.
 ...
PMID:Cross-talk between tumor cells and neutrophils through the Fas (APO-1, CD95)/FasL system: human glioma cells enhance cell viability and stimulate cytokine production in neutrophils. 1262 50

In order to explore the new methods of biological treatment of human gliomas, this project is to study the biological properties of gliomas from four different aspects, the results show that there is a IL-6 autocrine loop in human gliomas and the growth of gliomas will be inhibited when the autocrine loop is broken. There is a magnificent predominant expression of Th2 cytokines in human gliomas and human glioma cells, the switching of Th2 to Th1 can inhibit the proliferation of glioma cells. The dosage of 100 micrograms/ml of erythromycin is the best of therapeutic effect. Angiostatin can not only inhibit the vascular endothelial growth, but also have the inhibitory role on the growth of glioma cells in vivo. The above studies have provided some new ideas and will be very helpful for the treatment of glioma patients.
 ...
PMID:[The study of biological properties of gliomas]. 1290 17

Experimental in vivo tumor models are essential for comprehending the dynamic process of human cancer progression, identifying therapeutic targets, and evaluating antitumor drugs. However, current rodent models are limited by high costs, long experimental duration, variability, restricted accessibility to the tumor, and major ethical concerns. To avoid these shortcomings, we investigated whether tumor growth on the chick chorio-allantoic membrane after human glioblastoma cell grafting would replicate characteristics of the human disease. Avascular tumors consistently formed within 2 days, then progressed through vascular endothelial growth factor receptor 2-dependent angiogenesis, associated with hemorrhage, necrosis, and peritumoral edema. Blocking of vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor signaling pathways by using small-molecule receptor tyrosine kinase inhibitors abrogated tumor development. Gene regulation during the angiogenic switch was analyzed by oligonucleotide microarrays. Defined sample selection for gene profiling permitted identification of regulated genes whose functions are associated mainly with tumor vascularization and growth. Furthermore, expression of known tumor progression genes identified in the screen (IL-6 and cysteine-rich angiogenic inducer 61) as well as potential regulators (lumican and F-box-only 6) follow similar patterns in patient glioma. The model reliably simulates key features of human glioma growth in a few days and thus could considerably increase the speed and efficacy of research on human tumor progression and preclinical drug screening.
 ...
PMID:Accessing key steps of human tumor progression in vivo by using an avian embryo model. 1566

Intratumoral heterogeneity and genetic instability within gliomas may allow intrinsically immunoresistant (IR) cells to escape alloreactive cytotoxic T lymphocyte (aCTL) cellular immunotherapy. The potential existence of aCTL-resistant variants prompted us to investigate whether cellular immunotherapy resistant glioma models could be isolated. To generate the models, repeated intermittent or continuous selective pressure (ISP or CSP) with multiple aCTL populations was applied to a low-passage glioblastoma cell explant, 13-06-MG, obtained from a patient at initial diagnosis. IL-6 and IL-8 secretion was greater in coincubates of aCTL cells with 13-06-ISP and 13-06-CSP immunoselected cells than those with 13-06-MG parental cells. Initially, the immunoselected cells were less sensitive to aCTL lysis; however, the reduced aCTL-sensitivity was not maintained upon further selection. We therefore isolated IR clones from continuously immunoselected cells (13-06-CSP). The frequency of IR clones was 1-6 cells per 10,000 immunoselected cells. Two clones selected for further study, 13-06-IR29 and 13-06-IR30, resisted aCTL lysis in the absence of immunoselective pressure. Cytogenetic analyses revealed structural anomalies and genomic imbalances unique to the IR clones. Based on these findings, a hypothetical model is proposed that traces the origin of the IR clones to a clonal variant within the 13-06-CSP and 13-06-MG populations.
 ...
PMID:Isolation of immunoresistant human glioma cell clones after selection with alloreactive cytotoxic T lymphocytes: cytogenetic and molecular cytogenetic characterization. 1652 6

Malignant gliomas are typically angiogenic and secrete high levels of VEGF. Hypoxia has been identified as an important regulator of VEGF. However, malignant gliomas express high levels of VEGF in both hypoxic perinecrotic and vital tumor areas. In this study, we examined intracellular signaling pathways involved in the secretion of VEGF in glioma cells under normoxic conditions. Human malignant glioma cell lines, T98G, U373MG, U87MG, and A172, and human fetal lung fibroblasts (HFL) were cultured both with and without IL-1beta under normoxic conditions. VEGF, IL-1, IL-6, and TNF-alpha were measured with ELISA. VEGF mRNA levels were estimated by RT-PCR. Inhibitors of COX-2, MAPK, and phosphatidyl inositol 3-kinase (PI3-K), and blocking antibodies to TGF-beta II and TNF-alpha, or IL-1 receptor antagonist, were used to examine their effects on VEGF secretion. Phosphorylation of MAPK was examined by immunoblotting. The basal levels of VEGF secretion were significantly higher in U87MG, U373MG, and T98G, than HFL. IL-1beta significantly stimulated VEGF secretion in these glioma cells. Inhibitors of p38 MAPK and/or JNK significantly suppressed VEGF secretion both in the presence and absence of IL-1beta, while inhibitors of COX-2, ERK1/2, and PI3-K did not. Constitutive phosphorylation of p38 MAPK and JNK was observed in these glioma cells. The levels of IL-1beta in U87MG were significantly higher than in other glioma cell lines, and IL-1 receptor antagonist suppressed basal secretion of VEGF from U87MG. In conclusion, p38 MAPK and JNK pathways play an important role in VEGF secretion from malignant glioma cells under normoxic conditions, possibly contributing to VEGF-induced angiogenesis in malignant gliomas at vital tumor areas where there is no hypoxia.
 ...
PMID:Activation of p38 MAPK and/or JNK contributes to increased levels of VEGF secretion in human malignant glioma cells. 1696 94

Malignant gliomas are able to secrete large amounts of immunosuppressive cytokines like transforming growth factor beta 2 (TGF-beta2) and regularly escape from immune surveillance. Many strategies have been developed to induce potent anti-glioma responses, among those the use of dendritic cells (DC) as therapeutic vaccines. Here, we report that both mature DC and IL-12 secretion are necessary to overcome T-cell inhibition by TGF-beta2. Flow cytometric analyses showed that TGF-beta2 does not suppress the upregulation of MHC (major histocompatibility complex) class II molecules and the T cell stimulatory capacity of human DC that were stimulated with a strong cytokine cocktail containing tumor necrosis factor alpha (TNF-alpha), IL-1beta, IL-6 and prostaglandin E2 (PGE2). Moreover, TGF-beta2 signaling studies revealed that these cytokine-matured DC become unresponsive to TGF-beta2. Although both mature and immature DC expressed comparable amounts of the TGF-beta receptor type II, Smad2 phosphorylation and subsequent upregulation of Smad7 was inhibited in mature DC, but not immature DC. However, further analysis revealed that mature DC alone are not sufficient to mediate full T cell activation in the presence of TGF-beta2, unless IL-12 is added to the DC/T-cell coculture. Finally, we demonstrate that MHC class II expression and IL-12 secretion by DC are not disturbed by TGF-beta2 after DC stimulation with a modified maturation cocktail containing the Toll-like receptor (TLR)-ligands Poly I:C or R848, TNF-alpha, IL-1beta and INF-gamma. These data imply that mature DC retaining their capacity to produce IL-12 are of favorable use in glioma immunotherapy and suggest that TLR triggering of DC plays an important role to elicit a strong immune response in the immunosuppressive environment of malignant gliomas.
 ...
PMID:Toll-like receptor triggered dendritic cell maturation and IL-12 secretion are necessary to overcome T-cell inhibition by glioma-associated TGF-beta2. 1710 49

Methylmercury (MeHg) is an environmental toxin that causes severe neurological complications in humans and experimental animals. MeHg caused IL-6 release from the rat C6 glioma cells, the human U251HF glioma cells and the human retina pigment epithelial (ARPE-19) cells. These results plus those we reported earlier using mouse N9 microglia cells indicate that IL-6 induction may be a general property of MeHg among various glial cell types across species. MeHg caused a concentration-dependent increase of cellular oxidation with a maximal level reached by approximately 10 microM MeHg, which was similar to that caused by 30 microM H2O2 or t-butyl hydroperoxide (tBH). The ability of MeHg to induce IL-6 release was not affected by exogenously added H2O2 or t-butyl hydroperoxide. Furthermore, IL-6 release was not accompanied by other cytokine release. Given the reports by others that IL-6 could modulate neuronal survival, glia may affect MeHg neurotoxicity by their IL-6 release when exposed to this neurotoxin.
 ...
PMID:Methylmercury causes glial IL-6 release. 1736 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>