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 role of oleic acid in the modulation of gap junction permeability was studied in cultured rat astrocytes by the scrape-loading/Lucifer yellow transfer technique. Incubation with oleic acid caused a dose-dependent inhibition of gap junction permeability by 79.5% at 50 microM, and no further inhibition was observed by increasing the oleic acid concentration to 100 microM. The oleic acid-mediated inhibition of gap junction permeability was reversible and was prevented by bovine serum albumin. The potency of oleic acid-related compounds in inhibiting gap junction permeability was arachidonic acid > oleic acid > oleyl alcohol > palmitoleic acid > stearic acid > octanol > caprylic acid > palmitic acid > methyloleyl ester. Oleic acid and arachidonic acid, but not methyloleyl ester, increased glucose uptake by astrocytes. Neither oleic acid nor arachidonic acid increased glucose uptake in the poorly coupled glioma C6 cells. These results support that the inhibition of gap junction permeability is associated with the increase in glucose uptake. We suggest that oleic acid may be a physiological mediator of the transduction pathway leading to the inhibition of intercellular communication.
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PMID:Oleic acid inhibits gap junction permeability and increases glucose uptake in cultured rat astrocytes. 923 32

In the present study we investigate the effect of exogenous sphingosine, sphingosine 1-phosphate and sphingosylphosphorylcholine on phospholipase D (PLD) activity in glioma C6 cells. The cells were prelabeled with [1-14C]palmitic acid and PLD-mediated synthesis of [14C]phosphatidylethanol was measured. Sphingosine 1-phosphate and sphingosylphosphorylcholine did not stimulate [14C]phosphatidylethanol formation either at low (0.1-10 microM) or high (25-100 microM) concentrations. On the other hand, sphingosine at concentrations of 100-250 microM strongly stimulated PLD activity as compared to the effect of phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), known as a PLD activator. The effect of TPA on PLD is linked to the activation of protein kinase C. The present study also shows that sphingosine additively enhances TPA-mediated PLD activity. This is in contrast to the postulated role of sphingosine as a protein kinase C inhibitor. These results demonstrate that in glioma C6 cells sphingosine not only affects PLD independently of its effect on protein kinase C, but also is unable to block TPA-mediated PLD activity.
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PMID:Exogenous sphingosine 1-phosphate and sphingosylphosphorylcholine do not stimulate phospholipase D in C6 glioma cells. 1045 85

The effect of extracellular ATP, a nucleotide receptor agonist in the central nervous system, was investigated in glioma C6 cells on the intracellular Ca2+ level and the formation of phosphatidylethanol and phosphatidic acid in the presence and absence of ethanol (150 mM). In the cells prelabeled with [14C]palmitic acid, 100 microM ATP induced both the hydrolysis and the transphosphatidylation reactions leading to the formation of [14C]phosphatidic acid; addition of ethanol generated [14C]phosphatidylethanol. However, ATP-mediated increase in the level of [14C]phosphatidic acid was not inhibited by ethanol. Furthermore, ethanol augmented ATP-induced transient and sustained increase in the intracellular Ca2+ concentration, whereas ethanol alone did not produce any change in the intracellular Ca2+ level. These results indicate that in glioma C6 cells, ATP induces activation of polyphosphoinositide-specific phospholipase C and phospholipase D and that ethanol enhances this effect. In the present investigation we have also shown that long-term (2 days) ethanol treatment, at concentration relevant to chronic alcoholism (100 mM), decreased the incorporation of [14C]serine into phosphatidylserine. Since the effect of ethanol on ATP-induced activities of phospholipase C and phospholipase D and on serine base-exchange in glioma C6 cells differs significantly from that in cultured neuronal cells, these results may contribute to a better understanding of the mechanisms of ethanol action in cells of glial origin.
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PMID:Effect of ethanol on ATP-induced phospholipases C and D and serine base exchange in glioma C6 cells. 1067 76

In has been found that sphingosine, propranolol, imipramine and phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA) have a stimulatory effect on phospholipase D activity in glioma C6 cells. The cells were prelabelled with [1-(14)C]palmitic acid and phospholipase D-mediated synthesis of [(14)C]phosphatidylethanol was measured. The enhancing effect of TPA was almost completely blocked by a specific protein kinase C inhibitor, GF 109203X. In contrast, GF 109203X failed to inhibit the sphingosine, imipramine and propranolol stimulatory effects, indicating that their stimulation was independent of protein kinase C. The effect of TPA on phospholipase D was also blocked by imipramine and propranolol, whereas sphingosine additively potentiated TPA-mediated phospholipase D activity, both at shorter and longer (2-60 min) times of incubation. These results suggest that in glioma C6 cells, sphingosine is not only involved in a different phospholipase D activation than the TPA regulatory system, but also that it operates in a different compartment of the cell.
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PMID:Different regulation of phospholipase D activity in glioma C6 cells by sphingosine, propranolol, imipramine and phorbol ester. 1088 69

Malignant gliomas are highly angiogenic and aggressive tumors. IFN-beta has been used for the treatment of patients with malignant glioma; however, its antitumor mechanism in vivo remains unclear. To understand the in vivo antitumor effect and mechanism of recombinant human IFN-beta (rhIFN-beta) depending on the stages of tumor development or progression, we used orthotopic xenograft brain tumors generated by stereotactic intracerebral implantation of U-87 human glioma cells in nude mice. Mice bearing tumors 7 days (group 1) and 21 days (group 2) postimplant were treated with 2 x 10(5) IU/day of rhIFN-beta or saline i.p. for 15 days, respectively. Tumor growth was suppressed by 69.6% in group 1 and 10.8% in group 2 compared with tumors of each control group treated with saline. rhIFN-beta-treated group 1 animals showed 38% reduction in vascularization along with a 2.5-fold increase of the apoptotic index and no change in the proliferative index as compared with untreated tumors. The expression level of vascular endothelial cell growth factor and basic fibroblast growth factor was not affected by rhIFN-beta treatment. rhIFN-beta showed inhibitory activity on proliferation of U-87 cells, human umbilical vein endothelial cells, and PAM 212 murine keratinocytes in vitro. Our results indicate that the in vivo antitumor effect of rhIFN-beta on malignant gliomas may be mediated, at least in part, via angiogenesis inhibition rather than antiproliferative activity and that rhIFN-beta may be more effective for the treatment of malignant glioma patients at an early stage with minimal or microscopic tumor burdens rather than at an advanced stage of tumor development.
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PMID:Efficient inhibition of in vivo human malignant glioma growth and angiogenesis by interferon-beta treatment at early stage of tumor development. 1095 23

During aerobic metabolism, a small amount of partially reduced oxygen is produced, yielding reactive oxygen species (ROS). Peroxisomes and mitochondria are major contributors to cellular ROS production, which is normally balanced by consumption by antioxidants. The fatty acid analogue tetradecylthioacetic acid (TTA) promotes mitochondrial and peroxisomal proliferation, and may induce oxidative stress and change the growth potential of cancer cells. In the present study, we found that TTA reduced [(3)H]thymidine incorporation in the glioma cell lines BT4Cn (rat), D54Mg (human), and GaMg (human) in a dose- and time-dependent manner. The 50% inhibitory TTA doses were approximately 125 microM for BT4Cn and D54Mg cells and 40 microM for GaMg cells after 4 days. alpha-Tochopherol counteracted this inhibition in GaMg cells. TTA enhanced the oxidation of [1-(14)C]palmitic acid, which could be explained by stimulation of enzymes involved in peroxisomal (fatty acyl-CoA oxidase) and/or mitochondrial (carnitine palmitoyltransferase) fatty acid oxidation. The glutathione content and the activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase were differentially affected. Increased malondialdehyde (MDA) production was seen in TTA-treated GaMg and D54Mg cells, but not in BT4Cn cells, in vitro. In BT4Cn tumor tissue from TTA-treated rats, MDA was increased while the alpha-tocopherol content tended to decrease. TTA increased the level of cytosolic cytochrome c in BT4Cn cells, which suggests induction of apoptotic cascades. Although several mechanisms are likely to be involved in the TTA-mediated effects on growth, we propose that modulation of cellular redox conditions caused by changes in fatty acid metabolism may be of vital importance.
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PMID:Growth reduction in glioma cells after treatment with tetradecylthioacetic acid: changes in fatty acid metabolism and oxidative status. 1126 48

Antiproliferative properties of molecular regulators of lipid metabolism have been increasingly studied during recent years. Discussion is ongoing concerning optimal treatment conditions and assays used for monitoring proliferation and cytotoxicity. The objective of the present work was to optimize methods and treatment conditions used for studying antiproliferative effects of fatty acids and analogs, represented by palmitic acid (PA) and the beta-oxidation-restricted fatty acid analog tetradecylthioacetic acid (TTA), in rat (BT4Cn) and human (D54Mg and GaMg) glioma cell lines. Changes in [3H]thymidine incorporation preceded changes in cell number in TTA-treated glioma cell cultures, and the growth inhibition was more significantly expressed by [3H]thymidine incorporation than cell number. Addition of bovine serum albumin decreased cellular fatty acid uptake and reduced the effects of TTA and PA on [3H]thymidine incorporation. Determination of the antiproliferative effect of TTA in BT4Cn cells by MTT conversion and [3H]thymidine incorporation yielded concordant results. TTA-mediated reduction in cell number corresponded to reduction in cellular protein and total DNA content in BT4Cn cells. Reduced growth potential in TTA-treated multicellular D54Mg and GaMg spheroids supported the findings from monolayer cultures. In conclusion, cell density, treatment period, fatty acid administration, and methods for growth determination may profoundly influence the outcome of cell growth experiments. Thus, experimental conditions should be carefully controlled when performing cell growth experiments, and effects on cell growth should preferably be confirmed by different methods.
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PMID:Optimization of methods and treatment conditions for studying effects of fatty acids on cell growth. 1133 87

Tetradecylthioacetic acid (TTA), which cannot be beta-oxidized, exerts growth-limiting properties in glioma cells. In order to investigate the importance of modulated lipid metabolism and alterations in mitochondrial properties in this cell death process, we incubated glioma cells both with TTA and the oxidizable fatty acid palmitic acid (PA), in the presence of L-carnitine and the carnitine palmitoyltransferase inhibitors etomoxir and aminocarnitine. L-carnitine partly abolished the PA-mediated growth reduction of glioma cells, whereas etomoxir and aminocarnitine enhanced the antiproliferative effect of PA. The production of acid-soluble products increased and the incorporation of PA into glycerolipids decreased after L-carnitine supplementation. L-carnitine was found to enhance the antiproliferative effect of TTA, but did not affect the incorporation of TTA into glycerolipids, or ceramide. PDMP, sphingosine 1-phosphate, desipramine, fumonisin B(1), and L-cycloserine were able not to rescue the glioma cells from PA and TTA-induced growth inhibition, suggesting that increased ceramide production is not important in the growth reduction. TTA-mediated growth inhibition was accompanied with an increased uptake of PA and increased incorporation of PA into triacylglycerol (TG). Our data suggest that mitochondrial functions are involved in fatty acid-mediated growth inhibition. Whether there is a causal relationship between TG accumulation and the apoptotic process remains to be determined.
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PMID:Impact of mitochondrial beta-oxidation in fatty acid-mediated inhibition of glioma cell proliferation. 1251 30

A novel polyacrylamide superparamagnetic iron oxide nanoparticle platform is described which has been synthetically prepared such that multiple crystals of iron oxide are encapsulated within a single polyacrylamide matrix (PolyAcrylamide Magnetic [PAM] nanoparticles). This formulation provides for an extremely large T2 and T2* relaxivity of between 620 and 1140 sec(-1) mM(-1). Administration of PAM nanoparticles into rats bearing orthotopic 9L gliomas allowed quantitative pharmacokinetic analysis of the uptake of nanoparticles in the vasculature, brain, and glioma. Addition of polyethylene glycol of varying sizes (0.6, 2, and 10 kDa) to the surface of the PAM nanoparticles resulted in an increase in plasma half-life and affected tumor uptake and retention of the nanoparticles as quantified by changes in tissue contrast using MRI. The flexible formulation of these nanoparticles suggests that future modifications could be accomplished allowing for their use as a targeted molecular imaging contrast agent and/or therapeutic platform for multiple indications.
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PMID:A novel polyacrylamide magnetic nanoparticle contrast agent for molecular imaging using MRI. 1471 31

Malignant astrocytoma includes anaplastic astrocytoma (grade III) and glioblastoma (grade IV). Among them, glioblastoma is the most common primary brain tumor with dismal responses to all therapeutic modalities. We performed a large-scale, genome-wide microRNA (miRNA) (n=756) expression profiling of 26 glioblastoma, 13 anaplastic astrocytoma and 7 normal brain samples with an aim to find deregulated miRNA in malignant astrocytoma. We identified several differentially regulated miRNAs between these groups, which could differentiate glioma grades and normal brain as recognized by PCA. More importantly, we identified a most discriminatory 23-miRNA expression signature, by using PAM, which precisely distinguished glioblastoma from anaplastic astrocytoma with an accuracy of 95%. The differential expression pattern of nine miRNAs was further validated by real-time RT-PCR on an independent set of malignant astrocytomas (n=72) and normal samples (n=7). Inhibition of two glioblastoma-upregulated miRNAs (miR-21 and miR-23a) and exogenous overexpression of two glioblastoma-downregulated miRNAs (miR-218 and miR-219-5p) resulted in reduced soft agar colony formation but showed varying effects on cell proliferation and chemosensitivity. Thus we have identified the miRNA expression signature for malignant astrocytoma, in particular glioblastoma, and showed the miRNA involvement and their importance in astrocytoma development.
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PMID:Genome-wide expression profiling identifies deregulated miRNAs in malignant astrocytoma. 2071 Nov 71


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