UMLS:C0017638 - FACTA Search

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)

Three variants of murine serotonin transporter (5-HTT) mRNA, which consist of a different exon-one (exon 1a, exon 1b or exon 1c) and the same exon-two to exon-five, were identified. The promoter region for each exon 1 (p1a, p1b and p1c, respectively), ligated to pGL-3 enhancer vector, had activities significantly higher than the empty vector in all cell lines tested except p1c in PC-12, whereas the activity of p1c was significantly lower than the others. Effects of the treatment of dibutyryl-cyclic AMP, human interferon-alpha or mouse interferon-gamma have different profiles among COS-7, PC-12, C6 glioma and immortalized rat serotonergic raphe neurons, RN46A. These three promoter regions may play a role in the transcription of the 5-HTT and could offer a model of the regulation of 5-HTT production in humans and further the pathogenesis of depression.
...
PMID:Novel variants of murine serotonin transporter mRNA and the promoter activity of its upstream site. 1275 93

CXC ligand 10 (CXCL10) and CXCL9 are chemoattractants for activated T cells and possess angiostatic activity. Both CXCL9 and CXCL10 have been considered as important components for the anti-tumour activities of interferon-gamma (IFNgamma) and interleukin-12 in animal models. In this article we show that the CXCL9 and CXCL10 genes in some types of human tumour cell lines are not inducible by IFNgamma and we describe experiments designed to explore the molecular mechanisms involved in this impaired induction. The human oral squamous carcinoma line Ca9-22 and the glioma line A172 failed to express CXCL9 and CXCL10 mRNAs in response to IFNgamma, whereas other carcinoma lines including HSC-2 did express these mRNAs. Production of these chemokine proteins was also impaired in Ca9-22 cells. The impaired expression was not due to any deficiency in the IFNgamma/signal transducer and activator of transcription 1 (STAT1)-dependent signalling pathway. Instead, analysis of nuclear factor kappaB (NF-kappaB) activity revealed that the constitutive low level of NF-kappaB activity, which is seen in cells that express these chemokines, was absent in Ca9-22 and A172 cells. Activation of NF-kappaB in Ca9-22 cells restored the expression of IFNgamma-stimulated CXCL9 and CXCL10 mRNAs. In contrast, inhibition of the constitutive NF-kappaB in HSC-2 cells by adenovirus-mediated gene transfer of a dominant-negative IkappaBalpha suppressed the IFNgamma-induced expression of the CXCL9 and CXCL10 mRNAs. These results indicate that constitutive NF-kappaB activity, which is often associated with tumour development, is required for the induced expression of CXCL9 and CXCL10 genes in human tumour cell lines in response to IFNgamma.
...
PMID:Constitutive nuclear factor kappaB activity is required to elicit interferon-gamma-induced expression of chemokine CXC ligand 9 (CXCL9) and CXCL10 in human tumour cell lines. 1294 68

By flow cytometry, a panel of 18 primary glioma cell explants exhibited high expression of class I HLA-A, B, C, but class II HLA-DR expression was absent. Freshly isolated normal brain cells displayed little or no HLA antigens. Alloreactive cytotoxic T lymphocytes (aCTL), sensitized to the HLA of the patient, were generated in a one-way mixed lymphocyte response (MLR). The specificity of aCTL was confirmed to be to target cells (patient glioma cells or lymphoblasts) expressing the relevant HLA antigens. However, nontumor patient-specific aCTL did not lyse normal brain cells. Titration of antibodies to HLA class I into cytotoxicity assays blocked lysis of gliomas by aCTL, confirming aCTL T cell receptor (TCR) interactions with the class I antigen on gliomas. Furthermore, aCTL interactions with glioma cells caused their apoptosis. Coincubations of aCTL with gliomas resulted in upregulated cytokine secretion. Importantly, dexamethasone, an immunosuppressive steroid used for brain edema, did not affect aCTL lytic function against tumor, indicating that steroid-dependent patients may benefit from the immunotherapy. We also explored the use of interferon-gamma (IFN-gamma) to increase aCTL tumor recognition. Coincubation of gliomas with exogenous IFN-gamma (500 U/ml, 48 h) caused a 3-fold upregulation of HLA class I and a slight induction of class II antigen expression. Gene-modified glioma cells producing IFN-gamma similarly displayed upregulated HLA expression. Glioma cells incubated with exogenous IFN-gamma or IFN-gamma-transduced glioma cells were more susceptible to lysis by aCTL than their parental counterparts, thus supporting the concept of combining IFN-gamma cytokine gene therapy with adoptive aCTL immunotherapy for brain tumor treatment.
...
PMID:Human alloreactive CTL interactions with gliomas and with those having upregulated HLA expression from exogenous IFN-gamma or IFN-gamma gene modification. 1451 64

Human glioblastoma is a highly lethal tumor known for its capability of interfering with effective antitumor immune responses. Costimulatory signals are of critical relevance in both the inductive and effector phases of immune responses. Inducible costimulator-ligand (ICOSL), a member of the B7 family of costimulatory molecules related to CD80/CD86, regulates CD4 as well as CD8 T-cell responses via interaction with its receptor, ICOS, on activated T cells. We report the expression of ICOSL by glioma cells in vitro and in vivo. In contrast to CD80 (B7.1) and CD86 (B7.2), ICOSL protein and mRNA was expressed in 7 of 12 glioma cell lines. ICOSL expression is upregulated by the inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), whereas interferon-gamma (IFN-gamma) has no such effect. Further, immunohistochemical analysis of human brain tumors demonstrates the expression of ICOSL in three of four tissue samples. ICOSL expression is functional in that a neutralizing ICOSL antibody (HIL-131) reduces Th1 and Th2 cytokine levels in cocultures of peripheral blood lymphocytes or T-cell subsets (CD4 and CD8) with glioma cells. However, ICOSL gene transfer into glioma cells does not alter their immunogenicity under primary or secondary alloreactive coculture assays.
...
PMID:Expression of the B7-related molecule ICOSL by human glioma cells in vitro and in vivo. 1460 70

The aim is to investigate the radiosensitivity of noninfected cultured human glioma cells to ascertain that intracutaneously administered cells are viable enough to produce interferon-gamma but not able to proliferate. Cell cultures were established from five patients undergoing brain tumour surgery. By karyotyping, we found four malignant (three glioblastoma multiforme (GBM), one giant cell glioma) and one normal. The cells were irradiated with (137)Cs-gamma rays at absorbed dose levels of 0, 20, 40, 60, 80, 100 and 120 Gy. The fraction of viable cells was examined by MTT incorporation assay. The average of the data obtained from three GBM cell cultures was fitted to an exponential model. The parameters were: extrapolation number n=0.85+/-0.10, mean lethal dose D(0)=12.4+/-3.2 Gy and an additional uncertainty parameter deltaS=0.14+/-0.03. By setting deltaS=0, the corresponding values of the parameters were n=0.86+/-0.16 and D(0)=30.0+/-8.1 Gy. The rate of proliferation was examined by (3)H-thymidine incorporation. The average of the proliferation data obtained from three GBM cell cultures was fitted to an exponential model yielding n=0.943+/-0.005 and D(0)=5.8+/-0.5 Gy for deltaS=0.057+/-0.005, and by setting deltaS=0, n=1.00+/-0.02 and D(0)=8.4+/-1.6 Gy. No outgrowth of plated cells was observed after 4 weeks at an absorbed dose of 100 Gy. This absorbed dose is recommended for irradiation of 2 x 10(6) glioma cells used for clinical immunisation.
...
PMID:Radiation sterilisation of cultured human brain tumour cells for clinical immune tumour therapy. 1471 Feb 5

Lipopolysaccharide (LPS) and interferon-gamma (IFN) treatment of C6 rat glioma cells increased the intracellular ceramide level and the expression of the inducible nitric oxide synthase (iNOS) gene. To delineate the possible role of ceramide in the induction of iNOS, we examined the source of intracellular ceramide and associated signal transduction pathway(s) with the use of inhibitors of intracellular ceramide generation. The inhibitor of neutral sphingomyelinase (3-O-methylsphingomyelin, MSM) inhibited the induction of iNOS, whereas inhibitor of acidic sphingomyelinase (SR33557) or that of ceramide de novo synthesis (fumonisin B1) had no effect on the induction of iNOS. MSM-mediated inhibition of iNOS induction was reversed by the supplementation of exogenous C8-ceramide, suggesting that ceramide production by neutral sphingomyelinase (nSMase) is a key mediator in the induction of iNOS. The MSM-mediated inhibition of iNOS gene expression correlated with the decrease in the activity of ras. Inhibition of co-transfected iNOS promoter activity by dominant negative ras supported the role of ras in the nSMase-dependent regulation of iNOS gene. NF-kappaB DNA binding activity and its transactivity were also reduced by MSM pretreatment, and were completely reversed by the supplementation of C8-ceramide. As the dominant negative ras also reduced NF-kappaB transactivity, NF-kappaB activation may be downstream of ras. Our results suggest that ceramide generated by nSMase may be a critical mediator in the regulation of iNOS gene expression via ras-mediated NF-kappaB activation under inflammatory conditions.
...
PMID:The role of neutral sphingomyelinase produced ceramide in lipopolysaccharide-mediated expression of inducible nitric oxide synthase. 1472 Feb 8

We first classified 12 malignant glioma cell lines into three different groups (types 1-3) with respect to major histocompatibility complex (MHC) class II expression and analyzed each group based on the different expression status of the class II transactivator (CIITA) gene. Glioma type 1 (2 of 12) showed constitutive expression of all class II molecules that might be mediated by activation of B cell-specific CIITA promoter III. Glioma type 2 represented the major phenotype (66.7 %) of malignant glioma cell lines, and MHC class II expression was induced by interferon-gamma (IFN-gamma) in this phenotype. Analysis of glioma tissue samples revealed that CIITA promoter IV was detected in 9 of 11 patients (81.8%); however, promoter III was only in two (18.2%). Moreover, cultured glioma cells obtained from a fresh tumor sample upregulated expression of CIITA and class II molecules in the presence of IFN-gamma, strongly suggesting that glioma type 2 might be predominant in glioma tissues. Glioma type 3 (2 of 12) showed CIITA transcripts but loss of MHC class II expression even in the presence of IFN-gamma. In addition, we determined that the constitutive MHC class II expression in the glioma cell lines (type 1) was the result of transcriptional activation of the CIITA gene. This phenomenon was mediated by global histone acetylation over 6 kb upstream from the transcriptional start site of CIITA promoter III. Moreover, stable transfection of CIITA promoter IV as well as promoter III into MHC class II inducible cell lines restored the constitutive expression of all class II molecules. These studies lay the foundation to understand the molecular basis for the expression of class II molecules in gliomas.
...
PMID:Regulation of MHC class II expression in glioma cells by class II transactivator (CIITA). 1496 70

Brain tumors carry a poor prognosis, and newer approaches to their therapy are urgently needed. Natural killer T (NKT) cells are distinct innate lymphocytes with antitumor potentials. Defects in NKT cell function have been observed in patients with other forms of cancer. Here we show that both the frequency and interferon-gamma-producing function of NKT cells are well preserved in adult patients with glioma (n=9) and comparable to findings in healthy controls (n=9). These cells can be readily expanded in culture using autologous mature dendritic cells loaded with the NKT ligand, alpha-galactosyl ceramide. The expanded NKT cells from glioma patients are functional and, importantly, kill glioma cells in a ligand- and CD1d-dependent manner. Expression of CD1d is detected both on primary glioma cells as well as endothelial cells in infiltrating new blood vessels by immunohistochemistry of glioma tissue sections. These data suggest that targeting NKT cells may provide a novel strategy for immunotherapy of glioma.
...
PMID:Invariant natural killer T cells are preserved in patients with glioma and exhibit antitumor lytic activity following dendritic cell-mediated expansion. 1502 23

Halofuginone, a widely used alkaloid coccidiostat, is a potent inhibitor of collagen alpha 1 (I) and matrix metalloproteinase 2 gene expression. Halofuginone also suppresses extracellular matrix deposition and fibroblast proliferation. It was recently shown to be effective in suppression of bladder carcinoma and glioma. This study sought to evaluate the effect of treatment with halofuginone on growth of hepatocellular carcinoma (HCC) in mice. Athymic Balb/c mice were injected subcutaneously with 10(7) human hepatoma cells (Hep3B), followed by treatment with halofuginone administered in the diet (750 microg/kg) starting on day 3, before tumour innoculation. The control group was received a normal diet. Mice were followed for survival, tumour volume and serum alpha-fetoprotein (alpha FP). The mechanism of the anti-tumour effect of halofuginone was determined in vitro by assessing tumour cell growth, and by measuring the serum concentrations of interferon-gamma (IFN gamma) and interleukin 2 (IL2). Halofuginone treatment induced almost complete tumour suppression in treated mice. Mortality rates were 10% and 50%, in halofuginone-treated and control mice, respectively (P<0.001). No visible tumour was observed in treated mice, as compared with a 364 mm3 tumour in control mice. Serum alpha FP were 0.1 and 212 ng/ml in treated and control mice, respectively (P<0.005). Halofuginone significantly inhibited HCC proliferation in vitro. Maximal inhibition of 64% of tumour cell growth was observed at a concentration of 10(-8) M. The anti-tumour effect was mediated via a significant increase in IFN gamma and IL2 (90 vs. 35, and 210 vs. 34 pg/ml in treated and control groups, respectively, P<0.005). Treatment with halofuginone effectively suppressed the progression of HCC in mice. This effect may be associated with a direct anti-tumour effect, and/or enhancement of a systemic immune response.
...
PMID:Suppression of hepatocellular carcinoma growth in mice by the alkaloid coccidiostat halofuginone. 1517 99

Adenosine is a potent inhibitor of inflammatory processes, and the A(2A) adenosine receptor (A(2A)AR) plays a key nonredundant role as a suppresser of inflammatory responses in vivo. In this study, we demonstrate that increasing A(2A)AR gene expression suppressed multiple inflammatory responses in both human umbilical vein endothelial cells (HUVECs) and rat C6 glioma cells in vitro. In particular, the induction of the adhesion molecule E-selectin by either tumor necrosis factor alpha (TNFalpha) or Escherichia coli lipopolysaccharide (LPS) was reduced by more than 70% in HUVECs, whereas inducible nitric-oxide synthase (iNOS) induction was abolished in C6 cells after exposure to interferon-gamma in combination with LPS and TNFalpha, suggesting that the receptor inhibited a common step in the induction of each of these pro-inflammatory genes. Consistent with this hypothesis, A(2A)AR expression inhibited the activation of NF-kappaB, a key transcription factor whose proper function was essential for optimal iNOS and E-selectin induction. However, although NF-kappaB binding to target DNA was severely compromised in both cell types, the mechanisms by which this occurred were distinct. In C6 cells, A(2A)AR expression blocked IkappaBalpha degradation by inhibiting stimulus-induced phosphorylation, whereas in HUVECs, A(2A)AR expression inhibited NF-kappaB translocation to the nucleus independently of any effect on IkappaBalpha degradation. Together, these observations suggest that A(2A)AR-mediated inhibition NF-kappaB activation is a critical aspect of its anti-inflammatory signaling properties and that the molecular basis of this inhibition varies in a cell type-specific manner.
...
PMID:Specific inhibition of nuclear factor-kappaB-dependent inflammatory responses by cell type-specific mechanisms upon A2A adenosine receptor gene transfer. 1528 8

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