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)

Alterations of cell surface expression of HLA (class I, class II DR, DP and DQ) and EGF-receptor on two malignant glioma cell lines (U-343MG and U-563MG) induced with cytokines (IFN-gamma, TNF-alpha, IL-1 alpha) and differentiation promoters (all-trans retinoic acid, phorbol ester TPA) were analyzed with the aid of flow cytometry. IFN-gamma induced a 10-15fold increase of HLA class I. TNF-alpha alone induced a two- to fivefold increase of HLA class I cell surface density and increased the IFN-gamma induced upregulation of HLA class I to approximately 20-24 times the antigen density of uninduced cells. TNF-alpha was able to increase HLA class II DR and DP cell surface expression on glioma lines, but it enhanced only the IFN-gamma-induced HLA class II DR upregulation. All-trans retinoic acid and TPA regulated in the opposite way the EGF-receptor cell surface expression on U-563MG cells.
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PMID:Modulation of cell surface EGF receptor and HLA expression on glioma cell lines induced with cytokines and differentiation promoters. 789 57

Viral infection results in enhancement of HLA-class I expression in a number of cell types, including glial cells, which normally do not express these molecules. This enhancement may occur through a direct interaction between a viral component and the HLA-class I gene or indirectly through virus-induced soluble factors produced by infected cells. These include cytokines such as IFN-gamma, IFN-alpha/beta, and TNF-alpha, known to enhance class I expression. Measles virus (MV) infection of a human glioma cell line (U-105 MG) and of primary human umbilical vein endothelial cells enhances the expression of HLA-class I molecules on these cells. The enhancement of HLA-class I is dependent on infectious virus, as antibody-neutralized MV has no effect on class I expression. In this study, we demonstrate the presence of an HLA-class I-enhancing factor in supernatants from MV-infected cells. The supernatant class I-enhancing factor is not IFN-gamma, IFN-alpha, or TNF-alpha because MV-infected cells did not produce measurable levels of these cytokines as detected by immunoassay or polymerase chain reaction. In contrast, IFN-beta is produced by the infected cells and the supernatant class I-enhancing factor could be entirely neutralized by antibodies to IFN-beta, but not antibodies to IFN-alpha, TNF-alpha, or non-immune sera. Furthermore, preincubation of cells with neutralizing antibodies to IFN-beta prior to infection blocked MV enhancement of HLA-class I completely in the U-105 MG cells and by as much as 74% in the umbilical vein endothelial cells. The results of these experiments provide direct evidence that enhanced HLA-class I expression in MV-infected cells is mediated primarily by IFN-beta.
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PMID:Direct evidence that interferon-beta mediates enhanced HLA-class I expression in measles virus-infected cells. 824 64

35 patients suffering from malignant stage III/IV glioma were enrolled into a prospectively randomized clinical trial. All patients were provided with standard oncologic treatment (neurosurgery, radiation, basic clinical care according to protocol and indication) and randomly divided into a) treatment group: receiving subcutaneous injections of a ML (a galactoside-specific lectin from mistletoe) standardized mistletoe extract, 1 ng ML-1/kg BW, twice a week for 3 months, starting on day 1 post surgery, b) control group: without additional complementary treatment. Immunophenotyping of peripheral blood leukocytes was done by flow cytometry (pre surgery; day 1, week 1, month 3 and 6 post surgery) to evaluate the immunomodulating capacity of ML-1 standardized mistletoe extract. Standard tumor destructive treatment of glioma proved to be suppressive for peripheral blood lymphocytes, since all subsets tested revealed statistically significant down regulation. Unlike the lymphocyte counts and activities of patients from the control group who gave preoperative values after 3-6 months), mistletoe treatment induced a statistically significant up regulation of cell counts (CD-3, CD4, CD-8 cells) and activities (CD-25, HLA/DR positive cells) after 3 months, as compared to preoperative values. Obviously, a strong immunoprotective/immunostimulatory effect was induced by the treatment of glioma patients with ML-1 standardized mistletoe extract which correlated with an improved quality of life, as determined by a standard questionnaire (Spitzer).
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PMID:Immunoprotective activity of the galactoside-specific lectin from mistletoe after tumor destructive therapy in glioma patients. 904 60

CMV and other viruses down-regulate the cell surface expression of class I HLA, and while this allows them to evade CTL, it may make infected cells more susceptible to lysis by NK cells, due to the failure to engage class I inhibitory receptors on the NK cell. We studied CMV infection and found that fibroblasts infected with virus strains Towne, Toledo, Davis, and C1FE were refractory to NK lysis, while those infected with strains AD169, C1F, or R7 were susceptible. All viral strains down-regulated class I HLA to a similar extent, and we concluded that there was no evidence for any correlation between the latter and susceptibility to NK lysis. In contrast, there was a strong correlation between NK killing of CMV-infected cells and cell surface levels of lymphocyte function-associated antigen-3 (LFA-3). Fibroblasts infected with the Towne, Toledo, Davis, and C1FE strains of CMV down-regulated LFA-3 expression and were refractory to lysis, while strains AD169, C1F, and R7 up-regulated LFA-3 and were susceptible to NK killing. U373 MG (malignant glioma) cells expressed constitutively high levels of LFA-3 and were sensitive to NK lysis when infected with any of the above-listed CMV strains. We estimated that a minimum of between 29,000 and 71,000 LFA-3 molecules per target cell were needed for NK susceptibility. The effects on LFA-3 expression were due to immediate early/early viral gene products. We also demonstrated that fibroblasts infected with the strains Towne, Toledo, Davis, and C1FE expressed a ganciclovir-sensitive late CMV gene product, which delivered an inhibitory signal to NK cells.
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PMID:Natural killer cell lysis of cytomegalovirus (CMV)-infected cells correlates with virally induced changes in cell surface lymphocyte function-associated antigen-3 (LFA-3) expression and not with the CMV-induced down-regulation of cell surface class I HLA. 972 32

We have reported a tumor-rejection antigen, SART1(259), possessing tumor epitopes capable of inducing cytotoxic T lymphocytes (CTLs) in epithelial-cancer patients. This study investigated the expression of SART1(259) antigen in brain tumors, to explore for a potential molecule for use in specific immunotherapy of patients with brain tumors. The SART1(259) antigen was detected in the cytosol fraction of 13 of 18 (72%) glioma cell lines and in 12 of 34 (35%) brain-tumor tissues, with a higher rate of expression among malignant gliomas (5/10, 50%) and schwannomas (3/4). HLA-A24-restricted and SART1-specific CTLs recognized the HLA-A24+ and SART1(259)+ glioma cells, and the levels of recognition correlated both with HLA-A24-antigen expression level and with the concentration of the SART1 peptide antigen. Therefore, the SART1(259) antigen could be a target molecule for specific immunotherapy of patients with brain tumors expressing HLA-class-1 antigens.
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PMID:Expression of the tumor-rejection antigen SART1 in brain tumors. 1059 92

The authors recently reported on the SART3 tumor-rejection antigen, which possesses epitopes that can induce cytotoxic T lymphocytes (CTLs) in patients with epithelial cancer. To explore a new modality for treatment of patients with brain tumors, this study investigated the expression of the SART3 antigen in patients with brain tumors and the ability of SART3 peptides to induce CTLs from peripheral blood mononuclear cells (PBMCs) of these patients. The SART3 antigen was detected in the cytoplasmic fraction of all 18 glioma cell lines examined and in the majority (31 of 34; 91%) of brain tumor tissues irrespective of their histologies. It was also expressed in the nuclear fraction of all 18 glioma cell lines and in the majority (26 of 34; 76%) of brain tumor tissues. In contrast, the SART3 was not expressed in nontumorous brain tissues. Cytotoxic T lymphocytes were induced in patients with glioma by stimulation with two epitope peptides of SART3. These CTLs could eliminate glioma cells in a HLA-A24-restricted manner. Therefore, the SART3 peptides may be appropriate molecules for use in peptide-based specific immunotherapy of HLA-A24+ patients with brain tumors.
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PMID:Expression of the SART3 tumor-rejection antigen in brain tumors and induction of cytotoxic T lymphocytes by its peptides. 1100 44

It has been proposed that tumor cells frequently associated with partial or total loss of HLA class Ia expression may abnormally express HLA-G class Ib antigen. Such peculiar HLA class I expression would allow tumor cells to escape not only from CD8+T but also from NK-cell cytotoxicity. We studied the cell surface expression of HLA-G using flow cytometry with two HLA-G specific monoclonal antibodies (87G, 01G). The JEG-3 choriocarcinoma cell line, which constitutively expresses HLA-G antigens was used as a positive control. We did not detect the cell-surface HLA-G antigens in the following 75 tumor cell lines: melanoma (22), neuroblastoma (7), retinoblastoma (1), glioma (2), breast carcinoma (3), ovarian carcinoma (3), cervical carcinoma (1), colon carcinoma (3), bladder carcinoma (2), hepatocarcinoma (1), sarcoma (2) and leukemia cell lines: T-lymphocytes (6), B-lymphocytes (13) and myelo-monocytes (9). We found that some myelomonocytic cell lines express on their surface high affinity FcgammaRI (CD64) that may result in the binding of HLA-G specific mabs to their cell surface even in the absence of HLA-G molecules. Our panel of HLA-G negative tumor cell lines accommodated 62 cell lines for which similar analysis have not been reported and also contained 13 cell lines with total or partial loss of HLA class Ia molecules. Our observation imply that under normal culture conditions the cell surface HLA-G reactive with 87G and 01G mabs is absent in most tumor cell lines of different origin.
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PMID:Expression of the non-classical HLA-G antigen in tumor cell lines is extremely restricted. 1126 57

HLA-G is a nonclassical MHC molecule with highly limited tissue distribution that has been attributed chiefly immune regulatory functions. Glioblastoma is paradigmatic for the capability of human cancers to paralyze the immune system. To delineate the potential role of HLA-G in glioblastoma immunobiology, expression patterns and functional relevance of this MHC class Ib molecule were investigated in glioma cells and brain tissues. HLA-G mRNA expression was detected in six of 12 glioma cell lines in the absence of IFN-gamma and in 10 of 12 cell lines in the presence of IFN-gamma. HLA-G protein was detected in four of 12 cell lines in the absence of IFN-gamma and in eight of 12 cell lines in the presence of IFN-gamma. Immunohistochemical analysis of human brain tumors revealed expression of HLA-G in four of five tissue samples. Functional studies on the role of HLA-G in glioma cells were conducted with alloreactive PBMCs, NK cells, and T cell subpopulations. Expression of membrane-bound HLA-G1 and soluble HLA-G5 inhibited alloreactive and Ag-specific immune responses. Gene transfer of HLA-G1 or HLA-G5 into HLA-G-negative glioma cells (U87MG) rendered cells highly resistant to direct alloreactive lysis, inhibited the alloproliferative response, and prevented efficient priming of cytotoxic T cells. The inhibitory effects of HLA-G were directed against CD8 and CD4 T cells, but appeared to be NK cell independent. Interestingly, few HLA-G-positive cells within a population of HLA-G-negative tumor cells exerted significant immune inhibitory effects. We conclude that the aberrant expression of HLA-G may contribute to immune escape in human glioblastoma.
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PMID:A functional role of HLA-G expression in human gliomas: an alternative strategy of immune escape. 1197 Oct 28

Although specific immunotherapy is one candidate treatment of brain tumor, the molecular basis of T-cell-mediated recognition of brain tumors has not yet been elucidated. In this study, we tried to identify brain tumor antigens using HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes (CTLs). As an HLA-A2-restricted OK-CTL line contained CTLs capable of responding to HLA-A2+ malignant glioma cells, this cell line was used for identification of brain tumor antigens. After screening a cDNA library from brain tumor cells, this CTL line was found to produce interferon (IFN)-gamma when cultured with COS-7 cells, which were cotransfected with both a cDNA clone (clone 1) and HLA-A0207 cDNA. Data base searches indicated that the clone 1 was 98% identical to that of the human ADP-ribosylation factor 4-like (ARF4L). Two peptides, ARF4L 15-24 and ARF4L 69-77, possessed the ability to induce HLA-A2-restricted and tumor-reactive CTLs from peripheral blood mononuclear cells of patients with brain tumors. Although ARF4L seemed to be ubiquitously expressed at the mRNA level, ARF4L-reactive CTLs failed to exhibit cytotoxicity against normal lymphoid blasts. These results indicate that these two ARF4L peptides could be targets for immunotherapy of HLA-A2+ patients with brain tumors.
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PMID:Recognition of ADP-ribosylation factor 4-like by HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes from patients with brain tumors. 1247 61

A novel receptor, named 1C7 or NKp30 and involved in natural cytotoxicity, was recently identified. This receptor is encoded by the 1C7 gene, which is located within the class III region of the human MHC, HLA. It is a member of the immunoglobulin gene superfamily (IgSF) and, remarkably, is expressed at the mRNA level as six different splice variants in human. Recent investigations have indicated that the 1c7 gene of the mouse is silenced by in-frame stop codons. In this study, the molecular characterization of the rat 1c7 gene is described. cDNA derived from this gene encode a protein of 192 amino acid residues predicted to contain a single IgV-set domain in the extracellular region and a positively charged residue in the transmembrane region. Expression of the gene was detected in freshly isolated rat Natural Killer (NK) and T splenocytes. Transfection of rat 1C7 into the NK cell line RNK-16 induced cytolytic activity against glioma as well as lymphoma tumor cells. In addition, binding of a r1C7-Fc fusion protein by a panel of target cells correlated with susceptibility to killing by RNK-16-1C7 effector cells. These results indicate that the r1C7 molecule could function as an NK activating receptor as previously reported for the human NKp30 receptor molecule.
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PMID:Molecular characterization of the novel rat NK receptor 1C7. 1254 65


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