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)

Because a specific group of oligodendrogliomas is susceptible to adjuvant therapy, it is important to elucidate the biological characteristics of these tumors. In situ hybridization analyses have revealed that Olig genes are expressed in oligodendroglial lineage cells and are highly expressed in oligodendrogliomas. To clarify whether OLIG is a tumor-specific marker for oligodendrogliomas, we have investigated the expression of Olig transcripts by semiquantitative RT-PCR assay and OLIG2 protein with a new antibody in a variety of glial tumors. The semiquantitative RT-PCR revealed that high levels of expression of Olig1 and Olig2 mRNAs were present in anaplastic oligodendrogliomas and anaplastic astrocytomas, while expression of these mRNAs in grade IV glioblastomas was lower than in grade II and grade III gliomas (p < 0.01). Immunohistochemical analyses demonstrated that the mean immunopositive proportion of OLIG2 was 82% in anaplastic oligodendrogliomas but only 34% in anaplastic astrocytomas. Therefore, although OLIG2 expression was detected in a range of gliomas not specific for oligodendrogliomas, the expression level in anaplastic oligodendrogliomas was more uniform and intense than that in other glial tumors. In conclusion, combining Olig mRNA expression and immunohistochemistry of OLIG2 enables oligodendrogliomas to be distinguished from glioblastomas and other astrocytic glial tumors.
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PMID:Expression of the oligodendroglial lineage-associated markers Olig1 and Olig2 in different types of human gliomas. 1457 40

The oligodendrocyte lineage genes OLIG1 and OLIG2 have been reported as potential diagnostic markers for oligodendrogliomas [Lu et al. (2001) Proc Natl Acad Sci USA 98:10851-10856; Marie et al. (2001) Lancet 358:298-300]. We investigated the mRNA expression of OLIG1 and OLIG2, as well as four other genes involved in oligodendrocyte development ( E2A, HEB, NKX2.2, and PDGFRA) in a panel of 70 gliomas, including 9 oligodendrogliomas, 11 anaplastic oligodendrogliomas, 5 oligoastrocytomas, 10 anaplastic oligoastrocytomas, 10 diffuse astrocytomas, 10 anaplastic astrocytomas, and 15 glioblastomas. Most tumors demonstrated higher transcript levels of these genes as compared to non-neoplastic adult brain tissue. Four glioblastomas showed markedly increased PDGFRA mRNA expression due to PDGFRA gene amplification. Statistical analyses revealed no significant expression differences between oligodendroglial and astrocytic tumors. In oligodendroglial tumors, expression of the six genes was not significantly correlated to loss of heterozygosity on chromosome arms 1p and 19q. Thus, expression of the investigated oligodendrocyte lineage genes is up-regulated relative to non-neoplastic brain tissue in the majority of oligodendroglial and astrocytic tumors, suggesting that glioma cells are arrested in or recapitulate molecular phenotypes corresponding to early stages of glial development. However, the determination of mRNA expression of these genes by means of reverse transcription-PCR does not appear to be diagnostically useful as a marker for oligodendrogliomas.
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PMID:Expression of oligodendrocyte lineage genes in oligodendroglial and astrocytic gliomas. 1473 Apr 54

The basic helix-loop-helix transcription factor OLIG2 is specifically expressed in cells of the oligodendrocyte lineage. It is also expressed in various tumors originating from glial cells; however, the expression of OLIG2 is rare or weak in glioblastomas, the most malignant gliomas. The role of OLIG2 in glioma remains unclear. To investigate the function of OLIG2 in glial tumor cells, we have established a glioblastoma cell line, U12-1, in which the expression of OLIG2 is induced by the Tet-off system. Induction of OLIG2 resulted in suppression of both the proliferation and anchorage-independent growth of U12-1. It also resulted in an increase in the expression of p27(Kip1). A luciferase assay revealed that the CTF site of the p27(Kip1) gene promoter was essential for OLIG2-dependent activation of p27(Kip1) gene transcription. Electrophoretic mobility shift assays confirmed that a nuclear extract of OLIG2-expressing U12-1 cells contained a protein complex that binds to the CTF site of the p27(Kip1) gene promoter. Furthermore, siRNA against p27(Kip1) rescued the OLIG2-mediated growth and DNA synthesis inhibition of U12-1 cells. These results indicate that OLIG2 suppresses the proliferation of U12-1 and that this effect is mediated by transactivation of the p27(Kip1) gene, and low expression of OLIG2 may be related to the malignant behavior of human glioblastoma.
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PMID:A novel function of OLIG2 to suppress human glial tumor cell growth via p27Kip1 transactivation. 1655 41

Recent studies have identified stem cells in brain cancer. However, their relationship to normal CNS progenitors, including dependence on common lineage-restricted pathways, is unclear. We observe expression of the CNS-restricted transcription factor, OLIG2, in human glioma stem and progenitor cells reminiscent of type C transit-amplifying cells in germinal zones of the adult brain. Olig2 function is required for proliferation of neural progenitors and for glioma formation in a genetically relevant murine model. Moreover, we show p21(WAF1/CIP1), a tumor suppressor and inhibitor of stem cell proliferation, is directly repressed by OLIG2 in neural progenitors and gliomas. Our findings identify an Olig2-regulated lineage-restricted pathway critical for proliferation of normal and tumorigenic CNS stem cells.
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PMID:Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma. 1729 53

OLIG2 is a basic helix-loop-helix transcription factor regulating the generation of oligodendrocytes from neural progenitor cells, and the function of OLIG2 is inhibited posttranslationally through the interaction with ID2. This study aims to examine if the analysis of OLIG2 and ID2 expression in glioma tissues helps the differential diagnosis of chemosensitive oligodendroglial tumors from astrocytic tumors. Expression levels of OLIG2 and ID2 in 11 oligodendroglial and 27 astrocytic tumors were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR, and immunohistochemistry. The mean expression level of OLIG2 was higher in oligodendroglial tumors than astrocytic tumors, but some astrocytic tumors showed high OLIG2 expression, indicating that OLIG2 cannot be an independent marker of oligodendroglial tumors. No significant difference was observed between ID2 expression in oligodendroglial tumors and astrocytic tumors. It was notable that OLIG2 expression was predominant over ID2 expression in oligodendroglial tumors, while ID2 expression was predominant over OLIG2 expression in astrocytic tumors. Comparative genomic hybridization revealed that gliomas with loss on chromosome 1p, which is closely associated with chemosensitivity, also showed the predominant expression of OLIG2 over ID2. These results indicate that the immunohistochemical study on the relative expression level of OLIG2 to ID2 can be a useful screening for oligodendroglial tumors.
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PMID:Predominant expression of OLIG2 over ID2 in oligodendroglial tumors. 1743 71

The basic helix-loop-helix transcription factor, oligodendrocyte lineage transcription factor 2 (OLIG2), is specifically expressed in the developing and mature central nervous system and plays an important role in oligodendrogenesis from neural progenitors. It is also expressed in various types of glial tumors, but rarely in glioblastoma. Although we previously showed that OLIG2 expression inhibits glioma cell growth, its role in tumorigenesis remains incompletely understood. Here, we investigated the effect of OLIG2 expression on the migration of the human glioblastoma cell line U12-1. In these cells, OLIG2 expression is controlled by the Tet-off system. Induction of OLIG2 expression inhibited both the migration and invasiveness of U12-1 cells. OLIG2 expression also increased the activity of the GTPase RhoA as well as inducing the cells to form stress fibers and focal adhesions. Experiments using short interfering RNA against p27(Kip1) revealed that up-regulation of the p27(Kip1) protein was not essential for RhoA activation, rather it contributed independently to the decreased motility of OLIG2-expressing U12-1 cells. Alternatively, semiquantitative reverse transcription-PCR analysis revealed that mRNA expression of RhoGAP8, which regulates cell migration, was decreased by OLIG2 expression. Furthermore, expression of C3 transferase, which inhibits Rho via ADP ribosylation, attenuated the OLIG2-induced inhibition of cell motility. Imaging by fluorescence resonance energy transfer revealed that in U12-1 cells lacking OLIG2, the active form of RhoA was localized to protrusions of the cell membrane. In contrast, in OLIG2-expressing cells, it lined almost the entire plasma membrane. Thus, OLIG2 suppresses the motile phenotype of glioblastoma cells by activating RhoA.
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PMID:Oligodendrocyte lineage transcription factor 2 inhibits the motility of a human glial tumor cell line by activating RhoA. 1795 9

Recent developments in molecular analysis have revealed genetic alterations in human gliomas. Loss of heterozygosity (LOH) is a critical molecular marker for classification of human glioma, and is useful for predicting outcome. Our previous LOH study identified a small subgroup of glioblastoma (GBM), with 1p/19q co-deletion, with a favorable clinical outcome. In this study, we investigated molecular pathological features of eight GBM with 1p/19q co-deletion compared with "classic" GBM and anaplastic oligodendroglioma (AO). We estimated EGFR gene amplification, EGFRvIII expression, CDKN2A (p16) homozygous deletion, and isocitrate dehydrogenase 1/2 (IDH1/2) gene mutations. We also conducted an analysis of the expression of proneural genes (DLL3, OLIG2, SOX2). On histopathological review, only one GBM was diagnosed as glioblastoma with oligodendroglioma component (GBMO). Loss of chromosomes 10 and 17p is common, and neither IDH1/2 mutations nor EGFRvIII expression were detected in GBM with 1p/19q co-deletion. The expression profile revealed high expression of the OLIG2 gene in this subgroup. High expression of proneural gene OLIG2 without EGFRvIII expression may be associated with a favorable clinical outcome; however, IDH1/2 gene status and the extent of LOH regions may indicate that this small subgroup of GBM is a distinct genetic subgroup from oligodendroglial tumors.
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PMID:Molecular characteristics of glioblastoma with 1p/19q co-deletion. 2273 34

The subclassification of glioblastoma (GBM) into clinically relevant subtypes using microRNA (miRNA)- and messenger RNA (mRNA)-based integrated analysis has been attempted. Because miRNAs regulate multiple gene-signaling pathways, understanding miRNA-mRNA interactions is a prerequisite for understanding glioma biology. However, such associations have not been thoroughly examined using high-throughput integrated analysis. To identify significant miRNA-mRNA correlations, we selected and quantified signature miRNAs and mRNAs in 82 gliomas (grade II: 14, III: 16, IV: 52) using real-time reverse-transcriptase polymerase chain reaction. Quantitative expression data were integrated into a single analysis platform that evaluated the expression relationship between miRNAs and mRNAs. The 21 miRNAs include miR-15b, -21, -34a, -105, -124a, -128a, -135b, -184, -196a-b, -200a-c, -203, -302a-d, -363, -367, and -504. In addition, we examined 23 genes, including proneural markers (DLL3, BCAN, and OLIG2), mesenchymal markers (YKL-40, CD44, and Vimentin), cancer stem cell-related markers, and receptor tyrosine kinase genes. Primary GBM was characterized exclusively by upregulation of mesenchymal markers, whereas secondary GBM was characterized by significant downregulation of mesenchymal markers, miR-21, and -34a, and by upregulation of proneural markers and miR-504. Statistical analysis showed that expression of miR-128a, -504, -124a, and -184 each negatively correlated with the expression of mesenchymal markers in GBM. Our functional analysis of miR-128a and -504 as inhibitors demonstrated that suppression of miR-128a and -504 increased the expression of mesenchymal markers in glioblastoma cell lines. Mesenchymal signaling in GBM may be negatively regulated by miR-128a and -504.
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PMID:Associations between microRNA expression and mesenchymal marker gene expression in glioblastoma. 2284 9

Platelet-derived growth factor receptor alpha-positive oligodendrocyte progenitor cells (OPC) located within the mature central nervous system may remain quiescent, proliferate, or differentiate into oligodendrocytes. Human glioblastoma multiforme tumors often contain rapidly proliferating oligodendrocyte lineage transcription factor 2 (Olig2)-positive cells that resemble OPCs. In this study, we sought to identify candidate pathways that promote OPC differentiation or quiescence rather than proliferation. Gene expression profiling conducted in both normal murine OPCs and highly proliferative Olig2-positive glioma cells identified all the transcripts associated with the highly proliferative state of these cells and showed that among the various cell types found within the brain, Olig2-positive tumor cells are most similar to OPCs. We then subtracted OPC transcripts found in tumor samples from those found in normal brain samples and identified 28 OPC transcripts as candidates for promoting differentiation or quiescence. Systematic analysis of human glioma data revealed that these genes have similar expression profiles in human tumors and were significantly enriched in genomic deletions, suggesting an antiproliferative role. Treatment of primary murine glioblastoma cells with agonists of one candidate gene, Gpr17, resulted in a decreased number of neurospheres. Together, our findings show that comparison of the molecular phenotype of progenitor cells in tumors to the equivalent cells in the normal brain represents a novel approach for the identification of targeted therapies.
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PMID:Candidate pathways for promoting differentiation or quiescence of oligodendrocyte progenitor-like cells in glioma. 2286 58

Glioblastoma (GBM) is the most common primary brain tumor in adults and has a dismal prognosis despite multimodality treatment. Given the resistance of glioma stem cells (GSC) to chemotherapy and radiation therapy, their eradication could prevent tumor recurrence. We sought to evaluate the antitumor activity of measles virus (MV) derivatives against GSC. We generated neurosphere cultures from patient-derived primary tumor GBM xenografts, and we characterized them for the GSC markers CD133, SOX2, Nestin, ATF5 and OLIG2. Using the MV-strains MV-GFP, MV-CEA and MV-NIS we demonstrated infection, viral replication and significant cytopathic effect in vitro against GSC lines. In tumorigenicity experiments, GBM44 GSC were infected with MV in vitro and subsequently implanted into the right caudate nucleus of nude mice: significant prolongation of survival in mice implanted with infected GSC was observed, compared with mock-infected controls (P=0.0483). In therapy experiments in GBM6 and GBM12 GSC xenograft models, there was significant prolongation of survival in MV-GFP-treated animals compared with inactivated virus-treated controls (GBM6 P=0.0021, GBM12 P=0.0416). Abundant syncytia and viral replication was demonstrated in tumors of MV-treated mice. Measles virus derivatives have significant antitumor activity against glioma-derived stem cells in vitro and in vivo.
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PMID:Oncolytic measles virus strains have significant antitumor activity against glioma stem cells. 2291 95


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