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)

To identify therapeutic molecular targets for glioma, we performed modified serological identification of antigens by recombinant complementary DNA (cDNA) expression cloning using sera from a mouse glioma model. Two clones, kinesin family member 23 (Kif23) and structural maintenance of chromosomes 4 (Smc4), were identified as antigens through immunological reaction with sera from mice harboring synergic GL261 mouse glioma and intratumoral inoculation with a mutant herpes simplex virus. The human Kif23 homolog KIF23 is a nuclear protein that localizes to the interzone of mitotic spindles, acting as a plus-end-directed motor enzyme that moves antiparallel microtubules in vitro. Expression analysis revealed a higher level of KIF23 expression in glioma tissues than in normal brain tissue. The introduction of small interfering RNA (siRNA) targeting KIF23 into two different glioma cell lines, U87MG and SF126, downregulated KIF23 expression, which significantly suppressed glioma cell proliferation in vitro. KIF23 siRNA-treated glioma cells exhibited larger cell bodies with two or more nuclei compared with control cells. In vivo analysis using mouse xenograft showed that KIF23 siRNA/DNA chimera-treated tumors were significantly smaller than tumors treated with control siRNA/DNA chimera. Taken together, our results indicate that downregulation of KIF23 decreases proliferation of glioma cells and that KIF23 may be a novel therapeutic target in malignant glioma.
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PMID:Downregulation of KIF23 suppresses glioma proliferation. 2190 57

To improve treatment strategies of glioma, microarray data were applied to screen target molecules that were regulated by microRNAs (miRNAs). GSE31262 was downloaded from Gene Expression Omnibus, including five neural stem cells samples from normal human and nine stem cells samples from glioma patients. Differentially expressed genes (DEGs) were identified with Multtest package and Limma package of R language, and false discovery rate < 0.05 and |log2FC (fold change)| >1 were chosen as cut-off criterion. Hierarchical clustering and pathway enrichment analysis of DEGs were performed using pheatmap package of R language and KOBAS software, respectively. miRNAs related to up- and down-regulated DEGs were, respectively, predicted by WebGestalt software and its miRNAs-target DEGs interaction network were, respectively, constructed by STRING database. Bingo plug-in in Cytoscape software was applied to analyze Gene Ontology functional enrichment analysis for up- and down-regulated DEGs in network, respectively. A total of 428 DEGs were selected, including 331 down-regulated and 97 up-regulated DEGs. Hierarchical clustering analysis showed that glioma samples and normal samples were completely separated. Pathway analysis indicated that CDK2 and WEE1 participated in the cell cycle. miR-124 could simultaneously regulate up-regulated (ELAVL1 and EZH2) and down-regulated (BACE1) DEGs. The down-regulated genes (KIF23, WEE1 and CDK2) were associated with cell division, while the up-regulated genes (PLP1 and MBP) were related to myelination of neurons. miR-124 might participate in development of glioma by regulating BACE1, ELAVL1 and EZH2. The biomarkers (KIF23, WEE1, CDK2, PLP1 and MBP) were considered as therapeutic targets of glioma.
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PMID:Gene expression analyses to explore the biomarkers and therapeutic targets for gliomas. 2628 16

Low-grade gliomas (LGGs) are a highly heterogeneous group of slow-growing, lethal, diffusive brain tumors. Temozolomide (TMZ) is a frequently used primary chemotherapeutic agent for LGGs. Currently there is no consensus as to the optimal biomarkers to predict the efficacy of TMZ, which calls for decision-making for each patient while considering molecular profiles. Low-grade glioma data sets were retrieved from The Cancer Genome Atlas. Cox regression and survival analyses were applied to identify clinical features significantly associated with survival. Subsequently, Ordinal logistic regression, co-expression, and Cox regression analyses were applied to identify genes that correlate significantly with response rate, disease-free survival, and overall survival of patients receiving TMZ as primary therapy. Finally, gene expression and methylation analyses were exploited to explain the mechanism between these gene expression and TMZ efficacy in LGG patients. Overall survival was significantly correlated with age, Karnofsky Performance Status score, and histological grade, but not with IDH1 mutation status. Using 3 distinct efficacy end points, regression and co-expression analyses further identified a novel 4-gene signature of ASPM, CCNB1, EXO1, and KIF23 which negatively correlated with response to TMZ therapy. In addition, expression of the 4-gene signature was associated with those of genes involved in homologous recombination. Finally, expression and methylation profiling identified a largely unknown olfactory receptor OR51F2 as potential mediator of the roles of the 4-gene signature in reducing TMZ efficacy. Taken together, these findings propose the 4-gene signature as a novel panel of efficacy predictors of TMZ therapy, as well as potential downstream mechanisms, including homologous recombination, OR51F2, and DNA methylation independent of MGMT.
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PMID:Comprehensive Analysis Reveals a 4-Gene Signature in Predicting Response to Temozolomide in Low-Grade Glioma Patients. 3116 46