OBJECTIVEThis overview seeked to bring together the microRNA (miRNA) researches on biogenesis and bio-function in these areas of clinical diagnosis and therapy for malignant glioma.

DATA SOURCESUsing the keyword terms "glioma" and "miRNA," we performed the literature search in PubMed, Ovid, and web.metstr.com databases from their inception to October 2014.

STUDY SELECTIONIn screening out the quality of the articles, factors such as clinical setting of the study, the size of clinical samples were taken into consideration. Animal studied for verification and reviews article were also included in our data collection.

RESULTSDespite many advance in miRNA for malignant glioma, further studies were still required to focus on the following aspects: (i) Improving the understanding about biogenesis of miRNA and up-down regulation; (ii) utilizing high-throughput miRNA expression analysis to screen out the core miRNA for glioma; (iii) Focusing related miRNAs on the signal transduction pathways that regulate the proliferation and growth of glioma.

CONCLUSIONSWe discussed the most promising miRNA, correlative signaling pathway and their relation with gliomas in the way of prompting miRNA target into being a clinical therapeutic strategy.

Brain Neoplasms ; genetics ; pathology ; Gene Expression Regulation, Neoplastic ; Glioma ; genetics ; pathology ; Humans ; MicroRNAs ; genetics

OBJECTIVETo establish malignant progression associated gene expression profiles in human brain glioma.

METHODSThe primary (WHO grade II), recurrent (WHO grade III) and re-recurrent (WHO grade IV) glioma specimens were sequentially collected from one single patient. Gene expression of different tumor specimens and normal brain tissue of the same patient was compared by microarrary techniques.

RESULTS197 differentially expressed genes with differential ratio > or = 3 were observed when compared with normal brain tissue. When the specimens (3 tumor, 1 normal brain) were paired with each other, 7 groups containing 489 genes (upregulated 193, downregulated 296) were observed. According to the descending frequency of the 109 genes with known function, they were the genes associated with development, metabolism, differentiation, signal transduction, DNA binding transcription, cellular receptor, immunity, ion-channel transportation, protein translation, cell backbone motion, stress, protooncogene and anti-oncogene and cell apoptosis, respectively.

CONCLUSIONFrom the 197 differentially expressed genes found in one glioma patient experiencing tumor malignant progression, 17 genes screened out by bioinformatics assay, may offer valuable information on molecular mechanisms on genesis and malignant progression of glioma.

Brain Neoplasms ; genetics ; pathology ; Gene Expression Profiling ; Glioma ; genetics ; pathology ; Humans ; Oligonucleotide Array Sequence Analysis

Brain Neoplasms ; pathology ; physiopathology ; DNA Repair ; genetics ; Glioma ; pathology ; physiopathology ; Humans ; Statistics as Topic ; Targeted Gene Repair

To evaluate the effect of wild-type p53 gene on the growth and radiotherapeutic sensitivity of human glioma cells, plasmid PC53-SN3 carrying wild-type p53 gene was transfected into U251 cells. p53 gene expression in transfected cells was detected by RT-PCR, and the cell growth inhibition and apoptosis in the absence or presence of irradiation were assessed by MTT and flow cytometry. The transfection of p53 gene into U251 cells was confirmed by RT-PCR. MTT showed that p53 gene alone induced strong inhibitory effect on the growth of U251 cells (inhibition rate (IR), (79.60 +/- 5.69)%). The killing effect of irradiation alone on U251 cells was not strong (IR: (17.06 +/- 4.35)% (17.39 +/- 1.67)% (18.73 +/- 4.68)%) and increased with the irradiation doses (3, 6, 9 Gy). When combined treatment of wild-type p53 gene transfection and irradiation was used, the effect was significantly increased (IR:(80.60 +/- 5.35)%. (90.30 +/- 1.67)%, (91.30 +/- 2.01)%). The apoptosis rate of U251 cells induced by p53 gene transfection was 17.38%. The rate induced by irradiation increased (4.61%, 4.84%, 5.40%) with the irradiation doses (3, 6, 9 Gy). The apoptosis rate was also significantly increased (17.80%, 20.03%, 22.34%) after combined treatment of p53 and irradiation with different doses (3, 6, 9 Gy). It is concluded that wild-type p53 gene and irradiation could result in synergistic inhibitory effect on the growth of human glioma cells.
Apoptosis/*radiation effects ; Brain Neoplasms/genetics ; Brain Neoplasms/*pathology ; Genes, p53/*radiation effects ; Glioma/genetics ; Glioma/*pathology ; Transfection ; Tumor Cells, Cultured

Animals ; Brain Neoplasms ; genetics ; pathology ; Cell Differentiation ; Cell Transformation, Neoplastic ; genetics ; Glioma ; genetics ; pathology ; Humans ; Neoplastic Stem Cells ; pathology ; Neural Stem Cells ; pathology ; Neuroglia ; pathology ; Neurons ; pathology

BACKGROUND: Mixed gliomas, such as oligoastrocytomas (OA), anaplastic oligoastrocytomas, and glioblastomas (GBMs) with an oligodendroglial component (GBMO) are defined as tumors composed of a mixture of two distinct neoplastic cell types, astrocytic and oligodendroglial. Recently, mutations ATRX and TP53, and codeletion of 1p/19q are shown to be genetic hallmarks of astrocytic and oligodendroglial tumors, respectively. Subsequent molecular analyses of mixed gliomas preferred the reclassification to either oligodendroglioma or astrocytoma. This study was designed to apply genetically integrated diagnostic criteria to mixed gliomas and determine usefulness and prognostic value of new classification in Korean patients. METHODS: Fifty-eight cases of mixed OAs and GBMOs were retrieved from the pathology archives of Seoul National University Hospital from 2004 to 2015. Reclassification was performed according to genetic and immunohistochemical properties. Clinicopathological characteristics of each subgroup were evaluated. Overall survival was assessed and compared between subgroups. RESULTS: We could reclassify all mixed OAs and GBMOs into either astrocytic or oligodendroglial tumors. Notably, 29 GBMOs could be reclassified into 11 cases of GBM, IDH-mutant, 16 cases of GBM, IDH-wildtype, and two cases of anaplastic oligodendroglioma, IDH mutant. Overall survival was significantly different among these new groups (p<.001). Overall survival and progression-free survival were statistically better in gliomas with IDH mutation, ATRX mutation, no microscopic necrosis, and young patient age (cut off, 45 years old). CONCLUSIONS: Our results strongly suggest that a genetically integrated diagnosis of glioma better reflects prognosis than former morphology-based methods.
Astrocytoma ; Classification ; Diagnosis ; Disease-Free Survival ; Genetics ; Glioblastoma ; Glioma ; Humans ; Necrosis ; Oligodendroglioma ; Pathology ; Prognosis ; Seoul

Objective: To investigate the clinicopathological features of pediatric diffuse midline glioma with H3K27 alteration and to analyze their relationship with prognosis. Methods: Forty-one cases of childhood diffuse midline glioma with H3K27 alteration were collected at Children's Hospital of Fudan University (39 cases) and Xi'an Children's Hospital (2 cases), from July 2016 to July 2020. The clinical manifestations, imaging data, histopathology, immunohistochemical phenotype and molecular genetics features, tumor size, site and histological grading were evaluated. Results: Among the 41 cases, 21 were males and 20 females, the age of onset was 3-14 years, the average and median age was 7.6 years and 7.0 years, respectively. The tumor sites were brain stem (n=36) and other locations (n=5). The clinical manifestations were dizziness, gait disturbance, and limb weakness, etc. The MRI features were variable. The histology varied from low-grade to high-grade glioma with neuron differentiation. Immunohistochemistry showed that the tumor cells expressed H3K27M, GFAP, and Olig2. Genetic study showed that 76% (16/21) of tumors had H3F3A gene mutation, mostly accompanied by TP53 (62%, 13/21) missense mutation; five tumors (24%, 5/21) had HIST1H3B gene mutation, accompanied by missense mutations in ACVR1 and PI3K pathway-related gene PIK3CA (4/5) and PIK3R1 (1/5) mutations. The prognosis was dismal with only one alive and others died. The average and median overall survival time was 7 months and 4 months, respectively. Cox multivariate regression analysis showed that age, tumor location, radiologically maximum tumor diameter, histologic grading, and surgical methods were not significantly associated with overall survival rate (P>0.05). Conclusions: Pediatric diffuse midline gliomas with H3K27 alteration have unique clinicopathological and genetic characteristics. The prognosis is poor. The tumor location and histopathologic grading are not related to prognosis. New specific drugs and comprehensive treatment are needed to improve the prognosis.
Adolescent ; Brain Neoplasms/genetics* ; Child ; Child, Preschool ; Female ; Glioma/pathology* ; Histones/genetics* ; Humans ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Prognosis

To investigate the inhibitory effect and anti-cancer mechanism of adenovirus mediated IL-24 gene expression on the human U251 glioma cell. U251 glioma cells were infected with Ad-IL-24 at various multiplicity of infection (MOIs). Cell proliferation was determined by MTT assay. Cell apoptosis was detected by flow cytometry and Hochest staining. The transcription of apoptosis-related genes was analyzed by reverse transcription-PCR (RT-PCR), and the expression of Cleaved Caspase-3 was analyzed by Western blotting. The result showed that the growth of U251 glioma cells was significantly inhibited by Ad-IL-24 at the MOI of 100. The apoptotic rate of U251 glioma cells was 42% 72 h after infection with Ad-IL-24. Four days after infection, the growth of the U251 glioma cells was inhibited to 50%. RT-PCR showed that Ad-IL-24 not only up-regulated expression of bax/bcl-2, ICE, C-myc, p53 and down-regulated the expression of HIF-1alpha, but also enhanced Caspase-3 activation, eventually resulting apoptosis. Taken together, these results suggest that infection of U251 glioma cells with Ad-IL-24 can inhibit growth and induce apoptosis significantly by the regulation of apoptosis-related genes.
Adenoviridae ; genetics ; metabolism ; Apoptosis ; Brain Neoplasms ; genetics ; pathology ; Cell Proliferation ; drug effects ; Genetic Therapy ; Glioma ; genetics ; pathology ; Humans ; Interleukins ; genetics ; metabolism ; Recombination, Genetic ; Tumor Cells, Cultured

OBJECTIVETo study the expression of RAS protein in human glioma tissues and its influence on tumor growth.

METHODSRAS protein expression in glioma tissues was determined by immunohistochemical (IHC) staining. Subsequently, MTT cell proliferation assay, flow cytometry and Western blotting were used to assay U251 cells with reduced RAS expression.

RESULTSThe expression of RAS in glioma was increased and strongly correlated with pathological grade. Downregulation of RAS resulted in glioma cells growth suppression and increased apoptosis.

CONCLUSIONThe expression level of RAS protein in human glioma was increased. Downregulation of RAS can inhibit glioblastoma cell growth through the RAS signal pathway.

Brain Neoplasms ; genetics ; metabolism ; pathology ; Cell Growth Processes ; genetics ; Cell Line, Tumor ; Down-Regulation ; Glioma ; genetics ; pathology ; Humans ; Immunohistochemistry ; ras Proteins ; biosynthesis ; genetics

OBJECTIVETo study the mechanism involved in the control of glioma cell proliferation with transfection of connexin (Cx) 43 gene.

METHODSC6 rat glioma and TJ905 human glioblastoma cell lines without Cx43 gene expression were transfected with Cx43cDNA mediated by lipofectamine. Northern blot, in situ hybridization and immunohistochemical technology were used to detect the expression of Cx43mRNA and its protein with MTT assay and silver colloid stain for the detection of cell proliferation, TUNEL method for determination of cell apoptosis, scrape loading dye transfer (SLDT) for GJIC, Western blot and immunohistochemical technology for bFGF, PDGF, EGFR, IGF-I and IGFBP3 expression.

RESULTSCx 43 gene transfected glioma cells showed decreased proliferation, restored GJIC and decreased bFGF, PDGF, IGFBP3, except EGFR expression and cell apoptosis which showed no change.

CONCLUSIONThe mechanism of Cx 43 gene inhibiting gliomas cell proliferation is the restoration of GJIC and decreased autocrine growth factors.

Animals ; Apoptosis ; Cell Division ; physiology ; Connexin 43 ; genetics ; physiology ; DNA, Complementary ; genetics ; Glioma ; pathology ; Rats ; Transfection ; Tumor Cells, Cultured