Patients with glioblastoma (GBM) generally have a bad prognosis and short overall survival after being treated with surgery, chemotherapy or radiotherapy due to the histological heterogeneity, strong invasive ability and rapid postoperative recurrence of GBM. The components of GBM cell-derived exosome (GBM-exo) can regulate the proliferation and migration of GBM cell via cytokines, miRNAs, DNA molecules and proteins, promote the angiogenesis via angiogenic proteins and non-coding RNAs, mediate tumor immune evasion by targeting immune checkpoints with regulatory factors, proteins and drugs, and reduce drug resistance of GBM cells through non-coding RNAs. GBM-exo is expected to be an important target for the personalized treatment of GBM and a marker for diagnosis and prognosis of this kind of disease. This review summarizes the preparation methods, biological characteristics, functions and molecular mechanisms of GBM-exo on cell proliferation, angiogenesis, immune evasion and drug resistance of GBM to facilitate developing new strategies for the diagnosis and treatment of GBM.
Humans ; Glioblastoma/genetics* ; Exosomes/metabolism* ; MicroRNAs/metabolism* ; Prognosis ; Cell Proliferation ; Brain Neoplasms/genetics* ; Cell Line, Tumor

Astrocytoma ; genetics ; metabolism ; Brain Neoplasms ; genetics ; metabolism ; Frizzled Receptors ; genetics ; metabolism ; Glioblastoma ; genetics ; metabolism ; Glioma ; genetics ; metabolism ; Humans ; Paraffin Embedding ; RNA, Messenger ; metabolism ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Signal Transduction ; Wnt2 Protein ; genetics ; metabolism ; beta Catenin ; genetics ; metabolism

Animals ; Antigens, Neoplasm ; genetics ; metabolism ; Biomarkers, Tumor ; genetics ; metabolism ; Brain Neoplasms ; metabolism ; Cell Adhesion Molecules ; genetics ; metabolism ; Digestive System Neoplasms ; metabolism ; Female ; Genital Neoplasms, Female ; metabolism ; Glioma ; metabolism ; Head and Neck Neoplasms ; metabolism ; Humans ; Immunotherapy ; Male ; Prostatic Neoplasms ; metabolism ; Signal Transduction

OBJECTIVETo investigate the differential gene expression of ependymomas.

METHODSFour fresh samples of ependymomas and 1 of normal brain tissue were collected during operation. The extracted total RNAs were converted as (32)P tagged cDNA probes, which were then hybridized with the Atlas Human Cancer Array, producing the array based hybridization maps following the protocol provided with the kit. A set of special software was applied to the analysis and RT-PCR was performed to test the result.

RESULTIn comparison with the normal brain tissue, there were 31 upregulated gene and 1 downregulated gene in ependymomas, most of which were firstly found to be differentially expressed in this kind of tumor.

CONCLUSIONThe discrepancy of gene expression profiles between ependymomas and normal brain tissues is highly put through and effectively detected with cDNA array, which provides new information for the further research on the molecular mechanisms of this lesion.

Brain ; metabolism ; Brain Neoplasms ; genetics ; Ependymoma ; genetics ; Gene Expression Profiling ; Humans ; Oligonucleotide Array Sequence Analysis ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVE: To determine the mRNA and protein expressions of RCAS1 in human astrocytic tumors, and to explore the relation between their expression and the genesis and development of tumor. METHODS: The RCAS1 mRNA expression in human astrocytic tumors was evaluated by RT-PCR, and the RCAS1 protein expression was studied by immunohistochemical staining. RESULTS: The quantities of RCAS1 mRNA expression between diffusive astrocytoma(Grade II) and anaplastic astrocytoma(Grade III), anaplastic astrocytoma and glioblastoma(Grade IV) were significantly different(P<0.05), while the expression scores of RCAS1 protein were different only between the anaplastic astrocytoma and glioblastoma(P<0.01). RCAS1 protein expression was positively correlated with the tumor grade (r=0.573,P<0.001). The RCAS1 protein was not detected in normal brain tissues by immunohistochemical staining. CONCLUSION The RCAS1 expression is related to the histological grade of astrocytic tumor. In astrocytic tumors, the RCAS1 expression is regulated transcriptionally and posttranscriptionally.
Adolescent ; Adult ; Aged ; Antigens, Neoplasm ; genetics ; metabolism ; Astrocytoma ; genetics ; metabolism ; Brain Neoplasms ; genetics ; metabolism ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Young Adult

Alzheimer Disease ; metabolism ; Animals ; Brain ; metabolism ; Calcium-Binding Proteins ; biosynthesis ; chemistry ; genetics ; Gastrointestinal Tract ; metabolism ; Humans ; Islets of Langerhans ; metabolism ; Neoplasms ; metabolism ; RNA, Messenger ; metabolism ; Secretagogins ; Thyroid Gland ; metabolism

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 correlate the presence of chromosome 1p/19q deletion with the expression of R132H mutant IDH1 status in oligodendroglial tumors, and to explore molecular markers for predicting chemosensitivity of oligodendroglial tumors.

METHODSThe study included 75 oligodendroglial tumors (38 oligodendrogliomas and 37 oligoastrocytomas). Immunohistochemistry was used to detect the expression of R132H mutant IDH1 protein, and fluorescence in situ hybridization (FISH) was employed to detect 1p/19q deletion.

RESULTSDeletion of chromosome 1p and/or 19q was detected in 37 cases (37/75, 49.3%), among which co-deletion of 1p and 19q was seen in 34 cases (closely correlated, P < 0.01). Oligodendrogliomas WHOIIhad a slightly higher deletion rate than oligodendrogliomas WHO III, although without statistical significance. Oligodendrogliomas WHO IIand WHO III had a significantly higher deletion rate of chromosome 1p/19q than oligoastrocytomas WHO II and WHO III (P < 0.05). While combined loss of 1p/19q was always detected in oligodendrogliomas when FISH was positive, isolated 1p or 19q deletion was only found in oligoastrocytomas. The expression of R132H mutant IDH1 was detected in 51 of 75 cases (68.0%), in which oligodendrogliomas had a higher positive rate than oligoastrocytomas. Statistical analysis demonstrated a significant correlation between the expression of R132H mutant IDH1 protein and the presence of combined 1p/19q deletion in oligodendrogliomas (P < 0.05).

CONCLUSIONSA significant correlation was observed between the expression of R132H mutant protein and 1p/19q LOH.Expression of 132H mutant IDH1 protein is the potential biomarker for predicating the presence of 1p/19q deletion in oligodendrogliomas.

Aged ; Brain Neoplasms ; genetics ; metabolism ; Chromosome Deletion ; Chromosomes, Human, 19-20 ; genetics ; Chromosomes, Human, Pair 1 ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Isocitrate Dehydrogenase ; genetics ; metabolism ; Middle Aged ; Mutant Proteins ; metabolism ; Neoplasm Proteins ; genetics ; metabolism ; Oligodendroglioma ; genetics ; metabolism

At this time, brain tumor stem cells remain a controversial hypothesis while malignant brain tumors continue to present a dire prognosis of severe morbidity and mortality. Yet, brain tumor stem cells may represent an essential cellular target for glioma therapy as they are postulated to be the tumorigenic cells responsible for recurrence. Targeting oncogenic pathways that are essential to the survival and growth of brain tumor stem cells represents a promising area for developing therapeutics. However, due to the multiple oncogenic pathways involved in glioma, it is necessary to determine which pathways are the essential targets for therapy. Furthermore, research still needs to comprehend the morphogenic processes of cell populations involved in tumor formation. Here, we review research and discuss perspectives on models of glioma in order to delineate the current issues in defining brain tumor stem cells as therapeutic targets in models of glioma.
1-Phosphatidylinositol 3-Kinase/genetics/metabolism ; Animals ; Brain Neoplasms/genetics/*metabolism/*pathology/therapy ; Glioma/genetics/*metabolism/*pathology/therapy ; Humans ; Neoplastic Stem Cells/*metabolism/*pathology ; Receptors, Notch/genetics/metabolism ; Signal Transduction/genetics/physiology

OBJECTIVETo investigate the effects of leucine-rich repeats and immunoglobulin-like domains 3 (LRIG3) on the biological activity of glioblastoma cell line GL15.

METHODSGlioblastoma GL15 cells were cultured and transfected with LRIG3-EGFP plasmid. The location of LRIG3 in GL15 cells was observed with confocal microscopy. The proliferation and invasiveness of GL15 cells were detected with methyl thiazolyl tetrazolium (MTT) and Transwell methods respectively; the expression of epidermal growth factor receptor (EGFR) and LRIG3 mRNA and protein were detected with reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot respectively.

RESULTAfter transfection with the plasmid LRIG-EGFP, LRIG3 fusion protein was found in cytoplasm of GL15 cells and cell proliferative and invasiveness were reduced. The expression of EGFR and LRIG3 varied with the duration of EGF treatment (100 ng/ml): the expression of EGFR decreased while the expression of LRIG3 increased as time prolonged.

CONCLUSIONLRIG3 can inhibit the proliferation and invasiveness of glioblastoma cells and may be used as a target gene in gene therapy of glioblastoma.

Brain Neoplasms ; pathology ; Cell Proliferation ; Epidermal Growth Factor ; genetics ; Glioblastoma ; pathology ; Humans ; Membrane Proteins ; genetics ; metabolism ; Neoplasm Invasiveness ; Plasmids ; genetics ; RNA, Messenger ; genetics ; metabolism ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Recombinant Fusion Proteins ; genetics ; metabolism ; Transfection ; Tumor Cells, Cultured