Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to study the clinicopathological features, histogenesis and prognosis, 12 cases of gliosarcoma were reported representing 0.4% of a series of 2743 patients undergoing biopsy for CNS tumors. All the tumors originated from the cerebral hemispheres with a predilection for the temporal lobes. Half of the cases show more firm consistency and are rather well demarcated from brain tissue. Clinically, they are sometimes mistaken for meningiomas. Of the 10 patients with follow-up, 9 have died. The mean survival period after operation was 8 months, 1 cases is still alive and well for 3.2 years. There were some cases in which the origin of spindle cell populations could not be determined by H & E staining. Glioblastoma and malignant fibrous histiocytoma (MFH) element of the tumor was confirmed by electron microscopical examination and immunohistochemical stains for GFAP, Mac 387, VIM, FV III RA, etc. Osteosarcoma component in the tumor was detected in one case. It was accepted that MFH arose from the primitive uncommited mesenchyme.
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PMID:[A clinical and pathological study of gliosarcoma]. 927 62

Experimental models relating to human glioblastoma multiformes (hGBMs) involve the intracranial or intracerebral injection of human GBM cells into nude mice or rats. The aim of the present study was to compare a number of biological characteristics of hGBMs as opposed to experimental GBMs obtained by grafting either human U87 or U373 glioblastoma cells into the brains of nude mice. Biological assessments involve four distinct sets of parameters, i.e. i) the determination of the nuclear DNA content, ii) the determination of proliferative activity, iii) the assessment of p53 nuclear phosphoprotein immunohistochemical reactivity, and iv) the assessment of GFAP, VIM, LEU-7, S-100 and CAT D protein immunohistochemical reactivity. While most of the human glioblastoma multiformes (hGBMs) under study were immunohistochemically reactive to GFAP, S-100, LEU-7 and VIM as indeed were the experimental U373 GBMs, the U87 ones were reactive to VIM only. Furthermore, the U87 GBMs appeared to be more aggressive than the U373 ones since the former were associated with a shorter tumor-bearing mouse survival time than the latter. Such aggressiveness was further associated with a proliferative activity and a cathepsin D immunoreactivity, both of which were markedly higher in the U87 GBMs than in the U373 GBMs. These two experimental GBM models also exhibited tumors which were predominantly diploid. The present study shows that it is possible to set up experimentally in vivo models which strongly mimic human glioblastoma multiformes. Such models consist of grafting human glioblastoma cell lines, namely U87 and U373, into the brains of nude mice. However, while it is true that experimental GBMs closely resemble the hGBMs with respect to some biological characteristics, they also differ in many other significant biological characteristics.
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PMID:The characterization of nuclear-DNA content, the proliferative activity and the immunohistochemical expression of gfap, vim, leu-7, s-100, p53 and cathepsin-d in human glioblastoma multiformes (hgbms) versus human gbm cell-lines grafted into the brains of nude-mice. 2155 62

Molecular signatures in Glioblastoma (GBM) have been described that correlate with clinical outcome and response to therapy. The Proneural (PN) and Mesenchymal (MES) signatures have been identified most consistently, but others including Classical (CLAS) have also been reported. The molecular signatures have been detected by array techniques at RNA and DNA level, but these methods are costly and cannot take into account individual contributions of different cells within a tumor. Therefore, the aim of this study was to investigate whether subclasses of newly diagnosed GBMs could be assessed and assigned by application of standard pathology laboratory procedures. 123 newly diagnosed GBMs were analyzed for the tumor cell expression of 23 pre-identified proteins and EGFR amplification, together allowing for the subclassification of 65% of the tumors. Immunohistochemistry (IHC)-based profiling was found to be analogous to transcription-based profiling using a 9-gene transcriptional signature for PN and MES subclasses. Based on these data a novel, minimal IHC-based scheme for subclass assignment for GBMs is proposed. Positive staining for IDH1R132H can be used for PN subclass assignment, high EGFR expression for the CLAS subtype and a combined high expression of PTEN, VIM and/or YKL40 for the MES subclass. The application of the proposed scheme was evaluated in an independent tumor set, which resulted in similar subclass assignment rates as those observed in the training set. The IHC-based subclassification scheme proposed in this study therefore could provide very useful in future studies for stratification of individual patient samples.
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PMID:Subclassification of newly diagnosed glioblastomas through an immunohistochemical approach. 2554 4

The epithelial-to-mesenchymal (-like) transition (EMT), a crucial embryonic development program, has been linked to the regulation of glioblastoma (GBM) progression and invasion. Here, we investigated the role of MIR517C/miR-517c, which belongs to the C19MC microRNA cluster identified in our preliminary studies, in the pathogenesis of GBM. We found that MIR517C was associated with improved prognosis in patients with GBM. Furthermore, following treatment with the autophagy inducer temozolomide (TMZ) and low glucose (LG), MIR517C degraded KPNA2 (karyopherin alpha 2 [RAG cohort 1, importin alpha 1]) and subsequently disturbed the nuclear translocation of TP53 in the GBM cell line U87 in vitro. Interestingly, this microRNA could inhibit autophagy and reduce cell migration and infiltration in U87 cells harboring wild-type (WT) TP53, but not in U251 cells harboring mutant (MU) TP53. Moreover, the expression of epithelial markers (i.e., CDH13/T-cadherin and CLDN1 [claudin 1]) increased, while the expression of mesenchymal markers (i.e., CDH2/N-cadherin, SNAI1/Snail, and VIM [vimentin]) decreased, indicating that the EMT status was blocked by MIR517C in U87 cells. Compared with MIR517C overexpression, MIR517C knockdown promoted infiltration of U87 cells to the surrounding structures in nude mice in vivo. The above phenotypic changes were also observed in TP53(+/+) and TP53(-/-) HCT116 colon cancer cells. In summary, our study provided support for a link between autophagy and EMT status in WT TP53 GBM cells and provided evidence for the signaling pathway (MIR517C-KPNA2-cytoplasmic TP53) involved in attenuating autophagy and eliminating the increased migration and invasion during the EMT.
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PMID:MIR517C inhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation. 3092 Mar 34

Glioblastoma multiforme is the most frequent primary malignancy of the central nervous system. Despite remarkable progress towards an understanding of tumor biology, there is no efficient treatment and patient outcome remains poor. Here, we present a unique anti-proteomic approach for selection of nanobodies specific for overexpressed glioblastoma proteins. A phage-displayed nanobody library was enriched in protein extracts from NCH644 and NCH421K glioblastoma cell lines. Differential ELISA screenings revealed seven nanobodies that target the following antigens: the ACTB/NUCL complex, VIM, NAP1L1, TUFM, DPYSL2, CRMP1, and ALYREF. Western blots showed highest protein up-regulation for ALYREF, CRMP1, and VIM. Moreover, bioinformatic analysis with the OncoFinder software against the complete "Cancer Genome Atlas" brain tumor gene expression dataset suggests the involvement of different proteins in the WNT and ATM pathways, and in Aurora B, Sem3A, and E-cadherin signaling. We demonstrate the potential use of NAP1L1, NUCL, CRMP1, ACTB, and VIM for differentiation between glioblastoma and lower grade gliomas, with DPYSL2 as a promising "glioma versus reference" biomarker. A small scale validation study confirmed significant changes in mRNA expression levels of VIM, DPYSL2, ACTB and TRIM28. This work helps to fill the information gap in this field by defining novel differences in biochemical profiles between gliomas and reference samples. Thus, selected genes can be used to distinguish glioblastoma from lower grade gliomas, and from reference samples. These findings should be valuable for glioblastoma patients once they are validated on a larger sample size.
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PMID:Differentially expressed proteins in glioblastoma multiforme identified with a nanobody-based anti-proteome approach and confirmed by OncoFinder as possible tumor-class predictive biomarker candidates. 2849 3

As a hallmark for glioblastoma (GBM), high heterogeneity causes a variety of phenotypes and therapeutic responses among GBM patients, and it contributes to treatment failure. Moreover, hypoxia is a predominant feature of GBM and contributes greatly to its phenotype. To analyse the landscape of gene expression and hypoxic characteristics of GBM cells and their clinical significance in GBM patients, we performed transcriptome analysis of the GBM cell line U87-MG and the normal glial cell line HEB under normoxia and hypoxia conditions, with the results of which were analysed using established gene ontology databases as well as The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia. We revealed core signal pathways, including inflammation, angiogenesis and migration, and for the first time mapped the components of the toll-like receptor 6 pathway in GBM cells. Moreover, by investigating the signal pathways involved in homoeostasis, proliferation and adenosine triphosphate metabolism, the critical response of GBM to hypoxia was clarified. Experiments with cell lines, patient serum and tissue identified IL1B, CSF3 and TIMP1 as potential plasma markers and VIM, STC1, TGFB1 and HMOX1 as potential biopsy markers for GBM. In conclusion, our study provided a comprehensive understanding for signal pathways and hypoxic characteristics of GBM and identified new biomarkers for GBM patients.
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PMID:Integrated analysis identified core signal pathways and hypoxic characteristics of human glioblastoma. 3128 8

Glioblastoma (GBM), the most common primary brain tumor, is a complex and extremely aggressive disease. Despite recent advances in molecular biology, there is a lack of biomarkers, which would improve GBM's diagnosis, prognosis, and therapy. Here, we analyzed by qPCR the expression levels of a set of miRNAs in GBM and lower-grade glioma human tissue samples and performed a survival analysis in silico. We then determined the expression of same miRNAs and their selected target mRNAs in small extracellular vesicles (sEVs) of GBM cell lines. We showed that the expression of miR-21-5p was significantly increased in GBM tissue compared to lower-grade glioma and reference brain tissue, while miR-124-3p and miR-138-5p were overexpressed in reference brain tissue compared to GBM. We also demonstrated that miR-9-5p and miR-124-3p were overexpressed in the sEVs of GBM stem cell lines (NCH421k or NCH644, respectively) compared to the sEVs of all other GBM cell lines and astrocytes. VIM mRNA, a target of miR-124-3p and miR-138-5p, was overexpressed in the sEVs of U251 and U87 GBM cell lines compared to the sEVs of GBM stem cell line and also astrocytes. Our results suggest VIM mRNA, miR-9-5p miRNA, and miR-124-3p miRNA could serve as biomarkers of the sEVs of GBM cells.
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PMID:Analysis of miR-9-5p, miR-124-3p, miR-21-5p, miR-138-5p, and miR-1-3p in Glioblastoma Cell Lines and Extracellular Vesicles. 3318 34

The tumor resistance of glioblastoma cells in vivo is thought to be enhanced by their heterogeneity and plasticity, which are extremely difficult to curb in vitro. The external microenvironment shapes the molecular profile of tumor culture models, thus influencing potential therapy response. Our study examines the expression profile of selected lncRNAs involved in tumor resistance network in three different glioblastoma-derived models commonly utilized for testing drug response in vitro. Differential expression analysis revealed significant divergence in lncRNA profile between parental tumors and tumor-derived cell cultures in vitro, including the following particles: MALAT1, CASC2, H19, TUSC7, XIST, RP11-838N2.4, DLX6-AS1, GLIDR, MIR210HG, SOX2-OT. The examined lncRNAs influence the phenomenon of tumor resistance via their downstream target genes through a variety of processes: multi-drug resistance, epithelial-mesenchymal transition, autophagy, cell proliferation and viability, and DNA repair. A comparison of in vivo and in vitro expression identified differences in the levels of potential lncRNA targets, with the highest discrepancies detected for the MDR1, LRP1, BCRP and MRP1 genes. Co-expression analyses confirmed the following interrelations: MALAT1-TYMS, MALAT1-MRP5, H19-ZEB1, CASC2-VIM, CASC2-N-CAD; they additionally suggest the possibility of MALAT1-BCRP, MALAT1-mTOR and TUSC7-PTEN interconnections in glioblastoma. Although our results clearly demonstrate that the artificial ex vivo microenvironment changes the profile of lncRNAs related to tumor resistance, it is difficult to anticipate the final phenotypic effect, since this phenomenon is a complex one that involves a network of molecular interactions underlying a variety of cellular processes.
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PMID:If Artificial In Vitro Microenvironment Can Influence Tumor Drug Resistance Network via Modulation of lncRNA Expression?-Comparative Analysis of Glioblastoma-Derived Cell Culture Models and Initial Tumors In Vivo. 3324 8