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)

The purpose of this study is to investigate how the insulin-like growth factor I receptor (IGF-IR) affects cellular radiosensitivity when cells are cultured under different growth conditions. For this, A7(R) and A7(puro) cells were established from human glioblastoma GB A7 cells. The former were derived from the parent cells by stable cotransfection with plasmids carrying human IGF-IR cDNA and a puromycin resistance gene and the latter had the marker gene alone. The cells were either grown exponentially in monolayer cultures or grown in multicellular spheroids as an in vitro model for solid tumors. Spheroids were formed in the two different methods, liquid-overlay (LOC) and spinner (SPC) cultures. Although the growth rate of both cell lines in monolayer was exactly the same, the growth rate of A7(R) spheroids formed in LOC was higher than that of A7(puro) spheroids. A central necrosis region was histologically observed in A7(puro) spheroids, but the corresponding region in A7(R) spheroids was almost completely filled with intact cells in both LOC and SPC spheroids. Both cell lines showed the same radiosensitivity in monolayer cultures in terms of cell viability and clonogenic cell survival. When the spheroids formed in LOC were X-irradiated, the radiosensitivity of A7(R) and A7(puro) cells assayed for cellular clonogenicity was also the same. However, in the spheroids formed in SPC, A7(R) cells were significantly more radiosensitive than A7(puro) cells. The results indicate that overexpression of the IGF-IR could induce radiosensitization of human tumor cells in spheroids while inhibiting spontaneous necrosis formation. This may open a possibility to explore the novel function of the IGF-IR.
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PMID:Differential effects of the insulin-like growth factor I receptor on radiosensitivity and spontaneous necrosis formation of human glioblastoma cells grown in multicellular spheroids. 1038 24

Long-term survival remains low for most patients with glioblastoma (GBM), which reveals the need for markers of disease outcome and novel therapeutic targets. We describe that ODZ1 (also known as TENM1), a type II transmembrane protein involved in fetal brain development, plays a crucial role in the invasion of GBM cells. Differentiation of glioblastoma stem-like cells drives the nuclear translocation of an intracellular fragment of ODZ1 through proteolytic cleavage by signal peptide peptidase-like 2a. The intracellular fragment of ODZ1 promotes cytoskeletal remodelling of GBM cells and invasion of the surrounding environment both in vitro and in vivo. Absence of ODZ1 by gene deletion or downregulation of ODZ1 by small interfering RNAs drastically reduces the invasive capacity of GBM cells. This activity is mediated by an ODZ1-triggered transcriptional pathway, through the E-box binding Myc protein, that promotes the expression and activation of Ras homolog family member A (RhoA) and subsequent activation of Rho-associated, coiled-coil containing protein kinase (ROCK). Overexpression of ODZ1 in GBM cells reduced survival of xenografted mice. Consistently, analysis of 122 GBM tumour samples revealed that the number of ODZ1-positive cells inversely correlated with overall and progression-free survival. Our findings establish a novel marker of invading GBM cells and consequently a potential marker of disease progression and a therapeutic target in GBM.
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PMID:ODZ1 allows glioblastoma to sustain invasiveness through a Myc-dependent transcriptional upregulation of RhoA. 2764 32

MicroRNAs (miR) are known to be critical regulators in tumor progression. miR-7-5p was reported to be involved in several cancers, including glioblastoma, cervical cancer, and melanoma, but its prognostic value and biological function in non-small-cell lung cancer (NSCLC) remain unclear. In this study, using quantitative real-time PCR analysis, we found that miR-7-5p was significantly downregulated in NSCLC tissues and cell lines. Lower miR-7-5p expression was associated with tumor-node-metastasis stage and tumor size by chi-squared test. Deceased miR-7-5p expression was associated with a worse prognosis in patients with NSCLC using Kaplan-Meier survival analysis and multivariate Cox regression analysis. Experiments in NSCLC cell lines (A549 and H1299) demonstrated that upregulation of miR-7-5p significantly suppressed cell proliferation, but induced cell cycle G0/G1 phase arrest and apoptosis using Cell Counting Kit-8, colony formation, and flow cytometry analysis. Through loss-of-function assays, we further demonstrated that downregulation of miR-7-5p promoted cell proliferation and cell cycle G1/S transition, but decreased cell apoptosis in SPC-A1 cells. Furthermore, P21-activated kinase 2 (PAK2) was predicted and confirmed as a direct target gene of miR-7-5p in NSCLC cells by luciferase reporter assay. In addition, we found PAK2 overexpression could partially reverse the effects of miR-7-5p on cell proliferation, cell cycle distribution, and apoptosis. We thus concluded that lower expression of miR-7-5p was associated with poor prognosis and NSCLC progression by directly targeting PAK2.
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PMID:MicroRNA-7-5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non-small cell lung cancer. 3158 74