Similar Datasets
Project description:First in class small molecule inhibitor of oncogene AVIL in glioblastoma
| PRJNA1119199 | ENA
Project description:Glioblastoma multiforme (GBM) is a central nervous system tumour. The current standard care for GMB is surgical resection, followed by conventional radiotherapy (RT) often combined with daily drug (temozolomide) administration. However, these treatment modalities are not currently curative and the resistance to both chemotherapy and RT plans is the main cause of GBM care failures. In this scenario, proton therapy (PT) could be used as a successful strategy for GBM treatment, being able to regulate the balance between tumour control and the normal tissue tolerance. In addition, new drugs could be used as radiosensitizing agents combined with PT in order to optimize GBM care. In this work we analyzed the GEP of the U87 MG human glioblastoma cell line, after treatment with PT alone or in combination with a new targeted compound, named Si306 (property of Lead Discovery Siena, Siena, Italy). We described GEP induced by both treatments, highlighting for the first time, the cell pathways induced by Si306. Summarizing, our results suggesting this compound as a novel possible candidate to treat GBM in combination with PT.
2019-11-04 | GSE127989 | GEO
Project description:Angiogenesis inhibitors, such as sunitinib, represent a promising strategy to improve glioblastoma (GBM) tumor response. In this study, we used the O6-methylguanine methyltransferase (MGMT)-negative GBM cell line U87MG stably transfected with MGMT (U87/MGMT) to assess whether MGMT expression affects the response to sunitinib. We showed that the addition of sunitinib to standard therapy (temozolomide [TMZ] and radiation therapy [RT]) significantly improved the response of MGMT positive but not of MGMT-negative cells. Gene expression profiling revealed alterations in the angiogenic profile, as well as differential expression of several receptor tyrosine kinases targeted by sunitinib. MGMT-positive cells displayed higher levels of vascular endothelial growth factor receptor 1 (VEGFR-1) compared with U87/EV cells, whereas they displayed decreased levels of VEGFR-2. Depleting MGMT using O6-benzylguanine suggested that the expression of these receptors was directly related to the MGMT status. Also, we showed that MGMT expression was associated with a dramatic increase in the soluble VEGFR-1/VEGFA ratio, thereby suggesting a decrease in bioactive VEGFA and a shift towards an antiangiogenic profile. The reduced angiogenic potential of MGMT-positive cells is supported by: (i) the decreased ability of their secreted factors to induce endothelial tube formation in vitro and (ii) their low tumorigenicity in vivo compared with the MGMT-negative cells. Our study is the first to show a direct link between MGMT expression and decreased angiogenicity and tumorigenicity of GBM cells and suggests the combination of sunitinib and standard therapy as an alternative strategy for GBM patients with MGMT-positive tumors. RNA was isolated from parental U87 (U87_EV) and MGMT-transfected U87 (U87_MGMT) triplicate. Pairwise gene expression differences were compared between the two cell lines. Features selected had more than 2-fold up-or down-regulated (P values of >05, unpaired Studentâs t-test with Bonferroni multiple testing correction) were identified. Database for annotation, visualization, and integrated discovery23 was used to identify enriched gene ontology (GO) biological themes.24 The GO data mining was conducted at a term specificity level 3.25 The EASE score was set at 0.05 and the minimum number of genes in a category was 5.
2012-09-11 | E-GEOD-40776 | biostudies-arrayexpress
Project description:To investigate the function of GNE987 in the regulation of gene expression, we treated U87 cells with control (DMSO) or GNE987, respectively. We then performed gene expression profiling analysis using data obtained from RNA-seq of control and GNE987 treatment.
2022-11-09 | GSE202362 | GEO
Project description:The transcriptome dataset has been used to validate on a GBM patient cohort (n=117) the IRE1-dependent gene expression signature identified in U87 cell line.
2018-01-09 | E-MTAB-6326 | biostudies-arrayexpress
Project description:Glioblastomas (GBM) are one of the most frequent and aggressive brain tumors. In these malignancies, progesterone (P4) promotes proliferation, migration, and invasion. The P4 metabolite allopregnanolone (3α-THP) similarly promotes cell proliferation in the U87 human GBM cell line. Here, we evaluated global changes in gene expression of U87 cells treated with 3α-THP, P4, and the 5α-reductase inhibitor, finasteride (F).
2018-02-11 | GSE108998 | GEO
Project description:We report the application of mRNA sequencing technology for high-throughput profiling of genes expression changes in U87 glioblastoma cells after treatment with compound YZ129 that we identified in our screen. By analyzing the total mRNA sequencing between YZ129 treatment group and the DMSO control group, we identified that 181 genes were significantly downregulated (changed >2 folds), while 226 genes were significantly upregulated (changed >2 folds). The downregulated genes were mainly associated with hypoxia (ALDOC, TMEM45A, F3, FOS, GFBP1, etc), glycolysis (SLC2A1, ANGPTL4, ENO2, LDHA, PGM, PFKFB3, etc.), PI3K/AKT/mTOR pathway (AK4, SLC2A1, PDK1, PGM1, PLOD2, TUBA4A, etc.), EMT (epithelial-mesenchymal transition) (VEGFA, ID2, COL1A1, FOXC2, LOXL2, etc.), G2/M checkpoint (UBE2C, FBXO5 (Emi1), TOP2A, MCM5/6), etc. some of the upregualted genes may contribute to the possible chemoresistance, such as FOSB, INHBA, EDN1, IRS2, KDM6B. This study yields a global view on molecular response to YZ29 treatment in GBM cells at mRNA level.
2018-10-01 | GSE108749 | GEO
Project description:Total RNA extracted from knockdown or overexpress AVIL in GBM U87 cells. and RNA-seq after sample quality control.
2020-06-08 | GSE95164 | GEO
Project description:Angiogenesis inhibitors, such as sunitinib, represent a promising strategy to improve glioblastoma (GBM) tumor response. In this study, we used the O6-methylguanine methyltransferase (MGMT)-negative GBM cell line U87MG stably transfected with MGMT (U87/MGMT) to assess whether MGMT expression affects the response to sunitinib. We showed that the addition of sunitinib to standard therapy (temozolomide [TMZ] and radiation therapy [RT]) significantly improved the response of MGMT positive but not of MGMT-negative cells. Gene expression profiling revealed alterations in the angiogenic profile, as well as differential expression of several receptor tyrosine kinases targeted by sunitinib. MGMT-positive cells displayed higher levels of vascular endothelial growth factor receptor 1 (VEGFR-1) compared with U87/EV cells, whereas they displayed decreased levels of VEGFR-2. Depleting MGMT using O6-benzylguanine suggested that the expression of these receptors was directly related to the MGMT status. Also, we showed that MGMT expression was associated with a dramatic increase in the soluble VEGFR-1/VEGFA ratio, thereby suggesting a decrease in bioactive VEGFA and a shift towards an antiangiogenic profile. The reduced angiogenic potential of MGMT-positive cells is supported by: (i) the decreased ability of their secreted factors to induce endothelial tube formation in vitro and (ii) their low tumorigenicity in vivo compared with the MGMT-negative cells. Our study is the first to show a direct link between MGMT expression and decreased angiogenicity and tumorigenicity of GBM cells and suggests the combination of sunitinib and standard therapy as an alternative strategy for GBM patients with MGMT-positive tumors.
2012-09-11 | GSE40776 | GEO
Project description:Purpose:Glioblastoma (GBM) is the most common primary brain tumor in adults with poor prognosis and short medial survival after therapy. we have utilized U87-MG cell line as a human GBM cell model and human brain HEB cell line as non-neoplastic brain cell cultured in normoxia and 1% O2 hypoxia for transcriptional profiling to gain further insight into the molecular underpinnings that maintained the properties of GBM andclarify the molecular mechanism of hypoxia resistance of GBM. Methods:We have utilized U87-MG cell line as a human GBM cell model and human brain HEB cell line as non-neoplastic brain cell cultured in normoxia and 1% O2 hypoxia for transcriptional profiling. And validating the analysis results with specimens of GBM patients. Results: Firstly, the resulting data set revealed previously unknown proteins, including AKR1B1, MT2A, UBC, EEF1A1 and MTRNR2l2 in U87-MG cells, which promoted GBM characters through MAPK pathway. Meanwhile, we found that toll-like pathway was a new avenue mediating the function of inflammatory response in GBM. Furthermore, The results suggested that cytokine TGF-β1 and HIFs’ targeted genes, including HMOX1 and STC1 could be regard as hypoxic markers for GBM. Conclusion:Taken together, our study identified new potential biomarkers and illustrated the genes associated with inflammation in GBM. More importantly, the unique pattern to hypoxia implied new insight for the GBM research of hypoxia resistance and recurrence in future.
2019-09-11 | GSE77307 | GEO