Microarray whole transcriptome profiling of Sepantronium bromide (YM-155) treated MDA-MB-231 cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE103089 | GEO | 2017/08/26
SECONDARY ACCESSION(S): PRJNA400175
REPOSITORIES: GEO
Similar Datasets
Project description:Microarray whole transcriptome profiling of Sepantronium bromide (YM-155) treated MDA-MB-231 cells
| PRJNA400175 | ENA
Project description:For the clinical treatment of chronic obstructive pulmonary disease (COPD), it is important not only to improve the airflow limitation by bronchodilation but also to suppress emphysema by controlling inflammation. In this study, we have screened for compounds that prevent elastase-induced airspace enlargement in mice from medicines already used clinically. Mepenzolate bromide, a muscarinic antagonist used to treat gastrointestinal disorders was selected. Intratracheal administration or inhalation of mepenzolate bromide decreased the severity of elastase-induced airspace enlargement, alteration of lung mechanics and respiratory dysfunction. While mepenzolate bromide showed bronchodilatory activity, most of other muscarinic antagonists tested did not improve the elastase-induced pulmonary disorders. Mepenzolate bromide suppressed elastase-induced pulmonary inflammatory responses and production of superoxide anions, and reduced the level of cigarette smoke-induced airspace enlargement and alteration of lung mechanics. Based on these results, we propose that this drug is therapeutically effective for COPD as a consequence of both its anti-inflammatory and bronchodilatory activities.
2013-11-13 | GSE50836 | GEO
Project description:Sepantronium bromide (YM155), a transcriptional inhibitor of anti-apoptotic protein survivin, is considered as a potential drug candidate for triple negative breast cancers (TNBC). Regardless of its excellent performance in pre-clinical models of TNBC, in patients, this drug was unable to outperform the standard chemotherapy docetaxel. The goal of this study was to identify the pathways/molecules affected by YM155 in TNBC cell lines. Detailed biochemical analysis of the paired YM155-sensitive and resistant cell lines indicates that induction of mitochondrial oxidative stress is a first-line response to the drug, ultimately leading to growth inhibition and induction of cell death. Multiple pathways involved in dampening oxidative stress-induced damages are differentially regulated in YM155-resistant cells. Furthermore, the emergence of YM155 resistance is associated with an extensive transcriptional reprogramming and alteration of many more biological pathways in addition to those identified by biochemical assays. Molecules associated with these biological pathways will potentially serve as biomarkers predicting YM155 sensitivity in TNBC cells.
2020-10-24 | GSE139364 | GEO
Project description:For the clinical treatment of chronic obstructive pulmonary disease (COPD), it is important not only to improve the airflow limitation by bronchodilation but also to suppress emphysema by controlling inflammation. In this study, we have screened for compounds that prevent elastase-induced airspace enlargement in mice from medicines already used clinically. Mepenzolate bromide, a muscarinic antagonist used to treat gastrointestinal disorders was selected. Intratracheal administration or inhalation of mepenzolate bromide decreased the severity of elastase-induced airspace enlargement, alteration of lung mechanics and respiratory dysfunction. While mepenzolate bromide showed bronchodilatory activity, most of other muscarinic antagonists tested did not improve the elastase-induced pulmonary disorders. Mepenzolate bromide suppressed elastase-induced pulmonary inflammatory responses and production of superoxide anions, and reduced the level of cigarette smoke-induced airspace enlargement and alteration of lung mechanics. Based on these results, we propose that this drug is therapeutically effective for COPD as a consequence of both its anti-inflammatory and bronchodilatory activities. In order to understand the mechanism governing mepenzolate-dependent decrease in inflammatory responses and oxidative stress, we performed DNA microarray analysis at the lung of mepenzolate-administered (or control) mice. We then analyzed gene sets that were differently expressed at 25 hours after administration of mepenzolate using Gene Set Enrichment Analysis (GSEA).
2013-11-13 | E-GEOD-50836 | biostudies-arrayexpress
Project description:Background: Survivin was described as strongly expressed in human cancer. To date, little is known about the association between Survivin splice variants and the other apoptosis-related genes. In this study, we analyzed the apoptosis gene signature of Survivin and its variant expression in breast cancer. Methods: Expression of the 5 transcripts was measured by RT-PCR in 135 breast carcinomas. Human Apoptosis Gene Arrays were used to screen the genes that could be associated with Survivin variants. Cox survival analysis was analyzed according to the breast cancer patient outcome. Results: Significant associations between Survivin transcript and the apoptotic gene array were found. Interestingly, Survivin-3B variant showed major inverse correlations with the pro-apoptotic gene array. Overexpression of Survivin-3B strongly inhibits 5-fluorouracil/epirubicin/Cyclophosphamide induced-apoptosis in breast tumor cell lines. In breast carcinomas, uni- and multivariate analysis showed patients with high level of survivin-3B expression had a shorter overall (p=0.030 and p=0.042, respectively) and disease-free (p=0.024 and p=0.009) survival. Conclusion: Our data indicate Survivin-3B could have an anti-apoptotic activity and its expression level might be used as a prognostic marker in breast carcinoma. The expression of 96 apoptosis genes and was analyzed in 41 breast carcinomas and 1 pool of normal mammary tissues. In parallel, every survivin isoform expression was quantified by real-time quantitative PCR. Data obtained with the macro-array were correlated with survivin isoform levels detected by RT-PCR.
2010-10-06 | E-GEOD-24556 | biostudies-arrayexpress
Project description:Background: Survivin was described as strongly expressed in human cancer. To date, little is known about the association between Survivin splice variants and the other apoptosis-related genes. In this study, we analyzed the apoptosis gene signature of Survivin and its variant expression in breast cancer. Methods: Expression of the 5 transcripts was measured by RT-PCR in 135 breast carcinomas. Human Apoptosis Gene Arrays were used to screen the genes that could be associated with Survivin variants. Cox survival analysis was analyzed according to the breast cancer patient outcome. Results: Significant associations between Survivin transcript and the apoptotic gene array were found. Interestingly, Survivin-3B variant showed major inverse correlations with the pro-apoptotic gene array. Overexpression of Survivin-3B strongly inhibits 5-fluorouracil/epirubicin/Cyclophosphamide induced-apoptosis in breast tumor cell lines. In breast carcinomas, uni- and multivariate analysis showed patients with high level of survivin-3B expression had a shorter overall (p=0.030 and p=0.042, respectively) and disease-free (p=0.024 and p=0.009) survival. Conclusion: Our data indicate Survivin-3B could have an anti-apoptotic activity and its expression level might be used as a prognostic marker in breast carcinoma.
2010-10-06 | GSE24556 | GEO
Project description:RNA seq of human fibroblasts treated with Rocuronium bromide
| PRJEB52816 | ENA
Project description:Genetically encoded unnatural amino acids (Uaas) with electrophilic moieties are excellent tools to investigate protein-protein interactions (PPIs) both in vitro and in vivo. These Uaas, including a series of alkyl bromide-based Uaas, mainly target cysteine residues to form protein-protein cross-links. Although some reactivities towards lysine and tyrosine residues have been reported, a comprehensive understanding of their reactivity towards a broad range of nucleophilic amino acids is lacking. Here we used a recently developed OpenUaa search engine to perform an in-depth analysis of mass spec data generated for Thioredoxin and its direct binding proteins cross-linked with an alkyl bromide-based Uaa, BprY. The analysis showed that, besides cysteine residues, BprY also targeted a broad range of nucleophilic amino acids. We validated this broad reactivity of BprY with Affibody/Z protein complex. We then successfully applied BprY to map a binding interface between SUMO2 and SUMO-interacting motifs (SIMs). BprY was further applied to probe SUMO2 interaction partners. We identified 264 SUMO2 binders, including several validated SUMO2 binders and many new binders. Our data demonstrated that BprY can be effectively used to probe protein-protein interfaces even without cysteine residues, which will greatly expand the power of BprY in studying PPIs.
2022-04-04 | PXD031159 | Pride
Project description:The liver possesses remarkable regenerative capacity in response to injury. Upon partial hepatectomy (PHx), terminally differentiated hepatocytes in the remaining liver enter the cell cycle and restore the liver mass and function within weeks. However, liver regeneration is often impaired in livers with chronic diseases. Survivin, an inhibitor of apoptosis protein (IAP) and member of chromosome passenger complex (CPC), plays versatile roles in cell mitosis and apoptosis. We and others found that the expression of Survivin was highly increased in liver during PHx-induced liver regeneration, which indicated that Survivin played important roles in this process. However, the function of Survivin in liver regeneration remains largely undefined. Here, using mice with genetic deletion of Survivin, we found that during PHx-induced liver regeneration Survivin regulated both hepatocyte G1/S phase transition by inhibiting the expression of p21 and G2/M phase transition by regulating the localization of CPC. Moreover, restoration of Survivin expression in Survivin-deficient hepatocytes inhibited p21 expression and promote both hepatocyte G1/S and G2/M transition during PHx-induced liver regeneration.
2017-01-01 | GSE83598 | GEO
Project description:Stem cells (SCs) and not progenitors (Ps) act as cells of origin of Basal Cell Carcinoma (BCC). The mechanisms promoting BCC formation in SCs or restricting tumour development in Ps are currently unknown. In this study, we transcriptionally profiled SCs and Ps and found that Survivin, a pleiotropic factor that promotes cell division and inhibits apoptosis was preferentially expressed in SCs. Using genetic gain and loss of function mouse models, we showed that Survivin deletion in oncogene-expressing SCs prevents BCC formation. Survivin overexpression renders Ps competent to BCC formation by promoting cell survival and division while preventing apoptosis and differentiation. We identified SGK1, as a key downstream factor of Survivin, and its inhibition prevents BCC formation. This study uncovers the role and mechanisms by which Survivin regulates the competence of SCs to initiate BCC formation promoting the survival of oncogene-expressing SCs and self-renewing division while restricting differentiation and apoptosis.
2024-11-06 | GSE277554 | GEO