Ena-DATASET-DFCI-19-12-2017-12:35:35:004-102 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001003887 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Sequencing was performed using OncoPanel v.2 (OPv2), an Agilent SureSelect custom designed bait set consisting of the coding regions of 504 genes, previously linked to human cancer. Sequencing wa sperformed on an Illumina HiSeq 2500. 14 highly differentiated, fusion-negative rhabdomyosarcoma tumor samples, and 8 non-matched normal skeletal muscle samples weer sequenced. BAM files are available for download.
| EGAD00001003746 | EGA
Project description:Pediatric PAX-FOXO1 fusion-negative rhabdomyosarcoma represents a diverse spectrum of tumors. In this study, the mutational spectrum of 22 fusion-negative rhabdomyosarcomas with high, rhabdomyoma-like levels of differentiation was evaluated using OncoPanel v.2 (OPv2), an Agilent SureSelect custom designed bait set consisting of the coding regions of 504 cancer-relevant genes. Corresponding normal tissue was not available. Discarded normal human skeletal muscle, obtained from 7 donors without tumor history, were also included in the sequencing run.
| EGAS00001002630 | EGA
Project description:Pediatric PAX-FOXO1 fusion-negative rhabdomyosarcoma represents a diverse spectrum of tumors. In this study, the mutational spectrum of 22 fusion-negative rhabdomyosarcomas with high, rhabdomyoma-like levels of differentiation was evaluated using OncoPanel v.2 (OPv2), an Agilent SureSelect custom designed bait set consisting of the coding regions of 504 cancer-relevant genes. Corresponding normal tissue was not available. Discarded normal human skeletal muscle, obtained from 7 donors without tumor history, were also included in the sequencing run.
| EGAS00001002771 | EGA
Project description:RNA-Seq analysis using WA-treated 22Rv1 human prostate cancer cells revealed upregulation and downregulation of 6993 and 6607 genes, respectively when compared to the vehicle-treated control. The pathways with significantly upregulated gene expression following WA treatment included mitogen-activated protein kinases, focal adhesion, endocytosis, and autophagy as revealed by KEGG and gene ontology analyses. WA treatment also resulted in downregulation of genes associated with metabolic pathways, oxidative phosphorylation, tricarboxylic acid cycle, cell cycle, and base excision repair. This study identifies novel mechanistic targets of WA in prostate cancer.
2019-09-17 | GSE137519 | GEO
Project description:High-risk neuroblastoma is a devastating malignancy with few therapeutic options. We identify withaferin A (WA) as a natural ferroptosis inducing agent in neuroblastoma, which acts through a novel double-edged mechanism. WA targets and inactivates glutathione peroxidase 4, as well as increases intracellular labile Fe(II) upon excessive activation of heme oxygenase-1, which both independently result in ferroptosis. This double-edged mechanism results in a high efficacy of WA compared to etoposide in killing a heterogeneous panel of high-risk neuroblastoma cells, and in suppressing neuroblastoma xenografts growth and relapse rate. Nano-targeting of WA allows systemic application and suppressed tumor growth due to an enhanced targeting to the tumor site. Collectively, our data propose a novel therapeutic strategy to kill cancer cells by ferroptosis. High-risk neuroblastoma is a devastating malignancy with few therapeutic options. We identify withaferin A (WA) as a natural ferroptosis inducing agent in neuroblastoma, which acts through a novel double-edged mechanism. WA targets and inactivates glutathione peroxidase 4, as well as increases intracellular labile Fe(II) upon excessive activation of heme oxygenase-1, which both independently result in ferroptosis. This double-edged mechanism results in a high efficacy of WA compared to etoposide in killing a heterogeneous panel of high-risk neuroblastoma cells, and in suppressing neuroblastoma xenografts growth and relapse rate. Nano-targeting of WA allows systemic application and suppressed tumor growth due to an enhanced targeting to the tumor site. Collectively, our data propose a novel therapeutic strategy to kill cancer cells by ferroptosis.
2018-05-01 | GSE112384 | GEO
Project description:Background and purposeGerstmann-Sträussler-Scheinker disease (GSS) with a proline-to-leucine mutation at codon 102 (P102L) in the PRNP gene is the most frequently reported GSS subtype worldwide. This study aimed to determine the epidemiological, clinical, genetic, and laboratory characteristics of 12 Chinese patients with P102L-associated GSS (henceforth P102L GSS).MethodsThe enrolled P102L GSS cases were analyzed according to the diagnostic criteria for Creutzfeldt-Jakob disease (CJD) issued by the China National Health Commission.ResultsThe median onset age was 50 years (range 34 to 67 years) and sex ratio was 1:2 (males:females). Most patients displayed more than one foremost symptom. Movement symptoms were frequently reported (9 of the 12 cases), followed by rapidly progressing dementia (7 cases), mental problems (5 cases), and slowly progressing dementia (2 cases). Almost all cases displayed more sporadic CJD (sCJD)-associated neurological symptoms and signs as time progressed. Five (45.5%) of 11 cases were cerebrospinal fluid 14-3-3 positive, and 2 (25%) of 8 cases exhibited periodic sharp wave complexes in electroencephalograms. MRI abnormalities were detected in all 11 of the scanned patients. Methionine homozygous genotype at codon 129 (M129M) and glutamic acid homozygous at codon 219 (E219E) homozygosity was present in 11 cases, while 1 case was M129M homozygous and glutamic acid/lysine heterozygous at codon 219 (E219K) heterozygous. Ten of the 12 cases recalled a disease-related family history during the clinical interviews. The median survival from symptom onset of the seven dead cases was 16 months (range 10 to 44 months). Patients showing the sCJD phenotype (rapidly progressing dementia) appeared to be associated with a shorter survival time.ConclusionsThe indistinguishable clinical features of P102L GSS patients with sCJD, especially in the early stage, support the importance of PRNP testing for diagnosing GSS.
| S-EPMC6444146 | biostudies-literature
Project description:Multiple myeloma (MM) is an incurable hematological malignancy characterized by the uncontrolled growth of plasma cells in the bone marrow. The major barrier in treating MM is the occurrence of primary and acquired therapy resistance to multiple existing anti-cancer drugs. Often, this therapy resistance is associated with constitutive activation of Bruton tyrosine kinase (BTK) dependent B-cell receptor (BCR) signaling. Novel kinase inhibitors covalently targeting BCR signaling, including the clinically approved BTK inhibitor ibrutinib (IBR) and the preclinical phytochemical Withaferin A (WA), have therefore gained pharmaceutical interest. Remarkably, glucocorticoid (GC)-resistant MM cells overexpressing BTK are more sensitive to WA then to IBR. To further characterize the kinase inhibitor profiles of WA and IBR in GC-resistant MM cells, we applied phosphopeptidome- and transcriptome-specific tyrosine kinome profiling. Our results demonstrate that WA treatment triggers dual inhibition of BCR signaling by transcriptional downregulation and covalent cysteine-dependent kinase inhibition of BTK. Covalent interaction between WA and BTK could further be confirmed by biotin-based affinity purification and confocal imaging microscopy. Altogether, we show that covalent BCR-BTK kinase inhibition by WA represents an attractive strategy to treat GC-resistant MM.
2021-03-31 | GSE162475 | GEO
Project description:Withaferin A (WA) is a lactone extracted from Withania somnifera commonly known as Ashwagandha. WA has several therapeutic benefits. The current study was aimed to identify biomarkers that could be targeted by WA in prostate cancer (PCA) cells. We have used SILAC approach to identify WA-regulated proteins at 4 h and 24 time points in three PCA cell lines such as LNCaP, 22Rv1 and DU-145. Ontology prediction suggested that WA treatment can upregulate stress-responsive pathways and shutdown translation and cell metabolism to conserve energy. The cytoprotective stress granule (SG) protein G3BP1 showed upregulation in all the three tested cell lines in response to WA treatment, and subsequently, SGs formed at a higher rate in the WA treated cells. Knockdown (KD) of G3BP1 blocked WA-induced SG formation and reduced the cell survival. We speculate that the activation of G3BP1 and the formation of SGs might constitute a mechanism by which PCA cells induce cell protection after WA- treatment. Knock down of SG proteins such as G3BP1 could help to evade the cytoprotective effects of WA and to assist in the sensitization of cells.
2021-07-21 | PXD016759 | Pride
Project description:PurposeTo describe the clinical course of untreated intermittent exotropia (IXT) in children 12-35 months of age followed for 3 years.MethodsWe enrolled 97 children 12-35 months of age with previously untreated IXT who had been randomly assigned to the observation arm of a randomised trial of short-term occlusion versus observation. Participants were observed unless deterioration criteria were met at a follow-up visit occurring at 3 months, 6 months, and 6-month intervals thereafter for 3 years. The primary outcome was deterioration of the IXT by 3 years, defined as (1) a constant exotropia ≥10 prism dioptres (∆) at distance and near (i.e., motor deterioration) or (2) treatment prescribed despite not having met motor deterioration. The primary analysis used the Kaplan-Meier method to determine the cumulative proportion of participants meeting deterioration by three years and 95% confidence interval (CI).ResultsThe cumulative probability of deterioration by 3 years was 28% (95% CI = 20%-39%). Of the 24 participants meeting the primary outcome of deterioration, seven met motor deterioration and 17 were prescribed treatment without meeting motor deterioration. The cumulative probability of motor deterioration by 3 years was 10% (95% CI = 5%-19%).ConclusionsGiven the modest rate of motor deterioration over three years, watchful waiting may be a reasonable management approach in 12- to 35-month-old children with IXT. To confirm this recommendation would require a long-term randomised trial of immediate treatment versus observation followed by deferred treatment if needed.
| S-EPMC8411390 | biostudies-literature
Project description:We recently identified a subset of down-regulated miRNAs such as miR-489 and miR-504 in HNSCC. Cell growth inhibitions occurred in miR-489 and miR-504 transfectants compared with the controls, suggesting that both miRNAs function as tumor suppressors. The aims of our expression studies were identification of these miRNAs target genes.
2010-01-05 | GSE19718 | GEO