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Synergistic effects of TRAIL and taurolidine on soft tissue sarcoma cell lines

ABSTRACT: Microarray analysis revealed differential gene expression patterns of rhabdomyosarcoma (A-204), leiomyosarcoma (SK-LMS-1) and epithelioid cell sarcoma (VA-ES-BJ) cells treated with TRAIL and/or taurolidine. To explore new therapeutic options in the treatment of sarcomas, we tested the antibiotic taurolidine (TRD) on A-204, SK-LMS-1 and VA-ES-BJ carcinoma cell lines alone and in combination with rhTRAIL (TNF related apoptosis-inducing ligand). Gene expression was analysed by RNA microarray. Cell lines were treated with Taurolidine, Trail and a combination of both and compaired to untreated cells

ORGANISM(S): Homo sapiens

SUBMITTER: Ludger Klein-Hitpass

PROVIDER: E-GEOD-36572 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Synergistic effects of TRAIL and taurolidine on soft tissue sarcoma cell lines

Project description:Microarray analysis revealed differential gene expression patterns of rhabdomyosarcoma (A-204), leiomyosarcoma (SK-LMS-1) and epithelioid cell sarcoma (VA-ES-BJ) cells treated with TRAIL and/or taurolidine. To explore new therapeutic options in the treatment of sarcomas, we tested the antibiotic taurolidine (TRD) on A-204, SK-LMS-1 and VA-ES-BJ carcinoma cell lines alone and in combination with rhTRAIL (TNF related apoptosis-inducing ligand). Gene expression was analysed by RNA microarray.

2013-03-17 | GSE36572 | GEO

Fatty Acid Synthase Reprograms the Epigenome in Uterine Leiomyosarcomas

Project description:SK-UT-1 uterine leiomyosarcomas (Ut-LMS) cells were transduced with a fatty acid synthase (FASN)-containing retroviral vector to recapitulate the “lipogenic phenotype of cancer.” Consistent with this model, forced expression of FASN enhanced SK-UT-1 proliferation, migration, and cellular motion. Further investigation showed FASN promotes trimethylation of H3K9 (H3K9me3) and acetylation of H3K27 (H3K27ac) in SK-UT-1 cells. In contrast, siRNA targeting of FASN in high endogenous FASN expressing SK-LMS-1 Ut-LMS cells inhibits trimethylation of H3K9 and acetylation of H3K27. Palmitate, the predominant fatty acid product of FASN, increased H3K9me3, H3K27ac and H3K27me3 detection in SK-UT-1 cells. FASN promoted histone 3 methylation and acetylation through alteration of histone 3-modifying enzymatic activities (HDAC, HDM, HMT and HAT).ChIP-seq in SK-UT-1-FASN cells with anti-H3K9me3 antibody identified regions of enriched binding compared to vector-only cells. One differentially-enriched gene, CRISP1, was investigated further by ChIP-PCR. The transcriptionally repressive function of H3K9me3 was confirmed in CRISP1. Our results provide mechanistic insight into the pathobiology of the “lipogenic phenotype of cancer.” Here, FASN reprograms the Ut-LMS epigenome through chromatin remodeling to promote the “malignant phenotype.”

2017-06-14 | GSE98557 | GEO

UV (UVC, 10J/m2) light irradiation effect on Ewing Sarcoma cells

Project description:LAP-35 and SK-N_MC cells were treated with 10 J/m2 UV light versus untreated Alternative pre-mRNA processing plays a key role in the response to DNA damage as well as in neoplastic transformation. We found that two Ewing Sarcoma (ES) cell lines exhibit different sensitivity to UV light irradiation, with SK-N-MC cells being more sensitive than LAP-35 cells. RNA profiling during the response to low doses of UV light irradiation revealed genes differentially regulated between the two cell lines. In particular, UV light irradiation induced a novel isoform of the RNA helicase DHX9 which is targeted to nonsense-mediated decay (NMD) and therefore causes down-regulation of DHX9 in SK-N-MC cells, but not in LAP-35 cells. DHX9 protein forms a complex with RNA polymerase II (RNAPII) and EWS-FLI1 to enhance transcription, and we found that down-regulation of DHX9 by UV light irradiation in SK-N-MC cells impairs the recruitment of EWS-FLI1 to target genes and increases sensitivity to DNA damage. Notably, sensitivity of SK-N-MC cells to irradiation correlated with enhanced phosphorylation and decreased processivity of RNAPII upon irradiation, which in turn causes inclusion of the novel DHX9 exon in SK-N-MC cells exposed to UV light, an observation that could be recapitulated in LAP35 cells by pharmacological reduction of RNAPII processivity. Our data suggest that EWS-FLI1 oncogene activity could be targeted by modulation of DHX9 gene expression. Three biological replicates were labeled in direct and dye-swap microarray experiments and hybridized onto an Agilent custom splicing-sensitive microarray platform

2015-10-20 | E-GEOD-59889 | biostudies-arrayexpress

Xenograft tumors of neuroblastoma cell lines

Project description:Neuroblastoma cell lines SK-N-AS(-TRAIL) and SH-SY5Y were xenografted in mice to study them in vivo

2021-10-01 | GSE125058 | GEO

Proteotoxic stress-induced apoptosis in cancer cells: understanding the susceptibility and enhancing the potency

Project description:Leiomyosarcoma (LMS) is an aggressive cancer with few therapeutic options. LMS cells are more sensitive to proteotoxic stress compared to normal smooth muscle cells. We used small compound 2c to induce proteotoxic stress and compare the transcriptomic adaptations of immortalized human uterine smooth muscle cells (HUtSMC) and LMS cells SK-UT-1. We found that the expression of the heat shock proteins (HSP) gene family is upregulated with higher efficiency in normal cells. In contrast, upregulation of BH3-only proteins is higher in LMS cells. HSF1, the master regulator of HSP transcription, is sequestered into transcriptionally incompetent nuclear foci only in LMS cells, which explains the lower HSP upregulation. We also found that several compounds can enhance the cell death response to proteotoxic stress. Specifically, when low doses were used, an inhibitor of salt-inducible kinases (SIKs) and the inhibitor of IRE1, a key element of the unfolded protein response (UPR), support proteotoxic-induced cell death with strength in LMS cells and without effects on the survival of normal cells. Overall, our data provide an explanation for the higher susceptibility of LMS cells to proteotoxic stress and suggest a potential option for co-treatment strategies.

2022-10-03 | GSE205596 | GEO

Detection of Early Prognostic Biomarkers for Metastasis of Ewing’s Sarcoma in Pediatric Patients

Project description:Ewing’s sarcoma (ES) is a highly aggressive bone tumor, and the second most prevalent pediatric bone malignancy. The presence of metastasis at diagnosis decreases the three-year survival rate to 20% and contributes to diminished prognosis. Researches are indispensable for the early characterization of the disease and prediction of metastatic-prone patients, through biomarkers identification. Moreover, there is currently no available data on ES utilizing non-biopsy samples, such as plasma. This study utilizes a proteomic analysis of Ewing's sarcoma patient’s plasma samples and biopsies. Initially, the ES group was compared with the control counterpart. In a next step, the ES arm was further stratified into either initially metastatic and non-metastatic, or poor and good chemotherapy responder groups to identify protein expression profiles that can predict metastatic proneness and chemotherapy response, respectively.

2023-12-19 | PXD035812 | Pride

5- AZA treatment of EWS cell lines

Project description:The Ewing Sarcoma cell lines A673, SK-ES-1, and SK-N-MC were treated with without 5-AZA to identify upregulated genes A673, SK-ES-1, and SK-N-MC were treated with 5-AZA

2012-09-01 | E-GEOD-36858 | biostudies-arrayexpress

5- AZA treatment of EWS cell lines

Project description:The Ewing Sarcoma cell lines A673, SK-ES-1, and SK-N-MC were treated with without 5-AZA to identify upregulated genes

2012-09-01 | GSE36858 | GEO

Effects of miR-106a~363 blocking sponge on Sk-ES-1 Ewing Sarcoma Cell line Gene Expression Profile

Project description:The objective of this study was to determine the effects of miR-106a~363 blockade on the gene expression profile of Ewing Sarcoma cell lines (Sk-ES-1 cells) Microarray analysis was performed on 3 samples from Sk-ES-1 cells stably expressing the control CXCR4 miRNA sponge and 3 samples from Sk-ES-1 cells stably expressing the miR-106a~363 cluster blocking miRNA sponge

2013-12-01 | E-GEOD-45205 | biostudies-arrayexpress

Transcriptome analysis of RNA-sequencing data for 2-D08-treated SK-LMS-1 cells

Project description:2ʹ,3ʹ,4ʹ-trihydroxyflavone (2-D08) is a synthetic flavone that mechanistically has been identified as a specific inhibitor of protein SUMOylation. Recent studies have demonstrated that 2-D08 has various biological functions, including anticancer. We aimed to obtain additional insights into the effects of 2-D08 and conducted transcriptome analyses using RNA-sequencing (RNA-seq) in SK-LMS-1 leiomyosarcoma cells.

2024-04-23 | GSE264332 | GEO

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