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Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor SGI-110 in Hepatocellular Carcinoma Cells

ABSTRACT: Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor SGI-110 in Hepatocellular Carcinoma Cells

PROVIDER: PRJNA414564 | ENA |

REPOSITORIES: ENA

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Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor SGI-110 in Hepatocellular Carcinoma Cells [gene expression]

Project description:There is an urgent need for developing more effective therapies for aggressive hepatocellular carcinoma (HCC). Guadecitabine (SGI-110) is a second-generation DNA methyltransferase inhibitor (DNMTi) currently in clinical trials for HCC and shows greater stability and performance over first generation DNMTis. The aim of this study is to identify potential therapeutic targets of SGI-110 for clinical trials.

2018-06-26 | GSE105065 | GEO

Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor SGI-110 in Hepatocellular Carcinoma Cells [methylation]

Project description:Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor SGI-110 in Hepatocellular Carcinoma Cells [methylation]

| PRJNA414577 | ENA

Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor SGI-110 in Hepatocellular Carcinoma Cells [gene expression]

Project description:Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor SGI-110 in Hepatocellular Carcinoma Cells [gene expression]

| PRJNA414576 | ENA

RNAseq of rhabdomyosarcoma cells after treatment with SGI-110 and/or Dasatinib

Project description:Patients with metastatic or recurrent rhabdomyosarcoma, the most common childhood soft tissue sarcoma, continue to do poorly and new treatments are needed. In this study we evaluated a novel combination therapy using a dna methyltransferase inhibitor, SGI-110, and the SRC family kinase inhibitor, Dasatinib. To understand the transcriptional changes that occur after treatment with SGI-110 with and without Dasatinib we performed RNAseq on two human RMS cell lines (Rh30 and RD) after 5 days of drug treatment.

2021-04-30 | GSE147240 | GEO

Effects of SGI-110 on A2780 ovarian cancer xenografts

Project description:Genome-wide DNA methylation profiles of SGI-110-treated ovarian cancer xenografts were obtained using next generation Illumina Infinium 450k assay which includes over 450,000 GpG sites. DNA from 6 samples were hybridized to the Illumina's Infinium HumanMethylation 450 BeadChip

2014-10-02 | E-GEOD-55613 | biostudies-arrayexpress

Effects of SGI-110 on A2780 ovarian cancer xenografts

2014-10-02 | GSE55613 | GEO

Gene expression profiling of SGI-110-treated MDA-MB-231 cells

Project description:In this study we analyse the effect og DNMT inhibitor SGI-110 on the gene expression of MDA-MB-231 cells

2020-12-19 | GSE163468 | GEO

Illumina Infinium HumanMethylationEPIC array after SGI-110 treatment in rhabodmyosarcoma cell lines

Project description:Genome wide methylation microarray was performed on two RD and Rh30 rhabdomyosarcoma cell lines treated with 0.5µM of the dna methyltrasferase inhibitor SGI-110 for 5 days or DMSO control.

2021-04-30 | GSE147246 | GEO

Next-generation hypomethylating agent SGI-110 primes acute myeloid leukemia cells to IAP antagonist by activating extrinsic and intrinsic apoptosis pathways

Project description:Therapeutic efficacy of first-generation hypomethylating agents (HMAs) is limited in elderly acute myeloid leukemia (AML) patients. Therefore, combination strategies with targeted therapies are urgently needed. Here, we discover that priming with SGI-110 (guadecitabine), a next-generation HMA, sensitizes AML cells to ASTX660, a novel antagonist of cellular Inhibitor of Apoptosis Protein 1 and 2 (cIAP1/2) and X-linked IAP (XIAP). Importantly, SGI-110 and ASTX660 synergistically induced cell death in a panel of AML cell lines as well as in primary AML samples while largely sparing normal CD34+ human progenitor cells, underlining the translational relevance of this combination. Unbiased transcriptome analysis revealed that SGI-110 alone or in combination with ASTX660 upregulated the expression of key regulators of both extrinsic and intrinsic apoptosis signaling pathways such as TNFRSF10B (DR5), FAS and BAX. Individual knockdown of the death receptors TNFR1, DR5 and FAS significantly reduced SGI-110/ASTX660-mediated cell death, whereas blocking antibodies for TRAIL or FASLG failed to provide protection. Also, TNF-blocking antibody Enbrel had little protective effect on SGI110/ASTX660-induced cell death. Further, SGI-110 and ASTX660 acted in concert to promote cleavage of caspase-8 and BID, thereby providing a link between extrinsic and intrinsic apoptotic pathways. Consistently, sequential treatment with SGI-110 and ASTX660 triggered loss of mitochondrial membrane potential (MMP) and BAX activation, which contributes to cell death as BAX silencing significantly protected from SGI-110/ASTX660-mediated apoptosis. Together, these events culminated in activation of caspases-3/-7, nuclear fragmentation and cell death. In conclusion, SGI-110 and ASTX660 cooperatively induced apoptosis in AML cells by engaging extrinsic and intrinsic apoptosis pathways, highlighting the therapeutic potential of this combination for AML.

2019-10-03 | GSE138322 | GEO

Phase I/II Study of SGI-110 With Irinotecan Versus Regorafenib or TAS-102 in Metastatic Colorectal Cancer

Project description:This is a phase I/II study of the combination of Guadecitabine (SGI-110) and previously treated metastatic colorectal cancer patients. This study will be conducted in two components. First, patients will be enrolled in a phase I study of SGI-110 combined with irinotecan in a standard 3+3 design. After the maximum tolerated dose (MTD) is determined, patients will subsequently be enrolled in a 2:1 randomized phase II study of SGI-110 and irinotecan versus the standard of care regorafenib or Lonsurf (TAS-102).

| 2148118 | ecrin-mdr-crc

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