The effect of decitabine (DAC) treatment on glioma cells
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ABSTRACT:
PROVIDER: PRJNA642730 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR12105780.fastq.gz | Fastqsanger.gz | |||
| SRR12105781.fastq.gz | Fastqsanger.gz | |||
| SRR12105782.fastq.gz | Fastqsanger.gz | |||
| SRR12105783.fastq.gz | Fastqsanger.gz | |||
| SRR12105784.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:The objective of this study is to identify molecular determinants of DAC response in gliomas
2020-10-01 | GSE153443 | GEO
Project description:Our study had shown that DAC treatment enhanced immunogenecity of EL4 cells. To explore the mechanisms of DAC-induced tumor immunity, we carried out cDNA microarray analyses to compare the differential expression of genes between DAC and PBS treated EL4 cells. Two-condition experiment, PBS treated EL4 vs. Decitabine treated EL4 cells. Biological replicates: 3 PBS treated, 3 Decitabine treated, independently treatment and harvested. One replicate per array.
2013-02-15 | E-GEOD-38473 | biostudies-arrayexpress
Project description:Reversal of gene promoter DNA hypermethylation and associated abnormal gene silencing is an attractive approach to cancer therapy. The DNA methylation inhibitor, decitabine (5-aza-2'-deoxycitidine), is proving efficacious for hematological neoplasms especially at lower, less toxic, doses. Experimentally, high doses induce rapid DNA damage and cytotoxicity, but these may not explain the prolonged time to response seen in patients. Transient exposure of leukemic and solid tumor cells to clinically-relevant nanomolar doses, without causing immediate cytotoxicity or apoptosis, produces sustained reduced tumorigenicity, and for leukemia cells, diminished long-term self-renewal. These effects appear triggered by cellular reprogramming and include sustained decreases in promoter DNA methylation with associated gene re-expression, and anti-tumor changes in multiple key cellular regulatory pathways, most of which are high priority targets for pharmacologic anti-cancer strategies. Thus, low dose decitabine regimens appear to have broad applicability for cancer management. [Gene expression profiling] Leukemia cell lines Kasumi-1 and KG1A are treated with 10nM DAC during 72 hours and gene expression was assayed at day 3, 7 and 14 after the start of the treatment. Appropriate mock treated samples were used as control in each case. In addition, Kasumi-1 cells were also treated with a higher dose of DAC (500nM), 100nM ARA-C and 300 nM TSA, again controlled against mock treated Kasumi-1 cells, to separate dose and agent dependent effects. MCF7 was studied as an example of a solid tumor cell line. Therefore MCF7 cells were treated with 100nM DAC and results were assayed at day 1, day 3 and day 10. [Methylation profiling] The effects of the demethylating agent DAC were studied in the leukemia cell line Kasumi-1 over a 28 day time course. Intermediate time points were studied at days 3, 7, 14 and 21. These results were verfied in KG1A and KG1 leukemia cell lines, at one selected time point. The effects on one primary sample were also studied. Four normal leukemia samples (PL1, 2, 4 and 5) were used as general controls. The effect of DAC was compared to ARA-C, TSA. Both mock treated and day 3 DAC treated Kasumi-1 cells were repeated. These results were verified at one selected time point for the DAC treated MCF7 breast cancer cell line.
2012-03-21 | E-GEOD-20945 | biostudies-arrayexpress
Project description:Genome-wide DNA methylation profiling of primary AML samples treated with 100nM decitabine (DAC), cytarabine (AraC), or DMSO. Eight distinct AML samples were grown using an in vitro stromal co-culture system for 4 days and then treated with either DAC, Ara-C or DMSO for 3 days. DNA was prepared for genome-wide methylation analysis with the Illumina Infinium 450k Human DNA methylation BeadChip. DNA from each sample/treatment was analyzed on duplicate arrays.
2012-12-18 | GSE40870 | GEO
Project description:The combination of the demethylating agent Decitabine (DAC) and the retinoic acid ATRA has shown potent antileukemic action both in vitro and in vivo. The likely synergistic mechanism of action remains unknown. Both DAC and retinoid acids are known to affect methylation. DAC inhibits DNA-methyltransferases by covalent bonding, thereby causing demethylation after several replication cycles (Stresemann and Lyko, 2008). Depending on gene and entity, both demethylation (Das et al., 2010; Di Croce et al., 2002) as well as hypermethylation (Das et al., 2010) have been induced by treatment with retinoids. Therefore, a synergistic mechanism of action regarding the methylome to explain the combinatorial strong antileukemic effect of DAC+ATRA was investigated.
2022-06-30 | GSE181960 | GEO
Project description:Genome-wide DNA methylation profiling of primary AML samples treated with 100nM decitabine (DAC), cytarabine (AraC), or DMSO. Eight distinct AML samples were grown using an in vitro stromal co-culture system for 4 days and then treated with either DAC, Ara-C or DMSO for 3 days. DNA was prepared for genome-wide methylation analysis with the Illumina Infinium 450k Human DNA methylation BeadChip. DNA from each sample/treatment was analyzed on duplicate arrays. Bisulfite-converted DNA from 24 samples was hybridised to the Illumina Infinium 450k Human Methylation Beadchip in duplicate (replicates are indicated by array plate number).
2012-12-18 | E-GEOD-40870 | biostudies-arrayexpress
Project description:In order to further study the mechanism of decitabine (DAC) on MDS cell lines, 1uM DAC was used to treat SKM-1 and MDS-L cell lines, and the molecular pathway changes regulated by DAC were explored. Genes whose expression changes more than 2.0 times after drug treatment are defined as regulated genes. Taking the intersection change of the two cell lines, it was found that compared with the control, 541 genes were up-regulated in the intersection of gene changes treated with DAC, and 762 genes were down-regulated. Gene expression profile analysis shows that DAC can significantly affect various cell biological processes, including antiviral response, immune response, inflammatory response and cell apoptosis.
2021-01-26 | GSE164744 | GEO
Project description:A novel hypomethylating agent NTX-301 is a promising therapeutic agent for AML patients. To examine its mechanisms of action, we produced methylome data upon treatment with NTX-301 or decitabine (DAC) in MV4-11 cell line.
2022-11-30 | GSE187291 | GEO
Project description:Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, often characterized by poor prognosis following standard induction therapy. The DNA methyltransferase inhibitor decitabine (DAC) is an alternative to intensive chemotherapy in elderly and relapsed/refractory AML patients. Despite some efficacy, DAC monotherapy does not promote complete remission and overall survival rates are very poor. Therefore, novel therapeutic regimens for AML are warranted. CD105 (endoglin), a receptor for the TGF-β superfamily, is expressed in various hematopoietic malignancies, including AML in which high expression correlates with poor prognosis. We have recently demonstrated that targeting CD105+ AML blasts with the TRC105 monoclonal antibody abrogates leukemogenesis in vivo. Based on these encouraging findings, here we investigated whether TRC105 in combination with DAC could represent a novel therapeutic option to treat relapsed/refractory AML. Treatment of leukemic mice with DAC in combination with TRC105 resulted in superior survival and significant reduction of leukemia burden in the bone marrow (BM) of AML xenografts compared to DAC monotherapy. To determine if TRC105 anti-leukemogenic effect is mediated by NK cells, we performed in vitro and in vivo studies. In the latter, we tested TRC105 in the context of NK depletion by injecting mice with an antibody to CD122. TRC105 treatment resulted in comparable reduction of leukemia burden in xenografts regardless of NK depletion, demonstrating that the anti-leukemogenic effect of TRC105 in AML is independent of NK cells. Altogether, our findings provide proof-of-principle for the clinical evaluation of TRC105 in combination with DAC in AML patients.
2020-10-27 | GSE147503 | GEO
Project description:Purpose: We aimed to investigate the effect of several anti-leukemia drugs in combination with decitabine (DAC) on the proliferation of myeloid leukemia cells in vitro and in vivo, to select the most efficient combination group and explore associated mechanisms of these combination therapies. Experimental Design: After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway. Results: The sequential combination of DAC and IDA showed synergistic induction of cell death in U937, HEL, SKM-1 and cells isolated from AML patients. Importantly, the inhibition of tumor growth in the sequential combination group was found to be significantly higher than that of single drug group or control group in vivo. Moreover, sequential treatment with DAC and IDA induced apoptosis and depression of the Wnt/β-catenin pathway in both culture and animal studies. Conclusions: Our findings showed that sequentially combining decitabine with idarubicin had a synergistic anti-leukemia effect. These findings were attributed to demethylation of Wnt pathway inhibitors and downregulation of Wnt pathway nuclear targets observed in vitro and in vivo. After comparing with five anti-leukemia drugs in several different kinds of cell lines, the combination effect of idarubicin (IDA) with DAC was best. In vivo, by using microPET, TUNEL, and transmission electron microscopy, the inhibitory effects obtained by sequentially combining DAC with IDA, evidenced by evaluating tumor cell proliferation and cell apoptosis. Molecular studies were conducted using gene chip, which was used to explore associated pathways, and real-time quantitative reverse transcription-PCR, western blot and immunohistochemistry (IHC), used to assess regulation of Wnt/β-catenin pathway.
2014-02-13 | E-GEOD-54918 | biostudies-arrayexpress