Gene expression analysis of 5-aza-dC treated pancreatic cancer associated fibroblasts
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE20911 | GEO | 2010/11/20
SECONDARY ACCESSION(S): PRJNA124451
REPOSITORIES: GEO
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Project description:Gene expression analysis of 5-aza-dC treated pancreatic cancer associated fibroblasts To identify genes silenced by methylation in pancreatic CAFs, we performed gene expression profiling on 5-aza-dC treated pancreatic cancer associated fibroblast cultures using Affymetrix Exon arrays. We analyzed 5 untreated and 5-aza-dC-treated pancreatic cancer associated fibroblast cultures using the Affymetrix Human Exon 1.0 ST platform. Gene expression levels were compared using Partek (version 6.3beta).
2010-11-20 | E-GEOD-20911 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that resists current treatments. To test epigenetic therapy against this cancer we used the DNA demethylating drug 5-aza-2’-deoxycytidine (DAC) in a KrasLSL-G12D; p53LSL-R270H/+; Pdx1-cre; Brca1flex2/flex2 (KPC-Brca1) mouse model of aggressive stroma-rich PDAC. In untreated tumors, we found globally decreased 5-methyl-cytosine (5mC) in malignant epithelial cells and in cancer-associated myofibroblasts (CAFs), and increased amounts of 5-hydroxymethyl-cytosine (5HmC) in CAFs, in progression from pancreatic intraepithelial neoplasia (PanIN) to PDAC. DAC further reduced DNA methylation and slowed PDAC progression, markedly extending survival in an early treatment protocol and significantly though transiently inhibiting tumor growth when initiated later, without adverse side effects. Escaping tumors contained areas of sarcomatoid transformation with disappearance of CAFs. Mixing-allografting experiments and proliferation indices showed that DAC efficacy was due to inhibition of both the malignant epithelial cells and the stromal CAFs. Expression profiling and immunohistochemistry highlighted DAC-induction of STAT1 in the tumors, and DAC plus gamma-interferon produced an additive anti-proliferative effect on PDAC cells. DAC induced strong expression of the testis antigen DAZL in CAFs. These data show that DAC is effective against PDAC in vivo and provide a rationale for future studies combining hypomethylating agents with cytokines and immunotherapy. Treatment of a short-term explant culture of cancer-associated fibroblasts (CAFs) from a KPC-Brca1 mouse pancreatic carcinoma, with 2 micromolar 5-aza-dC (decitabine; DAC) for 48 hours. The experiment includes 3 replicate plates untreated and 3 replicates treated.
2013-01-01 | E-GEOD-42364 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that resists current treatments. To test epigenetic therapy against this cancer we used the DNA demethylating drug 5-aza-2’-deoxycytidine (DAC) in a KrasLSL-G12D; p53LSL-R270H/+; Pdx1-cre; Brca1flex2/flex2 (KPC-Brca1) mouse model of aggressive stroma-rich PDAC. In untreated tumors, we found globally decreased 5-methyl-cytosine (5mC) in malignant epithelial cells and in cancer-associated myofibroblasts (CAFs), and increased amounts of 5-hydroxymethyl-cytosine (5HmC) in CAFs, in progression from pancreatic intraepithelial neoplasia (PanIN) to PDAC. DAC further reduced DNA methylation and slowed PDAC progression, markedly extending survival in an early treatment protocol and significantly though transiently inhibiting tumor growth when initiated later, without adverse side effects. Escaping tumors contained areas of sarcomatoid transformation with disappearance of CAFs. Mixing-allografting experiments and proliferation indices showed that DAC efficacy was due to inhibition of both the malignant epithelial cells and the stromal CAFs. Expression profiling and immunohistochemistry highlighted DAC-induction of STAT1 in the tumors, and DAC plus gamma-interferon produced an additive anti-proliferative effect on PDAC cells. DAC induced strong expression of the testis antigen DAZL in CAFs. These data show that DAC is effective against PDAC in vivo and provide a rationale for future studies combining hypomethylating agents with cytokines and immunotherapy. Treatment of a short-term explant culture of malignant epithelial cells from a KPC-Brca1 mouse pancreatic carcinoma, with 0.5 micromolar 5-aza-dC (decitabine; DAC) for 48 hours. The experiment includes 3 replicate plates untreated and 3 replicates treated.
2013-01-01 | E-GEOD-42365 | biostudies-arrayexpress
Project description:In microarray analysis, combinational treatment with PJ-34 and 5-aza-dC caused dissimilar broad changes in gene expression profiles compared with their single treatments in both HCT116 and RKO cells. Profiles of reactivation of silenced genes were also different in combination of PJ-34 and 5-aza-dC and their single treatments. The results suggest that combinational use of 5-aza-dC and PARP inhibitor may be useful by causing distinct transcriptional profile changes.
2022-09-20 | GSE211027 | GEO
Project description:A neuroblasoma cell line, TGW, was treated with a DNA demethylating agents (5-aza-2'-deoxycytidine: 5-aza-dC). Genome-wide DNA methylation was analyzed using the Infinium Human MethylationEPIC BeadChip.
2021-07-23 | GSE180660 | GEO
Project description:A neuroblastoma cell line, NB-1, was treated with mock, a DNA demethylating agent (5-aza-2'-deoxycytidine: 5-aza-dC), a synthetic retinoic acid (tamibarotene: TBT), and the combination of 5-aza-dC and TBT. A genome-wide gene expression analysis was performed using SurePrint G3 Human Gene Expression 8 x 60K v2 Microarray.
2021-07-23 | GSE180645 | GEO
Project description:A neuroblasoma cell line, NB-1, was treated with a DNA demethylating agents (5-aza-2'-deoxycytidine: 5-aza-dC). Genome-wide DNA methylation was analyzed using the Infinium HumanMethylation450 BeadChip.
2021-07-29 | GSE180929 | GEO
Project description:Expression data from pancreatic cancer cell lines and non-neoplastic pancreatic cell line HPDE To identify genes epigenetically silenced and regulated in pancreatic cancer We compared the gene expression profiles of 6 pancreatic cancer cell lines (panc215, A32-1, A38-5, panc2.5, panc2.8, and panc3.014), to the non-neoplastic pancreas cell line, HPDE. We also compared the baseline gene expression of the pancreatic cancer cell lines to expression patterns after treatment with 5-aza-dC alone, TSA alone, and to a combination of 5-aza-dC/TSA.
2010-04-14 | E-GEOD-21163 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that resists current treatments. To test epigenetic therapy against this cancer we used the DNA demethylating drug 5-aza-2’-deoxycytidine (DAC) in a KrasLSL-G12D; p53LSL-R270H/+; Pdx1-cre; Brca1flex2/flex2 (KPC-Brca1) mouse model of aggressive stroma-rich PDAC. In untreated tumors, we found globally decreased 5-methyl-cytosine (5mC) in malignant epithelial cells and in cancer-associated myofibroblasts (CAFs), and increased amounts of 5-hydroxymethyl-cytosine (5HmC) in CAFs, in progression from pancreatic intraepithelial neoplasia (PanIN) to PDAC. DAC further reduced DNA methylation and slowed PDAC progression, markedly extending survival in an early treatment protocol and significantly though transiently inhibiting tumor growth when initiated later, without adverse side effects. Escaping tumors contained areas of sarcomatoid transformation with disappearance of CAFs. Mixing-allografting experiments and proliferation indices showed that DAC efficacy was due to inhibition of both the malignant epithelial cells and the stromal CAFs. Expression profiling and immunohistochemistry highlighted DAC-induction of STAT1 in the tumors, and DAC plus gamma-interferon produced an additive anti-proliferative effect on PDAC cells. DAC induced strong expression of the testis antigen DAZL in CAFs. These data show that DAC is effective against PDAC in vivo and provide a rationale for future studies combining hypomethylating agents with cytokines and immunotherapy.
2013-01-01 | GSE42365 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that resists current treatments. To test epigenetic therapy against this cancer we used the DNA demethylating drug 5-aza-2’-deoxycytidine (DAC) in a KrasLSL-G12D; p53LSL-R270H/+; Pdx1-cre; Brca1flex2/flex2 (KPC-Brca1) mouse model of aggressive stroma-rich PDAC. In untreated tumors, we found globally decreased 5-methyl-cytosine (5mC) in malignant epithelial cells and in cancer-associated myofibroblasts (CAFs), and increased amounts of 5-hydroxymethyl-cytosine (5HmC) in CAFs, in progression from pancreatic intraepithelial neoplasia (PanIN) to PDAC. DAC further reduced DNA methylation and slowed PDAC progression, markedly extending survival in an early treatment protocol and significantly though transiently inhibiting tumor growth when initiated later, without adverse side effects. Escaping tumors contained areas of sarcomatoid transformation with disappearance of CAFs. Mixing-allografting experiments and proliferation indices showed that DAC efficacy was due to inhibition of both the malignant epithelial cells and the stromal CAFs. Expression profiling and immunohistochemistry highlighted DAC-induction of STAT1 in the tumors, and DAC plus gamma-interferon produced an additive anti-proliferative effect on PDAC cells. DAC induced strong expression of the testis antigen DAZL in CAFs. These data show that DAC is effective against PDAC in vivo and provide a rationale for future studies combining hypomethylating agents with cytokines and immunotherapy.
2013-01-01 | GSE42364 | GEO