Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The antifolate pemetrexed induces innate tolerance in human macrophages

ABSTRACT: Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. GM-CSF drives the generation of human monocyte-derived macrophages with a potent pro-inflammatory activity upon stimulation. One-carbon metabolism (OCM) is a complex network of biosynthetic pathways that includes de novo biosynthesis of purines and thymidylate, amino acid metabolism, and methylation reactions. We explored the molecular impact of blocking OCM with the anti-folate pemetrexed (PMX) on the gene expression profile in LPS-activated GM-CSF-primed human monocyte derived macrophages. The specificity of blocking OCM with the anti-folate PMX was demonstrated with folinic acid.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159380 | GEO | 2021/10/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Human monocyte-derived macrophages polarized by GM-CSF in the presence or absence of 50 nanomolar Pemetrexed

Project description:Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. GM-CSF drives the generation of human monocyte-derived macrophages with a potent pro-inflammatory activity upon stimulation. One-carbon metabolism (OCM) is a complex network of biosynthetic pathways that includes de novo biosynthesis of purines and thymidylate, amino acid metabolism, and methylation reactions. We explored the molecular impact of blocking OCM with the anti-folate pemetrexed (PMX) on the gene expression profile in GM-CSF-primed human monocyte derived macrophages.

2021-10-28 | GSE159349 | GEO

The role of the antifolate methotrexate in LPS response in human macrophages

Project description:Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. One-carbon metabolism (OCM) is a complex network of biosynthetic pathways that includes de novo biosynthesis of purines and thymidylate, amino acid metabolism, and methylation reactions. We explored the molecular impact of blocking OCM with high-doses of the anti-folate methotrexate (MTX) on the gene expression profile in M-CSF-primed human monocyte derived macrophages during LPS activation.

2023-11-25 | GSE189740 | GEO

Pemetrexed alters inflammatory profile in EA.hy 926 cells grown under low-folate conditions.

2012-10-03 | GSE31986 | GEO

Pemetrexed alters inflammatory profile in EA.hy 926 cells grown under low-folate conditions.

Project description:Pemetrexed is an antifolate drug used in the treatment of lung cancer. EA.hy 926 cells grown under low (Lo) and normal (Hi) folate conditions were treated with PMX. Microarray analysis was used to examine changes in gene expression due to PMX treatment. Hi and Lo cells were grown to confluence and maintained in fresh medium for 24 hours prior to treatment with 0.5uM PMX for 48 hours.

2012-10-03 | E-GEOD-31986 | biostudies-arrayexpress

Human monocyte-derived macrophages polarized by M-CSF in the presence or absence of 5 micromolar Methotrexate

Project description:Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. One-carbon metabolism (OCM) is a complex network of biosynthetic pathways that includes de novo biosynthesis of purines and thymidylate, amino acid metabolism, and methylation reactions. We explored the molecular impact of blocking OCM with high-doses of the anti-folate methotrexate (MTX) on the gene expression profile in M-CSF-primed human monocyte derived macrophages.

2023-10-16 | GSE186151 | GEO

The role of GSK3 on macrophage re-programming by high-dose methotrexate

Project description:Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. One-carbon metabolism (OCM) is a complex network of biosynthetic pathways that includes de novo biosynthesis of purines and thymidylate, amino acid metabolism, and methylation reactions. Methotrexate (MTX) is an anti-folate drug used for Acute Lymphoblastic Leukemia treatment. We explored the molecular impact of blocking GSK3 a/b on the transcriptional effect of high-doses of MTX in M-CSF-primed human monocyte derived macrophages.

2023-10-01 | GSE185872 | GEO

Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non-Small Cell Lung Cancer - The Piedmont Study

Project description:The Piedmont study is a prospectively designed retrospective evaluation of a new 48-gene antifolate response signature (AF-PRS) in patients with locally advanced/metastatic NS-NSCLC treated with pemetrexed-containing platinum doublet chemotherapy (PMX-PDC). The study tested the hypothesis that the AF-PRS selects for patients with NS-NSCLC that preferentially respond to PMX-PDC, with a goal of providing clinical support for AF-PRS as potential diagnostic test. Overall, 53% of patients were AF-PRS(+), which was associated with extended PFS, but not OS, vs. AF-PRS(-) (16.6 vs. 6.6 mo; p = 0.025). In patients who were Stage I-III patients at time of treatment, PFS, but not OS, was further extended in AF-PRS(+) vs. AF-PRS(-) (36.2 vs. 9.3 mo; p = 0.03). A complete response (CR) to therapy was noted in 14 of 95 patients. AF-PRS(+) preferentially selected a majority (79%) of CRs, which were evenly split between patients Stage I-III (6 of 7) and Stage IV (5 of 7) at time of treatment. AF-PRS identified a significant population of patients with extended survival and/or clinical response following PMX-PDC treatment. AF-PRS may be a useful diagnostic test for patients indicated for systemic chemotherapy, especially when determining the optimal PDC regimen for locally advanced disease.

2023-05-23 | GSE232569 | GEO

Cytotoxic mechanisms of pemetrexed and HDAC inhibition in non-small cell lung cancer cells

Project description:The cytotoxic effects of thymidylate synthase (TYMS) inhibitors, such as the multitarget antifolate pemetrexed (PMX), are not fully understood. Recent studies suggest that the combination of PMX with histone deacetylase inhibitors may be effective in the treatment of non- small cell lung cancer (NSCLC). To investigate this further, A549 NSCLC cells were exposed to various combinations of PMX and the HDAC inhibitor MS275 (entinostat) and Vorinostat (SAHA) and monitored for cell survival, cell cycle alterations and genotoxic markers. MS275 increased PMX sensitivity in A549 cells when added after preincubation with PMX. Both HeLa (p53 negative) and A549 (p53-naïve) exhibited robust activation of γH2AX upon treatment with the combination. Interestingly, CRISPR-Cas9 UNG knockout did not affect γH2AX activation or sensitivity to PMX. Proteomic analysis revealed that MS275 altered expression of known PMX targets, several proteins involved in pyrimidine metabolism, and several DNA repair proteins (RNaseH2, TOP1, RAD51C, PCNA). Contra to the prevailing model of antifolate toxicity mediated by uracil excision and repeated futile repair cycles caused by reincorporation of uracil, we propose that ribonucleotide incorporation in nuclear and mitochondrial DNA is a major contributor to cytotoxicity antifolates such as PMX, and likely also for fluorinated pyrimidine analogs. The DNA lesions induced by these agents and how their processing can be modulated by HDAC inhibition to potentiate cytotoxicity, warrants further investigation in clinical models.

2024-12-18 | PXD051824 | Pride

Human monocyte-derived macrophages polarized by GM-CSF in the presence or absence of 50 nanomolar Pemetrexed

Project description:Human monocyte-derived macrophages polarized by GM-CSF in the presence or absence of 50 nanomolar Pemetrexed

| PRJNA668525 | ENA

Transcription profiling by array of mesothelioma pre- and post-resistance biopsies in order to determine a resistance signature to pemetrexed/carboplatin treatment

Project description:Pemetrexed, a multi-folate inhibitor combined with a platinum compound is the first-line treatment of malignant mesothelioma, but median survival is still one year. Innate and acquired resistance to pemetrexed is common, but its biological basis is obscure. Here we report for the first time a genome-wide profile of acquired resistance in the tumour from an exceptional case with advanced pleural mesothelioma and almost six years survival after 39 cycles of second-line pemetrexed/carboplatin treatment.

2012-10-01 | E-MTAB-1109 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data