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

CSF attenuates methotrexate efficacy

Project description:CSF attenuates methotrexate efficacy

| PRJNA1148197 | ENA

CSF attenuates methotrexate efficacy

Project description:Treatment and prophylaxis of the central nervous system (CNS) is a critical component of acute lymphoblastic leukemia (ALL) therapy. However, CNS-directed therapies are a significant cause of morbidity and CNS relapse remains a cause of treatment failure. CNS-directed ALL therapies must target leukemia cells within cerebrospinal fluid (CSF), a fluid that is compositionally distinct from plasma and has been shown to impact leukemia biology. Herein, we demonstrate that human CSF attenuates the potency and efficacy of anti-folate drugs including methotrexate, the primary CNS-directed chemotherapeutic for over six decades. Importantly, this effect of CSF on leukemia methotrexate sensitivity was reversible. Additional mechanistic studies support that diminished proliferation and activation of the integrated stress response (ISR) in leukemia cells in CSF contribute to this resistance. Our findings suggest potential strategies to enhance methotrexate efficacy in CNS-directed ALL therapy and highlight the need to critically reassess even established standards of care.

2024-09-23 | GSE274857 | GEO

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

Transcription profiling of human monocytes cultured in the presence of M-CSF for 7 days and polarized to M1 or M2 cells to characterize human monocyte-to-macrophage differentiation and polarization

Project description:Monocytes mature to macrophages in the presence of the lineage determining cytokine M-CSF. They can be further polarized into M1 or M2 macrophages with distinct functional properties. We used microarrays to detail the global programme of gene expression underlying macrophage maturation and polarization and identified distinct classes of up-regulated genes during this process. Experiment Overall Design: Freshly isolated monocytes were cultured in the presence of M-CSF for 7 days, and then polarized to M1 or M2 cells. The study includes Monocytes at day 0, macrophages at day 3 and 7, M1 and m2 polarized macrophages.

2007-11-02 | E-GEOD-5099 | biostudies-arrayexpress

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

Human monocyte-derived macrophages polarized by GM-CSF or M-CSF

Project description:Identification of genes differentially expressed between human monocyte-macrophages generated in the presence of either GM-CSF (termed M1) or M-CSF (termed M2)

2012-04-13 | GSE27792 | GEO

Human monocyte-derived macrophages polarized by GM-CSF or M-CSF

Project description:Identification of genes differentially expressed between human monocyte-macrophages generated in the presence of either GM-CSF (termed M1) or M-CSF (termed M2) Human peripheral blood monocytes from three independent healthy donors (#1, #2 and #3) were isolated by anti-CD14-labeled magnetic microbeads. CD14+ monocytes were cultured for 7 days in RPMI 10% FCS containing either GM-CSF or M-CSF. Total RNA from each condition was extracted and purified using the RNeasy kit (Qiagen). Labelled RNA was used as hybridization probes on human Codelink Whole genome Bioarray. All experimental procedures were performed following manufacturer instructions. Microarrays were scanned with a GenePix 4000B (Axon Instruments) scanner. Scanned images and raw data were processed using the Codelink Expression Software.

2012-04-12 | E-GEOD-27792 | biostudies-arrayexpress

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