Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA225789 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Colon cancer is one of the most common tumors worldwide. Recent reports showed that patients treated with the antidepressant fluoxetine had reduced colon cancer risk, with effects similar to the chemotherapeutic 5-fluoro-uracil. Here, we examined the effects of fluoxetine and 5-fluoro-uracil on gene expression of HT29 colon cancer cell xenografts. HT29 xenografts in NOD/SCID mice were treated with vehicle (physiological solution), fluoxetine (30mg/kg/day), or 5-Fluoro-uracil (50 mg/kg/day).
2015-06-09 | E-GEOD-51904 | biostudies-arrayexpress
Project description:Colon cancer is one of the most common tumors worldwide. Recent reports showed that patients treated with the antidepressant fluoxetine had reduced colon cancer risk, with effects similar to the chemotherapeutic 5-fluoro-uracil. Here, we examined the effects of fluoxetine and 5-fluoro-uracil on gene expression of HT29 colon cancer cell xenografts.
2015-06-09 | GSE51904 | GEO
Project description:Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are the most common treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems relate to treatment responses may be critical for understanding antidepressant resistance. Transcriptome profiling allows for the simultaneous measurement of expression levels for thousands of genes and the opportunity to utilize this information to determine mechanisms underlying antidepressant treatment responses. However, the best way to relate this immense amount of information to treatment resistance remains unclear. We take a novel approach to this question by examining dentate gyrus transcriptomes from the perspective of a stereotyped fluoxetine-induced gene expression program. Expression programs usually represent stereotyped changes in expression levels that occur as cells transition phenotypes. Fluoxetine will shift transcriptomes so they lie somewhere between a baseline state and a full-response at the end of the program. The position along this fluoxetine-induced gene expression program (program status) was measured using principal components analysis (PCA). The same expression program was initiated in treatment-responsive and resistant mice but treatment response was associated with further progression along the fluoxetine-induced gene expression program. The study of treatment-related differences in gene expression program status represents a novel way to conceptualize differences in treatment responses at a transcriptome level. Understanding how antidepressant-induced gene expression program progression is modulated represents an important area for future research and could guide efforts to develop novel augmentation strategies for antidepressant treatment resistant individuals. 38 samples, 2 dentate regions (dorsal/ventral), 3 groups (control, antidepressant resistant (4 mice), antidepressant responsive (7 mice), untreated (8 mice).
2013-12-31 | E-GEOD-43261 | biostudies-arrayexpress
Project description:We constructed a comprehensive multi-omics map of the molecular effects of fluoxetine (an SSRI antidepressant) in 27 rat brain regions. We profiled gene expression (bulk RNA-seq, 210 datasets) and chromatin state (bulk chromatin immunoprecipitation sequencing (ChIP-seq) for the histone marker H3K27ac, 100 datasets) in a broad, unbiased panel of 27 brain regions across the entire rodent brain, in naive and fluoxetine-treated animals. We complemented this approach with single-cell RNA-seq (scRNA-seq) analysis of two brain regions (20 datasets). Remarkably, in the single-cell RNA-seq profiling we observed profound changes in the transcripts of hippocampal dorDG and venDG (~500 DEGs in specific cell types). Using diverse integrative data analysis techniques we characterized the complex and multifaceted effects of fluoxetine on region-specific and cell-type-specific gene regulatory networks and pathways. We leveraged this atlas to identify fluoxetine-modulated genes and gene-regulatory loci, predict enriched motifs that suggest potential upstream regulators, and validate global mechanisms of fluoxetine action.
2022-09-04 | GSE197622 | GEO
Project description:We constructed a comprehensive multi-omics map of the molecular effects of fluoxetine (an SSRI antidepressant), in 27 rat brain regions. We profiled gene expression (bulk RNA-seq, 210 datasets) and chromatin state (bulk chromatin immunoprecipitation sequencing (ChIP-seq) for the histone marker H3K27ac, 100 datasets) in a broad, unbiased panel of 27 brain regions across the entire rodent brain, in naive and fluoxetine-treated animals. We complemented this approach with single-cell RNA-seq (scRNA-seq) analysis of two brain regions. Using diverse integrative data analysis techniques we characterized the complex and multifaceted effects of fluoxetine on region-specific and cell-type-specific gene regulatory networks and pathways. Remarkably, we observed profound molecular changes across the brain (>4,000 differentially expressed genes and differentially acetylated ChIP-seq peaks each) that were highly region-dependent. We leveraged this atlas to identify fluoxetine-moduated genes and gene-regulatory loci, predict enriched motifs that suggest potential upstream regulators, and validate global mechanisms of fluoxetine action.
2022-09-04 | GSE194289 | GEO
Project description:We constructed a comprehensive multi-omics map of the molecular effects of fluoxetine (an SSRI antidepressant), in 27 rat brain regions. We profiled gene expression (bulk RNA-seq, 210 datasets) and chromatin state (bulk chromatin immunoprecipitation sequencing (ChIP-seq) for the histone marker H3K27ac, 100 datasets) in a broad, unbiased panel of 27 brain regions across the entire rodent brain, in naive and fluoxetine-treated animals. We complemented this approach with single-cell RNA-seq (scRNA-seq) analysis of two brain regions. Using diverse integrative data analysis techniques we characterized the complex and multifaceted effects of fluoxetine on region-specific and cell-type-specific gene regulatory networks and pathways. Remarkably, we observed profound molecular changes across the brain (>4,000 differentially expressed genes and differentially acetylated ChIP-seq peaks each) that were highly region-dependent. We leveraged this atlas to identify fluoxetine-moduated genes and gene-regulatory loci, predict enriched motifs that suggest potential upstream regulators, and validate global mechanisms of fluoxetine action.
2022-09-04 | GSE193040 | GEO
Project description:Here, we performed a high-throughput drug screening and identified fluoxetine, originally an FDA-approved antidepressant, as candidate therapeutic agent for NEPC. In vitro experiments revealed that fluoxetine effectively curbed the neuroendocrine differentiation and inhibited the cell viability by targeting the AKT pathway. Altogether, this work repurposed fluoxetine for antitumor application, and supported its clinical development for NEPC therapy, which may provide a promising therapeutic strategy.
2023-04-05 | GSE224715 | GEO
Project description:Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are the most common treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems relate to treatment responses may be critical for understanding antidepressant resistance. Transcriptome profiling allows for the simultaneous measurement of expression levels for thousands of genes and the opportunity to utilize this information to determine mechanisms underlying antidepressant treatment responses. However, the best way to relate this immense amount of information to treatment resistance remains unclear. We take a novel approach to this question by examining dentate gyrus transcriptomes from the perspective of a stereotyped fluoxetine-induced gene expression program. Expression programs usually represent stereotyped changes in expression levels that occur as cells transition phenotypes. Fluoxetine will shift transcriptomes so they lie somewhere between a baseline state and a full-response at the end of the program. The position along this fluoxetine-induced gene expression program (program status) was measured using principal components analysis (PCA). The same expression program was initiated in treatment-responsive and resistant mice but treatment response was associated with further progression along the fluoxetine-induced gene expression program. The study of treatment-related differences in gene expression program status represents a novel way to conceptualize differences in treatment responses at a transcriptome level. Understanding how antidepressant-induced gene expression program progression is modulated represents an important area for future research and could guide efforts to develop novel augmentation strategies for antidepressant treatment resistant individuals.
2013-12-31 | GSE43261 | GEO
Project description:Acid sphingomyelinase (ASM) inhibitors, which are clinically used as anti-depressants for ~60 years, have recently been shown to enhance stroke recovery in rodents. Using mice and cerebral microvascular endothelial cells exposed to ischemia/reperfusion (I/R) we show that the antidepressants amitriptyline, fluoxetine and desipramine induce angiogenesis in an ASM-dependent way by releasing small extracellular vesicles (sEVs) from endothelial cells, which have bona fide characteristics of exosomes and which, similar to sEVs released during I/R, promote angiogenesis. Post-I/R, ASM inhibition elicits a profound brain remodeling response with increased blood-brain barrier integrity, reduced brain leukocyte infiltrates and increased neuronal survival. The ASM inhibitor-mediated release of sEVs has disclosed an elegant target, via which stroke recovery can be amplified. Key words: Antidepressant, ceramide, exosome, focal cerebral ischemia, middle cerebral artery occlusion, sphingomyelin, stroke recovery
2022-10-14 | PXD024106 | Pride
Project description:Erlotinib, as an EGFR small molecule inhibitor for pancreatic cancer, its efficacy as monotherapy is limited. Combination of erlotinib and gemcitabine has shown improvement in multiple survival indicators. However, drug resistance remains a challenge. Agrimoniin, the main active ingredient in Agrimonia pilosa, has anticancer potential. Whether it can serve as a synergistic or resistance-reversing drug for erlotinib require further research. In this study, we performed subcutaneous xenograft tumor experiments, CCK8, EdU assays, flow cytometry, HE staining, immunohistochemical and western blot to explore the synergistic effects of agrimoniin and erlotinib in inhibiting pancreatic cancer. Single-cell RNA sequencing was used to explore the relationship between their synergistic effects and tumor microenvironment. Through western blot and colorimetric assays for lactic acid, we studied the connection between their synergistic effects and aerobic glycolysis as well as lactic acid expression. By employing signal pathway inhibitors and agonists, we studied the positive feedback regulatory mechanism between relevant signal pathways and lactic acid expression. We found that agrimoniin and erlotinib synergistically inhibits the proliferation and promotes the apoptosis of pancreatic cancer cells. Together, they effectively suppress signal interaction among tumor cells, stromal cells and macrophages within subcutaneous tumors. They synergistically inhibit aerobic glycolysis and lactic acid expression in pancreatic cancer. Notably, we uncover the vicious cycle between the PI3K/AKT//HIF-1α/HK2, MEK/ERK/HIF-1α/HK2 signaling pathways and lactic acid expression. Combination of agrimoniin and erlotinib remodels tumor microenvironment, reprograms aerobic glycolysis, disrupts the positive feedback loop between lactic acid and two signaling pathways, thus synergistically inhibits the proliferation of pancreatic cancer cells.
2025-03-01 | GSE278383 | GEO