Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA237112 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Male and female CD-1 mice were administered dietary Phenobarbital for 2 or 7 days. In-life, enzyme activity, cell proliferation, genomic analysis, and Bench-mark dose modeling was carried out. The goal was to exmaine low-dose PB effects on early key events in CAR-mediated hepatocarcinogenesis. PB at 0, 0.15, 1.5, 15, 75, or 150 mg/kg-day for 2 or 7 days to characterize multiple apical and molecular endpoints.
2014-02-01 | E-GEOD-54597 | biostudies-arrayexpress
Project description:Male and female CD-1 mice were administered dietary Phenobarbital for 2 or 7 days. In-life, enzyme activity, cell proliferation, genomic analysis, and Bench-mark dose modeling was carried out. The goal was to exmaine low-dose PB effects on early key events in CAR-mediated hepatocarcinogenesis.
2014-02-01 | GSE54597 | GEO
Project description:The modes of triazole reproductive toxicity have been characterized by an observed increased in serum testosterone and reduced insemination and fertility indices. The key events involved in the disruption in testosterone homeostasis and reduced fertility remain unclear. Gene expression analysis was conducted on liver and testis from Wistar Han IGS rats fed myclobutanil (M: 500, 2000 ppm), propiconazole (P: 500, 2500 ppm), or triadimefon (T: 500, 1800 ppm) from gestation day six to postnatal day 92. Pathway-based analysis highlighted key biological processes affected by all three triazoles in the liver including fatty acid catabolism, steroid metabolism, and xenobiotic metabolism. Triadimefon induced a distinctive expression profile of genes involved in liver sterol biosynthesis. There were no common pathways modulated by all three triazoles in the testis. Within the pathways identified in the liver, specific genes involved in phase I-III metabolism (Aldh1a1, Cyp1a1, Cyp2b2, Cyp3a1, Slco1a4, Udpgtr2), fatty acid metabolism (Cyp4a10, Pc, Ppap2b), and steroid metabolism (Srd5a1, Ugt1a1, Ugt2a1) were affected by all three triazoles. These modulated genes are part of a network of lipid and testosterone homeostasis pathways regulated by the constitutive androstane (CAR) and pregnane X (PXR) receptors. Gene expression profiles from this study indicate triazoles activate CAR and PXR; increase fatty acid catabolism, sterol biosynthesis, and steroid metabolism in the liver; constituting a plausible series of key events contributing to the observed disruption in testosterone homeostasis. Experiment Overall Design: A total of 34 testis samples were analyzed. Seven biological replicates for control, 4 biological replicates for mid dose myclobutanil, 5 biological replicates for high dose myclobutanil, 4 biological replicates for mid dose propiconazole, 5 biological replicates for high dose propiconazole, 4 biological replicates for mid dose triadimefon, and 5 biological replicates for high dose triadimefon.
2008-04-09 | E-GEOD-10412 | biostudies-arrayexpress
Project description:The modes of triazole reproductive toxicity have been characterized by an observed increased in serum testosterone and reduced insemination and fertility indices. The key events involved in the disruption in testosterone homeostasis and reduced fertility remain unclear. Gene expression analysis was conducted on liver and testis from Wistar Han IGS rats fed myclobutanil (M: 500, 2000 ppm), propiconazole (P: 500, 2500 ppm), or triadimefon (T: 500, 1800 ppm) from gestation day six to postnatal day 92. Pathway-based analysis highlighted key biological processes affected by all three triazoles in the liver including fatty acid catabolism, steroid metabolism, and xenobiotic metabolism. Triadimefon induced a distinctive expression profile of genes involved in liver sterol biosynthesis. There were no common pathways modulated by all three triazoles in the testis. Within the pathways identified in the liver, specific genes involved in phase I-III metabolism (Aldh1a1, Cyp1a1, Cyp2b2, Cyp3a1, Slco1a4, Udpgtr2), fatty acid metabolism (Cyp4a10, Pc, Ppap2b), and steroid metabolism (Srd5a1, Ugt1a1, Ugt2a1) were affected by all three triazoles. These modulated genes are part of a network of lipid and testosterone homeostasis pathways regulated by the constitutive androstane (CAR) and pregnane X (PXR) receptors. Gene expression profiles from this study indicate triazoles activate CAR and PXR; increase fatty acid catabolism, sterol biosynthesis, and steroid metabolism in the liver; constituting a plausible series of key events contributing to the observed disruption in testosterone homeostasis. Experiment Overall Design: A total of 35 liver samples were analyzed. Seven biological replicates for the controls, 5 biological replicates for mid dose myclobutanil and 5 biological replicates for high dose mylcobutanil. There are 5 biological replicates for mid dose propiconazole, 4 biological replicates for high dose propiconazole, 5 biological replicates for mid dose triadimefon, and 4 biological replicates for triadimefon.
2008-04-09 | E-GEOD-10411 | biostudies-arrayexpress
Project description:Studies on gene and/or microRNA (miRNA) dysregulation in the early stages of hepatocarcinogenesis are hampered by the difficulty of diagnosing early lesions in humans. Experimental models recapitulating human hepatocellular carcinoma (HCC) are then entailed to perform this analysis. We performed miRNA and gene expression profiling to characterize the molecular events involved in the multistep process of hepatocarcinogenesis in the Resistant-Hepatocyte rat model. A high percentage of dysregulated miRNAs/genes in HCC were similarly altered in early preneoplastic lesions positive for the stem/progenitor cell marker cytokeratin-19, indicating that several HCC-associated alterations occur from the very beginning of the carcinogenic process. Our analysis also identified miRNA/gene-target networks aberrantly activated at the initial stage of hepatocarcinogenesis. Activation of the NRF2 pathway and up-regulation of the miR-200 family were among the most prominent changes. The relevance of these alterations in the development of HCC was confirmed by the observation that NRF2 silencing impaired while miR-200a overexpression promoted HCC cell proliferation in vitro. Moreover, T3-induced in vivo inhibition of the NRF2 pathway accompanied the regression of cytokeratin-19 positive nodules, suggesting that activation of this transcription factor contributes to the onset and progression of preneoplastic lesions towards malignancy. The finding that 78% of genes and 57% of dysregulated miRNAs in rat HCC have been previously associated to human HCC as well underlines the translational value of our results. Conclusions: this study indicates that most of the molecular changes found in HCC occur in the very early stages of hepatocarcinogenesis. Among these, the NRF2 pathway plays a relevant role and may represent a new therapeutic target. 20 nodules (10 weeks after initiation with DENA), 4 adenomas (10 months), 5 eHCCs (10 months) and 9 aHCCs (14 months) were dissected. 10 controls also included.
2013-02-07 | E-GEOD-44106 | biostudies-arrayexpress
Project description:Studies on gene and/or microRNA (miRNA) dysregulation in the early stages of hepatocarcinogenesis are hampered by the difficulty of diagnosing early lesions in humans. Experimental models recapitulating human hepatocellular carcinoma (HCC) are then entailed to perform this analysis. We performed miRNA and gene expression profiling to characterize the molecular events involved in the multistep process of hepatocarcinogenesis in the Resistant-Hepatocyte rat model. A high percentage of dysregulated miRNAs/genes in HCC were similarly altered in early preneoplastic lesions positive for the stem/progenitor cell marker cytokeratin-19, indicating that several HCC-associated alterations occur from the very beginning of the carcinogenic process. Our analysis also identified miRNA/gene-target networks aberrantly activated at the initial stage of hepatocarcinogenesis. Activation of the NRF2 pathway and up-regulation of the miR-200 family were among the most prominent changes. The relevance of these alterations in the development of HCC was confirmed by the observation that NRF2 silencing impaired while miR-200a overexpression promoted HCC cell proliferation in vitro. Moreover, T3-induced in vivo inhibition of the NRF2 pathway accompanied the regression of cytokeratin-19 positive nodules, suggesting that activation of this transcription factor contributes to the onset and progression of preneoplastic lesions towards malignancy. The finding that 78% of genes and 57% of dysregulated miRNAs in rat HCC have been previously associated to human HCC as well underlines the translational value of our results. Conclusions: this study indicates that most of the molecular changes found in HCC occur in the very early stages of hepatocarcinogenesis. Among these, the NRF2 pathway plays a relevant role and may represent a new therapeutic target.
2013-02-07 | GSE44106 | GEO
Project description:Dose and Effect Thresholds for Early Key Events in a PPARα Tumorigenic Mode of Action
| PRJNA270349 | ENA
Project description:Oncogene activation drives changes in pathways related to cell proliferation, metabolism, and immune evasion, offering insights into molecular events underpinning hepatocarcinogenesis
2026-04-16 | PXD064126 | Pride
Project description:Background/Issue and Objectives: Health risks from chronic low dose radiation exposures encountered in environmental and occupational settings are uncertain. A key aspect to understanding health risks is precise and accurate modelling of the dose-response relationship. Benchmark dose (BMD) modeling is an approach used in chemical hazard assessments to identify the dose at which a pre-defined (e.g., 10%) change relative to background occurs. Herein, this method is being explored for radiation hazard assessments along with Adverse Outcome Pathways (AOPs), a knowledge framework of causally linked chains of key events (KEs) from a molecular initiating event to an adverse outcome (AO). Design/Method/Description: Blood was drawn from human participants (6 females and 8 males), and lymphocytes were isolated, cultured and X-irradiated at a lower dose-rate (LDR: 0.05 Gy/minute) and higher dose-rate (HDR: 1 Gy/minute) across nine different doses (0, 0.05, 0.10 0.25, 0.5, 1, 2, 4 and 6 Gy). Transcriptomic and proteomic changes were then assessed 24 hours post-exposure. Concurrently, cell membrane integrity and cellular ATP level were also measured, which are markers of radiation injuries. BMD values were then derived for each endpoint and pathways enriched in omics data were compared with Kes in an existing AOP to leukemia (www.aopwiki.org/aop/432). Conclusions/Impacts/Outcomes/Implications/Next Steps: By using AOPs as an organizational framework and BMD modeling for dose-response analysis, it provides a pragmatic platform to analyse complex data for radiation hazard assessment. Future work will entail in-depth analysis of the responses specific to LDR and HDR and effects of confounding factors on BMD values.
2025-02-28 | GSE260589 | GEO
Project description:To clarify the regulatory molecular mechanisms behind cell cycle aberrations related to the early stages of hepatocarcinogenesis. We investigated the early stage of hepatocarcinogenesis using global expression analyses.
2012-12-21 | GSE43066 | GEO