BPhaCar
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB70849 | ENA |
REPOSITORIES: ENA
Similar Datasets
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Project description:Although up to 80% small-cell lung cancer (SCLC) patients response good for first-line chemotherapy regimen, most patients develop recurrence of the disease within weeks to months. Here, we report cytostatic effect of Leflu and Teri on SCLC cell proliferation through inhibition of DRP1 phosphorylation at Ser616 and decreased mitochondrial fragmentation. When administered together, Teri and carboplatin (Carbo) acted synergistically to significantly inhibit cell proliferation and DRP1 phosphorylation, reduce abundance of intermediates in pyrimidine de novo pathway, and increase apoptosis and DNA damage. Combination of Leflu&Carbo has anti-tumorigenic effect in vivo. Additionally, lurbinectedin (Lur) and Teri potently and synergistically inhibited spheroid growth, and depleted uridine and DRP1 phosphorylation in mouse tumors. Our results suggest combinations of Carbo and Lur with Teri or Leflu are efficacious and underscore how the relationship between DRP1/DHODH and mitochondrial plasticity serves as a potential therapeutic target to validate these treatment strategies in SCLC clinical trials.
2024-05-22 | GSE267928 | GEO
Project description:Modern 21st century toxicity testing makes use of omics technologies to address critical questions in toxicology and chemical management. Of interest are questions relating to chemical mechanisms of toxicity, differences in species sensitivity, and translation of molecular effects to observable apical endpoints. Our study addressed these questions by comparing apical outcomes and multiple omics responses in early-life stage exposure studies with Japanese quail (JQ; Coturnix japonica) and double crested cormorant (DCCO; Phalacrocorax auritus), representing a model and ecological species, respectively. Specifically, we investigated the dose-dependent response of apical outcomes, transcriptomics, and metabolomics in the liver in each species exposed to chlorpyrifos (CPF), a widely used organophosphate pesticide. Our results revealed a clear pattern of dose-dependent disruption of gene expression and metabolic profiles in JQ but not DCCO at similar CPF exposure concentrations. The difference in effect sensitivity between species was likely due to higher metabolic transformation of CPF in the precocial JQ compared to the more altricial DCCO. The most impacted biological pathways after CPF exposure in JQ included hepatic metabolism, oxidative stress, endocrine disruption (steroid and non-steroid hormones), and metabolic disease (lipid and fatty acid metabolism). Importantly, we show consistent responses across biological scales, suggesting that significant disruption at the level of gene expression and metabolite profiles leads to observable apical responses at the organism level. Our study demonstrates the utility of evaluating effects at multiple biological levels of organization to understand how modern toxicity testing relates to outomes of regulatory relevance, while also highlighting important, yet poorly understood, species differences in sensitivity to chemical exposure.
2021-07-15 | GSE179770 | GEO