Iron chelation as a new therapeutic approach to prevent senescence and liver fibrosis progression.

Iron overload and cellular senescence have been implicated in liver fibrosis, but their possible mechanistic connection has not been explored. To address this, we have delved into the role of iron and senescence in an experimental model of chronic liver injury, analyzing whether an iron chelator would prevent liver fibrosis by decreasing hepatocyte senescence. The model of carbon tetrachloride (CCl) in mice was used as an experimental model of liver fibrosis.

The hepatocyte epidermal growth factor receptor (EGFR) pathway regulates the cellular interactome within the liver fibrotic niche.

Liver fibrosis is the consequence of chronic liver injury in the presence of an inflammatory component. Although the main executors of this activation are known, the mechanisms that lead to the inflammatory process that mediates the production of pro-fibrotic factors are not well characterized. Epidermal growth factor receptor (EGFR) signaling in hepatocytes is essential for the regenerative processes of the liver; however, its potential role in regulating the fibrotic niche is not yet clear.

Transcriptional analysis of landmark molecular pathways in lung adenocarcinoma results in a clinically relevant classification with potential therapeutic implications.

Lung adenocarcinoma (LUAD) is a molecularly heterogeneous disease. In addition to genomic alterations, cancer transcriptional profiling can be helpful to tailor cancer treatment and to estimate each patient's outcome. Transcriptional activity levels of 50 molecular pathways were inferred in 4573 LUAD patients using Gene Set Variation Analysis (GSVA) method.

Dissecting the role of the NADPH oxidase NOX4 in TGF-beta signaling in hepatocellular carcinoma.

The NADPH oxidase NOX4 has been proposed as necessary for the apoptosis induced by the Transforming Growth Factor-beta (TGF-β) in hepatocytes and hepatocellular carcinoma (HCC) cells. However, whether NOX4 is required for TGF-β-induced canonical (SMADs) or non-canonical signals is not fully understood yet, neither its potential involvement in other parallel actions induced by TGF-β. In this work we have used CRISPR Cas9 technology to stable attenuate NOX4 expression in HCC cells.

The NADPH oxidase NOX4 regulates redox and metabolic homeostasis preventing HCC progression.

Background And Aims: The NADPH oxidase NOX4 plays a tumor-suppressor function in HCC. Silencing NOX4 confers higher proliferative and migratory capacity to HCC cells and increases their in vivo tumorigenic potential in xenografts in mice. NOX4 gene deletions are frequent in HCC, correlating with higher tumor grade and worse recurrence-free and overall survival rates.

Breast cancer dormancy is associated with a 4NG1 state and not senescence.

Reactivation of dormant cancer cells can lead to cancer relapse, metastasis, and patient death. Dormancy is a nonproliferative state and is linked to late relapse and death. No targeted therapy is currently available to eliminate dormant cells, highlighting the need for a deeper understanding and reliable models.

Gene Expression Profiling as a Potential Tool for Precision Oncology in Non-Small Cell Lung Cancer.

Recent technological advances and the application of high-throughput mutation and transcriptome analyses have improved our understanding of cancer diseases, including non-small cell lung cancer. For instance, genomic profiling has allowed the identification of mutational events which can be treated with specific agents. However, detection of DNA alterations does not fully recapitulate the complexity of the disease and it does not allow selection of patients that benefit from chemo- or immunotherapy.

Efficacy of CDK4/6 inhibitors in preclinical models of malignant pleural mesothelioma.

Background: There is no effective therapy for patients with malignant pleural mesothelioma (MPM) who progressed to platinum-based chemotherapy and immunotherapy.

Methods: We aimed to investigate the antitumor activity of CDK4/6 inhibitors using in vitro and in vivo preclinical models of MPM.

Results: Based on publicly available transcriptomic data of MPM, patients with CDK4 or CDK6 overexpression had shorter overall survival.

Clathrin switches transforming growth factor-β role to pro-tumorigenic in liver cancer.

Background & Aims: Upon ligand binding, tyrosine kinase receptors, such as epidermal growth factor receptor (EGFR), are recruited into clathrin-coated pits for internalization by endocytosis, which is relevant for signalling and/or receptor degradation. In liver cells, transforming growth factor-β (TGF-β) induces both pro- and anti-apoptotic signals; the latter are mediated by the EGFR pathway. Since EGFR mainly traffics via clathrin-coated vesicles, we aimed to analyse the potential role of clathrin in TGF-β-induced signalling in liver cells and its relevance in liver cancer.

Evaluation and comparison of bioinformatic tools for the enrichment analysis of metabolomics data.

Background: Bioinformatic tools for the enrichment of 'omics' datasets facilitate interpretation and understanding of data. To date few are suitable for metabolomics datasets. The main objective of this work is to give a critical overview, for the first time, of the performance of these tools.