The EGFR Signaling Modulates in Mesenchymal Stem Cells the Expression of miRNAs Involved in the Interaction with Breast Cancer Cells.

We previously demonstrated that the epidermal growth factor receptor (EGFR) modulates in mesenchymal stem cells (MSCs) the expression of a number of genes coding for secreted proteins that promote breast cancer progression. However, the role of the EGFR in modulating in MSCs the expression of miRNAs potentially involved in the progression of breast cancer remains largely unexplored. Following small RNA-sequencing, we identified 36 miRNAs differentially expressed between MSCs untreated or treated with the EGFR ligand transforming growth factor α (TGFα), with a fold change (FC) < 0.

SARS-CoV-2 complete genome sequencing from the Italian Campania region using a highly automated next generation sequencing system.

Background: Since the first complete genome sequencing of SARS-CoV-2 in December 2019, more than 550,000 genomes have been submitted into the GISAID database. Sequencing of the SARS-CoV-2 genome might allow identification of variants with increased contagiousness, different clinical patterns and/or different response to vaccines. A highly automated next generation sequencing (NGS)-based method might facilitate an active genomic surveillance of the virus.

Challenges in bioinformatics approaches to tumor mutation burden analysis.

Several immune checkpoint inhibitors (ICIs) have already been introduced into clinical practice or are in advanced phases of clinical experimentation. Extensive efforts are being made to identify robust biomarkers to select patients who may benefit from treatment with ICIs. Tumor mutation burden (TMB) may be a relevant biomarker of response to ICIs in different tumor types; however, its clinical use is challenged by the analytical methods required for its evaluation.

Targeted sequencing analysis of cell-free DNA from metastatic non-small-cell lung cancer patients: clinical and biological implications.

Background: Sequencing artifacts, clonal hematopoietic mutations of indeterminate potential (CHIP) and tumor heterogeneity have been hypothesized to contribute to the low concordance between tissue and cell-free DNA (cfDNA) molecular profiling with targeted sequencing.

Methods: We analyzed by targeted sequencing cfDNA from 30 healthy individuals, and cfDNA and matched tumor samples from 30 EGFR-mutant and 77 EGFR wild-type metastatic non-small-cell lung cancer (mNSCLC) patients. Discordant cases were solved by droplet digital PCR (ddPCR).

Measuring tumor mutation burden in non-small cell lung cancer: tissue versus liquid biopsy.

The introduction in the clinic of immune checkpoint inhibitors (IOs) has represented an important improvement for the treatment of patients with advanced non-small cell lung cancer (NSCLC). These drugs have shown a higher activity as compared with chemotherapy in both first- and second-line of treatment, with some patients experiencing a long-lasting response. More recently, combinations of IOs have entered clinical trials in different tumor types including NSCLC.

The role of circulating free DNA in the management of NSCLC.

Circulating cell-free DNA (cfDNA) testing has emerged as an alternative to tumor tissue analyses for the management of metastatic non-small-cell lung cancer (NSCLC) patients. Analysis of cfDNA is a minimally invasive procedure that might better reflect tumor heterogeneity and allows repeated testing over the time. Areas covered: This review article covers the different applications of cfDNA testing in NSCLC: early diagnosis of the disease; detection of minimal residual disease in early lung cancer; identification of predictive and prognostic markers in advanced NSCLC patients; monitoring the response to therapy; assessment of tumor mutation burden.

Human lung adenocarcinoma cell cultures derived from malignant pleural effusions as model system to predict patients chemosensitivity.

Background: Lung cancer is the leading cause of cancer related deaths and Malignant Pleural Effusion (MPE) is a frequent complication. Current therapies suffer from lack of efficacy in a great percentage of cases, especially when cancer is diagnosed at a late stage. Moreover patients' responses vary and the outcome is unpredictable.

The gene expression profiling of hepatocellular carcinoma by a network analysis approach shows a dominance of intrinsically disordered proteins (IDPs) between hub nodes.

We have analyzed the transcriptomic data from patients with hepatocellular carcinoma (HCC) after viral HCV infection at the various stages of the disease by means of a networking analysis using the publicly available E-MTAB-950 dataset. The data was compared with those obtained in our group from HepG2 cells, a cancer cell line that lacks the viral infection. By sequential pruning of data, and also taking into account the data from cells of healthy patients as blanks, we were able to obtain a distribution of hub genes for the various stages that characterize the disease and finally, we isolated a metabolic sub-net specific to HCC alone.

Structure-fluctuation-function relationships of seven pro-angiogenic isoforms of VEGFA, important mediators of tumorigenesis.

Vascular endothelial growth factor A (VEGFA) has different biological activities and plays a central role in tumor proliferation, angiogenesis and metastasis. Different VEGFA isoforms are generated by alternative splice site selection of exons 6, 7 and 8. In this paper, we analyzed the physical and chemical properties of the VEGFA exon 6 sequence, and modeled the three-dimensional structures of the regions corresponding to exons 6, 7 and 8 of six different pro-angiogenic isoforms of VEGFA in comparison to the experimental structure of VEGFA_165 by a combined approach of fold recognition and comparative modeling strategies and molecular dynamics simulations.

RNA-seq analysis reveals significant effects of EGFR signalling on the secretome of mesenchymal stem cells.

Bone marrow-derived mesenchymal stem cells (MSCs) contribute to breast cancer progression by releasing soluble factors that sustain tumor progression. MSCs express functional epidermal growth factor receptor (EGFR) and breast cancer cells secrete EGFR-ligands including transforming growth factor-α (TGFα). Using RNA-sequencing, we analysed the whole transcriptome of MSCs stimulated with TGFα.

Structure-function relationship and evolutionary history of the human selenoprotein M (SelM) found over-expressed in hepatocellular carcinoma.

In humans we know 25 selenoproteins that play important roles in redox regulation, detoxification, immune-system protection and viral suppression. In particular, selenoprotein M (SelM) may function as thiol disulfide oxidoreductase that participates in the formation of disulfide bonds, and can be implicated in calcium responses. However, it presents a redox motif (CXXU), where U is a selenocysteine, and may also function as redox regulator because its decreased or increased expression regulated by dietary selenium alters redox homeostasis.

Molecular diagnostics and personalized medicine in oncology: challenges and opportunities.

Increasing evidence demonstrates that target-based agents are active only in molecularly selected populations of patients. Therefore, the identification of predictive biomarkers has become mandatory to improve the clinical development of these novel drugs. Mutations of the epidermal growth factor receptor (EGFR) or rearrangements of the ALK gene in non-small-cell lung cancer, and BRAF mutations in melanoma are clear examples of driver mutations and predictive biomarkers of response to treatment with specific inhibitors.