Infantile hemangiomas (IHs) are benign vascular neoplasms of childhood (prevalence 5-10%) due to the abnormal proliferation of endothelial cells. IHs are characterized by a peculiar natural life cycle enclosing three phases: proliferative (≤12 months), involuting (≥13 months), and involuted (up to 4-7 years). The mechanisms underlying this neoplastic disease still remain uncovered.
View Article and Find Full Text PDFThe combination of BRAF and MEK inhibitors demonstrated significant clinical benefit in patients with BRAF-mutant non-small cell lung cancer (NSCLC). However, the molecular mechanisms of acquired resistance to BRAF and MEK inhibition in NSCLC are still unknown. Herein, we report a case of a 76-year-old man with a history of smoking who was diagnosed with BRAF V600E-mutant lung adenocarcinoma (PD-L1 > 50%) and subsequently candidate to first-line therapy with pembrolizumab.
View Article and Find Full Text PDFBackground: Resistance to osimertinib in advanced EGFR-mutated non-small cell lung cancer (NSCLC) constitutes a significant challenge for clinicians either in terms of molecular diagnosis and subsequent therapeutic implications.
Methods: This is a prospective single-centre study with the primary objective of characterising resistance mechanisms to osimertinib in advanced EGFR-mutated NSCLC patients treated both in first- and in second-line. Next-Generation Sequencing analysis was conducted on paired tissue biopsies and plasma samples.
Background: Idiopathic pulmonary fibrosis (IPF) is an irreversible disorder with a poor prognosis. The incomplete understanding of IPF pathogenesis and the lack of accurate animal models is limiting the development of effective treatments. Thus, the selection of clinically relevant animal models endowed with similarities with the human disease in terms of lung anatomy, cell biology, pathways involved and genetics is essential.
View Article and Find Full Text PDFMalignant pleural mesothelioma is an asbestos-related tumor originating in mesothelial cells of the pleura that poorly responds to chemotherapeutic approaches. Adult mesenchymal stromal cells derived either from bone marrow or from adipose tissue may be considered a good model for cell-based therapy, a treatment which has experienced significant interest in recent years. The present study confirms that Paclitaxel is effective on mesothelioma cell proliferation in 2D and 3D in vitro cultures, and that 80,000 mesenchymal stromal cells loaded with Paclitaxel inhibit tumor growth at a higher extent than Paclitaxel alone.
View Article and Find Full Text PDFBackground: The Intensive Care Unit (ICU) Complexity Assessment and Monitoring to Ensure Optimal Outcomes (CAMEO) acuity tool quantifies patient acuity in terms of nursing cognitive workload complexity.
Objectives: The aim of this study was to refine the ICU CAMEO II acuity tool. An expert panel of nursing staff from 4 pediatric ICUs convened to refine the CAMEO II across a large, freestanding children's hospital in the United States.
Background: Malignant pleural mesothelioma is a pathology with no effective therapy and a poor prognosis. Our previous study demonstrated an in vitro inhibitory effect on mesothelioma cell lines of both the lysate and secretome of adipose tissue-derived Mesenchymal Stromal Cells. The inhibitory activity on tumor growth has been demonstrated also : five million Mesenchymal Stromal Cells, injected , produced a significant therapeutic efficacy against MSTO-211H xenograft equivalent to that observed after the systemic administration of paclitaxel.
View Article and Find Full Text PDFUnlabelled: The mechanisms underlying the success of propranolol in the treatment of infantile hemangioma (IH) remain elusive and do not fully explain the rapid regression of hemangiomatous lesions following drug administration. As autophagy is critically implicated in vascular homeostasis, we determined whether β-blockers trigger the autophagic flux on infantile hemangioma-derived endothelial cells (Hem-ECs) in vitro.
Material And Methods: Fresh tissue specimens, surgically removed for therapeutic purpose to seven children affected by proliferative IH, were subjected to enzymatic digestion.
Corneal injuries induced by various toxicants result in similar clinical presentations such as corneal opacity and neovascularization. Many studies suggest that several weeks post-exposure a convergence of the molecular mechanisms drives these progressive pathologies. However, chemical agents vary in toxicological properties, and early molecular responses are anticipated to be somewhat dissimilar for different toxicants.
View Article and Find Full Text PDFBackground: The aim of the present study was to dissect the clinical outcome of GB patients through the integration of molecular, immunophenotypic and MR imaging features.
Methods: We enrolled 57 histologically proven and molecularly tested GB patients (5.3% IDH-1 mutant).
Arrhythmogenic cardiomyopathy (ACM) is a genetic disease associated with sudden cardiac death and cardiac fibro-fatty replacement. Over the last years, several works have demonstrated that different epigenetic enzymes can affect not only gene expression changes in cardiac diseases but also cellular metabolism. Specifically, the histone acetyltransferase GCN5 is known to facilitate adipogenesis and modulate cardiac metabolism in heart failure.
View Article and Find Full Text PDFBackground: The Intensive Care Unit Complexity Assessment and Monitoring to Ensure Optimal Outcomes (ICU CAMEO III) acuity tool measures patient acuity in terms of the complexity of nursing cognitive workload.
Objective: To validate the ICU CAMEO III acuity tool in US children's hospitals.
Methods: Using a convenience sample, 9 sites enrolled children admitted to pediatric intensive care units (ICUs).
Introduction: ALK tyrosine kinase inhibitors (TKIs) are the standard treatment for advanced ALK-positive NSCLC. Nevertheless, drug resistance inevitably occurs. Here, we report a case of a patient with metastatic ALK-positive lung adenocarcinoma with an impressive resistance to sequential treatment with ALK TKIs mediated by and amplification in a contest of epithelial-to-mesenchymal transition and high progressive chromosomal instability.
View Article and Find Full Text PDFBackground: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor that has a significant incidence related to asbestos exposure with no effective therapy and poor prognosis. The role of mesenchymal stromal cells (MSCs) in cancer is controversial due to their opposite effects on tumor growth and in particular, only a few data are reported on MSCs and MPM.
Methods: We investigated the in vitro efficacy of adipose tissue-derived MSCs, their lysates and secretome against different MPM cell lines.
Radiomics has emerged as a noninvasive tool endowed with the potential to intercept tumor characteristics thereby predicting clinical outcome. In a recent study on resected non-small cell lung cancer (NSCLC), we identified highly prognostic computed tomography (CT) -derived radiomic features (RFs), which in turn were able to discriminate hot from cold tumor immune microenvironment (TIME). We aimed at validating a radiomic model capable of dissecting specific TIME profiles bearing prognostic power in resected NSCLC.
View Article and Find Full Text PDFOsimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) used both as the first-line treatment of EGFR-mutated non-small cell lung cancer patients and in second-line after T790M-positive disease progression to first- or second-generation TKIs. Unfortunately, patients unavoidably experience disease progression to osimertinib and the current research is focused on resistance mechanisms and the relative therapeutic strategy. We report the case of a patient with advanced EGFR-mutated (exon 19 deletion and T790M-positive) non-small cell lung cancer who developed disease progression to osimertinib characterized by the loss of T790M concurrently with the emergence of G724S EGFR mutation, which was tackled by subsequent afatinib treatment.
View Article and Find Full Text PDFIn recent years, there has been an increasing interest toward the covalent binding of bioactive peptides from extracellular matrix proteins on scaffolds as a promising functionalization strategy in the development of biomimetic matrices for tissue engineering. A totally new approach for scaffold functionalization with peptides is based on Molecular Imprinting technology. In this work, imprinted particles with recognition properties toward laminin and fibronectin bioactive moieties were synthetized and used for the functionalization of biomimetic sponges, which were based on a blend of alginate, gelatin, and elastin.
View Article and Find Full Text PDFBackground: There is limited data describing the characteristics of paediatric post-operative cardiac surgery patients who develop pneumothoraces after chest tube removal. Patient management after chest tube removal is not standardised across paediatric cardiac surgery programmes. The purposes of this study were to describe the frequency of pneumothorax after chest tube removal in paediatric post-operative cardiac surgical patients and to describe the patient and clinical characteristics of those patients who developed a clinically significant pneumothorax requiring intervention.
View Article and Find Full Text PDFThe use of injectable scaffolds to repair the infarcted heart is receiving great interest. Thermosensitive polymers, polymerization, cross-linking, and self-assembling peptides are the most investigated approaches to obtain injectability.Aim of the present work was the preparation and characterization of a novel bioactive scaffold, in form of injectable microspheres, for cardiac repair.
View Article and Find Full Text PDFThe immune regulation of cancer growth and regression has been underscored by the recent success of immunotherapy. The possibility that immune microenvironmental factors may impact on clinical outcome and treatment response still requires intense investigations. Hereby, supporting data of the research article "Integrated CT Imaging and Tissue Immune Features Disclose a Radio-Immune Signature with High Prognostic Impact on Surgically Resected NSCLC" [1], are presented.
View Article and Find Full Text PDFThe ATP-binding cassette (ABC) transporters P-glycoprotein (MDR1/), multidrug resistance-associated protein 1 (MRP1/), and breast cancer resistance protein (BCRP/) play a crucial role in the translocation of a broad range of drugs; data about their expression and activity in lung tissue are controversial. Here, we address their expression, localization and function in EpiAirway™, a three-dimensional (3D)-model of human airways; Calu-3 cells, a representative in vitro model of bronchial epithelium, are used for comparison. Transporter expression has been evaluated with RT-qPCR and Western blot, the localization with immunocytochemistry, and the activity by measuring the apical-to-basolateral and basolateral-to-apical fluxes of specific substrates in the presence of inhibitors.
View Article and Find Full Text PDFObjectives: Qualitative and quantitative CT imaging features might intercept the multifaceted tumor immune microenvironment (TIME), providing a non-invasive approach to design new prognostic models in NSCLC patients.
Materials And Methods: Our study population consisted of 100 surgically resected NSCLC patients among which 31 served as a validation cohort for quantitative image analysis. TIME was classified according to PD-L1 expression and the magnitude of Tumor Infiltrating Lymphocytes (TILs) and further defined as hot or cold by the tissue analysis of effector (CD8-to-CD3/PD-1-to-CD8) or inert (CD8-to-CD3/PD-1-to-CD8) phenotypes.