Β-blockers activate autophagy on infantile hemangioma-derived endothelial cells in vitro.

Unlabelled: 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.

Integrated MRI-Immune-Genomic Features Enclose a Risk Stratification Model in Patients Affected by Glioblastoma.

Background: 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).

and Amplifications as Synergistic Resistance Mechanisms to Different Generation ALK Tyrosine Kinase Inhibitors in Advanced NSCLC: Brief Report of Clinical and Preclinical Proofs.

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.

Inhibition of Human Malignant Pleural Mesothelioma Growth by Mesenchymal Stromal Cells.

Background: 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.

Validation of a radiomic approach to decipher NSCLC immune microenvironment in surgically resected patients.

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.

Development of Biomimetic Alginate/Gelatin/Elastin Sponges with Recognition Properties toward Bioactive Peptides for Cardiac Tissue Engineering.

In 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.

IGF-1 loaded injectable microspheres for potential repair of the infarcted myocardium.

The 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.

Dataset on the identification of a prognostic radio-immune signature in surgically resected Non Small Cell Lung Cancer.

The 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.

Integrated CT imaging and tissue immune features disclose a radio-immune signature with high prognostic impact on surgically resected NSCLC.

Objectives: 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.

Spatial architecture of tumour-infiltrating lymphocytes as a prognostic parameter in resected non-small-cell lung cancer.

Objectives: Tumour-infiltrating lymphocytes (TILs) are critically implicated in the clinical outcome and response to immunotherapy in non-small-cell lung cancer (NSCLC) patients. The functional competence of lymphocyte subpopulations is strongly conditioned by their spatial arrangement within the tumour immune microenvironment. The aim of this study was to determine whether the tissue localization of specific TIL subpopulations might have an impact on the risk of recurrence in surgically resected NSCLC.

Clinico-Immunological Profile of a 67-Year-Old Woman Affected by HER2-Positive Breast Cancer and Autoimmune Dermatomyositis.

A patient with HER2-positive early breast cancer (BC) developed dermatomyositis (DM), which disappeared after the first administration of adjuvant trastuzumab. No HER2 overexpression/amplification was observed in DM skin biopsies. Both BC and skin immune infiltrates were composed mostly of CD3+ T-lymphocytes.

Third generation EGFR inhibitor osimertinib combined with pemetrexed or cisplatin exerts long-lasting anti-tumor effect in EGFR-mutated pre-clinical models of NSCLC.

Background: The third generation Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) osimertinib has been initially approved for T790M positive Non-Small Cell Lung Cancer (NSCLC) and more recently for first-line treatment of EGFR-mutant T790M negative NSCLC patients. Similarly to previous generation TKIs, despite the high response rate, disease progression eventually occurs and current clinical research is focused on novel strategies to delay the emergence of osimertinib resistance. In this study we investigated the combination of osimertinib with pemetrexed or cisplatin in EGFR-mutated NSCLC cell lines and xenografts.

The circulating pool of functionally competent NK and CD8+ cells predicts the outcome of anti-PD1 treatment in advanced NSCLC.

Introduction: A prospective investigation of the circulating immune profile in NSCLC patients receiving nivolumab was performed to identify potentially predictive parameters.

Methods: Flow Cytometry of peripheral blood (PB) CD3+, CD8+, CD4+, NK, Treg and MDSCs was prospectively performed in 31 consecutive advanced NSCLC patients at baseline (T0) and after 2 (T1) and 4 (T2) cycles of bi-weekly nivolumab. Functional molecules (PD-1, CD3ζ, Granzyme B, Perforin), cell proliferation (Ki67) and NK receptors (NKG2 A, NKG2D, NKp30) were also explored.

Influence of injectable microparticle size on cardiac progenitor cell response.

Introduction: Injectable scaffolds are emerging as a promising strategy in the field of myocardial tissue engineering. Among injectable scaffolds, microparticles have been poorly investigated. The goal of this study was the development of novel gelatin/gellan microparticles that could be used as an injectable scaffold to repair the infarcted myocardium.

Blood and lymphatic vessels contribute to the impact of the immune microenvironment on clinical outcome in non-small-cell lung cancer.

Objectives: Lymphangiogenesis plays a critical role in the immune response, tumour progression and therapy effectiveness. The aim of this study was to determine whether the interplay between the lymphatic and the blood microvasculature, tumour-infiltrating lymphocytes and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint constitutes an immune microenvironment affecting the clinical outcome of patients with non-small-cell lung cancer.

Methods: Samples from 50 squamous cell carcinomas and 42 adenocarcinomas were subjected to immunofluorescence to detect blood and lymphatic vessels.

Enhancement of the anti-tumor activity of FGFR1 inhibition in squamous cell lung cancer by targeting downstream signaling involved in glucose metabolism.

Fibroblast Growth Factor Receptor (FGFR) signaling is a complex pathway which controls several processes, including cell proliferation, survival, migration, and metabolism. FGFR1 signaling is frequently deregulated via amplification/over-expression in NSCLC of squamous histotype (SQCLC), however its inhibition has not been successfully translated in clinical setting. We determined whether targeting downstream signaling implicated in FGFR1 effects on glucose metabolism potentiates the anti-tumor activity of FGFR1 inhibition in SQCLC.

Low PD-1 Expression in Cytotoxic CD8 Tumor-Infiltrating Lymphocytes Confers an Immune-Privileged Tissue Microenvironment in NSCLC with a Prognostic and Predictive Value.

The success of immune checkpoint inhibitors strengthens the notion that tumor growth and regression are immune regulated. To determine whether distinct tissue immune microenvironments differentially affect clinical outcome in non-small cell lung cancer (NSCLC), an extended analysis of PD-L1 and tumor-infiltrating lymphocytes (TIL) was performed. Samples from resected adenocarcinoma (ADC 42), squamous cell carcinoma (SCC 58), and 26 advanced diseases (13 ADC and 13 SCC) treated with nivolumab were analyzed.

Imatinib mesylate-induced cardiomyopathy involves resident cardiac progenitors.

Cardiovascular complications are included among the systemic effects of tyrosine kinase inhibitor (TKI)-based therapeutic strategies. To test the hypothesis that inhibition of Kit tyrosine kinase that promotes cardiac progenitor cell (CPC) survival and function may be one of the triggering mechanisms of imatinib mesylate (IM)-related cardiovascular effects, the anatomical, structural and ultrastructural changes in the heart of IM-treated rats were evaluated. Cardiac anatomy in IM-exposed rats showed a dose-dependent, restrictive type of remodeling and depressed hemodynamic performance in the absence of remarkable myocardial fibrosis.

Enhanced efficacy of AKT and FAK kinase combined inhibition in squamous cell lung carcinomas with stable reduction in PTEN.

Squamous cell lung carcinoma (SCC) accounts for 30% of patients with NSCLC and to date, no molecular targeted agents are approved for this type of tumor. However, recent studies have revealed several oncogenic mutations in SCC patients, including an alteration of the PI3K/AKT pathway, i.e.

Combined Inhibition of CDK4/6 and PI3K/AKT/mTOR Pathways Induces a Synergistic Anti-Tumor Effect in Malignant Pleural Mesothelioma Cells.

Malignant pleural mesothelioma (MPM) is a progressive malignancy associated to the exposure of asbestos fibers. The most frequently inactivated tumor suppressor gene in MPM is CDKN2A/ARF, encoding for the cell cycle inhibitors p16 and p14, deleted in about 70% of MPM cases. Considering the high frequency of alterations of this gene, we tested in MPM cells the efficacy of palbociclib (PD-0332991), a highly selective inhibitor of cyclin-dependent kinase (CDK) 4/6.

Parenchymal and Stromal Cells Contribute to Pro-Inflammatory Myocardial Environment at Early Stages of Diabetes: Protective Role of Resveratrol.

Little information is currently available concerning the relative contribution of cardiac parenchymal and stromal cells in the activation of the pro-inflammatory signal cascade, at the initial stages of diabetes. Similarly, the effects of early resveratrol (RSV) treatment on the negative impact of diabetes on the different myocardial cell compartments remain to be defined. In vitro challenge of neonatal cardiomyocytes and fibroblasts to high glucose and in vivo/ex vivo experiments on a rat model of Streptozotocin-induced diabetes were used to specifically address these issues.

A Versatile Bioreactor for Dynamic Suspension Cell Culture. Application to the Culture of Cancer Cell Spheroids.

A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress conditions has been developed and preliminarily tested culturing cancer cell spheroids. By adopting simple technological solutions and avoiding rotating components, the bioreactor exploits the laminar hydrodynamics establishing within the culture chamber enabling dynamic cell suspension in an environment favourable to mass transport, under a wide range of tunable shear stress conditions. The design phase of the device has been supported by multiphysics modelling and has provided a comprehensive analysis of the operating principles of the bioreactor.

Combination of Gefitinib and Pemetrexed Prevents the Acquisition of TKI Resistance in NSCLC Cell Lines Carrying EGFR-Activating Mutation.

Introduction: Development of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors is a clinical issue in patients with epidermal growth factor receptor gene (EGFR)-mutated non-small cell lung cancer (NSCLC). The aim of this study was to investigate the potential of combining gefitinib and pemetrexed in preventing the acquisition of resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines harboring EGFR exon 19 deletion.

Methods: The effect of different combinatorial schedules of gefitinib and pemetrexed on cell proliferation, cell cycle, apoptosis, and acquisition of gefitinib resistance in PC9 and HCC827 NSCLC cell lines and in PC9 xenograft models was investigated.

Isolation and Characterization of Human Lung Lymphatic Endothelial Cells.

Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied.