Pulmonary Cell News Volume 6.07 | Feb 23 2017

TOP STORY

Cellular Senescence Mediates Fibrotic Pulmonary Disease

Scientists demonstrated elevated abundance of senescence biomarkers in idiopathic pulmonary fibrosis lung, with p16 expression increasing with disease severity. They showed that the secretome of senescent fibroblasts, which are selectively killed by a senolytic cocktail, dasatinib plus quercetin, is fibrogenic. [Nat Commun] Full Article | Press Release

(Ranked by impact factor of the journal)

Intelectin Contributes to Allergen-Induced IL-25, IL-33, and TSLP Expression and Type 2 Response in Asthma and Atopic Dermatitis

Intelectin (ITLN) is expressed in airway epithelial cells and promotes allergic airway inflammation. Researchers hypothesized that ITLN is required for allergen-induced IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) expression. In two asthma models, Itln knockdown reduced allergen-induced increases in Il-25, Il-33, and Tslp and development of type 2 response, eosinophilic inflammation, mucus overproduction, and airway hyperresponsiveness. [Mucosal Immunol] Abstract

Lyn Regulates Mucus Secretion and MUC5AC via the STAT6 Signaling Pathway during Allergic Airway Inflammation

Scientists demonstrated that Lyn overexpression decreased the mucus hypersecretion and levels of the muc5ac transcript in mice exposed to ovalbumin (OVA). Chromatin immunoprecipitation analysis confirmed that Lyn overexpression decreased the binding of STAT6 to the promoter region of Muc5ac in mice exposed to OVA. [Sci Rep] Full Article

β2-Microglobulin Participates in Development of Lung Emphysema by Inducing Lung Epithelial Cells Senescence

Scientists investigated the effect of β2-microglobulin (β2m) in development of lung emphysema. They found that concentrations of β2m in plasma were significantly elevated in patients with lung emphysema than those in normal control subjects. [Am J Physiol Lung Cell Mol Physiol] Abstract

Maresin1 Stimulates Alveolar Fluid Clearance through the Alveolar Epithelial Sodium Channel Na,K-ATPase via the ALX/PI3K/Nedd4-2 Pathway

Researchers sought to investigate the effect and underlining mechanisms of Maresin1 (MaR1) in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. In primary rat alveolar type II epithelial cells, MaR1 was added to the culture medium with lipopolysaccharide. MaR1 markedly stimulated AFC in LPS-induced lung injury, with the outcome of decreased pulmonary edema and lung injury. [Lab Invest] Abstract

LUNG CANCER

Tumor-Associated Neutrophils and Loss of Epithelial PTEN Can Promote Corticosteroid-Insensitive MMP-9 Expression in the Chronically Inflamed Lung Microenvironment

Matrix metalloproteinase-9 (MMP-9) transcript measured within the tumor region from patients with non-small-cell lung cancer and coexisting COPD was found to be uniformly increased relative to adjacent tumor-free tissue. To explore whether PTEN can regulate epithelial MMP-9 expression, the authors used a small interfering RNA knockdown strategy was used in Beas-2B bronchial epithelial cells. PTEN knockdown by siRNA selectively increased MMP-9 expression in response to lipopolysaccharide in a corticosteroid-insensitive manner. [Thorax] Full Article

Context-Dependent Effects of Amplified MAPK Signaling during Lung Adenocarcinoma Initiation and Progression

To better understand the effects of mitogen-activated protein kinase (MAPK) signaling downstream of Kras^G12D expression, scientists capitalized on the ability of Braf inhibition to selectively amplify MAPK pathway signaling in Kras^G12D-expressing epithelial cells. [Cell Rep] Full Article | Graphical Abstract

miR-203 Enhances Let-7 Biogenesis by Targeting LIN28B to Suppress Tumor Growth in Lung Cancer

Investigators report that microRNA (miR)-203 enhances the biogenesis of tumor suppressor let-7 in lung cancer by directly targeting LIN28B. They found that the LIN28B protein levels were dramatically increased in lung cancer tissues, but its mRNA levels did not differ significantly, suggesting that a post-transcriptional mechanism is involved in LIN28B regulation. [Sci Rep] Full Article

DDA1, a Novel Oncogene, Promotes Lung Cancer Progression through Regulation of Cell Cycle

Scientists aimed to investigate whether DET1 and DDB1 associated 1 (DDA1) contributes to tumorigenesis and progression of lung cancer. They found that the expression of DDA1 in normal lung cells and tissue was significantly lower than that in lung cancer and was associated with poor prognosis. DDA1 overexpression promoted proliferation of lung tumor cells and facilitated cell cycle progression in vitro and subcutaneous xenograft tumor progression in vivo. [J Cell Mol Med] Full Article

Oxidative Stress in COPD: Sources, Markers, and Potential Mechanisms

Markers of oxidative stress are increased in chronic obstructive pulmonary disease (COPD) and reactive oxygen species (ROS) are able to alter biological molecules, signaling pathways and antioxidant molecule function, many of which have been implicated in the pathogenesis of COPD. The authors discuss the sources of ROS, and the defences that have evolved to protect against their harmful effects. [J Clin Med] Full Article | Graphical Abstract

Visit our reviews page to see a complete list of reviews in the pulmonary cell research field.

Novartis Drug Zykadia Receives FDA Priority Review for First-Line Use in Patients with ALK⁺ Metastatic NSCLC

Novartis announced that the US Food and Drug Administration (FDA) accepted the company’s supplemental New Drug Application for filing, and granted Priority Review for the expanded use of Zykadia^® as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. The FDA also granted Breakthrough Therapy designation to Zykadia for the first-line treatment of patients with ALK⁺ metastatic NSCLC with metastases to the brain. [Novartis] Press Release

US FDA Expands Approval of Tiotropium Respimat^® for Maintenance Treatment of Asthma in Children

Boehringer Ingelheim announced that the U.S. Food and Drug Administration (FDA) approved tiotropium Respimat^® for the long-term, once-daily maintenance treatment of people with asthma aged six years and older who continue to experience symptoms despite their other maintenance therapy – usually either inhaled corticosteroid alone, or a combination of inhaled corticosteroids/long-acting beta agonists. [Boehringer Ingelheim] Press Release

Updated: Will They or Won’t They? What Science Groups Are Saying About Joining the March for Science

The March for Science is creating a buzz in the scientific community. The march arose as a grassroots reaction to concerns about the conduct of science under President Donald Trump. And it has spurred debate over whether it will help boost public support for research, or make scientists look like another special-interest group, adding to political polarization. [Science Insider] Editorial

Firing of Veteran NIH Scientist Prompts Protests over Publication Ban

At least two dozen junior and senior researchers are stuck in scientific limbo after being barred from publishing data collected over a 25-year period at a National Institutes of Health (NIH) lab. The unusual ban follows the firing last summer of veteran neurologist Allen Braun by the National Institute on Deafness and Other Communication Disorders for what many scientists have told Science are relatively minor, if widespread, violations of his lab’s experimental protocol. [ScienceInsider] Editorial

Why British Universities Are Unlikely to Accept Invitation to Set Up Campuses in France

A consortium of academic institutes near Paris is hoping to lure British universities to create research campuses in France, dangling as bait the possibility of access to European Union research funds after Brexit. [Nature News] Editorial

NEW ESMO Symposium on Signaling Pathways in Cancer 2017
March 17-18, 2017
Barcelona, Spain

NEW 4^th Immunotherapy of Cancer Conference
March 20-22, 2017
Prague, Czech Republic

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Opportunity – RNA and Cancer Biology (Yale University)

NEW PhD Student – Asthma Research (Karolinska Institute)

NEW Postdoctoral Fellow – Translation Cancer Research (UiT The Arctic University of Norway)

NEW Postdoctoral Fellow – Impaired Progenitors Emphysema Deficient Repair (AstraZeneca)

Postdoctoral Fellow – Airway Biology (Harvard T.H. Chan School of Public Health)

PhD Student – Lung Cancer (Max Planck Institute for Heart and Lung Research)

Principal Scientist – Translational Development (Celgene Corporation)

Postdoctoral Position – Cellular Therapeutics in Chronic Lung Disease (Helmholtz Zentrum München)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Research Fellow – Cancer Genetics/Epigenetics (Fred Hutchinson Cancer Research Center)

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