Volume 2.09 | Mar 7

Pulmonary Cell News 2.09 March 7, 2013
Pulmonary Cell News
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
Tumor VEGF:VEGFR2 Autocrine Feed-Forward Loop Triggers Angiogenesis in Lung Cancer
By combining chemical genetics with multimodal imaging, investigators identified an autocrine feed-forward loop in tumor cells in which tumor-derived VEGF stimulates VEGF production via VEGFR2-dependent activation of mTOR, substantially amplifying the initial proangiogenic signal. Disruption of this feed-forward loop by chemical perturbation or knockdown of VEGFR2 in tumor cells dramatically inhibited production of VEGF in vitro and in vivo. [J Clin Invest] Full Article

Air-Liquid Interface Culture for Respiratory Research: Watch Q&A Video
PUBLICATIONS (Ranked by impact factor of the journal)

MicroRNA-375 Regulation of Thymic Stromal Lymphopoietin by Diesel Exhaust Particles and Ambient Particulate Matter in Human Bronchial Epithelial Cells
Scientists showed that diesel exhaust particles (DEP) and ambient fine particulate matter upregulate thymic stromal lymphopoietin (TSLP) mRNA and human microRNA (hsa-miR)-375 in primary human bronchial epithelial cells (pHBEC). Moreover, transfection of pHBEC with anti-hsa-miR-375 reduced TSLP mRNA in DEP but not TNF-α-treated cells. [J Immunol] Abstract

miR-145 Regulates Myofibroblast Differentiation and Lung Fibrosis
Investigators found that miR-145 expression is upregulated in TGF-β1-reated lung fibroblasts. miR-145 expression is also increased in the lungs of patients with idiopathic pulmonary fibrosis as compared to in normal human lungs. [FASEB J] Abstract

Sphingosine-1-Phosphate, FTY720 and Sphingosine-1-Phosphate Receptors in the Pathobiology of Acute Lung Injury
Scientists demonstrated that sphingosine 1-phosphate (S1P) is a potent angiogenic factor that enhances lung endothelial cell integrity and an inhibitor of vascular permeability and alveolar flooding in pre-clinical animal models of acute lung injury. [Am J Resp Cell Mol] Abstract

A Novel Anti-Inflammatory and Pro-Resolving Role for Resolvin D1 in Acute Cigarette Smoke-Induced Lung Inflammation
Primary human lung fibroblasts, small airway epithelial cells and blood monocytes were treated with IL-1β or cigarette smoke extract in combination with resolvin D1 (RvD1) in vitro, production of pro-inflammatory mediators was measured. Investigators report that RvD1 suppressed production of pro-inflammatory mediators by primary human cells in a dose-dependent manner. [PLoS One] Full Article

Influenza Matrix Protein 2 Alters CFTR Expression and Function through Its Ion Channel Activity
Researchers investigated whether influenza matrix protein (M2), a pH-activated proton (H+) channel that traffics to the plasma membrane of infected cells, altered cystic fibrosis transmembrane conductance regulator (CFTR) expression and function. M2 decreased CFTR activity in: (1) Xenopus oocytes injected with human CFTR; (2) epithelial cells (HEK-293) stably transfected with CFTR; (3) human bronchial epithelial cells (16HBE14o-) expressing native CFTR. [Am J Physiol-Lung C] Abstract

Inhibitory Effects of Simvastatin on Staphylococcus aureus Lipoteichoic Acid-Induced Inflammation in Human Alveolar Macrophages
Researchers aimed to define the role of Staphylococcus aureus lipoteichoic acid (LTA) in human alveolar macrophages (AMs) and the effects of simvastatin on LTA-stimulated human AMs. They showed that LTA induced tumor necrosis factor-alpha, interleukin(IL)-1beta, IL-8 mRNA expression, and suppressed IL-10 mRNA expression in human AMs. [Clin Exp Med] Abstract

LUNG CANCER

Upregulation of c-FLIP-short in Response to TRAIL Promotes Survival of NSCLC Cells, Which Could Be Suppressed by Inhibition of Ca2+/Calmodulin Signaling
Scientists report that TNF-related apoptosis-inducing ligand (TRAIL) rapidly activates caspase-8 in a panel of non-small-cell lung carcinomas (NSCLCs). The results revealed that the upregulation of DR4 and caspase-8 expression in NSCLC cells make them more susceptible to TRAIL. However, these cells could survive TRAIL treatment via upregulation of cellular-FLIP-short (c-FLIPS), and it is suggested that blocking c-FLIPS expression by inhibition of Ca2+/calmodulin signaling significantly overcomes the acquired resistance of NSCLC cells to TRAIL. [Cell Death Dis] Full Article

MAPK p38 and JNK have Opposing Activities on TRAIL-Induced Apoptosis Activation in NSCLC H460 Cells that Involves RIP1 and Caspase-8 and Is Mediated by Mcl-1
Scientists examined the consequences and mechanisms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced MAPKs, p38 and JNK in non-small cell lung cancer (NSCLC) cells. In apoptosis sensitive H460 cells, these kinases were phosphorylated, but not in resistant A549 cells. [Apoptosis] Abstract

Human Lung Epithelial Cells Progressed to Malignancy Through Specific Oncogenic Manipulations
Investigators used CDK4/hTERT-immortalized normal human bronchial epithelial cells (HBECs) from several individuals to study lung cancer pathogenesis by introducing combinations of common lung cancer oncogenic changes (p53, KRAS, MYC) and followed the stepwise transformation of HBECs to full malignancy. [Mol Cancer Res] Abstract

Differential Effects of Mesenchymal Stem Cells on a Heterogeneous Cell Population within Lung Cancer Cell Lines
The effects of mesenchymal stem cells (MSCs) on the growth and microsphere formation of heterogeneous cell populations within two lung cancer cell lines (A549 and H446) were compared. Researchers report that MSCs inhibited the in vitro proliferation of both cell lines, but significantly accelerated tumor formation and stimulated tumor growth in vivo. [Mol Cell Biochem] Abstract

Model the Human Respiratory Epithelium with PneumaCult™-ALI. Click to View Data.

REVIEWS

Mechanistic Links between COPD and Lung Cancer
The author discusses the nature of the link between the two diseases and considers specific mechanisms that operate in both chronic obstructive pulmonary disease (COPD) and lung cancer, some of which might represent either chemopreventive or chemotherapeutic targets. [Nat Rev Cancer] Abstract

Nonsmall Cell Lung Cancer
This review reports the Clinical Year in Review proceedings in the field of nonsmall cell lung cancer that were presented at the 2012 European Respiratory Society Congress in Vienna, Austria. Various topics are reviewed, including epidemiology, screening, diagnosis, treatment, prognosis, and palliative and end of life care. [Eur Respir J] Full Article

INDUSTRY NEWS

PatientsLikeMe and Boehringer Ingelheim Establish Health Information Collaboration for Patients with Idiopathic Pulmonary Fibrosis
PatientsLikeMe announced a new collaboration with Boehringer Ingelheim to enhance its online patient community for people with idiopathic pulmonary fibrosis, a rare lung condition with no known cause, treatment or cure. [PatientsLikeMe] Press Release

BioLineRx’s EDP-14, for Treatment of Severe and Persistent Asthma, to Enter the Company’s Main Therapeutic Pipeline as BL-9010
BioLineRx announced that following pre-clinical data, EDP-14, for the treatment of severe and persistent asthma, has been added to the Company’s main therapeutic pipeline. [BiolineRx] Press Release

POLICY NEWS

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

EVENTS

Gordon Research Conference: Cilia, Mucus & Mucociliary Interactions
April 7-11, 2013
Lucca, Italy

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

JOB OPPORTUNITIES

Postdoctoral Fellowship – Translational Studies of Interstitial Lung Disease (University of California San Francisco)

Postdoctoral/ Research Associate/ Senior Research Associate – Lung Alveolar Epithelial Cell Biology (University of Southern California)

PhD Studentship – Toxicology (CRP – Gabriel Lippmann)

PhD Studentship – Impaired Mucosal Immunity in Severe Asthma (Université Catholique de Louvain)

Postdoctoral Associate – Molecular Cell Biology (Weill Cornell Medical College in Qatar)

Postdoctoral Position – Cardiopulmonary Molecular Biology (Hannover Medical School)

Postdoctoral Position – Lung Fibrosis (Research Institute of the McGill University Health Center)

Postdoctoral Research Associate – Lung and Vascular Biology (University of Illinois at Chicago)


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