Volume 2.08 | Feb 28

Pulmonary Cell News 2.08 February 28, 2013
Pulmonary Cell News
     In this issue: Publications | Reviews | Science News | Industry News | Policy News | Events | Jobs
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TOP STORY
Penn Medicine: Tweaking Gene Expression to Repair Lungs
Using genetic and pharmacological approaches, investigators showed that development of progenitor cells in the lung is specifically regulated by the combined function of two highly related HDACs, HDAC/1 and /2. [Press release from The University of Pennsylvania discussing online prepublication in Developmental Cell]
Press Release | Abstract | Graphical Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

Contribution of α7 Nicotinic Receptor to Airway Epithelium Dysfunction under Nicotine Exposure
Nicotinic acetylcholine receptors (nAChRs) bind nicotine and nicotine-derived nitrosamines and thus mediate many of the tobacco-related deleterious effects in the lung. Researchers identified α7 nAChR as a key regulator of cystic fibrosis transmembrane conductance regulator in the airways. [Proc Natl Acad Sci USA] Abstract

Lipoxin A4 Regulates Natural Killer Cell and Type 2 Innate Lymphoid Cell Activation in Asthma
Researchers identified both natural killer (NK) cells and innate lymphoid cell type 2 (ILC2)s in human lung and peripheral blood in healthy and asthmatic subjects. NK cells were highly activated in severe asthma, were linked to eosinophilia, and interacted with autologous eosinophils to promote their apoptosis. ILC2s generated antigen-independent interleukin-13 (IL-13) in response to the mast cell product prostaglandin D2 alone and in a synergistic manner with the airway epithelial cytokines IL-25 and IL-33. [Science Transl Med] Abstract

IL-1 Receptor Regulates MicroRNA-135b Expression in a Negative Feedback Mechanism during Cigarette Smoke-Induced Inflammation
Investigators report that in vitro activation of the IL-1R1 pathway in mouse embryonic fibroblast (NIH3T3) and lung epithelial (FE1) cells resulted in increased microRNA-135b, which was blocked by IL-1R1 antagonists or small interfering RNA-mediated silencing of IL-1R1 expression. [J Immunol] Full Article

PI3K p110γ Overexpression in Idiopathic Pulmonary Fibrosis Lung Tissue and Fibroblast Cells: In Vitro Effects of Its Inhibition
Scientists assessed the expression of class I PI3K p110 isoforms in idiopathic pulmonary fibrosis (IPF) lung tissue as well as in tissue-derived fibroblast cell lines. They also investigated the in vitro effects of the selective inhibition of p110 isoforms on IPF fibroblast proliferation and fibrogenic activity. [Lab Invest] Abstract

Proteomic Analysis of the NOS2 Interactome in Human Airway Epithelial Cells
Scientists overexpressed Flag-tagged, catalytically-inactive nitric oxide synthase (NOS2) in A549 cells and used mass spectrometry to qualitatively identify NOS2 co-immunoprecipitating proteins. Stable isotope labeling of amino acids in cell culture was used to quantify the coordinate effects of cytokine stimulation on NOS2-protein interactions. [Nitric Oxide-Biol Ch] Abstract

Linoleic Acid Metabolite Drives Severe Asthma by Causing Airway Epithelial Injury
Scientists showed that extracellular 13-S-hydroxyoctadecadienoic acid induces mitochondrial dysfunction and airway epithelial apoptosis. This was associated with features of severe airway obstruction, lung remodeling, increase in epithelial stress related proinflammatory cytokines and drastic airway neutrophilia in mouse. [Sci Rep] Full Article

LUNG CANCER


Notch Pathway Activity Identifies Cells with Cancer Stem Cell-Like Properties and Correlates with Worse Survival in Lung Adenocarcinoma
Scientists investigated the role of Notch activity in lung adenocarcinoma utilizing a Notch GFP-reporter construct and a gamma-secretase inhibitor, which inhibits Notch pathway activity. Transduction of lung cancer cells with Notch GFP-reporter construct identified a subset of cells with high Notch activity (GFP-bright). GFP-bright cells had the ability to form more tumor spheres in serum-free media, and were able to generate both GFP-bright and GFP-dim (lower Notch activity) cell populations. [Clin Cancer Res] Abstract

Klotho Sensitizes Human Lung Cancer Cell Line to Cisplatin via PI3k/Akt Pathway
Investigators demonstrated that klotho could attenuate the resistance of lung cancer to cisplatin based chemotherapy and the apoptosis of the resistant cells with klotho overexpression was markedly increased. [PLoS One] Full Article

Claudin-7 Increases Chemosensitivity to Cisplatin through the Up-Regulation of Caspase Pathway in Human NCI-H522 Lung Cancer Cells
To investigate the role of claudin-7 in lung cancer cells after anti-cancer drug treatments, the authors transfected claudin-7 cDNA into human NCI-H522 lung cancer cells, which have no detectable expression of claudin-7 protein. Flow cytometry analysis demonstrated that cells transfected with claudin-7 had a significantly higher percentage of cell apoptosis when compared to that of vector transfected cell population. [Cancer Sci] Abstract

Silence of Ezrin Modifies Migration and Actin Cytoskeleton Rearrangements and Enhances Chemosensitivity of Lung Cancer Cells In Vitro
Researchers chose highly metastatic human lung carcinoma 95D cells, which highly express the ezrin proteins, as a model to examine the functional roles of ezrin in tumor suppression. An ezrin-silenced 95D cell line was established using lentivirus-mediated short hairpin RNA method. CCK-8 assay and soft agar assay analysis showed that downregulation of ezrin significantly suppressed the tumorigenicity and proliferation of 95D cells in vitro. [Mol Cell Biochem] Abstract

Differentiation Doesn't Have to be Difficult: Get Easy, Standardized hPSC Differentiation

REVIEWS
Current Status and Future Strategies for Multimodality Treatment of Unresectable Stage III Non-Small-Cell Lung Cancer
The authors consider the rationale for combining new agents with chemoradiotherapy and the evidence from clinical studies assessing multimodal strategies for the management of patients with unresectable stage III non-small-cell lung cancer. [Eur Respir J] Abstract
SCIENCE NEWS

KaloBios Presents Clinical Results with Anti-GM-CSF Antibody in Persistent Asthma
KaloBios Pharmaceuticals, Inc. presented data from its Phase I/II study in persistent asthma for KB002. The findings demonstrated preliminary safety, tolerability, and signs of activity of anti-GM-CSF antibodies in asthma and support continued development of the company’s Humaneered® KB003 anti-GM-CSF monoclonal antibody in severe asthma. [Press release from PR Newswire Association LLC. discussing research presented at the American Academy of Allergy, Asthma & Immunology Annual Meeting, San Antonio] Press Release

Phase III Results: Tiotropium Respimat® Is Effective in Symptomatic Asthma Patients Irrespective of Their Allergic Status
Tiotropium delivered once daily via Respimat™ significantly improved lung function and reduced asthma exacerbations in patients who remain symptomatic despite treatment with at least inhaled corticosteroids/long-acting beta2-agonists, irrespective of their allergic status. [Press release from Boehringer Ingelhein GmbH discussing research presented at the 2013 American Academy of Allergy, Asthma & Immunology Annual Meeting, San Antonio] Press Release

INDUSTRY NEWS

UAB First in United States to Test New Emphysema Procedure
A patient at the University of Alabama at Birmingham (UAB) became the first person in America to undergo an investigational therapy for emphysema that uses a foam sealant sprayed into the lungs. The therapy, approved for use in parts of Europe and Israel, is undergoing investigation in the United States as a potential method of reducing lung volume in patients with severe emphysema. [University of Alabama at Birmingham] Press Release

Broadway’s Best Gather to Raise Funds and Awareness for the Pulmonary Fibrosis Foundation
With honors ranging from the Golden Globes to the Tony Awards, Broadway’s best performers gathered Monday night to raise awareness of the rare disease, pulmonary fibrosis, and honor the memory of Associated Press theater critic, Michael Kuchwara. [Pulmonary Fibrosis Foundation] Press Release

Vertex Announces Initiation of Pivotal Phase III Program of VX-809 in Combination with Ivacaftor for the Treatment of People with Cystic Fibrosis Who Have Two Copies of the F508del Mutation
Vertex Pharmaceuticals Inc. plans to conduct two 24-week Phase III studies to support approval of the combination of VX-809 and ivacaftor in people with cystic fibrosis ages 12 and older. The studies, TRAFFIC and TRANSPORT, will each include two treatment groups that will evaluate VX-809 in combination with ivacaftor compared to a placebo group. [Vertex Pharmaceuticals Inc.] Press Release

CytRx Reaches Patient Enrollment Target in Global Phase IIb Clinical Trial with Tamibarotene as First-Line Treatment for Non-Small-Cell Lung Cancer
CytRx Corporation announced that enrollment of 140 evaluable patients has been completed in the Company’s global Phase IIb clinical trial with its oral retinoid compound tamibarotene in combination with chemotherapeutic agents as a first-line treatment for patients with advanced non-small-cell lung cancer. [CytRx Corporation] Press Release

POLICY NEWS

Expanding Public Access to the Results of Federally Funded Research
In a policy memorandum, Office of Science and Technology Policy Director John Holdren has directed Federal agencies with more than $100 million in R&D expenditures to develop plans to make the published results of federally funded research freely available to the public within one year of publication and requiring researchers to better account for and manage the digital data resulting from federally funded scientific research. [Office of Science and Technology Policy, The White House, United States] Press Release

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

NEW European Respiratory Society Lung Science Conference
March 15-17, 2013
Estoril, Portugal


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)



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