Volume 2.11 | Mar 21

Pulmonary Cell News 2.11 March 21, 2013
Pulmonary Cell News
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
Nkx2-1 Represses a Latent Gastric Differentiation Program in Lung Adenocarcinoma
Investigators used conditional murine genetics to determine how the identity of lung epithelial cells changed upon loss of their master cell-fate regulator. Nkx2-1 deletion in normal and neoplastic lungs caused not only loss of pulmonary identity but also conversion to a gastric lineage. [Mol Cell] Abstract

Video Protocol: Mucociliary Differentiation of Primary Bronchial Epithelial Cells
PUBLICATIONS (Ranked by impact factor of the journal)

NAC Protects Murine Alveolar Type II Cells from Cigarette Smoke Injury in an Nrf2-Independent Manner
Scientists studied the protective role of N-acetylcysteine (NAC) against injury of alveolar type II (ATII) cells induced by cigarette smoke (CS) in vivo and in vitro. They found that CS induced higher injury in ATII cells obtained from Nrf2-/- mice than from wild-type mice. [Am J Resp Cell Mol] Abstract

Ciprofloxacin Is Actively Transported across Bronchial Lung Epithelial Using a Calu-3 Air-Interface Cell Model
Researchers investigated the contributions of specific transporters including multidrug efflux transporters, organic cation transporters and organic anion transporting polypeptide transporters on the uptake of ciprofloxacin in vitro using an air interface bronchial epithelial model. [Antimicrob Agents Ch] Abstract

Adiponectin Affects Lung Epithelial A549 Cell Viability Counteracting TNFα and IL-1β Toxicity through AdipoR1
Researchers investigated the effects of Acrp30 on A549, a human alveolar epithelial cell line, showing how, in a time and dose-dependent manner, it decreases cell viability and increases apoptosis through ERK1/2 and AKT. [Int J Biochem Cell B] Abstract

Combustion Derived Ultrafine Particles Induce Cytochrome P450 Expression in Specific Lung Compartments in the Developing Neonatal and Adult Rat
Although aryl hydrocarbon receptor (AhR) activation and induction has been widely studied, its context within particulate matter (PM) exposure and impact on the developing lung is poorly understood. In response, scientists have developed a replicable ultrafine premixed flame particle generating system and used in vitro and in vivo models to define PM effects on AhR activation in the developing lung. [Am J Physiol – Lung C] Abstract

Antiviral Effects of Modified Dingchuan Decoction against Respiratory Syncytial Virus Infection In Vitro and in an Immunosuppressive Mouse Model
Modified Dingchuan decoction (MDD) and its components were evaluated for antiviral efficacy against respiratory syncytial virus (RSV) in vitro in cell culture. MDD exhibited significant antiviral and anti-inflammatory effects on decreasing levels of Eotaxin, IL-4 and IFN-γ in serum and lung tissue, inhibiting pneumonia, decreasing lung viral loads and reversaling RSV-induced inflammation through down-regulation of TLR4 and NF-κB mRNA expression in the lung tissue of RSV-infected mice. [J Ethnopharmacol]
Abstract | Graphical Abstract

IL-8 Production in Response to Cigarette Smoke Is Decreased in Epithelial Cells from COPD Patients
Researchers aimed at comparing the intracellular response of normal human bronchial/tracheal epithelial cells (NHBE) and chronic obstructive pulmonary disease (COPD)-diseased human bronchial/tracheal epithelial cells (DHBE) to cigarette smoke. NHBE cells increased IL-8 production in a dose-dependent manner in response to cigarette smoke condensate (CSC) while DHBE cells did not show any significant difference and had a much lower production of IL-8 in response to CSC compared to NHBE cells. [Pulm Pharmacol Ther] Abstract

LUNG CANCER

Dachshund Binds p53 to Block The Growth of Lung Adenocarcinoma Cells
Given the importance of EGFR signaling in lung cancer etiology, researchers examined the role of DACH1 expression in lung cancer development. DACH1 protein and mRNA expression was reduced in human non-small cell lung cancer (NSCLC). Re-expression of DACH1 reduced NSCLC colony formation and tumor growth in vivo via p53. [Cancer Res] Abstract

Reduction of the ST6GAL1-Catalyzed Sialylation of Nectin-Like Molecule 2/Cell Adhesion Molecule 1 and Enhancement of the ErbB2/ErbB3 Signaling by MicroRNA-199a
Researchers studied the relationship between nectin-like molecule 2 (Necl-2) and microRNA-199a (miR-199a) that is up-regulated or down-regulated in a variety of cancers. miR-199a did not directly target the Necl-2 mRNA or affect its mRNA level in human lung cancer A549 cells and human embryonic kidney HEK293 cells. [J Biol Chem] Full Article

α-Lipoic Acid-Induced Inhibition of Proliferation and Met Phosphorylation in Human Non-Small Cell Lung Cancer Cells
Scientists investigated the effects of α-lipoic acid (α-LA) on the proliferation and activation status of definitive receptor tyrosine kinases, epidermal growth factor receptor (EGFR) and Met/hepatocyte growth factor receptor, in gefitinib-sensitive human non-small cell lung cancer cells harboring EGFRs with an activating mutation. The enantiomers R-α-LA and S-α-LA suppressed cell proliferation and increased the level of reactive oxygen species in HCC-827 and PC-9 human non-small cell lung cancer cells in an indistinguishable dose-dependent fashion. [Cancer Lett] Abstract

Synergistic Effect of Afatinib with Su11274 in Non-Small Cell Lung Cancer Cells Resistant to Gefitinib or Erlotinib
Researchers investigated the combination of targeting epidermal growth factor receptor (EGFR) and c-MET pathways in non-small cell lung cancer cells resistant to receptor tyrosine kinase inhibitors (TKIs), using RNA interference and inhibition by TKIs. The results showed that the cell lines that were relatively resistant to EGFR TKIs, especially the H1975 cell line containing the resistance T790M mutation, were found to be more sensitive to EGFR-specific-siRNA. [PLoS One] Full Article

Visit The Cilia Samba Blog for Respiratory Research Commentary, News and Interviews.

REVIEWS
The Fibroproliferative Response in ARDS: Mechanisms and Clinical Significance
The authors review the current understanding of the contribution of pulmonary dysfunction to mortality and to quality of life in survivors of acute respiratory distress syndrome (ARDS), the mechanisms driving pathological fibroproliferation, and potential therapeutic approaches to prevent or attenuate fibroproliferative lung disease. [Eur Respir J] Abstract
INDUSTRY NEWS

Novartis Compound LDK378 Receives FDA Breakthrough Therapy Designation for ALK+ Non-Small Cell Lung Cancer
Novartis announced that its investigational compound LDK378 has received Breakthrough Therapy designation by the US Food and Drug Administration (FDA) for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer who had progressed during treatment with, or were intolerant to, crizotinib. [Novartis] Press Release

Savara Pharmaceuticals Completes Second Tranche of $16 Million Series B Financing to Advance Treatment of MRSA Lung Infection in Cystic Fibrosis Patients
Savara Pharmaceuticals announced that it has closed a $7.4 million second tranche of its Series B financing resulting in a total raise of $16 million. Additionally, Savara was awarded a $4 million grant by the National Heart, Lung and Blood Institute of the National Institutes of Health. All private equity and non-dilutive funds will support the Phase II development of AeroVanc™, the first inhaled antibiotic being developed to treat the increasing number of persistent pulmonary methicillin-resistant Staphylococcus aureus (MRSA) infections in patients with cystic fibrosis. [Savara Pharmaceuticals] Press Release

Dr. James Hogg Given National Award for Leadership in Medicine
The Gairdner Foundation has recognized Dr. James Hogg with the Canada Gairdner Wightman Award, the premier honor for leadership in medical science in Canada. Dr. Hogg was selected for his research leadership in Chronic Obstructive Pulmonary Disease. [The University of British Columbia] 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

NEW American Society of Gene & Cell Therapy (ASGCT) 16th Annual Meeting
May 15-18, 2013
Salt Lake City, United States

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

JOB OPPORTUNITIES

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

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)

Postdoctoral Researcher – Inhalation/Immunology (Louisiana State University)

Research Associate (University of Chicago – Department of Medicine)


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