Volume 2.13 | Apr 4

Pulmonary Cell News 2.13 April 4, 2013
Pulmonary Cell News
     In this issue: Publications | Reviews | Science News | Industry News | Policy News | Events | Jobs
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TOP STORY
NeuroD1 Regulates Survival and Migration of Neuroendocrine Lung Carcinomas via Signaling Molecules TrkB and NCAM
Researchers demonstrated that neurogenic differentiation 1 (NeuroD1) is a regulatory hub securing cross talk among survival and migratory-inducing signaling pathways in neuroendocrine lung carcinomas. They found that NeuroD1 promotes tumor cell survival and metastasis in aggressive neuroendocrine lung tumors through regulation of the receptor tyrosine kinase tropomyosin-related kinase B (TrkB). [Proc Natl Acad Sci USA] Abstract

View On-Demand Webinar: Optimized Differentiation of Bronchial Epithelial Cells
PUBLICATIONS (Ranked by impact factor of the journal)

IFNβ/TNFα Synergism Induces a Non-Canonical STAT2/IRF9-Dependent Pathway Triggering a Novel DUOX2 NADPH Oxidase-Mediated Airway Antiviral Response
Investigators unveiled a novel delayed antiviral response in the airways, which is initiated by the synergistic autocrine/paracrine action of IFNβ and TNFα, and signals through a non-canonical STAT2- and IRF9-dependent, but STAT1-independent cascade. [Cell Res] Abstract

Physico-Chemical Characterization of African Urban Aerosols (Bamako in Mali and Dakar in Senegal) and Their Toxic Effects in Human Bronchial Epithelial Cells: Description of a Worrying Situation
Researchers aimed to characterize the biological reactivity of urban African aerosols on human bronchial epithelial cells in relation to particulate matter’s physico-chemical properties to identify toxic sources. [Part Fibre Toxicol] Abstract | Full Article

Trolox Contributes to Nrf2-Mediated Protection of Human and Murine Primary Alveolar Type II Cells from Injury by Cigarette Smoke
Scientists studied the effect of oxidative stress generated by cigarette smoke (CS) both in vivo and in vitro on murine primary alveolar type II (ATII) cells isolated from nuclear erythroid 2-related factor-2 (Nrf2)−/− mice. They found that ATII cells isolated from Nrf2−/− mice are more susceptible to CS-induced oxidative DNA damage mediated by p53/53BP1 both in vivo and in vitro compared with wild-type mice. [Cell Death Dis]
Full Article

Lipopolysaccharide-Treated Macrophages Cytokines Repress Surfactant Protein B in Lung Epithelial Cells
To investigate the mechanism of surfactant protein B (SFTPB) repression, the human pulmonary epithelial NCI-H441 and NCI-H820 cells and RAW264.7 macrophages were treated with lipopolysaccharide (LPS). Whereas LPS did not decrease SFTPB transcripts in H441 or H820 cells, conditioned medium of LPS-treated RAW264.7 cells decreased SFTPB transcripts in H441 and H820 cells and inhibited SFTPB promoter activity in H441 cells. [Am J Resp Cell Mol] Abstract

Non-Antibiotic Macrolides Prevent Human Neutrophil Elastase-Induced Mucus Stasis and Airway Surface Liquid Volume Depletion
Since neutrophilia frequently occurs in chronic lung disease and human neutrophil elastase (HNE) induces mucus stasis by activating the epithelial sodium channel, researchers tested the ability of 2′-desoxy-9-(S)-erythromycylamine (GS-459755) to protect against HNE-induced mucus stasis. GS-459755 had no effect on HNE activity. However, GS-459755 pretreatment protected against HNE-induced airway surface liquid volume depletion in human bronchial epithelial cells. [Am J Physiol-Lung C] Abstract

Jagged1 Is the Major Regulator of Notch-Dependent Cell Fate in Proximal Airways
Scientists report that Jagged1 is expressed in a subset of bronchial and bronchiolar epithelial cells, where it controls proximal airway cell fate and differentiation. In agreement with previous studies involving disruption of all Notch signaling, they found that deletion of Jagged1 in airway epithelium increased the number of ciliated cells at the expense of Clara cells, a phenotype associated with downregulation of Hes1. [Dev Dynam] Abstract

LUNG CANCER

Acquired Resistance to EGFR Inhibitors Is Associated with a Manifestation of Stem Cell-Like Properties in Cancer Cells
Scientists investigated the molecular and cellular profiles of the acquired resistant cells to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor in EGFR mutant lung cancers. Four EGFR-mutant cell lines were exposed to gefitinib by stepwise escalation and high-concentration exposure methods, and resistant sublines to gefitinib were established. [Cancer Res] Full Article

Lysine Acetyltransferase GCN5 Potentiates the Growth of Non-Small Cell Lung Cancer via Promotion of E2F1, Cyclin D1 and Cyclin E1 Expression
Researchers report that GCN5 is highly expressed in non-small cell lung cancer tissues and that its expression correlates with tumor size. They found that the expression of GCN5 promotes cell growth and the G1/S phase transition in multiple lung cancer cell lines. [J Biol Chem] Full Article

DNA Methylation Profiles at Precancerous Stages Associated with Recurrence of Lung Adenocarcinoma
Using single-CpG resolution Infinium array, genome-wide DNA methylation analysis was performed in 36 samples of normal lung tissue obtained from patients without any primary lung tumor, 145 samples of non-cancerous lung tissue obtained from patients with lung adenocarcinomas, and 145 samples of tumorous tissue. [PLoS One] Full Article

Ionizing Radiation Potentiates Dihydroartemisinin-Induced Apoptosis of A549 Cells via a Caspase-8-Dependent Pathway
Scientists explored the molecular mechanism by which dihydroartemisinin (DHA) and ionizing radiation induce apoptosis in human lung adenocarcinoma A549 cells. DHA treatment induced a concentration- and time-dependent reactive oxygen species-mediated cell death with typical apoptotic characteristics such as breakdown of mitochondrial membrane potential, caspases activation, DNA fragmentation and phosphatidylserine externalization. [PLoS One] Full Article

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

REVIEWS
Leptin As Regulator of Pulmonary Immune Responses: Involvement in Respiratory Diseases
The authors review the current understanding of leptin and its functional role on the different resident cell types of the lung in health as well as in the context of three major respiratory conditions being chronic obstructive pulmonary disease, asthma, and pneumonia. [Pulm Pharmacol Ther] Abstract

Visit our reviews page to see a complete list of reviews in the pulmonary cell research field.
SCIENCE NEWS
N30 Announces Presentation of Preclinical Data at the Basic Science Meeting of the European Cystic Fibrosis Society
N30 Pharmaceuticals, Inc., a clinical stage, biopharmaceutical company focused on the development of therapies for cystic fibrosis, announced the presentation of key preclinical data for its novel inhibitors of S-nitrosoglutathione reductase. [Press release from N30 Pharmaceuticals discussing results presented at the 10th Basic Science Meeting of the European Cystic Fibrosis Society in Malaga, Spain] Press Release
INDUSTRY NEWS

Preliminary Results of a Phase II Study Indicates that Axelar’s AXL1717 Is Efficacious in 2nd Line Treatment of Patients with Lung Cancer
Axelar AB, announced that preliminary interim results of its Phase II study AXL-003 indicate that AXL1717 is effective in treating patients with non-small cell lung cancer. Thus, the company assesses that it has sufficient data to guide further development of the drug, and will finalize the study with fewer patients than initially planned. [Axelar AB] Press Release

COPD Foundation Applauds First-Time Inclusion of COPD in Hard-Hitting Anti-Smoking Ad Campaign
The COPD Foundation announced that the Centers for Disease Control and Prevention will, for the first time, depict the impact of Chronic Obstructive Pulmonary Disease (COPD) in its national ad campaign, Tips From Former Smokers. The campaign highlights the overwhelming human and financial toll on the nation caused by smoking. [COPD Foundation] Press Release

Merrimack Pharmaceuticals Announces Top-Line Results from a Single Arm Phase II Advanced Lung Cancer Study in Patients with Resistance to an Anti-EGFR Tyrosine Kinase Inhibitor
Merrimack Pharmaceuticals, Inc. announced that one cohort of a Phase II non-small cell lung cancer (NSCLC) study did not meet its primary endpoint. The cohort evaluated MM-121 in combination with erlotinib to treat patients with NSCLC whose disease progressed on an anti-EGFR tyrosine kinase inhibitor. MM-121 is being evaluated in two additional NSCLC cohorts as well as Phase II studies for the treatment of advanced ovarian cancer, hormone-receptor positive breast cancer and HER2 negative breast cancer. [Merrimack Pharmaceuticals] 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 World Stem Cells & Regenerative Medicine Congress
May 21-23, 2013
London, United Kingdom


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

JOB OPPORTUNITIES

Postdoctoral Position – Cardiopulmonary Molecular Biology (Hannover Medical School)

Research Associate (University of Chicago – Department of Medicine)

Postdoctoral Research Associate (University of North Carolina – Chapel Hill)

Professor for Oncological Pneumology (Friedrich Schiller University Jena)

PhD Studentship – T Cell Immunity in the Lung (University of Bonn, Germany)

Senior Lecturer or Reader In Lung Oncology (Brighton & Sussex Medical School / University of Sussex)


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