Pulmonary Cell News Volume 2.06 | Feb 14 2013

Silica Induces NLRP3 Inflammasome Activation in Human Lung Epithelial Cells
Scientists investigated lung epithelial cells as a target for silica-induced inflammasome activation. They were able to show transcriptional and translational upregulation of the components of the NLRP3 intracellular platform, as well as activation of caspase-1. [Part Fibre Toxicol] Full Article

γδT Cells Suppress Inflammation and Disease during Rhinovirus-Induced Asthma Exacerbations
Researchers found that airway and blood γδT-cell numbers were associated with increased airways obstruction and airways hyper-reactivity. Airway γδT-cell number was also positively correlated with bronchoalveolar lavage (BAL) virus load and BAL eosinophils and lymphocytes during rhinovirus infection. [Mucosal Immunol] Full Article

The Level of p38α MAPK Activation in Airway Epithelial Cells Determines the Onset of Innate Immune Responses to Planktonic and Biofilm Pseudomonas aeruginosa
Investigators report that in airway epithelial cells a threshold of p38α MAPK activation is required to trigger neutrophil recruitment, which is influenced by extrinsic and intrinsic factors. [J Infect Dis] Abstract

Muscarinic Receptor Subtype-Specific Effects on Cigarette Smoke-Induced Inflammation in Mice
The contribution of the muscarinic M1, M2 and M3 receptor subtypes to cigarette smoke-induced airway inflammation was investigated by exposing muscarinic receptor subtype deficient mice to cigarette smoke for four days. Researchers report that in wild-type mice, cigarette smoke induced an increase in macrophages, neutrophils and lymphocytes in bronchoalveolar lavage fluid. [Eur Respir J] Abstract

Heme Oxygenase-1 Induces 15-Lipoxygenase Expression during Hypoxia-Induced Pulmonary Hypertension
Researchers studied the role of heme oxygenase-1 (HO-1) in hypoxic pulmonary arterial hypertension and 15-lipoxygenase (15-LO)/15-hydroxyeicosatetraenoic acid (15-HETE) expression. They found increased right ventricular systolic pressure and pulmonary arteries (PAs) reactivity to vasoconstrictors as well as intima-to-media ratio of PAs in HO-1 overexpressing transgenic mice. Moreover, HO-1 up-regulated 15-LO transcription and translation as well as 15-HETE in both transgenic mice and cultured pulmonary arterial smooth muscle cells. [Int J Biochem Cell B] Abstract

LUNG CANCER

βArrestin-1 and Mcl-1 Modulate Self-Renewal Growth of Cancer Stem-Like Side-Population Cells in Non-Small Cell Lung Cancer
Side population (SP) cells have been reported to have properties of cancer stem-like cells in non-small cell lung carcinoma (NSCLC), yet their molecular features have not been fully elucidated. Researchers showed that NSCLC-SP cells enriched in the G₀/G₁ phase of the cell cycle had higher aldehyde dehydrogenase activity as well as higher clonogenic and self-renewing ability compared to main population cells. [PLoS One] Full Article

Spheroid Culture of Primary Lung Cancer Cells with Neuregulin 1/HER3 Pathway Activation
Cancer tissue-originated spheroids were subjected to sensitivity assay and signal transduction assay for the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib. In vitro assay results showed that EGFR mutation status and expression levels corresponded with erlotinib sensitivity, confirming previous clinical findings. [J Thorac Oncol] Abstract

Cyclin-Dependent Kinase 2-Associated Protein 1 Suppresses Growth and Tumorigenesis of Lung Cancer
A lentivirus-based system was used to specifically downregulate or upregulate cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) expression. A549 lung cancer cells were treated with RNA interference or lentiviral vectors for overexpression. Ectopic overexpression of CDK2AP1 in A549 cells in vitro greatly impaired their proliferation and colony-forming ability and enhanced their chemosensitivity to cisplatin and paclitaxel and caused cell cycle arrest at G1/S transition accompanied by the reduction of expression of CDK4 and CDK7. [Int J Oncol] Abstract

Lipocalin-2 Is Associated with Radioresistance in Oral Cancer and Lung Cancer Cells
The authors report that when the LCN2 gene was knocked down in oral squamous cell carcinoma cells (Ca9-22 and HSC-2) and lung cancer cells (A549) by using small interfering RNA, the radiosensitivity of these cells was enhanced. [Int J Oncol] Abstract

The Role of Hypoxia in Pulmonary Vascular Diseases: A Perspective
The authors summarize pivotal results of clinical and preclinical research on hypoxia, which still have important implications for researchers today. [Am J Physiol – Lung C] Abstract

Grant Awarded to Study Novel Therapies for Muco-Obstructive Diseases Includes Studies on Cempra’s Solithromycin (CEM-101) in a Cystic Fibrosis Anti-inflammatory Model
Cempra, Inc., announced that the National Institute of Allergy and Infectious Diseases awarded a grant to Richard C. Boucher, M.D., Kenan Professor of Medicine and director of the Cystic Fibrosis and Pulmonary Research and Treatment Center at the University of North Carolina School of Medicine, to investigate the anti-inflammatory activity of solithromycin and its effect on mucin secretion in models for cystic fibrosis. [Cempra, Inc.] Press Release

World’s First FDA Cleared ALK Automated Gene Scanner for Lung Cancer Therapy-Selection Available from ASI
Applied Spectral Imaging Inc. (ASI), announced that its GenASIs Scan & Analysis automated microscopy platform has received FDA clearance as an aid in ALK gene analysis for lung cancer therapy selection. The introduction of automation in ALK therapy selection represents a new era in personalized medicine for patients with non-small cell lung cancer. [Applied Spectral Imaging Inc.] Press Release

Oncolytics Biotech^® Inc. Announces Additional Positive REOLYSIN^® Clinical Trial Data from Phase II Study in Squamous Cell Carcinoma of the Lung
Oncolytics Biotech Inc., announced results examining percent overall tumor shrinkage data from its U.S. Phase II clinical trial in patients with squamous cell carcinoma of the lung using intravenous administration of REOLYSIN^® in combination with carboplatin and paclitaxel. [Oncolytics Biotech Inc.] 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)

International Symposium on Respiratory Viral Infections
March 14-17, 2013
Rotterdam, The Netherlands

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Postdoctoral Fellows – Gene, RNA and Epigenetic Regulation, Protein Science, Signal Transduction, Cell and Stem Cell, Cancer and Other Diseases (Shanghai Institute of Biochemistry and Cell Biology)

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)

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