Pulmonary Cell News Volume 2.22 | Jun 6 2013

Pulmonary Inflammation Induced by Bacteria-Free Outer Membrane Vesicles from Pseudomonas aeruginosa
Scientists determined whether outer membrane vesicles (OMVs) from P. aeruginosa can induce pulmonary inflammation in vivo, and elucidated mechanisms involved. OMVs given to the mouse lung caused a dose- and time-dependent pulmonary cellular inflammation. [Am J Resp Cell Mol Biol] Abstract

The Role of Interleukin-1 and Interleukin-18 in Pro-Inflammatory and Anti-Viral Responses to Rhinovirus in Primary Bronchial Epithelial Cells
Interleukin-1alpha, interleukin-1beta and interleukin-18 have critical roles in the establishment of neutrophilic inflammation, which is commonly seen in airways viral infection and thought to be detrimental in respiratory disease. The authors therefore investigated the roles of these molecules in human Rhinovirus infection of primary human epithelial cells. They found that all three cytokines were released from infected epithelia. [PLoS One] Full Article

Distinct Transcriptome Profiles Identified in Normal Human Bronchial Epithelial Cells after Exposure to Gamma-Rays and Different Elemental Particles of High Z and Energy
Researchers performed transcriptome profiling using human bronchial epithelial cells after exposure to gamma-rays and to two different high atomic number (Z) and energy (HZE) particles (28Si and 56Fe) with different energy transfer properties to characterize the molecular response to HZE particles and gamma-rays as a function of dose, energy deposition pattern, and time post-irradiation. [BMC Genomics]
Abstract | Full Article

The Expression of Protease-Activated Receptors in Chronic Rhinosinusitis
Researchers compared the expression and distribution of protease-activated receptors (PARs) in biopsy specimens obtained from chronic rhinosinusitis (CRS) and control patients. Both the epithelium and the infiltrating inflammatory cells in the CRS with asthma groups showed significant upregulation of the expression of PAR-2 and PAR-3 compared with the CRS without asthma group and the control group. [Int Arch Allergy Immunol] Abstract

Efficient Biodistribution and Gene Silencing in the Lung Epithelium via Intravenous Liposomal Delivery of siRNA
Scientists showed that 45 ± 2% of epithelial murine lung cells received short interfering RNA (siRNA) delivery upon intravenous liposomal administration. Furthermore, they demonstrated that liposomal siRNA delivery resulted in targeted gene and protein knockdown throughout the lung, including lung epithelium. [Mol Ther Nucleic Acids] Full Article

LUNG CANCER

IL-10 Promotes Tumor Aggressiveness via Upregulation of CIP2A Transcription in Lung Adenocarcinoma
To investigate how IL-10 is regulated by HPV E6, an IL-10 promoter was constructed to understand which transcriptional factor could be responsible for its transcription. Mechanistic studies showed that IL-10 protein and mRNA expression was decreased in E6-knockdown TL1 cells and increased in E6-overexpressing TL4 cells. [Clin Cancer Res] Abstract

Pharmacological Activation of PKM2 Slows Lung Tumor Xenograft Growth
To test the hypothesis that tumor growth may be inhibited through the pyruvate kinase (PKM2) pathway, investigators generated a series of small molecule PKM2 activators. The compounds exhibited low nM activity in both biochemical and cell-based PKM2 activity assays. [Mol Cancer Ther] Abstract

MicroRNA-449a Is Downregulated in Non-Small Cell Lung Cancer and Inhibits Migration and Invasion by Targeting c-Met
To identify the function of microRNA (miR)-449a in non-small cell lung cancer (NSCLC), scientists discussed the potential relevance of miR-449a to clinicopathological characteristics and prognosis in NSCLC. MiR-449a was downregulated in both NSCLC tissues and cell lines. [PLoS One] Full Article

Enhancing Effect of Poly(Amino Acid)s on Albumin Uptake in Human Lung Epithelial A549 Cells
Researchers investigated the effect of poly(amino acid)s such as poly-L-ornithine (PLO) on albumin uptake in cultured lung epithelial cell line A549. FITC-albumin uptake as well as cell surface binding was markedly stimulated by co-incubation with PLO, and there was a good correlation between them. [Drug Metab Pharmacokinet] Abstract | Full Article

Dipalmitoyl-Phosphatidylcholine Biosynthesis is Induced by Non-Injurious Mechanical Stretch in a Model of Alveolar Type II Cells
The authors investigated whether a low magnitude, non-injurious static mode of mechanical stretch can induce phosphatidylcholine biosynthesis and its remodeling to dipalmitoylphosphatidylcholine in the A549 cell-line, a model of alveolar type II cells. The deformation of A549 cells did not cause any release of lactate dehydrogenase, or phospholipids into the cell culture supernatants. [Lipids] Abstract

How and When to Use Genetic Markers for Non-Small Cell Lung Cancer
The authors reviewed recent research on clinically relevant genetic and molecular tests for patients with non-small cell lung cancer, with an emphasis on the tests linked to actionable mutations that influence therapy and improve outcomes. [Curr Opin Pulm Med] Abstract

Visit our reviews page to see a complete list of reviews in the pulmonary cell research field.

Clovis Oncology’s CO-1686 Demonstrates Encouraging Results from Ongoing Phase I/II Study in EGFR-Mutant Non-Small Cell Lung Cancer
Clovis Oncology announced initial findings from the Phase I portion of its ongoing Phase I/II clinical study of CO-1686, the Company’s novel, oral, targeted covalent (irreversible) inhibitor of mutant forms of the epidermal growth factor receptor (EGFR) for the treatment of non-small cell lung cancer in patients with initial activating EGFR mutations as well as the dominant resistance mutation T790M. [Press release from Clovis Oncology discussing research presented at the American Society of Clinical Oncology Annual Meeting, Chicago] Press Release

ARIAD Presents Updated Phase I Data on AP26113 in Patients with Non-Small Cell Lung Cancer
ARIAD Pharmaceuticals, Inc. announced updated clinical results on its investigational tyrosine kinase inhibitor, AP26113, in patients with advanced non-small cell lung cancer from an ongoing Phase I/II trial. [Press release from ARIAD Pharmaceuticals, Inc. discussing research presented at the American Society of Clinical Oncology Annual Meeting, Chicago] Press Release

Novartis Breakthrough Therapy LDK378 Shows a Marked Clinical Response in Patients with ALK+ Non-Small Cell Lung Cancer
Novartis announced data on its investigational compound LDK378 showing a marked clinical response in 78 patients with anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer who had progressed during or after crizotinib therapy or had not been previously treated with crizotinib. [Press release from Novartis AG discussing research presented at the American Society of Clinical Oncology Annual Meeting, Chicago] Press Release

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Inspiro Medical Ltd. Completes a Successful First Clinical Trial in Asthmatic Children
Inspiro Medical, recently completed a successful clinical trial for Inspiromatic^TM, its innovative, breath-synchronized, active dry powder inhaler. [PR Newswire Association LLC] Press Release

American Lung Association Report: Women at Greater Risk of COPD; Half Don’t Know They Have It
Women are 37 percent more likely to have chronic obstructive pulmonary disease (COPD) than men and now account for more than half of all deaths attributed to COPD in the United States. [American Lung Association] Press Release

Genoa Pharmaceuticals and McMaster University Demonstrate In Vivo Benefit of Inhaled Pirfenidone Offering Greater Pulmonary Fibrosis Efficacy than Oral Therapy
Genoa Pharmaceuticals, and collaborators Drs. Martin Kolb and Kjetil Ask at McMaster University announced the measured advantages of inhaled GP-101 (aerosol pirfenidone) in the treatment of pulmonary fibrosis. [Genoa Pharmaceuticals] Press Release

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NEW World Conference on Regenerative Medicine
October 23-25, 2013
Leipzig, Germany

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

NEW Postdoctoral Associate – Mechanisms of Pathogenesis in Idiopathic Pulmonary Fibrosis (University of Minnesota)

Postdoctoral Position – Idiopathic Pulmonary Fibrosis (MedImmune UK Ltd)

Postdoctoral Position – Lung Development and Repair (Boston University Pulmonary Center)

PhD Studentships – Pulmonary Biology and Medicine (University of Giessen and Marburg Lung Center)

PhD Studentship – Pulmonary Medicine (Erasmus MC)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

Postdoctoral Position – Respiratory Research (INSERM)

Postdoctoral Position – Cardiopulmonary Molecular Biology (Hannover Medical School)

Post-doctoral Position – Mucosal Immunology (University of Southern California)

PhD Opportunity – Biofunctionalization of Liposomes for Tumor-Targeted Drug Delivery (University of East Anglia)

Postdoctoral Position – Pulmonary Research (Cedars-Sinai Medical Center)

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