Pulmonary Cell News Volume 2.27 | Jul 11 2013

Increased Acid Stability of the Hemagglutinin Protein Enhances H5N1 Influenza Virus Growth in the Upper Respiratory Tract but Is Insufficient for Transmission in Ferrets
Scientists investigated how a decrease in hemagglutinin (HA) activation pH influences the properties of highly pathogenic H5N1 influenza virus in mammalian hosts. The VN1203-HA2-K58I virus had similar replication kinetics compared to VN1203-wild-type in MDCK and normal human bronchial epithelial cells yet reduced growth in human alveolar A549 cells, which were found to have a higher endosomal pH than MDCK cells. [J Virol] Abstract

Bilateral Entry and Release of Middle East Respiratory Syndrome-Coronavirus Induces Profound Apoptosis of Human Bronchial Epithelial Cells
The newly emerged MERS-CoV infects human bronchial epithelial Calu-3 cells. Unlike SARS-CoV which exclusively infects and releases through the apical route, this virus can do so through either side of polarized Calu-3 cells. Infection results in profound apoptosis within 24 hours irrespective of its production of titers that are lower than those of SARS-CoV. [J Virol] Abstract

Gamma-Glutamyltransferase Catabolism of S-Nitroso-Glutathione Modulates IL-8 Expression in Cystic Fibrosis Bronchial Epithelial Cells
Scientists evaluated the effect of S-Nitrosoglutathione (GSNO) catabolism mediated by gamma-glutamyltransferase (GGT) on production of IL-8 in CFTR-mutated IB3-1 bronchial cells. The rapid, GGT-catalyzed catabolism of GSNO caused a decrease of both basal and LPS-stimulated IL-8 production in IB3-1 cells, by modulating both NF-?B and ERK1/2 pathways, along with a decrease of cell proliferation. [Free Radical Bio Med] Abstract

Identification of Different Subsets of Lung Cells Using Raman Microspectroscopy and Whole Cell Nucleus Isolation
Raman spectroscopy has been widely used to study its possible clinical application in cancer diagnosis. However, in order to make it into clinical practice, it is important that this technique is able not only to identify cancer cells from their normal counterparts, but also from the array of cells present in human tissues. To this purpose, the authors used Raman spectroscopy to assess whether this technique was able to differentiate not only between lung cancer cells and lung epithelial cells but also from lung fibroblasts. [Analyst] Abstract

Diethyl Sulfate-Induced Cell Cycle Arrest and Apoptosis in Human Bronchial Epithelial 16HBE Cells
Researchers investigated the effects of diethyl sulfate (DES) on cell proliferation, cell cycle progression and apoptosis in human bronchial epithelial 16HBE cells. The results showed that DES inhibited cell proliferation in a dose- and time-dependent manner, and induced significant apoptosis in 16HBE cells. [Chem Biol Interact] Abstract

LUNG CANCER

Targeted Genetic Dependency Screen Facilitates Identification of Actionable Mutations in FGFR4, MAP3K9, and PAK5 in Lung Cancer
Investigators identified three kinases with gain-of-function mutations in lung cancer, namely FGFR4, MAP3K9, and PAK5. Mutations in these kinases are activating toward the ERK pathway, and targeted depletion of the mutated kinases inhibits proliferation, suppresses constitutive activation of downstream signaling pathways, and results in specific killing of the lung cancer cells. [Proc Natl Acad Sci USA]
Abstract | Full Article | Press Release

Novel Small Molecule Inhibitors of Bcl-XL to Treat Lung Cancer
The authors identified two new Bcl-XL inhibitors that exhibit selective toxicity against lung cancer cells compared with normal human bronchial epithelial cells. Fluorescence polarization assay revealed that BXI-61 and BXI-72 preferentially bind to Bcl-XL protein but not Bcl2, Bcl-w, Bfl-1/A1 or Mcl-1 in vitro with high binding affinities. [Cancer Res] Abstract

Nuclear Factor-?B-Mediated Inflammation Leading to EMT via miR-200c Is Involved in Cell Transformation Induced by Cigarette Smoke Extract
Scientists evaluated the roles of inflammation and the epithelial-mesenchymal transition (EMT) in cigarette smoke extract (CSE)-induced transformation of human bronchial epithelial cells. The results showed that chronic exposure to CSE induced EMT and transformation of these cells. [Toxicol Sci] Abstract

Involvement of TRPC Channels in Lung Cancer Cell Differentiation and the Correlation Analysis in Human Non-Small Cell Lung Cancer
The authors investigated the involvement of canonical transient receptor potentials (TRPCs) in the cell differentiation of lung cancer. Blockade of TRPC channels inhibited A549 cell proliferation, while overexpression of TRPCs increased the proliferation. [PLoS One] Full Article

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Vertex Receives Australian Approval for KALYDECO™ (ivacaftor), the First Medicine to Treat the Underlying Cause of Cystic Fibrosis in People with a Specific Genetic Mutation (G551D)
Vertex Pharmaceuticals Incorporated announced that the Therapeutic Goods Administration of Australia has approved KALYDECO™ (ivacaftor) for people with cystic fibrosis ages 6 and older who have at least one copy of the G551D mutation in the cystic fibrosis transmembrane conductance regulator gene. [Vertex Pharmaceuticals Incorporated] Press Release

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NEW Postdoctoral Fellow – ERK3 Kinase Signaling in Cancer Progression and Metastasis (Wright State University)

NEW Postdoctoral Researcher – Molecular Determinants of Resistance to Chemotherapy and Radiation (The Ohio State University – Comprehensive Cancer Center)

Postdoctoral Position – Idiopathic Pulmonary Fibrosis (University of Minnesota – Twin Cities)

Postdoctoral Fellow – Translational Oncology (The University of Texas MD Anderson Cancer Center)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

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

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