Pulmonary Cell News Volume 2.34 | Aug 29 2013

Role of Survivin in Acute Lung Injury: Epithelial Cells of Mice and Humans
Whether survivin would be toxic to human lung cells and tissues has not been determined. Investigators clarified the involvement of survivin in acute lung injury. [Lab Invest] Abstract

Fate of Toll-Like Receptor (TLR)-1/TLR-2 Agonist Functionalized pDNA Nanoparticles upon Deposition at the Human Bronchial Epithelium In Vitro
Plasmid DNA vaccination is a promising approach, but studies in non-human primates and humans failed to achieve protective immunity. To optimize this technology further with focus on pulmonary administration, scientists developed and evaluated an adjuvant-equipped DNA carrier system based on the biopolymer chitosan. [J Nanobiotechnology] Full Article

Normal CFTR Inhibits Epidermal Growth Factor Receptor-Dependent Pro-Inflammatory Chemokine Production in Human Airway Epithelial Cells
Investigators hypothesized that normal cystic fibrosis transmembrane conductance regulator (CFTR) suppresses epidermal growth factor receptor (EGFR)-dependent interleukin (IL)-8 production and that loss of CFTR at the surface exaggerates IL-8 production via activation of a pro-inflammatory EGFR cascade. [PLoS One] Full Article

Beclomethasone Dipropionate and Formoterol Reduce Oxidative/Nitrosative Stress Generated by Cigarette Smoke Extracts and IL-17A in Human Bronchial Epithelial Cells
Researchers investigated whether recombinant human interleukin-17A (IL-17A), in combination with cigarette smoke extracts, increases the levels of inducibile nitric oxide synthase, reactive oxygen species, nitrotyrosine and the activation of signal transducer and activator of transcription 1 in normal human bronchial epithelial cells. [Eur J Pharmacol] Abstract

HspA1A Facilitates DNA Repair in Human Bronchial Epithelial Cells Exposed to Benzo[a]pyrene and Interacts with Casein Kinase 2
Human bronchial epithelial cells stably transfected with plasmids carrying heat shock protein (Hsp)A1A gene or shRNAs against HspA1A were treated with benzo[a]pyrene. Results suggested that HspA1A could protect cells against DNA damage and facilitate the decrease of DNA damage levels during the first two hours of DNA repair. [Cell Stress Chaperones] Abstract

LUNG CANCER

Integrative Radiogenomic Profiling of Squamous Cell Lung Cancer
Scientists report the development of a high-throughput platform for measuring radiation survival in vitro and its validation by comparison to conventional clonogenic radiation survival analysis. They combined results from this high-throughput assay with genomic parameters in cell lines from squamous cell lung carcinoma, which is standardly treated by radiation therapy, to identify parameters that predict radiation sensitivity. [Cancer Res] Abstract | Full Article

Capillary Isoelectric-Focusing Immunoassays to Study Dynamic Oncoprotein Phosphorylation and Drug Response to Targeted Therapies in Non-Small Cell Lung Cancer
A novel capillary isoelectricfocusing immunoassay system was used to study the dynamic phosphorylation status of signaling molecules in non-small cell lung cancer cells treated with EGFR tyrosine kinase and MEK inhibitors. [Mol Cancer Ther] Abstract

Succinate Dehydrogenase 5(SDH5) Regulate (GSK)-3ß-ß-Catenin-Mediated Lung Cancer Metastasis
Researchers demonstrated that loss of SDH5 expression initiates epithelial-mesenchymal transition, which is visualized by the repression of E-cadherin and up-regulation of vimentin in lung cancer cell lines and clinical lung cancer specimens. [J Biol Chem] Abstract | Full Article

Neferine, an Alkaloid from Lotus Seed Embryo, Inhibits Human Lung Cancer Cell Growth by MAPK Activation and Cell Cycle Arrest
The effects of neferine were evaluated and characterized in A549 cells. Neferine induced apoptosis in a dose-dependent manner with the hypergeneration of reactive oxygen species, activation of MAPKs, lipid peroxidation, depletion of cellular antioxidant pool, loss of mitochondrial membrane potential, and intracellular calcium accumulation. [Biofactors] Abstract

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Clovis Oncology Announces First Patient Treated with Hydrobromide Salt Tablet Formulation of CO-1686 in Its Ongoing Phase I/II Clinical Study
Clovis Oncology announced that it has dosed the first patient with its new hydrobromide salt tablet formulation of CO-1686 in its ongoing Phase I dose-finding portion of its Phase I/II clinical study. CO-1686 is the Company’s novel, oral, targeted covalent (irreversible) inhibitor of mutant forms of the epidermal growth factor receptor for the treatment of non-small cell lung cancer in patients with initial activating mutations as well as the dominant resistance mutation T790M. [Clovis Oncology] Press Release

Gilotrif^TM (Afatinib) Tablets Will Be Available in the United States the Week of September 2
The United States Food and Drug Administration (FDA) approved GILOTRIF on July 12, 2013 as a new first-line – or initial – treatment for patients with metastatic non-small cell lung cancer with common epidermal growth factor receptor mutations as detected by an FDA-approved test. [Boehringer Ingelheim Pharmaceuticals, Inc.] Press Release

Rigel’s R343 Did not Meet Primary Endpoint in Asthma Study
Rigel Pharmaceuticals, Inc. announced that R343, an inhaled SYK inhibitor being evaluated as a potential therapeutic for patients with allergic asthma, did not meet the primary or secondary endpoints in a recently completed Phase II clinical study. [Rigel Pharmaceuticals, Inc.] Press Release

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PhD (Early Stage Researcher) Position – Investigation of Mucus as a Barrier for Pulmonary Drug Delivery (Helmholtz Institute for Pharmaceutical Research Saarland)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Postdoctoral Associate – Lung Cancer (Yale Cancer Center)

Professor of Immunology Centre for Infection and Immunity (Queen’s University Belfast)

Postdoctoral Research Fellow – Cancer Genomics (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Scientist – Asthma (Columbia University)

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

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

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