Pulmonary Cell News Volume 3.42 | Oct 30 2014

Inflammatory Response of Lung Macrophages and Epithelial Cells after Exposure to Redox-Active Nanoparticles: Effect of Solubility and Antioxidant Treatment
The effects of an exposure to three mass-produced metal oxide nanoparticles – similar in size and specific surface area, but different in redox activity and solubility – were studied in rat alveolar macrophages and epithelial cells. Researchers hypothesized that the cell response depends on the particle redox activity and solubility determining the amount of reactive oxygen species formation and subsequent inflammatory response. [Environ Sci Technol] Abstract

Cigarette Smoke Extract Affects Mitochondrial Function in Alveolar Epithelial Cells
Investigators analyzed the mitochondrial response to mild and non-toxic doses of cigarette smoke extract (CSE) in alveolar epithelial cells. Murine lung epithelial 12, as well as primary mouse alveolar epithelial cells revealed pronounced mitochondrial hyperfusion upon treatment with CSE, accompanied by increased expression of the mitochondrial fusion protein mitofusin 2 and increased metabolic activity.
[Am J Physiol Lung Cell Mol Physiol] Abstract

Zinc and Zinc Transporters in Macrophages and Their Roles in Efferocytosis in COPD
Impaired efferocytic clearance of apoptotic epithelial cells by alveolar macrophages occurs in chronic obstructive pulmonary disease (COPD), cigarette-smoking and other lung inflammatory diseases. Investigators show that zinc is a factor in impaired macrophage efferocytosis in COPD. [PLoS One] Full Article

LUNG CANCER

Alectinib Shows Potent Antitumor Activity Against RET-Rearranged Non-Small Cell Lung Cancer
Alectinib/CH5424802 is a known inhibitor of anaplastic lymphoma kinase (ALK) and is being evaluated in clinical trials for the treatment of ALK fusion-positive non-small cell lung cancer. Researchers explored additional target indications of alectinib by testing its ability to inhibit the activity of kinases other than ALK. [Mol Cancer Ther] Abstract

Pim-1 Kinase Is a Target of miR-486-5p and Eukaryotic Translation Initiation Factor 4E, and Plays a Critical Role in Lung Cancer
Scientists investigated if Pim-1 has important functions in non-small-cell lung cancer (NSCLC) by evaluating the clinicopathologic significance of Pim-1 through analyzing its expression in 101 human NSCLCs tissues using quantitative PCR, Western Blot and immunohistochemical studies, determining its role in NSCLC and drug resistance using in vitro assays, and investigating the regulatory mechanism of Pim-1 dysregulation in lung tumorigenesis. [Mol Cancer] Full Article

Melatonin Induces Apoptosis through Biomolecular Changes, in SK-LU-1 Human Lung Adenocarcinoma Cells
Anti-cancer effects of melatonin have been widely reported, however, little has been known, regarding its mechanism(s) of action in lung cancer. Scientists investigated its induction of apoptosis through biomolecular changes (lipid, protein and nucleic acid/DNA) in the SK-LU-1 human lung cancer cell line. [Cell Prolif] Abstract

BYL719, a Selective Inhibitor of Phosphoinositide 3-Kinase α, Enhances the Effect of Selumetinib (AZD6244, ARRY-142886) in KRAS-Mutant Non-Small Cell Lung Cancer
Researchers evaluated the effects of selumetinib and BYL719 in vitro and in vivo in non-small cell lung cancers (NSCLC) cell lines. The combination of BYL719 and selumetinib resulted in synergistic cytotoxic activity compared with the single agents alone in KRAS-mutant NSCLC cells. [Invest New Drugs] Abstract

Multiple Roles of Extracellular Fibroblast Growth Factors in Lung Cancer Cells
Researchers determined whether extracellular fibroblast growth factors (FGFs) can affect the biology of lung cancer cells and aimed to understand how extracellular FGFs affect the biology of lung cancer cells, including non-small cell lung cancer and small cell lung cancer cells. [Int J Oncol] Abstract

Trim44 Facilitates the Migration and Invasion of Human Lung Cancer Cells via the NF-κB Signaling Pathway
Researchers analyzed 30 pairs of non-small cell lung cancer (NSCLC) tumors and the matched adjacent normal tissue to define the relationship between tripartite motif-containing protein (Trim) 44 and NSCLC tumors. The function of Trim44 in cell migration and invasion was determined by overexpression of Trim44 in normal bronchial epithelial cell line 16HE or knockdown of Trim44 in A549 cells, respectively. [Int J Clin Oncol] Abstract

Cellular and Molecular Immunology of Lung Cancer: Therapeutic Implications
Key immune cells involved in the pathogenesis of lung cancer include CD4⁺ T lymphocytes, macrophages, dendritic cells and NK cells. The growing understanding of these cells indicates a highly complex and intertwined network of their involvement in each stage of lung cancer. Immune cell types and numbers affect prognosis and could offer an opportunity for clinical therapeutic applications. [Expert Rev Clin Immunol] Abstract

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Xcovery Raises $20M through Equity Investment from China’s Betta Pharmaceuticals for Development of ALK Inhibitor
Xcovery announced a commitment for a $20 million equity investment from Betta Pharmaceuticals Co., a leading Chinese pharmaceutical company focused on discovering, developing and delivering innovative medicines. In addition to the equity investment in Xcovery, Betta will gain Chinese rights to X-396, a potent small molecule anaplastic lymphoma kinase (ALK) inhibitor currently in a Phase I/II expansion cohort. [Xcovery] Press Release

Five Prime Therapeutics Announces Expansion of Respiratory Disease Research Collaboration and License Agreement with GSK
Five Prime Therapeutics, Inc. announced an expansion of its respiratory disease research collaboration with GlaxoSmithKline (GSK) that was established in 2012 to identify first-in-class agents and new mechanisms for the treatment of refractory asthma and chronic obstructive pulmonary disease. [Five Prime Therapeutics, Inc.] Press Release

Clovis Oncology Announces First Patient Enrolled in Lucitanib Phase II Study in Squamous Non-Small Cell Lung Cancer
Clovis Oncology, Inc. announced that its global Phase II study of lucitanib in patients with FGFR1-amplified squamous non-small cell lung cancer has commenced and the first patient has been dosed at a U.S. study site. [Clovis Oncology, Inc. (Business Wire)] Press Release

Compugen Discloses Successful Validation Results for Novel B7/CD28-Like Cancer Immunotherapy Target Candidate
Compugen Ltd. disclosed successful experimental data for CGEN-15027, a Compugen-discovered immune checkpoint target candidate. The experimental results include its expression in the cancer microenvironment, both on cancer cells derived from lung, breast, and liver cancer patients, and on tumor infiltrating immune cells. [Compugen Ltd.] Press Release

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Scientist – Experimental Lung Lab (Charite – Universitaetsmedizin Berlin)

PhD Student – Functional Relevance of MicroRNAs in COPD (University Medical Center Groningen)

PhD Positions – Cardiovascular-Pulmonary Science (Chonbuk National University)

Postdoctoral Researcher – Metabolomics of Pulmonary Medicine (Karolinska Institute)

Postdoctoral Fellow – Experimental Pulmonary Hypertension (Brigham and Women’s Hospital Harvard Medical School)

Investigator – Multiple Positions in Cellular & Molecular Medicine (Cleveland Clinic Lerner Research Institute)

Postdoctoral Fellow – Cardiopulmonary Molecular Biology (Hannover Medical School)

Postdoctoral Position – Pulmonary Research (University of Chicago)

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

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