Volume 3.42 | Oct 30

Pulmonary Cell News 3.42 October 30, 2014
Pulmonary Cell News
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IL-33-Dependent Type 2 Inflammation during Rhinovirus-Induced Asthma Exacerbations In Vivo
Researchers tested whether the epithelial-derived cytokine IL-33 plays a central role in exacerbation pathogenesis through augmentation of type 2 inflammation. They cultured human T cells and type 2 innate lymphoid cells with the supernatants of rhinovirus-infected bronchial epithelial cells to assess type 2 cytokine production in the presence or absence of IL-33 receptor blockade. [Am J Respir Crit Care Med] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Cystic Fibrosis Airway Epithelium Remodelling: Involvement of Inflammation
The authors evaluated the involvement of alterations of cystic fibrosis (CF) human airway epithelial (HAE) cells in airway epithelium remodelling. HAE cells from non-CF and CF patients were cultured in an air-liquid interface with and without inflammatory stimulation along the regeneration process, and the remodelling of the reconstituted epithelium was analyzed. [J Pathol] Abstract

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]

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


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

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Airway Basal Cells: The “Smoking Gun” of COPD
When confronted by the chronic stress of smoking airway basal cells become disorderly, regress to a more primitive state, behave as dictated by their inheritance, are susceptible to acquired changes in their genome, lose the capacity to regenerate the epithelium, are responsible for the major changes in the airway that characterize COPD, and with persistent stress can undergo malignant transformation.
[Am J Respir Crit Care Med]

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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Phase II Objective Response Rate and Survival Data for Opdivo (Nivolumab) in Heavily Pre-treated Advanced Squamous Cell Non-Small Cell Lung Cancer
Bristol-Myers Squibb Company announced results from CheckMate -063, a Phase II single-arm, open-label study of Opdivo (nivolumab), an investigational PD-1 immune checkpoint inhibitor, administered as a single agent in patients with advanced squamous cell non-small cell lung cancer who have progressed after at least two prior systemic treatments with 65% receiving three or more prior therapies. [Press release from Bristol-Myers Squibb discussing research to be presented at the 2014 Multidisciplinary Symposium on Thoracic Oncology, Chicago] Press Release

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Merck Receives FDA Breakthrough Therapy Designation for KEYTRUDA® (Pembrolizumab) in Advanced Non-Small Cell Lung Cancer
Merck announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of patients with epidermal growth factor receptor mutation-negative, and anaplastic lymphoma kinase rearrangement-negative non-small cell lung cancer whose disease has progressed on or following platinum-based chemotherapy. [Merck & Co.] Press Release

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
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)
NEW 16th International Congress on Hormonal Steroids and Hormones and Cancer
December 2-4, 2014
Riyadh, Saudi Arabia

Visit our events page to see a complete list of events in the pulmonary cell community.
NEW PhD Student – Functional Relevance of MicroRNAs in COPD (University Medical Center Groningen)

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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