Pulmonary Cell News Volume 2.21 | May 30 2013

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    Pulmonary Cell News 2.21 May 30, 2013
    Pulmonary Cell News
         In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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    TOP STORY
    Control of Alveolar Differentiation by the Lineage Transcription Factors GATA6 and HOPX Inhibits Lung Adenocarcinoma Metastasis
    In lung cancers, scientists uncovered a transcriptional program that is preferentially associated with distal airway epithelial differentiation and lung adenocarcinoma (ADC) progression. This program is regulated in part by the lineage transcription factors GATA6 and HOPX. These factors can cooperatively limit the metastatic competence of ADC cells, by modulating overlapping alveolar differentiation and invasogenic target genes. [Cancer Cell] Abstract | Graphical Abstract

    Find protocols, tools and video at the Human Immunology Portal

    PUBLICATIONS (Ranked by impact factor of the journal)

    Evidence for Multiple Roles for Grainyheadlike 2 in the Establishment and Maintenance of Human Mucociliary Airway Epithelium
    Researchers focused on the role of grainyheadlike (GRHL)2 in primary human bronchial epithelial cells, both as undifferentiated progenitors and as they differentiate in air-liquid interface culture into an organized mucociliary epithelium with transepithelial resistance. Using a dominant-negative protein or shRNA to inhibit GRHL2, they followed changes in epithelial phenotype and gene transcription using RNA sequencing or microarray analysis. [Proc Natl Acad Sci USA] Abstract | Full Article

    Dysregulation of Alveolar Macrophages Unleashes Dendritic Cell-Mediated Mechanisms of Allergic Airway Inflammation
    To understand the implication of alveolar macrophages (AM) in lung immunity, the authors investigated the influence of AM sensitization status on lung dendritic cell (DC) activation induced by allergen challenge in vivo. Rat sensitized to ovalbumin developed airway inflammation and demonstrated myeloid DC activation following allergen exposure. [Mucosal Immun] Abstract

    Metformin Reduces Airway Glucose Permeability and Hyperglycemia-Induced Staphylococcus aureus Load Independently of Effects on Blood Glucose
    Scientists investigated whether elevation of basolateral/blood glucose concentration promotes airway Staphylococcus aureus growth and whether pretreatment with the antidiabetic drug metformin affects this relationship. Apical S. aureus growth increased with basolateral glucose concentration in an in vitro airway epithelia-bacteria co-culture model. [Thorax] Full Article

    Eosinophils Promote Epithelial to Mesenchymal Transition of Bronchial Epithelial Cells
    Researchers hypothesized that infiltrating eosinophils promote airway remodeling in bronchial asthma. To demonstrate this hypothesis they evaluated the effect of eosinophils on epithelial to mesenchymal transition by in vitro and in vivo studies. [PLoS One] Full Article

    The Activation of HMGB1 as a Progression Factor on Inflammation Response in Normal Human Bronchial Epithelial Cells through RAGE/JNK/NF-κB Pathway
    The inflammation response in normal human bronchial epithelial cells was stimulated by 2.5, 5, and 10 μg/ml high-mobility group box-1 (HMGB-1). However, the receptor for advanced glycation end products (RAGE) blocker RAGE-Ab or 10 μM c-Jun N-terminal kinases (JNK) inhibitor SP600125 could inhibit HMGB1-induced the release of inflammation cytokines including TNF-α, IL-8, IL-10, and MCP-1 in a dose-dependent manner. [Mol Cell Biochem] Abstract

    LUNG CANCER

    Ectopic Activation of Germline and Placental Genes Identifies Aggressive Metastasis-Prone Lung Cancers
    Activation of normally silent tissue-specific genes and the resulting cell “identity crisis” are the unexplored consequences of malignant epigenetic reprogramming. Scientists designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic cells and then detecting their expression in cancer. [Sci Transl Med] Abstract

    Sarcomatoid Lung Carcinomas Show High Levels of Programmed Death Ligand-1 (PD-L1)
    Investigators report the expression of PD-L1 in 13 sarcomatoid carcinomas (SCs) from two large retrospective lung cancer cohorts. Using automated quantitative immunofloresence and a mouse monoclonal antibody directed against the extracellular domain of PD-L1, they showed that 9 of 13 patients with SCs are positive for PD-L1 and their levels are higher than in conventional non-small-cell lung carcinoma. [J Thorac Oncol] Abstract

    Involvement of Intermediate Filament Nestin in Cell Growth of Small-Cell Lung Cancer
    Researchers investigated the expression and function of nestin in small-cell lung cancer (SCLC). Nestin was expressed in nine of ten SCLC cell lines. The nestin expression level was significantly higher in SCLC cell lines than in NSCLC cell lines. [Lung Cancer] Abstract

    The MicroRNA-200 Family Targets Multiple Non-Small Cell Lung Cancer Prognostic Markers in H1299 Cells and BEAS-2B Cells
    Scientists investigated whether the microRNA-200 (miR-200) family regulates our previously identified non-small cell lung cancer prognostic marker genes associated with metastasis, as potential molecular targets. Reinforced miR-200b expression results in downregulation of DLC1, HNRNPA3 and HFE. Additionally, miR-200 family downregulates HNRNPR3, HFE and ATRX in BEAS-2B immortalized lung epithelial cells in quantitative RT-PCR and western blot assays. [Int J Oncol] Abstract

    PRC2 Overexpression and PRC2-Target Gene Repression Relating to Poorer Prognosis in Small Cell Lung Cancer
    Small cell lung cancer (SCLC) is a subtype of lung cancer with poor prognosis. Treatment with EZH2 inhibitors, DZNep and GSK126, resulted in growth repression of SCLC cell lines. [Sci Rep] Full Article

    PneumaCult™-ALI Medium for Bronchial Epithelial Cells: Watch the Video

    REVIEWS

    Adapting Global Influenza Management Strategies to Address Emerging Viruses
    Although the influenza pandemic of 2009 emphasized the need for the rapid standardization of global surveillance methods and the preparation and dissemination of global assay standards for improved reporting and diagnostic tools, outbreaks of novel influenza strains continue to occur, and current efforts must be enhanced by aggressive public education programs to promote increased vaccination rates in the global population. [Am J Physiol-Lung C] Abstract | Full Article | Press Release

    Airway Inflammation in Cystic Fibrosis: Molecular Mechanisms and Clinical Implications
    Airway epithelial cells and immune cells participate in the inflammatory process responsible for much of the pathology found in the lung of patients with cystic fibrosis (CF). Intense bronchial neutrophilic inflammation and release of proteases and oxygen radicals perpetuate the vicious cycle and progressively damage the airways. In vitro studies suggest that CF transmembrane conductance regulator-deficient airway epithelial cells display signaling abnormalities and aberrant intracellular processes which lead to transcription of inflammatory mediators. [Thorax] Abstract

    Mesenchymal Stem Cells as Vectors for Lung Cancer Therapy
    This review outlines various agents which can be delivered by mesenchymal stem cells with substantial emphasis on TRAIL (tumor necrosis factor-related apoptosis-inducing ligand). [Respiration] Full Article

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

    INDUSTRY NEWS

    OncoGenex Announces Plans for the Initiation of the Cedar™ Clinical Trial Evaluating OGX-427 in Combination with Chemotherapy in Advanced Squamous Cell Lung Cancer
    OncoGenex Pharmaceuticals, Inc. announced plans for the initiation of the Cedar™ clinical trial, an investigator-sponsored, randomized, open-label Phase II trial evaluating OGX-427 in previously untreated patients with advanced squamous cell lung cancer. [OncoGenex Pharmaceuticals, Inc.] Press Release

    GTx to Present on Enobosarm for Muscle Wasting in Non-Small Cell Lung Cancer at an Industry Expert Theater During the 2013 ASCO Annual Meeting
    GTx, Inc. announced that the company will showcase the development of enobosarm at an Industry Expert Theater Presentation during the upcoming 2013 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. [GTx, Inc.] Press Release

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    POLICY NEWS

    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)

    EVENTS

    NEW 14th International TNF Conference: Tumor Necrosis Factor 2013
    July 3-7, 2013
    Quebec City, Canada

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

    JOB OPPORTUNITIES

    NEW 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 Researcher – Sensory Pathways in Mammalian Airway Epithelia (Washington University)

    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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