Pulmonary Cell News Volume 3.38 | Oct 2 2014

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    Pulmonary Cell News 3.38 October 2, 2014

    Pulmonary Cell News

         In this issue: Publications | Reviews | Science News | Industry News | Policy News | Events | Jobs
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    TOP STORY
    ASCL1 Is a Lineage Oncogene Providing Therapeutic Targets for High-Grade Neuroendocrine Lung Cancers
    Scientists discovered an achaete-scute homolog 1 (ASCL1) target 72-gene expression signature that identifies neuroendocrine differentiation in non-small cell lung cancer (NSCLC) cell lines, is predictive of poor prognosis in resected NSCLC specimens from three datasets, and represents novel “druggable” targets. [Proc Natl Acad Sci USA] Abstract | Full Article
    Model the Human Respiratory Epithelium with PneumaCult™-ALI. Click to View Data.

     
    PUBLICATIONS (Ranked by impact factor of the journal)
    Hyperoxia Inhibits Nitric Oxide Treatment Effects in Alveolar Epithelial Cells via Effects on L-Type Amino Acid Transporter-1
    Hyperoxia impaired nitric oxide effects on S-nitrosothiol accumulation and soluble guanylyl cyclase activation in proportion to the magnitude of hyperoxia and the duration of exposure, up to 12 hours, in type I-like and type II-like rat and human alveolar epithelial cells. [Antioxid Redox Signal] Abstract

    Cathepsin B Contributes to Na+ Hyperabsorption in Cystic Fibrosis Airway Epithelial Cultures
    In bronchial epithelia from both normal and cystic fibrosis (CF) donor lungs, cathepsin B (CTSB) localized to the apical membrane. In normal and CF human bronchial epithelial cultures, CTSB was detected at the apical plasma membrane and in the airway surface liquid. [J Physiol] Abstract

    Oxidative Stress Regulates CFTR Gene Expression in Human Airway Epithelial Cells through a Distal Antioxidant Response Element
    Cystic fibrosis transmembrane conductance regulator gene (CFTR) expression in human airway epithelial cells involves the recruitment of distal cis-regulatory elements, which are associated with airway-selective DNase hypersensitive sites at -44kb and -35kb from the gene. Scientists investigated the -44 kb element, which also has enhancer activity in vitro in airway epithelial cells but is inactive in intestinal epithelial cells. [Am J Respir Cell Mol Biol] Abstract

    Phospholipase Cε, an Effector of Ras and Rap Small GTPases, Is Required for Airway Inflammatory Response in a Mouse Model of Bronchial Asthma
    Primary-cultured bronchial epithelial cells prepared from phospholipase Cε (PLCε)ΔX/ΔX mice showed attenuated pro-inflammatory cytokine production when stimulated with tumor necrosis factor-α, suggesting that reduced cytokine production in PLCεΔX/ΔX mice was due to cell-autonomous effect of PLCε deficiency. [PLoS One]
    Full Article

    Insulin Upregulates the Expression of Epithelial Sodium Channel In Vitro and in a Mouse Model of Acute Lung Injury: Role of mTORC2/SGK1 Pathway
    In alveolar epithelial cells, insulin increased the expression of α-, β-, and γ-epithelial sodium channel, which was blocked by the mammalian target of rapamycin complex 2 (mTORC2) inhibitor or knockdown of Rictor, and serum and glucocorticoid induced kinase-1 (SGK1) inhibitor, respectively. [Exp Cell Res] Abstract

    Stanniocalcin-1 Is Induced by Hypoxia Inducible Factor in Rat Alveolar Epithelial Cells
    Scientists found that stanniocalcin-1 (STC1) was induced by hypoxia and hypoxia inducible factor in rat alveolar type II cells, and this induction occurred rapidly and reversibly. They also show that recombinant human STC1 enhanced cell motility with extended lamellipodia formation in alveolar epithelial cell monolayers but did not inhibit the oxidative damage induced by LPS. [Biochem Biophys Res Commun] Abstract

    LUNG CANCER

    Tissue Inhibitor of Metalloproteinases-1 Induces a Pro-Tumorigenic Increase of miR-210 in Lung Adenocarcinoma Cells and Their Exosomes
    Researchers demonstrate that an increase of both exogenous and endogenous tissue inhibitor of metalloproteinases-1 led to the upregulation of miR-210 in a CD63/PI3K/AKT/HIF-1-dependent pathway in lung adenocarcinoma cells. [Oncogene] Abstract

    RET Mutation and Expression in Small-Cell Lung Cancer
    Stable overexpression of both mutant M918T and wild-type RET in two small-cell lung cancer cell lines, H1048 and SW1271, activated ERK signaling, MYC expression, and increased cell proliferation, particularly by mutant RET. [J Thorac Oncol] Full Article

    miR-630 Inhibits Proliferation by Targeting CDC7 Kinase, but Maintains the Apoptotic Balance by Targeting Multiple Modulators in Human Lung Cancer A549 Cells
    Scientists found that microRNA-630 (miR-630) was highly expressed in A549 and NIH3T3 cells where cell-cycle kinase 7 (CDC7) was downregulated, but lower in H1299, MCF7, MDA-MB-231, HeLa and 2BS cells where CDC7 was upregulated. The induction of miR-630 occurred commonly in a variety of human cancer and immortalized cells in response to genotoxic agents. [Cell Death Dis] Full Article

    MicroRNA-191, by Promoting the EMT and Increasing CSC-Like Properties, Is Involved in Neoplastic and Metastatic Properties of Transformed Human Bronchial Epithelial Cells
    High-throughput microarray analysis showed that 51 microRNAs were differentially expressed in transformed human bronchial epithelial (HBE) cells relative to normal HBE cells. In particular, microRNA-191 was up-regulated in transformed cells. [Mol Carcinog] Abstract

    Listen Now: Podcast on ALDH in Breast Cancer Treatment Response

     
    REVIEWS
    Advances in Pharmacotherapy of Small Cell Lung Cancer
    For patients with extensive-stage small cell lung cancer (SCLC), survival can be increased with combination platinum-based chemotherapy, but the disease remains incurable. The author looks at the current advances in pharmacotherapy for SCLC. [Expert Opin Pharmacother] Abstract

    Molecular Biomarkers in Idiopathic Pulmonary Fibrosis
    Currently, there are no molecular biomarkers in widespread clinical use for idiopathic pulmonary fibrosis (IPF), and the search for potential markers remains in its infancy. Proposed core mechanisms in the pathogenesis of IPF for which candidate markers have been offered include alveolar epithelial cell dysfunction, immune dysregulation, and fibrogenesis. [Am J Physiol Lung Cell Mol Physiol] Abstract

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

     
    SCIENCE NEWS
    Results of LUX-Lung 8, the Largest Prospective Trial to Compare EGFR TKIs in Patients with Relapsed/Refractory Squamous Cell Carcinoma of the Lung
    In the LUX-Lung 8, global, randomized, Phase III study the progression-free survival and disease control rate were significantly better in patients with relapsed/refractory squamous cell carcinoma of the lung treated with afatinib than in those treated with erlotinib. [Press release from European Society for Medical Oncology (ESMO) discussing research presented at the ESMO 2014 Congress, Madrid] Press Release

    Adjuvant Treatment with MAGE-A3 Cancer Immunotherapeutic in Patients with Resected NSCLC Does Not Increase Disease-Free Survival
    The MAGRIT global trial assessed the efficacy of the recMAGE-A3 + AS15 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small cell lung cancer (NSCLC). In this study, treatment with MAGE-A3 cancer immunotherapeutic did not increase disease-free survival compared to placebo in either the overall population or in patients who did not receive adjuvant chemotherapy. [Press release from European Society for Medical Oncology (ESMO) discussing research presented at the ESMO 2014 Congress, Madrid] Press Release

    Customizing Chemotherapy in Lung Cancer: New Phase II Data Reported in Two Late-Breaking Studies
    Measuring the expression levels of an enzyme involved in DNA synthesis can help predict the response of lung cancers to certain treatments, a Korean study has shown. [Press release from European Society for Medical Oncology (ESMO) discussing research presented at the ESMO 2014 Congress, Madrid] Press Release

    Promising Results Shown with Targeted Approaches in Subsets of Non-Small-Cell Lung Cancer
    The BRAF inhibitor dabrafenib has significant anti-tumor activity in patients with advanced BRAF V600E mutant non-small cell lung cancer whose disease has progressed after chemotherapy, according to Phase II data. [Press release from European Society for Medical Oncology (ESMO) discussing research presented at the ESMO 2014 Congress, Madrid] Press Release

    Targeted Treatments for Subsets of NSCLC Patients with Folate-Receptor-Positive, BRAF V600E-Mutant, and with Tumors Carrying HER2 Somatic Mutations
    Findings from three Phase II studies revealed clinically meaningful improvement across all efficacy endpoints with vintafolide/docetaxel over single-agent docetaxel in second-line treatment of folate-receptor-positive non-small cell lung cancer (NSCLC). [Press release from European Society for Medical Oncology (ESMO) discussing research presented at the ESMO 2014 Congress, Madrid] Press Release

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    INDUSTRY NEWS
    CytRx Initiates Global Phase IIb Clinical Trial of Aldoxorubicin for the Treatment of Relapsed/Refractory Small Cell Lung Cancer
    CytRx Corporation announced the initiation of a global Phase IIb clinical trial evaluating aldoxorubicin compared to topotecan in subjects with extensive-stage small cell lung cancer who have relapsed or were refractory to prior chemotherapy. [CytRx Corporation] Press Release

    CytRx Receives Multiple FDA Orphan Drug Designations for Aldoxorubicin for the Treatment of Glioblastoma, Small Cell Lung Cancer and Ovarian Cancer
    CytRx Corporation announced that the U.S. Food and Drug Administration (FDA) has granted multiple orphan drug designations for the company’s lead drug candidate, aldoxorubicin, in three indications: glioblastoma multiforme, small cell lung cancer and ovarian cancer. [CytRx Corporation] Press Release

    ARIAD’s AP26113 Receives FDA Breakthrough Therapy Designation For ALK+ Non-Small Cell Lung Cancer Resistant to Crizotinib
    ARIAD Pharmaceuticals, Inc. announced that its investigational cancer medicine, AP26113, has received Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer who are resistant to crizotinib. [ARIAD Pharmaceuticals, Inc.] Press Release

     
    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 Translational Cancer Research for Basic Scientists Workshop
    October 26-31, 2014
    Boston, United States

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

     
    JOB OPPORTUNITIES
    NEW PhD Position – Development of a Lung-on-a-Chip (University of Twente)

    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)

    PhD Studentship – Pediatric Respiratory Epidemiology (University of Bern)

    Postdoctoral Fellow – Cardiopulmonary Molecular Biology (Hannover Medical School)

    Postdoctoral Position – Pulmonary Research (University of Chicago)

    Postdoctoral Researcher – Cancer (Ohio State University)

    Postdoctoral Research Trainee – Acute Lung Injury (University of Tennessee Health Science Center)

    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.)

    Research Associate – Cell Separation (STEMCELL Technologies Inc.)


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