Pulmonary Cell News Volume 6.29 | Jul 27 2017

TOP STORY

Local Lung Hypoxia Determines Epithelial Fate Decisions during Alveolar Regeneration

Researchers showed that local lung hypoxia, through hypoxia-inducible factor, drives Notch signaling and Krt5^pos basal-like cell expansion. Single-cell transcriptional profiling of human alveolar type II cells from fibrotic lungs revealed a hypoxic subpopulation with activated Notch, suppressed surfactant protein C, and transdifferentiation toward a Krt5^pos basal-like state. [Nat Cell Biol] Abstract

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Mitogenic Stimulation Accelerates Influenza-Induced Mortality by Increasing Susceptibility of Alveolar Type II Cells to Infection

Investigators found that mitogenic stimulation with keratinocyte growth factor (KGF) markedly accelerated mortality after infectious challenge with influenza A virus (IAV). Coadministration of KGF with IAV markedly accelerated the spread of viral infection from the airways to alveoli compared with challenge with IAV alone, based on spatial and temporal analyses of viral nucleoprotein staining of lung tissue sections and dissociated lung cells. [Proc Natl Acad Sci USA] Full Article

Zinc Oxide Nanoparticles Harness Autophagy to Induce Cell Death in Lung Epithelial Cells

The authors investigated the regulatory mechanism of autophagy and the link between autophagy and reactive oxygen species in zinc oxide nanoparticles (ZnONPs)-treated lung epithelial cells. They demonstrated that ZnONPs could induce autophagy, and this process could enhance the dissolution of ZnONPs in lysosomes to release zinc ions. [Cell Death Dis] Full Article

Effects on Human Bronchial Epithelial Cells following Low-Dose Chronic Exposure to Nanomaterials: A Six-Month Transformation Study

Scientists hypothesized that long-term exposure of human bronchial epithelial cells with a normal phenotype could be a valuable assay for testing carcinogenicity of nanomaterials. They assessed carcinogenic potential of chronic exposure to low doses of multi-walled carbon nanotubes and TiO₂ materials. [Toxicol In Vitro] Abstract

Irx1 Regulates Dental Outer Enamel Epithelial and Lung Alveolar Type II Epithelial Differentiation

The Iroquois homeobox 1 (Irx1) transcription factor was functionally disrupted using a LacZ insert and LacZ expression demonstrated stage-specific expression during embryogenesis. Irx1^-/- mice showed delayed lung maturation characterized by defective surfactant protein secretion and Irx1 marked a population of SP-C expressing alveolar type II cells. [Dev Biol] Abstract

Temporal Dynamics of Ovine Airway Epithelial Cell Differentiation at an Air-Liquid Interface

Scientists expanded on previous knowledge of differentiated ovine tracheal epithelial cells by analyzing the progression of differentiation over an extensive time course at an air-liquid interface (ALI). They observed a pseudo-stratified epithelium with ciliation and a concurrent increase in cell layer thickness from nine days post-ALI with ciliation approaching a maximum level at day 24. [PLoS One] Full Article

LUNG CANCER

NFATc2 Enhances Tumor-Initiating Phenotypes through the NFATc2/SOX2/ALDH Axis in Lung Adenocarcinoma

The authors showed the calcium pathway transcription factor NFATc2 is a novel regulator of lung tumor initiating cell phenotypes, including tumorspheres, cell motility, tumorigenesis, as well as in vitro and in vivo responses to chemotherapy and targeted therapy. In human lung cancers, high NFATc2 expression predicted poor tumor differentiation, adverse recurrence-free and cancer-specific overall survivals. [eLife] Full Article

Surfactant Protein D Inhibits Activation of Non-Small Cell Lung Cancer-Associated Mutant EGFR and Affects Clinical Outcomes of Patients

Scientists demonstrated that pulmonary surfactant protein D downregulates ligand-independent signaling in cells harboring epidermal growth factor receptor (EGFR) mutations such as tyrosine kinase inhibitor (TKI)-sensitive exon 19 deletion and L858R mutation as well as TKI-resistant T790M mutation, subsequently suppressing cellular growth and motility. [Oncogene] Abstract

Alantolactone Induces Apoptosis, Promotes STAT3 Glutathionylation and Enhances Chemosensitivity of A549 Lung Adenocarcinoma Cells to Doxorubicin via Oxidative Stress

Investigators found that alantolactone (ALT) effectively inhibits proliferation and triggers oxidative stress mediated-apoptosis in A549 lung adenocarcinoma cells by inducing ER stress and mitochondrial dysfunction. This ALT-mediated apoptosis was inhibited by NAC while diamide potentiated it. [Sci Rep] Full Article

MicroRNA-31 Regulates Chemosensitivity in Malignant Pleural Mesothelioma

The authors hypothesized that miR-31 alters chemosensitivity and that miR-31 reconstitution may influence sensitivity to chemotherapeutics in malignant pleural mesothelioma. Reintroduction of miR-31 into miR-31 null NCI-H2452 cells significantly enhanced clonogenic resistance to cisplatin and carboplatin. [Mol Ther Nucleic Acids] Full Article

A Potent Indolylquinoline Alleviates Growth of Human Lung Cancer Cell Tumorspheres

Researchers exploited if 3-((7-ethyl-1H-indol-3-yl)-methyl)-2-methylquinoline (EMMQ) can impede the propagation of tumorspheres stemmed from non-small cell lung cancer cells. EMMQ inhibited proliferation of spheroids in culture. In animal models, administration of the drug attenuated the spheroid tumorigenicity. [Apoptosis] Abstract

Family Matters: How MYC Family Oncogenes Impact Small Cell Lung Cancer

The authors compare the distinct molecular features of the three MYC family members and address the potential implications for targeted therapy of small cell lung cancer. [Cell Cycle] Abstract

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AstraZeneca Reports Initial Results from the Ongoing MYSTIC Trial in Stage IV Lung Cancer

AstraZeneca and MedImmune announced progression-free survival (PFS) results for the Phase III MYSTIC trial, a randomized, open-label, multi-centre, global trial of Imfinzi monotherapy or Imfinzi in combination with tremelimumab versus platinum-based standard-of-care (SoC) chemotherapy in previously-untreated patients with metastatic (Stage IV) first-line non-small cell lung cancer. The combination of Imfinzi and tremelimumab did not meet the primary endpoint of improving PFS compared to SoC in patients whose tumors express PD-L1 on 25% or more of their cancer cells. [AstraZeneca] Press Release

Samumed Receives Orphan Drug Designation from FDA for SM04646 as a Treatment for Idiopathic Pulmonary Fibrosis (IPF)

Samumed announced that the U.S. FDA has granted SM04646, a novel small molecule Wnt pathway inhibitor, an Orphan Drug Designation for IPF. [Samumed, LLC] Press Release

Aradigm Submits New Drug Application (NDA) to FDA for U.S. Marketing Approval of Linhaliq in Non-Cystic Fibrosis Bronchiectasis

Aradigm Corporation announced it has submitted its NDA to the U.S. FDA for Linhaliq^™ for the treatment of non-cystic fibrosis bronchiectasis patients with chronic lung infections with Pseudomonas aeruginosa. [Aradigm Corporation] Press Release

GSK Submits US Regulatory Filing of Arnuity Ellipta in Children with Asthma

GlaxoSmithKline plc (GSK) announced the filing of a supplementary New Drug Application to the US FDA for the use of Arnuity Ellipta as maintenance treatment of asthma as prophylactic therapy in children aged five to eleven years. [GlaxoSmithKline plc.] Press Release

GSK Submits EU Filing for Extended Use of Relvar Ellipta in Patients with Controlled Asthma on an ICS/LABA Combination

GlaxoSmithKline plc (GSK) and Innoviva, Inc. announced a submission to the European Medicines Agency for the extended use of once-daily Relvar Ellipta, an inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) combination, in patients already adequately controlled on an ICS/LABA combination. [GlaxoSmithKline plc.] Press Release

Roche Gains CE Label Expansion for Companion Diagnostic to Identify ALK-Positive Non-Small Cell Lung Cancer Patients

Roche announced that it has obtained a CE mark for the VENTANA anti-ALK rabbit monoclonal primary antibody as a companion diagnostic to identify ALK-positive non-small cell lung cancer patients eligible for treatment with the Novartis drug ZYKADIA. [Roche (PR Newswire Association LLC.)] Press Release

The Bonnie J. Addario Lung Cancer Foundation Honors One of the World’s Leading Lung Cancer Oncologists with the 2017 Addario Lectureship Award

The Bonnie J. Addario Lung Cancer Foundation will honor Frances A. Shepherd, M.D., FRCPC, with the 2017 Addario Lectureship Award for her leadership in improving treatment options and helping people with advanced lung cancer live longer. [The Bonnie J. Addario Lung Cancer Foundation (PR Newswire Association LLC.)] Press Release

First Human Embryos Edited in U.S.

The first known attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon. [MIT Technology Review] Editorial

Ding, Ding, Ding! CRISPR Patent Fight Enters Next Round

The University of California has fired another legal salvo in the prolonged patent battle over CRISPR, the revolutionary gene-editing technology that has spawned a billion dollar industry. [ScienceInsider] Editorial

Budding UK Innovation Agency Gains Cash — and Clout

UK scientists fearful for their research funds ahead of Brexit were cheered when the government announced it would plough an extra £4.7 billion into research and development by 2020–21. But the biggest winner from the largely industry-focused cash may be a government innovation agency that is rapidly gaining clout. [Nature News] Editorial

NEW Lung Cancer Centre of Excellence 2017
December 3-5, 2017
Manchester, United Kingdom

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NEW Faculty Position – Cancer Biology (Cold Spring Harbor Laboratory)

Clinical Research Fellow – Respiratory Medicine (University of Oxford)

Postdoctoral Position – Cell Signaling/Cancer Biology (Rutgers Cancer Institute of New Jersey)

Postdoctoral Fellow – Allergy and Immunology (New York University Medical Center)

Postdoctoral Fellow – Pathogenesis of Lung Diseases (Oklahoma State University)

Postdoctoral Fellow – Lung Microengineering (University of Colorado)

PhD Position – Lung Disease (Helmholtz Zentrum München)

Postdoctoral Associate – Lung Cancer Research (Weill Cornell Medicine)

Research Fellow – Cancer Research (National University of Singapore)

Staff Research Scientist – Lung Injury (St. Michael’s Hospital)

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