Pulmonary Cell News Volume 6.45 | Nov 16 2017

TOP STORY

Airway Surface Liquid pH Is Not Acidic in Children with Cystic Fibrosis

Scientists showed that airway surface liquid (ASL) pH in children with CF is similar to that of children without CF. Findings were supported by highly controlled direct pH measurements in primary human airway epithelial cell culture models, which also suggests that the potential ASL pH gradient produced by defective apical ion transport was balanced out by paracellular shunting of acid/base. [Nat Commun] Full Article

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F₂-Isoprostanes Can Mediate Bleomycin-Induced Lung Fibrosis

Researchers investigated the potential key role of F₂-isoprostanes as markers and mediators of bleomycin-induced pulmonary fibrosis in rats. [Free Radic Biol Med] Full Article | Graphical Abstract

Upregulation of MicroRNA-4417 and Its Target Genes Contribute to Nickel Chloride-Promoted Lung Epithelial Cell Fibrogenesis and Tumorigenesis

Scientists investigated the miRNA-dependent mechanisms involved in nickel-induced epithelial-mesenchymal transition in lung epithelial cells. [Sci Rep] Full Article

Divergent Roles for Clusterin in Lung Injury and Repair

In vitro and in vivo studies demonstrated that extracellular clusterin promoted epithelial cell apoptosis while intercellular clusterin modulated the expression of the DNA repair proteins, MSH2, MSH6, OGG1 and BRCA1. [Sci Rep] Full Article

LUNG CANCER

RASA1 and NF1 Are Preferentially Co-Mutated and Define a Distinct Genetic Subset of Smoking-Associated Non-Small Cell Lung Carcinomas Sensitive to MEK Inhibition

Large genomic datasets of non-small cell lung cancer (NSCLC) were analyzed to define concurrent mutations and clinical features of RASA1-mutated NSCLCs. Functional studies were performed using immortalized human bronchial epithelial cells and NSCLC lines with Ras-GTPase activating protein truncating mutations in RASA1, NF1, or both. [Clin Cancer Res] Abstract

AC-93253 Iodide, a Novel Src Inhibitor, Suppresses NSCLC Progression by Modulating Multiple Src-Related Signaling Pathways

The authors identified compounds that directly or indirectly modulate Src to suppress lung cancer cell growth and motility and investigated the molecular mechanisms underlying the effects of these compounds. [J Hematol Oncol] Full Article

Hdac7 Promotes Lung Tumorigenesis by Inhibiting Stat3 Activation

Hdac7^+/−/K-Ras mice and HDAC7-depleted human lung cancer cell lines were used as models for studying the function of Hdac7 gene in lung cancer. [Mol Cancer] Full Article

Musashi1 Promotes Non-Small Cell Lung Carcinoma Malignancy and Chemoresistance via Activating the Akt Signaling Pathway

Scientists investigated the role of Musashi1 in non-small cell lung cancer malignancy and chemoresistance. Colony formation, MTT, glucose uptake and lactate production assays were employed to study lung cancer cell malignancy and chemoresistance. [Cell Physiol Biochem] Full Article

YAP-Dependent AXL Overexpression Mediates Resistance to EGFR Inhibitors in NSCLC

Investigators evaluated the role of Yes-associated protein (YAP) in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in lung cancer. [Neoplasia] Full Article

TGFβ Pathway Inhibition in the Treatment of Non-Small Cell Lung Cancer

The authors examine the mechanisms underlying transforming growth factor beta (TGFβ)-mediated drug resistance in non-small cell lung cancer (NSCLC), and consider TGFβ as a combinatorial therapeutic intervention to circumvent or delay the development of NSCLC treatment resistance. [Pharmacol Ther] Abstract

The Potential of Interleukin-37 as an Effective Therapeutic Agent in Asthma

Scientists describe the current evidence regarding the role of interleukin (IL)-37 in the pathophysiology of asthma and evaluate both the potential of IL-37 as a biomarker for airway inflammation and a therapeutic target for the treatment of asthma. [Respir Res] Full Article

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Phase III Trial with Zepsyre^® in Small-Cell Lung Cancer (ATLANTIS) to Continue on the Basis of Positive Recommendation by IDMC

PharmaMar announced that the Independent Data Monitoring Committee (IDMC) has notified the company of its recommendation that the Phase III trial currently under way with Zepsyre^® in combination with doxorubicin in small-cell lung cancer patients should continue without any changes. [PharmaMar] Press Release

Fasenra (Benralizumab) Receives US FDA Approval for Severe Eosinophilic Asthma

AstraZeneca and MedImmune announced that the FDA has approved Fasenra for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. [AstraZeneca plc] Press Release

Theravance Biopharma and Mylan Submit New Drug Application to FDA for Revefenacin (TD-4208) in Adults with Chronic Obstructive Pulmonary Disease

Theravance Biopharma, Inc. and Mylan N.V. announced the submission of a New Drug Application to the FDA for revefenacin, an investigational long-acting muscarinic antagonist as a once-daily, nebulized bronchodilator in development for the treatment of COPD. [Theravance Biopharma, Inc.] Press Release

Trelegy Ellipta Once-Daily Single Inhaler Triple Therapy Gains Marketing Authorization in Europe for the Treatment of COPD

GlaxoSmithKline plc and Innoviva, Inc. announced that the European Commission has granted marketing authorization for Trelegy Ellipta as a maintenance treatment in adult patients with moderate to severe COPD who are not adequately treated by a combination of an inhaled corticosteroid and a long-acting beta2-agonist. [GlaxoSmithKline plc] Press Release

African Scientists Get Their Own Open-Access Publishing Platform

Africa’s academy of science has announced that it will launch an open-access publishing platform — the first of its kind aimed exclusively at scientists on the continent. [Nature News] Editorial

Graduate Students Face Alarming Tax Hike

The last thing that graduate students need is a tax hike. But that is what many would face under a clause in the federal-tax-reform bill passed by the US House of Representatives. It will need to be reconciled with the Senate’s tax-reform bill (which retains many existing student tax benefits), and signed by the president. [Nature News] Editorial

NEW MDI Biological Laboratory: Applications of Organoid Technology
May 27-June 2, 2018
Bar Harbor, Maine, United States

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NEW Senior Scientist – Lung Repair and Regeneration (AstraZeneca)

NEW Postdoctoral Position – Lung Cancer (Helmholtz Centre for Environmental Research)

Postdoctoral Fellow – Disease Mechanism (University of California, San Diego)

Postdoctoral Fellow – Lung Cancer (Moffitt Cancer Center)

Postdoctoral Position – Immunology & Respiratory Diseases (Boehringer Ingelheim)

Faculty Position – Cancer Experimental Therapeutics (University of New Mexico)

PhD Position – Pulmonary Research (Helmholtz Zentrum München)

Postdoctoral Position – Immunology/Molecular Biology (Helmholtz Zentrum München)

Postdoctoral Position – Lung Adenocarcinoma (University of California, San Francisco)

PhD Position – Molecular Pharmacology (University of Groningen)

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