Pulmonary Cell News Volume 8.09 | Mar 14 2019

TOP STORY

Small-Molecule Ion Channels Increase Host Defences in Cystic Fibrosis Airway Epithelia

Amphotericin B restored airway surface liquid pH, viscosity, and antibacterial activity in primary cultures of airway epithelia from people with cystic fibrosis caused by different mutations, including ones that do not yield cystic fibrosis transmembrane conductance regulator (CFTR), and increased airway surface liquid pH in CFTR-null pigs in vivo. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Live Imaging of Alveologenesis in Precision-Cut Lung Slices Reveals Dynamic Epithelial Cell Behavior

Researchers showed live alveologenesis, using long-term, time-lapse imaging of precision-cut lung slices. They revealed that during this process, epithelial cells are highly mobile and identified specific cell behaviors that contribute to alveologenesis: cell clustering, hollowing and cell extension. [Nat Commun] Full Article

Streptococcus pneumoniae Cell Wall-Localized Trigger Factor Elicits a Protective Immune Response and Contributes to Bacterial Adhesion to the Host

Recombinant trigger factor (rTF) and an anti-rTF antiserum inhibited bacterial adhesion to human lung derived epithelial cells, indicating that TF contributes to the bacterial adhesion to the host. Moreover, bacteria lacking TF demonstrated reduced adhesion, in vitro, to lung-derived epithelial cells, neural cells and glial cells. [Sci Rep] Full Article

Defining the Activated Fibroblast Population in Lung Fibrosis Using Single Cell Sequencing

Lung cells were isolated on day 11 to capture emerging fibrosis and gene expression was analyzed by three complementary techniques which together generated a 49-gene signature that defined an activated subpopulation of fibroblasts. However, none of the identified genes were specific to the activated cells or to the disease setting, implying that the activated fibroblasts are not uniquely defined but exhibit a similar, yet amplified, gene expression pattern to control cells. [Am J Respir Cell Mol Biol] Abstract

LUNG CANCER

The Aryl Hydrocarbon Receptor Mediates Tobacco-Induced PD-L1 Expression and Is Associated with Response to Immunotherapy

Scientists report that cigarette smoke and the carcinogen benzo(a)pyrene (BaP) induced PD-L1 expression on lung epithelial cells in vitro and in vivo, which was mediated by aryl hydrocarbon receptor (AhR). Anti-PD-L1 antibody or deficiency in AhR significantly suppressed BaP-induced lung cancer. [Nat Commun] Full Article

Drug Library Screen Reveals Benzimidazole Derivatives as Selective Cytotoxic Agents for KRAS-Mutant Lung Cancer

Researchers investigated molecular targets for KRAS-activated lung cancer cells using a drug library. A total of 1,271 small molecules were screened in KRAS-mutant and wild-type lung cancer cell lines. The screening identified the cytotoxic effects of benzimidazole derivatives on KRAS-mutant lung cancer cells. [Cancer Lett] Abstract

Overexpression of HIF-2α-Dependent NEAT1 Promotes the Progression of Non-Small Cell Lung Cancer through miR-101-3p/SOX9/Wnt/β-Catenin Signal Pathway

Quantitative realtime PCR was used to measure NEAT1 expression in non-small cell lung cancer tissues and cells. MTT assay and transwell assay were performed to detect cell proliferation, migration and invasion. Potential target genes were identified via luciferase reporter assay. Protein analysis was performed through western blotting. [Cell Physiol Biochem] Full Article

Network Pharmacology-Based Identification of Pharmacological Mechanism of SQFZ Injection in Combination with Docetaxel on Lung Cancer

In vivo and in vitro experiments were applied to verify the predicted targets from network pharmacology. Researchers established a mouse lung cancer model and injected it with docetaxel and Shenqi Fuzheng (SQFZ) injection. Tumor weight, spleen index, thymus index, immunohistochemical staining and ELISA were conducted to evaluate the effect and underlying mechanisms of docetaxel and SQFZ injection. [Sci Rep] Full Article

MicroRNA-148b Regulates Tumor Growth of Non-Small Cell Lung Cancer through Targeting MAPK/JNK Pathway

The authors found that over-expression of miR148b could significantly inhibit tumor growth, while knocking down miR148b could obviously promote tumor growth. Further experiments showed that miR-148b inhibited tumor cell proliferation. Over-expression of miR148b decreased the G2/M phase population of the cell cycle by preventing non small cell lung cancer cells from entering the mitotic phase and enhanced tumor cell apoptosis. [BMC Cancer] Full Article

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Acute Respiratory Distress Syndrome

The authors assess the current diagnose methods, treatment and mechanisms of acute respiratory distress syndrome. [Nat Rev Dis Primers] Abstract

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STEMCELL Technologies Wins Deloitte Best Managed Companies Award

STEMCELL Technologies announced that the company has been selected as a winner of Canada’s Best Managed Companies program for 2019. Canada’s Best Managed Companies is the country’s leading business awards program, recognizing excellence in the management abilities and practices of Canadian owned and managed companies with revenues over $15 million. [STEMCELL Technologies, Inc.] Press Release

Vertex Receives Approval for Symdeko^® (Tezacaftor/Ivacaftor and Ivacaftor) in Australia, to Treat the Underlying Cause of Cystic Fibrosis in People Aged 12 and Older with Certain CFTR Gene Mutations

Vertex Pharmaceuticals Incorporated announced that the Therapeutic Goods Administration of Australia has granted registration to SYMDEKO^® for the treatment of people with cystic fibrosis aged 12 years and older who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence. [Vertex Pharmaceuticals Incorporated] Press Release

Lilly’s Cyramza^® (Ramucirumab) Phase III Relay Trial Met Primary Endpoint, Significantly Improving Progression-Free Survival in First-Line Treatment of Patients with Metastatic EGFR-Mutated Non-Small Cell Lung Cancer

Eli Lilly and Company announced that its Phase III RELAY study of CYRAMZA^® (ramucirumab) met its primary endpoint of progression-free survival, demonstrating a statistically significant improvement in the time patients lived without their cancer growing or spreading after starting treatment. [Eli Lilly and Company] Press Release

Network Pharmacology-Based Identification of Pharmacological Mechanism of SQFZ Injection in Combination with Docetaxel on Lung Cancer

Merck announced that the European Commission has approved KEYTRUDA, the company’s anti-PD1 therapy, in combination with carboplatin and either paclitaxel or nab-paclitaxel, for the first-line treatment of adults with metastatic squamous non-small cell lung cancer. [Merck Sharp & Dohme Corp] Press Release

Norway Joins List of Countries Canceling Elsevier Contracts

Norway has become latest country to cancel its contracts with Elsevier following a dispute over access to research papers. In a statement published March 12, the Norwegian Directorate for ICT and Joint Services in Higher Education and Research, which represents a consortium of research institutions in the country, rejected Elsevier’s offer to lower some of its costs for Norwegian institutions because it didn’t go far enough to promote free access to published research. [The Scientist] Editorial

In a First, U.S. Private Sector Employs Nearly as Many Ph.D.s as Schools Do

The job market for U.S. science and engineering Ph.D.s is about to pass a long-anticipated milestone. For decades, educational institutions have been the largest employer of Ph.D.s. In 1997, for instance, they eclipsed private sector employment by 11 percentage points, according to the U.S. National Science Foundation’s biennial Survey of Doctorate Recipients. [ScienceInsider] Editorial

NEW Shortening the Duration of Tuberculosis Chemotherapy
July 7-12, 2019
Barcelona, Spain

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NEW Group Leaders – Cardiopulmonary Research (Max Planck Institute for Heart and Lung Research)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

Associate Professor – Primary Ciliary Dyskinesia (University of Southampton)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Lung Disease (Icahn School of Medicine at Mount Sinai)

Principal Investigator Positions – Stem Cell Research (The GDL-MP Institute for Stem Cell and Regenerative Biomedicine)

Assistant/Associate/Full Professor – Lung Cancer (University of Cincinnati College of Medicine)

Postdoctoral Position – Lung Biology & Disease (Helmholtz-Center München – German Research Center for Environmental Health)

PhD Position – Lung Squamous Cell Carcinoma (Cancer Research UK Manchester Institute)

Postdoctoral Position – Respiratory Research (Monell Chemical Senses Center)

Postdoctoral Position – Lung Cancer (Albert Einstein College of Medicine of Yeshiva University)

Associate Professor – Oncology (University of California, Davis)

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