Pulmonary Cell News Volume 6.30 | Aug 3 2017

TOP STORY

A Braf Kinase-Inactive Mutant Induces Lung Adenocarcinoma

The authors demonstrated that the expression of an endogenous Braf(D631A) kinase-inactive isoform in mice triggers lung adenocarcinoma in vivo, indicating that BRAF-inactivating mutations are initiating events in lung oncogenesis. Inactivating BRAF mutations were also identified in a subset of KRAS-driven human lung tumors. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

cAMP-Dependent Activation of Protein Kinase A Attenuates Respiratory Syncytial Virus-Induced Human Airway Epithelial Barrier Disruption

Researchers investigated effects of increased cyclic adenosine monophosphate (cAMP) level on the disruption of model airway epithelial barrier caused by respiratory syncytial virus (RSV) infection and the molecular mechanisms underlying cAMP actions. Increased cAMP level reduced RSV-induced reorganization of the actin cytoskeleton, including apical accumulation of an essential actin-binding protein, cortactin, and inhibited expression of the RSV F protein. [PLoS One] Full Article

Low Levels of the AhR in Chronic Obstructive Pulmonary Disease (COPD)-Derived Lung Cells Increases COX-2 Protein by Altering mRNA Stability

The authors investigated the expression of cyclooxygenase-2 (COX-2) as well as the expression of miR-146a, a miRNA known to regulate COX-2 levels, in primary lung fibroblasts derived from non-smokers and smokers with and without COPD. Basal expression of COX-2 protein was higher in COPD lung fibroblasts compared to normal or smoker fibroblasts but there was no difference in Cox–2 mRNA. [PLoS One] Full Article

Influenza Virus NS1 Protein Mutations at Position 171 Impact Innate Interferon Responses by Respiratory Epithelial Cells

Investigators made mutations to the NS1 protein based on these sequence differences, and assessed the impact of these changes on host cell interferon responses. They found that viruses with mutations at position 171 replicated efficiently but did not induce expression of interferon genes as effectively as wild-type viruses in A459 lung epithelial cells. [Virus Res] Full Article

Lack of Epithelial PPARγ Causes Cystic Adenomatoid Malformations in Mouse Fetal Lung

Cell culture studies revealed that peroxisome proliferator-activated receptor-γ (PPARγ) could bind to promoter region of Pthlh gene as a repressor in the immortalized mouse lung epithelial cell line MLE-15. Phenotypic changes in MLE-15-shPparg cells, stably transfected with shPparg plasmid, were similar to the Pparg^ΔLuEpC mice model. [Biochem Biophys Res Commun] Abstract

The Role of C/EBPβ Phosphorylation in Modulating Membrane Phospholipids Repairing in LPS-Induced Human Lung/Bronchial Epithelial Cells

Scientists developed an in vitro model of acute lung injury via lipopolysaccharide (LPS) stimulation of a human bronchial epithelial cell line, BEAS-2B, and assessed the mRNA and protein levels of clara cell secretory protein 1 (CCSP1) and phospholipase A2 (PLA2) in the model cells. The results demonstrated LPS induction inhibited the transcription and protein expression of CCSP1, but only the protein level of membrane associated PLA2 was increased. [Gene] Abstract

LUNG CANCER

Spi-B-Mediated Silencing of Claudin-2 Promotes Early Dissemination of Lung Cancer Cells from Primary Tumors

The authors found that a lymphocyte lineage-restricted transcription factor, Spi-B, is frequently expressed in human lung cancer tissues. The Spi-B-expressing cancer cells coexpressed Vimentin but repressed E-cadherin and exhibited invasive behavior. [Cancer Res] Abstract | Full Article

Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma

Scientists demonstrated that short-term treatment with the Chk1 inhibitor AZD7762 reduces metabolism in Kras/p53/Lkb1 tumors, synergizing with the DNA damaging drug gemcitabine to reduce tumor size in these models. [Cancer Res] Abstract | Full Article

An Alternative MicroRNA-Mediated Post-Transcriptional Regulation of GADD45A by p53 in Human Non-Small-Cell Lung Cancer Cells

The authors found that miR-138 specifically targeted AGO2, which affects the stability and maturation of miR-130b. Decreased expression of miR-130b promoted the expression of growth arrest and DNA damage inducible alpha (GADD45A) and resulted in the G2/M phase arrest and proliferation inhibition in human non-small-cell lung cancer cells. [Sci Rep] Full Article

Inhibition of AKT1 Signaling Promotes Invasion and Metastasis of Non-Small Cell Lung Cancer Cells with K-RAS or EGFR Mutations

Researchers found that AKT1 is an important regulator of metastasis and down-regulation of its activity is associated with increased metastatic potential of A549 cells. Inhibition of AKT1 enhanced migration and invasion in KRAS- or EGFR-mutant non-small cell lung cancer cells. [Sci Rep] Full Article

miR-151a Induces Partial EMT by Regulating E-Cadherin in NSCLC Cells

Investigators demonstrated that miR-151a is overexpressed in non-small cell lung cancer (NSCLC) patient specimens, as compared to healthy lung. In addition, miR-151a overexpression promoted proliferation, epithelial-to-mesenchymal transition (EMT) and induced tumor cell migration and invasion of NSCLC cells. [Oncogenesis] Full Article

miR-206/133b Cluster: A Weapon against Lung Cancer?

The authors summarize the role and potential mechanisms of the miR-206/133b cluster in lung cancer. [Mol Ther Nucleic Acids] Full Article

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Tagrisso Significantly Improves Progression-Free Survival in the Phase III FLAURA Trial for Lung Cancer

AstraZeneca announced that the Phase III FLAURA trial showed a statistically-significant and clinically-meaningful progression-free survival benefit with Tagrisso compared to current first-line standard-of-care treatment in previously-untreated patients with locally-advanced or metastatic epidermal growth factor receptor mutation-positive non-small cell lung cancer. [AstraZeneca] Press Release

Aridis Pharmaceuticals Enrolls First Patients in Global Pivotal Clinical Trial of Novel Monoclonal Antibody for Treating Acute Pneumonia

Aridis Pharmaceuticals, Inc. announced that it is actively enrolling patients in a global pivotal study of Aerucin^®, the company’s broadly reactive monoclonal antibody being developed to treat acute pneumonia caused by Gram-negative bacteria Pseudomonas aeruginosa. [Aridis Pharmaceuticals, Inc.] Press Release

FDA Approves KALYDECO^® (Ivacaftor) for More than 600 People Ages Two and Older with Cystic Fibrosis Who Have Certain Residual Function Mutations

Vertex Pharmaceuticals Incorporated announced that the U.S. FDA has approved KALYDECO^® for use in more than 600 people with CF ages two and older who have one of five residual function mutations that result in a splicing defect in the CF transmembrane conductance regulator gene. [Vertex Pharmaceuticals Incorporated] Press Release

FDA Grants Genentech’s Alecensa Priority Review for Initial Treatment of People with ALK-Positive Lung Cancer

Genentech announced that the U.S. FDA has accepted the company’s supplemental New Drug Application and granted Priority Review for Alecensa^® as an initial treatment for people with anaplastic lymphoma kinase (ALK)-positive, locally advanced or metastatic non-small cell lung cancer as detected by an FDA-approved test. [Genentech, Inc.] Press Release

Team Receives $6 Million for Research that Could Lower Drug Prices

Sarah W. Harcum of Clemson University is leading a team that has received $6 million for research that could help lower the cost of several drugs that run into the thousands of dollars per treatment and fight some of the world’s most debilitating ailments. [Clemson University] Press Release

After French Drug Trial Tragedy, European Union Issues New Rules to Protect Study Volunteers

The European Medicines Agency has issued new, stricter rules for studies that test drugs in people for the first time. They aim to better protect participants in such first-in-human studies—often healthy volunteers who receive a financial reward. [ScienceInsider] Editorial

University of Tokyo Probe Says Chromosome Team Doctored Images

After a nearly year-long investigation into anonymous allegations of data and image falsification in numerous papers, a University of Tokyo committee announced it had confirmed that one research group falsified images and graphs in five papers. The panel cleared five other research groups of wrongdoing. [ScienceInsider] Editorial

Why Would a University Pay a Scientist Found Guilty of Misconduct to Leave?

In June 2016, investigators at the University of Georgia in Athens concluded that Azza El-Remessy, a faculty member who studied the impact of diabetes on the eye, had committed misconduct and recommended she be terminated. El-Remessy hired a lawyer to dispute the findings, but the following October she gave up her challenge after the university paid her $100,000—essentially to leave. [ScienceInsider] Editorial

NEW Keystone Symposia: Tumor Metabolism
January 21-25, 2018
Snowbird, Utah, United States

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NEW Postdoctoral Fellow – Pulmonary Research (University of Maryland)

NEW Postdoctoral Position – Cardio/Pulmonary/Mitochondrial Research (University of Pittsburgh)

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)

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