Pulmonary Cell News Volume 5.34 | Sep 1 2016

TOP STORY

Lung Epithelial Tip Progenitors Integrate Glucocorticoid and STAT3-Mediated Signals to Control Progeny Fate

The authors developed a novel grafting assay to test if lung epithelial progenitors are intrinsically programmed or if alveolar cell identity is determined by environmental factors. These experiments revealed that embryonic lung epithelial identity is extrinsically determined. [Development] Full Article

(Ranked by impact factor of the journal)

Cystic Fibrosis Gene Modifier SLC26A9 Modulates Airway Response to CFTR-Directed Therapeutics

The genetic modifier SLC26A9 contributes to disease severity in the cystic fibrosis (CF) pancreas and intestine at birth and researchers assessed its relationship with disease severity and therapeutic response in the CF lungs. [Hum Mol Genet] Abstract | Full Article

L-Citrulline Prevents Asymmetric Dimethylarginine-Mediated Reductions in Nitric Oxide and Nitrosative Stress in Primary Human Airway Epithelial Cells

Subjects with asthma and healthy controls underwent bronchoscopy to obtain human bronchial epithelial cells, which were cultured and stimulated with IL-13 and IFNγ to determine the effects of asymmetric dimethylarginine and varying concentrations of L-arginine, on nitric oxide – metabolites, hydrogen peroxide and nitrotyrosine levels. [Clin Exp Allergy] Abstract

Acetylated α-Tubulin Regulated by N-Acetyl-Seryl-Aspartyl-Lysyl-Proline(Ac-SDKP) Exerts the Anti-Fibrotic Effect in Rat Lung Fibrosis Induced by Silica

The authors screened various proteins related to mechanisms of the pathogenesis of silicosis underlying the anti-fibrotic effect of Ac-SDKP using proteomic profile analysis. They also aimed to explore a potential mechanism of acetylated α-tubulin α-Ac-Tub regulation by Ac-SDKP. [Sci Rep] Full Article

Inflammatory Effects Induced by Selected Limonene Oxidation Products: 4-OPA, IPOH, 4-AMCH in Human Bronchial (16HBE14o-) and Alveolar (A549) Epithelial Cell Lines

Researchers evaluated the cytotoxic effects of the selected limonene oxidation products on human bronchial epithelial and alveolar epithelial cell lines by generating concentration-response curves using the neutral red uptake assay and analyzing the inflammatory response with a series of cytokines/chemokines. [Toxicol Lett] Abstract

Non-Typeable Haemophilus influenzae Protects Human Airway Epithelial Cells from a Subsequent Respiratory Syncytial Virus Challenge

The authors examined the impact of non-typeable Haemophilus influenzae (NTHi) exposure on a subsequent respiratory syncytial virus (RSV) infection of human bronchial epithelial cells (16HBE14o-). Co-culture of 16HBE14o- cells with NTHi resulted in inhibition of viral gene expression following RSV infection. [Virology] Abstract

Oxidative Stress Facilitates IFN-γ-Induced Mimic Extracellular Trap Cell Death in A549 Lung Epithelial Cancer Cells

Investigators previously demonstrated that IFN-γ induces an autophagy-regulated mimic extracellular trap cell death (ETosis) in A549 human lung cancer cells. Regarding reactive oxygen species are involved in ETosis, this study investigated the role of oxidative stress. [PLoS One] Full Article

LUNG CANCER

PD-L1 Expression in Basaloid Squamous Cell Lung Carcinoma: Relationship to PD-1⁺ and CD8⁺ Tumor-Infiltrating T Cells and Outcome

PD-1/PD-L1 inhibitors demonstrated durable clinical responses in patients with lung squamous cell carcinoma. However, the expression pattern of PD-L1 and the presence of CD8⁺ and PD-1⁺ tumor-infiltrating T cells in the basaloid variant of squamous cell carcinoma remain unknown. [Mod Pathol] Abstract

Loss of Long Noncoding RNA FOXF1-AS1 Regulates Epithelial-Mesenchymal Transition, Stemness and Metastasis of Non-Small Cell Lung Cancer Cells

To identify novel long noncoding RNAs (lncRNAs) in non-small cell lung cancer (NSCLC), investigators profile NSCLC tumor and matched normal samples using GeneChip^® Human Gene 2.0 ST Array, which provides the most accurate, sensitive, and comprehensive measurement of protein coding and lncRNA transcripts. They identified a panel of key factors dysregulated in lung cancer. [Oncotarget] Full Article

Extracellular ATP a New Player in Cancer Metabolism: NSCLC Cells Internalize ATP In Vitro and In Vivo Using Multiple Endocytic Mechanisms

Using a non-hydrolyzable fluorescent ATP radioactive and regular ATP, coupled with high and low molecular weight dextrans as endocytosis tracers and fluorescence microscopy and ATP assays; cultured human NSCLC A549 and H1299 cells as well as A549 tumor xenografts were found to internalize extracellular ATP at concentrations within the reported intratumoral extracellular ATP concentration range. [Mol Cancer Res] Abstract

Tumor Volume Determines the Feasibility of Cell-Free DNA Sequencing for Mutation Detection in Non-Small Cell Lung Cancer

Scientists evaluated the feasibility of cell-free DNA sequencing for mutation detection in patients with non-small cell lung cancer (NSCLC) at earlier stages. A total of 150 matched tumor and serum samples were collected from NSCLC patients at stages IA-IIIA. [Cancer Sci] Abstract

Autophagy in Pulmonary Diseases

Emerging studies have identified that autophagy plays important roles in the pathogenesis of various lung diseases. In addition, autophagy has been shown to selectively degrade sub-cellular targets including proteins, organelles, and pathogens. The authors highlight the recent advances in the molecular regulation and function of autophagy in lung diseases. [Am J Respir Crit Care Med] Full Article

Incremental Innovation and Progress in Advanced Squamous Cell Lung Cancer: Current Status and Future Impact of Treatment

The reviewers discuss the current therapeutic landscape for patients with squamous cell lung cancer versus non-squamous non-small-cell lung cancer. Current evidence indicates that new targeted treatments, notably monoclonal antibodies such as ramucirumab and necitumumab, and immunotherapies such as nivolumab and pembrolizumab can provide survival prolongation, although the benefits are still relatively modest. [J Thorac Oncol] Abstract

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

XALKORI^® (Crizotinib) Receives Approval in European Union for the Treatment of Patients with ROS1-Positive Advanced Non-Small Cell Lung Cancer

Pfizer Inc. announced that the European Commission has approved XALKORI^® for the treatment of adults with ROS1-positive advanced non-small cell lung cancer (NSCLC). In the European Union, XALKORI is also indicated for treatment of adults with anaplastic lymphoma kinase-positive advanced NSCLC. [Pfizer Inc.] Press Release

ARIAD Completes Rolling Submission of New Drug Application for Brigatinib to the U.S. Food and Drug Administration

ARIAD Pharmaceuticals, Inc. announced it has completed the rolling submission of the New Drug Application for its investigational anaplastic lymphoma kinase (ALK) inhibitor, brigatinib, to the U.S. Food and Drug Administration. ARIAD is seeking U.S. marketing approval of brigatinib for patients with metastatic ALK-positive non-small cell lung cancer who are resistant or intolerant to crizotinib. [ARIAD Pharmaceuticals, Inc.] Press Release

Phase III Study Showed Genentech’s Cancer Immunotherapy TECENTRIQTM (Atezolizumab) Helped People with a Specific Type of Lung Cancer Live Significantly Longer Compared to Chemotherapy

Genentech announced positive results for TECENTRIQ from the Phase III study, OAK. The study met its co-primary endpoints and showed a statistically significant and clinically meaningful improvement in overall survival compared with docetaxel chemotherapy in people with locally advanced or metastatic non-small cell lung cancer whose disease progressed on or after treatment with platinum-based chemotherapy. [Genentech] Press Release

FDA Reaches Agreement with Generics Industry on New GDUFA Commitments

The Food and Drug Administration and the generic drug manufacturing industry —including representatives of generic pharmaceutical manufacturers, active pharmaceutical ingredient manufacturers and contract manufacturing organizations — have reached agreement on a package of program enhancements and resource commitments to reauthorize the Generic Drug User Fee Amendments of 2012 (GDUFA), which are set to expire next year. [Drug Store News] Editorial

NSF Proposes Changes in Use of Costly Rotators for Senior Positions

The National Science Foundation (NSF) believes that having academics spend anywhere from two to four years at the agency before returning to campus helps it identify and fund cutting-edge research. Last year 176 scientists, about 28% of NSF’s scientific workforce, were on such temporary assignments. But NSF’s heavy use of these so-called rotators is unique among government research agencies. And some members of Congress are worried that the government is paying too steep a price for that management strategy. [ScienceInsider] Editorial

NEW European Society for Medical Oncology (ESMO) 2017 Congress
September 8-12, 2017
Madrid, Spain

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

NEW Postdoctoral Fellow – Directed Differentiation of Human Pluripotent Stem Cells into Lung and Airway Epithelial Cells (Columbia University Medical Center)

Tenure-Track Faculty Positions – Inflammation and Inflammatory Lung Diseases (Temple University)

Postdoctoral Research Fellowship – Translational Fibrosis Research (RWTH Aachen University)

Postdoctoral Fellow – Cell and Animal Models of Lung Cancer (University of Kentucky Markey Cancer Center)

Bioinformatician – Genomics of Mesothelioma (Imperial College London)

Research Associate – Development of Mesothelioma (Imperial College London)

MRF Research Associate – Pathogenesis of Cystic Fibrosis Lung Disease (Newcastle University)

Robert Stowell Chair – Experimental Pathology (University of California, Davis)

PhD Studentships – Pulmonary Medicine and Biology (University of Giessen School of Medicine)

Postdoctoral Research Fellow – Complex Lung Diseases (National Jewish Health)

Non-Clinical Lecturer – Reader in Respiratory Science (Imperial College London)

Scientific Director – Oncology (Merck)

Associate Service Fellow – Pulmonary Toxicology and Pharmacology (National Institute for Occupational Safety and Health)

Director Clinical Research – Medical Oncology (Fred Hutchinson Cancer Research Center)

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