Pulmonary Cell News Volume 5.31 | Aug 11 2016

TOP STORY

Tumor Exosomal RNAs Promote Lung Pre-Metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils

Scientists demonstrated that lung epithelial cells are critical for initiating neutrophil recruitment and lung metastatic niche formation by sensing tumor exosomal RNAs via Toll-like receptor 3 (TLR3). [Cancer Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Loss-of-Function Mutations in the RNA Biogenesis Factor NAF1 Predispose to Pulmonary Fibrosis–Emphysema

The mutant NAF1 lacked a conserved carboxyl-terminal motif, which the authors showed is required for nuclear localization. To understand the disease mechanism, they used CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein-9 nuclease) to generate Naf1^+/− mice and found that they had half the levels of telomerase RNA. [Sci Transl Med] Abstract

Evidence for Chemokine Synergy during Neutrophil Migration in ARDS

The factors that regulate neutrophil infiltration into the inflamed lung and the understanding of the pathomechanisms in acute respiratory distress syndrome (ARDS) remain incomplete. The authors determinined the role of the chemokine ligand (CCL)2 and CCL7 in ARDS. [Thorax] Full Article

Tsr Chemoreceptor Interacts with IL-8 Provoking E. Coli Transmigration Across Human Lung Epithelial Cells

Bacterial colonization of epithelial surfaces and subsequent transmigration across the mucosal barrier are essential for the development of infection. Scientists hypothesized that the methyl-accepting proteins, known as chemoreceptors expressed on Escherichia coli bacterial surface, play an important role in mediating bacterial transmigration. [Sci Rep] Full Article

A Novel Role for β2-Microglobulin: A Precursor of Antibacterial Chemokine in Respiratory Epithelial Cells

Researchers analyzed a panel of cationic molecules secreted in the culture medium of human respiratory epithelial cells upon activation by IL-1β and different pathogen-associated molecular patterns. A 9 kDa fragment derived from β2-microglobulin (B2M) was identified and named shed 9 kDa B2M. [Sci Rep] Full Article

TLR2 Activation Limits Rhinovirus-Stimulated CXCL-10 by Attenuating IRAK-1-Dependent IL-33 Receptor Signaling in Human Bronchial Epithelial Cells.

The authors examined the role of TLR2 and ILR-associated kinase-1 (IRAK-1) in rhinovirus (RV)-induced IFN-β, IFN-λ1, and CXCL-10, which require signaling by viral RNA. In airway epithelial cells, blocking TLR2 enhanced RV-induced expression of IFNs and CXCL-10. [J Immunol] Abstract

Amplification of TGFβ Induced ITGB6 Gene Transcription May Promote Pulmonary Fibrosis

Investigators showed that TGFβ1-induced integrin β6 subunit gene (ITGB6) expression occurs via canonical Smad signaling since dominant negative constructs directed against Smad3 and 4 inhibit ITGB6 transcriptional activity. [PLoS One] Full Article

LUNG CANCER

ZEB1 Drives Epithelial-To-Mesenchymal Transition in Lung Cancer

Scientists modeled malignant transformation in human bronchial epithelial cells and determined that epithelial-to-mesenchymal transition and zinc finger E-box binding homeobox 1 (ZEB1) expression are early, critical events in lung cancer pathogenesis. [J Clin Invest] Full Article

Elevated Hydrostatic Pressure Enhances the Motility and Enlarges the Size of the Lung Cancer Cells through Aquaporin Upregulation Mediated by Caveolin-1 and ERK1/2 Signaling

Using cell-culture devices that simulated increased interstitial fluid pressure conditions by applying hydrostatic pressure (HP) ranging from 0 to 20 mm Hg to the cells, investigators found that the elevated HPs increased the migration speeds, invasiveness, cell volume, filopodial number and aquaporin-1, Snail and vinculin expression levels, as well as phosphorylation of caveolin-1 and extracellular signal–regulated kinase1/2 (ERK1/2), in the lung cancer cells CL1-5 and A549. [Oncogene] Abstract

Migration and Epithelial-To-Mesenchymal Transition of Lung Cancer Can Be Targeted via Translation Initiation Factors eIF4E and eIF4GI

Researchers aimed to expand their understanding of the translation initiation factors significance to non-small cell lung cancer characteristics, particularly epithelial-to-mesenchymal transition and migration, supportive of metastasis. [Lab Invest] Abstract

Minnelide/Triptolide Impairs Mitochondrial Function by Regulating SIRT3 in P53-Dependent Manner in Non-Small Cell Lung Cancer

Minnelide/Triptolide (TL) has recently emerged as a potent anticancer drug in non-small cell lung cancer. However, the precise mechanism of its action remains ambiguous. Researchers elucidated the molecular basis for TL-induced cell death in context to p53 status. [PLoS One] Full Article

Predictors of Chemotherapy Efficacy in Non-Small Cell Lung Cancer : A Challenging Landscape

The authors reviewed preclinical and clinical studies that assessed potential predictive biomarkers of conventional cytotoxic chemotherapy used in non-small cell lung cancer. Biomarker evaluation method, analytical validity and robustness are described and challenged for each biomarker. [Ann Oncol] Abstract | Full Article

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

Oncolytics Biotech^® Inc. Reports Additional Data from Randomized Phase II Study of REOLYSIN^® in Non-Small Cell Lung Cancer

Oncolytics Biotech Inc. announced additional data from IND 211, a randomized, Phase II clinical study of REOLYSIN^® in patients with non-small cell lung cancer. The study enrolled patients with both non-squamous (adenocarcinoma) and squamous cell histology. [Oncolytics Biotech Inc.] Press Release

AstraZeneca Announces Positive Top-Line Data From Two Phase III SYMBICORT Studies

AstraZeneca announced positive top-line results from two international, multicenter studies in adult and pediatric patients with chronic obstructive pulmonary disease and asthma, respectively, that showed SYMBICORT^® Inhalation Aerosol was well tolerated and achieved the primary endpoints in both studies. [AstraZeneca] Press Release

Windtree Receives $2.6 Million SBIR Grant to Support AEROSURF^® Phase IIb Clinical Trial

Windtree Therapeutics, Inc. announced that the company has been awarded a Phase II Small Business Innovation Research Grant valued at up to $2.6 million from the National Heart, Lung, and Blood Institute of the National Institutes of Health to support the AEROSURF^® Phase IIb clinical trial in premature infants 26 to 32 week gestational age receiving nasal continuous positive airway pressure for respiratory distress syndrome. [Windtree Therapeutics, Inc.] Press Release

NIH Sets New Postdoc Stipend Levels

In response to a new rule governing overtime pay in the United States, the National Institutes of Health announced its new, increased postdoc stipend levels, which will go into effect 1 December 2016. [Science Careers] Editorial | Notice

The FDA Is Prohibited from Going Germline

A potentially renewable provision of the Consolidated Appropriation Act of 2016 forestalling the prospect of human germline modification was signed into law on December 18th, 2015. The provision has since been incorporated again into the House and Senate appropriation bills for the fiscal year. [ScienceInsider] Editorial

US Agency Lifts Ban on Funding Human–Animal Hybrids

Researchers in the United States will soon be able to resume creating chimera-based projects. [Nature News] Editorial

US Grants for Zebrafish Studies on the Rise

Zebrafish are the rising stars of model-organism research, an analysis of grants from the US National Institutes of Health shows. [Nature Trend Watch] Editorial | Article 1 | Article 2

NEW IASLC World Conference on Lung Cancer
December 4-7, 2016
Vienna, Austria

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

NEW 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)

Postdoctoral Scientist – Transcriptional Networks in Lung Cancer (Cancer Research UK Manchester Institute)

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

Postdoctoral Position – Respiratory Sciences (Novartis Institute for BioMedical Research)

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

Scientific Director – Global Medical Affairs (Celgene Corporation)

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

Postdoctoral Associate – Pulmonary Genetic Medicine (Weill Cornell Medicine)

Scientific Director – Oncology (Merck)

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

Group Leaders – Cardiovascular or Pulmonary Science (Excellence Cluster Cardiopulmonary System)

Associate Professor – Oxidative Lung Injury (Temple University)

Research Fellow – Pulmonary and Critical Care (Mayo Clinic)

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

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