Pulmonary Cell News Volume 5.29 | Jul 28 2016

TOP STORY

Why Working the Night Shift Can Pose a Cancer Risk

A handful of large studies of cancer risk factors have found that working the night shift, as nearly 15 percent of Americans do, boosts the chances of developing cancer. Massachusetts Institute of Technology biologists have now found a link that may explain this heightened risk. [Massachusetts Institute of Technology] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Antiinflammatory Effects of Bromodomain and Extraterminal Domain Inhibition in Cystic Fibrosis Lung Inflammation

Researchers showed that, in vitro, bromodomain and extraterminal domain inhibition potently suppressed Th17 cell responses in explanted cystic fibrosis tissue and inhibited IL-17–driven chemokine production in human bronchial epithelial cells. [J Clin Invest] Full Article | Press Release

TP53-Dependent Autophagy Links the ATR-CHEK1 Axis Activation to Proinflammatory VEGFA Production in Human Bronchial Epithelial Cells Exposed to Fine Particulate Matter (PM2.5)

Researchers found that exposing human bronchial epithelial cells to PM2.5 collected in the winter in Wuhan, a city in southern China, induced a significant upregulation of vascular endothelial growth factor A (VEGFA) production, a signaling event that typically functions to control chronic airway inflammation and vascular remodeling. [Autophagy] Abstract

Sarcoidosis Activates Diverse Transcriptional Programs in Bronchoalveolar Lavage Cells

Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. Scientists hypothesized that an unbiased approach to identify pathways activated in bronchoalveolar lavage cells can shed light on the pathogenesis of this complex disease. [Respir Res] Full Article

LUNG CANCER

A Genetic Cell Context-Dependent Role for ZEB1 in Lung Cancer

The zinc-finger E-box-binding Homeobox-1 (ZEB1) is a transcription factor that promotes epithelial–mesenchymal transition and acts as an oncogene in KRAS-mutated lung cancer models. The authors report that ZEB1 exerts the opposite effect in EGFR-mutated lung cancer cells, where it suppresses growth by increasing microRNA-200 targets to antagonize ERBB3, a driver of mutant EGFR-dependent cell growth. [Nat Commun] Full Article

Fatty Acid Oxidation Mediated by Acyl-CoA Synthetase Long Chain 3 Is Required for Mutant KRAS Lung Tumorigenesis

Scientists report that mutant KRAS regulates intracellular fatty acid metabolism through Acyl-coenzyme A (CoA) synthetase long-chain family member 3 (ACSL3), which converts fatty acids into fatty Acyl-CoA esters, the substrates for lipid synthesis and β-oxidation. ACSL3 suppression was associated with depletion of cellular ATP and caused the death of lung cancer cells. [Cell Rep] Full Article | Press Release | Graphical Abstract

A Novel Combinatorial Strategy using Seliciclib^® and Belinostat^® for Eradication of Non-Small Cell Lung Cancer via Apoptosis Induction and BID Activation

With conventional anticancer agents for non-small cell lung cancer reaching therapeutic ceiling, the novel combination using histone deacetylase inhibitor, PXD101 (Belinostat^®) and CDK inhibitor, CYC202 (Seliciclib^®) was investigated as alternative anticancer strategy. [Cancer Lett] Abstract

Autocrine Activity of BDNF Induced by the STAT3 Signaling Pathway Causes Prolonged TrkB Activation and Promotes Human Non-Small-Cell Lung Cancer Proliferation

The authors report the significant expression of brain-derived neurotrophic factor (BDNF) in non-small-cell lung cancer samples and showed that BDNF stimulation increases the synthesis of BDNF itself through activation of STAT3 in lung cancer cells. The release of BDNF can in turn activate tropomyosin related kinase B (TrkB) signaling. [Sci Rep] Full Article

Loss of Asparagine Synthetase Suppresses the Growth of Human Lung Cancer Cells by Arresting Cell Cycle at G0/G1 Phase

It was found that knockdown of human asparagine synthetase (ASNS) inhibited the growth and colony formation abilities of A549 and 95D cells. Flow cytometry showed that ASNS silencing arrested cell cycle progression at G0/G1 phase in A549 cells, probably through regulating the expression of cell cycle molecules such as CDK2 and Cyclin E1 as shown by quantitative real-time PCR. [Cancer Gene Ther] Abstract

Prostaglandin D2 Receptor Antagonists in Early Development as Potential Therapeutic Options for Asthma

The authors present an overview of the pathogenetic molecular mechanisms sustaining the chronic inflammatory response in asthma; the focus is then directed on the mediators of the prostaglandin D2 pathway, the chemoattractant receptor-homologous molecule expressed on TH2 cells, and the latest antagonists developed. [Expert Opin Investig Drugs] Abstract

α1-Antitrypsin Deficiency

α1-Antitrypsin deficiency is an inherited disorder caused by mutations in SERPINA1, leading to liver and lung disease. It is not a rare disorder but frequently goes underdiagnosed or misdiagnosed as asthma, chronic obstructive pulmonary disease or cryptogenic liver disease. [Nature Reviews Disease Primers] Full Article

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

First Study Initiated to Evaluate the Effect of Ofev^® Treatment on Biomarkers that May Predict IPF Progression

Boehringer Ingelheim Pharmaceuticals, Inc. announced the initiation of a new clinical study, INMARK™, investigating the effect of Ofev^® (nintedanib) on specific blood biomarkers that may identify greater scarring and loss of lung function in patients with idiopathic pulmonary fibrosis (IPF). [Boehringer Ingelheim Pharmaceuticals, Inc.] Press Release

National Jewish Health Awarded $11.5 Million in Department of Defense Grants

Researchers at National Jewish Health will seek to understand why warfighters deployed to Southwest Asia suffer increased rates of respiratory disease and test potential treatments thanks to $11.5 million in grants from the U.S. Department of Defense. [National Jewish Health] Press Release

Halozyme Resumes Patient Enrollment and Dosing in PEGPH20 Clinical Trial with KEYTRUDA

Halozyme Therapeutics, Inc. announced that it has resumed the enrollment and dosing of patients in its ongoing Phase Ib trial evaluating its investigational new drug, PEGPH20, in combination with KEYTRUDA (pembrolizumab) in patients with advanced non-small cell lung and gastric cancers under a revised clinical protocol. [Halozyme Therapeutics, Inc.] Press Release

UA Health Sciences Study of Devastating Lung Disorders in the Critically Ill Receives $11.4 Million Boost

Cutting-edge research investigating the genetic basis for devastating disorders in the critically ill – acute respiratory distress syndrome and ventilator-induced lung injury – will receive a major boost thanks to an $11.4 million, five-year program project grant. [University of Arizona Health Sciences] Press Release

Major Review Calls Time on Gaming in UK Research Assessment

The UK’s mammoth periodic audit of its research is set for a shake-up that could change the way universities hire academics – and might also encourage scientists to spend more time on public engagement. [Nature News] Editorial

More Support for Clinical Trials in Children

A cancer diagnosis is a shock, but adults with the disease can take some comfort in the numerous treatments available to them — both through clinical trials and as drugs that are already on the market. Children cannot. [Nature] Editorial

Trump vs Clinton: Worlds Apart on Science

Presidential candidates begin to make clear their stark differences on climate change, energy production and stem-cell research. [Nature News] Editorial

Europe Overhauls Rules for ‘First-In-Human’ Trials in Wake of French Disaster

The European Union is beefing up protections for volunteers in Phase I clinical trials in the wake of a disastrous clinical study in Rennes, France, that resulted in the death of one volunteer and the hospitalization of five others. The European Medicines Agency (EMA) in London announced in a “concept paper” that it wants to improve strategies to identify and reduce risks in “first-in-human” studies on healthy volunteers. EMA is asking for input from stakeholders. [ScienceInsider] Editorial | Article

Chinese Scientists to Pioneer First Human CRISPR Trial

Chinese scientists are on the verge of being first in the world to inject people with cells modified using the CRISPR–Cas9 gene-editing technique. A team led by Lu You, an oncologist at Sichuan University’s West China Hospital in Chengdu, plans to start testing such cells in people with lung cancer next month. [Nature News] Editorial

Scientific Literature: Information Overload

Recent bibliometrics show that the number of published scientific papers has climbed by 8–9% each year over the past several decades. In the biomedical field alone, more than 1 million papers pour into the PubMed database each year — about two papers per minute. [Nature Careers] Editorial

Science Advice for Europe

Exactly one month after Britain’s momentous decision to leave the European Union, around 4500 scientists and friends of science will assemble in Manchester, UK, for the opening of the EuroScience Open Forum, Europe’s largest interdisciplinary research conference. [Science] Editorial

NEW European Society for Medical Oncology (ESMO) Asia 2016 Congress
December 16-19, 2016
Singapore, Singapore

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

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

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

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

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

NEW 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)

PhD Program – Pulmonary Hypertension and Cor Pulmonale (Giessen Graduate Centre for the Life Sciences)

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)

Postdoctoral Fellow – Vascular/Lung Biology (Yale University School of Medicine)

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

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