Volume 2.42 | Oct 24

Pulmonary Cell News 2.42 October 24, 2013
Pulmonary Cell News
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
Systematic Identification of Molecular Subtype-Selective Vulnerabilities in Non-Small-Cell Lung Cancer
Researchers applied parallel screening of chemical and genetic perturbations within a panel of molecularly annotated NSCLC lines to identify intervention opportunities tightly linked to molecular response indicators predictive of target sensitivity. [Cell] Abstract | Graphical Abstract
Model the Human Respiratory Epithelium with PneumaCult™-ALI. Click to View Data.
 
PUBLICATIONS (Ranked by impact factor of the journal)
Alveolar Epithelial Differentiation of Human Induced Pluripotent Stem Cells in a Rotating Bioreactor
Induced pluripotent stem cell-derived type II pneumocytes as well as native isolated human type II pneumocytes were differentiated toward a type I phenotype using a unique air-liquid interface system that relies on a rotating apparatus that mimics in vivo respiratory conditions. [Biomaterials] Abstract

TLR3 and MDA5 Signaling though Not Expression, Is Impaired in Asthmatic Epithelial Cells in Response to Rhinovirus Infection
Researchers assessed the relative importance of pathogen recognition receptors (PRRs) in primary bronchial epithelial cells (pBEC) from healthy controls and asthmatics following rhinovirus infection and determined if deficient innate immune responses in asthmatic pBECs were due to abnormal signaling via these PRRs. [Clin Exp Allergy] Abstract

Methemoglobin Induced Signaling and Chemokine Responses in Human Alveolar Epithelial Cells
Researchers investigated the hypothesis that exposure of human alveolar epithelial cells to hemoglobin and its breakdown products regulates chemokine release via iron and oxidant mediated activation of the transcription factor NF-κB. [Am J Physiol Lung Cell Mol Physiol] Abstract

Moraxella catarrhalis Expresses a Cardiolipin Synthase that Impacts Adherence to Human Epithelial Cells
Scientists discovered that M. catarrhalis expresses a cardiolipin synthase, termed MclS, that is responsible for the synthesis of cardiolipin within the bacterium. M. catarrhalis, which depends on adherence to epithelial cells for colonization of the human host, displays significantly reduced levels of adherence to HEp-2 and A549 cell lines in the mclS mutant strains compared to wild-type bacteria. [J Bacteriol] Abstract

The ER Stress-Mediated Decrease in DDAH1 Expression Is Involved in Formaldehyde-Induced Apoptosis in Lung Epithelial Cells
Scientists assessed the effect of formaldehyde (FA) on dimethylarginine dimethylaminohydrolase (DDAH) expression and endoplasmic reticulum (ER) stress in A549 cells. They also investigated the preventive effect of DDAH overexpression on ER stress and apoptosis in FA-induced cell death. [Food Chem Toxicol] Abstract

Protective Effect of Demethylation Treatment on Cigarette Smoke Extract-Induced Mouse Emphysema Model
Researchers explored the effects of demethylation in a cigarette smoke extract (CSE)-induced mouse emphysema model. CSE significantly induced lung cell apoptosis and decreased lung function and lung mitochondrial cytochrome c oxidase activity, which was mostly restored by 5-aza-2′-deoxycytidine. [J Pharmacol Sci] Abstract | Full Article

LUNG CANCER

LHX6 Acts as a Novel Potential Tumor Suppressor with Epigenetic Inactivation in Lung Cancer
The effects of LIM homeobox domain 6 (LHX6) expression on tumorigenesis were studied in vitro and in vivo. LHX6 was readily expressed in normal lung tissues without methylation, but was downregulated or silenced in lung cancer cell lines and tissues with hypermethylation status. [Cell Death Dis] Full Article

Synergistic Inhibition of Lung Cancer Cell Lines by (-)-Epigallocatechin-3-Gallate in Combination with Clinically-Used Nitrocatechol Inhibitors of Catechol-O-Methyltransferase
Scientists investigated the synergistic effects of entacapone/tolcapone and (-)-epigallocatechin-3-gallate (EGCG) against lung cancer cell lines in culture. EGCG, entacapone, and tolcapone inhibited the growth of H1299 human lung cancer cells and CL-13 murine lung cancer cells as single agents following treatment for 72 hours. [Carcinogenesis] Abstract

Inhibition of ZNF746 Suppresses Invasion and Epithelial to Mesenchymal Transition in H460 Non-Small Cell Lung Cancer Cells
The role of ZNF746 in the invasion and epithelial to mesenchymal transition in H460 non-small cell lung cancer (NSCLC) cells was investigated. Invasion assay showed that inhibition of ZNF746 using siRNA transfection inhibited the invasion of H460 NSCLC cells using a Boyden chamber. [Oncol Rep] Abstract

SGOL1 Variant B Induces Abnormal Mitosis and Resistance to Taxane in Non-Small Cell Lung Cancers
Scientists studied the role of Shugoshin-like 1 (SGOL1) and its splice variants in non-small cell lung cancer (NSCLC) using 82 frozen NSCLC tissue samples. SGOL1-B expression was prevalent in smokers, in cases with a wild-type EGFR status, and in cases with the focal copy number amplification of genes that are known to be important for defining the biological behaviors of NSCLC. [Sci Rep] Full Article

Pluripotent Stem Cell Protein Sox2 Confers Sensitivity to LSD1 Inhibition in Cancer Cells
Investigators showed that the expression of LSD1/KDM1 histone demethylase is significantly elevated in Sox2-expressing lung squamous cell carcinomas (SCCs). LSD1-specific inhibitors selectively impair the growth of Sox2-expressing lung SCCs, but not that of Sox2-negative cells. [Cell Rep]
Abstract | Graphical Abstract

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REVIEWS
DAMPs Activating Innate and Adaptive Immune Responses in COPD
The authors discuss the novel role of damage-associated molecular patterns (DAMPs) in chronic obstructive pulmonary disease (COPD) pathogenesis. Relevant DAMPs are categorized based on their subcellular origin, i.e., cytoplasm, endoplasmic reticulum, nucleus, and mitochondria. Furthermore, their potential role in the pathophysiology of COPD is discussed. [Mucosal Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the pulmonary cell research field.
 
INDUSTRY NEWS
AstraZeneca Initiates Phase III Clinical Trial for Selumetinib in Non-Small Cell Lung Cancer
AstraZeneca announced the first patient randomized in a Phase III clinical trial for selumetinib, an oral, potent, selective MEK inhibitor, being investigated as second-line therapy in patients with advanced or metastatic non-small-cell lung cancer whose tumors are KRAS mutation-positive. [Array BioPharma] Press Release

Nektar and Roswell Park Cancer Institute Announce Initiation of Investigator-Sponsored Trial Evaluating Etirinotecan Pegol (NKTR-102) as a Second-Line Treatment in Patients with Relapsed or Refractory Small Cell Lung Cancer (SCLC)
Nektar Therapeutics and Roswell Park Cancer Institute announced that the first patients have been dosed in a Phase II investigator-sponsored study of etirinotecan pegol in patients with relapsed or refractory Small-Cell Lung Cancer (SCLC). [Nektar Therapeutics] Press Release

Questcor to Commence Phase II Study of Acthar for Acute Respiratory Distress Syndrome
Questcor Pharmaceuticals, Inc. announced that it will commence a Phase II study to explore the efficacy and safety of H.P. Acthar® Gel (repository corticotropin injection) for Acute Respiratory Distress Syndrome. [Questcor Pharmaceuticals, Inc.] Press Release

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POLICY NEWS
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
 
EVENTS
NEW VI International Epithelial-Mesenchymal Transition Meeting
November 13-16, 2013
Alicante, Spain

Visit our events page to see a complete list of events in the pulmonary cell community.
 
JOB OPPORTUNITIES
NEW Research Laboratory Manager – Mechanisms of Inflammation and Remodeling in Murine Models of Allergic Airways Disease (Imperial College London)

Postdoctoral Research Associate – Molecular Mechanisms of Endothelial Permeability, Vascular Inflammation, and Pulmonary Injury (University of Illinois)

Postdoctoral Research Fellow – Emphysema (University College Dublin)

Postdoctoral Research Associate – Airway Innate Defense and Biology (University of North Carolina – Chapel Hill)

Senior Postdoctoral Fellow – Mechanisms of Lung Injuries (University of Texas Health Science Center at Tyler)

Postdoctoral Fellow – Lung Research (Brigham & Women’s Hospital – Harvard Medical School)

Postdoctoral Research Candidate – Chronic Lung Diseases (European Respiratory Society / Marie Curie)

Postdoctoral Research Position – Molecular and Cellular Mechanism of Pulmonary Vascular Inflammation and Dysfunction (University of Oklahoma Health Sciences Center)

Postdoctoral Researcher – Respiratory Diseases Research (Boehringer Ingelheim Pharma GmbH & Co. KG)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)


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