Pulmonary Cell News Volume 5.36 | Sep 15 2016

TOP STORY

Functional Polyesters Enable Selective SiRNA Delivery to Lung Cancer over Matched Normal Cells

Conventional chemotherapeutics nonselectively kill all rapidly dividing cells, which produces numerous side effects. To address this challenge, researchers report the discovery of functional polyesters that are capable of delivering siRNA drugs selectively to lung cancer cells and not to normal lung cells. [Proc Natl Acad Sci USA] Abstract | Press Release

(Ranked by impact factor of the journal)

Airway and Peripheral uPAR Is Elevated in Asthma, and Identifies a Severe, Non-Atopic Subset of Patients

Scientists aimed to comprehensively determine the urokinase plasminogen activator receptor (uPAR) expression profile in asthma and control subjects utilizing bronchial biopsies and serum, and to relate uPAR expression to asthma clinical features. [Allergy] Abstract

Blockade of β-Catenin Signaling Attenuates Toluene Diisocyanate-Induced Experimental Asthma

Investigators evaluated the therapeutic efficacy of two small molecules XAV-939 and ICG-001 in toluene diisocyanate (TDI)-asthmatic male BALB/c mice, which selectively block β-catenin mediated transcription. Their results showed that β-catenin is a principal mediator of TDI-induced asthma, proposing β-catenin as a promising therapeutic target in asthma. [Allergy] Abstract

Omentin Protects Against LPS-Induced ARDS through Suppressing Pulmonary Inflammation and Promoting Endothelial Barrier via an Akt/eNOS-Dependent Mechanism

Investigators found ad-omentin protected against LPS-induced acute respiratory distress syndrome (ARDS) by alleviating the pulmonary inflammatory response and endothelial barrier injury in mice, accompanied by Akt/eNOS pathway activation. Treatment of pulmonary endothelial cells with rh-omentin attenuated inflammatory response and restored adherens junctions, and cytoskeleton organization promoted endothelial barrier after lipopolysaccharide insult. [Cell Death Dis] Full Article

Fungal Aflatoxins Reduce Respiratory Mucosal Ciliary Function

Geven that many respiratory pathogens secrete toxins to impair mucociliary immunity, researchers examined the effects of acute exposure to aflatoxins on airway cell physiology. Using air-liquid interface cultures of primary human sinonasal and bronchial cells, they imaged ciliary beat frequency, intracellular calcium, and nitric oxide. [Sci Rep] Full Article

Ubiquitin Carboxyl-Terminal Hydrolase-L5 Promotes TGFβ-1 Signaling by De-Ubiquitinating and Stabilizing Smad2/Smad3 in Pulmonary Fibrosis

The molecular regulation of Smad2/Smad3 proteins stability remains a mystery. The authors showed that ubiquitin carboxyl-terminal hydrolase-L5 (UCHL5 or UCH37) de-ubiquitinates both Smad2 and Smad3, up-regulates their stability, and promotes TGFβ-1-induced expression of profibrotic proteins, such as fibronectin (FN) and α-smooth muscle actin (α-SMA). Inhibition or down-regulation of UCHL5 reduced Smad2/Smad3 levels and TGFβ-1-induced the expression of FN and α-SMA in human lung fibroblasts. [Sci Rep] Full Article

Development of a Three-Dimensional Bioengineering Technology to Generate Lung Tissue for Personalized Disease Modeling

Investigators present a method for the generation of self-assembled human lung tissue and its potential for disease modeling and drug discovery for lung diseases characterized by progressive and irreversible scarring such as idiopathic pulmonary fibrosis. [Stem Cells Transl Med] Full Article | Press Release

Lentiviral-Mediated Phenotypic Correction of Cystic Fibrosis Pigs

The authors found that functional in vivo CF transmembrane conductance regulator channel activity was restored in the airways of cystic fibrosis pigs using a feline immunodeficiency virus–based lentiviral vector pseudotyped with the GP64 envelope. [JCI Insight] Full Article | Press Release

LUNG CANCER

Acquired Resistance Mechanisms to Combination Met-TKI/EGFR-TKI Exposure in Met-Amplified EGFR-TKI Resistant Lung Adenocarcinoma Harboring an Activating EGFR Mutation

Investigators described the acquisition of dual resistance mechanisms in non-small cell lung cancer harboring an activating epidermal growth factor receptor (EGFR) mutation to Met-TKI and EGFR-tyrosine kinase inhibitor (TKI) following previous EGFR-TKI treatment. [Mol Cancer Ther] Abstract

DRG1 Is a Potential Oncogene in Lung Adenocarcinoma and Promotes Tumor Progression via Spindle Checkpoint Signaling Regulation

Scientists demonstrated that developmentally regulated GTP binding protein 1 (DRG1) is elevated in lung adenocarcinomas while weakly expressed in adjacent lung tissues. [Oncotarget] Full Article

The Extracellular Matrix – the Under-Recognised Element in Lung Disease?

The lung is built of airways and lung parenchyma and the extracellular matrix (ECM) contains the main building blocks of both components. The ECM provides physical support and stability to the lung, and as such it has in the past been regarded as an inert structure. The authors discuss recent research that has provided novel insights revealing that ECM is also a bioactive environment that orchestrates the cellular responses in its environs. [J Pathol] Abstract

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

Personal Genome Diagnostic Reports Positive Data on Utility of Liquid Biopsy Testing in Small Cell Lung Cancer Patients

Personal Genome Diagnostics Inc. announced that data from a collaborative effort with Takeda Pharmaceuticals to assess the feasibility of liquid biopsy genomic testing for cancer drug development will be presented at the 2016 Precision: Lung Cancer World R&D Summit in Boston Massachusetts. [Press release from Personal Genome Diagnostics Inc. discussing research presented at the 2016 Precision: Lung Cancer World R&D Summit, Boston, Massachusetts] Press Release

Cystic Fibrosis Foundation Opens Drug Discovery Lab

The cystic fibrosis foundation is officially opening its own independent laboratory in Lexington, Massachusetts, to speed drug development, funded primarily from the success of the two drugs it previously helped bring to fruition. [Science] Press Release

OGT Expands Cytocell FISH Probe Portfolio for Lung Cancers

Oxford Gene Technology (OGT), has launched two new CE-IVD labelled fluorescence in situ hybridisation (FISH) probes, further expanding its extensive lung cancer portfolio. The Cytocell Aquarius^® ROS1 Plus Breakapart and RET Breakapart probes specifically and accurately detect rearrangements in the genome associated with the most common form of lung cancer — non-small cell lung cancer. [Oxford Gene Technology] Press Release

Orphan Drug Designation Granted to Nintedanib for Treatment of Systemic Sclerosis, Including Associated Interstitial Lung Disease

Boehringer Ingelheim announced that the European Commission and U.S. Food and Drug Administration have granted Orphan Drug Designation to nintedanib for the treatment of systemic sclerosis, including the associated interstitial lung disease. [Boehringer Ingelheim Pharmaceuticals, Inc.] Press Release

Europe Proposes Copyright Reform to Help Scientists Mine Research Papers

The European Commission has announced long-awaited plans to make it easier for researchers to harvest facts and data from research papers — by freeing the computer-aided activity from the shackles of copyright law. [Nature News] Editorial

Illusory Fears Must Not Stifle Chimaera Research

After more than a decade of controversy, the United States is nudging towards approving research on human–animal embryos. The National Institutes of Health closed a month-long public consultation on ‘chimaera research’, and is widely expected to lift a moratorium that forbids federal funding for such work. [Nature News] Editorial

Reproducibility: Respect Your Cells!

Numerous variables can torpedo attempts to replicate cell experiments, from the batch of serum to the shape of growth plates. But there are ways to ensure reliability. [Nature News] Editorial

Outsourcing, Coming Soon to a Lab near You

A move toward outsourcing could offer entrepreneurial opportunities for scientists who have expertise that can be applied to doing experimental work for clients. Traditionally, companies started by scientists have sold products coming out of academic research. Scientific outsourcing firms, on the other hand, would sell the research process itself. [Science Careers] Editorial

NEW American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting
March 3-6, 2017
Atlanta, Georgia, United States

NEW Stem Cells in Drug Discovery
March 6-7, 2017
Cambridge, United Kingdom

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

NEW Postdoctoral Fellow – Regenerative Medicine/Biomedical Science (University of California (UCSF))

Scientist/Senior Scientist – Nanoparticle Research and Drug Delivery (Moderna Therapeutics)

Chair in Medical Biology – Head of the Department of Biology (Masaryk University)

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)

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

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

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

Scientific Director – Oncology (Merck)

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

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