Pulmonary Cell News Volume 7.11 | Mar 22 2018

TOP STORY

Aberrant Epithelial Differentiation by Cigarette Smoke Dysregulates Respiratory Host Defense

Expression of pIgR, SLPI, long and short PLUNC was restricted to luminal cells and exposure of differentiating primary bronchial epithelial cells to cigarette smoke resulted in a selective reduction of the expression of these luminal cell-restricted respiratory host defense proteins compared to controls. [Eur Respir J] Abstract

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Pulmonary Surfactant Protein SP-B Promotes Exocytosis of Lamellar Bodies in Alveolar Type II Cells

Scientists report that membrane-associated surfactant protein (SP)-B efficiently induced secretion of pulmonary surfactant by alveolar type II (ATII) cells, at the same level as potent secretagogues such as ATP. The presence in the extracellular medium of lipid-protein complexes containing SP-B activated the P2Y₂ purinergic signaling pathway that ultimately triggers exocytosis of lamellar bodies by ATII cells. [FASEB J] Abstract | Full Article

Influenza A Virus-Induced Autophagy Contributes to Enhancement of Virus Infectivity by SOD1 Downregulation in Alveolar Epithelial Cells

Investigators demonstrated that the autophagy pathway is activated by influenza A virus infection and involved in enhanced reactive oxygen species (ROS) generation in the early phase of infection. Silencing of the microtubule-associated protein 1A/1B-light chain 3 gene in A549 cells supported the critical role of autophagy in the ROS increase. [Biochem Biophys Res Commun] Abstract

CC16 Levels Correlate with Cigarette Smoke Exposure in Bronchial Epithelial Cells and with Lung Function Decline in Smokers

There was a significant association between forced vital capacity decline and serum club cell protein-16 (CC16) levels in smokers. Bronchial epithelial cells showed significant decrease in CC16 expression after exposure to cigarette smoke extract (CSE), followed by a subsequent rise in CC16 expression upon removal of CSE. [BMC Pulm Med] Full Article

LUNG CANCER

HSP90 Inhibition Targets Autophagy and Induces a CASP9-Dependent Resistance Mechanism in NSCLC

Investigators provide evidence that heat shock protein 90 (HSP90) inhibition diminishes the expression of ATG7, thereby impeding the cellular capability of mounting an effective autophagic response in NSCLC cells. [Autophagy] Abstract

miR-16 Regulates the Pro-Tumorigenic Potential of Lung Fibroblasts through the Inhibition of HGF Production in an FGFR-1- and MEK1-Dependent Manner

The authors identified miR-16 as a master regulator of fibroblast secretome and showed that its upregulation reduces HGF secretion by fibroblasts, impairing their capacity to promote cancer cell migration. [J Hematol Oncol] Full Article

Stomatin-Like Protein 2 Regulates Survivin Expression in Non-Small Cell Lung Cancer Cells through β-Catenin Signaling Pathway

Investigators transfected a number of non-small cell lung cancer (NSCLC) cells with an stomatin-like protein-2 (SLP-2) small hairpin RNA-expressing vector and examined its possible effects on cell growth and apoptosis. They found that suppression of SLP-2 expression inhibited cell growth, and that the apoptosis induced by SLP-2 suppression was correlated with decreased survivin protein expression. [Cell Death Dis] Full Article

Downregulation of Lumican Accelerates Lung Cancer Cell Invasion through p120 Catenin

Researchers found lumican functioned as a tubulin-binding protein and the depletion of lumican by transfection with its specific shRNA increased lung cancer cell invasion. Such alterations led to morphological changes and actin cytoskeleton remodeling, including the induction of membrane ruffling or protrusion and stress fiber formation, correlated with the increased activities of Rac and Rho. [Cell Death Dis] Full Article

Tumor-Suppressive Effect of LRIG1, a Negative Regulator of ErbB, in Non-Small Cell Lung Cancer Harboring Mutant EGFR

Scientists confirmed that the expression levels of leucine-rich repeat and immunoglobulin-like domain protein-1 (LRIG1) were much lower in non-small cell lung cancer (NSCLC) than in non-malignant cells or tissues. They also focused on the effect of LRIG1 in NSCLC. Transfection of LRIG1 was associated with a decrease in the expression and phosphorylation levels of epidermal growth factor receptor (EGFR) in the HCC827, HCC4011, and NCI-H1975 cells. [Carcinogenesis] Abstract

Current and Future Therapeutic Approaches for the Treatment of Small Cell Lung Cancer

The authors focus on the current results and the future development of the therapeutic approaches for the treatment of small-cell lung cancer. [Expert Rev Anticancer Ther] Abstract

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Phase III IMpower131 Study Showed Roche’s TECENTRIQ (Atezolizumab) plus Chemotherapy (Carboplatin and Abraxane) Reduced the Risk of Disease Worsening or Death in the Initial Treatment of People with a Type of Advanced Squamous Lung Cancer

Roche announced that the Phase III IMpower131 study met its co-primary endpoint of progression-free survival and demonstrated that the combination of TECENTRIQ plus chemotherapy reduced the risk of disease worsening or death compared with chemotherapy alone in the initial treatment of people with advanced squamous non-small cell lung cancer. [F. Hoffmann-La Roche Ltd] Press Release

AbbVie Announces Results from Phase II Study Evaluating Rovalpituzumab Tesirine (Rova-T) for Third-Line Treatment of Patients with DLL3-Expressing Relapsed/Refractory Small Cell Lung Cancer

AbbVie announced that after consulting with the FDA, it will not seek accelerated approval for Rova-T in third-line relapsed/refractory small cell lung cancer based on magnitude of effect across multiple parameters in this single-arm study. [AbbVie Inc.] Press Release

FDA Grants Fast Track Designation to Nintedanib for the Treatment of Systemic Sclerosis with Associated Interstitial Lung Disease

Boehringer Ingelheim announced that the FDA has granted Fast Track Designation to nintedanib for the treatment of systemic sclerosis with associated interstitial lung disease. [Boehringer Ingelheim International GmbH] Press Release

U.S. Spending Deal Contains Largest Research Spending Increase in a Decade

Lawmakers released a $1.3 trillion spending package that largely rejects deep cuts to research agencies proposed by President Donald Trump and, in many cases, provides substantial increases. [ScienceInsider] Editorial

HIV Researcher Is New Head of US Public-Health Agency

HIV researcher Robert Redfield will lead the Centers for Disease Control and Prevention, Secretary of Health and Human Services Alex Azar announced. [Nature News] Editorial

Expectations Are High for UKRI, the United Kingdom’s New £6 Billion Research Behemoth

Combine U.S. agencies akin to the National Institutes of Health, National Science Foundation, and National Endowment for the Humanities. Toss in some energy and innovation research and fuel it all with the largest boost in R&D spending in recent history. Then put one person in charge. That’s what the United Kingdom has done in a major reorganization of research funding that unites all the research councils that support U.K. science. [ScienceInsider] Editorial

NEW Goodbye Flat Biology: In Vivo Inspired Cancer Biology and Therapy
September 9-12, 2018
Berlin, Germany

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NEW Research Technologist – Pulmonary (STEMCELL Technologies Inc.)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

Senior Research Scientist – Lung Epithelium (AstraZeneca)

Research Scientist – Cell Biologist (MedImmune)

Full Professorship and Director – Lung Biology (Ludwig-Maximilians-Universität München)

Postdoctoral Traveling Fellowship – Lung Cancer (Cancer Research UK)

Doctoral Researcher Positions – Deciphering Therapeutic Targets in Lung Toxicology (Ludwig-Maximilians-Universität München)

Postdoctoral Position – Immune Oncology (H. Lee Moffitt Cancer & Research Institute)

Postdoctoral Scholar – Autoimmune Diseases Affecting the Lung (University of California, San Francisco)

Research Fellow – Ex Vivo Response to PD-1 Blockade (Dana-Farber Cancer Institute)

Assistant Professor – Pulmonary Physiology (University of California, Riverside)

Multiple Positions – Pulmonary (University of Alabama at Birmingham)

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