Pulmonary Cell News Volume 6.44 | Nov 9 2017

TOP STORY

Evolution and Clinical Impact of Co-Occurring Genetic Alterations in Advanced-Stage EGFR-Mutant Lung Cancers

Through genomic analysis of 1,122 epidermal growth factor receptor (EGFR)-mutant lung cancer cell-free DNA samples and whole-exome analysis of seven longitudinally collected tumor samples from a patient with EGFR-mutant lung cancer, researchers identified critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers. [Nat Genet] Abstract | Press Release

(Ranked by impact factor of the journal)

Isolation and 3D Expansion of Multipotent Sox9⁺ Mouse Lung Progenitors

The authors showed that mouse Sox9⁺ multipotent embryonic lung progenitors can be isolated and expanded long term in 3D culture. Cultured Sox9⁺ progenitors transcriptionally resembled their in vivo counterparts and generated both airway and alveolar cell types in vitro. [Nat Methods] Abstract

HIF and HOIL-1L–Mediated PKCζ Degradation Stabilizes Plasma Membrane Na,K-ATPase to Protect against Hypoxia-Induced Lung Injury

Scientists report a mechanism of prosurvival adaptation of alveolar epithelial cells to prolonged hypoxia where protein kinase C zeta (PKCζ) degradation allows plasma membrane Na,K-ATPase stabilization at ∼50% of normoxic levels, preventing its excessive down-regulation and cell death. [Proc Natl Acad Sci USA] Abstract

HDAC2 Suppresses IL17A-Mediated Airway Remodeling in Human and Experimental Modeling of COPD

The relationships between histone deacetylase (HDAC) 2, IL17A, and airway remodeling were investigated. The effect of HDAC2 on IL17A-mediated airway remodeling was assessed using in vivo models of COPD induced by cigarette smoke (CS) and in vitro culture of human bronchial epithelial cells and primary human fibroblasts exposed to CS extract, IL17A, or both. [Chest] Abstract

Thalidomide Inhibits TGF-β1-Induced Epithelial to Mesenchymal Transition in Alveolar Epithelial Cells via Smad-Dependent and Smad-Independent Signaling Pathways

Researchers investigated whether thalidomide regulates alveolar epithelial to mesenchymal transition and the possible mechanisms underlying this process. [Sci Rep] Full Article

Mechanisms and Modulation of Microvesicle Uptake in a Model of Alveolar Cell Communication

Investigators concluded that microvesicle internalization occurs via a pathway more consistent with fluid-phase than receptordependent endocytosis, and is subject to bidirectional modulation by relevant pathologic perturbations. [J Biol Chem] Abstract

LUNG CANCER

Stress Hormones Promote EGFR Inhibitor Resistance in NSCLC: Implications for Combinations with β-Blockers

The authors identified a targetable mechanism of epidermal growth factor receptor (EGFR) inhibitor resistance whereby stress hormones activate β₂-adrenergic receptors on non–small cell lung cancer (NSCLC) cells, which cooperatively signal with mutant EGFR, resulting in the inactivation of the tumor suppressor, liver kinase B1, and subsequently induce interleukin-6 expression. [Sci Transl Med] Full Article | Press Release

MLKL-PITPα Signaling-Mediated Necroptosis Contributes to Cisplatin-Triggered Cell Death in Lung Cancer A549 Cells

Investigators showed that cisplatin-treated lung cancer cells undergo a new type of programmed cell death called necroptosis and shed new light on how mixed lineage kinase domain-like protein (MLKL) translocates to the plasma membrane. [Cancer Lett] Abstract

ADAM9 Promotes Lung Cancer Progression through Vascular Remodeling by VEGFA, ANGPT2, and PLAT

Researchers showed that the expression levels of vascular endothelial growth factor A (VEGFA), angiopoietin-2 (ANGPT2), and tissue plasminogen activator (PLAT) were suppressed in ADAM9-silenced cells, which in turn lead to decreases in angiogenesis, vascular remodeling, and tumor growth in vivo. [Sci Rep] Full Article

Cucurbitacin I Inhibits STAT3, but Enhances STAT1 Signaling in Human Cancer Cells In Vitro through Disrupting Actin Filaments

Scientists investigated the function and mechanisms of cucurbitacin I (CuI) in regulating signal transducers and activators of transcription (STAT) signaling in human cancer cells in vitro. CuI dose-dependently inhibited the phosphorylation of STAT3, and enhanced the phosphorylation of STAT1 in lung adenocarcinoma A549 cells possibly through disrupting actin filaments. [Acta Pharmacol Sin] Full Article

Antialarmins for Treatment of Asthma: Future Perspectives

The authors discuss the recent advances in the role of alarmins in asthma and the potential of future targeted therapies in asthma. [Curr Opin Pulm Med] Abstract

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Pique Therapeutics Announces Positive Results in Phase II Clinical Trial of Lead Immunotherapy for Non-Small Cell Lung Cancer

Pique Therapeutics, Inc. announced positive results for PT 107 from its Phase II clinical trial in patients with late-stage, second-line non-small cell lung cancer. [Press release from PR Newswire Association LLC discussing research to be presented at the Society for the Immunotherapy of Cancer’s (SITC) 32^nd Annual Meeting, National Harbor] Press Release

FDA Approves Genentech’s Alecensa (Alectinib) as First-Line Treatment for People with Specific Type of Lung Cancer

Genentech announced that the FDA approved the supplemental New Drug Application for Alecensa^® for the treatment of people with anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer as detected by an FDA-approved test. [Genentech, Inc.] Press Release

Debiopharm International SA Announces Dosing of First Patient in a Combination Trial of Debio 1143 and Avelumab in Patients with Solid Tumors Including Non-Small Cell Lung Cancer (NSCLC)

Debiopharm International SA announced the dosing of the first patient in a Phase Ib study of Debio 1143, an oral, small molecule inhibitor of inhibitors of apoptosis proteins, in combination with avelumab, a human anti-PD-L1 IgG1 monoclonal antibody, in patients with advanced solid tumors including NSCLC. [Debiopharm International SA] Press Release

Lung Cancer Research Foundation Awards $1.6 Million in Research Grants

The Lung Cancer Research Foundation (LCRF) announced the recipients of its 2017 Scientific Grant Program Awards at the 12^th Annual Lung Cancer Awareness Luncheon. LCRF awarded $1.6 million in research grants to ten investigators. [Lung Cancer Research Foundation] Press Release

WHO Calls for Restrictions on Use of Antibiotics in Food Animal Production

The World Health Organization (WHO) is urging countries to restrict the amount of antibiotics given in food animal production by prohibiting their routine use in growth promotion and disease prevention. The recommendation is one of a number the WHO issued aimed at preserving the effectiveness of antibiotics. [STAT News] Editorial

UK Government Appoints Next Chief Scientific Adviser

Patrick Vallance, president of research and development at the pharmaceutical giant GlaxoSmithKline, has been appointed as chief scientific adviser, the UK government announced. [Nature News] Editorial

Indian Scientists Urged to Speak Out about Pseudoscience

A leading Indian science-advocacy group is urging the country’s researchers to speak out against pseudoscience, which it fears has gained a foothold in the past few years, partly through support from some agencies of the Indian government. [Nature News] Editorial

Court Demands that Search Engines and Internet Service Providers Block Sci-Hub

The American Chemical Society (ACS) has won a lawsuit against Sci-Hub, a website providing illicit free access to millions of paywalled scientific papers. ACS had alleged copyright infringement, trademark counterfeiting and trademark infringement; a district court in Virginia ruled that Sci-Hub should pay the ACS $4.8 million in damages after Sci-Hub representatives failed to attend court. [ScienceInsider] Editorial

NEW EMBO-EMBL Symposia: Organoids: Modeling Organ Development and Disease in 3D Culture
September 10-13, 2018
Heidelberg, Germany

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