Pulmonary Cell News Volume 8.22 | Jun 13 2019

TOP STORY

YES1 Drives Lung Cancer Growth and Progression and Predicts Sensitivity to Dasatinib

Functional significance was evaluated by in vivo models of non-small cell lung cancer and metastasis and patient-derived xenografts. The efficacy of pharmacological and genetic YES1 abrogation was also evaluated. In vitro functional assays for signaling, survival and invasion were also performed. [Am J Respir Crit Care Med] Abstract

(Ranked by impact factor of the journal)

Electronic Cigarette Vapor with Nicotine Causes Airway Mucociliary Dysfunction Preferentially via TRPA1 Receptors

Mucociliary parameters were measured in human bronchial epithelial cells (HBECs) and in sheep. Systemic nicotine delivery to sheep was quantified using plasma cotinine levels, measured by ELISA. In vitro, exposure to electronic cigarette vapor reduced airway surface liquid hydration and increased mucus viscosity of HBECs in a nicotine-dependent manner. [Am J Respir Crit Care Med] Abstract

A Study of the Endocytosis Mechanism and Transendothelial Activity of Lung-Targeted GALA-Modified Liposomes

Investigators report that liposomes modified with GALA peptide (GALA-LPs) were internalized into endothelial cells (ECs) via a clathrin-mediated pathway. Surprisingly, GALA-LPs had the ability to pass lung ECs and reach other cells through transcytosis. GALA-LPs were taken up by >70% of lung ECs, while they also accumulated in ~30% of type I alveolar epithelium. [J Control Release] Abstract

Transitional Human Alveolar Type II Epithelial Cells Suppress Extracellular Matrix and Growth Factor Gene Expression in Lung Fibroblasts

Scientists developed co-culture systems to define the effects of adult human alveolar epithelial cells on lung fibroblasts. Alveolar type II cells cultured on floating collagen gels reduced the expression of type 1 collagen and alpha smooth muscle actin in fibroblasts. [Am J Physiol Lung Cell Mol Physiol] Abstract

NF-κB-Regulation of miR-155, via SOCS1/STAT3, Is Involved in the PM_2.5-Accelerated Cell Cycle and Proliferation of Human Bronchial Epithelial Cells

Researchers found that different concentrations of particulate matter under 2.5μm in size (PM_2.5) caused a biphasic effect on proliferation of human bronchial epithelial (HBE) cells. PM_2.5 induced an aberrant cell cycle and proliferation of HBE cells, and up-regulated miR-155 levels in a concentration-dependent manner. [Toxicol Appl Pharmacol] Abstract | Graphical Abstract

In Vitro Expansion of Endogenous Human Alveolar Epithelial Type II Cells in Fibroblast-Free Spheroid Culture

Investigators showed that endogenous human alveolar epithelial type II cells (AEC2s) could be cultured and passaged using a three-dimensional culture system with a specific combination of signal ligands and inhibitors. The culture system was suitable for retroviral gene transduction into AEC2s. [Biochem Biophys Res Commun] Abstract

Ursolic Acid Alleviates Airway-Vessel Remodeling and Muscle Consumption in Cigarette Smoke-Induced Emphysema Rats

Emphysema was induced in a rat model with three months of cigarette smoke exposure. Histology and immunohistochemistry stains were used to assess airway-vessel remodeling and muscle atrophy-associated changes. Levels of cleaved-caspase3, 8-OHdG, and S100A4 were measured in airways and associated vessels to evaluate cell apoptosis, oxidant stress, epithelial-to-mesenchymal transition, and endothelial-to-mesenchymal transition-associated factors. [BMC Pulm Med] Full Article

LUNG CANCER

SHOC2 Phosphatase-Dependent RAF Dimerization Mediates Resistance to MEK Inhibition in RAS-Mutant Cancers

Investigators showed that genetic inhibition of SHOC2 suppressed tumorigenic growth in a subset of KRAS-mutant non-small cell lung (NSCLC) cancer cell lines and prominently inhibited tumor development in autochthonous murine KRAS-driven lung cancer models. On the other hand, systemic SHOC2 ablation in adult mice was relatively well tolerated. [Nat Commun] Full Article

Tumor Heterogeneity Underlies Differential Cisplatin Sensitivity in Mouse Models of Small-Cell Lung Cancer

The authors describe small cell lung cancer subtypes in Mycl- and Nfib-driven GEMM that included CDH1-high peripheral primary tumor lesions and CDH1-negative, aggressive intrapulmonary metastases. Cisplatin treatment preferentially eliminated the latter, thus revealing a striking differential response. [Cell Rep] Full Article | Graphical Abstract

STYK1 Promotes Tumor Growth and Metastasis by Reducing SPINT2/HAI-2 Expression in Non-Small Cell Lung Cancer

Serine threonine tyrosine kinase 1 (STYK1) overexpression promoted non-small cell lung cancer cells’ (NSCLCs’) proliferation, migration, and invasion. STYK1 also induced epithelial–mesenchymal transition by E-cadherin downregulation and Snail upregulation. Moreover, RNA-seq, quantitative polymerase chain reaction, and western blot analyses confirmed that STYK1 overexpression significantly decreased the serine peptidase inhibitor Kunitz type 2 level in NSCLC cells. [Cell Death Dis] Full Article

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Staphylococcus aureus Orchestrates Type 2 Airway Diseases

The novel concept of a Staphylococcus aureus-driven chronic airway inflammatory disease suggests a new understanding of disease triggers. The authors review the role of S. aureus in chronic inflammatory airway diseases and discuss possible therapeutic approaches to target S. aureus. [Trends Mol Med] Abstract

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

AnaptysBio Presents Updated Data from Etokimab Phase IIa Proof-of-Concept Clinical Trial in Severe Eosinophilic Asthma

AnaptysBio, Inc. presented updated proof-of-concept data for etokimab, its investigational anti-IL-33 therapeutic antibody, in a single dose Phase IIa clinical trial in adult patients with severe eosinophilic asthma. [Press release from AnaptysBio, Inc. discussing research presented at the 2019 European Academy of Allergy and Clinical Immunology (EAACI) Congress, Lisbon] Press Release

Savara Announces Results of IMPALA, a Phase III Study of Molgradex for the Treatment of Autoimmune Alveolar Pulmonary Proteinosis (aPA)

Savara Inc. announced top line data from IMPALA, a pivotal Phase III clinical study evaluating Molgradex, an inhaled formulation of recombinant human granulocyte-macrophage colony-stimulating factor, for the treatment of aPAP. [Savara Inc.] Press Release

Immutep Completes Recruitment of Initial Cohort in 1^st Line NSCLC Patients for TACTI-002 Trial

Immutep Limited announced that 17 patients have been enrolled into the first cohort of the first line non-small cell lung cancer arm of the Phase II TACTI-002 clinical trial. This completes patient recruitment of the initial cohort of the study Part A. [Immutep Limited] Press Release

Xynomic Completes Pre-IND Meeting with US FDA for XP-102, a Novel Pan-RAF Inhibitor against Colorectal Cancer and Lung Cancer

Xynomic Pharmaceuticals Holdings, Inc. announced that it recently held a pre-IND meeting with the FDA for its pan-PAF inhibitor XP-102 for the treatment of cancers. The FDA addressed Xynomic’ questions related to CMC, nonclinical and clinical protocol, and provided valuable advice on overall clinical development plan to advance this drug candidate. Xynomic is on track to file this Investigational New Drug application in the second half of 2019. [Xynomic Pharmaceuticals Holdings, Inc. (GlobeNewswire, Inc.)] Press Release

OSE Immunotherapeutics Receives US Patent Notice of Allowance for Use Of Tedopi^® to Treat Brain Metastasis

OSE Immunotherapeutics announced that the United States Patent and Trademark Office has issued the notice of allowance for a new patent family related to Tedopi^® for use in the treatment of brain metastasis originating from cancers, including non-small cell lung cancer, in HLA-A2 positive patients. [OSE Immunotherapeutics] Press Release

FDA Finalizes Guidance for Premarket Tobacco Product Applications for Electronic Nicotine Delivery Systems as Part of Commitment to Continuing a Strong Oversight of E-Cigarettes

The US FDA finalized its guidance for manufacturers submitting new tobacco product applications through the premarket tobacco product application pathway for electronic nicotine delivery systems, such as e-cigarettes or “vapes,” and the liquid nicotine and nicotine-containing e-liquids used with such products, as part of the agency’s continued commitment to its oversight of tobacco products. [The US Food and Drug Administration] Editorial

Emory Scientist Was Told to Vacate His Office. He Says Move Is Reprisal for Activism on Asian Ties

A tenured professor of anesthesiology at Emory University in Atlanta says he is being targeted by school administrators because of a letter he and other faculty members sent its president urging her to defend foreign scientists on campus and the value of international collaborations. [ScienceInsider] Editorial

NEW 2^nd Cologne Conference on Lung Cancer
July 26-27, 2019
Cologne, Germany

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

NEW Researcher Position – Translational Cancer Research (University of Tromsø)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Cystic Fibrosis Stem Cell Models (The University of Alabama at Birmingham)

Postdoctoral Researcher – Lung Lineage Development (Hospital for Sick Children)

Assistant Professor – Lung Disease Research (University of McGill)

Senior Scientific Officer – Lung Cancer Liquid Biopsy Biomarker Research (Cancer Research UK Manchester Institute)

Postdoctoral Fellowship – RNA in Lung Sepsis and Inflammation (Boston University)

Postdoctoral Fellowship – Respiratory and Ophthalmic Diseases (Queen’s University Belfast)

Postdoctoral Researcher – Stem Cell Biology of the Lung and Intestines (Stanford School of Medicine)

Associate Professor – Oncology (University of California, Davis)

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