Pulmonary Cell News Volume 8.21 | Jun 6 2019

TOP STORY

Autophagy Is Required for Lung Development and Morphogenesis

Researchers investigated the occurrence of autophagy in the developing mouse lung and its regulatory role in airway branching and terminal sacculi formation. They found two windows of epithelial autophagy activation in the developing mouse lung, both resulting from AMPK activation. Inhibition of AMPK-mediated autophagy led to reduced lung branching in vitro. [J Clin Invest] Abstract

(Ranked by impact factor of the journal)

MicroRNA-328 in Exosomes Derived from M2 Macrophages Exerts a Promotive Effect on the Progression of Pulmonary Fibrosis via FAM13A in a Rat Model

In vitro experiments demonstrated that M2 macrophage-derived exosomes overexpressing miR-328 contributed to enhanced pulmonary interstitial fibroblast proliferation and promoted (pulmonary fibrosis) PF. Furthermore, in vivo experiments confirmed the promotive effects of M2 macrophage-derived exosomes overexpressing miR-328 on the progression of PF. [Exp Mol Med] Full Article

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

The authors 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

LUNG CANCER

Acquired Resistance to EGFR Tyrosine Kinase Inhibitors Is Mediated by the Reactivation of STC2/JUN/AXL Signaling in Lung Cancer

The authors investigated a novel strategy to overcome epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance by targeting the stanniocalcin 2 (STC2)-JUN-AXL pathway. They revealed that STC2 was expressed at significantly higher levels in EGFR TKI-resistant cells. [Int J Cancer] Abstract

Activation of Aurora A Kinase Increases YAP Stability via Blockage of Autophagy

Investigators found that Aurora A kinase expression was positively correlated with Yes-associated protein (YAP) in lung cancer. Aurora A depletion suppressed lung cancer cell colony formation, which could be reversed by YAP ectopic overexpression. [Cell Death Dis] Full Article

Knockdown of TRIM65 Inhibits Autophagy and Cisplatin Resistance in A549/DDP Cells by Regulating miR-138-5p/ATG7

Scientists found that tripartite motif (TRIM65) was significantly increased in cisplatin-resistant non-small-cell lung cancer cell line (A549/DDP) as compared to the parental cell line. Knockdown of TRIM65 can enhance cisplatin-induced apoptosis and inhibit autophagy in A549/DDP cells, as indicated by Annexin V/PI staining, caspase3 activity test, and LC3-II immunofluorescence staining. [Cell Death Dis] Full Article

EPHB6 Mutation Induces Cell Adhesion-Mediated Paclitaxel Resistance via EPHA2 and CDH11 Expression

EPHB6 mutation-induced paclitaxel resistance was mediated by an interaction with EPHA2, which promoted c-Jun N-terminal kinase-mediated cadherin 11 (CDH11) expression. Researchers demonstrated that EPHB6-mutated cells acquired cell adhesion-mediated drug resistance in association with CDH11 expression and RhoA/focal adhesion kinase activation. [Exp Mol Med] Full Article

Mechanistic Study of TTF-1 Modulation of Cellular Sensitivity to Cisplatin

Investigators showed that thyroid transcription factor-1 (TTF-1) sensitized the KRAS-mutated A549 and NCI-H460 lung cancer cells to cisplatin, a common chemotherapy used to treat lung cancer. This chemosensitization activity did not appear to be mediated by a TTF-1-imposed alteration on nucleotide excision repair. [Sci Rep] Full Article

Doxycycline Inhibits Electric Field-Induced Migration of Non-Small Cell Lung Cancer (NSCLC) Cells

After direct current electric fields stimulation, NCI-H460 and NCI-H520 cells, which both exhibited epithelial-like morphology, migrated towards the cathode, while MRC-5 cells, which had fibroblast-like morphology, migrated towards the anode. The effect of doxycycline, a common antibiotic, on electrotaxis of MRC-5, NCI-H460 and NCI-H520 cells was examined. [Sci Rep] Full Article

Apoptosis Induction and AKT/NF-κB Inactivation Are Associated with Regroafenib-Inhibited Tumor Progression in Non-Small Cell Lung Cancer In Vitro and In Vivo

CL-1-5-F4 cells were treated with regorafenib, NF-κB or AKT inhibitor for 24 or 48 hours. The authors performed cell viability assay, NF-κB reporter gene assay, transwell invasion assay and apoptosis related flow cytometry assay on cellular level to verify anti-cancer effect and mechanism of regorafenib. [Biomed Pharmacother] Full Article | Graphical Abstract

Identifying Non-Small-Cell Lung Tumors Bearing the T790M EGFR TKI Resistance Mutation Using PET Imaging

Scientists attempted to radiolabel WZ4002 in order to assess the specificity of binding to tumors with the T790M mutation in vivo. [¹⁸F]FEWZ was assessed in vitro to determine efficacy relative to the starting compound and in vivo to measure the biodistribution and specificity of binding to EGFR wild type, L858R and T790M bearing tumors. [J Labelled Comp Radiopharm] Abstract

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Abandoning the Notion of Non-Small Cell Lung Cancer

Lung cancers are classified as small-cell or non-small cell. Such distinction reflects the different clinical presentation, disease course, and therapeutic options of the two subgroups. However, recent advances question the reason for categorizing together heterogeneous NSCLC subtypes such as adenocarcinomas and squamous cell carcinomas. [Trends Mol Med] Abstract

Oligonucleotide Therapy: An Emerging Focus Area for Drug Delivery in Chronic Inflammatory Respiratory Diseases

Review authors focus on various novel dosage forms like nanoparticles, liposomes that can be used efficiently for the delivery of various oligonucleotides such as siRNA and miRNA. They also discuss the future perspectives and targets for oligonucleotides in the management of respiratory diseases. [Chem Biol Interact] Abstract

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

Lung Cancer Research Abstracts

The official listing of submitted abstracts regarding non-small cell lung cancer. [Press releases discussing research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Abstracts One | Abstracts Two

New Data from GEOMETRY Mono-1 Study Show Clinically Meaningful Results in Patients with Non-Small Cell Lung Cancer with MET Exon-14 Skipping Mutation Treated with Capmatinib

Incyte announced primary efficacy results from the Novartis-sponsored GEOMETRY mono-1 Phase II clinical trial of capmatinib, an investigational, selective MET inhibitor. The results demonstrate that capmatinib shows promise as a potential treatment option for patients with locally advanced or metastatic non-small cell lung cancer that harbor a MET exon-14 skipping mutation. [Incyte] Press Release

Cotinga Pharmaceuticals Announces Initiation of Next Cohort of Phase Ib/IIa Combination Trial of COTI-2 in Solid Tumors

Cotinga Pharmaceuticals Inc. announced that the company has initiated the third cohort of its ongoing Phase Ib/IIa clinical trial of COTI-2 plus cisplatin in solid tumors. The objective of the third cohort is to continue to evaluate the safety and tolerability of COTI-2 in combination with standard-of-care cisplatin. [Cotinga Pharmaceuticals Inc. (Globe Newswire, Inc.)] Press Release

Turning Point Therapeutics Announces Updated Interim Clinical Data of Repotrectinib in Advanced ROS1⁺ Non-Small Cell Lung Cancer

Turning Point Therapeutics, Inc. announced updated interim data from its ongoing Phase I/II TRIDENT-1 clinical study of lead drug candidate repotrectinib in ROS1-positive non-small cell lung cancer patients. [Turning Point Therapeutics, Inc.] Press Release

Powerful US Senator Calls for Vetting NIH Grantees at Hearing on Foreign Influences

Research typically enjoys bipartisan support in the US Congress. But when it comes to the increasingly contentious topic of academic espionage by foreign governments, politics is never far from the surface. At a hearing of the Senate Committee on Finance, Chairman Chuck Grassley urged federal agencies to do more to thwart “real, aggressive, and ongoing” attempts by foreign entities to steal the fruits of US-funded research. [ScienceInsider] Editorial

Hungarians Protest against Proposed Government Takeover of Science

Thousands of scientists and their supporters marched through the streets of Budapest on 2 June to protest against a proposed law that would give the Hungarian government direct control of the country’s top research institutes. [Nature News] Editorial

NEW Perspectives in Thoratic Oncology
October 18-19, 2019
New York, New York, United States

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

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

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

NEW Assistant Professor – Lung Disease Research (University of McGill)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Pulmonary and Cardiovascular Diseases (Oslo University Hospital)

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)

Postdoctoral Fellow – Vascular & Lung Biology (Ann & Robert H. Lurie Children’s Hospital of Chicago)

Postdoctoral Researcher – Regenerative Medicine for Lung Conditions (United Therapeutics)

Postdoctoral Researcher – Causes of Allergies and Asthma (Stanford University)

Associate Professor – Oncology (University of California, Davis)

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