Pulmonary Cell News Volume 8.43 | Nov 7 2019

TOP STORY

Antitumor Activity of an Engineered Decoy Receptor Targeting CLCF1-CNTFR Signaling in Lung Adenocarcinoma

eCNTFR-Fc inhibited tumor growth in multiple xenograft models and in an autochthonous, highly aggressive genetically engineered mouse model of lung adenocarcinoma, driven by activation of oncogenic Kras and loss of Trp53. [Nat Med] Abstract

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Generation of Functional Lungs via Conditional Blastocyst Complementation Using Pluripotent Stem Cells

Researchers report the successful generation of functional lungs in mice through a conditional blastocyst complementation approach that vacates a specific niche in chimeric hosts and allows for initiation of organogenesis by donor mouse pluripotent stem cells. [Nat Med] Abstract

Concomitant Deletion of HRAS and NRAS Leads to Pulmonary Immaturity, Respiratory Failure and Neonatal Death in Mice

The lungs of newborn double knockout mice showed normal organ structure and branching but displayed marked defects of maturation including much-reduced alveolar space with thick separating septa and significant alterations of differentiation of alveolar and bronchiolar cell lineages. [Cell Death Dis] Full Article

LncRNA LOC101927514 Regulates PM_2.5-Driven Inflammation in Human Bronchial Epithelial Cells through Binding p-STAT3 Protein

Researchers set up a cell inflammation model by using normal bronchial 16HBE cells exposed to fine particulate matter (PM_2.5). High-throughput sequencing, as well as real-time fluorescent quantitative PCR detection and validation, was performed on the inflamed cells to evaluate the expression level of long chain noncoding RNA that helped to identify the LncRNA LOC101927514. [Toxicol Lett] Abstract | Graphical Abstract

LUNG CANCER

Identification of DHODH as a Therapeutic Target in Small Cell Lung Cancer

Pharmacological inhibition of dihydroorotate dehydrogenase (DHODH) reduced the viability of small cell lung cancer cells (SCLCs) in vitro and strongly suppressed SCLC tumor growth in human patient-derived xenograft models and in an autochthonous mouse model. [Sci Transl Med] Full Article

Nestin Regulates Cellular Redox Homeostasis in Lung Cancer through the Keap1-Nrf2 Feedback Loop

Scientists identified a feedback loop between Nestin and Nrf2 maintaining the redox homeostasis. Mechanistically, the ESGE motif of Nestin interacted with the Kelch domain of Keap1 and competed with Nrf2 for Keap1 binding, leading to Nrf2 escaping from Keap1-mediated degradation, subsequently promoting antioxidant enzyme generation. [Nat Commun] Full Article

Epigenetic Regulation of Lung Cancer Cell Proliferation and Migration by the Chromatin Remodeling Protein BRG1

Small interfering RNA mediated depletion or pharmaceutical inhibition of BRG1 suppressed proliferation and migration of lung cancer cells. [Oncogenesis] Full Article

Analysis of Tumor Vascularization in a Mouse Model of Metastatic Lung Cancer

Investigators showed that obstructive metastatic foci in lung arterioles decreased the pulmonary vascular network. To generate a mouse model of lung metastasis activation, luciferase-expressing tumor cells were inoculated into the subiliac lymph node (SiLN) of an MXH10/Mo-lpr/lpr mouse, and metastatic tumor cells in the lungs were activated by SiLN resection. [Sci Rep] Full Article

LINC00467 Promotes Cell Proliferation and Stemness in Lung Adenocarcinoma by Sponging miR-4779 and miR-7978

LINC00467 expressed higher in lung adenocarcinoma tissues and cell lines, and increased LINC00467 indicated a poor prognosis. Knockdown of LINC00467 inhibited cell proliferation, the expressions of tumor stem cell-related genes, and cell spheroid formation ability, while it promoted cell apoptosis. [J Cell Biochem] Abstract

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Mitochondria: At the Crossroads of Regulating Lung Epithelial Cell Function in Chronic Obstructive Pulmonary Disease

The authors provide a comprehensive overview of the impact of cigarette smoke on the development of mitochondrial dysfunction in the lung epithelium and highlight the consequences for cell function, innate immune responses, epithelial remodeling and epithelial barrier function in COPD. [Am J Physiol Lung Cell Mol Physiol] Abstract

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Regeneron Provides Updates on Phase III Libtayo^® (Cemiplimab) Development Program in Advanced Non-Small Cell Lung Cancer

Regeneron Pharmaceuticals, Inc. provided an update on the ongoing Phase III development program evaluating Libtayo^®, a PD-1 inhibitor, as monotherapy and combination therapy in first-line patients with advanced non-small cell lung cancer. [Regeneron Pharmaceuticals, Inc.] Press Release

EpicentRx Initiates Dosing in Phase III Trial of Immunotherapy RRx-001 for Third-Line Small Cell Lung Cancer

EpicentRx, Inc. announced that it has dosed the first patient in the Phase III REPLATINUM trial evaluating RRx-001 for the treatment of third-line and beyond small cell lung cancer. [EpicentRx, Inc. (Business Wire, Inc.)] Press Release

BerGenbio’s Bemcentinib Meets Primary Endpoint in First Cohort of Phase II NSCLC Study in Combination with Keytruda^®

BerGenBio ASA announced that the primary endpoint of overall response rate has been met in Cohort A of its Phase II clinical trial evaluating bemcentinib, its first in class selective AXL inhibitor, in combination with the MSD’s, anti-PD-1 therapy KEYTRUDA^®, as a potential new treatment regimen for previously treated advanced non-small cell lung cancer. [BerGenBio ASA] Press Release

Texas Voters Approve Second Life for State Cancer Funding Agency

On 5 November, Texas voters approved (64% to 36%) a ballot measure to extend the life of its pioneering state cancer research funding agency, CPRIT, by doubling, to $6 billion, the amount of bonds that can be issued to support the agency. [ScienceInsider] Editorial

South Korea Clamps Down on Academics Attending ‘Weak’ Conferences

South Korea’s education ministry wants to stop academics from participating in conferences that it considers “weak” and of little academic value. The ministry announced on 17 October that it will require all universities to adopt measures to vet academics’ travel to overseas conferences so as to “prevent researchers from engaging in poor academic activities”. [Nature News] Editorial

NEW Molecular Machines: From Biophysics to Physiology to Disease
July 12-17, 2020
West Dover, Vermont, United States

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NEW Postdoctoral Fellow – Pulmonary Research (Universitätsklinikum Erlangen)

Postdoctoral Fellow – Lung Cancer Epigenomics (Icahn School of Medicine at Mount Sinai)

Postdoctoral Research Fellow – Small Cell Lung Cancer (University Hospital of Cologne)

PhD Studentship – Small Cell Lung Cancer (Cancer Research UK Manchester Institute)

Postdoctoral Research Fellow – Lung Development and Disease (Center for Regenerative Medicine)

Research Fellow – Lung Cancer (Dana-Farber Cancer Institute)

Faculty Position – Pulmonary and Critical Care Medicine (Mayo Clinic Comprehensive Cancer Center)

Research Scientist – Fibrosis (Gilead Sciences, Inc.)

Postdoctoral Positions – Sepsis and Pulmonary Injury (University of Maryland)

Postdoctoral Fellowship – Lung Epithelium (Boston University)

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