Pulmonary Cell News Volume 8.16 | May 2 2019

TOP STORY

Nf1 Loss Promotes Kras-Driven Lung Adenocarcinoma and Results in Psat1-Mediated Glutamate Dependence

Researchers evaluated the impact of Nf1 loss on lung adenocarcinomas (LUAD) development using a CRISPR/Cas9 platform in a murine model of Kras-mutant LUAD. They discovered that Nf1 deactivation was associated with focal adhesion kinase 1 hyperactivation and phosphoserine aminotransferase 1 upregulation in mice. Nf1 loss also accelerated murine Kras-driven LUAD tumorigenesis. [EMBO Mol Med] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Urban Airborne Particle Exposure Impairs Human Lung and Blood Mycobacterium tuberculosis Immunity

Cellular toxicity, M. tuberculosis and PM2.5 phagocytosis, cytokine-producing cells, and signalling pathway markers were examined in bronchoalveolar cells and peripheral blood mononuclear cells from healthy, non-smoking, residents of Mexico City. [Thorax] Abstract

Mesenchymal Stem Cells Increase Alveolar Differentiation in Lung Progenitor Organoid Cultures

Investigators added mesenchymal stem cells (MSCs) to lung progenitor 3D cultures. MSC stimulated Epcam⁺ Sca-1⁺ derived organoid formation, increased alveolar differentiation and decreased self-renewal. MSC-conditioned media was sufficient to promote alveolar organoid formation, demonstrating that soluble factors secreted by MSC were likely responsible for the response. [Sci Rep] Full Article

LUNG CANCER

AKR1B10 (Aldo-Keto Reductase Family 1 B10) Promotes Brain Metastasis of Lung Cancer Cells in a Multi-Organ Microfluidic Chip Model

Researchers developed a multi-organ microfluidic chip as a new methodological platform to study brain metastasis (BM). The chip consisted of two bionic organ units – an upstream “lung” and a downstream “brain” characterized by a functional “blood–brain barrier (BBB)” structure, allowing real-time visual monitoring of the entire BM process, from the growth of primary tumor to its breaking through the BBB, and finally reaching the brain parenchyma. [Acta Biomater] Full Article | Graphical Abstract

Activity and Molecular Targets of Pioglitazone via Blockade of Proliferation, Invasiveness and Bioenergetics in Human NSCLC

The authors investigated the anti-tumor effects of pioglitazone in in vitro models of non small cell lung cancer (NSCLC) and also generated ex-vivo three-dimensional cultures from human lung adenocarcinoma as a model to test drug efficacy observed in vitro. The inhibitory effect of pioglitazone on cell proliferation, apoptosis and cell invasion in a panel of human NSCLC cell lines was evaluated by multiple assays. [J Exp Clin Cancer Res] Full Article

Cisplatin Resistant Lung Cancer Cells Promoted M2 Polarization of Tumor-Associated Macrophages via the Src/CD155/MIF Functional Pathway

The authors investigated the tumor-associated microphage-modulating potential of cisplatin-resistant non-small cell lung cancer cell lines, A549R and H460R by using bioinformatics approach, immunoblotting, immunofluorescence staining, migration, invasion, colony, lung sphere formation and xenograft tumorigenecity assays. [J Exp Clin Cancer Res] Full Article | Graphical Abstract

SIRT1 Deacetylated and Stabilized XRCC1 to Promote Chemoresistance in Lung Cancer

SIRT1 was upregulated in chemoresistant lung cancer cells, genetic knockdown or chemical inhibition of SIRT1 reversed chemoresistance by enhancing DNA damage and apoptosis activation, accompanied with XRCC1 degradation. E3 ligase β-TrCP catalyzed the poly-ubiquitination of XRCC1 to promote its proteasome-dependent degradation. SIRT1 bound and deacetylated XRCC1 at lysine K260, K298 and K431, preventing it from β-TrCP-dependent ubiquitination. [Cell Death Dis] Full Article

Effects of β-Adrenergic Antagonists on Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

Scientists investigated the effects of the non-selective beta-blocker propranolol on two human lung adenocarcinoma cell lines treated with radiation or cisplatin. They retrospectively evaluated 77 patients with Stage IIIA non-small cell lung cancer who received induction chemoradiation followed by surgery. Pathological and imaging response, metastatic rate, and survival were analyzed using SPSS v22.0 and PrismGraphpad6. [J Clin Med] Full Article

Identification of a Clinically Relevant Signature for Early Progression in KRAS-Driven Lung Adenocarcinoma

Investigators developed an inducible mouse model of progressive lung adenocarcinoma that combined sporadic activation of oncogenic KRas^G12D with modest overexpression of c-MYC. Histological examination revealed a highly reproducible spontaneous transition from low-grade adenocarcinoma to locally invasive adenocarcinoma within six weeks of oncogene activation. [Cancers] Abstract | Download Full Article

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Role of Oxidative Stress in Neonatal Respiratory Distress Syndrome

The high reactivity of free radical leads to damage to a variety of molecules and may induce respiratory cell death. There is evidence that the oxidative stress involved in the physiopathology of this disease, is particularly related to oxygen supplementation, mechanical ventilation, inflammation/infection and diabetes. The authors summarize what is known regarding the connection between oxidative stress and respiratory distress syndrome. [Free Radic Biol Med] Abstract

Molecular and Morphological Profiling of Lung Cancer: A Foundation for “Next-Generation” Pathologists and Oncologists

Investigators focus on genetic and epigenetic abnormalities in non-small cell carcinoma, neuroendocrine tumor, and carcinoma with rare histological subtypes. In addition, they summarize the therapeutic targeted reagents that are currently available and undergoing clinical trials. [Cancers] Full Article

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

Abeona Therapeutics to Report New Preclinical Data Demonstrating Therapeutic Potential of ABO-401 for Treatment of Cystic Fibrosis

Abeona Therapeutics Inc. will report new preclinical data demonstrating that ABO-401, the company’s novel gene therapy for CF, efficiently delivered a highly-expressed, functional copy of human mini-CFTR to the lung of CF mice and restored CFTR function in human CF patient nasal and bronchial epithelial cells. [Press release from Abeona Therapeutics Inc. discussing research to be presented at the American Society of Gene and Cell Therapy 22^nd Annual Meeting, Washington, DC] Press Release

Sunovion to Present Data on LONHALA^® MAGNAIR^® Inhalation Solution and COPD

Sunovion Pharmaceuticals Inc. will present data from its portfolio of treatments for COPD. Lonhala^® Magnair^® Inhalation Solution was the first nebulized long-acting muscarinic antagonist approved for the treatment of COPD in the United States. [Press release from Sunovion Pharmaceuticals Inc. (Business Wire, Inc.) discussing research to be presented at the American Thoracic Society International Conference 2019, Dallas] Press Release

Verona Pharma to Present Clinical Trial Data of Ensifentrine for COPD Maintenance

Verona Pharma plc announced that it will present data from its COPD clinical trial program with lead product candidate, ensifentrine. The abstract reports post-hoc analyses of the four-week placebo controlled dose-ranging study, with patients sub-grouped by baseline reversibility of lung function measured pre- and post-albuterol administration. [Press release from Verona Pharma plc discussing research to be presented at the American Thoracic Society International Conference 2019, Dallas] Press Release

The Lung Cancer Research Foundation and Pfizer Announce Collaboration in Lung Cancer Research

The Lung Cancer Research Foundation and Pfizer Global Medical Grants announced a collaboration to fund over $1 million in research grants through a Competitive Research Grant Program. [Lung Cancer Research Foundation] Press Release

AstraZeneca Starts Artificial Intelligence Collaboration to Accelerate Drug Discovery

AstraZeneca and BenevolentAI began a long-term collaboration to use artificial intelligence and machine learning for the discovery and development of new treatments for chronic kidney disease and idiopathic pulmonary fibrosis. [AstraZeneca] Press Release

Motif Bio Signs Agreement with Lamellar Biomedical

Motif Bio plc announced that the company has signed an agreement with Lamellar Biomedical Limited under which Motif Bio will conduct an in vivo pre-clinical study evaluating iclaprim in combination with Lamellar’s patented LAMELLASOME™ technology. Iclaprim has been granted US orphan drug designation for Staphylococcus aureus pneumonia in patients with CF. [Motif Bio] Press Release

Phase III CAPTAIN Study of Trelegy Ellipta in Patients with Asthma Meets Primary Endpoint

GlaxoSmithKline plc and Innoviva, Inc. announced headline results from the pivotal Phase III CAPTAIN study of once-daily single inhaler triple therapy Trelegy Ellipta compared to Relvar/Breo Ellipta, in the treatment of patients living with uncontrolled asthma. [GlaxoSmithKline plc] Press Release

L-DOS47 Phase II Randomized Study Advances to Second Cohort

Helix BioPharma Corp. has announced that the Trial Steering Committee (TSC) reviewed safety data from the first dosing cohort of the company’s LDOS003 study. No serious adverse events or dose limiting toxicities were observed. The TSC recommended that Helix begin enrollment of patients into the second dosing cohort. [Helix BioPharma Corp. (GlobeNewswire, Inc.)] Press Release

Checkpoint Therapeutics Announces Positive Interim Clinical Results of Anti-PD-L1 Antibody Cosibelimab

Checkpoint Therapeutics, Inc. announced positive interim results from its ongoing multicenter Phase I clinical trial of cosibelimab. Cosibelimab is a high affinity, fully-human IgG1 monoclonal antibody that directly binds to programmed death ligand-1 and blocks the PD-L1 interaction with the programmed death receptor-1 and B7.1 receptors. [Checkpoint Therapeutics, Inc.] Press Release

FDA Approves KALYDECO^® (Ivacaftor) as First and Only CFTR Modulator to Treat Eligible Infants with CF as Early as Six Months of Age

Vertex Pharmaceuticals Incorporated announced the FDA approved KALYDECO^® for use in children with CF ages six months to less than 12 months who have at least one mutation in their CF transmembrane conductance regulator gene that is responsive to KALYDECO based on clinical and/or in vitro assay data. KALYDECO is already approved in the US, Canada and EU for the treatment of CF in patients ages 12 months and older. [Vertex Pharmaceuticals Incorporated] Press Release

Male Researchers’ ‘Vague’ Language More Likely to Win Grants

Grant reviewers award lower scores to proposals from women than to those from men, even when they don’t know the gender of the applicant, an analysis of thousands of submissions to the Bill and Melinda Gates Foundation has found. That’s because male and female scientists use different types of word on grant applications, according to the study, published by the US National Bureau of Economic Research. [Nature News] Editorial

Analysis: US Science Adviser Has a Vision for Cutting Research Red Tape, but Details Are Scarce

US academic scientists and university officials have long complained about how much time they must spend complying with the many rules relating to the federal dollars they receive. But since President Donald Trump assumed office, most scientists have refocused their angst on the president’s proposed large spending cuts to basic research and his administration’s seeming indifference to combatting climate change. [ScienceInsider] Editorial

NEW International Conference on Allergy and Asthma
July 18-29, 2019
Paris, France

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

NEW Postdoctoral Fellow – Inflammation Suppression & Lung Disease (National University of Singapore)

NEW Postdoctoral Professor – Basal Allergy and Immunology (Aarhus University)

NEW Postdoctoral Fellowship – Redox Systems in Lung and Breast Cancer (The Held Laboratory)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

Postdoctoral Studentship – Lung Adenocarcinoma Research (Max Delbrück Centrum for Molecular Medicine)

Postdoctoral Fellow – Machine Learning in Cancer Treatment (Institute of Cancer Research)

Postdoctoral Fellow – Bioinformatics of Chronic Respiratory Diseases (University of Technology Sydney)

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)

Postdoctoral Position – Pulmonary/Lung Carcinogenesis Translational Research (Albert Einstein College of Medicine)

Postdoctoral Position – Lung Research (Columbia University)

Postdoctoral Scholar – Acute Respiratory Distress Syndrome (University of California, San Francisco)

Associate Professor – Oncology (University of California, Davis)

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