Pulmonary Cell News Volume 7.30 | Aug 2 2018

TOP STORY

Researchers Discover New Type of Lung Cell, Critical Insights for Cystic Fibrosis

A comprehensive single-cell analysis of airway cells in mice, validated in human tissue, reveals molecular details critical to understanding lung disease. [Press release from the Broad Institute discussing online prepublication in Nature] Press Release | Press Release 2 | Abstract | Editorial

(Ranked by impact factor of the journal)

A Single-Cell Atlas of the Airway Epithelium Reveals the CFTR-Rich Pulmonary Ionocyte

Scientists identified a novel, rare cell type that they called the ‘pulmonary ionocyte’, which co-expressed FOXI1, multiple subunits of the vacuolar-type H⁺-ATPase and CFTR, the gene that is mutated in cystic fibrosis. [Nature] Abstract | Press Release | Editorial 1 | Editorial 2

Production and Transplantation of Bioengineered Lung into a Large-Animal Model

To advance the understanding of vascularization after bioengineered organ transplantation, investigators produced and transplanted a bioengineered lung without the creation of a pulmonary artery anastomosis in a porcine model. [Sci Transl Med] Abstract | Press Release

Airway Epithelial Cell Peroxisome Proliferator-Activated Receptor γ Regulates Inflammation and Mucin Expression in Allergic Airway Disease

The authors found that peroxisome proliferator-activated receptor γ (PPARγ) directly bound to a PPAR response element found in MUC5AC and repressed gene expression. PPARγ regulated mucin and inflammatory factors in primary human bronchial epithelial cells. [J Immunol] Abstract

A Novel Compound, “FA-1” Isolated from Prunus mume, Protects Human Bronchial Epithelial Cells and Keratinocytes from Cigarette Smoke Extract-Induced Damage

Scientists found that concentrated Japanese apricot extract protects against cigarette smoke extract-induced cytotoxicity and DNA damage accompanied by increased levels of aldehyde dehydrogenase 2, 3A1, and Werner’s syndrome protein in immortalized human bronchial epithelial cells and normal human epidermal keratinocytes. [Sci Rep] Full Article

Characterization, Localization and Comparison of c-Kit⁺ Lung Cells in Never Smokers and Smokers With and Without COPD

Researchers characterized and compared c-Kit⁺ cells in lung tissue of 12 never smokers, 15 smokers with normal spirometry and 44 chronic obstructive pulmonary disease (COPD) patients who required lung resectional surgery. Flow cytometry was used to characterize c-Kit⁺ cells in fresh lung tissue disaggregates, and immunofluorescence for further characterization and to determine their location in OCT- embedded lung tissue. [BMC Pulm Med] Full Article

LUNG CANCER

Auranofin Enhances Ibrutinib’s Anticancer Activity in EGFR-Mutant Lung Adenocarcinoma

While low concentrations of auranofin alone demonstrated mild anticancer activities, its presence dramatically enhanced ibrutinib’s activity in H1975, PC9 and H1650 cells, but had only mild effect on Calu3 and H460 cells, demonstrating that ibrutinib’s anti-EGFR activity is enhanced when it is combined with auranofin. [Mol Cancer Ther] Abstract

Synergistic Anticancer Activity of Combined Use of Caffeic Acid with Paclitaxel Enhances Apoptosis of Non-Small-Cell Lung Cancer H1299 Cells In Vivo and In Vitro

Combination treatment with low-dose caffeic acid (CA) and paclitaxel decreased the proliferation of non-small-cell lung cancer H1299 cells but not normal Beas-2b cells. The authors showed that H1299 cells were arrested in the sub-G1 phase and apoptosis was significantly increased in H1299 cells after CA treatment. [Cell Physiol Biochem] Abstract | Full Article

Dichloroacetic Acid (DCA) Synergizes with the SIRT2 Inhibitor Sirtinol and AGK2 to Enhance Anti-Tumor Efficacy in Non-Small Cell Lung Cancer

Researchers investigated the antitumor activity of sodium DCA in combination with SIRT2 inhibitor Sirtinol and AGK2. They found that combining DCA with Sirtinol produced a synergistic therapeutic benefit in A549 and H1299 NSCLC cells in vitro and in a mouse A549 xenograft model. [Cancer Biol Ther] Abstract

miR-145 and miR-497 Suppress TGF-β-Induced Epithelial-Mesenchymal Transition of Non-Small Cell Lung Cancer by Targeting MTDH

Scientists showed that miR-145 and miR-497 were downregulated in non-small cell lung cancer cell lines. Overexpression of miR-145 and miR-497 inhibited TGF-β-induced epithelial-mesenchymal transition and suppressed cancer cell migration and invasion, while the opposite results were observed in cells transfected with miR-145 or miR-497 inhibitor. [Cancer Cell Int] Full Article

In Vivo and In Vitro Effects of Hyperplasia Suppressor Gene on the Proliferation and Apoptosis of Lung Adenocarcinoma A549 Cells

Silenced hyperplasia suppressor gene (HSG) showed decreased mRNA and protein expressions of HSG, and elevated A549 cell survival rates at the time point of 24, 48 and 72 h. The ratio of cells at G0/G1 phase and apoptosis rate decreased and the ratio of cells at S and G2/M phase increased following the silence of HSG. [Biosci Rep] Abstract | Full Article

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Lung Cancers: Molecular Characterization, Clonal Heterogeneity and Evolution, and Cancer Stem Cells

Developments in the characterization of lung cancer molecular abnormalities provided a strong rationale for new therapeutic options and for understanding the mechanisms of drug resistance. [Cancers] Full Article

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European Medicines Agency Adopts Positive Opinion for KEYTRUDA^® (Pembrolizumab) Combination with Pemetrexed and Platinum Chemotherapy for the First-Line Treatment of Metastatic Nonsquamous Non-Small Cell Lung Cancer

Merck announced that the Committee for Medicinal Products for Human Use of the European Medicines Agency has adopted a positive opinion recommending approval of KEYTRUDA^®, Merck’s anti-PD-1 therapy, in combination with pemetrexed and platinum chemotherapy for the first-line treatment of metastatic nonsquamous non-small cell lung cancer in adults whose tumors have no EGFR or ALK genomic tumor aberrations, regardless of PD-L1 expression. [Merck & Co., Inc.] Press Release

Advaxis Announces FDA Allowance of IND Application for ADXS-HOT Drug Candidate for Non-Small Cell Lung Cancer

Advaxis, Inc. announced that the FDA has allowed the company’s IND application for its ADXS-HOT drug candidate for non-small cell lung cancer (NSCLC). Advaxis anticipates that because of this timely allowance, the first patient in the Phase I/II trial for this NSCLC drug candidate will be dosed by the end of 2018. [Advaxis, Inc.] Press Release

Immutep’s LAG-3 Immunostimulant Product Candidate, Efti, Receives IND Approval from U.S. FDA

Immutep Limited is pleased to announce the approval of its Investigational New Drug (IND) application by the FDA for eftilagimod alpha (efti), a LAG-3Ig fusion protein. [Immutep Limited] Press Release

Brexit Preparedness: EMA to Further Temporarily Scale Back and Suspend Activities

The European Medicines Agency (EMA) will launch the next phase of its business continuity plan on 1 October 2018 at the latest. This will allow the Agency to safeguard core activities related to the evaluation and supervision of medicines, while it has to intensify its preparations for the physical move to Amsterdam in March 2019 and cope with significant staff loss. [European Medicines Agency] Press Release

March of Dimes Abruptly Scales Back Research Funding

March of Dimes, the 80-year-old nonprofit organization that has funded pioneering studies on premature birth, infant mortality, and birth defects, is abruptly scaling back its investment in research amid financial struggles—catching scientists by surprise. [ScienceInsider] Editorial

Series of Ethical Stumbles Tests NIH’s Reliance on Private Sector for Research Funding

NIH officials told STAT the agency is completing a plan to ensure better ethical compliance and better delineate the actual process for private-sector collaboration. The officials said the plan will be presented to an advisory committee in December. [STAT News] Editorial

NEW 8^th InterAmerican Oncology Conference
October 17-18, 2019
Buenos Aires, Argentina

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NEW Postdoctoral Research Fellow – Respiratory Epithelial Cell Biology (STEMCELL Technologies Inc.)

NEW Research Associate – Cystic Fibrosis (Imperial College London)

NEW Cancer Research Scholar – Lung Cancer (University of California)

Postdoctoral Fellow – BCL-2 & Pathogenesis & Targeted Therapy of Lung Cancer (Memorial Sloan Kettering Cancer Center)

Postdoctoral Fellow – Non-Small Cell Lung Cancer (The University of Texas MD Anderson Cancer Center)

Postdoctoral Fellow – Lung and Vascular Diseases (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Cellular Therapeutics in Chronic Lung Disease (Helmholtz Zentrum München)

Postdoctoral Associate – Chemotherapy and Radiation Therapy (Baylor College of Medicine)

Principal Investigators – Cancer (University of Alabama Birmingham)

Postdoctoral Fellow – Immunology (NYU Langone Health)

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