Pulmonary Cell News Volume 7.06 | Feb 15 2018

TOP STORY

Decitibine Improves the Efficiency of Anti-PD-1 Therapy via Activating the Response of IFN/PD-L1 Signaling in Lung Cancer Cells

The authors investigated the methylation status of IFN-γ related genes IRF1/8 and IFN-α/β-related genes IRF3/7 in lung cancer tissues and found that only highly methylated IRF1 and 7 negatively correlated to cd274 (coding PD-L1) expression, similar to JAK mutation. [Oncogene] Abstract

(Ranked by impact factor of the journal)

Beta-Catenin Maintains Lung Epithelial Progenitors after Lung Specification

Using inducible, progenitor-specific genetic mosaic mouse models, scientists showed that beta-catenin maintains the lung progenitors by promoting a hierarchical lung progenitor gene signature, suppressing gastrointestinal genes, and regulating NKX2.1 and SOX2 in a developmental stage dependent manner. [Development] Abstract

Protein 4.1N Is Required for the Formation of the Lateral Membrane Domain in Human Bronchial Epithelial Cells

Researchers showed that protein 4.1N is located at the lateral membrane where it associates E-cadherin, β-catenin and βII spectrin. Importantly, depletion of 4.1N by RNAi in human bronchial epithelial cells resulted in decreased height of lateral membrane, which was reversed following re-expression of mouse 4.1N. [Biochim Biophys Acta] Abstract | Graphical Abstract

Involvement of Alveolar Epithelial Cell Necroptosis in IPF Pathogenesis

Investigators attempted to illuminate the involvement of RIPK3-regulated necroptosis in idiopathic pulmonary fibrosis (IPF) pathogenesis. Necrostatin-1 and RIPK3 knockdown experiments in alveolar epithelial cells revealed the participation of necroptosis in bleomycin and hydrogen peroxide-induced cell death. [Am J Respir Cell Mol Biol] Abstract

Cadherin-26 (CDH26) Regulates Airway Epithelial Cell Cytoskeletal Structure and Polarity

Using human airway epithelial cells (AECs) and cell lines, the authors demonstrated that CDH26 is abundantly expressed in differentiated AECs, localizes to the cell apices near ciliary membranes, and has functional cadherin domains with homotypic binding. [Cell Discov] Full Article

LUNG CANCER

2-Aminopurine Suppresses the TGF-β1-Induced Epithelial-Mesenchymal Transition and Attenuates Bleomycin-Induced Pulmonary Fibrosis

Scientists demonstrated that 2-aminopurine (2-AP) can restore E-cadherin expression and inhibit fibronectin and vimentin expression in TGF-β1-treated A549 lung cancer cells. Moreover, 2-AP could inhibit TGF-β1-induced metastasis of A549 cells. [Cell Death Discov] Full Article

Sotetsuflavone Suppresses Invasion and Metastasis in Non-Small-Cell Lung Cancer A549 Cells by Reversing EMT via the TNF-α/NF-κB and PI3K/AKT Signaling Pathway

Researchers demonstrated that sotetsuflavone inhibits metastasis of A549 cells, and epithelial-mesenchymal transition (EMT). This inhibition was reflected in the upregulation of E-cadherin, and downregulation of N-cadherin, vimentin, and Snail. [Cell Death Discov] Full Article

KRAS Induces Lung Tumorigenesis through MicroRNAs Modulation

By overexpressing wild type or mutant KRAS and using inducible human and mouse cell lines, investigators analyzed KRAS-regulated microRNAs in non-small-cell lung cancer. They showed that miR-30c and miR-21 are significantly upregulated by both KRAS isoforms and induce drug resistance and enhance cell migration/invasion via inhibiting crucial tumor suppressor genes, such as NF1, RASA1, BID, and RASSF8. [Cell Death Dis] Full Article

Gambogenic Acid Inhibits Fibroblast Growth Factor Receptor Signaling Pathway in Erlotinib-Resistant Non-Small-Cell Lung Cancer and Suppresses Patient-Derived Xenograft Growth

Scientists investigated the mechanism of action of gambogenic acid (GNA) in erlotinib-resistant non-small-cell lung cancer (NSCLC) and patient-derived cells. Both kinase assays and cell-based assays showed that GNA inhibits the phosphorylation of multiple kinases in FGFR signaling pathway in NSCLC. [Cell Death Dis] Full Article

Targeting Deubiquitinase USP28 for Cancer Therapy

The authors discuss the major mechanisms by which USP28 is involved in the cancer-related pathways, whereby USP28 regulates physiological homeostasis of ubiquitination process, DNA-damage response, and cell cycle during genotoxic stress. [Cell Death Dis] Full Article

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Cancer Research UK to Invest £45 Million in Clinical Trials

Cancer Research UK has announced that £45 million will be invested into its network of clinical trials units across the UK, one of the charity’s largest investments in clinical research to date. [Cancer Research UK] Press Release

National Cancer Institute Awards Tosk $2 Million Cancer Drug Development Grant

Tosk, Inc. announced that it has received a two-year, $2 million Phase II SIBR grant from the National Cancer Institute to support its kRAS oncogene drug research and development program. [Tosk, Inc. (Business Wire, Inc.)] Press Release

State Program Funds Lung Cancer Research at UC Santa Cruz

Biomedical researchers have won major funding to investigate lung cancer and COPD from the California Tobacco-Related Disease Research Program, which is supported by the state tax on cigarettes. [University of Califonia, Santa Cruz] Press Release

Merck KGaA, Darmstadt, Germany, and Pfizer Provide Update on Phase III JAVELIN Lung 200 Trial of Avelumab Monotherapy in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer

Merck KGaA, Darmstadt, Germany, and Pfizer Inc. announced results from the Phase III JAVELIN Lung 200 trial comparing avelumab to docetaxel in patients with unresectable, recurrent or metastatic non-small cell lung cancer whose disease progressed after treatment with a platinum-containing doublet therapy. [Merck & Co., Inc.] Press Release

Chi-Med Completes Enrollment of 527 Patients in Pivotal Phase III FALUCA Trial with Fruquintinib in Lung Cancer

Hutchison China MediTech Limited (Chi-Med) has completed patient enrollment of FALUCA, its Phase III pivotal trial of fruquintinib in advanced, third-line, non-small cell lung cancer patients in China. [Hutchison China MediTech Limited] Press Release

Kadmon Announces Positive Topline Results from Phase II Study of KD025 in Idiopathic Pulmonary Fibrosis

Kadmon Holdings, Inc. announced topline results from an ongoing Phase II clinical trial evaluating KD025, its Rho-associated coiled-coil kinase 2 inhibitor, in patients with idiopathic pulmonary fibrosis who were previously treated with or offered pirfenidone and/or nintedanib. [Kadmon Holdings, Inc.] Press Release

FDA Approves SYMDEKOTM (Tezacaftor/Ivacaftor and Ivacaftor) to Treat the Underlying Cause of Cystic Fibrosis in People Ages 12 and Older with Certain Mutations in the CFTR Gene

Vertex Pharmaceuticals Incorporated announced that the FDA approved SYMDEKO^™ for treating the underlying cause of CF in people ages 12 and older who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or who have at least one mutation that is responsive to tezacaftor/ivacaftor. [Vertex Pharmaceuticals Incorporated] Press Release

Theravance Biopharma Highlights Submission of Landmark IMPACT Data to EMA to Support Expanded Label for Trelegy Ellipta

Theravance Biopharma, Inc. highlighted the submission of the landmark IMPACT study data to the European Medicines Agency (EMA) as part of a type II variation to support an expanded label for Trelegy Ellipta in Europe for the maintenance treatment of moderate to severe COPD. [Theravance Biopharma, Inc.] Press Release

Trump’s Science Advisor, Age 31, Has a Political Science Degree

A job that’s been held by some of the nation’s top scientists is now occupied by a 31-year-old politics major from Princeton University. And it’s unlikely to change soon, observers say, leaving President Trump without a science adviser as the administration wrestles with a severe outbreak of the flu, lead-poisoned drinking water and record-breaking disasters that many scientists say are sharpened by rising temperatures. [Scientific American] Editorial

Few UK Universities Have Adopted Rules against Impact-Factor Abuse

Institutions have made little progress against the misuse of research metrics when hiring and promoting academics. [Nature News] Editorial

NEW Annual Meeting of the Israel Stem Cell Society 2018
May 31, 2018
Tel Aviv, Israel

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

NEW Assistant Professor – Pulmonary Physiology (University of California, Riverside)

NEW Multiple Positions – Pulmonary (University of Alabama at Birmingham)

NEW Professor – Lung Cancer (University of Cincinnati)

NEW Director – In Vitro Pharmacology (AstraZeneca)

Postdoctoral Fellow – Respiratory Therapy Area (AstraZeneca)

Postdoctoral Scholar – Stem Cell Biology and Cancer Biology (University of Iowa)

Postdoctoral Fellow – Lung Cancer (Van Ande Research Institute)

Postdoctoral Position – Biomedical Systems Biology (University of Zurich)

Postdoctoral Position – Pulmonary Disease Pathogenesis (Columbia University)

Postdoctoral Fellow – Lung Cancer (MD Anderson Cancer Center)

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