Pulmonary Cell News Volume 8.01 | Jan 17 2019

TOP STORY

HSP90 Inhibitor Geldanamycin Reverts IL-13- and IL-17-Induced Airway Goblet Cell Metaplasia

Investigators confirmed that geldanamycin and other HSP90 inhibitors prevented IL-13-induced goblet cell metaplasia in vitro and in vivo. Geldanamycin did not induce goblet cell death, nor did it solely block mucin synthesis or IL-13 receptor-proximal signaling. Geldanamycin affected the transcriptome of airway cells when exposed to IL-13, but not when exposed to vehicle. [J Clin Invest] Full Article

(Ranked by impact factor of the journal)

Long-Term Expanding Human Airway Organoids for Disease Modeling

Scientists describe a method to establish long-term-expanding human airway organoids from broncho-alveolar resections or lavage material. The pseudostratified airway organoids consisted of basal cells, functional multi-ciliated cells, mucus-producing secretory cells, and CC10-secreting club cells. Airway organoids derived from CF patients allowed assessment of CFTR function in an organoid swelling assay. [EMBO J] Full Article | Graphical Abstract

YAP1/Twist Promotes Fibroblast Activation and Lung Fibrosis That Conferred by miR-15a Loss in IPF

Knockdown of miR-15a resulted in fibroblast activation and lung fibrosis through promoting Twist expression by targeting inhibition of YAP1. In contrast, therapeutic restoration of miR-15a inhibited fibrogenesis in lung fibroblast and abrogated BLM-induced lung fibrosis in mice. [Cell Death Differ] Abstract

Hypercapnic Acidosis Induces Mitochondrial Dysfunction and Impairs the Ability of Mesenchymal Stem Cells to Promote Distal Lung Epithelial Repair

The authors demonstrated that hypercapnic acidosis attenuated the inflammatory response and reparative potential of primary human small airway epithelium and capillary endothelium and induced mitochondrial dysfunction. [FASEB J] Abstract

LUNG CANCER

LUBAC Determines Chemotherapy Resistance in Squamous Cell Lung Cancer

KF lung squamous cell carcinoma (LSCC) tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and scientists identified LUBAC-mediated NF-κB signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-κB activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment. [J Exp Med] Full Article

Proteasome Inhibition Boosts Autophagic Degradation of Ubiquitinated-AGR2 and Enhances the Antitumor Efficiency of Bevacizumab

Researchers observed that anterior gradient 2 (AGR2) expression was significantly suppressed by proteasome inhibitor MG132/bortezomib at mRNA and protein levels in lung cancer cells. MG132-mediated repression of AGR2 transcription was independent of ROS generation and ER stress induction, but partially resulted from the downregulated E2F1. [Oncogene] Full Article

Increased Type III TGF-β Receptor Shedding Decreases Tumorigenesis through Induction of Epithelial-to-Mesenchymal Transition

Scientists demonstrated that expressing type III TGF-β receptor (TβRIII)-super shedding (SS) in lung cancer cell models induced epithelial-to-mesenchymal (EMT) transition and that these TβRIII-SS (EMT) cells were less migratory, invasive and adhesive and more resistant to gemcitabine. [Oncogene] Abstract

Hypercapnic Tumor Microenvironment Confers Chemoresistance to Lung Cancer Cells by Reprogramming Mitochondrial Metabolism In Vitro

High CO₂ levels, ranging from 5% to 15%, protected lung cancer cells from anticancer agents, such as cisplatin, carboplatin and etoposide, by suppressing apoptosis. In contrast, high CO₂ levels did not affect cisplatin-mediated DNA damage responses or the expression of Bcl-2 family proteins. [Free Radic Biol Med] Abstract | Graphical Abstract

Antimalarial Drug Pyrimethamine Plays a Dual Role in Anti-Tumor Proliferation and Metastasis through Targeting DHFR and TP

Although pyrimethamine (Pyr) and methotrexate could inhibit the proliferation of lung cancer cells by targeting dihydrofolate reductase (DHFR), only Pyr could inhibit the epithelial-mesenchymal transition, metastasis and invasion of lung cancer cells. [Mol Cancer Ther] Abstract

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Safety and Tolerability of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer

The authors provide a comprehensive state-of-the-art review about the pharmacodynamics, pharmacokinetics, safety, and tolerability profiles of currently available and promising under-development anaplastic lymphoma kinase tyrosine kinase inhibitors. [Drug Saf] Abstract

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

LUNGevity Foundation Issues Request for Applications for 2019 Career Development Awards for Translational Research in Lung Cancer

LUNGevity has issued a Request for Applications for translational research for Career Development Awards that will be granted in 2019. Projects that will be funded in 2019 are expected to have a direct impact on the early detection of lung cancer and/or individualized lung cancer treatment, including through targeted therapy and immunotherapy. [LUNGevity Foundation] Press Release

Verona Pharma Reports Encouraging Top-Line Data from Three-Day Phase II Trial Evaluating Nebulized Ensifentrine (RPL554) on Top of Dual Bronchodilator Therapy for COPD Maintenance Treatment

Verona Pharma plc announced top-line data from its three-day Phase II clinical pharmacology trial evaluating the effect of two different doses of nebulized ensifentrine when used on top of an inhaled long-acting muscarinic antagonist/long-acting beta2 agonist, tiotropium/olodaterol. [Verona Pharma plc] Press Release

Bridge Biotherapeutics Announces FDA Orphan Drug Designation for BBT-877 in Idiopathic Pulmonary Fibrosis (IPF)

Bridge Biotherapeutics Inc. announced that the FDA has granted an orphan drug designation to BBT-877, a drug candidate under development for IPF treatment. BBT-877, a potent best-in-class autotaxin (ATX) inhibitor deregulates ATX, the enzyme found to be engaging in inflammation and fibrosis by generating the lipid signaling molecule. [Bridge Biotherapeutics Inc.] Press Release

FDA Accepts Genentech’s Supplemental Biologics License Application for Tecentriq plus Chemotherapy (Abraxane and Carboplatin) for the Initial Treatment of Metastatic Non-Squamous Non-Small Cell Lung Cancer

Genentech, announced that the FDA has accepted the company’s supplemental Biologics License Application for Tecentriq^® in combination with Abraxane^® and carboplatin for the initial treatment of people with metastatic non-squamous non-small cell lung cancer who do not have EGFR or ALK genomic tumor aberrations. [Genentech, Inc.] Press Release

Aradigm Announces Detailed Third Party Evaluation Results for Apulmiq (FDA)/Linhaliq (EMA)

Aradigm Corporation announced specific, detailed results of an independent third party evaluation of the Phase III clinical trial results for Apulmiq. [Aradigm Corporation] Press Release

How UK Scientists Are Planning for a Chaotic No-Deal Brexit

British scientists are ramping up preparations for a ‘no deal’ Brexit on 29 March — a situation that would instantly affect travel, data collection, clinical trials and crucial laboratory supplies. [Nature News] Editorial

German Institutions and Wiley Reach Open-Access Publishing Deal

Ater nearly three years of contract negotiations, a consortium of nearly 700 German libraries, research institutes, and universities called Project DEAL has forged an agreement with the scholarly publisher Wiley that moves the publishing industry towards more open access. [The Scientist] Editorial

NEW Gordon Research Seminar: New Views of Organogenesis and Tumorigenesis: From Single Molecules to Therapeutics
March 23-24, 2019
Ventura, California, United States

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

NEW Postdoctoral Scholar – Lung Repair & Regeneration (University of California San Francisco)

NEW Postdoctoral Position – Lung Cancer (Albert Einstein College of Medicine of Yeshiva University)

NEW Postdoctoral Fellow – Respiratory Research (Royal College of Surgeons Ireland)

Tenure Track Group Leader – Lung Epidemiology (Helmholtz-Center Munchen)

Tenure Track Investigator – Lung Cancer (Northwestern University)

Postdoctoral Research Associate – Lung Stem/Progenitor Cell Research (The University of Texas Health Science Center at Tyler)

Associate/Full Professor – Lung Biology & Medicine (University of California, Davis)

Postdoctoral Positions – Pluripotent Stem Cell-Derived Human Lung Organoids (Columbia University Irving Medical Center)

Postdoctoral Position – Asthma Epigenetics & Genomics (La Jolla Institute for Allergy & Immunology)

Associate Professor – Oncology (University of California, Davis)

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