Pulmonary Cell News Volume 7.50 | Dec 20 2018

TOP STORY

Muc5b Overexpression Causes Mucociliary Dysfunction and Enhances Lung Fibrosis in Mice

Researchers showed in humans that MUC5B, a mucin thought to be restricted to conducting airways, was co-expressed with surfactant protein C in type 2 alveolar epithelia and in epithelial cells lining honeycomb cysts, indicating that cell types involved in lung fibrosis in distal airspace express MUC5B. [Nat Commun] Full Article | Press Release

(Ranked by impact factor of the journal)

HIF-1α Triggers ER Stress and CHOP-Mediated Apoptosis in Alveolar Epithelial Cells, a Key Event in Pulmonary Fibrosis

In primary alveolar epithelial cells, hypoxia activated unfolded protein response pathways. Pharmacological endoplasmic reticulum (ER) stress inhibitors and pharmacological inhibition or silencing of hypoxia-inducible factor-1α (HIF-1α) both prevented hypoxia-induced upregulation of C/EBP homologous protein (CHOP) and apoptosis. [Sci Rep] Full Article

Isogenic Cell Models of Cystic Fibrosis-Causing Variants in Natively Expressing Pulmonary Epithelial Cells

Isogenic cell lines harboring CF transmembrane conductance regulator variants in the native genomic context were created through the development and utilization of a footprint-less, CRISPR/Cas9 gene editing pipeline in 16HBE14o- immortalized bronchial epithelial cells. [J Cyst Fibros] Abstract

Organic Barn Dust Inhibits Surfactant Protein D Production through Protein Kinase-C Alpha Dependent Increase of GPR116

Scientists provide evidence that agricultural organic dusts could inhibit mRNA and protein expression of surfactant protein D in a human alveolar epithelial cell line, and an in vivo mouse model. This inhibition was not a result of lipopolysaccharide or peptidoglycans, the two most commonly cited immune active components of these dusts. [PLoS One] Full Article

The Effect of Mesenchymal Stem Cell-Secreted Factors on Airway Epithelial Repair

An indirect in vitro coculture model of injured airway epithelium explant with mesenchymal stem cells (MSCs) was developed. LC-MS/MS analysis was performed to determine factors secreted by MSCs and their involvement in epithelium repair was evaluated by histopathological assessment. [Regen Med] Abstract

LUNG CANCER

Silenced Long Non-Coding RNA PVT1 Increased the Radiosensitivity of Non-Small Cell Lung Cancer through the MicroRNA-424-5p/lncRNA PVT1/CARM1 Signaling Pathway

The authors explored the role of long non-coding RNA (lncRNA) PVT1 on the radiosensitivity of non-small cell lung cancer via the miR-424-5p/lncRNA PVT1/CARM1 signaling pathway. The interaction between PVT1 and CARM1 and effect of miR-424-5p on cell biological processes were tested. [Mol Ther Nucleic Acids] Abstract | Full Article

miR-3607-3p Suppresses Non-Small Cell Lung Cancer (NSCLC) by Targeting TGFBR1 and CCNE2

Ectopic expression in NSCLC cells, xenografts, and metastasis models was used to evaluate the effects of miR-3607-3p on proliferation and migration of NSCLC. Luciferase assay and western blotting were performed to validate the potential targets of miR-3607-3p after preliminary screening by microarray analysis and computer-aided algorithms. [PLoS Genet] Full Article

Sinoporphyrin Sodium-Mediated Sonodynamic Therapy Inhibits RIP3 Expression and Induces Apoptosis in the H446 Small Cell Lung Cancer Cell Line

Researchers explored the anti-tumor effect of sonodynamic therapy with a new sonosensitizer, sinoporphyrin sodium, on the human small cell lung cancer H446 cell line in vitro and in vivo. [Cell Physiol Biochem] Full Article

A Positive Feedback Loop between ZNF205-AS1 and EGR4 Promotes Non-Small Cell Lung Cancer Growth

Investigators reported the identification of a novel non-small cell lung cancer-associated functional lncRNA ZNF205 antisense RNA 1 (ZNF205-AS1). They revealed that early growth response 4 (EGR4) directly bound to ZNF205-AS1 promoter, increased the promoter activity of ZNF205-AS1, and activated ZNF205-AS1 transcription. [J Cell Mol Med] Full Article

miR-608 and miR-4513 Significantly Contribute to the Prognosis of Lung Adenocarcinoma Treated with EGFR-TKIs

The impact of miR-608 and miR-4513 on the drug sensitivity of gefitinib was examined in lung adenocarcinoma cells. miR-608 significantly increased the anti-proliferation effect of gefitinib in both lung adenocarcinoma PC9 and H1299 cells, whereas miR-4513 increased cells’ resistance to gefitinib. [Lab Invest] Abstract

Ergosterol Peroxide from Marine Fungus Phoma sp. Induces ROS-Dependent Apoptosis and Autophagy in Human Lung Adenocarcinoma Cells

Ergosterol peroxide (EP) induced caspase-dependent apoptosis through mitochondrial damage in A549 cells. Additionally, EP-induced ROS generation and apoptosis were attenuated by ROS-generating enzymes inhibitors and antioxidant N-acetylcysteine, indicated that ROS played an important role in EP-mediated apoptosis in A549 cells. [Sci Rep] Full Article

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Lung Cancer Stem Cells: Origin, Features, Maintenance Mechanisms and Therapeutic Targeting

The authors highlight some examples on how lung cancer stem cells attain stemness through different molecular modifications and cellular assistance from the tumor microenvironment. The exploitation of these mechanistic features for the development of pharmacological therapy is also discussed. [Biochem Pharmacol] Abstract | Graphical Abstract

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InSphero and Path BioAnalytics Announce Partnership to Develop Advanced 3D Airway Tissue Model for Cystic Fibrosis Research

InSphero AG and Path BioAnalytics announced a partnership through which Path BioAnalytics will produce and test 3D cystic fibrosis organoid models from primary human bronchial and nasal epithelial cells using InSphero’s proprietary 3D cell-based technology, which enables formation of biologically-relevant, personalized organoids without the use of artificial matrices. [InSphero AG (GlobeNewswire, Inc.)] Press Release

Kyn Therapeutics Announces Initiation of Phase Ib/II Clinical Studies of ARY-007 in Collaboration with Merck

Kyn Therapeutics announced the initiation of two clinical trials of ARY-007, an EP4 receptor antagonist, in collaboration with Merck. ARY-007 will be assessed in combination with Merck’s anti-PD-1 therapy, KEYTRUDA in checkpoint-refractory and -resistant solid tumors, an area of high unmet medical need. [Kyn Therapeutics] Press Release

G1 Therapeutics Announces Positive Topline Results from Randomized Phase II Trial of Trilaciclib Showing Multi-Lineage Myelopreservation Benefits in 2nd-/3rd-Line Small Cell Lung Cancer

G1 Therapeutics, Inc. announced positive topline data showing multi-lineage myelopreservation benefits in its randomized, double-blind, placebo-controlled Phase II trial evaluating trilaciclib in combination with topotecan as a treatment for 2nd-/3rd-line small cell lung cancer. [G1 Therapeutics, Inc.] Press Release

Savara Announces Interim Results for OPTIMA Clinical Study of Molgradex for the Treatment of NTM

Savara Inc. announced interim results from OPTIMA, a Phase IIa clinical study evaluating its lead product candidate Molgradex, an inhaled formulation of recombinant human granulocyte-macrophage colony-stimulating factor, for the treatment of nontuberculous mycobacterial lung infection. [Savara Inc.] Press Release

Verona Pharma Initiates Phase II Clinical Trial to Evaluate Dry Powder Inhaler Formulation of RPL554 for Maintenance Treatment of COPD

Verona Pharma plc announced the initiation of a Phase II clinical trial to evaluate the pharmacokinetic profile, efficacy and safety of a dry powder inhaler formulation of RPL554 in patients with moderate to severe COPD. [Verona Pharma plc] Press Release

Bridge Biotherapeutics Announces FDA Clearance of IND for Its BBT-877, an Autotaxin Inhibitor for IPF

Bridge Biotherapeutics Inc. announced that the Investigational New Drug (IND) application for BBT-877, a potent best-in-class drug candidate for Idiopathic Pulmonary Fibrosis (IPF), has been cleared by the FDA. [Bridge Biotherapeutics Inc.] Press Release

Top Cancer Doctor Resigns as Editor of Medical Journal

Dr. José Baselga, the former chief medical officer of Memorial Sloan Kettering Cancer Center, resigned under pressure as one of the editors-in-chief of Cancer Discovery, a prominent scientific journal, after he failed to accurately disclose his conflicts of interest in dozens of articles in medical journals. [The New York Times] Editorial

Australia Cuts Research Funding for Universities

Australian scientists have expressed disappointment over an AU$328.5 million cut to research funding that had been expected over the next four years. In a budget update, the government announced that it will freeze funding increases for the program that supports research, facilities, and training, including of PhDs, at universities. [Nature News] Editorial

Canadian Government Ending Networks of Centres of Excellence Program

Canada’s federal government is ending a 30-year-old research funding program, the Networks of Centres of Excellence, leaving researchers uncertain about where future funding will come from, The Globe and Mail reports. The program will be phased out over the course of the next three years, according to a spokesperson for Science Minister Kirsty Duncan. [The Scientist] Editorial

NEW European CanCer Organisation (ECCO) 2019: European Cancer Summit
September 12-14, 2019
Brussels, Belgium

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

Assistant Professor – Cancer Biology (Cold Spring Harbor Laboratory)

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

Postdoctoral Researcher – Lung Cancer Research (University of Cologne)

Research Associate – Gene Therapy Lung Research (Imperial College of London)

Postdoctoral Position – Pulmonary Fibrosis Research (University of California San Francisco)

Staff Scientist/ Tier 2 Canada Research Chair – Lung Research (University of Toronto)

Faculty Positions – Cancer-Focused Target & Drug Discovery (University of New Mexico)

Postdoctoral Research Fellow – Sepsis & Lung Inflammation Pathogenesis Research (Boston University)

Associate Professor – Oncology (University of California, Davis)

Postdoctoral Scholar – Cancer Metabolism (The Moffitt Cancer Center)

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