Pulmonary Cell News Volume 7.46 | Nov 22 2018

TOP STORY

H3K9 Methyltransferases and Demethylases Control Lung Tumor-Propagating Cells and Lung Cancer Progression

Inhibition of G9a drove lung adenocarcinoma cells towards the tumor-propagating cell (TPC) phenotype by de-repressing genes which regulate the extracellular matrix. Depletion of G9a during tumorigenesis enriched tumors in TPCs and accelerated disease progression metastasis. [Nat Commun] Full Article | Press Release

(Ranked by impact factor of the journal)

Capitalizing on the Heterogeneous Effects of CFTR Nonsense and Frameshift Variants to Inform Therapeutic Strategy for Cystic Fibrosis

The authors selected 26 premature termination codons-generating variants from four regions of CFTR and determined their consequences on CFTR mRNA, protein and function using intron-containing mini genes expressed in three cell lines and patient-derived conditionally reprogrammed primary nasal epithelial cells. [PLoS Genet] Full Article

A Lung/Liver-on-a-Chip Platform for Acute and Chronic Toxicity Studies

Investigators report the development of a lung/liver-on-a-chip, connecting in a single circuit, normal human bronchial epithelial cells cultured at the air-liquid interface, and HepaRG^™ liver spheroids. [Lab Chip] Abstract | Full Article | Graphical Abstract

MUC1 Deficiency Mediates Corticosteroid Resistance in Chronic Obstructive Pulmonary Disease

MUC1-CT expression was downregulated in lung tissue, bronchial epithelial cells and lung neutrophils from smokers and COPD patients compared with healthy subjects. Cigarette smoke extract decreased the expression of MUC1 and induced corticosteroid resistance in human primary bronchial epithelial cells and human neutrophils. [Respir Res] Full Article

LUNG CANCER

Transmembrane Protease TMPRSS11B Promotes Lung Cancer Growth by Enhancing Lactate Export and Glycolytic Metabolism

Interrogation of a set of soluble receptors revealed that TMPRSS11B promoted solubilization of basigin, an obligate chaperone of the lactate monocarboxylate transporter MCT4. Basigin release mediated by TMPRSS11B enhanced lactate export and glycolytic metabolism, thereby promoting tumorigenesis. [Cell Rep] Full Article | Graphical Abstract

Targeting PRMT5/Akt Signaling Axis Prevents Human Lung Cancer Cell Growth

Scientists found that the down-regulation of protein arginine methyltransferase 5 (PRMT5) by shRNA or the inhibition of PRMT5 by specific inhibitor GSK591 dramatically suppressed cyclin E1 and cyclin D1 expression and cell proliferation. They uncovered that PRMT5 promoted lung cancer cell proliferation via regulation of Akt activation. [J Cell Mol Med] Full Article

The Novel PI3K Inhibitor S1 Synergizes with Sorafenib in Non-Small Cell Lung Cancer Cells Involving the Akt-S6 Signaling

S1 alone produced inhibitory effects on colony formation, cell migration and invasion and angiogenesis, with more pronounced inhibition when used with sorafenib. Researchers further revealed that S1 mainly inhibited Akt/S6 phosphorylation while sorafenib mostly decreased the phosphorylation of ERK. [Invest New Drugs] Abstract

THZ1 Suppresses Human Non-Small-Cell Lung Cancer Cells In Vitro through Interference with Cancer Metabolism

Treatment with THZ1 arrested cell cycle at G2/M phase and induced apoptosis in non-small-cell lung cancer cell lines. More importantly, scientists revealed that treatment with THZ1 blocked the glycolysis pathway but had no effect on glutamine metabolism. [Acta Pharmacol Sin] Abstract

TMEM106A Inhibits Cell Proliferation, Migration, and Induces Apoptosis of Lung Cancer Cells

In vitro assays showed that transmembrane protein 106A (TMEM106A) expression in non-small cell lung carcinoma (NSCLC) cell lines was much lower than that in the bronchial epithelial cell line. Overexpression of TMEM106A reduced cell proliferation, migration, and invasion, while induced cell apoptosis in NSCLC cells. [J Cell Biochem] Abstract

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Heparin-Binding Epidermal Growth Factor (HB-EGF) Drives EMT in Patients with COPD: Implications for Disease Pathogenesis and Novel Therapies

Investigators consider that improved molecular understanding of the intricate pathways associated with epithelial cell plasticity in smokers and patients with COPD will have major therapeutic implications. [Lab Invest] Abstract

Tissue-Informed Engineering Strategies for Modeling Human Pulmonary Diseases

The authors highlight how advances in lung tissue characterization reveal dynamic changes in the structure, mechanics and composition of the extracellular matrix in chronic pulmonary diseases, and how this information paves the way for tissue-informed engineering of more organotypic models of human pathology. [Am J Physiol Lung Cell Mol Physiol] Abstract

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Vertex Receives European CHMP Positive Opinion for ORKAMBI^® (Lumacaftor/Ivacaftor) for Treatment of Children with Cystic Fibrosis Aged 2 to 5 Years Old with Most Common Form of the Disease

Vertex Pharmaceuticals Limited announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for ORKAMBI^® for the treatment of people with cystic fibrosis aged 2 to 5 years old who have two copies of the F508del mutation, the most common form of the disease. [Vertex Pharmaceuticals Incorporated] Press Release

Chi-Med Announces Phase III FALUCA Trial Results for Fruquintinib in Third-Line, Advanced Non-Small Cell Lung Cancer in China

Hutchison China MediTech Limited (Chi-Med) announced the outcome of FALUCA, its Phase III trial of fruquintinib in advanced non-small cell lung cancer patients in China who have failed two lines of systemic chemotherapy. [Hutchison China MediTech Limited] Press Release

Pulmatrix Announces Positive Final Results from the Phase I/Ib Clinical Trial of Pulmazole – an Inhaled Dry-Powder iSPERSE^™ Formulation of Itraconazole

Pulmatrix, Inc. announced the results of the completed first-in-human study of Pulmazole – an inhaled iSPERSE^™ formulation of the anti-fungal drug itraconazole for the treatment of allergic bronchopulmonary aspergillosis in patients with asthma. [Pulmatrix, Inc.] Press Release

Neovacs Announces the Patent Filing in Europe and in the United States for Its New Therapeutic Vaccine Candidate Kinoid IL-4/IL-13 for the Treatment of Allergies

Neovacs announced patent filing after having achieved preclinical proof of concept with its new vaccine IL-4/IL-13 Kinoid for the treatment of asthma. [NEOVACS S.A. (GlobeNewswire, Inc.)] Press Release

Bridge Biotherapeutics Files Investigational New Drug Application for BBT-877, an Autotaxin Inhibitor for Idiopathic Pulmonary Fibrosis

Bridge Biotherapeutics Inc. announced that the company filed an Investigational New Drug application to the FDA to initiate Phase I study of BBT-877, a potent best-in-class drug candidate for Idiopathic Pulmonary Fibrosis treatment. [Bridge Biotherapeutics Inc.] Press Release

AI Peer Reviewers Unleashed to Ease Publishing Grind

A suite of automated tools is now available to assist with peer review but humans are still in the driver’s seat. A handful of academic publishers are piloting AI tools to do anything from selecting reviewers to checking statistics and summarizing a paper’s findings. [Nature News] Editorial

Stop Exploitation of Foreign Postdocs in the United States

A survey reveals some lab heads are using the need for visas to create unacceptable conditions for junior researchers. Some PIs are exploiting the fact that overseas scientists rely on them for continued visas. The responses suggest that senior scientists are using this reliance to force postdocs to work longer hours and endure unacceptable conditions. [Nature] Editorial

NEW AACR International Conference New Horizons in Cancer Research
May 3-5, 2019
Shenzhen, China

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

NEW 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)

Postdoctoral Position – Lung Cancer Biology (UT Southwestern Medical Center)

Postdoctoral Research Scientist – Modeling Infection in Human Lung Organoids (Columbia University)

Postdoctoral Position – Human Lung Organoid Research (Columbia University Medical Center)

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