Pulmonary Cell News Volume 4.39 | Oct 8 2015

High Mobility Group Box 1 (HMGB1) Promotes Extracellular Matrix Synthesis and Wound Repair in Human Bronchial Epithelial Cells
As epithelial cell responses are fundamental drivers of asthma, including abnormal repair-restitution linked to changes in extracellular matrix (ECM) synthesis, scientists tested the hypothesis that HMGB1 promotes bronchial epithelial cell wound repair via toll-like receptor 4 and/or receptor for advanced glycated end products signaling that regulates ECM and integrin protein abundance. [Am J Physiol Lung Cell Mol Physiol] Abstract

BARD1 Mediates TGF-β Signaling in Pulmonary Fibrosis
The authors investigated BARD1 expression as a function of TGF-β in cultured cells, in mice with experimentally induced lung fibrosis, and in lung biopsies from pulmonary fibrosis patients. Full length BARD1 and BARD1β were upregulated in response to TGF-β in epithelial cells and fibroblasts in vitro and in vivo. [Respir Res] Full Article

Correlation of Organic Cation/Carnitine Transporter 1 and Multidrug Resistance-Associated Protein 1 Transport Activities with Protein Expression Levels in Primary Cultured Human Tracheal, Bronchial, and Alveolar Epithelial Cells
Investigators evaluated whether differences in organic cation/carnitine transporter 1 and multidrug resistance-associated protein 1 protein expression govern the respective transport activity in primary cultured human lung cells. [J Pharm Sci] Abstract

LUNG CANCER

MicroRNA-92a Promotes Growth, Metastasis, and Chemoresistance in Non-Small Cell Lung Cancer Cells by Targeting PTEN
Function assays demonstrated that upregulation of microRNA-92a (miR-92a) in non-small cell lung cancer (NSCLC) cells promoted cell proliferation, migration, and invasion, decreased apoptosis and caspase-3 activity, and enhanced chemoresistance of NSCLC cells, whereas downregulation of miR-92a showed the opposite effects. [Tumour Biol] Abstract

Increased Insulin-Like Growth Factor 1 Receptor (IGF1R) Expression in Small Cell Lung Cancer and the Effect of Inhibition of IGF1R Expression by RNAi on Growth of Human Small Cell Lung Cancer NCI-H446 Cell
The expression and clinical significance of IGF1R were investigated in serum and lung cancer tissues from small cell lung cancinoma. Researchers also compared the effect of IGF1R up-regulation and IGF1R inhibition on viability and apoptosis of NCI-H446 cells. [Growth Factors] Abstract

Functional Analyses of ATM, ATR and Fanconi Anemia Proteins in Lung Carcinoma: ATM, ATR and FA in Lung Carcinoma
Scientists undertook functional analyses of ATM, ATR, Chk1 and Fanconi anemia (FA) proteins in lung cancer cell lines. No defects in ATM, ATR or Chk1 kinase activation, or FANCD2 monoubiquitination were identified in the lung cancer cell lines examined, including Calu6, and major alterations in these pathways were not identified in the cancer genome atlas database. [BMC Cancer] Full Article

Contrasting Effects of the Cytotoxic Anticancer Drug Gemcitabine and the EGFR Tyrosine Kinase Inhibitor Gefitinib on NK Cell-Mediated Cytotoxicity via Regulation of NKG2D Ligand in Non-Small-Cell Lung Cancer Cells
The authors examined the effect of the cytotoxic drug Gemcitabine and the EGFR tyrosine kinase inhibitor Gefitinib on the expression of NK group 2 member D (NKG2D) ligands as well as the sensitivity of non-small-cell lung cancer cells to the NK-mediated lysis. [PLoS One] Full Article

Post-Translational Modification of E-Cadherin by Core-Fucosylation Regulates Src Activation and Induces Epithelial-Mesenchymal Transition-Like Process in Lung Cancer Cells
Through gain and loss of fucosylation experiments in the giant lung carcinoma cell lines 95C and 95D, the authors revealed that E-cadherin core-fucosylation in 95C cells overexpressing α-1, 6-fucosyltransferase (Fut8) inhibited Fut8-95C cell migration, whereas knockdown of Fut8 in 95D cells enhanced migration of siFut8-95D cells. [Glycobiology] Abstract

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Pulmatrix’s PUR1900 Inhaled Cystic Fibrosis Drug Demonstrates High Lung Retention and Potency against Fungal Infection
Pulmatrix, Inc. announced preclinical data showing that PUR1900, which is being developed as the first inhaled antifungal medication for cystic fibrosis, was active and potent in vitro against Aspergillus fumigatus, a pathogen causing pulmonary infection in cystic fibrosis, while achieving high lung concentrations and low systemic exposure in rats. [Press release from Pulmatrix, Inc. discussing research presented at the 2015 North American Cystic Fibrosis Conference, Phoenix] Press Release

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FDA Approves KEYTRUDA^® (Pembrolizumab) for the Treatment of Patients with Metastatic Non-Small Cell Lung Cancer Whose Tumors Express PD-L1 with Disease Progression on or after Platinum-Containing Chemotherapy
Merck announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA^® monotherapy, the company’s anti-PD-1 (programmed death receptor-1) therapy, for the treatment of patients with metastatic non-small cell lung cancer whose tumors express PD-L1 as determined by an FDA-approved test and who have disease progression on or after platinum-containing chemotherapy. [Merck & Co., Inc.] Press Release

Supplemental New Drug Application for Use of KALYDECO^® (Ivacaftor) in People with Cystic Fibrosis Ages 2 and Older who have One of 23 Residual Function Mutations Accepted for Priority Review by U.S. FDA
Vertex Pharmaceuticals Incorporated announced that the U.S. Food and Drug Administration (FDA) has accepted for review a supplemental new drug application for the use of KALYDECO^® (ivacaftor) in people with cystic fibrosis ages 2 and older who have one of 23 residual function mutations. [Vertex Pharmaceuticals Incorporated] Press Release

Celtaxsys Begins US Enrollment for Phase II Trial of Acebilustat Anti-Inflammatory Therapy for Cystic Fibrosis
Celtaxsys announced the commencement of the US arm of an international Phase II clinical trial for its flagship compound, acebilustat, in patients with cystic fibrosis. [Celtaxsys] Press Release

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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Clinical Research Fellow – Small Cell Lung Cancer (Cancer Research UK Manchester Institute)

Postdoctoral Fellowships – Chronic Heart or Lung Disease (University of British Columbia)

Postdoctoral Fellow – Asthma (The University of Tennessee Health Science Center)

Postdoctoral Scholar – Autoimmune Diseases Affecting the Lung (University of California, San Francisco)

Postdoctoral Researcher – Epigenetic Modifiers (Van Andel Research Institute)

Postdoctoral Research Fellow – Small Cell Lung Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Lung Cancer (Van Andel Research Institute)

Postdoctoral Research Fellow – Cancer and Molecular Imaging (University of Michigan)

Postdoctoral Fellow – HMGA Chromatin Remodeling Proteins in Cancer and Stem Cell Biology (Johns Hopkins University School of Medicine)

Postdoctoral Fellow – Pulmonary Fibrosis (University of Colorado School of Medicine)

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