Pulmonary Cell News Volume 5.22 | Jun 9 2016

TOP STORY

Multi-Walled Carbon Nanotubes Directly Induce Epithelial-Mesenchymal Transition in Human Bronchial Epithelial Cells via the TGF-β-Mediated Akt/GSK-3β/SNAIL-1 Signaling Pathway

Fully characterized multi-walled carbon nanotubes (MWCNT) were able to induce epithelial-mesenchymal transition (EMT) in an in vitro human model after long-term incubation at sub-cytotoxic concentrations. MWCNT stimulate TGF-β secretion, Akt activation and GSK-3β inhibition, which induces nuclear accumulation of SNAIL-1 and its transcriptional activity, thus contributing to switch on the EMT program. [Part Fibre Toxicol] Full Article

(Ranked by impact factor of the journal)

Salvianolic Acid B Attenuates Experimental Pulmonary Fibrosis through Inhibition of the TGF-β Signaling Pathway

Experiments performed using a bleomycin-instilled mouse model of pulmonary fibrosis showed that salvianolic acid B, the major ingredient of Salviae miltiorrhiza, had strong anti-inflammatory and anti-fibrotic effects through its inhibition of inflammatory cell infiltration, alveolar structure disruption, and collagen deposition. [Sci Rep] Full Article

Suppression of IRG-1 Improves Immune Lung Injury after RSV Infection by Reducing ROS Production

The authors investigated immune responsive gene-1 (IRG1) expression during respiratory syncytial virus (RSV) infection since IRG1 has been shown to mediate innate immune response to intracellular bacterial pathogens by modulating reactive oxygen species (ROS) and itaconic acid production. They found that RSV infection induced IRG1 expression in human A549 cells and in the lung tissues of RSV-infected mice. [J Virol] Abstract

Exposure to Common Respiratory Bacteria Alters the Airway Epithelial Response to Subsequent Viral Infection

Bronchial epithelial cells were exposed to heat-inactivated Haemophilus influenzae, Pseudomonas aeruginosa or Streptococcus pneumoniae and subsequently infected with respiratory syncytial virus, type 2 human adenovirus or influenza B. Levels of pro-inflammatory cytokines, viral replication and expression of pattern recognition receptors were determined in culture supernatants and/or cell lysates. [Respir Res] Full Article

Cigarette Smoke Extract Alters the Cell Cycle via the Phospholipid Transfer Protein/Transforming Growth Factor-β1/CyclinD1/CDK4 Pathway

Male Wistar rats and the rat alveolar epithelial cell line, RLE-6TN, were exposed to normal air or different concentrations of cigarette smoke extract (CSE). Then phospholipid transfer protein siRNA was transfected into cells and an inhibitor of transforming growth factor-β1 was administered prior to CSE exposure. [Eur J Pharmacol] Abstract

LUNG CANCER

Upregulation of SIRT6 Predicts Poor Prognosis and Promotes Metastasis of Non-Small Cell Lung Cancer via the ERK1/2/MMP9 Pathway

Sirtuin6 (SIRT6) overexpression in non-small cell lung cancer cell lines increased extracellular signal-regulated kinase 1/2 phosphorylation, activated matrix metalloproteinase 9 (MMP9) and promoted tumor cell migration and invasion. [Oncotarget] Full Article

Cyclosporine A Sensitizes Human Non-Small Cell Lung Cancer Cells to Gefitinib through Inhibition of STAT3

Researchers found that cyclosporine A significantly augmented the anti-cancer effect of gefitinib in epidermal growth factor receptor tyrosine kinase inhibitors-sensitive and -resistant non-small cell lung cancer cells. [Cancer Lett] Abstract

Novel CHOP Activator LGH00168 Induces Necroptosis in A549 Human Lung Cancer Cells via ROS-Mediated ER Stress and NF-κB Inhibition

HEK293-C/EBP homologous protein (CHOP)-luc reporter cells were used in high-throughput screening to identify CHOP activators. The cytotoxicity against cancer cells in vitro was measured with MTT assay. The anticancer effects were further examined in A549 human non-small cell lung cancer xenograft mice. [Acta Pharmacol Sin] Abstract

Role of SGK1 for Fatty Acid Uptake, Cell Survival and Radioresistance of NCI-H460 Lung Cancer Cells Exposed to Acute or Chronic Cycling Severe Hypoxia

The authors studied the role of human serum and glucocorticoid-inducible kinase (SGK1) in the regulation of fatty acids uptake in cancer cells exposed to acute or chronic cycling hypoxia and explore its use as target for the radiosensitization of hypoxic cancer cells. [Radiat Oncol] Full Article

Alveolar Epithelial Disintegrity in Pulmonary Fibrosis

The authors report a case of hereditary muco-epithelial dysplasia that presented with pulmonary fibrosis and emphysema on high-resolution computed tomography. This case illustrates a more generalizable concept of epithelial disintegrity in the development of fibrotic lung diseases, which is explored in greater detail in this review article. [Am J Physiol Lung Cell Mol Physiol] Abstract

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

Pfizer Presents Promising Data from Next Generation ALK/ROS1 Inhibitor in Advanced Non-Small Cell Lung Cancer

Pfizer Inc. announced encouraging new data from a Phase I/II study of lorlatinib, the proposed generic name for PF-06463922, Pfizer’s investigational, next-generation ALK/ROS1 tyrosine kinase inhibitor. [Press release from Pfizer Inc. discussing research presented at the 52^nd Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

ARIAD Presents Long-Term Phase I/II Trial Follow up on Investigational Drug Brigatinib with Median Time on Treatment of 17 Months in ALK⁺ NSCLC Patients

ARIAD Pharmaceuticals, Inc. announced updated clinical data on its investigational tyrosine kinase inhibitor, brigatinib, in patients with anaplastic lymphoma kinase-positive (ALK⁺) advanced non-small cell lung cancer (NSCLC) from an ongoing Phase I/II trial. [Press release from ARIAD Pharmaceuticals, Inc. discussing research presented at the 52^nd Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

New Data Evaluating KEYTRUDA^® (Pembrolizumab) in Combination with Chemotherapy for First-Line Treatment of Non-Small Cell Lung Cancer Demonstrate Response Rates Ranging from 48 to 71 Percent

Merck announced findings from an initial proof-of-concept study of KEYTRUDA^®, the company’s anti-PD-1 therapy, combined with standard treatments, one with bevacizumab and others without, in non-small cell lung cancer (NSCLC) including chemotherapy in previously untreated patients with NSCLC. [Press release from Merck & Co., Inc. discussing research presented at the 52^nd Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

Xcovery Presents Results of Plasma Genotyping of Patients in the eXalt2 Study

Xcovery announced that results from an expansion cohort in the ongoing Phase I/II clinical study of its investigational tyrosine kinase inhibitor, ensartinib, in patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer were presented [Press release from Xcovery discussing research presented at the 52^nd Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

New Data on Olmutinib (BI 1482694) Presented Underscores Clinical Potential of Boehringer Ingelheim’s Next Generation Lung Cancer Compound

Boehringer Ingelheim will announce updated results from the Phase II part of the HM-EMSI-101 trial. [Press release from Boehringer Ingelheim GmbH discussing research presented at the 52^nd Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago] Press Release

Boehringer Ingelheim and Harvard Scientists Establish a Research Alliance to Find Novel Treatments for Severe Fibrotic Diseases

Boehringer Ingelheim announced it has established a research collaboration with the Harvard Stem Cell Institute’s – Harvard Fibrosis Network to discover new ways of treating fibrotic diseases such as idiopathic pulmonary fibrosis, chronic kidney disease and nonalcoholic steatohepatitis. [Boehringer Ingelheim GmbH] Press Release

MD Anderson and Bristol-Myers Squibb Announce New Research Collaboration in Immuno-Oncology Focused on Lung Cancer

Bristol-Myers Squibb Company and The University of Texas MD Anderson Cancer Center announced a new clinical research collaboration to evaluate innovative strategies for the potential use of Bristol-Myers Squibb’s immuno-oncology agents Opdivo and Yervoy to treat early- and advanced-stage lung cancer patients. [The University of Texas MD Anderson Cancer Center] Press Release

Boehringer Ingelheim Launches Ambitious ELUXA Trial Program to Broadly Investigate Promising Lung Cancer Compound Olmutinib

Boehringer Ingelheim has initiated the ELUXA trial program, designed to further investigate the therapeutic potential of olmutinib, a novel third-generation, epidermal growth factor receptor (EGFR) mutation-specific tyrosine kinase inhibitor for the treatment of EGFR mutation-positive non-small cell lung cancer. [Boehringer Ingelheim GmbH] Press Release

NEW Gordon Research Conference – Tissue Niches & Resident Stem Cells in Adult Epithelia
August 7-12, 2016
Hong Kong, China

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

NEW Postdoctoral Fellow – Cancer Immunobiology and Immunotherapy (Roswell Park Cancer Institute)

Scientific Communications and Publishing Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Cancer Immunology and Immunotherapy (Oslo University Hospital)

Postdoctoral Fellow – Vascular/Lung Biology (Yale University School of Medicine)

Postdoctoral Fellow – Lung Cancer (German Cancer Research Center)

Postdoctoral Position – Lung Alveolar Epithelial Cell Biology/Differentiation (University of Southern California)

Postdoctoral Researcher – Biochemistry/Molecular Biology (National Jewish Health)

Postdoctoral Fellow – Immunology (New York University Medical Center)

Postdoctoral Fellow – Lung Disease (Oklahoma State University)

Postdoctoral Fellow – Cell Biology (University of Chicago)

Director Clinical Research – Medical Oncology (Fred Hutchinson Cancer Research Center)

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