Volume 2.25 | Jun 27

Pulmonary Cell News 2.25 June 27, 2013
Pulmonary Cell News
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Towards a Rational Combination Therapy of Cystic Fibrosis: How Cystamine Restores the Stability of Mutant CFTR
Scientists demonstrated that the pharmacological inhibition of wild-type cystic fibrosis transmembrane conductance regulator (CFTR), in bronchial epithelial cells decreases the stability of the CFTR protein by inhibiting autophagy, elevating the abundance of SQSTM1/p62 and its interaction with CFTR at the plasma membrane, increasing the ubiqutination of CFTR, stimulating the lysosomal degradation of CFTR and avoiding its recycling. [Autophagy] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
The Effect of PPAR-? Ligands on In Vitro and In Vivo Models of COPD
The anti-inflammatory potential of peroxisome proliferator-activated receptor (PPAR)-? ligands, rosiglitazone and pioglitazone, were investigated using in vitro alveolar macrophage models and in vivo animal models relevant to COPD. PPAR-? protein expression was similar in COPD patients compared to controls, although increased gene expression levels were observed in COPD patients and smokers compared to never smokers. [Eur Respir J] Abstract

Novel Amino-Carbonitrile-Pyrazole Identified in a Small Molecule Screen Activates Wild Type and ?F508-CFTR in the Absence of a cAMP Agonist
Scientists developed a phenotype-based high-throughput screen to identify small-molecule activators of human airway epithelial Ca2+-activated Cl channels for cystic fibrosis (CF) therapy. Cact-A1 produced large and sustained CF transmembrane conductance regulator (CFTR) Cl currents in CFTR-expressing Fisher rat thyroid cells and in primary cultures of human bronchial epithelial cells, without increasing intracellular cAMP and in the absence of a cAMP agonist. [Mol Pharmacol] Abstract

Sugar Administration Is an Effective Adjunctive Therapy in the Treatment of Pseudomonas aeruginosa Pneumonia
Researchers described a novel adjunctive therapy in which administration of a mix of simple sugars – mannose, fucose, and galactose – inhibits bacterial attachment and lung damage, and potentiates standard antibiotic therapy. The sugar mixture inhibits adhesion of non-mucoid and mucoid P. aeruginosa strains to bronchial epithelial cells in vitro. [Am J Physiol Lung Cell Mol Physiol] Abstract

All-Trans Retinoic Acid Attenuates Airway Inflammation by Inhibiting Th2 and Th17 Response in Experimental Allergic Asthma
Scientists investigated the effects of all-trans retinoic acid (ATRA) in a mouse model of allergic airway inflammation. They showed that ATRA inhibited T helper (Th)17 and promoted inducible regulatory T-cell differentiation, whereas it did not induce an obvious effect on Th2 differentiation in vitro. [BMC Immunol] Abstract | Full Article

Relative Proximity of Chromosome Territories Influences Chromosome Exchange Partners in Radiation-Induced Chromosome Rearrangements in Primary Human Bronchial Epithelial Cells
Scientists characterized the complexity of radiation-induced chromosome exchanges in normal human bronchial epithelial (NHBE) cells by M-FISH analysis of PCC spreads and correlated the exchanges induced with their preferred interphase position, as determined by 1/2-colour 2D-FISH analysis, at the time of irradiation. They found that the frequency and complexity of aberrations induced were reduced in ellipsoid NHBE cells in comparison to previous observations in spherical cells, consistent with aberration complexity being dependent upon the number and proximity of damaged chromosome territories. [Mutat Res]
Full Article


ATP Citrate Lyase Knockdown Impacts Cancer Stem Cells In Vitro
Because epithelial-mesenchymal transition is often associated with processes that induce stemness, researchers hypothesized that ATP citrate lyase knockdown impacts cancer stem cells. By assessing tumorsphere formation and expression of stem cell markers, they showed this to be the case in A549 cells, which harbor a Ras mutation, and in two other non-small-cell lung cancer cell lines, H1975 and H1650, driven by activating EGFR mutations. [Cell Death Dis] Full Article

Genome-Wide Transcriptional Analysis of Apoptosis-Related Genes and Pathways Regulated by H2AX in Lung Cancer A549 Cells
The detailed mechanism and epigenetic regulation by H2AX remain elusive in cancer cells. Researchers showed that H2AX was involved in apoptosis of lung cancer A549 cells as in other tumor cells. Knockdown of H2AX strongly suppressed apoptosis of A549 cells. [Apoptosis] Abstract

Migration-Stimulating Factor (MSF) Is Over-Expressed in Non-Small Cell Lung Cancer and Promotes Cell Migration and Invasion in A549 Cells Over-Expressing MSF
To examine the effect of MSF on invasiveness, MSF was upregulated in A549 cells. Scientists demonstrated that migration and invasion of A549 cells increased substantially after upregulating MSF although proliferation remained unchanged. [Exp Cell Res] Abstract

Parthenolide Reverses Doxorubicin Resistance in Human Lung Carcinoma A549 Cells by Attenuating NF-?B Activation and HSP70 Up-Regulation
Parthenolide (PN), a naturally occurring small molecule found in the herb feverfew, has been used in clinical treatment. Although its importance in treating the chemotherapy resistance has been shown, the pharmacological benefits of PN for lung cancer with multidrug resistance are underappreciated. Using human lung epithelial carcinoma A549 and A549 derived DOX-resistant A549/DOX cell lines, scientists found that PN enhanced the apoptotic cytotoxicity of DOX in A549/DOX cells. [Toxicol Lett] Abstract

Down-Regulation of Ribosomal Protein L22 in Non-Small Cell Lung Cancer
Researchers compared the expression of ribosomal protein L22 (RPL22) gene in non-small cell lung cancer (NSCLC) tissues, plasma as well as human lung cancer cell line LTEP-a-2 with that in normal lung tissues and cells, using real-time RT-qPCR, Western blot, quantitative immunohistochemistry analysis, and ELISA. Their studies showed that the expression of RPL22 was significantly down-regulated in mRNA and protein expression level in NSCLC; however, there was no significant difference of RPL22 levels in plasma between normal and NSCLC patients. [Med Oncol] Abstract

Video Protocol: Mucociliary Differentiation of Primary Bronchial Epithelial Cells
The Role of Type 2 Innate Lymphoid Cells in Asthma
The authors review the recent data regarding innate lymphoid cells and their role in asthma. [J Leukoc Biol] Abstract

Crizotinib in the Treatment of Non-Small-Cell Lung Cancer
The authors give an overview of the molecular pathogenesis of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC), the pharmacokinetic and pharmacodynamic properties of crizotinib, and clinical trials of crizotinib for ALK-rearranged NSCLC. [Clin Lung Cancer] Abstract

Visit our reviews page to see a complete list of reviews in the pulmonary cell research field.
KaloBios Provides Update on Pipeline of Clinical Programs
KaloBios Pharmaceuticals, Inc. provided an update on the status of its ongoing clinical programs for KB003, KB001-A and KB004, its pipeline of proprietary monoclonal antibodies in development for severe respiratory diseases and cancer. [KaloBios Pharmaceuticals, Inc.] Press Release

Morphotek, Inc. Announces Initiation of a Phase I Study for MORAb-066
Morphotek®, Inc., announced that the Sarah Cannon Research Institute in Nashville, Tennessee has opened enrollment in a Phase I clinical study with MORAb-066 in patients with advanced or metastatic breast, pancreatic, colorectal or non-small cell lung cancer (adenocarcinoma) malignancies. The open-label Phase I study will assess the safety, tolerability and pharmacokinetics of MORAb-066 administered with weekly intravenous infusions. [Morphotek, Inc.] Press Release

LCA Applauds New Evidence Supporting Lung Screening
Lung Cancer Alliance (LCA) applauded a long awaited cost-benefit analysis, presented at a meeting of the National Cancer Institute’s Board of Scientific Advisors and National Cancer Advisory Board, which concluded that a CT lung cancer screening program based on NCI’s lung cancer screening trial meets generally accepted criteria for cost-effectiveness of a screening test. [Lung Cancer Alliance] Press Release

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NEW The 20th British Association for Lung Research Summer Meeting 2013
July 10-12, 2013
Nottingham, United Kingdom

Visit our events page to see a complete list of events in the pulmonary cell community.
NEW Postdoctoral Fellow – Translational Oncology (The University of Texas MD Anderson Cancer Center)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

Postdoctoral Position – Idiopathic Pulmonary Fibrosis (MedImmune UK Ltd)

Postdoctoral Position – Lung Development and Repair (Boston University Pulmonary Center)

PhD Studentships – Pulmonary Biology and Medicine (University of Giessen and Marburg Lung Center)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

Postdoctoral Position – Cardiopulmonary Molecular Biology (Hannover Medical School)

PhD Opportunity – Biofunctionalization of Liposomes for Tumor-Targeted Drug Delivery (University of East Anglia)

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