Pulmonary Cell News Volume 2.02 | Jan 17 2013

FOXO Transcription Factors Regulate Innate Immune Mechanisms in Respiratory Epithelial Cells
Scientists showed that bacterial pathogens potently activate forkhead box transcription factor family O (FOXO) transcription factors in cultured human respiratory epithelial cells in vitro. Infection of mice with bacterial pathogens resulted in the activation of FOXO transcription factors in alveolar and bronchial epithelial cells in vivo. [J Immunol] Abstract

Targeting Sphingosine Kinase 1 Attenuates Bleomycin-Induced Pulmonary Fibrosis
Researchers showed that knockdown of sphingosine kinase (SphK)1 or treatment with SphK inhibitor attenuated sphingosine-1-phosphate generation and transforming growth factor β secretion in a bleomycin-induced lung fibrosis mouse model that was accompanied by reduced phosphorylation of Smad2 and MAPKs in lung tissue. [FASEB J] Abstract

Alcohol Causes Alveolar Epithelial Oxidative Stress by Inhibiting the Nrf2/ARE Signaling Pathway
Scientists determined that alcohol ingestion in vivo or direct alcohol exposure in vitro down-regulated the Nrf2/ARE pathway in lung epithelial cells, decreased the expression of anti-oxidant genes, and lowered intracellular glutathione levels. [Am J Respir Cell Mol Biol] Abstract

Role of NOX Proteins in Pseudomonas aeruginosa Induced Lung Inflammation and Permeability
Researchers showed that P. aeruginosa lung infection up-regulates NADPH oxidase 2 and NADPH oxidase 4 expression, and reactive oxygen species generation, which play distinct roles in regulating lung inflammation, apoptosis and permeability. [Am J Respir Cell Mol Biol] Abstract
 
Role of β-Catenin-Regulated CCN Matricellular Proteins in Epithelial Repair after Inflammatory Lung Injury
Scientists examined which β-catenin transcriptional coactivators and target genes promote epithelial repair after inflammatory injury. They concluded that β-catenin/p300-dependent expression of WISP1 and Cyr61 is critical for epithelial repair. [Am J Physiol-Lung C] Abstract

Sustained Adenosine Exposure Causes Lung Endothelial Apoptosis: A Possible Contributor to Cigarette Smoke-Induced Endothelial Apoptosis and Lung Injury
Investigators demonstrated that sustained adenosine exposure caused lung endothelial cell apoptosis via nucleoside transporter facilitated, not adenosine receptor mediated, intracellular adenosine uptake, subsequent activation of p38 and JNK in mitochondria, and ultimately mitochondrial defects and activation of mitochondria-mediated intrinsic pathway of apoptosis. [Am J Physiol-Lung C] Abstract

LUNG CANCER

Id1 and Id3 Co-Expression Correlates with Clinical Outcome in Stage III-N2 Non-Small Cell Lung Cancer Patients Treated with Definitive Chemoradiotherapy
Researchers report that Id1 and Id3 co-expression seems associated with a poor clinical outcome in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiotherapy. [J Transl Med] Abstract | Full Article

AEG-1 Expression Characteristics in Human Non-Small Cell Lung Cancer and Its Relationship with Apoptosis
Investigators indicate that astrocyte-elevated gene-1 (AEG-1) played a crucial role in the carcinogenesis of non-small cell lung cancer and could inhibit apoptosis via activating cell survival signaling. [Med Oncol] Abstract

Concomitant High Gene Copy Number and Protein Overexpression of IGF1R and EGFR Negatively Affect Disease-Free Survival of Surgically Resected Non-Small-Cell-Lung Cancer Patients
Insulin-like growth factor 1 receptor (IGF1R) and epidermal growth factor receptor (EGFR) activation are essential to mediate tumor cell survival, proliferation, and invasion. This study investigated the prognostic role of IGF1R and EGFR in surgically resected non-small-cell-lung cancer. [Cancer Chemoth Pharm] Abstract

A Non-Surgical Method for Induction of Lung Cancer in Wistar Rats Using a Combination of NNK and High Dietary Fats
Investigators report the development of a novel rodent model by administering multiple doses of nicotine-derived nitrosamine ketone (NNK) to male Wistar rats and feeding them with high-fat and low-protein diet. Tumor cells in lungs were observed in approximately 98% rats after 8 months of NNK treatment, as evident by histopathological analysis. [Protoplasma] Abstract

KaloBios Initiates Phase II Study with KB001-A Humaneered® Monoclonal Antibody in Cystic Fibrosis Patients
KaloBios Pharmaceuticals, Inc. announced that dosing has begun in a randomized, double-blind, placebo-controlled Phase II clinical trial of KB001-A, the company’s anti-PcrV Humaneered®, PEGylated monoclonal antibody fragment. [KaloBios Pharmaceuticals, Inc.] Press Release

U.S. FDA Grants Priority Review to Boehringer Ingelheim’s Afatinib NDA for EGFR Mutation-Positive Advanced NSCLC
Boehringer Ingelheim announced that the New Drug Application (NDA) for its investigational oncology compound afatinib has been accepted for filing and granted Priority Review by the U.S. Food and Drug Administration (FDA). The application for afatinib is currently under review for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) mutation as detected by an FDA-approved test. [Boehringer Ingelheim, Inc.] Press Release

FDA Accepts Supplemental New Drug Application for Tarceva® (erlotinib) Tablets for Genetically Distinct Form of Advanced Lung Cancer
Astellas Pharma US, Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted for filing a supplemental New Drug Application for Tarceva® (erlotinib) for first-line use in people with locally advanced or metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor activating mutations. [Astellas Pharma US, Inc] Press Release

Genoa Pharmaceuticals and McMaster University to Collaborate on Idiopathic Pulmonary Fibrosis Research
Genoa Pharmaceuticals, announced it is collaborating with Dr. Martin Kolb and researchers at McMaster University to characterize the in vivo advantages and potential clinical impact of Genoa’s lead program, inhaled GP-101 for the treatment of idiopathic pulmonary fibrosis. [PR Newswire Association LLC]
Press Release

National Institutes of Health (United States)

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)

NEW Thomas L. Petty Aspen Lung Conference
June 5-8, 2013
Aurora, United States

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

Scientist or Engineer – hPSC Bioengineer (STEMCELL Technologies, Inc)

Postdoctoral Fellows – Gene, RNA and Epigenetic Regulation, Protein Science, Signal Transduction, Cell and Stem Cell, Cancer and Other Diseases (Shanghai Institute of Biochemistry and Cell Biology)

Postdoctoral Position – Host-Pathogen Interaction at Mucosal Surfaces (Sanford Burnham Medical Research Institute)

Senior Research Scientist – Cell Biology (Biosciences R&I Med)

Postdoctoral Fellow – Mouse Genetics/Cancer Genomics (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellowship – Translational Studies of Interstitial Lung Disease (University of California San Francisco)

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