Volume 3.38 | Oct 2

Pulmonary Cell News 3.38 October 2, 2014
Pulmonary Cell News
     In this issue: Publications | Reviews | Science News | Industry News | Policy News | Events | Jobs
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TOP STORY
ASCL1 Is a Lineage Oncogene Providing Therapeutic Targets for High-Grade Neuroendocrine Lung Cancers
Scientists discovered an achaete-scute homolog 1 (ASCL1) target 72-gene expression signature that identifies neuroendocrine differentiation in non-small cell lung cancer (NSCLC) cell lines, is predictive of poor prognosis in resected NSCLC specimens from three datasets, and represents novel “druggable” targets. [Proc Natl Acad Sci USA] Abstract | Full Article
Model the Human Respiratory Epithelium with PneumaCult™-ALI. Click to View Data.
 
PUBLICATIONS (Ranked by impact factor of the journal)
Hyperoxia Inhibits Nitric Oxide Treatment Effects in Alveolar Epithelial Cells via Effects on L-Type Amino Acid Transporter-1
Hyperoxia impaired nitric oxide effects on S-nitrosothiol accumulation and soluble guanylyl cyclase activation in proportion to the magnitude of hyperoxia and the duration of exposure, up to 12 hours, in type I-like and type II-like rat and human alveolar epithelial cells. [Antioxid Redox Signal] Abstract

Cathepsin B Contributes to Na+ Hyperabsorption in Cystic Fibrosis Airway Epithelial Cultures
In bronchial epithelia from both normal and cystic fibrosis (CF) donor lungs, cathepsin B (CTSB) localized to the apical membrane. In normal and CF human bronchial epithelial cultures, CTSB was detected at the apical plasma membrane and in the airway surface liquid. [J Physiol] Abstract

Oxidative Stress Regulates CFTR Gene Expression in Human Airway Epithelial Cells through a Distal Antioxidant Response Element
Cystic fibrosis transmembrane conductance regulator gene (CFTR) expression in human airway epithelial cells involves the recruitment of distal cis-regulatory elements, which are associated with airway-selective DNase hypersensitive sites at -44kb and -35kb from the gene. Scientists investigated the -44 kb element, which also has enhancer activity in vitro in airway epithelial cells but is inactive in intestinal epithelial cells. [Am J Respir Cell Mol Biol] Abstract

Phospholipase Cε, an Effector of Ras and Rap Small GTPases, Is Required for Airway Inflammatory Response in a Mouse Model of Bronchial Asthma
Primary-cultured bronchial epithelial cells prepared from phospholipase Cε (PLCε)ΔX/ΔX mice showed attenuated pro-inflammatory cytokine production when stimulated with tumor necrosis factor-α, suggesting that reduced cytokine production in PLCεΔX/ΔX mice was due to cell-autonomous effect of PLCε deficiency. [PLoS One]
Full Article

Insulin Upregulates the Expression of Epithelial Sodium Channel In Vitro and in a Mouse Model of Acute Lung Injury: Role of mTORC2/SGK1 Pathway
In alveolar epithelial cells, insulin increased the expression of α-, β-, and γ-epithelial sodium channel, which was blocked by the mammalian target of rapamycin complex 2 (mTORC2) inhibitor or knockdown of Rictor, and serum and glucocorticoid induced kinase-1 (SGK1) inhibitor, respectively. [Exp Cell Res] Abstract

Stanniocalcin-1 Is Induced by Hypoxia Inducible Factor in Rat Alveolar Epithelial Cells
Scientists found that stanniocalcin-1 (STC1) was induced by hypoxia and hypoxia inducible factor in rat alveolar type II cells, and this induction occurred rapidly and reversibly. They also show that recombinant human STC1 enhanced cell motility with extended lamellipodia formation in alveolar epithelial cell monolayers but did not inhibit the oxidative damage induced by LPS. [Biochem Biophys Res Commun] Abstract

LUNG CANCER

Tissue Inhibitor of Metalloproteinases-1 Induces a Pro-Tumorigenic Increase of miR-210 in Lung Adenocarcinoma Cells and Their Exosomes
Researchers demonstrate that an increase of both exogenous and endogenous tissue inhibitor of metalloproteinases-1 led to the upregulation of miR-210 in a CD63/PI3K/AKT/HIF-1-dependent pathway in lung adenocarcinoma cells. [Oncogene] Abstract

RET Mutation and Expression in Small-Cell Lung Cancer
Stable overexpression of both mutant M918T and wild-type RET in two small-cell lung cancer cell lines, H1048 and SW1271, activated ERK signaling, MYC expression, and increased cell proliferation, particularly by mutant RET. [J Thorac Oncol] Full Article

miR-630 Inhibits Proliferation by Targeting CDC7 Kinase, but Maintains the Apoptotic Balance by Targeting Multiple Modulators in Human Lung Cancer A549 Cells
Scientists found that microRNA-630 (miR-630) was highly expressed in A549 and NIH3T3 cells where cell-cycle kinase 7 (CDC7) was downregulated, but lower in H1299, MCF7, MDA-MB-231, HeLa and 2BS cells where CDC7 was upregulated. The induction of miR-630 occurred commonly in a variety of human cancer and immortalized cells in response to genotoxic agents. [Cell Death Dis] Full Article

MicroRNA-191, by Promoting the EMT and Increasing CSC-Like Properties, Is Involved in Neoplastic and Metastatic Properties of Transformed Human Bronchial Epithelial Cells
High-throughput microarray analysis showed that 51 microRNAs were differentially expressed in transformed human bronchial epithelial (HBE) cells relative to normal HBE cells. In particular, microRNA-191 was up-regulated in transformed cells. [Mol Carcinog] Abstract

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REVIEWS
Advances in Pharmacotherapy of Small Cell Lung Cancer
For patients with extensive-stage small cell lung cancer (SCLC), survival can be increased with combination platinum-based chemotherapy, but the disease remains incurable. The author looks at the current advances in pharmacotherapy for SCLC. [Expert Opin Pharmacother] Abstract

Molecular Biomarkers in Idiopathic Pulmonary Fibrosis
Currently, there are no molecular biomarkers in widespread clinical use for idiopathic pulmonary fibrosis (IPF), and the search for potential markers remains in its infancy. Proposed core mechanisms in the pathogenesis of IPF for which candidate markers have been offered include alveolar epithelial cell dysfunction, immune dysregulation, and fibrogenesis. [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.
 
SCIENCE NEWS
Results of LUX-Lung 8, the Largest Prospective Trial to Compare EGFR TKIs in Patients with Relapsed/Refractory Squamous Cell Carcinoma of the Lung
In the LUX-Lung 8, global, randomized, Phase III study the progression-free survival and disease control rate were significantly better in patients with relapsed/refractory squamous cell carcinoma of the lung treated with afatinib than in those treated with erlotinib. [Press release from European Society for Medical Oncology (ESMO) discussing research presented at the ESMO 2014 Congress, Madrid] Press Release

Adjuvant Treatment with MAGE-A3 Cancer Immunotherapeutic in Patients with Resected NSCLC Does Not Increase Disease-Free Survival
The MAGRIT global trial assessed the efficacy of the recMAGE-A3 + AS15 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small cell lung cancer (NSCLC). In this study, treatment with MAGE-A3 cancer immunotherapeutic did not increase disease-free survival compared to placebo in either the overall population or in patients who did not receive adjuvant chemotherapy. [Press release from European Society for Medical Oncology (ESMO) discussing research presented at the ESMO 2014 Congress, Madrid] Press Release

Customizing Chemotherapy in Lung Cancer: New Phase II Data Reported in Two Late-Breaking Studies
Measuring the expression levels of an enzyme involved in DNA synthesis can help predict the response of lung cancers to certain treatments, a Korean study has shown. [Press release from European Society for Medical Oncology (ESMO) discussing research presented at the ESMO 2014 Congress, Madrid] Press Release

Promising Results Shown with Targeted Approaches in Subsets of Non-Small-Cell Lung Cancer
The BRAF inhibitor dabrafenib has significant anti-tumor activity in patients with advanced BRAF V600E mutant non-small cell lung cancer whose disease has progressed after chemotherapy, according to Phase II data. [Press release from European Society for Medical Oncology (ESMO) discussing research presented at the ESMO 2014 Congress, Madrid] Press Release

Targeted Treatments for Subsets of NSCLC Patients with Folate-Receptor-Positive, BRAF V600E-Mutant, and with Tumors Carrying HER2 Somatic Mutations
Findings from three Phase II studies revealed clinically meaningful improvement across all efficacy endpoints with vintafolide/docetaxel over single-agent docetaxel in second-line treatment of folate-receptor-positive non-small cell lung cancer (NSCLC). [Press release from European Society for Medical Oncology (ESMO) discussing research presented at the ESMO 2014 Congress, Madrid] Press Release

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INDUSTRY NEWS
CytRx Initiates Global Phase IIb Clinical Trial of Aldoxorubicin for the Treatment of Relapsed/Refractory Small Cell Lung Cancer
CytRx Corporation announced the initiation of a global Phase IIb clinical trial evaluating aldoxorubicin compared to topotecan in subjects with extensive-stage small cell lung cancer who have relapsed or were refractory to prior chemotherapy. [CytRx Corporation] Press Release

CytRx Receives Multiple FDA Orphan Drug Designations for Aldoxorubicin for the Treatment of Glioblastoma, Small Cell Lung Cancer and Ovarian Cancer
CytRx Corporation announced that the U.S. Food and Drug Administration (FDA) has granted multiple orphan drug designations for the company’s lead drug candidate, aldoxorubicin, in three indications: glioblastoma multiforme, small cell lung cancer and ovarian cancer. [CytRx Corporation] Press Release

ARIAD’s AP26113 Receives FDA Breakthrough Therapy Designation For ALK+ Non-Small Cell Lung Cancer Resistant to Crizotinib
ARIAD Pharmaceuticals, Inc. announced that its investigational cancer medicine, AP26113, has received Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer who are resistant to crizotinib. [ARIAD Pharmaceuticals, Inc.] Press Release
 
POLICY NEWS
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)
 
EVENTS
NEW Translational Cancer Research for Basic Scientists Workshop
October 26-31, 2014
Boston, United States

Visit our events page to see a complete list of events in the pulmonary cell community.
 
JOB OPPORTUNITIES
NEW PhD Position – Development of a Lung-on-a-Chip (University of Twente)

Postdoctoral Fellow – Experimental Pulmonary Hypertension (Brigham and Women’s Hospital Harvard Medical School)

Investigator – Multiple Positions in Cellular & Molecular Medicine (Cleveland Clinic Lerner Research Institute)

PhD Studentship – Pediatric Respiratory Epidemiology (University of Bern)

Postdoctoral Fellow – Cardiopulmonary Molecular Biology (Hannover Medical School)

Postdoctoral Position – Pulmonary Research (University of Chicago)

Postdoctoral Researcher – Cancer (Ohio State University)

Postdoctoral Research Trainee – Acute Lung Injury (University of Tennessee Health Science Center)

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)


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