Pulmonary Cell News Volume 2.20 | May 23 2013

Prothymosin α Overexpression Contributes to the Development of Pulmonary Emphysema
Scientists showed that prothymosin α contributes to the pathogenesis of emphysema by increasing acetylation of histones and nuclear factor-kappaB, particularly upon cigarette smoke exposure. They found a positive correlation between prothymosin α levels and the severity of emphysema in prothymosin α transgenic mice and emphysema patients. [Nat Commun] Full Article

MicroRNA-135b Promotes Lung Cancer Metastasis by Regulating Multiple Targets in the Hippo Pathway and LZTS1
Researchers identified an intronic microRNA, miR-135b that is upregulated in highly invasive non-small-cell lung cancer cells. Expression of miR-135b enhances cancer cell invasive and migratory abilities in vitro and promotes cancer metastasis in vivo, while specific inhibition of miR-135b by a miR-135b-specific molecular sponge and antagomirs suppresses cancer cell invasion, orthotopic lung tumor growth and metastasis in a mouse model. [Nat Commun] Abstract

PKC Activation Induces Inflammatory Response and Cell Death in Human Bronchial Epithelial Cells
Investigators stimulated human bronchial lung epithelial cells with the phorbol ester Phorbol 12, 13-dibutyrate, and examined gene expression profile using microarrays. Microarray analysis suggests that protein kinase C (PKC) activation induced dramatic changes in gene expression related to multiple cellular functions. [PLoS One] Full Article

Lipoxin A₄ Mediated K_ATP Potassium Channel Activation Results in Cystic Fibrosis Airway Epithelial Repair
Researchers investigated the ability of Lipoxin A₄ to trigger epithelial repair through the initiation of proliferation and migration in non-cystic fibrosis (CF) and CF airway epithelia. Spontaneous repair and cell migration were significantly slower in CF epithelial cultures compared to controls. [Am J Physiol-Lung C] Abstract

Reduced Chromosome Aberration Complexity in Normal Human Bronchial Epithelial Cells Exposed to Low-LET γ-Rays and High-LET α-Particles
Researchers exposed normal human bronchial lung epithelial cells in vitro to 0.5 and 1 Gy low-linear energy transfer (LET) γ-rays and a low fluence of high-LET α-particles and assayed for chromosome aberrations in premature chromosome condensation spreads by 24-color multiplex-fluorescence in situ hybridization. [Int J Radiat Biol] Abstract

Essential Regulation of Lung Surfactant Homeostasis by the Orphan G Protein-Coupled Receptor GPR116
GPR116 expression analysis, bone marrow transplantation studies, and characterization of conditional knockout mice revealed that GPR116 expression in ATII cells is required for maintaining normal surfactant levels. [Cell Rep] Abstract | Graphical Abstract | Full Article

LUNG CANCER

The Ubiquitin-CXCR4 Axis Plays an Important Role in Acute Lung-Infection-Enhanced Lung Tumor Metastasis
The authors combined bacteria- and lipopolysaccharide (LPS)-induced acute lung injury/inflammation mouse models with mouse metastatic models to study the effect of acute inflammation on lung metastasis in mice. Both bacteria- and LPS-induced acute lung injury/inflammation significantly enhanced lung metastasis of four tail vein-injected mouse tumor cell lines. [Clin Cancer Res] Abstract

Deubiquitinase Inhibition of 19S Regulatory Particles by 4-Arylidene Curcumin Analogue AC17 Causes NF-κB Inhibition and p53 Reactivation in Human Lung Cancer Cells
The authors described the deubiquitinase inhibition of 19S regulatory particles by AC17, a 4-arylidene curcumin analogue synthesized in their laboratory. Although 4-arylidene curcumin analogues were reported to act as IκB kinase inhibitors, AC17 instead induced a rapid and marked accumulation of ubiquitinated proteins without inhibiting proteasome proteolytic activities. [Mol Cancer Ther] Abstract

mTOR Inhibitors Control the Growth of EGFR Mutant Lung Cancer Even after Acquiring Resistance by HGF
Scientists examined whether two clinically approved mammalian target of rapamycin (mTOR) inhibitors, temsirolimus and everolimus, overcome hepatocyte growth factor (HGF)-dependent resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in EGFR mutant lung cancer cells. Both temsirolimus and everolimus inhibited the phosphorylation of p70S6K and 4E-BP1, which are downstream targets of the mTOR pathway, and reduced the viability of EGFR mutant lung cancer cells, PC-9, and HCC827, even in the presence of HGF in vitro. [PLoS One] Full Article

High Expression of PRDM14 Correlates with Cell Differentiation and Is a Novel Prognostic Marker in Resected Non-Small Cell Lung Cancer
Researchers determined the frequency and prognostic significance of PRDI-BF1 and RIZ domain containing proteins (PRDM)1 and PRDM14 expression in a cohort of surgically resected non-small cell lung cancer patients. Increased expression of PRDM14 correlated with differentiation of tumor cells significantly. [Med Oncol] Abstract

Phase III Results: Tiotropium Respimat® Effective in Symptomatic Asthma Patients Despite at Least ICS/LABA Independent of Their Age, Allergic Status, Smoking Status and Bronchodilator Response
In patients with symptomatic asthma despite at least ICS/LABA therapy, tiotropium delivered by the Respimat® SoftMist^TM Inhaler increases time to first severe exacerbation and first episode of asthma worsening. This improvement is independent of age, allergic status, smoking status and bronchodilator response. [Press release from Boehringer Ingelheim GmbH discussing research presented at the 2013 American Thoracic Society International Conference, Philadelphia] Press Release

Promedior Presents Encouraging Results from Clinical Study of PRM-151 in Patients with Idiopathic Pulmonary Fibrosis
Promedior, Inc. unveiled data from a clinical study of PRM-151. The clinical data from a randomized, double-blind, placebo controlled Phase Ib multiple ascending dose study showed that PRM-151 was generally safe and well tolerated in patients with idiopathic pulmonary fibrosis. [Press release from Promedior, Inc. discussing research presented at the 2013 American Thoracic Society International Conference, Philadelphia] Press Release

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Grifols, S.A. and Aradigm Corporation Announce Signing of Worldwide Licensing Agreement to Develop and Commercialize Pulmaquin™
Grifols, S.A. and Aradigm Corporation announced the signing of an exclusive, worldwide license for Aradigm’s proprietary formulations of inhaled ciprofloxacin (Pulmaquin and Lipoquin™) for the treatment of severe respiratory diseases, including non-cystic fibrosis bronchiectasis (BE). Aradigm has completed Phase IIb clinical trials in BE patients with Pulmaquin and Lipoquin. [Aradigm Corporation] Press Release

Maryland Stem Cell Research Commission Funds 31 New Research Proposals in FY 2013
The Maryland Stem Cell Research Commission has completed its review of the 171 applications received in response to its FY 2013 Requests for Applications. The board of directors of the Maryland Technology Development Corporation approved the Commission’s recommendation to fund 31 new proposals with the Maryland Stem Cell Research Fund’s $10.4 million FY2013 budget. [Maryland Stem Cell Research Fund] Press Release

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Therapeutic Goods Administration (Australia)

NEW The European Cancer Congress 2013
September 27-October 1, 2013
Amsterdam, Netherlands

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

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

PhD Studentship – Pulmonary Medicine (Erasmus MC)

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

Postdoctoral Position – Respiratory Research (INSERM)

Postdoctoral Researcher – Sensory Pathways in Mammalian Airway Epithelia (Washington University)

Postdoctoral Position – Cardiopulmonary Molecular Biology (Hannover Medical School)

Post-doctoral Position – Mucosal Immunology (University of Southern California)

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

Postdoctoral Position – Pulmonary Research (Cedars-Sinai Medical Center)

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