Pulmonary Cell News Volume 2.35 | Sep 5 2013

Cigarette Smoke Enhances Human Rhinovirus-Induced CXCL8 Production via HuR-Mediated mRNA Stabilization in Human Airway Epithelial Cells
Primary human bronchial epithelial cells were cultured and treated with cigarette smoke extract (CSE) alone, human rhinovirus (HRV) alone or the combination of the two stimuli. Scientists showed that total expression of stabilizing/de-stabilizing proteins linked to CXCL8 regulation, including adenine/uridine-rich factor-1, KH-type splicing regulatory protein and human antigen R, are not altered by CSE, HRV or the combination of the two stimuli. [Respir Res] Abstract | Full Article

The Chitinase-Like Protein YKL-40 Increases Mucin5AC Production in Human Bronchial Epithelial Cells
Scientists explored the effect of YKL-40 on mucin5AC (MUC5AC) production in chronic inflammatory airway diseases and the potential signaling pathways involved in this process. They found that elevated YKL-40 levels increased the mRNA and protein expression of MUC5AC in a dose- and time-dependent manner, in association with the phosphorylation of extracellular signal-regulated kinase and nuclear factor ?B, reflecting their activation. [Exp Cell Res] Abstract

Effect of Apical Hyperosmotic Sodium Challenge and Amiloride on Sodium Transport in Human Bronchial Epithelial Cells from Cystic Fibrosis Donors
Hypertonic saline inhalation therapy benefits Cystic Fibrosis patients. Surprisingly, these benefits are long-lasting and are diminished by the epithelial Na⁺ channel blocker amiloride. Researchers aimed to explain these effects. [Am J Physiol Cell Physiol] Abstract

Rapamycin Regulates Connective Tissue Growth Factor Expression of Lung Epithelial Cells via Phosphoinositide 3-Kinase
Scientists determined the role of rapamycin in regulating epithelial cell migration and connective tissue growth factor (CTGF) expression. It was found that treatment of A549 and normal human alveolar or bronchial epithelial cells with rapamycin significantly promoted basal or transforming growth factor-ß1 induced CTGF expression. [Exp Biol Med] Abstract

Restoration of the Normal Clara Cell Phenotype after Chronic Allergic Inflammation
Bronchiolar Clara cells play a critical role in lung homoeostasis. Researchers evaluated the effects of chronic allergy on these cells and the efficacy of budesonide and montelukast in restoring their typical phenotypes after ovalbumin-induced chronic allergy in mice. [Int J Exp Pathol] Abstract

LUNG CANCER

Inhibition of Tumor Growth and Metastasis in Non-Small Cell Lung Cancer by LY2801653, an Inhibitor of Several Oncokinases, Including MET
Mechanistic studies demonstrated that treatment with LY2801653 inhibited the constitutive activation of MET-pathway signaling and resulted in inhibition of NCI-H441 cell proliferation, anchorage-independent growth, migration, and invasion. [Clin Cancer Res] Abstract

Pro Tumorigenic Actions of S100A2 Involves Regulation of PI3/Akt Signaling and Functional Interaction with Smad3
Investigators demonstrated that over expression of S100A2 in A549 lung cancer cells induced epithelial-mesenchymal transition followed by increased invasion, loose colony morphology in soft agar and enhanced Akt phosphorylation. [Carcinogenesis] Abstract

Cisplatin-Induced Downregulation of SOX1 Increases Drug Resistance by Activating Autophagy in Non-Small Cell Lung Cancer Cell
Scientists tested the hypothesis that cisplatin resistance is associated with alteration of SOX1 expression in non-small cell lung cancer. The level of SOX1 mRNA in cisplatin resistance cells was markedly reduced when compared to parental cells. [Biochem Biophys Res Commun] Abstract

IGF-1R/Epithelial-to-Mesenchymal Transition (EMT) Crosstalk Suppresses the Erlotinib-Sensitizing Effect of EGFR Exon 19 Deletion Mutations
Using non-small cell lung carcinoma cells harboring the erlotinib-sensitizing epidermal growth factor receptor (EGFR) exon 19 mutation delE746-A750, researchers developed erlotinib-refractory derivatives in which hyperactive insulin-like growth factor-1 receptor (IGF-1R) signaling associated with enrichment in EMT-related morphological and transcriptional features. [Sci Rep] Full Article

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Pfizer Completes Pneumococcal Pneumonia Case Accrual for CAPiTA, Adult Vaccine Clinical Trial of Prevenar 13
Pfizer Inc. announced the completion of pneumonia case accrual in the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) 65 years of age and older. CAPiTA was designed to evaluate whether Prevenar 13 is effective in preventing community-acquired pneumonia caused by the 13 pneumococcal serotypes included in the vaccine. [Pfizer Inc.] Press Release

Theravance Announces Positive Results from Phase IIb Study 0091 with Its LAMA Candidate, TD-4208, for the Treatment of COPD
Theravance, Inc. announced positive topline results from a dose-ranging 7-day cross-over design Phase IIb study of TD-4208, an investigational long-acting muscarinic antagonist (LAMA), administered once-a-day as a nebulized aqueous solution in patients with moderate to severe chronic obstructive pulmonary disease (COPD). [Theravance, Inc.] Press Release

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