Pulmonary pharmacology & therapeutics
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Pulm Pharmacol Ther · Jun 2014
Iron laden macrophages in idiopathic pulmonary fibrosis: the telltale of occult alveolar hemorrhage?
A number of observations suggest that iron accumulates in the lungs of patients with idiopathic pulmonary fibrosis (IPF) with vascular abnormalities, including pulmonary hypertension. ⋯ The data show exaggerated accumulation of iron in IPF broncho-alveolar ELF and alveolar cells with no association with tobacco smoke, thus suggesting, occult pulmonary hemorrhage as a likely cause.
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Pulm Pharmacol Ther · Jun 2014
β-Catenin overexpression is associated with gefitinib resistance in non-small cell lung cancer cells.
Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) presents great challenges in the treatment of non-small cell lung cancer (NSCLC) patients, while the mechanisms are still not well understood. The β-catenin signaling pathway has been found to be associated with chemoresistance and can activate the EGFR and its downstream pathways. This study aimed to investigate the role of β-catenin in acquired resistance to EGFR-TKIs in NSCLC cell lines. ⋯ β-catenin plays an important role in acquired resistance to EGFR-TKIs in NSCLC cell lines and may be a potential therapeutic target for NSCLC patients who have failed to respond to targeted therapy.
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Pulm Pharmacol Ther · Jun 2014
18:1/18:1-Dioleoyl-phosphatidylglycerol prevents alveolar epithelial apoptosis and profibrotic stimulus in a neonatal piglet model of acute respiratory distress syndrome.
18:1/18:1-Dioleoyl-phosphatidylgycerol (DOPG) is a surfactant phospholipid that is nearly non-detectable in neonatal surfactant films. When alveolar macrophages are exposed to DOPG in vitro, secretory phospholipase A2 (sPLA2) production is blocked, resulting in suppressed macrophage activity and improved surfactant function. We investigated whether the addition of DOPG to a commercially available surfactant preparation would improve lung function in a neonatal piglet model of acute respiratory distress syndrome. ⋯ We conclude that surfactant fortified by DOPG preserves lung function, and prevents alveolar epithelial injury and fibrous stimulus by reduction of sPLA2 in a neonatal model of acute respiratory distress syndrome without any relevant discernable side effects. Hence, DOPG supplementation in a neonatal lung exerts important function protecting effects and seems to be justified in cases of overwhelming pulmonary inflammation.