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Free Radic Biol Med. 2013 Dec;65:859-71. doi: 10.1016/j.freeradbiomed.2013.08.006. Epub 2013 Aug 13.

Oxidative stress and inflammation in the normal airways and blood of patients with lung cancer and COPD.

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1
Pulmonology Department, Muscle and Respiratory System Research Unit, IMIM-Institut Hospital del Mar, Parc de Salut Mar, and Health and Experimental Sciences Department, Universitat Pompeu Fabra, Universitat Autònoma de Barcelona, Parc de Recerca Biomèdica de Barcelona, E-08003 Barcelona, Spain; Centro de Investigación en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Bunyola, Majorca, Balearic Islands, Spain. Electronic address: ebarreiro@imim.es.

Abstract

Respiratory conditions such as chronic obstructive pulmonary disease (COPD) are associated with a greater risk for lung cancer (LC). Oxidative stress and inflammation are involved in LC pathophysiology. Studies conducted so far have focused solely on lung tumor parenchyma and not the airways. We explored levels of local and systemic oxidative stress and inflammation within normal bronchial epithelium and blood of patients with lung cancer (n=52), with and without COPD, and in control subjects (COPD and non-COPD, n=21). In normal bronchial epithelium specimens (bronchoscopy) and blood from patients with similar smoking history (LC-COPD and LC) and control subjects (both COPD and non-COPD), redox balance and inflammatory markers were measured (ELISA and immunoblotting). All subjects were clinically evaluated. Absence of malignant cells within the bronchial specimens was always pathologically confirmed. Bronchial levels of protein carbonylation, MDA-protein adducts, antioxidants, TNF-α, interferon-γ, TGF-β, and VEGF and blood levels of superoxide anion, oxidatively damaged DNA and proteins, TNF-α, interferon-γ, TGF-β, VEGF, and neutrophils were significantly greater in all LC patients compared to control subjects. Systemic levels of oxidatively damaged DNA, superoxide anion, and TNF-α and bronchial levels of TGF-β and TNF-α showed high sensitivity and specificity for LC among patients. Regardless of the presence of an underlying respiratory condition (COPD), protein oxidation, oxidatively damaged DNA, and inflammation were remarkably increased in the normal airways and blood of patients with LC. Furthermore, the potential predictive value for LC development of these molecular events warrants attention and should be explored in future larger longitudinal studies.

KEYWORDS:

Blood; COPD; Free radicals; Lung cancer; Normal bronchial epithelium; Oxidatively damaged DNA and proteins

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