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The aim of this study was to assess the association of serum C-reactive protein (CRP) levels with outcomes in 81 patients with epidermal growth factor receptor (EGFR)-mutated non-small cell...

Cigarette smoke (CS) causes both pulmonary and extrapulmonary disorders.To determine the pulmonary and extrapulmonary effects of acute CS exposure in regard to inflammation, oxidative stress and DNA damage.Mice were exposed to CS for 10 days and then their lungs, heart, liver, pancreas, kidneys, gastrocnemius muscle and subcutaneous (inguinal and flank) and visceral (retroperitoneum and periuterus) adipose tissues were excised. Bronchoalveolar lavage fluid samples were obtained for differential cell analysis. Inflammatory cell infiltration of the tissues was assessed by immunohistochemistry for Mac-3(+) cells, F4/80(+) cells and CD45(+) cells. Oxidative stress was determined by immunohistochemistry for thymidine glycol (a marker of DNA peroxidation) and 4-hydroxy hexenal (a marker of lipid peroxidation), by enzyme-linked immunosorbent assay for protein carbonyls (a marker of protein peroxidation) and by measurements of enzyme activities of glutathione peroxidase, superoxide dismutase and catalase. DNA double-strand breaks were assessed by immunohistochemistry for γH2AX.CS exposure-induced inflammatory cell infiltration, oxidative stress and DNA damage in the lung. Neither inflammatory cell infiltration nor DNA damage was observed in any extrapulmonary organs. However, oxidative stress was increased in the heart and inguinal adipose tissue.Induction of inflammatory cell infiltration and DNA damage by acute CS exposure was confined to the lung. However, an increased oxidative burden occurred in the heart and some adipose tissue, as well as in the lung.Although extrapulmonary effects of CS are relatively modest compared with the pulmonary effects, some extrapulmonary organs are vulnerable to CS-induced oxidative stress.

Transforming growth factor-beta (TGF-beta) is believed to play a central role in fibroblastic wound repair and subsequent scar formation. Fibroblasts undergo apoptosis as granulation tissue evolves into a scar. To determine whether TGF-beta influences fibroblast apoptosis, human lung fibroblasts (IMR-90) were treated with TGF-beta (2 to 10 ng/mL) and then exposed to H(2)O(2) (50 to 150 microM), an inducer of fibroblast apoptosis. Apoptosis was evaluated by nuclear staining with Hoechst33342 and terminal deoxynucleotidyl transferase (TdT)-mediated nucleotide nick-end labeling. TGF-beta alone did not induce fibroblast apoptosis, but it dose-dependently augmented the apoptosis induced by exposure to H(2)O(2). TGF-beta also increased the intracellular level of peroxides measured with carboxydichlorodihydrofluorescein, but it did not affect the protein levels of Bcl-2, Bax, Bad, or p53 proteins. These results suggest that TGF-beta promotes lung fibroblast apoptosis induced by H(2)O(2), probably by increasing intracellular peroxides. Thus, TGF-beta may promote the elimination of fibroblasts from wounds, particularly under conditions of exposure to enhanced oxidative stress in the lung.

The purpose of this study was to examine how lungs in early postnatal animals that are administered bromodeoxyuridine (BrdU), a thymidine analog known to be a cytogenetically toxic agent, change in adult life. BrdU was injected (1 mg/g body weight) intraperitoneally in suckling rats on day 6 after birth. Immunohistochemical studies revealed that BrdU was incorporated in alveolar cells, and infrequently in the mesothelium, endothelium, and bronchiolar epithelium. The number (per high-power field) of alveolar cells incorporating BrdU was 8.76 +/- 0.50 in the interstitium and 1.66 +/- 0.25 in the epithelium. The animals were sacrificed at 2 and 8 weeks and 12 months of age. Control animals were treated the same as the BrdU-treated animals except for the injection of BrdU. Body weight, body size (nose-tail length), and lung weight were identical between BrdU-treated animals and control animals at all experimental periods. The histopathology and physiology of these lungs were studied. At 2 weeks of age, the BrdU-treated animals appeared morphologically and functionally similar to control animals. At 8 weeks and 12 months of age, the lungs in the BrdU-treated animals showed abnormal enlargement of the airspace, few alveoli, and less complexity in pulmonary architecture with or without increased lung compliance. These findings suggest that lung injured cytogenetically in early postnatal life may develop functional and structural abnormalities in later life.