The burden of oxidative stress was observed to increase in COPD patients as judged by urinary 8-OHdG. A depletion of antioxidant vitamins in serum was not essential for this phenomenon. Elevated urinary 8-OHdG level may not be attributable to smoking status or to antioxidant vitamins in COPD.

Cell migration is essential for invasive and metastatic phenotypes of cancer cells. Potential chemopreventive agents of cancer-sulindac sulfide, caffeic acid phenethyl ester (CAPE), curcumin, and (+)-catechin-have been reported to interfere with several types of intracellular signaling. In this study, we examined the effects of these agents on transforming growth factorb(TGF-b)-induced motility and Akt phosphorylation in A549 cells. Judged by gold particle phagokinesis assay, sulindac sulfide, CAPE, and curcumin suppressed the motility of A549 cells promoted by TGF-b. LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt signaling, also suppressed TGF-b-induced motility and Akt phosphorylation. Sulindac sulfide and CAPE, but not curcumin, suppressed TGF-b-induced Akt phosphorylation. We conclude that sulindac sulfide and CAPE suppress the motility promoted by TGF-b in lung adenocarcinoma cells through the suppression of Akt. Our observations raise the possibility that these agents, except for (+)-catechin, can be applied not only as chemopreventive agents but also as anti-metastatic therapy.Keywords A549 AE Akt AE TGF-b AE Sulindac sulfide AE Caffeic acid phenethyl ester Abbreviations CAPE Caffeic acid phenethyl ester AE TGF-b Transforming growth factor-b AE FAK Focal adhesion kinase AE MMP-2 Matrix metalloproteinase-2

Nuclear factor-kappa B (NF-kappaB)/Rel transcription factors play an important role in the inducible regulation of a variety of cytokine genes in epithelial cells. We assessed accumulation of fluorescence-stained NF-kappaB into propidium iodide-stained nuclei using laser scanning cytometry. "Activity-specific" antibodies to the Rel A (p65) and NF-kappaB1 (p50) subunits of NF-kappaB were detected in the nuclei of A549 cells (an immortalized human type II alveolar epithelial cell line). Exposure to TNF-alpha caused p65 and p50 to translocate into nuclei in a dose- and time-dependent manner. Preincubation with dexamethasone for 24 h or 30 min, or with theophylline for 30 min before TNF-alpha stimulation attenuated the nuclear translocation of Rel A and p50. These findings suggest that theophylline, as well as dexamethasone, may inhibit translocation of NF-kappaB.

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Objective: New effective therapy is desirable for patients with non-small cell lung cancer (NSCLC) who have failed previous treatments. Fractionated administration of paclitaxel may be less toxic and more active against NSCLC. The aim of this study was to evaluate the activity and toxicity of weekly paclitaxel therapy for NSCLC in a second-line setting. Methods: Patients with pathological or cytological diagnosis of NSCLC, measurable lesions, and one or more prior therapies were enrolled. We administered weekly infusions of 80 mg/m² paclitaxel 3 times in a 4-week cycle. In the absence of progressive disease or intolerable toxicity, each patient was treated for a minimum of 4 cycles. Results: Of 39 patients enrolled, 1 patient achieved complete response and 11 patients achieved partial response (response rate, 31%: 95% confidence interval, 17–48%). The median survival time was 43 weeks (range, 7–128 weeks). Grade 3 or 4 leukopenia occurred in only 7 patients (18%). Neurotoxicity was the most frequent adverse effect (grades 1 and 2.26 and 5%, respectively). Although all patients recovered rapidly with corticosteroid treatment, drug-induced pneumonitis was observed in 3 patients (8%). Conclusion: Low-dose weekly paclitaxel is a promising therapy with high effectiveness for advanced NSCLC in patients with NSCLC who have failed previous treatments.

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: The aim of the study was to characterize patients at risk for exacerbations of their asthma as a result of the Tottori-Ken Seibu earthquake and to identify factors that predict exacerbation of asthma after an earthquake. A retrospective cohort study-analysis was conducted of 156 asthmatic patients, aged 18 to 89 years, who were out-patients of Tottori University Hospital and who had completely recorded their asthmatic symptoms and measured their peak expiratory flow (PEF) rates for more than one year prior to the earthquake. Seventeen (11%) patients who experienced the earthquake were identified as having an exacerbation within one month after the earthquake. Diurnal variability of PEF during the month after the earthquake was compared to values during a matched month one year previously. When factors associated with exacerbation were identified by a review of the medical case notes and the contribution of these factors to the exacerbation was determined using multivariate analysis, airflow limitation was shown to be independently associated with exacerbation after the earthquake. Acute asthma attacks are more likely to occur within the first week after the earthquake event without diurnal PEF variability. Asthma is likely to worsen after an earthquake. J. Med. Invest. 52 : 80-84, February, 2005