Mechanisms linking mitogenic and growth inhibitory cytokine signaling and the cell cycle have not been fully elucidated in either cancer or in normal cells. Here we show that activation of protein kinase B (PKB)/Akt, contributes to resistance to antiproliferative signals and breast cancer progression in part by impairing the nuclear import and action of p27. Akt transfection caused cytoplasmic p27 accumulation and resistance to cytokine-mediated G1 arrest. The nuclear localization signal of p27 contains an Akt consensus site at threonine 157, and p27 phosphorylation by Akt impaired its nuclear import in vitro. Akt phosphorylated wild-type p27 but not p27T157A. In cells transfected with constitutively active Akt(T308DS473D)(PKB(DD)), p27WT mislocalized to the cytoplasm, but p27T157A was nuclear. In cells with activated Akt, p27WT failed to cause G1 arrest, while the antiproliferative effect of p27T157A was not impaired. Cytoplasmic p27 was seen in 41% (52 of 128) of primary human breast cancers in conjunction with Akt activation and was correlated with a poor patient prognosis. Thus, we show a novel mechanism whereby Akt impairs p27 function that is associated with an aggressive phenotype in human breast cancer.

The severity of chronic obstructive pulmonary disease (COPD) is evaluated not only by airflow limitation but also by factors such as exercise capacity and body mass index. Recent advances in CT technology suggest that it might be a useful tool for evaluating the severity of the disease components of COPD. The aim of this study is to evaluate the correlation between the parameters measured on volumetric CT, including the extent of emphysema, air trapping, and airway thickening, and clinical parameters. CT scans were performed in 34 patients with COPD at full inspiration and expiration. We used in-house software to measure CT parameters, including volume fraction of emphysema (V(950)), mean lung density (MLD), CT air trapping index (CT ATI), segmental bronchial wall area (WA), lumen area (LA), and wall area percent (WA%). We found that the CT parameters were correlated with the pulmonary function test (PFT) results, body mass index (BMI), the modified Medical Research Council Dyspnea scale (MMRC scale), the six-minute-walk distance (6MWD), and the BODE index. V(950 insp) correlated to the BMI, FEV(1), 6MWD, and the BODE index. The CT ATI correlated with the physiologic ATI (VC-FVC) (R=0.345, p=0.045) and the MMRC scale (R=0.532, p=0.001). There was a positive correlation between the WA% and the BMI (R=0.563, p<0.001). MLD(exp) showed the strongest correlation with the BODE index (R= -0.756, p<0.001). We conclude that the severity of emphysema and air trapping measured on CT correlated with the PFT parameters 6MWD and BMI.

There have been few large-scale studies on the relationship between smoking and gut microbiota. We investigated the relationship between smoking status and the composition of gut microbiota. This was a population-based cross-sectional study using Healthcare Screening Center cohort data. A total of 758 men were selected and divided into three groups: never (n = 288), former (n = 267), and current smokers (n = 203). Among the three groups, there was no difference in alpha diversity, however, Jaccard-based beta diversity showed significant difference (p = 0.015). Pairwise permutational multivariate analysis of variance (PERMANOVA) tests between never and former smokers did not show a difference; however, there was significant difference between never and current smokers (p = 0.017) and between former and current smokers (p = 0.011). Weighted UniFrac-based beta diversity also showed significant difference among the three groups (p = 0.038), and pairwise PERMANOVA analysis of never and current smokers showed significant difference (p = 0.01). In the analysis of bacterial composition, current smokers had an increased proportion of the phylum Bacteroidetes with decreased Firmicutes and Proteobacteria compared with never smokers, whereas there were no differences between former and never smokers. In conclusion, gut microbiota composition of current smokers was significantly different from that of never smokers. Additionally, there was no difference in gut microbiota composition between never and former smokers.

In patients with overlap syndrome, both medical utilization and cost were higher than in COPD patients without asthma.

BackgroundGastroesophageal reflux disease (GERD) is one of the most common causes of chronic cough and a potential risk factor for exacerbation of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the prevalence and risk factors of GERD in patients with COPD and association between GERD and COPD exacerbation.MethodsData were collected from the National Health Insurance Database of Korea. The subjects were 40 years old and older, who had COPD as primary or secondary diagnosis codes and utilized health care resource to receive prescriptions of COPD medication at least twice in 2009. Univariate logistic regression was performed to understand the relationship between COPD and GERD, and multiple logistic regression analysis was performed with adjustment for several confounding factors.ResultsThe prevalence of GERD in COPD patients was 28% (39,987/141,057). Old age, female gender, medical aid insurance type, hospitalization, and emergency room (ER) visit were associated with GERD. Most of COPD medications except inhaled muscarinic antagonists were associated with GERD. The logistic regression analysis showed that the presence of GERD was associated with increased risk of hospitalization (OR 1.54, CI 1.50 to 1.58, p<0.001) and frequent ER visits (OR 1.55, CI 1.48 to 1.62, p<0.001).ConclusionsThe prevalence of GERD in patients with COPD was high. Old age, female gender, medical aid insurance type, and many COPD medications except inhaled muscarinic antagonists were associated with GERD. The presence of GERD was associated with COPD exacerbation.

BackgroundChronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB. We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects. We hypothesized that COPD patients with CB would have thicker airways and a greater history of smoking, acute bronchitis, allergic rhinitis, and occupational exposures compared to those without CB.MethodsWe divided 2703 GOLD 1–4 subjects in the Genetic Epidemiology of COPD (COPDGene®) Study into two groups based on symptoms: chronic bronchitis (CB+, n = 663, 24.5%) and no chronic bronchitis (CB-, n = 2040, 75.5%). Subjects underwent extensive clinical characterization, and quantitative CT analysis to calculate mean wall area percent (WA%) of 6 segmental airways was performed using VIDA PW2 (http://www.vidadiagnostics.com). Square roots of the wall areas of bronchi with internal perimeters 10 mm and 15 mm (Pi10 and Pi15, respectively), % emphysema, %gas trapping, were calculated using 3D Slicer (http://www.slicer.org).ResultsThere were no differences in % emphysema (11.4 ± 12.0 vs. 12.0 ± 12.6%, p = 0.347) or % gas trapping (35.3 ± 21.2 vs. 36.3 ± 20.6%, p = 0.272) between groups. Mean segmental WA% (63.0 ± 3.2 vs. 62.0 ± 3.1%, p < 0.0001), Pi10 (3.72 ± 0.15 vs. 3.69 ± 0.14 mm, p < 0.0001), and Pi15 (5.24 ± 0.22 vs. 5.17 ± 0.20, p < 0.0001) were greater in the CB + group. Greater percentages of gastroesophageal reflux, allergic rhinitis, histories of asthma and acute bronchitis, exposures to dusts and occupational exposures, and current smokers were seen in the CB + group. In multivariate binomial logistic regression, male gender, Caucasian race, a lower FEV1%, allergic rhinitis, history of acute bronchitis, current smoking, and increased airway wall thickness increased odds for having CB.ConclusionsHistories of asthma, allergic rhinitis, acute bronchitis, current smoking, a lower FEV1%, Caucasian race, male gender, and increased airway wall thickness are associated with CB. These data provide clinical and radiologic correlations to the clinical phenotype of CB.

Lung function in cases of chronic airflow obstruction (CAO) due to tuberculous destroyed lung, which is still common in Korea, has not been objectively investigated. We evaluated lung functions and postbronchodilator responses in 21 CAO patients with a forced expiratory volume in 1 s (FEV1) of 30-65% of the predicted value, and compared some of these results with those of age-, sex- and FEV1% predicted-matched patients with chronic obstructive pulmonary disease (COPD). In addition, we analyzed the lung functions of CAO patients with respect to wheezing. The forced vital capacity (FVC) (P < 0.05) and postbronchodilator FEV1 of CAO patients were lower than those of COPD patients (P < 0.05). When a positive bronchodilator response was defined as an absolute change of FEV1 (FEV1 delta(abs)) of more than 0.2 l (P < 0.05) and a percentage of initial FEV1 (FEV1 delta%init) of more than 12%, the positive rates in CAO patients were lower than in COPD patients (P < 0.05). Among the CAO patients, patients with wheezing showed lower forced expiratory flow 25%-75% (FEF(25-75%)) (P < 0.05) and higher airway resistance than those without wheezing (P < 0.05). CAO patients with wheezing were more responsive to bronchodilator than those without wheezing. Although the pathophysiology of CAO differs from that of COPD, bronchodilator therapy could be useful for treating CAO, especially in cases presenting with wheezing.

Iterative reconstruction allows ultra-low-dose CT and affords acceptable image quality, allowing size measurements of solid pulmonary nodules to be made.