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1.  EGFR potentiates MCM7-mediated DNA replication through tyrosine phosphorylation of Lyn kinase in human cancers 
Cancer cell  2013;23(6):796-810.
Summary
EGFR initiates a signaling cascade that leads to DNA synthesis and cell proliferation, but its role in regulating DNA replication licensing is unclear. Here, we show that activated EGFR phosphorylates the p56 isoform of Lyn, p56Lyn, at Y32, which then phosphorylates MCM7, a licensing factor critical for DNA replication, at Y600 to increase its association with other MCM complex proteins, thereby promoting DNA synthesis complex assembly and cell proliferation. Both p56Lyn Y32 and MCM7 Y600 phosphorylation are enhanced in proliferating cells and correlated with poor survival of breast cancer patients. These results establish a signaling cascade in which EGFR enhances MCM7 phosphorylation and DNA replication through Lyn phosphorylation in human cancer cells.
doi:10.1016/j.ccr.2013.04.027
PMCID: PMC3703149  PMID: 23764002
2.  The Role of the High-Sensitivity C-Reactive Protein in Patients with Stable Non-Cystic Fibrosis Bronchiectasis 
Pulmonary Medicine  2013;2013:795140.
Study Objectives. The aim of this study is to investigate the correlation between serum high-sensitivity C-reactive protein (hs-CRP) and other clinical tools including high-resolution computed tomography (HRCT) in patients with stable non-CF bronchiectasis. Design. A within-subject correlational study of a group of patients with stable non-CF bronchiectasis, who were recruited from our outpatient clinic, was done over a two-year period. Measurements. Sixty-nine stable non-CF bronchiectasis patients were evaluated in terms of hs-CRP, 6-minute walk test, pulmonary function tests, and HRCT. Results. Circulating hs-CRP levels were significantly correlated with HRCT scores (n = 69, r = 0.473, P < 0.001) and resting oxygenation saturation (r = −0.269, P = 0.025). HRCT severity scores significantly increased in patients with hs-CRP level of 4.26 mg/L or higher (mean ± SD 28.1 ± 13.1) compared to those with hs-CRP level less than 4.26 mg/L (31.7 ± 9.8, P = 0.004). Oxygenation saturation at rest was lower in those with hs-CRP level of 4.26 mg/L or higher (93.5 ± 4.4%) compared to those with hs-CRP level less than 4.26 mg/L (96.4 ± 1.6%, P = 0.001). Conclusion. There was a good correlation between serum hs-CRP and HRCT scores in the patients with stable non-CF bronchiectasis.
doi:10.1155/2013/795140
PMCID: PMC3870862  PMID: 24381758
3.  Feasibility of Bispectral Index-Guided Propofol Infusion for Flexible Bronchoscopy Sedation: A Randomized Controlled Trial 
PLoS ONE  2011;6(11):e27769.
Objectives
There are safety issues associated with propofol use for flexible bronchoscopy (FB). The bispectral index (BIS) correlates well with the level of consciousness. The aim of this study was to show that BIS-guided propofol infusion is safe and may provide better sedation, benefiting the patients and bronchoscopists.
Methods
After administering alfentanil bolus, 500 patients were randomized to either propofol infusion titrated to a BIS level of 65-75 (study group) or incremental midazolam bolus based on clinical judgment to achieve moderate sedation. The primary endpoint was safety, while the secondary endpoints were recovery time, patient tolerance, and cooperation.
Results
The proportion of patients with hypoxemia or hypotensive events were not different in the 2 groups (study vs. control groups: 39.9% vs. 35.7%, p = 0.340; 7.4% vs. 4.4%, p = 0.159, respectively). The mean lowest blood pressure was lower in the study group. Logistic regression revealed male gender, higher American Society of Anesthesiologists physical status, and electrocautery were associated with hypoxemia, whereas lower propofol dose for induction was associated with hypotension in the study group. The study group had better global tolerance (p<0.001), less procedural interference by movement or cough (13.6% vs. 36.1%, p<0.001; 30.0% vs. 44.2%, p = 0.001, respectively), and shorter time to orientation and ambulation (11.7±10.2 min vs. 29.7±26.8 min, p<0.001; 30.0±18.2 min vs. 55.7±40.6 min, p<0.001, respectively) compared to the control group.
Conclusions
BIS-guided propofol infusion combined with alfentanil for FB sedation provides excellent patient tolerance, with fast recovery and less procedure interference.
Trial Registration
ClinicalTrials. gov NCT00789815
doi:10.1371/journal.pone.0027769
PMCID: PMC3223212  PMID: 22132138

Results 1-3 (3)