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1.  Combined Inhibition of Epidermal Growth Factor Receptor and Cyclooxygenase-2 Leads to Greater Anti-tumor Activity of Docetaxel in Advanced Prostate Cancer  
PLoS ONE  2013;8(10):e76169.
The epidermal growth factor receptor (EGFR) and cyclooxygenase-2(COX-2) play a critical role in disease progression, relapse and therapeutic resistance of advanced prostate cancer (PCa). In this paper, we evaluated, for the first time, the therapeutic benefit of blocking EGRF and/or COX-2 (using gefitinib and NS-398, respectively) in terms of improving the efficacy of the conventional clinical chemotherapeutic drug docetaxel in vitro and vivo. We showed that EGFR and COX-2 expression was higher in metastatic than non-metastatic PCa tissues and cells. Docetaxel, alone or in combination with gefitinib or NS-398, resulted in a small decrease in cell viability. The three drug combination decreased cell viability to a greater extent than docetaxel alone or in combination with gefitinib or NS-398. Docetaxel resulted in a modest increase in apoptotic cell in metastatic and non-metastatic cell lines. NS-398 markedly enhanced docetaxel-induced cell apoptosis. The combination of the three drugs caused even more marked apoptosis and resulted in greater suppression of invasive potential than docetaxel alone or in association with gefitinib or NS-398. The combination of all three drugs also resulted in a more marked decrease in NF-ΚB, MMP-9 and VEGF levels in PC-3M cells. These in vitro findings were supported by in vivo studies showing that docetaxel in combination with gefitinib and NS-398 was significantly more effective than any individual agent. Based on previous preclinical research, we conclude that simultaneously blocking EGFR and COX-2 by gefitinib and NS-398 sensitizes advanced PCa cells to docetaxel-induced cytotoxicity.
PMCID: PMC3796533  PMID: 24155892
2.  Adaptive Modulation of Adult Brain Gray and White Matter to High Altitude: Structural MRI Studies 
PLoS ONE  2013;8(7):e68621.
The aim of this study was to investigate brain structural alterations in adult immigrants who adapted to high altitude (HA). Voxel-based morphometry analysis of gray matter (GM) volumes, surface-based analysis of cortical thickness, and Tract-Based Spatial Statistics analysis of white matter fractional anisotropy (FA) based on MRI images were conducted on 16 adults (20–22 years) who immigrated to the Qinghai-Tibet Plateau (2300–4400 m) for 2 years. They had no chronic mountain sickness. Control group consisted of 16 matched sea level subjects. A battery of neuropsychological tests was also conducted. HA immigrants showed significantly decreased GM volumes in the right postcentral gyrus and right superior frontal gyrus, and increased GM volumes in the right middle frontal gyrus, right parahippocampal gyrus, right inferior and middle temporal gyri, bilateral inferior ventral pons, and right cerebellum crus1. While there was some divergence in the left hemisphere, surface-based patterns of GM changes in the right hemisphere resembled those seen for VBM analysis. FA changes were observed in multiple WM tracts. HA immigrants showed significant impairment in pulmonary function, increase in reaction time, and deficit in mental rotation. Parahippocampal and middle frontal GM volumes correlated with vital capacity. Superior frontal GM volume correlated with mental rotation and postcentral GM correlated with reaction time. Paracentral lobule and frontal FA correlated with mental rotation reaction time. There might be structural modifications occurred in the adult immigrants during adaptation to HA. The changes in GM may be related to impaired respiratory function and psychological deficits.
PMCID: PMC3712920  PMID: 23874692
3.  Grey and white matter abnormalities in chronic obstructive pulmonary disease: a case–control study 
BMJ Open  2012;2(2):e000844.
The irreversible airflow limitation characterised by chronic obstructive pulmonary disease (COPD) causes a decrease in the oxygen supply to the brain. The aim of the present study was to investigate brain structural damage in COPD.
Retrospective case–control study. Patients with COPD and healthy volunteers were recruited. The two groups were matched in age, gender and educational background.
A hospital and a number of communities: they are all located in southern Fujian province, China.
25 stable patients and 25 controls were enrolled from December 2009 to May 2011.
Using voxel-based morphometry and tract-based spatial statistics based on MRI to analyse grey matter (GM) density and white matter fractional anisotropy (FA), respectively, and a battery of neuropsychological tests were performed.
Patients with COPD (vs controls) showed decreased GM density in the limbic and paralimbic structures, including right gyrus rectus, left precentral gyrus, bilateral anterior and middle cingulate gyri, bilateral superior temporal gyri, bilateral anterior insula extending to Rolandic operculum, bilateral thalamus/pulvinars and left caudate nucleus. Patients with COPD (vs controls) had decreased FA values in the bilateral superior corona radiata, bilateral superior and inferior longitudinal fasciculus, bilateral optic radiation, bilateral lingual gyri, left parahippocampal gyrus and fornix. Lower FA values in these regions were associated with increased radial diffusivity and no changes of longitudinal diffusivity. Patients with COPD had poor performances in the Mini-Mental State Examination, figure memory and visual reproduction. GM density in some decreased regions in COPD had positive correlations with arterial blood Po2, negative correlations with disease duration and also positive correlations with visual tasks.
The authors demonstrated that COPD exhibited loss of regional GM accompanied by impairment of white matter microstructural integrity, which was associated with disease severity and may underlie the pathophysiological and psychological changes of COPD.
Article summary
Article focus
Decreased oxygen supply to brain may cause neuronal damage in COPD. However, the damage remains largely uninvestigated.
Key messages
We found that COPD extends to the brain, with the loss of regional cortical grey matter accompanied by impairment in the white matter microstructural integrity.
Our findings would be help for clinical therapy of COPD.
Strengths and limitations of this study
Multiple analyses were used based on MR images. The statistic power for FA analysis was weak.
PMCID: PMC3341600  PMID: 22535793
4.  Effect of endothelin-1 on cyclooxygenase-2 expression in human hormone refractory prostate cancer cells 
Oncology Letters  2010;1(3):495-499.
The present study aimed to explore the effects and possible mechanisms of recombinant human endothelin (ET)-1 on cyclooxygenase (COX)-2 expression in human hormone refractory prostate cancer PC3 cells. PC3 cells were treated with 100 nmol/l ET-1 for the indicated times (3, 6, 9, 12 and 24 h) and concentrations (0.1, 1, 10 and 100 nmol/l) for 24 h. Moreover, 100 nmol/l ET-1 was used to treat PC3 cells alone or in combination with endothelin A receptor (ETAR) antagonist BQ123 (1 μmol/l), endothelin B receptor (ETBR) antagonist BQ788 (1 μmol/l), MAPK/extracellular signal-regulated kinase kinase (MEK)-selective inhibitor, PD98059 (10 μmol/l), p38 mitogen-activated protein kinase (MAPK) antagonist SB203580 (5 μmol/l) or epidermal growth factor receptor (EGFR) antagonist AG1478 (0.1 μmol/l) for 24 h. COX-2 mRNA and protein expression was detected in the PC3 cells by reverse transcription-polymerase chain reaction and Western blot analysis. ET-1 induced a time- and dose-dependent increase in the mRNA and protein expression of COX-2 in the PC3 cells. BQ123, LY294002, SC203580 and AG1478 prevented the expression of COX-2 in the PC3 cells (P<0.05), while BQ788 did not. ET-1 induced the up-regulation of COX-2 in the PC3 cells. ETAR may be involved in the process. Several signaling pathways, including p42/44 MAPK, p38 MAPK and EGFR, are therefore implicated in the regulation of COX-2 expression.
PMCID: PMC3436340  PMID: 22966331
endothelin-1; cyclooxygenase 2; prostate cancer; gene expression

Results 1-4 (4)