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Wu X.,Huazhong University of Science and Technology | Liu D.,Huazhong University of Science and Technology | Tao D.,Fifth Hospital of Wuhan | Xiang W.,First Hospital of Wuhan | And 7 more authors.
Molecular Cancer Therapeutics | Year: 2016

People who develop bladder cancer frequently succumb to the intractable disease. Current treatment strategies are limited presumably due to the underlying molecular complexity and insufficient comprehension. Therefore, exploration of new therapeutic targets in bladder cancer remains necessary. Here, we identify that bromodomain-4 protein (BRD4), an important epigenome reader of bromodomain and extraterminal domain (BET) family member, is a key upstream regulator of enhancer of zeste homologue 2 (EZH2), and represents a novel therapeutic target in bladder cancer. We found that BRD4 was significantly overexpressed in bladder cancer cells and tissues. Inhibition of BRD4 decreased bladder cancer cell proliferation concomitantly with the accumulation of cell apoptosis in vitro and suppressed tumor growth in vivo. We further found that suppression of BRD4 decreased the mRNA and protein levels of EZH2, which was reversed by ectopic expression of C-MYC. In particular, individual silencing of BRD4 using shRNA or the BET inhibitor JQ1 strikingly diminished the recruitment of C-MYC to EZH2 promoter in bladder cancer. Briefly, our research reveals that BRD4 positively regulates EZH2 transcription through upregulation of C-MYC, and is a novel promising target for pharmacologic treatment in transcriptional program intervention against this intractable disease. © 2016 AACR.

Hong L.-F.,Peking Union Medical College | Luo S.-H.,Fifth Hospital of Wuhan | Li J.-J.,Peking Union Medical College
Journal of Geriatric Cardiology | Year: 2013

Percutaneous coronary intervention (PCI) in an anomalous right coronary artery (RCA) can be technically difficult because selective cannulation of the vessel may not be easy. We thereby present two cases with unstable angina pectoris of anomalous originated RCA. The PCI were successfully performed in two patients with a special guiding wire manipulating skill which we called "gone with the flow" combined with balloon anchoring technology, providing excellent angiographic visualization and sound guide support for stent delivery throughout the procedure without severe cardiovascular adverse effects. Our primary data suggested that PCI for geriatric patients with an anomalous origin of RCA accompanied by severe atherosclerotic lesions might also be a safe, available, and feasible strategy. ©2013 JGC All rights reserved.

Miao H.-L.,Guangdong Medical College | Pan Z.-J.,Fifth Hospital of Wuhan | Lei C.-J.,Guangdong Medical College | Wen J.-Y.,Guangdong Medical College | And 6 more authors.
Journal of Cellular Biochemistry | Year: 2013

Glypican-3 (GPC3), a membrane-associated heparan sulfate proteoglycan, is frequently upregulated in hepatocellular carcinoma (HCC). Yes-associated protein (YAP) is also found over-expressed in HCC and has been identified as a key effector molecule in Hippo pathway, which could control the organ size in animals through the regulation of cell proliferation and apoptosis and plays an important role in the development of malignant tumors. Studies have reported that GPC3 and YAP might collaborate to regulate the development of HCC. To elucidate the role of GPC3 in the development of HCC and its relationship with YAP, siRNA technique was employed to knock down GPC3 in Huh7 HCC cells. Moreover, recombinant human YAP-1 was used to examine the effects of GPC3 on Huh7 cells. The results of flow cytometric analysis and Annexin-V-FLUOS apoptosis assay showed that knockdown of GPC3-induced apoptosis in Huh7 cells, resulting in inhibition of cell proliferation as examined by EdU incorporation assay, migration, and invasion. GPC3 knockdown also suppressed the expression of YAP in mRNA and protein levels, as examined by fluorescence quantitative PCR and Western blot analysis. Moreover, addition of recombinant human YAP-1 effectively rescued the cells from apoptosis triggered by GPC3 knockdown. Taken together, our findings suggest that GPC3 regulates HCC cell proliferation with the involvement of Hippo pathway. J. Cell. Biochem. 114: 625-631, 2013. © 2012 Wiley Periodicals, Inc.

Zhang J.,Renmin University of China | Wu J.,Wuhan Medical Treatment Center | Peng X.,Fifth Hospital of Wuhan | Song J.,Renmin University of China | And 2 more authors.
PLoS ONE | Year: 2014

Background:Many studies have investigated the associations between the signal transducer and activator of transcription 3 (STAT3) in the susceptibility to ulcerative colitis (UC) and Crohn's disease (CD). However, the results remain inconsistent. This meta-analysis determined the risk of STAT3 rs744166 polymorphism-conferred UC and CD susceptibility.Materials and Methods: Electronic databases, including PubMed, EMBASE and the Cochrane Library, were searched for all eligible studies that evaluated the association between STAT3 rs744166 polymorphisms with UC and CD risk up to August 21, 2014. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using fixed- or randomeffects models.Results: Twelve studies containing 10298 patients with CD, 4244 patients with UC and 11191 controls were included in this meta-analysis. The results indicated that the STAT3 rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, OR = 1.20, 95%CI, 1.11 -1.30, /2 = 0%, Punadjusted<0.00001, PBonferroni<0.00005, PFDR< 0.00001 ; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08-1.36, /2=1%, Punadjusted = 0.001, PBonferroni = 0.005, PFDR = 0.00125). In subgroup analyses by ethnicity, the significant association was found only among Caucasians. However, when grouped by age of onset, positive associations were found both among adults and children. In addition, when stratified by study design and genotyping methods, the risk of CD was significantly associated with the STAT3 rs744166 polymorphism in hospital-based and population-based groups and in SNP Array and SNPlex groups. For UC, significant associations were also found in population-based, PCR-RFLP and SNPlex groups. Moreover, these findings were sufficiently robust to withstand the Bonferroni correction and false discovery rate (FDR).Conclusion: This meta-analysis indicates that carriers of the STAT3 rs744166 'A' allele have a significantly greater risk of CD and UC, especially among Caucasians. © 2014 Zhang et al.

Gao L.,University of Newcastle | Xia L.,Renmin University of China | Pan S.-Q.,Renmin University of China | Xiong T.,Fifth Hospital of Wuhan | Li S.-C.,University of Newcastle
Epilepsia | Year: 2013

Purpose Generic preference-based health-related quality of life (HRQoL) instruments are increasingly used to estimate the quality-adjusted life years (QALYs) in cost-effectiveness/utility studies. However, no such tool has been used and validated in epilepsy patients in China. This study was conducted to validate a generic preference-based HRQoL instrument, namely the Quality of Well-Being Scale-Self-Administered (QWB-SA) in Chinese patients with epilepsy. Methods Accepted translation procedures were followed to develop the Chinese QWB-SA. An epilepsy group (adults with established diagnosis of epilepsy) and a control group (adults without manifested cognitive problems) were recruited between July and October, 2012, from two tertiary hospitals in China. After giving informed consent, each subject completed both the QWB-SA and the EuroQol (EQ-5D) as well as provided sociodemographic data. Construct validity was examined by six (convergent) and two (discriminative) a priori hypotheses. Sensitivity was compared by ability to differentiate epilepsy-specific variable-based subgroups. Agreement between the QWB-SA and EQ-5D was assessed by intraclass correlation coefficient (ICC) and Bland-Altman plot. Key Findings One hundred forty-four epilepsy patients and 323 control subjects were enrolled, respectively. The utility medians (interquartile range, IQR) for the QWB-SA and EQ-5D were 0.673 (0.172), 0.848 (0.275) for epilepsy group and 0.775 (0.258), 1.000 (0.152) for control group, respectively. The difference in utilities between the two measures were significant (p < 0.0001). Construct validity was demonstrated by six a priori hypotheses. In addition, the QWB-SA was able to discriminate across different seizure frequency and antiepileptic drug (AED) treatment subgroups. Agreement between the QWB-SA and EQ-5D was demonstrated by ICC (0.725). Finally, the multiple linear regression analysis indicated that group and the EQ-VAS had influences on the utility difference of these two measures, whereas seizure frequency and number of AEDs were predictors of HRQoL as measured by the QWB-SA. Significance The QWB-SA is a valid and sensitive HRQoL measure in Chinese patients with epilepsy. Compared to the EQ-5D, the QWB-SA showed superiority in coverage of health dimensions, sensitivity, and ceiling effects. However, future study is still needed to ascertain its responsiveness. © Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

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