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Zhong W.-D.,Guangzhou Medical College | Zhong W.-D.,Guangdong Key Laboratory of Urology | Liang Y.-X.,Southern Medical University | Lin S.X.,Harvard University | And 14 more authors.
International Journal of Cancer | Year: 2012

Novel molecular markers that are associated with prostate cancer (PCa) progression will provide valuable information in the diagnosis and treatment of the disease. Extracellular matrix metalloproteinase inducer (CD147) has been demonstrated to be involved in tumor invasion, metastasis, growth and survival. In our study, we examined whether the expression of CD147 can be used as a prognostic marker for predicting PCa progression. Tissue samples from 240 patients who received radical prostatectomy for PCa were obtained. CD147 expression in these samples was evaluated using immunohistochemical staining with a monoclonal antibody specifically against CD147. Increased expression of CD147 was correlated with higher Gleason scores (GS), positive surgical margin, prostate-specific antigen (PSA) failure, metastasis and reduced overall survival. Both univariate Cox regression analysis and multivariate analysis including competing biological variables demonstrated that increased CD147 expression was associated with increased risk for reduced PSA failure-free, metastasis-free and overall survival. Kaplan-Meier survival curves showed that the CD147 overexpression was a significant predictor for the PSA failure-free, metastasis-free and the overall survival in both pT2 and pT3 PCa patients. More significantly, higher expression of CD147 can serve as an independent prognostic predictor for PSA failure-free survival in PCa patients when they are stratified by GS. Our study results demonstrate the involvement of CD147 in PCa progression and suggest its potential role as an independent predictor of biochemical recurrence, development of metastasis and reduced overall survival in PCa. Copyright © 2011 UICC.


Qiu Y.,Tianjin Medical University | Qiu Y.,University of Oxford | Wang X.,University of Oxford | Zhang Y.,Beijing Hospital of Ministry of Public Health | And 5 more authors.
Journal of Tissue Engineering and Regenerative Medicine | Year: 2016

In order to examine the differentiation potential of the tenocytes expanded in our defined culture medium (reported previously) and the effect of sequential combination of the two culture conditions on human tenocytes, a two-dimensional and three-dimensional experimental approach was used. Human tenocytes were sequentially exposed to 1% fetal bovine serum (FBS)+50ng/ml platelet-derived growth factor-BB (PDGFBB) + 50ng/ml basic fibroblast growth factor (bFGF) for the first 14days (expansion phase) followed by a further 14-day culture in the presence of 10ng/ml transforming growth factor β-3 plus 50ng/ml insulin-like growth factor 1, but in the absence of serum (differentiation phase). The results showed that by sequential treatment of human tenocytes maintaining a long-term two-dimensional tenocyte culture in vitro for up to 28days was possible. These findings were further verified using a three-dimensional scaffold (Bombyx silk) whereby the tendon-like constructs formed resembled macroscopically and microscopically the constructs formed in 10% FBS supplemented culture media and the human hamstring tendon. These findings were further substantiated using haematoxylin and eosin staining, scanning electron microscopy and by immunohistochemical detection of type I collagen. In addition, the mechanical properties of the three-dimensional constructs were determined to be significantly superior to that of the natural human hamstring tendon. This is the first report to demonstrate a possible approach in expanding and differentiating human tenocytes for tendon tissue engineering. © 2013 John Wiley & Sons, Ltd.


Qiu Y.,Tianjin Medical University | Qiu Y.,University of Oxford | Wang X.,University of Oxford | Zhang Y.,Beijing Hospital of Ministry of Public Health | And 5 more authors.
Cells Tissues Organs | Year: 2013

We have established that human tenocytes can differentiate in the absence of exogenous fetal bovine serum (FBS) but in the presence of insulin-like growth factor-1 (IGF-1) and transforming growth factor-β3 (TGF-β3). The extent of tenocyte differentiation was assessed by examining cell survival, collagen synthesis, cell morphology and expression of tenocyte differentiation markers such as scleraxis (Scx), tenomodulin (Tnmd), collagen type I (Col-I) and decorin (Dcn). Our results indicate that 50 ng/ml IGF-1 and 10 ng/ml TGF-β3 (in the absence of FBS) were capable of maintaining in vitro human tenocyte survival in 14-day cultures. The extent of collagen synthesis and messenger ribonucleic acid expression of Scx, Tnmd, Col-I and Dcn were significantly upregulated in response to IGF-1 and TGF-β3. These findings have shown for the first time that human tenocytes can be maintained in long-term culture, in serum-free conditions, making this approach a suitable one for the purpose of tendon tissue engineering. © 2012 S. Karger AG, Basel.


Zhou J.,Shanghai JiaoTong University | Zheng F.,Zhejiang University | Guo X.,Peking University | Yang H.,Guangdong General Hospital | And 6 more authors.
Diabetes/Metabolism Research and Reviews | Year: 2015

Background: The aim of this study is to compare the efficacy and safety of once-daily insulin glargine plus gliclazide modified release combination therapy versus twice-daily premixed insulin monotherapy in Chinese type 2 diabetic patients insufficiently controlled by oral antidiabetic agents. Methods: In a 12-week, multicenter, randomized, parallel-group clinical trial, patients with poor glycaemic control (fasting plasma glucose≥7.0 mmol/L and 7.5%


Zhong W.-D.,Guangzhou Medical College | Chen Q.-B.,Guangzhou Medical College | Ye Y.-K.,Guangzhou Medical College | Han Z.-D.,Guangzhou Medical College | And 8 more authors.
Cancer Epidemiology | Year: 2010

Aim: Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to promote tumor invasion and metastasis via stimulating matrix metalloproteinase synthesis in neighboring fibroblasts, to enhance angiogenesis via vascular endothelial growth factor, to induce chemoresistant tumor cells via the production of hyaluronan, and to confer resistance of cancer cells to anoikis through inhibition of Bim. The purpose of this study was to investigate the expression of EMMPRIN in human primary bladder cancer and to evaluate its prognostic value. Methods: EMMPRIN expression patterns were detected by immunohistochemistry. In order to determine its prognostic value, overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results: Of the 101 cases with bladder cancers, 68 (67.3%) cases were positive for EMMPRIN expression. When categorized into negative vs. positive expression, EMMPRIN was associated with the stage (p=0.006), the grade (p=0.002), carcinoma in situ (p=0.01), the recurrence (p=0.009), the progression (p=0.009), and the death (p=0.01) of patients with bladder cancer. Moreover, positive EMMPRIN expression clearly predicted poorer PFS (p=0.008) and OS (p=0.006). In the multivariate analysis, positive EMMPRIN expression was an independent prognostic factor for PFS (p=0.03) and OS (p=0.03). Conclusion: EMMPRIN expression was greater in bladder cancers than in the adjacent normal tissues and may be a useful prognostic marker for patients with bladder cancer. © 2010 Elsevier Ltd.

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