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Beijing, China

Wang J.,Chinese University of Hong Kong | Zhao J.,Beijing 302 Hospital | Chu E.S.H.,Chinese University of Hong Kong | Mok M.T.S.,Chinese University of Hong Kong | And 7 more authors.
Journal of Pathology | Year: 2013

Smad7 is a principal inhibitor of the TGFβ-Smad signalling pathway. We have investigated the functional significance of Smad7 in hepatocellular carcinoma (HCC). Smad7 knockout (KO) and wild-type (WT) mice were injected with diethylnitrosamine (DEN) to induce HCC. The effects of Smad7 on cellular features were examined in HCC cells, using a Smad7 over-expression or deletion approach. Signalling pathway components modulated by Smad7 in HCC were evaluated using luciferase reporter assay and co-immunoprecipitation. Smad7 was down-regulated in human HCCs compared with the adjacent normal tissues (p < 0.001). Smad7 KO mice were more susceptible to DEN-induced HCC than WT mice (78% versus 22%, p < 0.05). HCCs from KO mice displayed a greater proliferation activity (p < 0.05) and a reduced apoptotic index compared with WT littermates (p < 0.05). Deletion of Smad7 promoted cell proliferation in primary cultured HCC cells. In addition, over-expression of Smad7 in HCC cell lines markedly suppressed cell growth (p < 0.0001) and colony formation (p < 0.01). Cell cycle analysis revealed an increase in the G1 phase and a reduction in the S-phase populations, accompanied by up-regulation of p27Kip1 and down-regulation of cyclin D1. Smad7 increased cell apoptosis (p < 0.01) by mediating an intrinsic [caspase-9, caspase-3 and poly(ADP-ribose) polymerase] apoptotic pathway. Moreover, Smad7 inhibited NF-κB signalling by interacting with TAB2, an upstream activator of NF-κB, and inhibited TGFβ signalling by suppressing phosphorylation of Smad3. In conclusion, loss of Smad7 enhances susceptibility to HCC. Smad7 suppresses HCC cell growth by inhibiting proliferation and G1-S phase transition and inducing apoptosis through attenuation of NF-κB and TGFβ signalling. Smad7 acts as a potential tumour suppressor in liver. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Source


Cheng J.,Beijing 302 Hospital | Kuai D.,Lu He Hospital | Zhang L.,Beijing 307 Hospital | Yang X.,Air Force General Hospital
Archives of Dermatological Research | Year: 2012

To evaluate the association between psoriasis and risk of diabetes, pertinent studies were identified by searching electronic databases and by reviewing the reference lists of retrieved articles. We included observational studies that examined the association between psoriasis and risk of diabetes. Two reviewers independently assessed eligibility and used a standardized form to collect data from published studies. The study quality was assessed by the Newcastle-Ottawa Scale. A total of 22 eligible studies that included 3,307,516 participants fulfilled the inclusion criteria. Compared to individuals without psoriasis, subjects with psoriasis had a 1.42-fold increased risk of diabetes (95% CI, 1.40-1.45). Findings from this meta-analysis suggest that individuals with psoriasis may have a modestly increased risk of diabetes. © 2011 Springer-Verlag. Source


Yao M.,Peking University | Zhao J.,Beijing 302 Hospital | Lu F.,Peking University
Oncotarget | Year: 2016

Use of serum alpha-fetoprotein (AFP) in clinical practices has been challenged in recent years, due to the lack of specificity and sensitivity. Here we conducted a retrospective study to evaluate the diagnostic and prognostic value of serum AFP among hepatocellular carcinoma (HCC) patients with their pathogenic features taken into consideration. The cohort for this study comprised 318 cases of hepatitis and 731 cases of cirrhosis, as well as 796 HCC patients. Using 11.62ng/mL as a cut-off value, the positive rate of AFP test among serum hepatitis B surface antigen (HBsAg) positive HCC patients was significantly higher than that in those HBsAg negative HCC patients (79.55% vs 56.49%, P < 0.000). Similarly, the median serum AFP level in HCC patients with serum HBsAg positive was significantly higher than that in those HBsAg negative HCC patients (423.89ng/ml vs 40.82ng/ml, P < 0.000). In addition, Kaplan-Meier curve analysis revealed that lower preoperative AFP level implicated a much higher overall survival rate. Of note, such prognosis predicting value was only seen in those chronic HBV infection-related HCC patients, but not among the HCC patients etiologically irrelevant to HBV infection. We believe that serum AFP is of diagnosis and prognostic predicting value for HCC with chronic HBV infection, and strongly suggest use of serum AFP as a biomarker in China and other HBV infection endemic area like Southeast Asia. Source


Zhang L.,Tianjin University | Wang Z.,Tianjin University | Xu C.,Beijing 302 Hospital | Li Y.,Tianjin University | And 3 more authors.
Journal of Materials Chemistry | Year: 2011

Polyvinyl alcohol (PVA) hydrogels have been proposed for use as promising biomaterials in biomedical and tissue engineering but their poor mechanical and water-retention properties have hindered their development. Graphene oxide (GO), an excellent nanofiller, was added to PVA to make GO/PVA composite hydrogels by a freeze/thaw method. The mechanical properties of the GO/PVA hydrogels were significantly improved. Compared to pure PVA hydrogels, a 132% increase in tensile strength and a 36% improvement of compressive strength were achieved with the addition of 0.8 wt% of GO, which suggests an excellent load transfer between the GO and the PVA matrix. The incorporation of certain amount of GO into composite hydrogels does not affect the toxicity of PVA to osteoblast cells. © 2011 The Royal Society of Chemistry. Source


Yan X.-L.,Beijing Institute of Transfusion Medicine | Jia Y.-L.,Beijing Institute of Transfusion Medicine | Chen L.,Beijing Institute of Transfusion Medicine | Zeng Q.,Beijing Institute of Transfusion Medicine | And 12 more authors.
Hepatology | Year: 2013

Cancer-associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer-associated MSCs (LC-MSCs) and hepatocellular carcinoma (HCC) remain unreported. Here, we identified the presence of MSCs in HCC tissues. We also showed that LC-MSCs significantly enhanced tumor growth in vivo and promoted tumor sphere formation in vitro. LC-MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. Complementary DNA (cDNA) microarray analysis showed that S100A4 expression was significantly higher in LC-MSCs compared with liver normal MSCs (LN-MSCs) from adjacent cancer-free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC-MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic microRNA (miR)-155 in HCC cells was significantly up-regulated by coculture with LC-MSCs and by S100A4 ectopic overexpression. The invasion-promoting effects of S100A4 were significantly attenuated by a miR-155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR-155 expression in HCC cells. We demonstrate that S100A4 secreted from LC-MSCs promotes the expression of miR-155, which mediates the down-regulation of suppressor of cytokine signaling 1, leading to the subsequent activation of STAT3 signaling. This promotes the expression of matrix metalloproteinases 9, which results in increased tumor invasiveness. Conclusion: S100A4 secreted from LC-MSCs is involved in the modulation of HCC progression, and may be a potential therapeutic target. © 2013 American Association for the Study of Liver Diseases. Source

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