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Shi S.,University of Chinese Academy of Sciences | Deng Y.-Z.,University of Chinese Academy of Sciences | Zhao J.-S.,University of Chinese Academy of Sciences | Ji X.-D.,University of Chinese Academy of Sciences | And 8 more authors.
Journal of Biological Chemistry | Year: 2012

Non-small-cell lung cancer (NSCLC) is a deadly disease due to lack of effective diagnosis biomarker and therapeutic target. Much effort has been made in defining gene defects in NSCLC, but its full molecular pathogenesis remains unexplored. Here, we found RACK1 (receptor of activated kinase 1) was elevated in most NSCLC, and its expression level correlated with key pathological characteristics including tumor differentiation, stage, and metastasis. In addition, RACK1 activated sonic hedgehog signaling pathway by interacting with and activating Smoothened to mediate Gli1-dependent transcription in NSCLC cells. And silencing RACK1 dramatically inhibited in vivo tumor growth and metastasis by blocking the sonic hedgehog signaling pathway. These results suggest that RACK1 represents a new promising diagnosis biomarker and therapeutic target for NSCLC. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.


Shang Y.,Beijing Normal University | Shang Y.,Tsinghua University | Xu X.,Tsinghua University | Duan X.,Second Peoples Hospital of Zhuhai | And 5 more authors.
Biochemical and Biophysical Research Communications | Year: 2014

Transforming growth factor-β (TGF-β) signaling plays an important role in regulation of a wide variety of cellular processes. Canonical TGF-β signaling is mediated by Smads which were further regulated by several factors. We previously reported that E3 ubiquitin ligase CHIP (carboxyl terminus of Hsc70-interacting protein, also named Stub1) controlled the sensitivity of TGF-β signaling by modulating the basal level of Smad3 through ubiquitin-mediated degradation. Here, we present evidence that Hsp70 and Hsp90 regulate the complex formation of Smad3/CHIP. Furthermore, we observed that over-expressed Hsp70 or inhibition of Hsp90 by geldanamycin (GA) leads to facilitated CHIP-induced ubiquitination and degradation of Smad3, which finally enhances TGF-β signaling. In contrast, over-expressed Hsp90 antagonizes CHIP mediated Smad3 ubiquitination and degradation and desensitizes cells in response to TGF-β signaling. Taken together, our data reveal an opposite role of Hsp70 and Hsp90 in regulating TGF-β signaling by implicating CHIP-mediated Smad3 ubiquitination and degradation. This study provides a new insight into understanding the regulation of the TGF-β signaling by chaperones. © 2014 Elsevier Inc. All rights reserved.


He X.-F.,Changzhi Medical College | Wei J.,Sun Yat Sen University | Liu Z.-Z.,Second Peoples Hospital of Zhuhai | Xie J.-J.,Second Peoples Hospital of Zhuhai | And 7 more authors.
PLoS ONE | Year: 2014

Background: The previous published data on the association between CYP1A2*F (rs762551), CYP1B1 Leu432Val (rs1056836), Asn453Ser (rs180040), and Arg48Gly (rs10012) polymorphisms and colorectal cancer risk remained controversial. Methodology/Principal Findings: The purpose of this study is to evaluate the role of CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly genotypes in colorectal cancer susceptibility. We performed a meta-analysis on all the eligible studies that provided 5,817 cases and 6,544 controls for CYP1A2*F (from 13 studies), 9219 cases and 10406 controls for CYP1B1 Leu432Val (from 12 studies), 6840 cases and 7761 controls for CYP1B1 Asn453Ser (from 8 studies), and 4302 cases and 4791 controls for CYP1B1Arg48Gly (from 6 studies). Overall, no significant association was found between CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly and colorectal cancer risk when all the eligible studies were pooled into the meta-analysis. And in the subgroup by ethnicity and source of controls, no evidence of significant association was observed in any subgroup analysis. Conclusions/Significance: In summary, this meta-analysis indicates that CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly polymorphisms do not support an association with colorectal cancer, and further studies are needed to investigate the association. In addition, our work also points out the importance of new studies for CYP1A2*F polymorphism in Asians, because high heterogeneity was found (dominant model: I2 = 81.3%; heterozygote model: I2 = 79.0). © 2014 He et al.


Dong W.,Sun Yat Sen University | Gong M.,Sun Yat Sen University | Shi Z.,Second Peoples Hospital of Zhuhai | Xiao J.,Sun Yat Sen University | And 2 more authors.
PLoS ONE | Year: 2016

Programmed cell death-1 (PD-1) plays an important inhibitory role in anti-tumor responses, so it is considered as a powerful candidate gene for individual's genetic susceptibility to cancer. Recently, some epidemiological studies have evaluated the association between PD-1 polymorphisms and cancer risk. However, the results of the studies are conflicting. Therefore, a meta-analysis was performed. We identified all studies reporting the relationship between PD-1 polymorphisms and cancers by electronically searches. According to the inclusion criteria and the quality assessment of Newcastle-Ottawa Scale (NOS), only high quality studies were included. A total of twelve relevant studies involving 5,206 cases and 5,174 controls were recruited. For PD-1.5 (rs2227981) polymorphism, significantly decreased cancer risks were obtained among overall population, Asians subgroup and population-based subgroup both in TT vs. CC and TT vs. CT+CC genetic models. In addition, a similar result was also found in T vs. C allele for overall population. However, there were no significant associations between either PD-1.9 (rs2227982) or PD-1 rs7421861 polymorphisms and cancer risks in all genetic models and alleles. For PD-1.3 (rs11568821) polymorphism, we found different cancer susceptibilities between GA vs. GG and AA vs. AG+GG genetic models, and no associations between AA vs. GG, AA+AG vs. GG genetic models or A vs. G allele and cancer risks. In general, our results firstly indicated that PD-1.5 (rs2227981) polymorphism is associated a strongly decreased risk of cancers. Additional epidemiological studies are needed to confirm our findings. © 2016 Dong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Gong M.,Sun Yat Sen University | Dong W.,Sun Yat Sen University | He T.,Sun Yat Sen University | Shi Z.,Second Peoples Hospital of Zhuhai | And 5 more authors.
PLoS ONE | Year: 2015

Background and Objectives: Methylenetetrahydrofolate reductase (MTHFR) polymorphism may be a risk factor for male infertility. However, the epidemiologic studies showed inconsistent results regarding MTHFR polymorphism and the risk of male infertility. Therefore, we performed a meta-analysis of published case-control studies to re-examine the controversy. Methods: Electronic searches of PubMed, EMBASE, Google Scholar and China National Knowledge Infrastructure (CNKI) were conducted to select eligible literatures for this meta-analysis (updated to June 19, 2014). According to our inclusion criteria and the Newcastle-Ottawa Scale (NOS), only high quality studies that observed the association between MTHFR polymorphism and male infertility risk were included. Crude odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of association between the MTHFR polymorphism and male infertility risk. Results: Twenty-six studies involving 5,575 cases and 5,447 controls were recruited. Overall, MTHFR 677C>T polymorphism showed significant associations with male infertility risk in both fixed effects (CT+TT vs. CC: OR = 1.34, 95% CI: 1.23-1.46) and random effects models (CT+TT vs. CC: OR = 1.39, 95% CI: 1.19-1.62). Further, when stratified by ethnicity, sperm concentration and control sources, the similar results were observed in Asians, Caucasians, Azoo or OAT subgroup and both in population-based and hospital-based controls. Nevertheless, no significant association was only observed in oligo subgroup. Conclusions: Our results indicated that the MTHFR polymorphism is associated with an increased risk of male infertility. Further well-designed analytical studies are necessary to confirm our conclusions and evaluate gene-environment interactions with male infertility risk. © 2015 Gong et al.


Wang W.,Beijing Zhendong Guangming Pharmaceutical Research Institute Co Ltd | Wang W.,Shanxi Zhendong Pharmaceutical Co Ltd | Wang W.,Second Peoples Hospital of Zhuhai | You R.-L.,Beijing Zhendong Guangming Pharmaceutical Research Institute Co Ltd | And 11 more authors.
Acta Pharmacologica Sinica | Year: 2015

Kushen (Radix Sophorae Flavescentis) has a long history of use for the treatment of tumors, inflammation and other diseases in traditional Chinese medicine. Compound Kushen Injection (CKI) is a mixture of natural compounds extracted from Kushen and Baituling (Rhizoma Smilacis Glabrae). The main principles of CKI are matrine (MT) and oxymatrine (OMT) that exhibit a variety of pharmacological activities, including anti-inflammatory, anti-allergic, anti-viral, anti-fibrotic and cardiovascular protective effects. Recent evidence shows that these compounds also produce anti-cancer actions, such as inhibiting cancer cell proliferation, inducing cell cycle arrest, accelerating apoptosis, restraining angiogenesis, inducing cell differentiation, inhibiting cancer metastasis and invasion, reversing multidrug resistance, and preventing or reducing chemotherapy- and/or radiotherapy-induced toxicity when combined with chemotherapeutic drugs. In this review, we summarize recent progress in studying the anti-cancer activities of MT, OMT and CKI and their potential molecular targets, which provide clues and references for further study. © 2015 CPS and SIMM.


Wang S.-X.,Second Peoples Hospital of Zhuhai | Zhou W.,Second Peoples Hospital of Zhuhai | He X.-J.,Second Peoples Hospital of Zhuhai
Journal of Clinical Neurology (China) | Year: 2012

Objective To explore the therapy of endovascular mechanical recanalization ( EMR ) on cerebral infarction ( CI) caused extracranial arterial occlusion. Methods Three CI patients with extracranial arterial occlusion diagnosed by digital subtraction angiography ( DSA) ( internal carotid artery occlusion from beginning segment to petrosal segment in 2 cases, left vertebral artery occlusion from beginning segment to near end of intervertebral foramen segment in 1 case) received EMR surgery. The score of National Institute of Health stroke scale (NIHSS) was assessed before and 3 d after the EMR surgery. Occluded vascular condition was observed by DSA after stents. Results Tin; endovascular interventional techniques were applied in the 3 patients. Immediately after the surgery, DSA was proved that the occluded arteries were reeanalizalized completely. After the surgery the symptoms were markedly improved in the 3 patients. The NIHSS scores in 2 cases were significantly decreased than before. Conclusion EMR can improve tin; neurologic impairment better in CI patients with extracranial arterial occlusion.


Zheng H.,Southern Medical University | Li W.,Southern Medical University | Wang Y.,Southern Medical University | Liu Z.,Southern Medical University | And 7 more authors.
European Journal of Cancer | Year: 2013

Fas signalling has been shown to induce the epithelial-mesenchymal transition (EMT) to promote gastrointestinal (GI) cancer metastasis, but its mechanism of action is still unknown. The effects of Fas-ligand (FasL) treatment and inhibition of Fas signalling on GI cancer cells were tested using invasion assay, immunofluorescence, immunoblot, Reverse Transcription Polymerase Chain Reaction (RT-PCR), quantitative Real-time PCR (qRT-PCR), immunoprecipitation and luciferase reporter assay. Immunohistochemistry was used to analyse the EMT-associated molecules in GI cancer specimens. FasL treatment inhibited E-cadherin transcription by upregulation of Snail in GI cancer cells. The nuclear expression and transcriptional activity of Snail and β-catenin were increased by inhibitory phosphorylation of glycogen synthase kinase-3 beta (GSK-3β) at Ser9 by FasL-induced extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signalling. Snail associated with β-catenin in the nucleus and, thus, increased β-catenin transcriptional activity. Evaluation of human GI cancer specimens showed that the expression of FasL, phospho-GSK-3β, Snail and β-catenin increase during GI cancer progression. An EMT phenotype was shown to correlate with an advanced cancer stage, and a non-EMT phenotype significantly correlated with a better prognosis. Collectively, these data indicate that GSK-3β regulates Snail and β-catenin expression during Fas-induced EMT in gastrointestinal cancer. © 2013 Elsevier Ltd. All rights reserved.


Wang B.-W.,Second Peoples Hospital of Zhuhai | Gao Y.,Nanlang Peoples Hospital of Zhongshan
Ophthalmology in China | Year: 2013

Objective To analyze the effect of a new phacoemulsification technique in the treatment of hard nuclear cataract. Design Retrospective case series. Participants One hundred ninety eight patients with hard nuclear cataract were enrolled in this study. Methods Phacoemulsification and intraocular lens implantation were performed. Patients were divided into two groups: A, burst mode using a crushing and chopping technique, and B, a continue mode with a divide and conquer technique. Main Outcome Measure Phaco power, phaco time, visual acuity, corneal edema and corneal endothelial cell loss were evaluated at day 1, and 1 week and 1 month postoperatively. Results Average phacoemulsification power in group A and group B were 8.1%±1.3% and 27.0%±3.4%, respectively. Average phaco time was 59.2±5.8 seconds and 256.1±14.5 seconds in group A and B, respectively. The differences were statistically significant (all P<0.001). Endothelial cells loss was 4.5±2.4% and 9.5±5.4% in group A and B, respectively. One day after surgery, 70 cases (68.0%) in group A and 12 cases (12.6%) in group B achieved corrected visual acuity of 0.5 or better. The difference was statistically significant (P<0.001). One day after surgery, 72(69.9%) and 13(13.6%) patients were found to have grade I corneal edema, and 6 (5.8%) and 35 (36.8%) cases had grade IV corneal edema, in group A and B respectively. Posterior capsular rupture only occurred in one case in group B. Conclusion Compared with the continue mode, phacoemulsification with the burst mode and an effective chop technique may reduce phaco power and time for the treatment of patients with hard nucleus. Burst mode seemed to be more effective with less complications.


Duan H.,Second Peoples Hospital of Zhuhai
Zhonghua Shiyan Yanke Zazhi/Chinese Journal of Experimental Ophthalmology | Year: 2014

Background: Cataract was directly associated with the damage to the structure and function of lens epithelial cells (LECs). In those patients who suffer from cataracts, morphologic changes of LECs is the most compelling evidence confirming loss of cellular structure and function of LECs. So, learning about the morphological changes of LECs of the different types of cataracts is very important for study on biological behaviors of LECs in different environments or diseases. Objective: This study was to evaluate the morphological and ultrastructural changes of the LECs in different types of cataracts. Methods: Anterior capsular member from age-related cataracts, diabetic cataracts and high myopia complicated cataract were obtained during the cataract surgery and 15 pieces for each. Trypan blue and alizarin red (TB-AR) stain, haematoxylin and eosin stain were performed in the samples to assess the viability and morphology of LECs. The ultrastructural change of LECs was observed under the transmission electron microscope. The features of the LECs were compared among the different types of cataract. Results: TB-AR stain showed that LECs were polygon in shape with the mosaic arrangement and round cell nucleus, and a few dead cells were seen in the samples age-related cataract. In the diabetic samples, LECs largened from swelling with different sizes. More dead cells were found in the high myopia complicated cataract. Haematoxylin and eosin stain exhibited that the anterior capsular membrane presented a homogeneuous membrane, and monolayer LECs attached firmly anterior capsular membrane in the samples of related cataract. Majority of the cells had the intact structure. However, the interspaces between cells and capsular membrane were found in diabetic cataract. Also, smaller LECs were seen in high myopia complicated cataract with the irregular cell morphology. Under the transmission electron microscope, LECs presented the normal shape, intact intercellular tight junction and well attachment between cells and capsular membrane in the samples of the age-related cataract. In the samples of the diabetic cataract, edema of LECs and large intercellular spaces were seen. In addition, the jogged pump and vacuolar degeneration of cytoplasm were revealed in the high myopia complicated cataract. Conclusions: The degeneration, necrosis and apoptosis was a common pathological basis of age-related cataract, diabetic cataract and high myopia complicated cataract. However, the damage of LECs was more serious in diabetic cataract and high myopia complicated cataract than that of age-related cataract. Copyright © 2014 by the Chinese Medical Association.

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