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Zhang J.,Shanghai University | Yang Y.,Shanghai University | Yang T.,Shanghai University | Yuan S.,Shanghai University | And 8 more authors.
Hepatology | Year: 2015

Growing evidence indicates that the aberrant expression of microRNAs (miRNAs) contributes to tumor development; however, the function of miRNAs in human hepatocellular carcinoma (HCC) remains largely undefined. In this study, we report that microRNA-422a (miR-422a) is significantly down-regulated in HCC tumor samples and cell lines compared with normal controls, and its expression level is negatively correlated with pathological grading, recurrence, and metastasis. The restoration of miR-422a expression in HCC tumor cells significantly inhibited cell proliferation and migration in vitro. At the same time, the overexpression of miR-422a in HCC tumor cells significantly inhibits tumor growth and liver metastasis in xenograft tumor models. A mechanistic study identified three genes, forkhead box G1 (FOXG1), FOXQ1, and FOXE1, as miR-422a targets in the regulation of HCC development. We also investigated the function of the three targets themselves in HCC tumorigenesis using RNAi manipulation and demonstrated that the knockdown of these targets led to significant inhibition of tumor cell proliferation and migration both in vitro and in vivo. More interestingly, a potential miR-422a promoter region was identified. Both the promoter activity and miR-422a expression were negatively regulated by the three targets, indicating that a double-negative feedback loop exists between miR-422a and its targets. Moreover, we explored the therapeutic potential of miR-422a in HCC treatment and found that the therapeutic delivery of miR-422a significantly inhibited tumor development in a xenograft tumor model and a diethylnitrosamine-induced primary HCC model. Conclusion: Our findings show the critical roles of miR-422a and its targets-FOXG1, FOXQ1, and FOXE1-in the regulation of HCC development and provide new potential candidates for HCC therapy. © 2014 by the American Association for the Study of Liver Diseases.


Yang Y.,Shanghai University | Yuan S.-X.,Shanghai University | Zhao L.-H.,Shanghai University | Wang C.,Shanghai University | And 6 more authors.
Molecular Pharmaceutics | Year: 2015

Targeted delivery system would be an interesting platform to enhance the therapeutic effect and to reduce the side effects of anticancer drugs. In this study, we have developed lactobionic acid (LA)-modified chitosan-stearic acid (CS-SA) (CSS-LA) to deliver doxorubicin (DOX) to hepatic cancer cells. The average particle size of CSS-LA/DOX was 100 nm with a high entrapment efficiency of >95%. Drug release studies showed that DOX release from pH-sensitive micelles is significantly faster at pH 5.0 than at pH 7.4. The LA conjugated micelles showed enhanced cellular uptake in HepG2 and BEL-7402 liver cancer cells than free drug and unconjugated micelles. Consistently, CSS-LA/DOX showed enhanced cell cytotoxicity in these two cell lines. Annexin-V/FITC and PI based apoptosis assay showed that the number of living cells greatly reduced in this group with marked presence of necrotic and apoptotic cells. LA-conjugated carrier induced typical chromatic condensation of cells; membrane blebbing and apoptotic bodies began to appear. In vivo, CSS-LA/DOX showed an excellent tumor regression profile with no toxic side effects. The active targeting moiety, long circulation profile, and EPR effect contributed to its superior anticancer effect in HepG2 based tumor. Our results showed that polymeric micelles conjugated with LA increased the therapeutic availability of DOX in the liver cancer cell based solid tumor without any toxic side effects. The active targeting ligand conjugated nanoparticulate system could be a promising therapeutic strategy in the treatment of hepatic cancers. © 2014 American Chemical Society.


Hu Z.,Nanjing Medical University | Liu Y.,Nanjing Medical University | Zhai X.,Centers for Disease Control and Prevention | Dai J.,Nanjing Medical University | And 25 more authors.
Nature Genetics | Year: 2013

Chronic hepatitis B virus (HBV) infection is a challenging global health problem. To identify genetic loci involved in chronic HBV infection, we designed a three-phase genome-wide association study in Han Chinese populations. The discovery phase included 951 HBV carriers (cases) and 937 individuals who had naturally cleared HBV infection (controls) and was followed by independent replications with a total of 2,248 cases and 3,051 controls and additional replications with 1,982 HBV carriers and 2,622 controls from the general population. We identified two new loci associated with chronic HBV infection: rs3130542 at 6p21.33 (near HLA-C, odds ratio (OR) = 1.33, P = 9.49 × 10-14) and rs4821116 at 22q11.21 (in UBE2L3, OR = 0.82, P = 1.71 × 10-12). Additionally, we replicated the previously identified associations of HLA-DP and HLA-DQ variants at 6p21.32 with chronic HBV infection. These findings highlight the importance of HLA-C and UBE2L3 in the clearance of HBV infection in addition to HLA-DP and HLA-DQ.


News Article | December 15, 2016
Site: en.prnasia.com

SHANGHAI, Dec. 15, 2016 /PRNewswire/ -- Youku Business Division (Youku BD), a unit of the Alibaba Digital Media & Entertainment Group, and Oriental DreamWorks, today announced a three-year licensing partnership for the release of a DreamWorks Animation premium family entertainment content bundle in China. The new content will be available exclusively to users of Youku, Tudou and Tmall Box, the set-top box developed by Alibaba home entertainment business Unit. The bundle is one of the largest of its kind in terms of volume and range, and will enrich even further the entertainment content for users of Youku, Tudou and Tmall Box -- three of the major platforms within Youku BD. These platforms continue to innovate and raise the bar in terms of a high-quality digital entertainment experience. With this partnership, Youku BD aims to further expand its content library and strengthen its leading position as a one-stop family entertainment content platform in China. Yang Weidong, President of Youku BD said, "The agreement is our largest in the family entertainment category to date, building on our leadership in animation -- one of the most popular categories on our platforms. Through providing quality content, Youku BD continues to grow in terms of reach and services delivered. The newly acquired family content will enable our platform to play a more important and integrated role and add the benefit of enhancing our business within the OTT (over-the-top) space." Frank Zhu, CEO of Oriental DreamWorks said: "We value the long and successful collaboration with Youku Business Division on content including Kung Fu Panda franchise, and we are delighted to enrich the family entertainment content for Chinese audience through this landmark partnership." The first content release is targeted for January 2017 and will include a wide assortment of well-known titles including the popular Kung Fu Panda, Shrek, and How to Train Your Dragon franchises. The bundle will also include upcoming feature films such as Boss Baby, Captain Underpants, and How to Train Your Dragon 3. TV series including Blackstar, Casper's, and the upcoming Troll Hunters will also be available to viewers. As China's leading digital entertainment platform, Youku BD has built the industry's most expansive content library with several thousand movie titles from around the world and covering approximately 95% of the movies shown in Chinese cinemas. Youku, Tudou and Alibaba home entertainment business collectively have become the No.1 destination of overseas content looking to reach China's internet viewers. The partnership was built on previous successful collaboration between the parties on the Kung Fu Panda franchise. Oriental DreamWorks achieved immense success and made the animated characters a part of Chinese consumers' everyday life through the support and channels made available by Alibaba and Youku. Youku Business Division, a pillar of the Alibaba Digital Media & Entertainment Group, has been formed through the combination of Youku, Tudou and Alibaba home entertainment business unit. Inaugurated in October 2016, Youku BD is China's leading digital entertainment platform and its business spans PC, TV and mobile devices. Its wide-ranging content contains copyrighted content, co-produced content, in-house productions, UGC/PGC (User/Professionally Generated Content), live webcast, and VR (Virtual Reality). Youku BD's business lines include subscription services, games, smart hardware and artists brokering, connecting content creation, marketing & promotion, merchandising and fans economy to form a complete value chain of media and entertainment. With its diverse content portfolio, strong platform and creative technologies, Youku BD delivers compelling audio & visual entertainment across devices, and caters to consumers' growing needs for interaction and innovation. Oriental DreamWorks is a joint venture backed by China Media Capital, Shanghai Media Group, Shanghai Alliance Investment Limited and Hollywood' s DreamWorks Animation SKG. Oriental DreamWorks thrives to create the highest level of family entertainment content and experience for Chinese and global consumers through services including but not limited to Film Production, Theatrical Marketing and Distribution, Copyright Operations, Ancillary Business (Consumer Product, Joint Promotion, Interactive Entertainment and Location-based Entertainment) development and operations. Oriental DreamWorks has also created and distributed the first American-Chinese animation "Kung Fu Panda 3," one of the most well-drawn animated films in China. For more information regarding the company, please visit our website at www.oriental-dreamworks.com. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/youku-businesses-partner-with-oriental-dreamworks-for-premium-content-300378946.html


Huang G.,Shanghai Alliance | Lau W.Y.,Shanghai Alliance | Lau W.Y.,Chinese University of Hong Kong | Wang Z.-G.,Shanghai Alliance | And 5 more authors.
Annals of Surgery | Year: 2015

Objective: A randomized controlled trial was conducted to find out whether antiviral therapy in patients with hepatitis B-related hepatocellular carcinoma (HCC) improves long-term survival after hepatic resection. Background: Despite advances in surgery and in multidisciplinary treatment, there is still no effective adjuvant treatment to prevent HCC recurrence after R0 resection for HCC. Whether antiviral therapy is useful in reducing postoperative HCC recurrence is unclear. Methods: Between May 2007 and April 2008, patients who received R0 hepatic resection for HBV-related HCC were randomly assigned to receive no treatment (the control group, n = 100) or antiviral therapy (adefovir 10 mg/d, the antiviral group, n = 100). Results: The baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.0%, 50.3%, 46.1% and 84.0%, 37.9%, 27.1%, respectively. The corresponding overall survival rates for the 2 groups were 96.0%, 77.6%, 63.1% and 94.0%, 67.4%, 41.5%, respectively. The recurrence-free survival and overall survival for the antiviral group were significantly better than the control group (P = 0.026, P = 0.001). After adjusting for the confounding prognostic factors in a Cox model, the relative risks of recurrence and death for antiviral treatment were 0.651 [95% confidence interval (CI): 0.451-0.938; P = 0.021] and 0.420 (95% CI: 0.271-0.651; P < 0.001). Antiviral therapy was an independent protective factor of late tumor recurrence (HR = 0.348, 95% CI: 0.177-0.687; P = 0.002) but not of early tumor recurrence [hazard ratio (HR) = 0.949, 95% CI: 0.617-1.459; P = 0.810]. Conclusions: In patients with hepatitis B-related HCC, adefovir antiviral therapy reduced late HCC recurrence and significantly improved overall survival after R0 hepatic resection. Copyright © 2014 by Lippincott Williams & Wilkins.


Huang G.,Shanghai Alliance | Chen X.,East China Normal University | Chen X.,Nanjing Political Academy | Lau W.Y.,Shanghai Alliance | And 6 more authors.
British Journal of Surgery | Year: 2014

Background Health-related quality of life (HRQL) is an important outcome measure in studies of cancer therapy. This study aimed to investigate HRQL and survival in patients with small hepatocellular carcinoma (HCC) treated with either surgical resection or percutaneous radiofrequency ablation (RFA). Methods Between January 2006 and June 2009, patients with newly diagnosed solitary, small (3 cm or less) HCC were invited to participate in this non-randomized prospective parallel cohort study. The Functional Assessment of Cancer Therapy - Hepatobiliary (FACT-Hep) instrument was used for assessing HRQL. HRQL and survival were compared between the two treatment groups. Results A total of 389 patients were enrolled. Questionnaires were completed fully by 99·7 per cent of invited participants (388 of 389) at baseline, 98·7 per cent (383 of 388) at 3 months, 99·0 per cent (379 of 383) at 6 months, 98·4 per cent (365 of 371) at 1 year, 96·6 per cent (336 of 348) at 2 years and 95·1 per cent (289 of 304) at 3 years. There were no significant differences in disease-free and overall survival between the two groups. Patients treated with percutaneous RFA had significantly better HRQL total scores after 3, 6, 12, 24 and 36 months than those who had surgical resection (P < 0·001, P < 0·001, P = 0·001, P = 0·003 and P = 0·025 respectively). On multivariable analysis, the presence of concomitant disease, cirrhosis and surgical resection were significant risk factors associated with a worse HRQL score after treatment. Conclusion Percutaneous RFA produced better post-treatment HRQL than surgical resection for patients with solitary small (no more than 3 cm) HCC. Radiofrequency ablation is a good alternative for surgery © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.


Wang W.,Shanghai Alliance | Xu G.,Shanghai Alliance | Ding C.-L.,Shanghai Alliance | Zhao L.-J.,Shanghai Alliance | And 3 more authors.
FEBS Journal | Year: 2013

As a therapeutic or chemopreventative agent for various cancers, all-trans retinoic acid (atRA) has been reported to inhibit growth, induce apoptosis or cause differentiation. It was found that atRA could protect hepatocellular carcinoma (HCC) cells against cell death induced by serum starvation. Furthermore, it was found that atRA could enhance cell adhesion, but had no effect on the cell cycle and apoptosis. Using an Illumina Human HT-12 v4 expression microarray, 207 upregulated and 173 downregulated genes were identified in HepG2 cells treated with atRA. The most upregulated genes are cytochrome P450 family 26 subfamily A polypeptide 1 (CYP26A1), histidine triad nucleotide binding protein 3 (HINT3), miR-1282 and cytochrome P450 family 26 subfamily B polypeptide 1 (CYP26B1), which showed more than fivefold greater expression. Using Gene Ontology analysis, the greatest significance was found in extracellular-matrix-related molecular functions and the cellular component in upregulated genes. The upregulation of collagen 8A2 (COL8A2) was further confirmed using quantitative RT-PCR and western blotting. Knockdown of COL8A2 blocked enhancement in the early stage of cell adhesion by atRA treatment. Re-expression of COL8A2 in COL8A2-knocked-down HCC cells reversed the effect of small interfering RNA-COL8A2. In addition, COL8A2 could increase HCC cell migration and invasion. Thus, COL8A2 was identified as the key protein involved in the enhancement of cell adhesion of atRA under serum-free conditions. In conclusion, atRA protects HCC cells against serum-starvation-induced cell death by enhancing cell adhesion, and COL8A2 plays an important role in HCC cell migration and invasion. As a therapeutic agent to various cancers, all-trans retinoic acid (atRA) has been reported to inhibit the growth, induce apoptosis or cause differentiation. In this study, atRA was found to protect HCC cells against serum starvation induced cell death, and COL8A2 was identified as the key protein involved in the enhancement of cell adhesion of atRA under serum free condition © 2013 FEBS.


News Article | May 11, 2005
Site: gigaom.com

Microsoft has formed a JV with a Chinese firm to launch MSN China and acquired assets of a local mobile software provider to offer MSN Mobile products and services in the country. It has partnered with Shanghai Alliance Investment to create the new Shanghai MSN Network Communications Technology Company…the venture plans to launch an MSN China portal in coming months, offering a range of content and services. MSN is also acquiring some assets of mobile software provider TSSX. Through the transaction, Microsoft plans to deliver enhanced MSN Mobile products and services, it said. The VC/M&A channel is sponsored by DeSilva & Phillips


News Article | May 11, 2005
Site: gigaom.com

Microsoft has formed a JV with a Chinese firm to launch MSN China and acquired assets of a local mobile software provider to offer MSN Mobile products and services in the country. It has partnered with Shanghai Alliance Investment to create the new Shanghai MSN Network Communications Technology Company…the venture plans to launch an MSN China portal in coming months, offering a range of content and services. MSN is also acquiring some assets of mobile software provider TSSX. Through the transaction, Microsoft plans to deliver enhanced MSN Mobile products and services, it said. MarketWatch: Under the deal with TSSX, Microsoft will acquire some the company’s assets and open a development center in Shenzhen. The development center will employ TSSX workers and integrate its technology and offerings with those of MSN.

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