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遗传学进步促进粮食安全与人口健康高峰论坛

作者： Fu Yang1,Ling Zhang1,Xi-song Huo1,Ji-hang Yuan1,Dan Xu1,Sheng-xian Yuan2,Nan Zhu3,Wei-ping Zhou2,Guang-shun Yang3,Yu-zhao Wang1,Jing-li Shang1,Chun-fang Gao4,Feng-rui Zhang5,Fang Wang1,Shu-han Sun1 department of medical Genetics,second military medical university,shanghai,china 2 The Third department of Hepatic Surgery,eastern hepatobiliary hospital,second military medical university,shanghai,china 3 The second department of Hepatic Surgery,eastern hepatobiliary hospital,second military medical university, shanghai,china 4 department of laboratory medicine,eastern hepatobiliary hospital,second military medical university,shanghai,china 5 department of hepatobiliary Surgery,Hebei Cancer hospital,Hebei medical university,Hebei,china.

Hepatocellular carcinoma(HCC) is one of the most common human cancers worldwide, particularly in Southeast Asia and *** than 70-80%of HCC cases occur in high hepatitis B virus(HBV) endemic regions,and 50%of HCC cases worldwide are attributable to chronic infection with ***,the 5-year survival rate of HBV-related HCC patients remains poor,and approximately 600,000 HCC patients die each year despite recent advances in surgical techniques and medical *** previous studies identified many aberrantly expressed protein-coding genes in HCC,novel molecular markers that can help in early diagnosis and risk assessment are still urgently *** is of paramount importance to understand the relationships between clinical symptoms and molecular changes in HCC for developing new diagnosis and treatment strategies for HCC and improving the prognosis of diagnosed patients. The human transcriptome comprises not only large numbers of protein-coding messenger RNAs(mRNAs) but also a large set of non-protein coding transcripts that have structural,regulatory or unknown *** studies of small non-coding RNAs(18 to 200 nucleotides(nt)) have dominated the field of RNA biology in recent years,a surprisingly wide array of cellular functions has also been associated with long non-coding RNAs(IncRNAs).IncRNAs,tentatively defined as non-coding RNAs more than 200 nt in length,are characterized by the complexity and diversity of their sequences and mechanisms of action.A handful of studies have implicated IncRNAs in a variety of disease states,and altered IncRNA levels can result in aberrant expression of gene products that may contribute to cancer ***,there are only preliminary studies on the role of IncRNAs in HCC,and the overall pathophysiological contributions of IncRNAs to HCC remain largely unknown. In this study,we have identified non-overlapping signatures of a small number of IncRNAs that are aberrantly expressed in human HBV

关键词： hepatocellular carcinoma noncoding RNAs PRC2 IncRNAs cell cycle

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Effect of Sirpα1 on the expression of nuclear factor-kappa B in hepatocellular carcinoma

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hepatobiliary & Pancreatic Diseases International 2007年第3期6卷 276-283页

作者： Jian-Min Qin,Xing-Wang Wan,Jin-Zhang Zeng and Meng-Chao Wu department of hepatobiliary and Pancreatic Surgery,Beijing Chaoyang hospital,Capital university of medical Sciences,Beijing 100020,china and eastern hepatobiliary Surgery hospital,second military medical university,shanghai 200438, china department of hepatobiliary and Pancreatic Surgery Beijing Chaoyang Hospital Capital University of Medical Sciences Beijing 100020 China. jianminqin@***

BACKGROUND:Signal regulatory protein alpha1(Sirpα1) is a member of Sirps families containing four immunoreceptor tyrosine-based inhibitory motifs(ITIMs) domains in the cytoplasm of and an activated substrate of receptor tyrosine kinase(RTK),that negatively regulates the RTK-dependent cell proliferating signal transduction *** we found that Sirpα1 was closely associated with the occurrence and development of hepatocellular carcinoma(HCC)as well as liver *** it is unclear about the regulatory mechanisms,we established the cell line transfected Sirpα1 gene and preliminarily clarified the mechanisms by which Sirpα1 negatively regulates the carcinogenesis and development of HCC. METHODS:Liver cancer Sk-Hep1 cell was respectively transfected with plasmids of pLXSN,pLXSN-Sirpα1 and pLXSN-Sirpα1Δ4Y 2 ,screened with the drug of G418(1200 μg/ml),and various transfected Sk-Hep1 cell lines were *** protein expressions of P65,P50,IκBα,cyclin D1 and Fas in various Sk-Hep1 cell lines were determined by Western blotting,and P65 and P50 were localized by the immunofluorescence technique. RESULTS:Sirpα1 could significantly upregulate the protein expression of IκBα(*** cell lines,P4Y 2 ,but in nucleus of the Sk-Hep1 cell with wild Sirpα1.P50 protein expression was localized in the cytoplasm and nucleus of the pLXSN Sk-Hep1 cell,but in the nucleus of the Sk-Hep1 cell with wild Sirpα1 and mutant Sirpα1Δ4Y 2 plasmid. CONCLUSIONS:Sirpα1 might negatively regulate and control the abnormal proliferation of liver cancer cells by influencing the protein content and localization of nuclear factor-kappa B,then influence the expression of cyclins such as cyclin D1 in the si

关键词： signal regulatory protein alpha1 carcinoma,hepatocellular nuclear transcription factor

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Combined invagination and duct-to-mucosa techniques with modifications:anew method of pancreaticojejunal anastomosis

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hepatobiliary & Pancreatic Diseases International 2011年第4期10卷 422-427页

作者： Bin Zhu,Li Geng,You-Gang Ma,Yong-Jie Zhang and Meng-Chao Wu second department of Biliary Surgery and department of Special Treatment,eastern hepatobiliary Surgery hospital,second military medical university,shanghai 200438,china [a] second department of Biliary Surgery Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 China [b] department of Special Treatment Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 China

BACKGROUND:Soft pancreatic texture and a small main pancreatic duct are thought to be the most significant risk factors for the occurrence of pancreatic fistula (PF),a common and serious complication after pancreaticoduodenectomy (PD).This is in part due to the technical difficulties of pancreaticojejunostomy (PJ) posed by a soft gland with a normal-sized *** deal with this problem,we developed a new anastomotic technique which combines the two most widely used techniques,namely,the invagination technique and the duct-to-mucosa technique,with a modification of the suture route and insertion of a temporary stent ***:Between January 2003 and December 2009,ninetytwo consecutive patients underwent PD in which the new PJ technique was *** and follow-up data of these patients were reviewed for operative details,early postoperative events,and outcomes at 6 months after the *** was defined by the International Study Group on Pancreatic Fistula (ISGPF) guidelines and graded (A,B or C) according to the clinical procedures and ***:In this group of 92 patients,there was only 1 early death from acute renal *** was observed in 11 patients (12.0%),8 in grade A,1 in grade B,and 2 in grade *** the 2 patients in grade C,PF was surgically *** were no early or late deaths attributable to *** months after the operation,all of the patients were free of PJ-related symptoms except for 2,who were found to have ***:Our modified technique is simple and safe in *** data suggest that this technique produces excellent early and medium-term results.

关键词： pancreaticoduodenectomy pancreaticojejunostomy pancreatic fistula

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The expression and antigenicity identification of recombinant rat TGF-β1 in bacteria

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Cell Research 2001年第2期11卷 95-100页

作者： GAO CHUN FANG, XIAN TAO KONG, AXEL M GRESSNER, RALF WEISKIRCHEN department of laboratory medicine, Changzheng hospital, second military medical university, shanghai 200003, china Institute of Clinical Chemistry and Pathobiochemistry, Central laboratory, R 1department of laboratory medicine Changzheng Hospital Second Military Medical University Shanghai 200003 China 1department of laboratory medicine Changzheng Hospital Second Military Medical University Shanghai 200003 China 2Institute of Clinical Chemistry and Pathobiochemistry Central Laboratory RWTH-University Hospital Pauwelsstr 30 D-52074 Aachen Germany 2Institute of Clinical Chemistry and Pathobiochemistry Central Laboratory RWTH-University Hospital Pauwelsstr 30 D-52074 Aachen Germany

In order to study structure-function details of TGF-β1, the recombinant mature form of rat TGF-β1 was expressed in bacteria. Synthesis of the 112 amino-acid carboxyl-terminal part of TGF-β1 (amino acid 279-390) was controlled by an inducible gene expression system based on bacteriophage T7 RNA polymerase. This system allowed an active and selective synthesis of recombinant TGF-β1. The molecular weight of expressed TGF-β1 monomer determined on SDS-polyacrylamide gel under reducing conditions was about 13 kD. Serial detergent washes combined with a single gel-filtration purification step were sufficient to purify the expression product to homogeneity. Amino-terminal sequencing revealed that the N-terminal of the recombinant protein was identical to the published data. In Western blot analysis the recombinant polypeptide showed excellent antigenicity against polyclonal TGF-β1 antibody. The mature recombinant rat TGF-β1 expressed in this study provides a useful tool for future detailed structural and functional studies.

关键词： TGF-β1 recombinant expression inclusion bodies purification antigenicity.

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Changes of serum alpha-fetoprotein and alpha-fetoprotein-L3 after hepatectomy for hepatocellular carcinoma: prognostic significance

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hepatobiliary & Pancreatic Diseases International 2012年第6期11卷 618-623页

作者： Xiao-Feng Zhang, Zheng-Feng Yin, Kui Wang, Zong-Qin Zhang, Hai-Hua Qian,Le-Hua ShiAuthor Affiliations: The 4th department of Hepatic Surgery ,Molecular Oncology laboratory , eastern hepatobiliary Surgery hospital, second military medical university, shanghai 200438, china [a] The 4th department of Hepatic Surgery Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 China [b] Molecular Oncology laboratory Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 China

BACKGROUND: Alpha-fetoprotein (AFP) is the most established tumor marker of hepatocellular carcinoma (HCC), but one of its limitations is non-specificity. Many studies have demonstrated that alpha-fetoprotein-L3 (AFP-L3) is more specific than AFP in the early diagnosis and prognosis of HCC. However, there is a lack of knowledge about the post-hepatectomy profiles of serum AFP and AFP-L3 values in HCC patients. To identify the profiles after surgical resection of HCC, we analyzed the correlation between the profiles and postoperative HCC recurrence or survival, and evaluated their utility in predicting postoperative therapeutic efficacy and prognosis. METHODS: From August 2003 to December 2004, 318 patients with positive serum AFP who had received surgical resections were enrolled in this study. Preoperative and postoperative serum AFP and AFP-L3 levels were measured simultaneously and regularly, and their postoperative profiles during a long term follow-up were recorded and summarized. RESULTS: A high ratio of AFP-L3 to total AFP was shown to correlate with pathologic features of aggressiveness. The overall 1-, 3-, and 5-year recurrence rates of the whole series were 28% 57%, and 84%, and the overall survival rates were 86%, 61% and 33%, respectively. The changes of serum AFP and AFP-L3 after hepatectomy for HCC were classified into 3 groups (group A: AFP-L3 undetectable; group B: AFP-L3 10%). Patients with positive postoperative AFP-L3had significantly earlier recurrence than those with negative results. The overall survival was significantly shorter in the positive groups than in the groups negative for postoperative ***: Post-hepatectomy changes in serum AFP and AFP-L3 levels occurred in three distinct patterns, which were closely correlated with HCC recurrence and patient survival with different prognostic values.

关键词： hepatocellular carcinoma hepatectomy alpha-fetoprotein alpha-fetoprotein-L3

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Prognostic factors in the surgical treatment of caudate lobe hepatocellular carcinoma

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World Journal of Gastroenterology 2010年第9期16卷 1123-1128页

作者： Peng Liu,Jia-Mei Yang,Wen-Yang Niu,Tong Kan,Feng Xie,Dian-Qi Li,Ye Wang,Yan-Ming Zhou,department of Special Treatment and Liver Transplantation,eastern hepatobiliary Surgery hospital,second military medical university,shanghai 200438,china Peng Liu,department of hepatobiliary Surgery,Navy General hospital,Beijing 100037,china department of Special Treatment and Liver Transplantation Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 China. jmyang@***

AIM:To evaluate the short-and long-term outcomes of liver resection for caudate lobe hepatocellular carcinoma (HCC).METHODS:We retrospectively analyzed 114 consecutive patients with HCC,originating from the caudate lobe,who underwent resection between January 2001 and January *** and multivariate analyses were performed on several clinicopathologic variables to determine the factors affecting long-term outcome and intrahepatic ***:Overall mortality and morbidity were 0% and 18%,*** a median follow-up of 31 mo (interquartile range,11-66 mo),tumor recurrence had occurred in 76 patients (66.7%).The 1-,3-,and 5-year disease-free survival rates were 65.7%,38.1%,and 18.4%,*** 1-,3-,and 5-year overall survival rates were 76.1%,54.7%,and 31.8%,*** analysis showed that subsegmental location of the tumor (45.7% vs 16.2%,P=0.01),liver cirrhosis (12.3% vs 47.9%,P=0.03),surgical margin (18.5% vs 54.6%,P=0.04),vascular invasion (37.9% vs 23.2%,P=0.04) and extended caudate resection (42.1% vs 15.4%,P=0.04) were related to poorer long-term *** analysis showed that only subsegmental location of the tumor,liver cirrhosis and surgical margin were significant independent prognostic ***:Hepatectomy was an effective treatment for HCC in the caudate *** subsegmental location of the tumor,liver cirrhosis and surgical margin affected long-term survival.

关键词： Hepatectomy Hepatocellular carcinoma Caudate lobe Prognostic factors

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Expression of HBx protein in hepatitis B virus-infected intrahepatic cholangiocarcinoma

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hepatobiliary & Pancreatic Diseases International 2012年第5期11卷 532-535页

作者： Yan-Ming Zhou, Lu Cao, Bin Li, Xiu-Zhong Zhang, Zheng-Feng Yin department of Hepato-Biliary-Pancreato-Vascular Surgery, First Affiliated hospital of Xiamen university, Xiamen 361003, china department of Molecular Oncology,department of Pathology, eastern hepatobiliary Surgery hospital,second military medical university, shanghai 200438, china [a] department of Hepato-Biliary-Pancreato-Vascular Surgery First Affiliated Hospital of Xiamen University Xiamen 361003 Shanghai China [b] department of Molecular Oncology Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 Shanghai China [c] department of Pathology Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 Shanghai China

BACKGROUND: Hepatitis B virus (HBV) is an etiological factor of intrahepatic cholangiocarcinoma (ICC), but the pathogenic mechanisms remain unclear. This study aimed to investigate the expression and possible role of HBx, an HBV- encoded potentially oncogenic protein, in HBV-infected ICC. METHODS: Tissue samples were obtained from 54 specimens of HBV-infected ICC. Forty-four specimens were of peripheral type and 10 hilar type. Formalin-fixed, paraffin-embedded sections of the specimens were immunohistochemically stained for HBx and p53. RESULTS: HBx expression was found in 70.4% (38/54) of the specimens, and it was more frequently seen in the peripheral type than in the hilar type (79.5% vs 30.0%, P=0.002). All three well-differentiated ICCs expressed HBx, whereas 76.9% (30/39) moderately-differentiated and 41.7% (5/12) poorly-differentiated ICCs had HBx expression (P=0.033). Patients with HBx expression had a significantly higher prevalence of elevated serum alpha-fetoprotein (P=0.033). p53 protein expression was found in 18 of 54 cases (33.3%), and was not correlated with that of HBx. CONCLUSIONS: HBx may contribute to the pathogenesis of ICC, particularly the peripheral type. p53 abnormality may not play a significant role in HBx-mediated oncogenicity during ICC carcinogenesis.

关键词： hepatitis B virus HBx protein p53 intrahepatic cholangiocarcinoma

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Risk factors of intrahepatic cholangiocarcinoma in patients with hepatolithiasis:a case-control study

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hepatobiliary & Pancreatic Diseases International 2011年第6期10卷 626-631页

作者： Zhen-Yu Liu,Yan-Ming Zhou,Le-Hua Shi and Zheng-Feng YinAuthor Affiliations:Molecular Oncology laboratory and department of Comprehensive Treatment I,eastern hepatobiliary Surgery hospital,second military medical university,shanghai 200438,china department of Hepato-Biliary-Pancreato-Vascular Surgery,First Affiliated hospital,Xiamen university,Xiamen 361003,china Molecular Oncology laboratory Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 China department of Comprehensive Treatment I Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 China department of Hepato-Biliary-Pancreato-Vascular Surgery First Affliated Hospital Xiamen University Xiamen 361003 China

BACKGROUND:Why 3.3% to 10% of all patients with hepatolithiasis develop intrahepatic cholangiocarcinoma (ICC) remains *** carried out a hospital-based case-control study to identify risk factors for the development of ICC in patients with hepatolithiasis in ***:Eighty-seven patients with pathologically diagnosed hepatolithiasis associated with ICC and 228 with hepatolithiasis alone matched by sex,age (±2 years),hospital admittance and place of residence were interviewed during the period of *** ratios (OR) and 95% confidence intervals (CI) were calculated for each risk ***:Among the patients with hepatolithiasis associated with ICC,the mean age was 57.7 years and 61.0% were female Univariate analysis showed that the significant risk factors for ICC development in hepatolithiasis were smoking,family history of cancer,appendectomy during childhood (under age 20),and duration of symptoms >10 *** multivariate stepwise logistic regression analysis,smoking (OR=1.931,95% CI:1.000-3.731),family history of cancer (OR=5.175,95% CI:1.216-22.022),and duration of symptoms >10 years (OR=2.348 95% CI:1.394-3.952) were independent ***:Smoking,family history of cancer and duration of symptoms >10 years may be risk factors for ICC in patients with hepatolithiasis.

关键词： risk factors intrahepatic cholangiocarcinoma hepatolithiasis case-control study

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Intrahepatic cholestasis after liver transplantation

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hepatobiliary & Pancreatic Diseases International 2002年第2期1卷 176-178页

作者： Jia-Mei Yang Bin Zhu From the department of Liver Transplantation, eastern Hapatobiliary Surgery hospital, the second military medical university, shanghai 200438, china department of Liver Transplantation Eastern Hepatobiliary Surgery Hospital the Second Military Medical University Shanghai 200438 China. jmyang@***

Intrahepatic cholestasis occurs commonly after liver transplantation and may be caused by infections, drugs, and acute or chronic rejection. Some disor- ders may be managed medically, but others often re- quire re-tra... 详细信息

关键词： intrahepatic cholestasis liver transplantation

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Gradual upregulation of OCI-5 expression during occurrence and progression of rat hepatocellular carcinoma

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hepatobiliary & Pancreatic Diseases International 2006年第2期5卷 257-261页

作者： Wei-Jun Jiang, Xiao-Bo Man, Liang Tang, Hong-Yin Song, Shen-Jing Li, Guo-Jun Cai, Xiu-Hua Qiu and He-Ping Hu department of Gastroenterology, shanghai Tongren hospital, shanghai 200050, china department of Gastroenterology, eastern hepatobiliary Surgery hospital, second military medical university, shanghai 200438, china department of Phannacology, second military medical university, shanghai 200433, china department of Gastroenterology Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 China.

BACKGROUND: OCI-5, the rat homologene of human glypican 3 ( GPC3), is confirmed upregulated in hepatocellular carcinoma (HCC). The present study was undertaken to detect gene expression change of OCI-5 during occurrence and progression of rat HCC. METHODS: Male Sprague-Dawley rats were given diethyl-nitrosamine ( DENA) to induce HCC. Three DENA-induced rats and one control rat were sacrificed every week for 18 weeks during the development of HCC. Tissues specimens were snap-frozen in liquid nitrogen and total RNA was isolated. Sk-Hepl cells were treated with DENA at different concentrations. The gene expression levels of OCI-5 and GPC3 were detected with the RT-PCR method. RESULTS: OCI-5 was not expressed in normal rat liver tissues. When HCC occurred and aggravated, OCI-5 expression was gradually elevated to a very high level. GPC3 was not expressed in the DENA-treated Sk-Hepl cells. CONCLUSIONS: OCI-5 was not expressed in normal rat liver tissues but in rat HCC tissues. High-expression of OCI-5 in DENA-induced rat HCC model was the gene expression change of HCC not the DENA-induced gene expression. The expression level of OCI-5 was not only elevated in rat HCC but also gradually along the occurrence and progression of HCC, indicating that GPC3 might serve as a sensitive marker of early stage HCC.

关键词： OCI-5 gene expression carcinoma, hepatocellular rat

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