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The prognostic molecular markers in hepatocellular carcinoma

World Journal of Gastroenterology 2002年第3期8卷 385-392页

作者： Lun-Xiu Qin Zhao-You Tang,Liver Cancer institute and Zhongshan Hospital,Fudan University,shanghai,china Liver Cancer institute and Zhongshan Hospital Fudan university 136 Yi Xue Yuan Road Shanghai 200032 China.

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) leve

关键词： Apoptosis Carcinogens Carcinoma, Hepatocellular Cell Adhesion Cell Division Cell Nucleus Extracellular Matrix Genes, p53 Humans Liver Neoplasms Neovascularization, Pathologic Ploidies Prognosis Proteome Telomerase Tumor Markers, Biological

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The prognostic significance of clinical and pathological features in hepatocellular carcinoma

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World Journal of Gastroenterology 2002年第2期8卷 193-199页

作者： Lun-Xiu Qin Zhao-You Tang,Liver Cancer institute and Zhongshan Hospital,Fudan University,shanghai,china Liver Cancer institute Zhongshan Hospital 136 Yi Xue Yuan Road Shanghai 200032 China.

The prognosis of patients with HCC still remains dismal. The life expectancy of HCC patients is hard to predict because of the high possibility of postoperative recurrence. Many factors, such as patient's general conditions, macroscopic tumor morphology, as well as tumor histopathology features, have been proven of prognostic significance. Female HCC patient often has a better prognosis than male patient, which might be due to the receptor of sex hormones. Younger patients often have tumors with higher invasiveness and metastatic potentials, and their survival and prognosis are worse than the older ones. Co-existing hepatitis status and hepatic functional reserve have been confirmed as risk factors for recurrence. Serum alpha-fetoprotein (AFP) is useful not only for diagnosis, but also as a prognostic indicator for HCC patients. AFP mRNA has been proposed as a predictive marker of HCC cells disseminated into the circulation and for metastatic recurrence. Many pathologic features, such as tumor size, number, capsule state, cell differentiation, venous invasion, intrahepatic spreading, and advanced pTNM stage, are the best-established risk factors for recurrence and important aspects affecting the prognosis of patients with HCC. Marked inflammatory cell infiltration in the tumor could predict a better prognosis. clinical stage is still the most important factor influencing on the prognosis. Extratumor spreading and lymph nodal metastasis are independent predictors for poor outcome. Some new predictive systems have recently been proposed. Different strategies of treatment might have significant different effects on the patients' prognosis. To date, surgical resection is still the only potentially curative treatment for HCC, including localized postoperative recurrences. Extent of resection, blood transfusion, occlusion of porta hepatis, and blood loss affect the survival and prognosis of HCC patients. Regional therapies provide alternative ways to improve the prognosis

关键词： Age Factors Carcinoma, Hepatocellular Hepatitis Humans Liver Cirrhosis Liver Neoplasms Neoplasm Staging Prognosis Recurrence Sex Factors alpha-Fetoproteins

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Pain research in china

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Science china(Life Sciences) 2010年第3期53卷 356-362页

作者： ZHANG Xu institute of Neuroscience,State Key Laboratory of Neuroscience,shanghai institutes for Biological Sciences,Chinese Academy of Sciences,shanghai 200031,china institute of Neuroscience State Key Laboratory of Neuroscience Shanghai Institutes for Biological Sciences Chinese Academy of Sciences

In addition to investigating the anatomy,neurochemistry and neurophysiology of pain pathways,Chinese researchers have extended their work into the molecular and cellular mechanisms of sensory afferent transmission at the spinal cord level as well as cognitive processing in the *** mechanism underlying acupuncture analgesia remains a subject of special interest for Chinese pain researchers,with the aim of combining clinical practice with the understanding of pain transmission and analgesic mechanism.

关键词： dorsal root ganglion spinal cord nociception receptors ion channels gene expression

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Expression of Hepatitis C Virus E2 Ectodomain in *** and Its Application in the Detection of Anti-E2 Antibodies in Human Sera

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Acta Biochimica et Biophysica Sinica 2004年第1期36卷 57-63页

作者： Jing LIU, Xin-Xin ZHANG, Shen-Ying ZHANG, Min LU, Yu-Ying KONG, Yuan WANG, and Guang-Di LI ( State Key Laboratory of Molecular Biology, institute of Biochemistry and Cell Biology, shanghai institutes for Biological Sciences, the Chinese Academy of Sciences, shanghai 200031, china 2 Department of Infectious Diseases, Ruijin Hospital, Second Medical University of shanghai, shanghai 200025, china ) State Key Laboratory of Molecular Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences the Chinese Academy of Sciences Shanghai 200031 China Department of Infectious Diseases Ruijin Hospital Second Medical University of Shanghai Shanghai 200025 China

The second envelope glycoprotein （E2） of hepatitis C virus has been shown to bind human target cells and has become a major target for the development of anti-HCV vaccines. Anti-E2 antibodies have been suggested to be of clinical significance in diagnosis, treatment and prognosis of hepatitis C. However, large-scale expression and purification of E2 proteins in mammalian cells is difficult. As an alternative, E2 fragment （aa 385-730） with a four-amino-acid mutation （aa 568-571 PCNI to RVTS） was expressed as hexa-histidine-tagged full length protein [E2N730（m）] in E. coli and purified to over 85% purity. Purified E2N730（m） was specifically recognized by homologous hepatitis C patient serum in Western blot, suggesting that it displayed E2specific antigenicity. Rabbit antiserum raised against E2N730（m） recognized E2 glyco-proteins expressed in mammalian cells in Western blot. Purified E2N730（m） was used to detect anti-E2 antibodies in human sera and showed better specificity and sensitivity than previousl

关键词： hepatitis C virus envelope protein E2 expression and purification Escherichia coll

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Prognostic role of diabetes mellitus in hepatocellular carcinoma patients after curative treatments:a meta-analysis

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Hepatobiliary & Pancreatic Diseases International 2011年第4期10卷 346-355页

作者： Wei-Min Wang,Yang Xu,Xin-Rong Yang,Yao-Hui Wang,Hai-Xiang Sun and Jia Fan institute of Biomedical Sciences,Fudan University,shanghai 200032,china Key Laboratory of Carcinogenesis and Cancer Invasion,Ministry of Education,and Liver Cancer institute,Zhongshan Hospital,Fudan University,shanghai 200032,china Fudan University shanghai Cancer Center,shanghai 200032,china institute of Biomedical Sciences Fudan University Shanghai 200032 China Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education and Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai 200032 China Fudan University shanghai Cancer Center Shanghai 200032 China

BACKGROUND:The prognostic role of diabetes mellitus (DM) coexisting with hepatocellular carcinoma (HCC) remains *** clarify its impact on survival in HCC patients after curative treatments,a meta-analysis was *** SOURCES:Eligible studies were identified through multiple search strategies in the databases PubMed (MEDLINE),EMBASE,the Cochrane Library and ACP Journal Club between January 1950 and March *** studies fulfilled the inclusion criteria,and data were aggregated comparing overall survival and recurrence-free survival in HCC patients according to DM ***:The pooled hazard ratios (HRs) estimate for overall survival was 1.34 (95% CI,1.18-1.51;Pclinical trials with consistent methodology,especially prospective studies.

关键词： hepatocellular carcinoma diabetes mellitus prognostic factors survival meta-analysis

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Progress in studies of huperzine A,a natural cholinesterase inhibitor from Chinese herbal medicine

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Acta Pharmacologica Sinica 2006年第1期27卷 1-26页

作者： Rui WANG Hart YAN Xi-can TANG State Key Lahoratory of Drug Research.shanghai institute of Materia Medica.shanghai institutes for Biological Sciences Chinese Academy of Sciences.shanghai 201203,china StateKeyLaboratoryofDrugResearch ShanghaiInstituteofMateriaMedicaShanghaiInstitutesforBiologicalSciencesChineseAcademyofSciencesShanghai201203China

Huperzine A (HupA),a novel alkaloid isolated flom the Chinese herb Huperziaserrata,is a potent,highly specific and reversible inhibitor of acetylcholinesterase(ACHE).Compared with tacrine,donepezil,and rivastigmine,HupA has betterpenetration through the blood-brain barrier,higher oral bioavailability,and longerduration of AChE inhibitory *** has been found to improve cognitivedeficits in a broad range of animal *** possesses the ability to protectcells against hydrogen peroxide,β-amyloid protein (or peptide),glutamate,ischemia and staurosporine-induced cytotoxicity and *** protec-tive effects are related to its ability to attenuate oxidative stress,regulate theexpression of apoptotic proteins ***,P53,and caspase-3,protectmitochondria,upregulate nerve growth factor and its receptors,and interfere withamyloid precursor protein *** effects of HupA on N-me-thyl-D-aspartate receptors and potassium currents may also contribute to itsneuroprotection as *** studies in rodents,canines,and healthyhuman volunteers indicated that HupA was absorbed rapidly,distributed widelyin the body,and eliminated at a moderate rate with the property of slow andprolonged release after oral *** and clinical safety tests showedthat HupA had no unexpected toxicity,particularly the dose-limiting hepalotoxic-ity induced by *** phase Ⅳ clinical trials in china have demonstratedthat HupA significantly improved memory deficits in elderly people with benignsenescent forgetfulness,and patients with Alzheimer disease and vasculardementia,with minimal peripheral cholinergic side effects and no *** can also be used as a protective agent against organophosphateintoxication.

关键词： huperzine A Alzheimer disease acetylcholinesterase cholinesterase inhibitors cognitive enhancer neuroprotect agents oxidative stress apoptosis

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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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Current research status of immunology in the genomic era

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Science china(Life Sciences) 2009年第1期52卷 43-49页

作者： LI HaoWen1,LI JinZhi1,ZHAO GuoPing2 & WANG Ying1,2 1 shanghai institute of Immunology,institute of Medical Science,shanghai Jiaotong University School of Medicine,shanghai 200025,china 2 shanghai-MOST Key Laboratory of Health and Disease Genomics,Chinese National Human Genome Center,shanghai 201203,china shanghai institute of Immunology Institute of Medical Science Shanghai Jiaotong University School of Medicine Shanghai 200025 China.

This review updates the current status of immunology research under the influence of genomics,both conceptually and *** particularly highlights the advantages of employing the high-throughput and large-scale technology,the large genomic database,and bioinformatic power in the immunology *** fast development in the fields of basic immunology,clinical immunology(tumor and infectious immunology) and vaccine designing is illustrated with respect to the successful usage of genomic *** also speculate the future research directions of immunology in the era of genomics and post-genomics.

关键词： genomics immunology clinical immunology vaccine design

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A 3-year clinical trial of lamivudine in treatment of patients with chronic hepatitis B

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Hepatobiliary & Pancreatic Diseases International 2004年第2期3卷 188-193页

作者： Guang-Bi Yao, Zhen-Yu Cui, Bao-En Wang, Ji-Lu Yao and Min-De Zeng shanghai, china shanghai Jing-An Qu Central Hospital, shanghai 200040, china Beijing Ditan Hospital, Beijing 100011 , china Beijing Friendship Hospital, Beijing 100050, china 3rd Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, chinaand shanghai Renji Hospital, shanghai Second Medical University, shanghai 200001 , china shanghai Jing-An Qu Central Hospital Shanghai 200040 China. yaogb@***

BACKGROUND: Lamivudine was approved for the treat- ment of chronic hepatitis B in china in 1999; however the long-term result has not yet been reported in detail. This clinical trial was to evaluate the long-term efficacy and safe- ty of 3-year lamivudine treatment for chronic hepatitis B and the impact of emergence of YMDD mutation of hepa- titis B virus (HBV). METHODS: This multi-center, randomized, double-blind, placebo controlled trial began from 1996 to 1999. A total of 429 patients with serum HBsAg, HBeAg and HBV DNA positive were randomized to receive either lamivudine 100 mg daily (322 patients) or placebo (107) for the first 12 weeks. All patients were given subsequently open labelled lamivudine 100 mg/d for a total of 156 weeks. RESULTS: After 12-week lamivudine therapy, the levels of serum HBV DNA decreased rapidly. The negativity of HBV DNA (2 × upper limit of normal (ULN) and ALT >5×ULN, the rates of HBeAg loss were 42.2% and 66.7%, and the rates of seroconversion were34.4% and 61.1% respectively (P<0.01) at the end of year 3. The levels of ALT at year 3 remained normal in 58.8% of patients whose baseline level of ALT was elevated

关键词： clinical trial hepatitis B virus chronic hepatitis B lamivudine

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Inhibition of Tumor Growth in Mice by Endostatin Derived from Abdominal Transplanted Encapsulated Cells

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Acta Biochimica et Biophysica Sinica 2007年第4期39卷 278-284页

作者： Huaining TENG~(1.3) Ying ZHANG~2 Wei WANG~2 Xiaojun MA~2* Jian FEI~1* 1 Laboratory of Molecular Cell Biology,institute of Biochemistry and Cell Biology,Model Organism Research Center,shanghai institutes for Biological Sciences,Chinese Academy of Sciences,shanghai 200031,china 2 Laboratory of Biomedical Material Engineering,Dalian institute of Chemical Physics,Chinese Academy of Sciences,Dolian 116023,china 3 Department of Urology,Changzheng Hospital,Second Military Medical University,shanghai 200003,china Laboratory of Molecular Cell Biology Institute of Biochemistry and Cell Biology Model Organism Research Center Shanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai 200031 China Department of Urology Changzheng Hospital Second Military Medical UniversityShanghai 200003 China Laboratory of Biomedical Material Engineering Dalian Institute of Chemical Physics Chinese Academy of SciencesDalian 116023 China

Endostatin,a C-terminal fragment of collagen 18a,inhibits the growth of established tumorsand metastases in vivo by inhibiting ***,the purification procedures required for large-scale production and the attendant cost of these processes,together with the low effectiveness in clinicaltests,suggest that alternative delivery methods might be required for efficient therapeutic use of *** the present study,we transfected Chinese hamster ovary(CHO)cells with a human endostatin geneexpression vector and encapsulated the CHO cells in alginate-poly-L-lysine *** release ofbiologically active endostatin was confirmed using the chicken chorioallantoic membrane *** encap-sulated endostatin-expressing CHO cells can inhibit the growth of primary tumors in a subcutaneous B 16tumor model when injected into the abdominal cavity of *** results widen the clinical applicationof the microencapsulated cell endostatin delivery system in cancer treatment.

关键词： microencapsulation endostatin CHO tumor gene therapy

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