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| 1 | Hepatocellular Carcinoma-Cause,Treatment and Metastasis显示文摘In the recent decades, the incidence of hepatocellular carcinoma (HCC) has been found to be increasing in males in some countries. In China, HCC ranked second of cancer mortality since 1990s. Hepatitis B and C viruses (HBV and HCV) and dietary aflatoxin intake remain the major causative factors of HCC. Surgery plays a major role in the treatment of HCC, particularly for small HCC. Downstaging unresectable huge HCC to smaller HCC and followed by resection will probably be a new approach for further study. Liver transplantation is indicated for small HCC, however, some issues remain to be solved.Different modes of 'regional cancer therapy for HCC' have been tried. Systemic chemotherapy has been disappointing in the past but the future can be promising.Biotherapy, such as cytokines, differentiation inducers,anti-angiogenic agents, gene therapy and tumor vaccine will probably play a role, particularly in the prevention of tumor recurrence. HCC invasiveness is currently the major target of study. Tremendous works have been done at the molecular level, which will provide clues for biomarker of HCC progressionas well as targets for intervention. | Zhao-You Tang Liver Cancer Institute & Zhongshan Hospital of Fudan University Professor of Surgery Chairman.Liver Cancer Institute of Fudan University(previous Liver Cancer Institute of Shanghai Medical University)136 Yixueyuan Road,Zhongshan Hospital,Shanghai 200032,China. | 2001 | World Journal of Gastroenterology2001，7，4： | 213 |
| 2 | Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97显示文摘ALM To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97. andbiological characteristics of the target clones selected by in vivo screening were studied.``RESULTS Two clones with high MHCC97-H and IowMHCC9--L1 metastatic potential were isolated from theparent cell line. Compared with MHCC97-L. MHCC97-H hadsmaller cell size average cell diameter 43 um vs 50 μmand faster in vitro and in vivo growth rate tumor celldoubling time was 34.2 h vs 60.0 h. The main ranges ofchromosomes were 5.5 58 in MHCC97-H and 57 62 inMHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was 137.5 - 11 .0) cellsfield for MHC_C99--H vs 17.7 - 6.3) field for MHCC97-L.The proportions of cells in GO Gl phase. S phase, and G_ M phase for MHCC97-H MHCC97-L were 0.56 6.65.0.28 0.25 and 0.l6 0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5 wk after orthotopic implantation of tumor tissue were ( 24666 μg. L for MHCC97-H and (91- 66) μg' L 1 for MHCC97L. The pulmonary metastatic rate was 100% (10-10) vs40% 4- 10).``CONCLUSION Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis. | Yan Li Zhao-You Tang Sheng-Long Ye Yin-Kun Liu Jie Chen Qiong Xue Jun Chen Dong-Mei Gao Wei-Hua Bao Liver Cancer Institute and Zhongshan Hospital of Fudan University (Former Liver Cancer Institute of Shanghai Medical University),Shanghai 200032,China | 2001 | World Journal of Gastroenterology2001，7，5： | 111 |
| 3 | The prognostic molecular markers in hepatocellular carcinoma显示文摘The prognosis of hepatocellular carcinoma (HCC) stillremains dismal, although many advances in its clinicalstudy have been made. It is important for tumor control toidentity the factors that predispose patients to death. Withnew discoveries in cancer biology, the pathological andbiological prognostic factors of HCC have been studied quiteextensively. Analyzing molecular markers (biomarkers) withprognostic significance is a complementary method. A largenumber of molecular factors have been shown to associatewith the invasiveness of HCC, and have potential prognosticsignificance. One important aspect is the analysis ofmolecular markers for the cellular malignancy phenotypeThese include alterations in DNA ploidy, cellularproliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, andCSE1L/CAS protein), nuclear morphology, the p53 geneand its related molecule MDM2, other cell cycle regulators(cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenesand their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members ), apoptosisrelated factors (Fas and FasL), as well as telomeraseactivity. Another important aspect is the analysis ofmolecular markers involved in the process of cancerinvasion and metastasis. Adhesion molecules (E-cadherin,catenins, serum intercellular adhesion molecule-1, CD44variants), proteinases involved in the clegradation ofextracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAl), aswell as other molecules have been regarded as biomarkersfor the malignant phenotype of HCC, and are related toprognosis and therapeutic outcomes. Tumor angiogenesisis critical to both the growth and metastasis of cancersincluding HCC, and has drawn much attention in recentyears. Many angiogenesis-related markers, such as vascularendothelial growth factor (VEGF), basic fibroblast growthfactor (bFGF), platelet-derived endothelial cell growth factor( PD-ECGF ), thrombospondin ( TSP ), angiogenin,pleiotrophin, and endostatin (ES) levels, as well asinratumor microvessel density (MVD) have been evaluatedand found to be of prognostic significance. Body fluid(particularly blood and urinary) testing for biomarkers iseasily accessible and useful in clinical patients. Theprognostic significance of circulating DNA in plasma orserum, and its genetic alterations in HCC are otherimportant trends. More attention should be paid to thesetwo areas in future. As the progress of the human genomeproject advances, so does a clearer understanding of tumorbiology, and more and more new prognostic markers withhigh sensitivity and specificity will be found and used inclinical assays. However, the combination of some items, i.e., the pathological features and some biomarkersmentioned above, seems to be more practical for now. | Lun-Xiu Qin Zhao-You Tang,Liver Cancer Institute and Zhongshan Hospital,Fudan University,Shanghai,China | 2002 | World Journal of Gastroenterology2002，8，3： | 162 |
| 4 | Multimodality treatment in hepatocellular carcinoma patients with tumor thrombi in portal vein显示文摘AIM To compare the therapeutic effect andsignificances of multimodality treatment forhepatocellular carcinoma (HCC) with tumorthrombi in portal vein (PVTT).METHODS HCC patients (n = 147) with tumortrombi in the main portal vein or the first branchof portal vein were divided into four groups bythe several therapeutic methods. There wereconservative treatment group in 18 out ofpatients (group A); and hepatic artery ligation(HAL) and/or hepatic artery infusion (HAl)group in 18 patients (group B), in whompostoberative chemoembolization was doneperiodically; group of removal of HCC with PVTTin 79 (group C) and group of transcatheterhepatic arterial chemoembolization (TACE) orHAl and/or portal vein infusion (PVI) afteroperation in 32 (group D).RESULTS The median survival period was 12months in our series and the 1-, 3-, and 5-yearsurvival rates were 44.3%, 24.5% and 15.2%,respectively. The median survival times were 2,5, 12 and 16 months in group A, B, C and D,respectively. The 1-, 3- and 5-year survival rateswere 5.6%, 0% and 0% in group A; 22.2%,5.6% and 0% in group B; 53.9%, 26.9% and16.6% in group C; 79.3%, 38.9% and 26.8% ingroup D, respectively. Significant differenceappeared in the survival rates among the groups(P<0.05).CONCLUSION Hepatic resection with removalof tumor thrombi and HCC should increase thecurative effects and be encouraged for theprolongation of life span and quality of life forHCC patients with PVTT, whereas the besttherapeutic method for HCC with PVTT is withregional hepatic chemotherapy orchemoemblization after hepatic resection withremoval of tumor thrombi. | Jia Fan Zhi Quan Wu Zhao You Tang Jian Zhou Shuang Jian Qiu Zeng Chen Ma Xin Da Zhou Sheng Long Ye Liver Cancer Institute, Zhongshan Hospital, Fudan University Medical Center (Former Shanghai University), 136 Yixueyuan Road, Shanghai 200032, China | 2001 | World Journal of Gastroenterology2001，7，1： | 80 |
| 5 | The prognostic significance of clinical and pathological features in hepatocellular carcinoma显示文摘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 hictopathology 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. Soma 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 of HCC patients who have no opportunity to receive surgical treatment or postoperative recurrence. The combination of these treatment modalities is hopeful to further improve the prognosis. The efficacies of neoadjuvant ( preoperative ) or adjuvant ( postoperative )chemotherapy or chemoembolization in preventing recurrence and on the HCC prognosis still remain great controversy, and deserve further evaluation.Biotherapy, including IFN-alpha therapy, will play more important role in preventing recurrence and metastasis of HCC after operation. | Lun-Xiu Qin Zhao-You Tang,Liver Cancer Institute and Zhongshan Hospital,Fudan University,Shanghai,China | 2002 | World Journal of Gastroenterology2002，8，2： | 77 |
| 6 | Hepatocellular carcinoma with obstructive jaundice: diagnosis, treatment and prognosis显示文摘Obstructive jaundice as the main clinical feature is uncommon in patients with hepatocellular carcinoma (HCC). Only 1-12 %of HCC patients manifest obstructive jaundice as the initial complaint. Such cases are clinically classified as 'icteric type hepatoma', or 'cholestatic type of HCC'. Identification of this group of patients is important, because surgical treatment may be beneficial. HCC may involve the biliary tract in several different ways: tumor thrombosis, hemobilia,tumor compression, and diffuse tumor infiltration. Bile duct thrombosis (BDT) is one of the main causes for obstructive jaundice, and the previously reported incidence is 1.2-9 %.BDT might be benign, malignant, or a combination of both.Benign thrombi could be blood clots, pus, or sludge.Malignant thrombi could be primary intrabiliary malignant tumors, HCC with invasion to bile ducts, or metastatic cancer with bile duct invasion. The common clinical features of this type of HCC include: high level of serum AFP; history of cholangitis with dilation of intrahepatic bile duct; aggravating jaundice and rapidly developing into liver dysfunction. It is usually difficult to make diagnosis before operation, because of the low incidence rate, ignorant of this disease, and the difficulty for the imaging diagnosis to find the BDT preoperatively. Despite recent remarkable improvements in the imaging tools for diagnosis of HCC, such cases are still incorrectly diagnosed as cholangiocarcinoma or choledocholithiases. Ultrasonography (US) and CT are helpful in showing hepatic tumors and dilated intrahepatic and/or extrahepatic ducts containing dense material corresponding to tumor debris. Direct cholangiography including percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP)remains the standard procedure to delineate the presence and level of biliary obstruction. Magnetic resonance cholangiopancreatography (MRCP) is superior to ERCP in interpreting the cause and depicting the anatomical extent of the perihilar obstructive jaundice, and is particularly distinctive in cases associated with tight biliary stenosis and along segmental biliary stricture. Choledochoscopy and bile duct brushing cytology could be alternative useful techniquesin the differentiating obstructions due to intraluminal mass,infiltrating ductal lesions or extrinsic mass compression applicable before and after duct exploration. Jaundice is not necessarily a contraindication for surgery. Host patients will have satisfactory palliation and occasional cure if appropriate procedures are selected and carried out safely, which can result in long-term resolution of symptoms and occasional long-term survival. However, the prognosis of icteric type HCC is generally dismal, but is better than those HCC patients who have jaundice caused by hepatic insufficiency. | Lun-Xin Qin Zhao-You Tang Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China | 2003 | World Journal of Gastroenterology2003，9，3： | 68 |
| 7 | Preventive treatments for recurrence after curative resection of hepatocellular carcinoma-A literature review of randomized control trials显示文摘To review the inhibitory effect of preventive approaches on recurrence after operation in patients with hepatocellular carcinoma (HCC), we summarized all available publications. reporting randomized control trial indexed in PubMed. The treatment approaches presented above included preoperative transcatheter arterial chemoembolization (TACE),post-operative TACE, systemic or locoregional chemotherapy,immunotherapy, Interferons and acyclic retinoic acid Although no standard treatment has been established,several approaches presented promising results, which were both effective and tolerable in post-operative patients. Preoperative TACE was not effective on prolonging survivals,while post-operative TACE was shown with both diseasefree survival and overall survival benefits in some papers,however, it was also questioned by others. Systemic chemotherapy was generally not effective on prolonging survival but also poorly tolerated for its significant toxicities.Adoptive immunotherapy using LAK cells was proved to be beneficial to patients' survival in a recent paper. Interferon and Interferon β can inhibit recurrence in HCC patients with HCV infection background, though the mechanism is not fully understood. Acyclic retinoic acid was shown to decrease multi-centric recurrence after operation, which was reported by only one group. In conclusion, several adjuvant approaches have been studied for their efficacy on recurrence in HCC patients in randomized control trials; however, multi-centric randomized control trial is still needed for further evaluation on their efficacy and systemic or local toxicities;in addition, new adjuvant treatment should be investigated to provide more effective and tolerable methods for the patients with HCC after operation. | Hui-Chuan Sun Zhao-You Tang Liver Cancer Institute and Zhong Shan Hospital,Fudan University,Shanghai 200032,China | 2003 | World Journal of Gastroenterology2003，9，4： | 63 |
| 8 | Alterations in metastatic properties of hepatocellular carcinoma cell following H-ras oncogene transfection显示文摘AIM To demonstrate the relationship betweenH-ras oncogene and hepatocellular carcinoma(HCC) metastasis.METHODS Activated H-ras oncogene wastransfected into SMMC 7721, a cell line derivedfrom human HCC, by calcium phosphatetransfection method. Some metastasis-relatedparameters were detected in vitro, includingadhesion assay, migration assay, expression ofcollagenase ⅣV (c ⅣV ase) and epidermal growthfactor receptor (EGFR).RESULTS The abilities of H-ras-transfected cellclones in adhesion to laminin (LN) or fibronectin(FN), migration, c Ⅳ ase secretion increasedmarkedly, and the expression of EGFR elevatedmoderately. More importantly, these alterationswere consistent positively with the expressionof p21, the protein product of H-ras oncogene.CONCLUSION H-ras oncogene could inducethe metastatic phenotype of HCC cell in vitro toraise its metastatic potential. | Qing Wang~1 Zhi Ying Lin~2 Xiao Li Feng~3 ~1Department of Microbiology,Medical Center of Fudan University.the former Shanghai Medical University,Shanghai 200032,China ~2Liver Cancer Institute,Zhongshan Hospital,Shanghai 200032,China ~3Shanghai Institute of Biochemistry,Academy Sinica,Shanghai 200031,ChinaQing Wang earned master degree from Shanghai Medical University in 1996,now a senior lecturer of microbiology,specialized in the role of oncogcncs on tumor metastasis,having 8 papers published. | 2001 | World Journal of Gastroenterology2001，7，3： | 48 |
| 9 | Inhibition on the production of collagen type Ⅰ, Ⅲ of activated hepatic stellate cells by antisense TIMP-1 recombinant plasmid显示文摘AIM: To investigate the inhibition effects on the productionof collagen type I, Ⅲ secreted by activated rat hepatic stellatecells (rHSCs) by antisense tissue inhibitors of metalloproteinase1 (TIMP-1) recombinant plasmid through elevating interstitialcollagenase activity.METHODS: rHSCs were extracted from normal rat liverby pronase and collagenase digestion and purified bycentrifugal elutriation, and were cultured on plastic dishesuntil they were activated to a myofibroblastic phenotypeafter 7-10 days. RT-Nest-PCR and gene recombinanttechniques were used to construct the rat antisense TIMP-1 recombinant plasmids which can express in eucaryoticcells. The recombinant plasmid and the pcDNA3 emptyplasmid were transfected in rHSCs by Effectene (QIAGEN)separately. Cells were selected after growing in DMEMcontaining 400 μg/ml G418 for 2-3 weeks. Expression ofexogenous gene was assessed by Northern blot, andexpression oflIMP-1 in rHSCs was determined by Northernblot and Western blot. We tested the interstitial collagenaseactivity with FITC-labled type I collagen as substrate.Ultimately, we quantified the type Ⅰ, Ⅲ collagen byWestern blot.RESULTS: The exogenous antisense TIMP-1 recombinantplasmid could be expressed in rHSCs well, which couldblock the expression of TIMP-1 greatly, the ratio of TIMP-1/GAPDH was 0.67, 2.41, and 2.97 separately at mRNAlevel (P<0.05); the ratio of TIMP-1/β-actin was 0.31, 0.98and 1.32 separately at protein level (P<0.05); It mightelevate active and latent interstitial collagenase activity,the collagenase activity was 0.3049, 0.1411 and 0.1196respectively. (P<0.05), which led to promotion thedegradation of type Ⅰ, Ⅲ collagen, the ratio of collagen I/β-actin was 0.63, 1.78 and 1.92 separately (P<0.05); andthe ratio of collagen Ⅲ/β-actin was 0.59, 1.81 and 1.98separately (P<0.05).CONCLUSION: These data shows that the antisense TIMP-1 recombinant plasmid has the inhibitory effects on theproduction of type Ⅰ, Ⅲ collagens secreted by activatedrHSCs in vitro. It could be a novel method to reverse hepaticfibrosis in the future. | Wen-Bin Liu Chang-Qing Yang Wei Jiang Yi-Qing Wang Jing-Sheng Guo Bo-Ming He Ji-Yao Wang Division of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China | 2003 | World Journal of Gastroenterology2003，9，2： | 42 |
| 10 | Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential显示文摘Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient like metastatic model of human HCC in nude mice (LCI-D20)and a Iow metastatic model of human HCC in nude mice LCI-D35 ) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding.Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-Iincreased gradually following tumor progression in LCID20 model, and correlated with tumor size and AFP level,Phasic expression of tissue intercellular adhesion molecule-I in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including antiangiogenesis, antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vivo and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence. | Zhao-You Tang Fan-Xian Sun Jian Tian Sheng-Long Ye Yin-Kun Liu Kang-Da Liu Qiong Xue Jie Chen Jing-Lin Xia Lun-Xiu Qin Hui-Chuan Sun Lu Wang Jian Zhou Yan Li Zeng-Chen Ma Xin-Da Zhou Zhi-Quan Wu Zhi-Ying Lin Bing-Hui Yang Liver Cancer Institute of Fudan University and Zhongshan Hospital,Shanghai 200032,China | 2001 | World Journal of Gastroenterology2001，7，5： | 34 |
| 11 | A meta-analysis of oxidative stress markers in schizophrenia显示文摘Oxidative stress has been identified as a possible element in the neuropathological processes of schizophrenia(SCZ).Alteration of oxidative stress markers has been reported in SCZ studies,but with inconsistent results.To evaluate the risk of oxidative stress to schizophrenia,a meta-analysis was conducted,including five markers of oxidative stress [thiobarbituric reactive substances(TBARS),nitric oxide(NO),catalase(CAT),glutathione peroxidase(GP) and superoxide dismutase(SOD)] in SCZ patients versus healthy controls.This study showed that TBARS and NO significantly increased in SCZ,while SOD activity significantly decreased in the disorganized type of SCZ patients.No significant effect size was found for the activities of GP and CAT in SCZ patients(P>0.05).Egger’s regression test observed no significant publication bias across the oxidative stress markers,but found high heterogeneities in all the 5 markers.The subgroup analysis suggested that the ethnicity,sample size of patients and sample sources may contribute to the heterogeneity of the results for TBARS,NO and SOD.The result further demonstrated the involvement of oxidative stress in the pathophysiology of schizophrenia. | ZHANG Ming1,2,ZHAO ZhongMing3,HE Lin1,2,4 & WAN ChunLing1,2 1 Bio-X Center,Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education),Shanghai Jiao Tong University,Shanghai 200030,China 2 Institutes for Nutritional Sciences,Shanghai Institute of Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China 3 Departments of Biomedical Informatics,Psychiatry,and Cancer Biology,Vanderbilt University Medical Center,Nashville,TN 37232,USA 4 Institutes of Biomedical Sciences,Fudan University,Shanghai 200032,China | 2010 | Science China(Life Sciences)2010，53，1： | 32 |
| 12 | Role and limitation of FMPSPGR dynamic contrast scanning in the follow-up of patients with hepatocellular carcinoma treated by TACE显示文摘AIM:To evaluate the role and limitation of fast multiplanarspoiled gradient-recalled (FMPSPGR) MR dynamiccontrast scanning in the follow-up of patients with HCCtreated by transarterial chemoembolization (TACE).METHODS:Twenty-two patients with 24 HCC lesionsconfirmed by biopsy or surgical resection underwentMR imaging in 4-9wks after TACE with a superconducting1.5 T MR scanner, including SE T1WI, T2WI and FMPSPGRdynamic contrast scanning. The signal intensities of alllesions on SE T1WI, T2WI and the enhancement patternson FMPSPGR dynamic contrast scanning were observed,and the comparison was made between MRI findingsand pathological results in ail the cases.RESULTS:Of the 24 lesions, the signal intensities werevarious on SE T1WI and T2WI. On T1WI, 13 lesionsappeared as hyperintense, 4 lesions were isointenseand the other 7 lesions were hypointensese.Histologically, hyperintense lesions showed on T1WIwere viable tumor or hemorrhage; isointensities werecoagulative necrosis or inflammatory infiltration;hypointensities were tumor, liquified necrosis,coagulative necrosis or inflammatory infiltration. OnT2WI, 15 lesions appeared as hyperintense, 3 lesionswere isointense and the other 6 lesions werehypointensese. Hyperintense lesions showed on T2WIwere residuals of viable tumor, hemorrhage, liquefiednecrosis or inflammatory infiltration; isointense lesionswere residuals of viable tumor or inflammatoryinfiltration; hypointense lesions were coagulativenecrosis. On FMPSPGR dynamic contrast scanning, 18of the 24 lesions enhanced on early-phase dynamicscanning conesponding to residuals of viable tumor andthe other 6 lesions had no enhancement at this phasebecause complete necrosis were seen in the histologicexamination. On delayed-phase dynamic scanning, 6lesions had permanent enhancement appeared asinhomogeneous hyperintensity and both residuals ofviable tumor and inflammatory infiltration were foundby histologic examination. 18 lesions were hypointenseat this phase and 8 of them coexisted with peripheralring-like enhancement of the lesions resulting fromviable tumors or inflammatory infiltration.CONCLUSION: FMPSPGR MR dynamic contrast scanningcan reflect the pathologic changes of HCC treated byTACE. Especially, early-phase dynamic scanning canevaluate accurately residuals of viable tumor andnecrosis in HCC lesions. FMPSPGR dynamic contrastscanning is useful in the follow-up of patients with HCCtreated by TACE combined with SE T1WI and T2WI, butit is difficult to differentiate peripheral viable tumorsfrom inflammatory infiltration. | Fu-Hua Yan Kang-Rong Zhou Jie-Min Cheng Jian-Hua Wang Zhi-Ping Yan Reng-Rong Da Department of Radiology,Zhongshan Hospital,Fudan University,Shanghai 200032,China Jia Fan Department of Hepatobiliary-surgery,Zhongshan Hospital,Fudan University,Shanghai 200032,China Yuan Ji Department of Pathology,Zhongshan Hospital,Fudan University,Shanghai 200032,China | 2002 | World Journal of Gastroenterology2002，8，4： | 32 |
| 13 | Sorafenib in treatment of patients with advanced hepatocellular carcinoma:a systematic review显示文摘BACKGROUND: Sorafenib has become the standard first-line treatment for patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of sorafenib in advanced HCC patients and explore its true value for specific subgroups. DATA SOURCES: A computer-based systematic search from January 2005 to June 2011 with 'sorafenib' and 'advanced hepatocellular carcinoma' as search terms was performed for possible clinical trials. Hazard ratios (HR) and their 95% confidence intervals (CI) for overall survival (OS) and time to progression (TTP), rates of partial response (PR), rates of toxicity effects, and details of subgroup analysis were extracted. Meta-analyses were done using the software Review Manager (version 5.0). RESULTS: Six trials with 1164 patients were included. Based on three randomized controlled trials, the pooled HR (sorafenib/ placebo) was 0.66 for OS (95% CI: 0.56-0.78; P<0.00001) and 0.57 for TTP (95% CI: 0.47-0.68; P<0.00001). The pooled odds ratio (OR) for PR was 2.96 (95% CI: 0.96-9.15; P=0.06). For three single-arm trials, the pooled HR was 0.69 for OS (95% CI: 0.56-0.84; P=0.0002) and 0.64 for TTP (95% CI: 0.52-0.78; P<0.00001). The pooled OR for PR in three single-arm trials was 3.56 (95% CI: 1.22-10.39; P=0.02). Subgroup analysis indicated that sorafenib was less effective in patients with extrahepatic spread (with: P=0.13 vs without: P<0.0001), with normal alpha-fetoprotein level (AFP) (P=0.15 vs elevated: P=0.0006), and with elevated level of serum bilirubin (P=0.06 vs normal: P=0.0009). Sorafenib-based therapy significantly increased the risk of grade 3/4 hand-foot skin reaction, diarrhea, fatigue, and rash/desquamation.CONCLUSIONS: Sorafenib-based therapy benefits advanced HCC patients. Meanwhile, sorafenib is less effective for patients with extrahepatic spread, with normal AFP level and with elevated level of bilirubin. | Xin Zhang, Xin-Rong Yang, Xiao-Wu Huang, Wei-Min Wang, Ruo-Yu Shi, Yang Xu, Zheng Wang, Shuang-Jian Qiu, Jia Fan ,Jian Zhou Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai Key Laboratory for Organ Transplantation, Shanghai 200032, China,Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China | 2012 | Hepatobiliary & Pancreatic Diseases International2012，11，5： | 29 |
| 14 | SEMI-GLOBAL C^1 SOLUTION TO THE MIXED INITIAL-BOUNDARY VALUE PROBLEM FOR QUASILINEAR HYPERBOLIC SYSTEMS显示文摘By means of an equivalent invariant form of boundary conditions, the authors get the exis- tence and uniqueness of semi-global C1 solution to the mixed initial-boundary value problem for quasilinear hyperbolic systems with general nonlinear boundary conditions. | LI TA-TSIEN (LI DAQIAN), JIN YI Department of Mathematics, Fudan University, Shanghai 200433, China. | 2001 | Chinese Annals of Mathematics,Series B2001，22，3： | 30 |
| 15 | Diagnosis and treatment of hepatic angiomyolipoma in 26 cases显示文摘AIM: To summarize the experience of the diagnosis and treatment of hepatic angiomyolipoma (HAML).METHODS: The clinical, imaging and pathological features,and treatment strategies of 26 patients with HAML treated at the authors′institute between October 1998 and January 2003 were retrospectively analyzed. All the patients received liver resection and were followed up till the study.Immunohistochemical assays were performed with a panel of antibodies.RESULTS: There was an obvious female predominance (21:5), and most of the patients (18/26) had no symptoms.Heterogeneous high echo was found in ultrasonography and punctiform or filiform vascular distribution pattern was found in color Doppler-sonography in most of the lesions (21/26).All of the 5 lesions further enhanced with Levovist showed early and prolonged enhancement. At contrast-enhanced spiral CT, the soft-tissue components of 24 lesions were markedly enhanced in the arterial phase and 18 lesions remained enhanced in the portal venous phase. MRI was performed in 9 patients, and showed hypointensity or hyperintensity on T1-weighted images and heterogeneous hyperintensity on T2-weighted images. Histopathologically,all lesions were composed of adipose tissues, smooth muscle and blood vessels with different proportions. Most lesions showed positive immunohistochemical staining for HMB45(26/26), A103 (24/26) and SMA (24/26). All of the 26 patients showed a benign course with no sign of recurrence.CONCLUSION: Preoperative radiological diagnosis of HAML is possible. The demonstration of intratumoral fat and central vessels is helpful in the diagnosis. HMB45, A103 and SMA are promising markers for pathologic diagnosis of HAML,and surgical resection is effective for the treatment of HAML. | Ning Ren Lun-Xiu Qin Zhao-You Tang Zhi-Quan Wu Jia Fan, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, China | 2003 | World Journal of Gastroenterology2003，9，8： | 25 |
| 16 | SF/HGF-c-Met autocrine and paracrine promote metastasis of hepatocellular carcinoma显示文摘AIM: To explore the role of SF/HGF-Met autocrine and parscrine in metastasis of hepatocellular carcinoma (HCC).METHODS: SF/HGF and c-met transcription and protein expression in HCC were examined by RT-PCR and Western Blot in 4 HCC cell lines, including HepG2, Hep3B,SMMC7721 and MHCC-1, the last cell line had a higher potential of metastasis. Sf/hgf cDNA was transfected by the method of Lipofectin into SMMC7721. SF/HGF and c-met antibody were used to stimulate and block SF/HGF-c-met signal transduction. Cell morphology, mobility, and proliferation were respectively compared by microscopic observation, wound healing assay and cell growth curve.RESULTS: HCC malignancy appeared to be relative to its met-SF/HGF expression. In MHCC-1, c-met expression was much stronger than that in other cell lines with lower potential of metastasis and only SF/HGF autocrine existed in MHCC-1. After sf/hgf cDNA transfection or conditioned medium of MHCC-1 stimulation, SMMC7721 changed into elongated morphology, and the abilities of proliferation ( P < 0.05) and mobility increased. Such bio-activity could he blocked by c-met antibody ( P< 0.05).CONCLUSION: The system of SF/HGF-c-met autocrine and paracrine played an important role in development and metastasis potential of HCC. Inhibition of SF/HGF-c-met signal transduction system may reduce the growth and metastasis of HCC. | Qian Xie Kang-Da Liu Mei-Yu Hu Kang Zhou Experimental Research Center of Zhongshan Hospital,Fudan University,Shanghai,200032,China | 2001 | World Journal of Gastroenterology2001，7，6： | 24 |
| 17 | Recurrence and metastasis of hepatocellular carcinoma: progress and prospects显示文摘Background: Recurrence after resection of hepatocellu-lar carcinoma(HCC) is a major obstacle to improveprognosis. Therefore, further improvement of long-term survival may depend on prevention and treat-ment of the recurrent tumor.Objective: To evaluate the progress of surgery forHCC, the risk factors for recurrence, and clinical andbasic studies on the prevention and management of re-currence and metastasis after resection of HCC.Data sources: A review of currently available data inthe mentioned areas.Data synthesis: Encouraging changes in the prognosticpattern were observed when the primary liver cancer(PLC) data of 1958-1967 (n=118), 1968-1977 (n=356), 1978-1987(n=715) and 1988-1997 (n=2038)were compared. The 5-year survival was 2.8%, 7.3%,27.1% and 52.5%, respectively, and the 10-yearsurvival 2.8%, 4.3%, 19.8% and 39.9%, respective-ly. Risk factors for recurrence included symptomaticpatient, high γ-glutamyl-peptidase (γ-PGT), largetumor size, portal vein embolus, advanced tumorstage, etc. Active hepatitis activity in the nontumorousliver and perioperative transfusion enhanced the re-currence. Molecular research into the invasiveness ofHCC identified some factors positively related to inva-siveness: p16 and p53 mutation, H-ras, c-cerbB2,mdm2, transforming growth factor (TGF), epidermalgrowth factor receptor (EGF-R), matrix metallopro-teinase-2 (MMP-2), urokinasetype plasminogen acti-vator (uPA), its receptor (uPA-R) and inhibitor(PAI-1), intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF),platelet-derived endothelial cell growth factor (PD-ECGF), and basic fibroblast growth factor (bFGF).In contrast, some factors were negatively related toHCC invasiveness: nm23-H1, Kai-1, tissue inhibitor ofmetalloproteinase-2 (TIMP-2), integrin 5, and E-cadherin. Re-resection of subclinical recurrence yield-ed a 5-year survival of 56.0% calculated from the firstresection (n=202) .Postoperative transarterialchemoembolization (TACE, n=103), hepatic arterycannulation during operation (n=105), postoperativebiotherapy (n=49), and cryohepatectomy (cryosurgeryfollowed by immediate resection of the frozen tumor,n=84) might decrease the recurrence rate, and the3-year recurrence rate was 7.6%, 18.0%, 11.1%, and30.1%, respectively. Minimal intraoperative blood lossand transfusion could reduce postoperative recurrence,although the exact mechanism remains to be elucidat-ed.Conlusions: HCC invasiveness is the major topic to bestudied, particularly in the molecular level. Anti-an-giogenesis, biotherapy, novel approach based on molec-ular findings, and multidisciplinary interventions mightalso be important for HCC. | Xin-Da Zhou From the Liver Cancer Institute, Zhong Shan Hospital, Fudan University Medical Center, Shanghai 200032, China | 2002 | Hepatobiliary & Pancreatic Diseases International2002，1，1： | 22 |
| 18 | Crosstalk between tumor cells and microenvironment via Wnt pathway in colorectal cancer dissemination显示文摘Invasion and metastasis are the deadly face of malignant tumors. Considering the high rate of incidence and mortality of colorectal cancer, it is critical to determine the mechanisms of its dissemination. In the parallel investigation of the invasive front and tumor center area of colorectal cancer (CRC), observation of heterogeneous β-catenin distribution and epithelial-mesenchymal transition (EMT) at the invasive front suggested that there might be a crosstalk between tumor cells and the tumor microenvironment. Wnt signaling pathway is also involved in the cancer progression due to its key role in CRC tumorigenesis. Moreover, in recent years, there is increasing evidence that the regulators of microenvironment, including extracellular matrix, growth factors and inflammatory factors, are associated with the activation of Wnt pathway and the mobility of tumor cells. In this review, we will try to explain how these molecules trigger metastasis via the Wnt pathway. | Dan Huang, Xiang Du, Department of Pathology, Cancer Hospital of Fudan University Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China | 2008 | World Journal of Gastroenterology2008，14，12： | 22 |
| 19 | Effects of retinoic acid on proliferation,phenotype and expression of cyclin-dependent kinase inhibitors in TGF-β1-stimulated rat hepatic stellate cells显示文摘AIM To study the molecular mechanisms ofretinoic acid(RA)on proliferation andexpression of cyclin-dependent kinase inhibitors(CKI),i.e.p16,p21 and p27 in cultured rathepatic stellate cells(HSC)stimulated withtransforming growth factor beta 1(TGF-β1).METHODS HSC were isolated from healthy ratlivers and cultured.After stimulated with1 mg/L TGF-β1,subcultured HSC were treatedwith or without 1 nmol/L RA.MTT assay,immunocytochemistry(ICC)for p16,p21,p27and α-smooth muscle actin(α-SMA)protein,insitu hybridization(ISH)for retinoic acidreceptor beta 2(RAR-β2)and p16,p21 and p27mRNA and quantitative image analysis(partially)were performed.RESULTS RA inhibited HSC proliferation(41.50%,P<0.05),decreased the protein levelof α-SMA(55.09%,P<0.05),and induced HSCto express RAR-β2 mRNA.In addition,RAincreased the protein level of p16(218.75%,P<0.05)and induced p21 protein expression;meanwhile,p27 was undetectable by ICC in bothcontrol and RA-treated HSC.However,RA hadno influence on the mRNA levels of p16,p21 orp27 as determined by ISH.CONCLISION Up-regulation of p16 and p21 on post-transcriptional level may contribule, in part to RA inhibition of TGF-β1-initiated rat HSC activation in vitro. | Guang Cun Huang Jin Sheng Zhang Yue E Zhang Department of Pathology School of Basic Medical Sciences,Fudan University.Shanghai 200032,China | 2000 | World Journal of Gastroenterology2000，6，6： | 23 |
| 20 | The anabolic effects of recombinant human growth hormone and glutamine on parenterally fed,short bowel rats显示文摘AIM: To evaluate the metabolic effects associated withadministration of rhGH and/or Gln in parenterally fed,short-bowel rats.METHODS: Forty SD rats subjected to 75 % intestinalresection and maintained with parenteral nutritionwere randomly divided into 4 groups as follows: -rhGH,-Gln; -rhGH, +Gln; +rhGH, -Gln; +rhGH, +Gln.Bodyweight and nitrogen balance were evaluated daily. After6 days of PN, rats were killed, various organs weredissected and weighted, the carcasses were used foranalysis of body composition. Serum GH and IGF-1 weredetermined by RIA method.RESULTS: Weight loss in rats with rhGH (17.4±12.8 g)and rhGH+Gln (23.8±3.5 g) was significantly less thanrats with PN alone (29.6±6. 9 g) and rats with Gln-supplemented PN (31.85±12.8 g), P<0.05. Theaccumulated NB in rats with rhGH (1252.9±294.3 mgN/d) and rhGH+Gin (1261.7±85.5 mg N/d) wassignificantly greater than those with PN alone (704.8±379.0 mg N/d) and with Gln-supplemented PN(856.7±284.4 mg N/d), P<0.05. The absolute weightof gastrocnemius muscle in rats with rhGH (2683.9±341.6 mg) and rhGH+Gln (2579.1±359.5 mg) wasgreater than those with PN alone (2176.3±167.1 mg)and with Gln-supplemented PN (2141.9±353.6 mg).Although the absolute weight of remnant smallintestine itself was not significantly different in 4experimental groups, the weight/length of thesegments was greater in rats with rhGH and/or Gln(48.7±5.5, 52.7±4.1 and 67.4±5.3 respectively) thanthose with PN alone(47.8±5.0), there were synergisticeffects between rhGH and Gln in improvement of theweight/length of remnant small intestine, P<0.05.Analyses of body carcass composition showed that ahigher percentage of carcass weight as protein and alower percentage of carcass weight as fat wereoccurred in rats with rhGH (20.8±4.0,6.0±2.6) andrhGH+Gin(21.3±2.4,4.4±1.5) than those with PNalone (16.4±2.4,9.2+3.7) and with Gln-supplementedPN (17.8±3.0,6.3±2.0), rhGH had significant effectson alteration of body composition, P<0.05. Serum GHand IGF-1 concentration in rats with rhGH(5.221±0.8and 425.1±19.2 ng/ml respectively)and rhGH+Gin(5.507±1.0 and 461.1±49.9 ng/ml respectively) weregreater than those with PN alone(3.327±1.7 and 325.8±29.6 ng/ml respectively) and with Gln-supplementedPN(3.433±0.1 and 347.7±55.7 ng/ml respectively),P<0.01.CONCLUSION: rhGH significantly improves theanabolism in parenterally fed. short bowel rats, anaboliceffect with Gln is less dramatic, there is no synergisticeffect between rhGH and Gln in improvement of wholebody anabolism. IGF-1 plays an important part ingrowth-promoting effects of rhGH. | Yan Gu Zhao-Han Wu Department of General Surgery,Zhongshan Hospital,Fudan University,Shanghai 200032,China | 2002 | World Journal of Gastroenterology2002，8，4： | 23 |
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