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| 1 | 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 |
| 2 | Hepatocellular carcinoma: current management and recent advances显示文摘BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem worldwide. It is the fifth most common cancer in the world, and the third most common cause of cancer-related death. Without specific treatment, the prognosis is very poor. The goal of management is 'cancer control' - a reduction in its incidence and mortality as well as an improvement in the quality of life of patients with HCC and their families. This article aims to review the current management of HCC and its recent advances. DATA SOURCES: A MEDLINE database search was performed to identify relevant article using the keyworks 'hepatocellular carcinoma', 'hepatectomy', 'liver transplantation', and 'local ablative therapy'. Additional papers and book chapters were identified by a manual search of the references from the key articles. RESULTS: Liver resection and liver transplantation remain the options that give the best chance of a cure. Recent evidence suggests that local ablative therapy may offer comparable survival results in patients with small HCC, and preserved liver function. Transarterial chemoembolization (TACE) is the most promising palliative modality for unresectable HCC, but other techniques, such as transarterial radioembolization (TARE), and local ablative therapy, have also shown comparable results. CONCLUSIONS: Early diagnosis of HCC remains a key goal in improving the prognosis of patients. During the last two decades, operative mortality and surgical outcome of liver resection and liver transplantation for HCC have improved. Progress also has been made in multi-modality therapy which can increase the chance of survival and improve the quality of life for patients with advanced HCC. | Wan-Yee Lau Eric C. H. Lai | 2008 | Hepatobiliary & Pancreatic Diseases International2008，7，3： | 100 |
| 3 | Quantitative analysis of vascular endothelial growth factor, microvascular density and their clinicopathologic features in human hepatocellular carcinoma显示文摘BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angiogenesis, but its significance and tumor pathologic features are un- clear in hepatocellular carcinoma (HCC). In the present study, we analyzed expression of tissue VEGF, alteration of microvascular density (MVD) in microvessel angiogenesis, development and metastasis of HCC, and level of serum VEGF in differential diagnosis of benign and malignant liv- er diseases. METHODS: Tumor specimens were prospectively collected from HCC patients undergoing resection. Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues. The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavi- din peroxidase (S-P) immunohistochemistry, respectively. The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay. RESULTS: The incidence of VEGF expression was 63.9% in HCCs (23/36 cases), 78.3% in non-encapsulated HCCs (18/23), and 90.9% in HCCs with extrahepatic metastasis (10/11), respectively. The VEGF expression was tightly correlated with MVD (P <0.01). The MVD in HCC with metastasis, low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule, high differentiation, or no metastasis. No significant diffe- rence was found between VEGF, MVD, tumor size, and hepatitis virus infection. The level of total RNA in HCC tis- sues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones (P<0.01). The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the me- tastasis and recurrence of tumors. CONCLUSION: The high expression of VEGF and abnor- mality of tissue MVD are useful predictors for vascular inva- sion and metastasis of liver tumors. | Deng-Fu Yao, Xin-Hua Wu, Yong Zhu, Gong-Sheng Shi, Zhi-Zhen Dong, Deng-Bing Yao, Wei Wu, Li-Wei Qiu and Xian-Yong Meng Nantong, China Research Center of Clinical Molecular Biology , Department of Pathology and Department of Gastroenterology , Affiliated Hos- pital of Nantong University Department of Diagnostics , and Institute of Neurosciences , Nantong University Nantong 226001, China | 2005 | Hepatobiliary & Pancreatic Diseases International2005，4，2： | 81 |
| 4 | Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial chemoembolization for massive unresectable hepatocellular carcinoma:a prospective non.randomized study显示文摘Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on large(> 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy(HAIC)might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX(mFOLFOX) regimen and those ofTACE in patients with massive unresectable HCC.Methods: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen(oxaliplatin, 85 mg/m^2 intra-arterial infusion; leucovorin,400 mg/m^2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m^2 continuous infusion)every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression(TTP), and safety were assessed.Results: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group(52.6% vs. 9.8%, P < 0.001;83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months(hazard radio[HR] = 2.35,95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection(10 vs. 3,P = 0.033). The proportions of grade 3-4 adverse events(AE) and serious adverse events(SAE) were lower in the HAIC group than in the TACE group(grade 3-4 AEs: 13 vs. 27, P = 0.007;SAEs: 6 vs. 15,p = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent(10 vs. 2,P = 0.026).Conclusions: HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC. | Min-Ke He Yong Le Qi-Jiong Li Zi-Shan Yu Shao-Hua Li Wei Wei Rong-Ping Guo Ming Shi | 2017 | Chinese Journal of Cancer2017，36，12： | 95 |
| 5 | Clinicopathological characteristics in the differential diagnosis of hepatoid adenocarcinoma:A literature review显示文摘Hepatoid adenocarcinoma (HAC) is a rare but important special type of extrahepatic adenocarcinoma with clinicopathological presentation mimicking hepatocellular carcinoma (HCC), and prompt and correct diagnosis can be a challenge, especially in endemic areas with a high incidence of HCC. To date, HAC has only been reported in case series or single case reports, so we aimed to review the clinicopathological characteristics of HAC to obtain a more complete picture of this rare form of extrahepatic adenocarcinoma. All the articles about HAC published from 2001 to 2011 were reviewed, and clinicopathological findings were extracted for analysis. A late middle-aged male with high serum α-fetoprotein and atypical image finding of HCC should raise the suspicion of HAC, and characteristic pathological immunohistochemical stains can help with the differential diagnosis. Novel immunohistochemical markers may be useful to clearly differentiate HAC from HCC. Once metastatic HAC is diagnosed, the primary tumor origin should be identified for adequate treatment. The majority of HAC originates from the stomach, so panendoscopy should be arranged first. | Jiann-Sheng Su Yu-Tso Chen Ren-Ching Wang Chun-Ying Wu Shou-Wu Lee Teng-Yu Lee | 2013 | World Journal of Gastroenterology2013，19，3： | 75 |
| 6 | Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21^(WAF1) expression and hepatic apoptosis显示文摘AIM To detect the expression of caspase 3gene in primary human hepatocellular carcinoma(HCC)and investigate its relationship to p21WAF1gene expression and HCC apoptosis.METHODS In situ hybridization was employedto determine caspase 3 and p21WAF1expression inHCC.In situ end-labeling was used to detecthepatocytic apoptosis in HCC.RESULTS Twenty-one of 39(53.8%)cases ofHCC were found to express caspase 3transcripts,while 45.2% of HCC failed toexpress caspase 3.Non-cancerous adjacent livertissues showed more positive caspase 3(87.5%,7/8)as compared with HCC(P<0.05).The expression of caspase 3 is correlated withHCC differentiation,72.2%(13/18)ofmoderately to highly differentiated HCC showedcaspase 3 transcripts positive,while only 38.1%of poorly differentiated HCC harbored caspase 3transcripts(P<0.05).No relationship wasfound between caspase 3 expression and tumorsize or grade or metastasis,although 52.5%(5/8)of HCC with metastasis were caspase 3positive and a little higher than that with nometastasis(51.6%,P>0.05).Expression of caspase 3 alone did not affect the apoptosisindex(AI)of HCC.The AI was 7.12%o in caspase3-positive tumors(n=21),while in caspase 3-negative cases(n=18)6.59%0(P>0.05).Expression of caspase 3 clearly segregated withp21WAF1positive tumors as compared withp21WAF1-negative cases(16 of 23,69.6% versus5 of 16,31.3%)with statistical significance(P=0.017).In the cases with positive caspase 3and negative p21WAF1,the Al was found slightlyhigher,but with no statistical significance,thanthat with expression of p21WAF1and caspase 3(7.21‰ vs 6.98‰,P>0.05).CONCLUSION Loss of caspase 3 expressionmay contribute to HCC carcinogenesis,althoughthe expression of caspase 3 does not correlatewell with cell apoptosis in HCC.p21WAF1may bemerely one of the inhibitors which can reducecaspase 3 mediated cell apoptosis in HCCs. | Bao Hua Sun Jun Zhang Bao JǜWang Xi Ping Zhao You Kun Wang Zhi Qun Yu Dong Liang Yang Lian Jie Hao Department of Clinical Immunology,Tongji Hospital,Tongji Medical University,Wuhan 430030,Hubei Province,China | 2000 | World Journal of Gastroenterology2000，6，3： | 65 |
| 7 | Current and future treatments for hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC) represents a unique challenge for physicians and patients.There is no definitively curative treatment.Rather,many treatment and management modalities exist with differing advantages and disadvantages.Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC.In addition,quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies.Thus,considering all the options and their various pros and cons can quickly become complex for both clinicians and patients.In this review,we systematically discuss the current treatment modalities available for HCC,detailing relevant clinical data,risks and rewards and overall outcomes for each approach.Surgical options discussed include resection,transplantation and ablation.We also discuss the radiation modalities:conformal radiotherapy,yttrium 90 microspheres and proton and heavy ion radiotherapy.The biologic agent Sorafenib is discussed as a promising new approach,and recent clinical trials are reviewed.We then detail currently described molecular pathways implicated in the initiation and progression of HCC,and we explore the potential of each pathway as an avenue for drug exploitation.We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease. | Alexander Schlachterman Willie W Craft Jr Eric Hilgenfeldt Avir Mitra Roniel Cabrera | 2015 | World Journal of Gastroenterology2015，21，28： | 76 |
| 8 | Immune suppression in chronic hepatitis B infection associated liver disease: A review显示文摘Hepatitis B virus(HBV) infection is one the leading risk factors for chronic hepatitis, liver fibrosis, cirrhosis and hepatocellular cancer(HCC), which are a major global health problem. A large number of clinical studies have shown that chronic HBV persistent infection causes the dysfunction of innate and adaptive immune response involving monocytes/macrophages, dendritic cells, natural killer(NK) cells, T cells. Among these immune cells, cell subsets with suppressive features have been recognized such as myeloid derived suppressive cells(MDSC),NK-reg, T-reg, which represent a critical regulatory system during liver fibrogenesis or tumourigenesis. However, the mechanisms that link HBVinduced immune dysfunction and HBV-related liver diseases are not understood.In this review we summarize the recent studies on innate and adaptive immune cell dysfunction in chronic HBV infection, liver fibrosis, cirrhosis, and HCC, and further discuss the potential mechanism of HBV-induced immunosuppressive cascade in HBV infection and consequences. It is hoped that this article will help ongoing research about the pathogenesis of HBV-related hepatic fibrosis and HBV-related HCC. | Tian-Yang Li Yang Yang Guo Zhou Zheng-Kun Tu | 2019 | World Journal of Gastroenterology2019，25，27： | 69 |
| 9 | Expression of nuclear factor-KB in hepatocellular carcinoma and its relation with the X protein of hepatitis B virus显示文摘AIM In this study we investigated therelationship of the X protein of HBV and nuclearfactor-KB (NF-κB) and the expression of NF-KB inhuman hepatocellular carcinoma tissues.METHODS Immunohistochemistry SP methodwas used to detect the expression of NF-κB and the X protein of HBV in human hepatocellularcarcinoma tissues of 52 cases. Gene transfectionmediated by lipofectamine was used to transfectthe eukaryotic expression vector pCDNA3. 1-HBXof HBV x gene into human hepatocellularcarcinoma cell line HCC-9204 and NF-κB wasdetected.RESULTS NF-κB was widely expressed inhuman hepatocellular carcinoma tissues in atotal of 52 cases and its expression was relatedto the X protein of HBV. NF-KB was localizedboth in the cytoplasm and . The nuclei ofhepatocellular carcinoma cells in 11 cases whichwere positive for the X protein of HBV while in 41cases negative for the X protein of HBV, NF-Kbwas only localized in the cytoplasm ofhepatocellular carcinoma cells but translocatedto the nuclei of hepatocellular carcinoma cellsafter the eukaryotic expression vectorpCDNA3.1-HBX was transfected into HCC-9204cells.CONCLUSION This study strongly suggeststhat the nuclear factor NF-KB is widely expressedin hepatocellular carcinoma tissues in differentstyles according to the expression of the Xprotein of HBV. NF-κB is abnormally activated inhepatocellular carcinoma, which is probablyrelated to the X protein of HBV. The X protein ofHBV can activate NF-κB to translocate into nucleiof hepatocellular carcinoma cells. | Shuang Ping Guo~1 Wen Liang Wang~1 Yu Qiang Zhai~2 Yi Ling Zhao~1 ~1Department of Pathology,Xijing Hospital of the Fourth Military Medical University,Xi’an,China ~2Department of Urology,the Central Hospital of Xi’an,China | 2001 | World Journal of Gastroenterology2001，7，3： | 55 |
| 10 | Oncofetal antigen glypican-3 as a promising early diagnostic marker for hepatocellular carcinoma显示文摘BACKGROUND:Hepatocellular carcinoma (HCC) is characterized by a multi-cause,multi-stage and multi-focus process of tumor progression.Its prognosis is poor and early diagnosis is of utmost importance.This study was undertaken to investigate the dynamic expression of oncofetal antigen glypican-3 (GPC-3) and GPC-3 mRNA in hepatocarcinogenesis and to explore their early diagnostic value for HCC.METHODS:A hepatoma model was induced in male Sprague-Dawley rats with 0.05% 2-fluorenylacetamide and confirmed by hematoxylin and eosin staining and gamma-glutamyltransferase (GGT) expression.Total RNA was purified and transcribed into cDNA by reverse transcription.Fragments of the GPC-3 gene were amplified by nested RT-PCR,and confirmed by sequencing.GPC-3 was analyzed by immunohistochemistry,Western blotting or ELISA.RESULTS:Positive GPC-3 expression showed as brown granule-like staining localized in the cytoplasm.Histological examination of hepatocytes revealed three morphological stages of granule-like degeneration,atypical hyperplasia (precancerous),and cancer formation,with a progressive increase of liver total RNA and GGT expression.The incidence of liver GPC-3 mRNA and GPC-3,and serum GPC-3 was 100%,100% and 77.8% in the HCC group,100%,100%,and 66.7% in the precancerous group,83.3%,83.3%,and 38.9% in the degeneration group,and no expression in the liver or blood of the control group,respectively.There was a positive correlation between liver GPC-3 mRNA and total RNA level (r=0.475,P<0.05) or liver GPC-3 (r=1.0,P<0.001) or serum GPC-3 (r= 0.994,P<0.001).CONCLUSION:Abnormal oncofetal antigen GPC-3 and GPC-3 mRNA expression in hepatocarcinogenesis may be promising molecular markers for early diagnosis of HCC. | Research Center of Clinical Medicine,Affiliated Hospital of Nantong University,Nantong 226001,China (Yao M,Yao DF,Qiu LW,Wu W,Sai WL,Yang JL and Zhang HJ) Department of Oncology,Yancheng First People’s Hospital,Yancheng 224001,China (Bian YZ) Department of Oncology,Second Affiliated Hospital,Nanjing Medical University,Nanjing 210011,China (Zhang CG) | 2011 | Hepatobiliary & Pancreatic Diseases International2011，10，3： | 51 |
| 11 | Specific molecular markers in hepatocellular carcinoma显示文摘BACKGROUND: The carcinogenesis of hepatocellular carcinoma (HCC) is a multi-factorial, multistep and complex process. Its prognosis is poor, and early diagnosis and monitoring metastasis of HCC is of the utmost importance. Circulating diagnostic and prognostic biomarkers could be used in proper postoperative treatment of patients at an early stage of HCC development. This review summarizes recent studies of the specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. DATA SOURCES: An English-language literature search was conducted using MEDLINE (June 1998 to September 2006) on researches of some valuable specific biomarkers in diagnosis and monitoring metastasis or postoperative recurrence of HCC. RESULTS: Hepatoma tissues can synthesize various tumor-related proteins, polypeptides, and isoenzymes, such as alpha-fetoprotein (AFP), hepatoma-specific gamma-glutamyl transpeptidase (HS-GGT), etc, and then secrete into blood. The valuable early diagnostic and prognostic biomarkers could predict the development and metastases of HCC. Recent researches have confirmed that circulating hepatoma-specific AFP subfraction, transforming growth factor (TGF)-β1, HS-GGT, and free insulin-like growth factor (IGF)-Ⅱ may be more specific markers than total AFP level for early diagnosis for HCC. The circulating genetic markers such as AFP-mRNA, TGF-β1-mRNA, IGF-Ⅱ-mRNA, etc from peripheral blood mononuclear cells of HCC patients have been most extensively used in monitoring distal metastasis or postoperative recurrence of HCC. CONCLUSIONS: Hepatoma tissues synthesize and secrete valuable molecular markers into blood. The analyses of circulating hepatoma-specific biomarkers are usefulto early diagnosis of HCC or monitoring metastasis or postoperative recurrence of HCC. | Yao, Deng-Fu Dong, Zhi-Zhen Yao, Min | 2007 | Hepatobiliary & Pancreatic Diseases International2007，6，3： | 55 |
| 12 | Diagnostic value of AFP-L3 and PIVKA-Ⅱin hepatocellular carcinoma according to total-AFP显示文摘AIM:To evaluate diagnostic value ofα-fetoprotein (AFP)-L3 and prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ)in hepatocellular carcinoma(HCC). METHODS:One hundred and sixty-eight patients during routine HCC surveillance were included in this study.Of the 168 patients,90(53.6%)had HCC including newly developed HCC(n=82)or recurrent HCC after treatment(n=8).Sera were obtained during their first evaluation for HCC development and at the time of HCC diagnosis before commencing HCC treatment.HCC was diagnosed by histological examination,appropriate imaging characteristics-computed tomography or magnetic resonance imaging.Control sera were collected from 78 patients with benign liver disease(BLD),which were obtained during routine surveillance with a suspicion of HCC.AFP,AFP-L3 and PIVKA-Ⅱwere measured in the same serum by microchip capillary electrophoresis and liquid-phase binding assay on a micro-total analysis system Wako i30 auto analyzer.The performance characteristics of three tests and combined tests for the diagnosis of HCC were obtained using receiver operating characteristic curves in all populations and subgroups with AFP<20 ng/mL. RESULTS:Of 90 HCC patients,38(42.2%)patients had AFP<20 ng/mL,20(22.2%)patients had AFP 20-200 ng/mL and 32(35.6%)patients had AFP>200 ng/mL.Of the 78 BLD patients,74(94.9%)patients had AFP<20 ng/mL.After adjustment for age and HBV infection status,AFP-L3 levels were higher in HCC than in BLD among patients with low AFP levels(<20 ng/mL)(P<0.001).In a total of 168 patients,areas under the curve(AUC)for HCC were 0.879,0.887,0.801 and 0.939 for AFP,AFP-L3,PIVKA-Ⅱand the combined markers,respectively.The combined AUC for three markers showed higher value than the AUCs of individual marker(P<0.05).AFP-L3 had higher AUC value than PIVKA-Ⅱfor HCC detection in entire patients(P =0.043).With combination of AFP-L3(cut-off>5%) and PIVKA-Ⅱ(cut-off>40 AU/L),the sensitivity were 94.4%and specificity were 75.6%in all patients.In 112 patients with low AFP levels(<20 ng/mL),AUCs of AFP-L3,PIVKA-Ⅱand combine AFP-L3 and PIVKA-Ⅱtests were 0.824,0.774 and 0.939,respectively. AFP-L3 with a cut-off value of 5%showed sensitivity of 71.1%and specificity of 83.8%,and PIVKA-Ⅱwith a cut-off value of 40 AU/L had sensitivity of 57.9%and specificity of 95.9%in patients with low AFP levels. The combination of AFP-L3 and PIVKA-Ⅱincreased the sensitivity and specificity up to 92.1%and 79.7%, respectively,in low AFP group.Combined markers detected 81.8%of early stage HCC(Union for Inter-national Cancer Control stageⅠ),86.7%of small sized tumor(<2 cm)and 91.7%of single tumor of HCC in the low AFP group.In multivariate analysis,AFP-L3 was correlated with AFP and tumor size,and PIVKA-Ⅱwas correlated with laboratory tests including serum aspartate aminotransferase,total bilirubin,platelets and albumin levels.PIVKA-Ⅱhad no correlation with AFP,AFP-L3 or tumor characteristics. CONCLUSION:Combined determination of AFP-L3 and PIVKA-Ⅱcould improve the diagnostic value for HCC detection in patients with or without increased AFP levels. | Jong Young Choi Seung Won Jung Hee Yeon Kim Myungshin Kim Yonggoo Kim Dong Goo Kim Eun-Jee Oh | 2013 | World Journal of Gastroenterology2013，19，3： | 55 |
| 13 | Inhibitory effect of IGF-Ⅱ antisense RNA on malignant phenotype of hepatocellular carcinoma显示文摘INIRODUCTIONAccording to the therapeutic effect and strategy ofantisense RNA for hepatoccllular carcinoma(HCC),we have specifically synthesized partialcDNA of human insulin-like growth factor Ⅱ(IGF-Ⅱ)and constructed IGF-Ⅱ cDNA antisenseeukaryotic expression vector.The constructedvector was introduced into hepatoma cell lineSMMC-7721 to block the intrinsic IGF-Ⅱexpression.The biological behavior changes ofhepatoma cells were observed.All these | Dong Hua Yang Ming Qing Zhang Jiang Du Chong Xu Oiao Ming Liang Ji Fang Mao Han Rong Qin Zi Rong Fan Department of Gastroenterology,Zhujiang Hospital,the First Military Medical University,Guangzhou 510282,China Laboratory of Molecular Biology,Zhujiang Hospital,the First Military Medical University,Guangzhou,China Departrnent of Biochemistry,the Second Military Medical University,Shanghai,China | 2000 | World Journal of Gastroenterology2000，6，2： | 54 |
| 14 | Recurrence or metastasis of HCC:predictors,early detection and experimental antiangiogenic therapy显示文摘AIM To investigate the predictors forrecurrence or metastasis of HCC,and toevaluate the effect of antiangiogenic therapy onthe growth of transplantable human HCC in nudemice.METHODS RT-PCR was used to measure theexpression of matrix metalloproteinase-9(MMP-9)and vascular endothelial growth factor(VEGF)in 56 pairs of nontumorous liver andtumor samples.Sixty blood samples from humanHCC were examined by nested RT-PCR to find outAFP mRNA.Recombinant human endostatin andpolyclonal antibody against VEGF wereadministered to treat human HCC transplanted innude mice.RESULTS Thirty of 56 HCC samples showedstronger expression of MMP-9 in tumoroustissues than in nontumorous tissues.Fifteen ofthe 26 patients with relative expression level ofMMP-9 more than 0.34 developed tumorrecurrence or metastasis,whereas only 7 of 30patients with relative expression level less than0.34 developed tumor recurrence(P<0.05).There was no significant difference in therelative expression level of VEGF betweenpatients with postoperative recurrence ormetastasis and those without recurrence.AFPmRNA was detectable in 53.3% of patients withHCC.The sensitivity and specificity of AFPmRNA as a marker to detect hematogenousdissemination of HCC cells was 81.8% and84.4%,respectively.Recombinant human endostatin and polyclonal antibody against VEGFinhibited the growth of transplantable HCC innude mice by 52.2% and 45.7%,respectively.CONCLUSION MMP-9 expression in HCCcorrelates with the postoperative recurrence ormetastasis of HCC.Patients with high level ofMMP-9 expression in HCC are susceptible tometastasis.AFP mRNA could serve as anindicator of hematogenous spreading of HCCcells in circulation and a predictor of recurrenceor metastasis of HCC.Antiangiogenesis may bean adjuvant therapy for HCC. | Jiang YF Yang ZH Hu JQ | 2000 | World Journal of Gastroenterology2000，6，1： | 57 |
| 15 | Targeting Wnt/β-catenin pathway in hepatocellularcarcinoma treatment显示文摘Hepatocellular carcinoma(HCC) is one of the most common causes of cancer-related death worldwide. Liver cancer is generally related to hepatitis B or Cinfection and cirrhosis. Usually, patients with HCC are asymptomatic and are diagnosed at late stages when surgical treatment is no longer suitable. Limited treatment options for patients with advanced HCC are a major concern. Therefore, there is an urge for finding novel therapies to treat HCC. Liver cancer is highly heterogeneous and involved deregulation of several signaling pathways. Wnt/β-catenin pathway is frequently upregulated in HCC and it is implicated in maintenance of tumor initiating cells, drug resistance, tumor progression, and metastasis. A great effort in developing selective drugs to target components of the β-catenin pathway with anticancer activity is underway but only a few of them have reached phase Ⅰ clinical trials. We aim to review the role of β-catenin pathway on hepatocarcinogenesis and liver cancer stem cell maintenance. We also evaluated the use of small molecules targeting the Wnt/β-catenin pathway with potential application for treatment of HCC. | valery vilchez lilia turcios francesc marti roberto gedaly | 2016 | World Journal of Gastroenterology2016，22，2： | 51 |
| 16 | New advances in hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC)is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths.Most HCC are associated withwell known underlying risk factors,in fact,HCC arise in cirrhotic patients in up to 90%of cases,mainly due to chronic viral hepatitis and alcohol abuse.The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients.HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified.The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient atrisk for developing HCC.The diagnosis of HCC can be based on non-invasive criteria(only in cirrhotic patient)or pathology.Accurately staging patients is essential to oncology practice.The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function.Treatment allocation is based on several factors:Liver function,size and number of tumours,macrovascular invasion or extrahepatic spread.The recommendations in terms of selection for different treatment strategies must be based on evidence-based data.Resection,liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates.Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment.Finally,in patients with advanced HCC with preserved liver function,sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. | Sonia Pascual Iván Herrera Javier Irurzun | 2016 | World Journal of Hepatology2016，8，9： | 51 |
| 17 | Diagnostic value of PIVKA-Ⅱ and alpha-fetoprotein in hepatitis B virus-associated hepatocellular carcinoma显示文摘AIM: To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein(AFP) and prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ) in chronic hepatitis B(CHB).METHODS: A total of 1255 patients with CHB, including 157 patients with hepatocellular carcinoma(HCC), 879 with non-cirrhotic CHB and 219 with cirrhosis without HCC, were retrospectively enrolled. The areas under the receiver operating characteristic(AUROC) curves of PIVKA-Ⅱ, AFP and their combination were calculated and compared.RESULTS: The optimal cutoff values for PIVKA-Ⅱ and AFP were 40 m AU/m L and 10 ng/m L, respectively, for the differentiation of HCC from nonmalignant CHB. The sensitivity and specificity were 73.9% and 89.7%, respectively, for PIVKA-Ⅱ and 67.5% and 90.3% for AFP, respectively. The AUROC curves of both PIVKA-Ⅱ and AFP were not significantly different(0.854 vs 0.853, P = 0.965) for the differentiation of HCC from nonmalignant CHB, whereas the AUROC of PIVKA-Ⅱ was significantly better than that of AFP in patients with cirrhosis(0.870 vs 0.812, P = 0.042). When PIVKA-Ⅱ and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-Ⅱ alone for the differentiation of HCC from nonmalignant CHB(P < 0.05), especially when cirrhosis was present(P < 0.05).CONCLUSION: Serum PIVKA-Ⅱ might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB. | Seung In Seo Hyoung Su Kim Won Jin Kim Woon Geon Shin Doo Jin Kim Kyung Ho Kim Myoung Kuk Jang Jin Heon Lee Joo Seop Kim Hak Yang Kim Dong Joon Kim Myung Seok Lee Choong Kee Park | 2015 | World Journal of Gastroenterology2015，21，13： | 60 |
| 18 | Resection vs thermal ablation of small hepatocellular carcinoma:What's the first choice?显示文摘Nowadays,hepatocellular carcinoma(HCC) is frequently diagnosed at an early stage,opening good perspectives to radical treatment by means of liver transplantation,surgical resection,or percutaneous ablation.Liver transplantation is considered the best option,but the lack of liver donors represents a major limitation.Therefore,surgical resection,offering a 5-year-survival rate of over 50%,is considered the first-choice treatment for patients with early stage HCC,whereas percutaneous ablation is usually reserved to patients who are not candidate to surgery.However,in the recent years some trials showed that percutaneous radiofrequency ablation(RFA) can be as effective as surgical resection in terms of overall survival and recurrencefree survival rates in patients with small HCC,and a retrospective comparative study reported 1-,3-,and 5-year overall survival rates and recurrence-free survival rates significantly better in patients with central HCC measuring 2 cm or smaller treated with RFA than in those treated with surgical resection.RFA is less expensive,less invasive,with lower complication rate and shorter hospital stay than surgical resection,and on the basis of the results of these studies it should be considered the first option in the treatment of very early HCC.However,RFA is size-dependent,so at present the need to achieve an adequate safety margin around the tumor limits to about 2 cm the diameter of the nodules that can be ablated with long-term outcomes comparable to or better than surgical resection.The main goal of the next technical developments of the thermal ablation systems should be the achievement of larger ablation areas with a single needle insertion.In this regard,the recent improvements in microwave energy delivery systems seem to open interesting perspectives to percutaneous microwave ablation,which could become the ablation technique of choice in the next future. | Paola Tombesi Francesca Di Vece Sergio Sartori | 2013 | World Journal of Radiology2013，5，1： | 50 |
| 19 | Th1/Th2 cytokines and their genotypes as predictors of hepatitis B virus related hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC), the predominant type of primary liver cancer, is one of the most serious lifethreatening malignancies, worldwide. In majority of the cases, HCC develops after prolonged and persistent chronic liver disease. hepatitis B virus(HBV) or HCV infection is prominent etiological factors, attributing to this condition. It has been well documented that HBV, being the inducer of chronic inflammation, is the main causative agent in causing HCC, particularly in Asian countries. The HBV infection leads to a wide range of clinical symptoms from carrier state to malignancy. Cytokines being immune-modulatory molecules, are the key mediators in the defense mechanism against viral infection. In this regard, this review will detail the substantial role of key Th1: interleukin 1(IL-1), IL-2, IL-12, tumor necrosis factor-α, interferon-γ; Th2: IL-4, IL-10 and non Th1/Th2: IL-6, transforming growth factor-β1 cytokines genotypes in analyzing the variability in the clinical manifestations in an HBV-afflicted individual, which might finally, culminates into HCC. Since cytokine production is regulated genetically, the cytokine promoter region single-nucleotide polymorphisms induced changes, greatly affects the cytokine production, thus resulting into differential outcome of immune balance. | Roli Saxena Jyotdeep Kaur | 2015 | World Journal of Hepatology2015，7，11： | 50 |
| 20 | Guide for diagnosis and treatment of hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC) is ranked as the 5th common type of cancer worldwide and is considered as the 3rd common reason for cancer-related deaths. HCC often occurs on top of a cirrhotic liver. The prognosisis determined by several factors; tumour extension, alpha-fetoprotein(AFP) concentration, histologic subtype of the tumour, degree of liver dysfunction, and the patient's performance status. HCC prognosis is strongly correlated with diagnostic delay. To date, no ideal screening modality has been developed. Analysis of recent studies showed that AFP assessment lacks adequate sensitivity and specificity for effective surveillance and diagnosis. Many tumour markers have been tested in clinical trials without progressing to routine use in clinical practice. Thus, surveillance is still based on ultrasound(US) examination every 6 mo. Imaging studies for diagnosis of HCC can fall into one of two main categories: routine non-invasive studies such as US, computed tomography(CT), and magnetic resonance imaging, and more specialized invasive techniques including CT during hepatic arteriography and CT arterial portography in addition to the conventional hepatic angiography. This article provides an overview and spotlight on the different diagnostic modalities and treatment options of HCC. | Magdy Hamed Attwa Shahira Aly El-Etreby | 2015 | World Journal of Hepatology2015，7，12： | 47 |
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