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| 1 | 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 |
| 2 | DNA-PKcs subunits in radiosensitization by hyperthermia on hepatocellular carcinoma hepG_2 cell line显示文摘AIM: To investigate the role of DNA-PKcs subunits inradiosensitization by hyperthermia on hepatocellularcarcinoma HepG2 cell lines.METHODS: Hep G2 cells were exposed to hyperthermiaand irradiation. Hyperthermia was given at 45.5 ℃Cellsurvival was determined by an in vitro clonogenic assay forthe cells treated with or without hyperthermia at varioustime points. DNA DSB rejoining was measured usingasymmetric field inversion gel electrophoresis (AFIGE). TheDNA-PKcs activities were measured using DNA-PKcs enzymeassay system.RESULTS: Hyperthermia can significantly enhanceirradiation-killing cells. Thermal enhancement ratio ascalculated at 10 % survival was 2.02. The difference inradiosensitivity between two treatment modes manifestedas a difference in the α components and the almost sameβ components, which α value was considerably higher inthe cells of combined radiation and hyperthermia ascompared with irradiating cells (1.07 Gy-1 versus 0.44 Gy1). Survival fraction showed 1 logarithm increase after an8-hour interval between heat and irradiation, whereas DNA-PKcs activity did not show any recovery. The cells wereexposed to heat 5 minutes only, DNA-PKcs activity wasinhibited at the nadir, even though the exposure time waslengthened. Whereas the ability of DNA DSB rejoining wasinhibited with the increase of the length of hyperthermictime. The repair kinetics of DNA DSB rejoining aftertreatment with Wortmannin is different from thehyperthermic group due to the striking high slow rejoiningcomponent.CONCLUSION: Determination with the cell extracts andthe peptide phosphorylation assay, DNA-PKcs activity wasinactivated by heat treatment at 45.5 C, and could notrestore. Cell survival is not associated with the DNA-PKcsinactivity after heat. DNA-PKcs is not a unique factor affectingthe DNA DSB repair. This suggests that DNA-PKcs do notplay a crucial role in the enhancement of cellularradiosensitivity by hyperthermia. | Walter J.Curran George Iliakis | 2002 | World Journal of Gastroenterology2002，8，5： | 87 |
| 3 | Effect of arsenic trioxide on rat hepatocarcinoma and its renal cytotoxicity显示文摘AIM: To study the effect of arsenic trioxide (As2O3) on rat experimental hepatocarcinoma and its renal cytotoxicity.METHODS: The hepatocarcinoma model was established by diethaylnitrosamine perfusion in stomach of 120 Wistar rats, and the treatment began at the end of 20 weeks.Before the treatment, the rat models were randomly divided into 5 groups. In the treatment groups, three doses of As2O3 were injected into rat abdominal cavity, the total time of drug administration was 4 weeks. Cisplatin control or the blank group was injected into abdominal cavity with equal amount of cisplatin or saline at the same time,respectively. On the 7th, 14th and 28th day after the treatment, the hepatocarcinoma nodules were obtained and the morphologic changes of hepatocarcinoma cells were observed under light and electron microscopes;Immunohistochemistry (S-P methods) was employed to detect the expression of bcl-2, bax and PCNA in hepatocarcinoma tissues; flow cytometry (TUNEL assay)was used to detect the apoptosis of liver cancer cells and the change of cytokinetics. On the 28th day, the kidneys were obtained and their histologic changes were observed under light microscope, and immunohistochemistry (SP stain) was also employed to detect the expression of bcl-2and PCNA. Cisplatin and saline solution were used as the control.RESULTS: As2O3 could induce the apoptosis of rat liver cancer cells and exhibited typical morphologic changes.The incidence of apoptosis of hapatocarcinoma cells was elevated (P=0.001). The elevation was the most higher in the group of middle-dose of As2O3 (1 mg.kg-1), significantly higher than that of the other arsenic groups and the controls (P=0.001). Large dose of As2O3 (5 mg.kg-1) was able to arise the incidence of apoptosis, but also produced a large amount of necrosis and inflammatory reaction. Middle dose of As2O3 dramatically increased the cell number in G2/M phase (P=0.0001), and apoptosis happened apparently.The expression of bcl-2 and bax was related to the dose of As2O3. With the up-regulation of apoptotic incidence, the ratio of bcl-2/bak decreased. But the incidence of apoptosis was not the highest status and the ratio of bcl-2/bax was at the lowest when the highest-dose of As2O3 was used.There was significant difference among the PCNA indexes (PCNA L1) of the five groups. Of them, three arsenic groups all showed decrease of different degrees, and this downregulation was most obvious in group A. There was significant difference among the three groups (P=0.016).Under the light microscope, the rat kidney in the cisplatin group exhibited tubular epithelium swelling and degeneration, protein casts in collecting tubules; While all arsenic groups didn't show the significant changes (P=0.013).In the arsenic groups, the expression of bcl-2 in the renal tubular epithelium was increased (P=0.005), no obvious changes happened to PCNA L1. But in the group of cisplatin,the PCNA L1 increased significantly (P=0.001).CONCLUSION: AS2O3 can induce apoptosis of rat hepatocellular carcinoma cells. And there is optimum dose;too high dose will induce the cytotoxic effect, while certain dose of As2O3 is able to block the cell cycle at G2/M phase.As2O3 had the most remarkable influence on G2/M cells,and it can also induce apoptosis to cells at other phases.As2O3 can restrain the proliferation of rat hepatocellular carcinoma cells, in a dose-time dependent manner.Compared with cisplatin, As2O3 didn't show obvious renal toxicity, which was related to the increasing expression of bcl-2 in renal tubular epithelium, the inhibition of apoptosis and the anti-oxidation effects. | Shao-Shan Wang Ti Zhang Xi-Lu Wang Li Hong Department of Surgery of Dagang Hospital 300270,Tianjin,China Qing-Hui Qi Department of Chinese and Western Integral Surgery of Master Hospital of Tianjin Medical University 300052,Tianjin,China | 2003 | World Journal of Gastroenterology2003，9，5： | 17 |
| 4 | Role of preoperative selective portal vein embolization in two-step curative hepatectomy for hepatocellular carcinoma显示文摘AIM: To determine the feasibility and role of ultrasoundguided preoperative selective portal vein embolization (POSPVE) in the two-step hepatectomy of patients with advanced primary hepatocellular carcinoma (HCC).METHODS: Fifty patients with advanced HCC who were not suitable for curative hepatectomy were treated by ultrasound-guided percutaneous transhepatic POSPVE with fine needles. The successful rate, side effects and complications of POSPVE, changes of hepatic lobe volume and two-step curative hepatectomy rate after POSPVE were observed.RESULTS: POSPVE was successfully performed in 47(94.0 %) patients. In patients whose right portal vein branches were embolized, their right hepatic volume decreased and left hepatic volume increased gradually. The ratio of right hepatic volume to total hepatic volume decreased from 62.4 % before POSPVE to 60.5 %, 57.2 %and 52.8 % after 1, 2 and 3 weeks respectively. The side effects included different degree of pain in liver area (38cases), slight fever (27 cases), nausea and vomiting (9cases). The level of aspartate alanine transaminase (AST),alanine transaminase (ALT) and total bilirubin (TBIL)increased after POSPVE, but returned to preoperative level in 1 week. After 2-4 weeks, two-step curative hepatectomy for HCC was successfully performed on 23 (52.3 %) patients.There were no such severe complications as ectopic embolization, local hemorrhage and bile leakage.CONCLUSION: Ultrasound-guided percutaneous transhepatic POSPVE with fine needles is feasible and safe. It can extend the indications of curative hepatectomy of HCC, and increase the safety of hepatectomy. | WuJi Jie-ShouLi Ung-TangLi Wu-HongLiu Kuan-ShengMa Xiang-TianWang Zhen-PingHe Jia-HongDong | 2003 | World Journal of Gastroenterology2003，9，8： | 15 |
| 5 | Significance and relationship between infiltrating inflammatory cell and tumor angiogenesis in hepatocellular carcinoma tissues显示文摘AIM: To investigate the relationship between infiltrating inflammatory cell and tumor angiogenesis in hepatocellular carcinoma (HCC) tissues and their clinicopathological features.METHODS: The paraffin-embedded specimens from 70 cases with HCC were stained using EliVision immunohistochemistry with mAbs against CD68, tryptase,and CD34. The counts of tumor-associated macrophage (TAM), mast cell (MC) and tumor microvessel (MV) were performed in the tissue sections.RESULTS: The mean counts of TAM, MC, and MV in HCC tissues were significantly higher than those in pericarcinomatous liver tissues (TAM: 69.31± 11.58 vs 40.23±10.36; MC: 16.74±5.67 vs 7.59±4.18; MV:70.11±12.45 vs 38.52± 11.16, P<0.01). The MV count in the patients with metastasis was markedly higher than that with non-metastasis (P<0.01). In addition, the MC count in the patients with poorly differentiated HCC was obviously higher than that with well differentiated HCC (P< 0.01). The correlation analysis showed that the TAM count was significantly correlated with the count of MV(r=0.712, P<0.01), and the MC count was obviously correlated with the MV count (r= 0.336, P< 0.05).CONCLUSION: TAM and MC might be closely related to the enhancement of tumor angiogenesis. The MV count might be associated with tumor invasion and metastasis.Moreover, the MC count might be associated with tumor differentiation and prognosis of HCC. | Shao-Hua Peng Hong Deng Jian-Feng Yang Ping-Ping Xie Cheng Li Hao Li De-Yun Feng | 2005 | World Journal of Gastroenterology2005，11，41： | 13 |
| 6 | Prognosis of hepatocellular carcinoma accompanied by microscopic portal vein invasion显示文摘AIM:To investigate the prognostic factors in patients with hepatocellular carcinoma(HCC) accompanied by microscopic portal vein invasion(PVI).METHODS:Of the 267 patients with HCC undergoing hepatic resection at Aso Iizuka Hospital,71 had PVI.After excluding 16 patients with HCC that invaded the main trunk and the first and second branches of the portal vein,55 patients with microscopic PVI were enrolled.RESULTS:The patients with HCC accompanied by microscopic invasion were divided into two groups:solitary PVI(PVI-S:n = 44),and multiple PVIs(PVI-M:n = 11).The number of portal vein branches invaded by tumor thrombi was 5.4 ± 3.8(2-16) in patients with PVI-M.In cumulative survival,PVI-M was found to be a significantly poor prognostic factor(P = 0.0019);while PVI-M and non-anatomical resection were significantly poor prognostic factors in disease-free survival(P = 0.0213,and 0.0115,respectively).In patients with PVI-M,multiple intrahepatic recurrence was more common than in the patients with PVI-S(P = 0.0049).In patients with PVI-S,non-anatomical resection was a significantly poor prognostic factor in disease-free survival(P = 0.0370).Operative procedure was not a significant prognostic factor in patients with PVI-M.CONCLUSION:The presence of PVI-M was a poor prognostic factor in patients with HCC,accompanied by microscopic PVI.Anatomical resection is recommended in these patients with HCC.Patients with HCC and PVI-M may also be good candidates for adjuvant chemotherapy. | Ken Shirabe Kiyoshi Kajiyama Norifumi Harimoto Hideaki Masumoto Tatsuro Fukuya Masafumi Ooya Yoshihiko Maehara | 2009 | World Journal of Gastroenterology2009，15，21： | 10 |
| 7 | Gene expression profiles of hepatoma cell line HLE显示文摘AIM: To investigate the global gene expression of cancer related genes in hepatoma cell line HLE using Atlas Human Cancer Array membranes with 588 well-characterized human genes related with cancer and tumor biology.METHODS: Hybridization of cDNA blotting membrane was performed with 32P-labeled cDNA probes synthesized from RNA isolated from Human hepatoma cell line HLE and noncirrhotic normal liver which was liver transplantation donor.AtlasImage, a software specific to array, was used to analyze the result. The expression pattern of some genes identified by Atlas arrays hybridization was confirmed by reverse transcription polymerase chain reaction (RT-PCR)in 24 pairs of specimens and Northern blot of 4 pairs of specimens.RESULTS: The differential expression of cell cycle/growth regulator in hepatocellular carcinoma (HCC) showed a stronger tendency toward cell proliferation with more than 1.5-fold up-regulation of Cyclin C, ERK5, ERK6, E2F-3, TFDP2 and CK4. The anti-apoptotic factors such as Akt-1 were up-regulated, whereas the promotive genes of apoptosis such as ABL2 were down-regulated. Among oncogene/tumors suppressors, SKY was down-regulated. Some genes such as Integrin beta 8, Integrin beta 7, DNA-PK, CSPCP,byglycan, Tenacin and DNA Topo were up-regulated. A number of genes, including LAR, MEK1, eps15, TDGF1,ARHGDIA were down-regulated. In general, expression of the cancer progression genes was up-regulated, while expression of anti-cancer progression genes was downregulated. These differentially expressed genes tested with RT-PCR were in consistent with cDNA array findings.CONCLUSION: Investigation of these genes in HCC is helpful in disclosing molecular mechanism of pathogenesis and progression of HCC. For the first time few genes were discovered in HCC. Further study is required for the precise relationship between the altered genes and their correlation with the pathogenesis of HCC. | Lian-XinLiu Zhi-HuaLiu Hong-ChiJiang Wei-HuiZhang Shu-YiQi JieHu Xiu-QinWang MinWu | 2003 | World Journal of Gastroenterology2003，9，4： | 10 |
| 8 | The Chinese classification system compared with TNM staging in prognosis of patients with primary hepatic carcinoma after resection显示文摘BACKGROUND: The life expectancy of a patient with primary hepatic carcinoma (PHC) is hard to predict, and it is related to many prognostic factors. The Chinese classification system including five parameters: tumor, vascular thrombosis, lymph node metastasis, distant metastasis and Child-Pugh stage developed in 1999 was adopted by the 8th National Conference on liver Cancer of the Chinese Anti-Cancer Association in 2001. In this study, the discriminatory ability of the Chinese classification system -was compared with that of the TNM staging in patients for resection of PHC, in addition to the evaluation of prognostic value. METHODS: The data of 246 patients who had undergone resection of PHC from January 1986 to December 2000 (average age, 51 years; male/female ratio, 213/33) were retrospectively studied. Among the 246 patients, 227 were followed up for at least 3 years. RESULTS: The 1-, 3-, 5-, 7-, and 10-year tumor-free survival rates were 55% , 30% , 25% , 20% and 18% , respectively. The Chinese classification system was better than the TNM staging system in predicting survival rate of patients with PHC, as confirmed by survival curves shown by the Kaplain-Meier method. The mean survival time was 155, 70, 39, 16, and 4 months in patients with die Chinese classification stages Ⅰa, Ⅰb, Ⅱa,Ⅱb, and Ⅲ, respectively. The 1-, 3-, 5-, 7-, and 10-year tumor-free survival rates of the Chinese classification system and TNM staging were statistically significant and had a slightly positive relationship. The predictive capacity of the Chinese classification system was confirmed in any two subgroups of patients undergoing operation. COX proportional hazards regression analysis showed that the Chinese classification system was the only independent prognostic factor for survival. CONCLUSIONS: Taking both tumor extension and liver function into account, we consider that the Chinese classification system making up for the deficiency of UICC TNM staging is more precise in predicting the prognosis of patients with resection of PHC. | Jian-Ming Sheng, Wen-He Zhao, Fu-Sheng Wu, Zhi-Min Ma, Yi-Zheng Feng, Xing-Ren Zhou and Li-Song Teng Department of Oncological Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003 , China | 2005 | Hepatobiliary & Pancreatic Diseases International2005，4，4： | 9 |
| 9 | 肝癌组织HSP70和caspase 3的表达意义显示文摘目的:研究热休克蛋白70和caspase 3在肝细胞癌及癌旁肝组织中的表达及其临床意义. 方法:利用免疫组织化学检测70例肝细胞癌及其癌旁肝组织中HSP70和caspase 3蛋白的表达. 结果:HCC中HSP70的阳性率和阳性强度明显高于癌旁肝组织(68.6%VS 31.4%,P<0.01),而caspase3蛋白的阳性率和阳性强度明显低于癌旁肝组织(17.1%vs 35.7%,P<0.01). 在HCC中HSP70和caspase3蛋白的表达强度与HCC的分化程度和肿瘤的大小明显相关,分化愈差和肿瘤愈大HSP70表达愈强(分别为:F=5.219和5.421,P均<0.01)而caspase3蛋白表达愈弱(分别为F=5.944和4.571,P均<0.01). 统计学分析显示在HCC及其癌旁肝组织中HSP70和caspase 3蛋白的表达呈明显负相关(分别为:r=0.4126和-0.5237,P均<0.01). 结论:本文结果提示在HCC发生过程中HSP70的表达可能通过促进细胞的转化和增生及抑制细胞的凋亡,使HCC呈现无限制的生长及恶性程度不断增高;检测HSP70有望能成为判断HCC预后的重要指标之一. | 彭绍华 邓虹 冯德云 郑晖 | 2004 | 世界华人消化杂志2004，12，4： | 8 |
| 10 | 原发性肝癌的中国分期与TNM分期对肝癌切除的预后价值的比较研究显示文摘目的探讨原发性肝癌中国分期与TNM分期对判断手术切除肝癌预后的意义。方法回顾性分析我院1986年1月至2000年12月对246例原发性肝癌患者行手术切除病例的临床资料,其中227例患者随访3年以上。生存率计算采用KaplanMeier法,Longrang比较生存曲线。结果全组术后1、3、5、7、10年无瘤生存率分别为55%、30%、25%、20%及18%。新分期Ⅰa、Ⅰb、Ⅱa、Ⅱb及Ⅲ期术后1、3、5、7、10年无瘤生存期各期间差异均有统计学意义,并与TNM分期有一定相关性。TNM分期Ⅰ、Ⅱ、Ⅲ及Ⅳ期术后1、3、5、7、10年无瘤生存期差异有统计学意义,然Ⅲ、Ⅳ期间比较统计学差异无统计学意义。结论肝癌中国分期由于兼顾肿瘤与宿主肝功能两方面因素,分期更加精确,在反映切除肝癌预后方面具有重要价值。 | 盛建明 赵文和 马志敏 冯懿正 周杏仁 方宝山 | 2005 | 中华普通外科杂志2005，20，10： | 7 |
| 11 | Local recurrence is an important prognostic factor of hepatocellular carcinoma显示文摘AIM: To clarify the importance of complete treatment by PEIT.METHODS: A total of 140 previously untreated cases of HCC were enrolled in this study from 1988 to 2002. The inclusion criteria were: a solitary tumor less than 4 cm in diameter or multiple tumors, fewer than four in number and less than 3 cm in diameter, without extrahepatic metastasis or vessel invasion. As general principles for the treatment of HCC, the patients underwent transcatheter arterial chemoembolization (TACE) prior to PEIT. After the initial treatment of the patients,ultrasonography and computed tomography were performed, and measurement of serum levels of α-fetoprotein (AFP) was determined. When tumor recurrences were detected, PEIT and/or TACE were repeated whenever the hepatic functional reserve of the patient permitted. We then analyzed the variables that could influence prognosis, including tumor size and number, the serum levels of AFP, the parameters of hepatic function (albumin, bilirubin, ALT, hepaplastin test,platelet number, and indocyanine green retention at 15min [ICG-R15]), combined therapy with TACE, distant recurrence, and local recurrence.RESULTS: Univariate analysis identified the ICG test,serum levels of AFP and albumin, tumor size and number,and local recurrence, but not distant recurrence, as significant prognostic variables. In multivariate analysis using those five parameters, the ICG test, tumor size, tumor number,and local recurrence were identified as significant prognostic factors. In both univariate and multivariate analyses, the relative risk for the ICG test was the highest, followed by local recurrence.CONCLUSION: We found that local recurrence is an independent prognostic factor of HCC, indicating that achieving complete treatment for HCC on first treatment is important for improving the prognosis of patients with HCC. | Eiichirou Arimura Kazuhiro Kotoh Makoto Nakamuta Shusuke Morizono Munechika Enjoji Hajime Nawata | 2005 | World Journal of Gastroenterology2005，11，36： | 7 |
| 12 | LHRH类似物对肝癌裸鼠移植瘤生长的影响显示文摘目的:观察LHRH类似物的体内抗肝癌细胞增生活性,为LHRH类似物用于肝癌的内分泌治疗提供实验依据。方法:实验选用5-7周龄♂BALB/c裸鼠20只,分治疗组(丙氨瑞林瘤内注射组)和对照组(生理盐水瘤内注射组),用人肝癌hHCC细胞系建立肝癌荷瘤裸鼠模型,观察LHRH类似物丙氨瑞林(LHRH-A)对裸鼠移植瘤生长的影响;并分别用H-E染色和免疫细胞化学技术检测瘤组织的病理组织学改变和GnRH受体及凋亡蛋白Bax表达的变化。结果:LHRH-A瘤内注射(剂量为75μg/d)可显著抑制肝癌移植瘤的生长。治疗3 wk后治疗组裸鼠肿瘤体积(1885.9±738.3mm^3)明显小于对照组裸鼠的肿瘤体积(4223.4±1027.6mm^3),两组间有统计学差异(P<0.005);LHRH-A治疗3wk后的抑瘤率可达58%;治疗组裸鼠存活期(87.8±5.3d)较对照组(64.6±6.8d)显著延长(P<0.05);治疗3wk后病理组织学发现治疗组瘤组织中癌细胞核分裂象减少,腺样癌组织、凋亡细胞数增多;治疗组瘤组织中表达GnRH受体的癌细胞数增加(72.5% vs 56.4%,P<0.05),Bax阳性细胞比率增加(53.8% vs 41.5%,P<0.05)。结论:LHRH-A具有显著抑制肝癌裸鼠移植瘤细胞增生的活性,LHRH受体和凋亡蛋白Bax可能参与了LHRH-A对肝癌细胞增生的抑制作用。 | 张金山 王红 黄威权 孙岚 黄高升 张远强 | 2002 | 世界华人消化杂志2002，10，7： | 6 |
| 13 | Expression of co-stimulator 4-1BB molecule in hepatocellular carcinoma and adjacent non-tumor liver tissue,and its possible role in tumor immunity显示文摘AIM:To investigate the expression of 4-1BB molecule in hepatocellular carcinoma (HCC) and its adjacent tissues.METHODS:Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of 4-1BB in hepatocarcinoma and its adjacent tissues,and peripheral blood mononuclear cells (PBMCs) from both HCC and health control groups.Flow cytometry was used to analyse the phenotypes of T cell subsets from the blood of HCC patients and healthy volunteers,and further to determine whether 4-1BB molecules were also expressed on the surface of CD4+ and CD8+ T cells. The localization of 4-1BB proteins on tumor infiltrating T cells was determined by direct immunofluorescence cytochemical staining and detected by confocal microscopy.RESULTS:4-1BB mRNA, which was not detectable in normal liver,was found in 19 liver tissues adjacent to tumor edge(<1.0cm).Low expression of 4-1BB mRNA was shown in 8 tumor tissues and 6 liver tissues located within 1 to 5cm away from tumor edge. In PBMCs, 4-1BB mRNA was almost not detected. Percentage of CD4^+, CD8^+ and CD3^+/CD25^+ T cells, as well as ratio of CD4 to CD8 revealed no difference between groups (P>0.05,respectively),while a significant lower percentage of CD3^+ T cell was found in HCC group as compared to healthy control group (P<0.05).However, 4-1BB molecules were almost not found on the surface of CD4+ and CD8+ T cells in HCC and healthy control group.Double-staining of 4-1BB^+/CD4^+ and 4-1BB^+/CD8^+ immunofluorescence on tumor infiltrating T cells was detected in 13 liver tissues adjacent to tumor edge (<1.0cm) by confocal microscopy.CONCLUSION: Although HCC may escape from immune attack by weak immunogenicity or downregulated expression of MHC-1 molecules on the tumor cell surface,tumor infiltrating T cells can be activated via other costimulatory signal pathways to exert a limited antitumor effect on local microenvironment. The present study also implicates that modulating 4-1BB/4-1BBL costimulatory pathway may be an effective immunotherapy strategy to augment the host response. | Wan, YL Zheng, SS Zhao, ZC Li, MW Jia, CK Zhang, H | 2004 | World Journal of Gastroenterology2004，10，2： | 6 |
| 14 | 汉防己甲素抑制肝癌细胞增生的作用显示文摘目的:研究汉防己甲素(tetrandrine,TTD)对肝癌细胞的作用及其机制。方法:采用MTT比色法观察了TTD对肝癌细胞增生的影响;采用流式细胞仪法观察了TTD对肝癌细胞内活性氧的影响;采用琼脂凝胶电泳法观察了DNA片断化的梯形条带。结果:10 and 20μmol/L TTD作用于肝癌细胞系24,48,72h后其增生率分别为90.1±1.0% and 77.5±2.0%,70.2±2.9% and 56.6±1.6%,61.6±2.0% and 47.2±1.9%(F=40.025,P<0.001);0、10和20μmol/L TTD作用于肝癌细胞系2h后O_2^-为35%、36.6%、63.2%;H_2O_2为24.5%、40.5%、84.6%。48h后20μmol/L TTD组肝癌细胞出现典型的凋亡表现。结论:TTD能够通过诱导肝癌细胞内活性氧的产生,而引起细胞凋亡,呈明显的剂量依赖性。 | 荆绪斌 李涛 杨绮华 郭光华 胡辉 陈素钻 | 2003 | 世界华人消化杂志2003，11，8： | 6 |
| 15 | Laser ablation of hepatocellular carcinoma-A review显示文摘A wide range of local thermal ablative therapies have been developed in the treatment of non resectable hepatocellular carcinoma(HCC) in the last decade.Laser ablation(LA) and radiofrequency ablation(RFA) are the two most widely used of these.This article provides an up to date overview of the role of laser ablation in the local treatment of HCC.General principles,technique,image guidance and patient selection are discussed.A review of published data on treatment efficacy,long term outcome and complication rates of laser ablation is included and comparison with RFA made.The role of laser ablation in combination with transcatheter arterial chemoembolisation is also discussed. | Antony Lawrence Gough-Palmer Wladyslaw Michal Witold Gedroyc | 2008 | World Journal of Gastroenterology2008，14，47： | 5 |
| 16 | Increased nociceptin/orphanin FQ plasma levels in hepatocellular carcinoma显示文摘AIM: The heptadecapeptide nociceptin alias orphanin FQ is the endogenous agonist of opioid receptor-like1 receptor. It is involved in modulation of pain and cognition. High blood level was reported in patients with acute and chronic pain,and in Wilson disease. An accidental observation led us to investigate nociceptin in hepatocellular carcinoma. METHODS: Plasma nociceptin level was measured by radioimmunoassay, aprotinin was used as protease inhibitor. Hepatocellular carcinoma was diagnosed by laboratory, ultrasound, other imaging, and confirmed by fine needle biopsy. Results were compared to healthy controls and patients with other chronic liver diseases. RESULTS: Although nociceptin levels were elevated in patients with Wilson disease (14.0±2.7 pg/mL, n=26),primary biliary cirrhosis (12.1±3.2 pg/mL, n=21) and liver cirrhosis (12.8±4.0 pg/mL, n=15) compared to the healthy controls (9.2±1.8 pg/mL, n=29, P<0.001 for each), in patients with hepatocellular carcinoma a ten-fold increase was found(105.9±14.4 pg/mL, n=29, P<0.0001). High plasma levels were found in each hepatocellular carcinoma patient including those with normal alpha fetoprotein and those with pain (104.9±14.9 pg/mL, n=-12) and without (107.7±14.5pg/mL, n=6). CONCLUSION: A very high nociceptin plasma level seems to be an indicator for hepatocellular carcinoma. Further research is needed to clarify the mechanism and clinical significance of this novel finding. | FerencSzalay AndreaHorvath PeterL.Lakatos AnikoFolhoffer KingaDunkel DalmaHegedus KornéliaTekes MónikaBHantos | 2004 | World Journal of Gastroenterology2004，10，1： | 5 |
| 17 | 经皮穿刺氩氦刀冷冻治疗肝癌31例显示文摘目的:探讨氩氦刀冷冻治疗肝脏恶性肿瘤的适应证、疗效及临床意义。方法:2001-07/2002-01肝癌患者31例在B超引导下行经皮穿刺氩氦刀冷冻治疗肝脏肿瘤术。术后患者定期复查血清肿瘤标记物、B超检查及CT或MRI。结果:患者肝功能Child A级26例,Child B级4例,Child C级1例,原发性肝癌21例,转移性肝癌10例,小肝癌(肿瘤直径≤5cm)甲胎蛋白阳性者治疗后转阴占80%(8/10),甲胎蛋白阴性者治疗后CT或MRI复查病灶完全坏死达66.7%(2/3),转移性肝癌治疗后瘤标降至正常或CT、MRI提示病灶完全坏死者占50%(5/10)。结论:氩氦刀冷冻治疗肝癌是一种微创、安全、疗效可靠的新方法,对于不适宜行手术治疗的肝癌患者是一种有效的治疗方法。 | 钱国军 陈汉 吴孟超 | 2003 | 世界华人消化杂志2003，11，6： | 3 |
| 18 | 应用氩氦刀治疗子宫肌瘤28例疗效分析显示文摘目的:探讨美国氩氦刀冷冻系统冷冻消融介入治疗子宫肌瘤的临床疗效。方法:在超声引导下经子宫颈穿刺采用氩氦刀治疗子宫肌瘤28例。结果:术后3个月肌瘤50%以上缩小者达80%。大部分病例临床症状改善或消失,其中有24例的月经量在冻融术后1年内恢复正常。结论:氩氦刀治疗子宫肌瘤具有操作简单,性能稳定,微创,安全可靠等优势,值得推广。 | 程国昌 何相明 | 2005 | 中国妇幼保健2005，20，22： | 3 |
| 19 | 原发性肝癌不同临床分期的比较显示文摘评估原发性肝癌患者的生存期较困难,临床分期与评估预后和治疗的选择密切相关,而至今尚无统一的分期法。本文对近年提出的各种不同的临床分期(包括Okuda分期,法国分期,Clip分期,BCLC分期,TNM分期,香港中文大学预后指数,国内分期等)进行综合论述,比较各分期法的差异并介绍最新的发展趋势。 | 许致远 吴万垠 | 2005 | 中国肿瘤临床2005，32，12： | 3 |
| 20 | IL-2联合IL-12激活A-NK细胞治疗人肝癌HepG-2显示文摘目的:研究A-NK细胞体外抗肿瘤作用及小鼠体内抗肿瘤作用. 方法:用淋巴细胞分离液分离健康人外周血中的血单个核细胞,PME(5 mmoL/L)室温处理40 min,PME处理后的人外周血单个核细胞重悬于AIMV中.分为四组分别为:IL-2 (6 MU/L)组,IL-2(1MU/L)组,IL-12(5 ug/L)组,IL-2 (1 MU/L)+IL-12(5 ug/L)组;每瓶细胞浓度为5×109/L,于37℃,50 mL/L CO2饱和湿化空气的培养箱中水平培养4- 5h,移去含未黏附于塑料表面的细胞悬液,收集黏附于塑料表面的细胞(即A-NK细胞),MTT比色法检测A-NK细胞体外细胞毒作用;然后建立肝癌细胞株裸鼠皮下移植瘤模型,以肿瘤体积、抑瘤率、生存期等指标观察A-NK对移植瘤的抑制作用. 结果:A-NK+IL-2+IL-12组细胞毒活性明显高于其他三组(aP<0.05),体内实验表明A-NK+IL-2+EL-4/IL-12治疗组的移植瘤生长速度缓慢,体积明显小于生理盐水对照组(bP<0.05),生存期显著延长(cP<0.05). 结论:IL-12辅助IL-2激活的A-NK细胞的体外杀伤活性较单独用IL-2或IL-12强,体内实验显示具有明显的抗肿瘤作用. | 赵东陆 王志华 张春艳 杨悦 | 2004 | 世界华人消化杂志2004，12，8： | 3 |
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