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Characterization of focal hepatic lesions with contrast-enhanced C-cube gray scale ultrasonography

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World Journal of Gastroenterology 2003年第8期9卷 1667-1674页

作者： Wen-pingwang HongDing QingQi FengMao Zhi-ZhangXu MasatoshiKudo DepartmentofUltrasound ZhongshanHospitalofFudanUniversity180FenglinRoadSlmnghai.200032China DepartmentofGastroenterologyandHepatology SchoolofMedicineKinkiUniversity377-2Ohno-HigashiOsaka-Sayama589-8511Japan

AIM: To characterize enhancement patterns of focal hepatic lesions using C-cube gray scale sonography with a microbubble contrast agent and to evaluate its usefulness in differential diagnosis of hepatic ***: Fifty-four patients with 58 focal hepatic lesions were examined with Levovist-enhanced C-cube gray scale sonography. The final diagnosis of hepatic lesions was 29primary liver cancers, 4 metastases, 8 hemangiomas, 12focal nodular hyperplasias, 2 inflammatory pseudotumors of the liver and 3 angiomyolipomas. The initiation time of enhancement in various lesions and enhancement duration after administration of contrast agent were *** findings in lesions were classified as peripheral enhancement, homogenous enhancement, mosaic enhancement and no enhancement depending on microbubble signals in the lesion relative to the liver ***: The initiation time of enhancement in hemangioma (48±12 s) was significantly later compared to other lesions (P＜0.05). The enhancement duration of malignancies (69±33 s in primary liver cancer, 61±23 s in metastasis) was significantly shorter compared to benign lesions (P＜0.05).Intranodular enhancement appearing at arterial phase and decreasing at portal venous phase was considered characteristic for malignancy. Intranodular enhancement did not appear earlier than the liver parenchyma, and peripheral enhancement pattern was regarded as positive findings for hemangioma. Intranodular enhancement appeared in the arterial phase, and homogenous enhancement pattern sustained in the whole portal venous phase were regarded as positive findings for focal nodular hyperplasia. No microbubble signals appeared in two inflammatory pseudotumors of the ***: C-cube gray scale sonography can demonstrate dynamic intranodular enhancement in various focal hepatic lesions. The information provided by this methodology may be useful in the differential diagnosis of hepatic lesions.

关键词：肝疾病诊断超声检查临床分析

Detection of CK20mRNA in peripheral blood of pancreatic cancer and its clinical significance

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World Journal of Gastroenterology 2005年第7期11卷 1023-1027页

作者： Yun-LiZhang Jian-GuoFeng Jian-MinGou Li-XinZhou pingwang DepartmentofHepato-Pancreatico-BilliarySurgery ZhejiangCancerHospitalHangzhou310022ZhejiangProvinceChina ZhejiangCancerInstitute Hangzhou310022ZhejiangProvinceChina

AIM: To detect the expression of CK20mRNA in peripheral blood of Pancreatic cancer and evaluate its clinical ***: Expression of CK20mRNA in peripheral blood was detected by fluorogenic qualitative reverse transcription-polymerase chain reaction (RT-PCR) in 40cases of pancreatic cancer at the night before operation,in 5 cases of benign pancreatic diseases, in 5 cases of healthy individuals. The relationships were investigated between CK20mRNA expression and the clinicopathological variables, and clinical follow-up outcome in those patients with pancreatic cancer having undergone radical ***: Of the 40 patients with pancreatic cancer, 23(57.5%) cases were positive for CK20mRNA ***20mRNA expression was significantly correlated with lymphatic metastasis (P = 0.008), histopathological grading (P = 0.009), and pathological stage (P = 0.021);there was no significant correlation between CK20mRNA expression and age, gender, tumor diameter, and depth of invasion. The cumulative metastasis rates of patients with CK20mRNA expression were higher than those of patients with no CK20mRNA expression within 6 mo (34.7%vs5.9%, P= 0.043) or 12 mo (73.9% vs35.3%, P= 0.02)after operation. CK20mRNA expression in peripheral blood of pancreatic cancer indicated poorer prognosis. The survival rate of patients with CK20mRNA expression was lower than that of patients with negative CK20mRNA expression (Log-Rank = 13.31, P = 0.0003).CONCLUSION: CK20mRNA is a sensitive and specific molecular marker for the detection of micrometastasis in peripheral blood of patients with pancreatic cancer. The CK20mRNA expression in peripheral blood is correlated with biological characteristic of pancreatic cancer. It can help to predict the prognosis of pancreatic cancer after operation, and to determine which patient will benefit from aggressive adjuvant therapies.

关键词： CK20mRNA Peripheral blood Pancreatic cancer

Antitumor immunity induced by DNA vaccine encoding alpha-fetoprotein/heat shock protein 70

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World Journal of Gastroenterology 2004年第21期10卷 3197-3200页

作者： Xiao-pingwang Guo-ZhenLiu Ai-LiSong Hai-YanLi YuLiu DepartmentofPathology CapitalUniversityofMedicalSciencesBeijing100054China

AIM:To construct a DNA vaccine encoding human alpha-fetoprotein (hAFP)/heat shock protein 70 (HSP70), and to study its ability to induce specific CTL response and its protective effect against AFP-expressing ***: A DNA vaccine was constructed by combiningh AFP gene with HSP70 gene. SP2/0 cells were stably transfected with pBBS212-hAFP and pBBS212-hAFP/HSP70 eukaryotic expression vectors. Mice were primed and boosted with DNA vaccine hAFP/HSP70 by intramuscular injection, whereas plasmid with hAFP or HSP70 was used as controls. ELISPOT and ELISA were used to detect IFN-γ-producing splenocytes and the level of serum anti-AFP antibody from immunized mice respectively. In vivo tumor challenge was measured to assess the immune effect of the DNA ***: By DNA vaccine immunization, the results of ELISPOT and ELISA showed that the number of IFN-γ-producing splenocytes and the level of serum anti-AFP antibody were significantly higher in rhAFP/HSP70 group than in hAFP and empty plasmid groups (95.50±10.90 IFN-γ spots/10^6 cells vs 23.60±11.80 IFN-γ spots/10^6 cells,7.17±4.24 IFN-γ spots/106 cells, P<0.01; 126.50±8.22μg/mL vs 51.72±3.40μg/mL, 5.83±3.79μg/mL, P<0.01). The tumor volume in rhAFP/HSP70 group was significantly smaller than that in pBBS212-hAFP and empty plasmid groups (37.41±7.34 mm^3 vs 381.13±15.48 mm^3, 817.51±16.25 mm^3,P<0.01). CONCLUSION: Sequential immunization with a recombinant DNA vaccine encoding AFP and heat shock protein70 could generate effective AFP-specific T cell responses and induce definite antitumor effects on AFP-producing tumors, which may be suitable for some clinical testing as a vaccine for HCC.

关键词：抗癌作用免疫性 DNA 疫苗编码 α-胎蛋白热损害蛋白70 hAFP

TIP30 regulates apoptosis-related genes in its apoptotic signal transduction pathway

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World Journal of Gastroenterology 2005年第2期11卷 221-227页

作者： MeiShi XiaZhang pingwang Hong-WeiZhang Bai-HeZhang Meng-ChaoWu DepartmentofClinicalSurgery EasternHepatobiliarySurgeryHospitalTheSecondMilitaryMedicalUniversity225ChanghaiRoadShanghai200438China ShandongUniversity Jinan250014ShandongProvinceChina DepartmentofOncology FuzhouGeneralHospitalofNanjingMilitaryCommandFuzhou350025FujianProvinceChina ShandongUniversity Jinan250014ShandongProvinceChina//DepartmentofClinicalSurgeryEasternHepatobiliarySurgeryHospitalTheSecondMilitaryMedicalUniversity225ChanghaiRoadShanghai200438China

AIM: To investigate the role of TIP30 in apoptotic signal pathway in hepatoblastoma cells and to provide a basis for TIP30 as a gene therapy candidate in the regression of hepatoblastoma cells. METHODS: Apoptosis of human hepatoblastoma cell lines HepG2 (p53 wild), Hep3B (p53 null) and PLC/RPF/5 (p53 mutant) infected with Ad-TIP30 (bearing a wild type human Tip30 gene) were analyzed and p53, Bax and Bcl-xl expression levels were compared among these cells. MTT assay, DNA fragmentation, in situ 3' end labeling of DNA, annexin-V FITC staining were used to detect cell death and apoptosis in cells at various time intervals subsequent to infection, and to determine whether TIP30 had an effect on the expression levels of some apoptosis-related gene products such as Bax, p53 and Bcl-xl. A similar time course experiment was performed by Western blotting. RESULTS: In MTT assay, the viability of HepG2 cells decreased significantly from 99.7% to 10% and displayed more massive cell death within 5-8 d than Hep3B and PLC/ RPF/5 cells, with their viability decreased from 97.8% to 44.3% and 98.1% to 50.4%, respectively. In annexin-V FITC assay, the percentage of apoptosis cells in HepG2 cells was two to three-fold higher than that in control cells (infected with Ad-GFP), two-fold higher than that in Hep3B cells and 1.4-fold higher than that in PLC/RPF/5 cells 36 h after infection, respectively. Moreover, in HepG2 cells, the p53 began to increase 6-8 h after infection, reaching a maximum level between 8 and 12 h after infection and then dropped. Bax showed a similar increase in the cells as p53 reached the maximum at 8-12 h and subsequently decreased. Interestingly, Bcl-xl protein levels were down regulated during 24 to 36 h after Ad-TIP30 infection. In contrast, ectopic expression of TIP30 in Hep3B and PLC/ RPF/5 cells had no effect on the regulation of Bax expression, but had an effect on Bcl-xl levels. In comparison with HepG2 cells, these data suggested that up-regulation of p53

关键词： Hepatoblastoma TIP30 Apoptosis Signa transduction

Pathobiological significance of vascular endothelial growth factor and Maspin expressions in human gastric carcinoma

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World Journal of Gastroenterology 2004年第18期10卷 2624-2627页

作者： Jian-JunLi YingChen Su-MinZhang Dong-YingWu Yan-pingwang YanXin No.4Laboratory CancerInstituteTheFirstAffiliatedHospitalChinaMedicalUniversityShenyang110001LiaoningProvinceChina ShenyangGynecologyandObstetricsHospital Shenyang110014LiaoningProvinceChina

AIM: To investigate the correlation between expression of vascular endothelial growth factor (VEGF) and cell differentiation, invasion, metastasis and Maspin expression in gastric ***: Formalin-fixed paraffin-embedded tissue specimens from 73 cases of gastric carcinoma were studied with SP immunohistochemistry, using anti-VEGF monoclonal antibody, and thirty-nine of them were studied using antiMaspin monoclonal antibody. VEGF expression was compared with the clinical stage, lymph node metastasis, and Borrmann's and WHO's classification of gastric ***: The positive rate of VEGF expression was significantly higher in adjacent non-carcinoma epithelia (ANCE) than in non-metaplastic, non-carcinoma gastric epithelia (NMNCE), which were at least 4 cm distant from the primary tumor (P = 0.000, x^2= 73.03). The positive rate of VEGF expression was significantly higher in advanced gastric carcinoma (AGC) than in early gastric carcinoma (EGC) (P = 0.032, x^2 = 4.62). The positive rate of VEGF expression in gastric carcinomas with lymph node metastases was significantly higher than that in those without metastasis (P = 0.006, x^2 = 7.47). Maspin was weakly expressed in 16 out of 39 cases of NMNCE, and the positive immunoreaction was limited to gland cells of the stomach body. There was no significant correlation between the expression of VEGF and histological or gross classifications, and correlation between the expressions of VEGF and Maspin in gastric carcinoma (P = 0.648, x^2 = 0.21).CONCLUSION: Expression of VEGF is significantly correlated to the malignant biological behaviors of gastric carcinoma,but there is no significant correlation between the expression of VEGF and Maspin.

关键词：病理学内皮细胞生长因素基因表达人类胃癌肿瘤 VEGF 单克隆抗体

Resistance index in differential diagnosis of liver lesions by color doppler ultrasonography

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World Journal of Gastroenterology 2004年第7期10卷 965-967页

作者： YanWang Wen-pingwang HongDing Bei-JianHuang FengMao Zhi-ZhangXu DepartmentofUltrasound ZhongshanHospitalofShanghaiFudanUniversityShanghai200032China

AIM: To investigate the specific value of resistance index (RI) in color Doppler ultrasonography in the diagnosis of focal hepatic lesions. METHODS: Eight hundred patients with 893 hepatic solid lesions were studied with color Doppler flow imagimg (CDFI) and pulsed Doppler, induding 644 malignant cases (596 primary malignant liver tumors, and 48 metastatic liver tumors), 156 benign cases. All were confirmed by operation and pathology. RESULTS: The detection rate of arterial flow in malignant tumors was 92%, and 52% in benign lesions. Doppler spectrum analysis showed that the resistance index in primary malignant tumors was 0.75±0.12, 0.73±0.09 in metastatic tumors, and was below 0.6 in benign lesions. The difference was significant (P<0.001). This difference was related with its histopathologic structure. CONCLUSION: The arterial flow with RI≥0.6 identified by CDFI within the liver lesion can be regarded as a criterion of malignant tumors, RI<0.6 can be regarded as benign disorders. RI is useful in differential diagnosis of liver neoplasms.

关键词：肝损害彩色多普勒超声阻抗系数影像学诊断血液流变学

Protective effect of melatonin against liver injury in mice induced by Bacillus Calmette-Guerin plus lipopolysaccharide

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World Journal of Gastroenterology 2004年第18期10卷 2690-2696页

作者： HuaWang WeiWei Yu-XianShen ChenDong Ling-LingZhang Ni-pingwang LiYue Shu-YunXu InstituteofC-linical-Pharmacology AnhuiMedicalUniversityHefei230032AnhuiProvinceChina

AIM: To investigate the effects and mechanisms of melatonin on immunological liver injury in ***: A model of liver injury was induced by tail vein injecton of Bad#us Calmet~ Guenn (BCG) and lipopolysaccharide(LPS) in mice. Kupffer cells and hepatocytes were isolated and cultured according to a modified two-step collagenase perfusion technique. Levels of alanine aminotransferase(ALT), aspartate aminotransferase (AST) and nitric oxide(NO), content of malondiadehyde (MDA), activity of superoxide dismutase (SOD), were measured by biochemical *** necrosis factor-α (TNF-α) activity was determined by RIA. Interleukin (IL)-1 activity was measured by thymocyte proliferation bioassay. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a ***: Immunological liver injury induced by BCG+LPS was successfully duplicated. Serum transaminase (ALT,AST) activities were significantly decreased by melatonin(0.25, 1.0, 4.0 mg/kg bm). Meanwhile, MDA content was decreased and SOD in liver homogenates was ***, pro-inflammatory mediators (TNF-α, IL-1, NO)in serum and liver homogenates were significantly reduced by melatonin. Histological examination demonstrated that melatonin could attenuate the area and extent of necrosis,reduce the immigration of inflammatory cells. In in vitro experiment, TNF-α was inhibited at the concentrations of 10^-8-10^-6 mol/L of melatonin, while IL-1 production of Kupffer cells induced by LPS (5 t^g/mL) was decreased only at the concentration of 10^-6 mol/L of melatonin, but no effect on NO production was observed. Immunological liver injury model in vitro was established by incubating hepatocytes with BCG- and LPS-induced Kupffer cells. Activities of ALT,TNF-α, IL-1, and MDA in supernatant were significantly increased. Melatonin had little effect on the level of ALT,but reduced the content of TNF-α and MDA at concentrations of 10^-7-10^-5 mol/L and decreased the content of

关键词：抗黑变激素肝损伤老鼠杆状菌卡介苗脂多糖免疫学

HLA-DRB1 allele polymorphisms in genetic susceptibility to esophageal carcinoma

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World Journal of Gastroenterology 2003年第3期9卷 412-416页

作者： JunLin Chang-ShengDeng JieSun Xian-GongZheng XingHuang YanZhou PingXiong Ya-pingwang DepartmentofGastroenterology ZhongnanHospitalWuhanUniversityWuhan430071HubeiProvinceChina DepartmentofImmunology TongjiMedicalCollgeofHuazhongUniversityofScienceandTechnologyWuhan430030HubeiProvinceChina StateKeyLab InstituteofHydrobiologyTheChineseAcademyofSciencesWuhan430077HubeiProvinceChina

AIM: To probe into the genetic susceptibility of HLA-DRB1 alleles to esophageal carcinoma in Han Chinese in Hubei ***: HLA-DRB1 allele polymorphisms were typed by polymerase chain reaction with sequence-specific primers (PCR-SSP) in 42 unrelated patients with esophageal cancer and 136 unrelated normal control subjects and the associated HLA-DRB1 allele was measured by nucleotide sequence analysis with *** software was used in ***: Allele frequency (AF) of HLA-DRB1·0901 was significantly higher in esophageal carcinoma patients than that in the normal controls (0.2500 vs0.1397, P=0.028, the odds ratio 2.053, etiologic fraction 0.1282). After analyzed the allele nucleotide sequence of HLA-DRB1·0901 which approachs to the corresponded exon 2 sequence of the allele in genebank. There was no association between patients and controls in the rested HLA-DRB1 ***: HLA-DRB1·0901 allele is more common in the patients with esophageal carcinoma than in the healthy controls, which is positively associated with the patients of Hubei Han Chinese. Individuals carrying HLA-DRB1·0901may be susceptible to esophageal carcinoma.

关键词： HLA-DRB1 等位基因 T细胞食道癌基因多态性遗传易感性 PCR-SSP

Heterogeneity in predisposition of hepatic cells to be induced into pancreatic endocrine cells by PDX-1

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World Journal of Gastroenterology 2005年第15期11卷 2277-2282页

作者： ShunLu Wei-pingwang Xiao-FeiWang Zong-MeiZheng PingChen Kang-TaoMa Chun-YanZhou DepartmentofBiochemistryandMolecularBiology SchoolofBasicMedicalSciencesPekingUniversityBeijing100083China PekingUniversityStemCellResearchCenter Beijing100083China

AIM: The role of Pancreatic and Duodenal Homeobox-1(PDX-1) as a major regulator of pancreatic development determines the function and phenotype of β cell. In this study, potential plasticity of liver cells into pancreatic endocrine cells induced by PDX-1 was ***: Human hepatoma cell line HepG2 was stably transfected with mammalian expression plasmid pcDNA3-PDX encoding human PDX-1 gene. Ectopic expression of PDX-1 and insulin were detected by RT-PCR,Western blot and/or immunostaining. PDX-1+ HepG2 cells were transplanted under renal capsule of STZ-induced diabetic nude mice (n = 16) to examine the inducing effect in ***: Exogenous PDX-1 transgene was proved to express effectively in HepG2 cell at both mRNA and protein levels. The expression of endogenous insulin and some βcell-specific differentiation markers and transcription factors were not induced in PDX-1+ HepG2 cells. When transplanted under renal capsule of STZ-induced diabetic nude mice, PDX-1+ HepG2 cells did not generate insulinproducing cells. These data indicated that stable transfected PDX-1 could not convert hepatoma cell line HepG2 to pancreatic cells in vitro or in vivo. Mature hepatocytes might need much more complicated or rigorous conditions to be shifted to insulin-producing ***: The expression of exogenous PDX-1 is not sufficient to induce relatively mature hepatocytes differentiating into insulin-producing cells.

关键词： PDX-1 HepG2, Insulin Transgene Diabetes