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Fumagillin treatment of hepatocellular carcinoma in rats: An in vivo study of antiangiogenesis

World Journal of Gastroenterology 2005年第6期11卷 771-777页

作者： I-ShyanSheen kuo-shyangjeng Wen-JueiJeng Chi-JueiJeng Yi-ChingWang Shu-LingGu Shin-YunTseng Chien-MingChu Chia-HuiLin kuo-MingChang LiverReserchUnit ChangGungMemorialHospitalTaipeiTaiwanChina DepartmentofSurgery MackayMemorialHospitalTaipeiTaiwanChina NationalYang-MingUniversityMedicalCollege TaipeiTaiwanChina NationalTaiwanUniversityMedicalCollege TaipeiTaiwanChina DepartmentofMedicalResearch MackayMemorialHospitalTaipeiTaiwanChina DepartmentofPathology MackayMemorialHospitalTaipeiTaiwanChina

AIM: To investigate the effect and possible mechanisms of antiangiogenesis therapy for HCC in ***: Adult male LEW/SsN rats were divided into 3groups, 25 animals each. Group A was the control *** B and C were given diethylnitrosamine, 5 mg/kg/*** addition, group C rats received an intraperitoneal injection of fumagillin, 30 mg/(kg.d). Five animals in each group were killed at 6th, 12th, 18th, 20th and 24th wk to evaluate the development of HCC and metastasis. Weight of the rats, liver tumors, and number of organs involved by HCC were measured at each stage. We compared methionine aminopeptidase-2 (MetAP-2) mRNA, Bcl-2mRNA, telomerase mRNA, and telomerase activity at 24th wk in the liver tissue of group A rats and tumor tissue of HCC from group B and C ***: No HCC developed in group A, but tumors were present in group B and C rats by the 18th wk. At wk 20 and 24, the median liver weight in group B was 0.64 g (range:0.58-0.70 g) and 0.79 g (range: 0.70-0.90 g) (P = 0.04),and that in group C was 0.37 g (range: 0.35-0.42 g) and 0.39 g (range: 0.35-0.47 g) (P = 0.67). The liver weight in group C rats was significantly lower than that in group B rats (P = 0.009). At the same time, the median metastasis score (number of organ systems involved) was 3 (range2-3)in group B, and 1 (range 1-2) in group C, a significant difference between the groups (P = 0.007, 0.004). The levels of MetAP-2 mRNA were significantly higher in groups B and C than in group A (P = 0.025), and significantly higher in group C than in group B (P = 0.047). The level of Bcl-2 mRNA was significantly higher in group B than in group A (P = 0.024), but lower in group C than in group B, although not significantly (P = 0.072). Telomerase mRNA was significantly higher in group B than in group A (P = 0.025), but significantly lower in group C than in group B (P = 0.016). The same inter-group relationship was also true for telomerase activity (P = 0.025 and 0.046).CONCLUSION: Fumagillin

关键词：烟曲霉素治疗方法肝细胞癌老鼠抗血管生成消化系统

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Prognostic significance of preoperative circulating vascular endothelial growth factor messenger RNA expression in resectable hepatocellular carcinoma:A prospective study

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World Journal of Gastroenterology 2004年第5期10卷 643-648页

作者： kuo-shyangjeng I-ShyanSheen Yi-ChingWang Shu-LingGu Chien-MingChu Shou-ChuanShih Po-Chuanwang Wen-HsingChang Horng-YuanWang DepartmentofSurgery MackayMemorialHospitalTaipeiTaiwan.China LiverResearchUnit ChangGungMemorialHospitalTaipeiTaiwanChina MedicalResearch MackayMemorialHospitalTaipeiTaiwanChina DepartmentofInternalMedicine MackayMemorialHospitalTaipeiTaiwanChina

AIM:To investigate the prognostic value of vascular endothelial growth factor messenger RNA (VEGF mRNA) in the peripheral blood (PB) of patients with hepatocellular carcinoma (HCC) undergoing curative ***:Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, VEGF mRNA in the PB was determined prospectively in 50 controls and in 50 consecutive patients undergoing curative resection for ***:Among the isoforms of VEGF mRNA, VEGF165 and VEGF121 were expressed. By multivariate analysis, a higher level of VEGF165 in preoperative PB correlated with a risk of HCC recurrence with borderline significance (P=0.050)and significantly with recurrence-related mortality (P=0.048);while VEGF121 did not. Other significant predictors of HCC recurrence included cellular dedifferentiation (P=0.033),an absent or incomplete capsule (P=0.020), vascular permeation (P=0.018), and daughter nodules (P=0.006).The other significant parameter of recurrence related mortality was cellular dedifferentiation (P=0.053). The level of circulating VEGF mRNA, however, did not significantly correlate with tumor size, cellular differentiation, capsule,daughter nodules, vascular permeation, necrosis and hemorrhage of ***: The preoperative level of circulating VEGF mRNA, especially isoform VEGF165, plays a significant role in the prediction of postoperative recurrence of HCC.

关键词：肝细胞癌 RNA信使血管内皮生长因子外科治疗 RT-PCR 血管内皮细胞

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Is the vascular endothelial growth factor messenger RNA expression in resectable hepatocellular carcinoma of prognostic value after resection?

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World Journal of Gastroenterology 2004年第5期10卷 676-681页

作者： kuo-shyangjeng I-ShyanSheen Yi-ChingWang Shu-LingGu Chien-MingChu Shou-ChuanShih Po-ChuanWang Wen-HsingChang Horng-YuanWang DepartmentofSurgery MackayMemorialHospitalTaipeiTaiwanChina LiverResearchUnit ChangGungMemorialHospitalTaipeiTaiwanChina MedicalResearch MackayMemorialHospitalMackayJuniorSchoolofNursingTaipeiTaiwanChina DepartmentofInternalMedicine MackayMemorialHospitalTaipeiTaiwanChina

AIM:To study whether vascular endothelial growth factor messenger RNA (VEGF mRNA) in the hepatocellular carcinoma (HCC) tissues obtained after curative resection has a prognostic ***: Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, VEGF mRNA was determined prospectively in liver tissues of 50 controls and in HCC tissues of 50 consecutive patients undergoing curative resection for ***: Among the isoforms of VEGF mRNA, VEGF165 and VEGF121 were expressed. By multivariate analysis, a higher level of VEGF165 in HCC tissue correlated with a significant risk of HCC recurrence (P=0.038) and significantly with recurrencerelated mortality (P=0.045); while VEGF121 did not. Other significant predictors of HCC recurrence included cellular dedifferentiation (P=0.033), an absent or incomplete capsule(P=0.020), vascular permeation (P=0.018), and daughter nodules (P=0.006). The other significant variables of recurrence related mortality consisted of vascular permeation (P=0.045),and cellular dedifferentiation (P=0.053). The level of VEGF mRNA in HCC tissues, however, did not significantly correlate with tumor size, cellular differentiation, capsule, daughter nodules,vascular permeation, necrosis and hemorrhage of ***: The expression of VEGF mRNA, especially isoform VEGF165,in HCC tissues, may play a significant and independant role in the prediction of postoperative recurrence of HCC.

关键词：血管内皮生长因子 RNA信使肝细胞癌肿瘤切除术术前评估 RT-PCR

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Do the expressions of gap junction gene connexin messenger RNA in noncancerous liver remnants of patients with hepatocellular carcinoma correlate with postoperative recurrences?

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World Journal of Gastroenterology 2005年第2期11卷 171-175页

作者： I-ShyanSheen kuo-shyangjeng Shou-ChuanShih Chin-RoaKao Po-ChuanWang Chih-ZenChen Wen-HsingChang Horng-YuanWang Li-RungShyung DepartmentsofInternalMedicine MackayMemorialHospitalTaipeiTaiwanChina DivisionofHepatogastroenterology ChangGungMemorialHospitalTaipeiTaiwanChina DepartmentsofSurgery MackayMemorialHospitalTaipeiTaiwanChina//MackayMedicineNursingandManagementCollegeTaipeiTaiwanChina

AIM: To investigate whether the changes of gap junction gene connexin messenger RNA in the noncancerous liver tissue of patients with hepatocellular carcinoma (HCC) could play a significant role in its postresection ***: Seventy-nine consecutive patients having undergone curative resection for HCC entered this *** a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, connexin (Cx) 26, connexin (Cx)32 and connexin (Cx) 43 mRNAs were determined prospectively in noncancerous liver tissues from these 79 patients and in the liver tissues from 15 controls. The correlations between connexin mRNA expression and the clinicopathological variables and outcomes (tumor recurrence and recurrence related mortality) were ***: Compared with liver tissues of control patients,the expression of Cx 32 mRNA in noncancerous liver tissues was significantly lower (mean: 0.715 vscontrol 1.225,P＜0.01), whereas the decreased Cx 26 mRNA (mean:0.700 vs of control 1.205,P＞0.05) and increased Cx 43 mRNA (mean: 0.241 vscontrol 0.100, P＞0.05) had no statistical significance. We defined the value of Cx 32 mRNA or Cx 26mRNA below 0.800 as a lower value. By multivariate analysis for noncancerous livers, a lower value of Cx 32 mRNA correlated significantly with a risk of HCC recurrence and recurrence-related mortality. The lower value of Cx 26 mRNA did not correlate with recurrence and mortality. The increased value of Cx43 mRNA also did not correlate with postoperative recurrence and recurrence-related mortality. By multivariate analysis, other significant predictors of HCC recurrence included vascular permeation, cellular dedifferentiation, and less encaps-ulation. The other significant parameter of recurrence related mortality was vascular ***: The decreased expression of Cx 32 mRNA in noncancerous liver tissues plays a significant role in the prediction of postoperative recurrence of HCC.

关键词：基因表达缺口连接基因连接蛋白信使RNA 肿瘤肝脏肝细胞癌手术治疗

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Clinical significance of the expression of isoform 165 vascular endothelial growth factor mRNA in noncancerous liver remnants of patients with hepatocellular carcinoma

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World Journal of Gastroenterology 2005年第2期11卷 187-192页

作者： I-ShyanSheen kuo-shyangjeng Shou-ChuanShih Chih-RoaKao Wen-HsingChang Horng-YuanWang Po-ChuanWang Tsang-EnWang Li-RungShyung Chih-ZenChen MedicalDepartment MackayMemorialHospitalTaipeiTaiwanChina LiverResearchUnit DivisionofHepatogastroenterologyChangGungMemorialHospitalTaipeiTaiwanChina DepartmentofSurgery MackayMemorialHospitalTaipeiTaiwanChina//MackayJuniorSchoolofNursingTaipeiTaiwanChina

AIM: To investigate the prognostic role of isoform 165 vascular endothelial growth factor messenger RNA (VEGF165 mRNA)in noncancerous liver tissues from patients with primary hepatocellular carcinoma (HCC).METHODS: Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, VEGF mRNA was determined prospectively in noncancerous liver tissues from 60 consecutive patients with HCC undergoing curative resection. We categorized the patients with VEGF165 mRNA over 0.500 in noncancerous liver tissues as group A, and those below 0.500 as group ***: Among the isoforms of VEGF mRNA by multivariate analysis, a higher level of VEGF165 mRNA in noncancerous liver tissue correlated significantly with a higher risk of HCC recurrence (P = 0.039) and recurrence-related mortality (P= 0.048), but VEGF121 did not. The other significant predictors of recurrence consisted of vascular permeation (P = 0.022),daughter nodules (P = 0.033), cellular dedifferentiation (P = 0.033), an absent or incomplete capsule (P = 0.037).A significant variable of recurrence-related mortality was Vascular permeation (P= 0.012). As to the clinical manifestations of 16 patients who developed recurrence,the recurrent tumor number over 2, recurrent extent over two-liver segments, and the median survival after recurrence,all significantly correlated with group A patients (P = 0.043,0.043, and 0.048, respectively). However, the presence of extrahepatic metastasis was not (P＞0.05). The difference in recurrence after treatment between the two groups had no statistical significance (P＞0.05).CONCLUSION: The higher expression of isoform VEGF165mRNA in noncancerous liver remnant of patients with HCC may be a significant biological indicator of the invasiveness of postoperative recurrence.

关键词： HCC 基因表达脉管内皮细胞细胞因子 mRNA 肝癌肝细胞癌肿瘤消化系统

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Does surgical resection of hepatocellular carcinoma accelerate cancer dissemination?

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World Journal of Gastroenterology 2004年第1期10卷 31-36页

作者： I-ShyanSheen kuo-shyangjeng Shou-ChuanShih Po-ChuanWang Wen-HsiungChang Horng-YuanWang Li-RungShyung Shee-ChanLin Chin-RoaKao Yi-ChunTsai Tsu-YenWu DivisionsofHepatogastroenterology ChangGungMemorialHospitalTaipeiTaiwanChina DepartmentsofSurgery MackayMemorialHospitalTaipeiTaiwanChina DepartmentofIntemalMedicine MackayMemorialHospitalTaipeiTaiwanChina MedicalResearch MackayMemorialHospitalTaipeiTaiwanChina

AIM: This study was to investigate whether surgery could increase cancer dissemination and postoperative recurrence in patients with hepatocellular carcinoma (HCC) by detection of human α-fetoprotein messenger RNA (hAFP mRNA), hAFP mRNA in the peripheral blood of patients with HCC has been considered as a surrogate marker for circulating tumor cells. METHODS: Eighty-one consecutive patients who underwent curative resection for HCC entered this prospective cohort study. We examined hAFP mRNA from the peripheral blood obtained preoperatively, perioperatively, and postoperatively to correlate the prognosis after curative resections from HCC patients and from the control subjects. Detection of hAFP mRNA by reverse transcriptase and polymerase chain reaction amplification (RT-PCR) was performed with primers specifically. The relations between the clinical variables (age,sex, associated liver cirrhosis, hepatitis B virus infection,hepatitis C virus infection, serum α-fetoprotein and ChildPugh class), the histological variables (size, capsule, vascular permeation, grade of differentiation, and daughter nodules),hAFP mRNA in peripheral blood of 3 different sessions, and postoperative course (recurrence, and recurrence related death) were analysed. RESULTS: No hAFP mRNA was detected in control group subjects. Twenty-two (27%), 24 (30%) and 19 (23%) of 81 HCC patients had hAFP mRNA positivity in the preoperative,perioperative and postoperative peripheral blood. The preoperative presence did not influence the risk of HCC recurrence (55% vs 41%, P=0.280). In contrast, patients with postoperative presence had a significantly higher recurrence (90% vs31%, P<0.001; odds ratio 19.2; 95% confidence interval: 4.0-91.7). In the multivariate analysis by COX proportional hazards model, postoperative positivity had a significant influence on recurrence (P=0.067) and recurrence related mortality (P=-0.017). Whereas, the perioperative positivity of hAFP mRNA did not increase HCC recurrence

关键词：肝细胞癌肿瘤切除术肿瘤转移 RT-PCR 肝动脉灌注化疗栓塞

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