BACKGROUND: OCI-5, the rat homologene of human glypican 3 ( GPC3), is confirmed upregulated in hepatocellular carcinoma (HCC). The present study was undertaken to detect gene expression change of OCI-5 during occurren...BACKGROUND: OCI-5, the rat homologene of human glypican 3 ( GPC3), is confirmed upregulated in hepatocellular carcinoma (HCC). The present study was undertaken to detect gene expression change of OCI-5 during occurrence and progression of rat HCC. METHODS: Male Sprague-Dawley rats were given diethyl-nitrosamine ( DENA) to induce HCC. Three DENA-induced rats and one control rat were sacrificed every week for 18 weeks during the development of HCC. Tissues specimens were snap-frozen in liquid nitrogen and total RNA was isolated. Sk-Hepl cells were treated with DENA at different concentrations. The gene expression levels of OCI-5 and GPC3 were detected with the RT-PCR method. RESULTS: OCI-5 was not expressed in normal rat liver tissues. When HCC occurred and aggravated, OCI-5 expression was gradually elevated to a very high level. GPC3 was not expressed in the DENA-treated Sk-Hepl cells. CONCLUSIONS: OCI-5 was not expressed in normal rat liver tissues but in rat HCC tissues. High-expression of OCI-5 in DENA-induced rat HCC model was the gene expression change of HCC not the DENA-induced gene expression. The expression level of OCI-5 was not only elevated in rat HCC but also gradually along the occurrence and progression of HCC, indicating that GPC3 might serve as a sensitive marker of early stage HCC.展开更多
BACKGROUND: Rat hepatocellular carcinoma ( HCC ) model which has a high analogy to clinical liver cancer is of great value in understanding the pathogenesis and evolution of liver cancer, in searching effective anti-c...BACKGROUND: Rat hepatocellular carcinoma ( HCC ) model which has a high analogy to clinical liver cancer is of great value in understanding the pathogenesis and evolution of liver cancer, in searching effective anti-cancer treat- ments ( drug, hepatectomy and liver transplantation ), and designing cancer prevention strategies. In this study we es- tablished a modified rat model of hepatocellular carcinoma to enhance rats' physique and surgical endurance. METHODS: Wistar rats were fed with diethylnitrosamine (DENA) by three methods for evaluation of general condi- tions for 130 days: Doppler ultrasonographic measurement, laparotomy and histopathological examination. RESULTS: No rat died in control group ( group A) and modified DENA-induction-HCC group ( group C), but 6 deaths in classical DENA-induction-HCC group (group B) (survival rate 80%). All survived rats in groups B and C de- veloped diffusive hepatocellular carcinoma and liver cirrho- sis. General appearance of rats in the group C was better than that in the group B. CONCLUSION: With good general conditions for surgery, the modified rat model for hepatocellular carcinoma has a high carcinogenic rate and a high survival rate.展开更多
Diethylnitrosamine (DENA) is able to induce various benign and malignant liver lesions in rats with a high success rate and a low mortality rate. It provides a more appropriate model that better simulates the various ...Diethylnitrosamine (DENA) is able to induce various benign and malignant liver lesions in rats with a high success rate and a low mortality rate. It provides a more appropriate model that better simulates the various lesions occurring in humans than the usual model of tumor implantations. The aim of the present study was to evaluate MRI liver examination in Sprague-Dawley(SD) rats as a routine method to detect hepatocellular carcinoma (HCC) nodules induced by DENA and to follow up their growth. METHODS:Hepatic carcinogenesis was induced in 80 male SD rats using oral DENA solution. All animals were imaged for liver tumor detection with a 1.5 Tesla magnet (Siemens Sonata,Erlangen, Germany) using correspondence scan parameters and a radio-frequency knee coil. Macroscopic examinations were performed along the axial MRI sections to evaluate magnetic resonance imaging (MRI) findings, and histopathological assessment was also performed. RESULTS:No false negative results were obtained on MR images. Hepatic tumors in 72 rats were confirmed macro-scopically and 68 rats were detected by MRI till the 20th week. The smallest and the largest nodules detected by MRI were 2 mm and 37 mm in diameter respectively. The agreement rate of MRI with macroscopic observation was 39. 1% and 97. 4% respectively for 2 mm to 5 mm and more than 5 mm nodules. CONCLUSIONS:The hepatic tumor induced by DENA provides a more representative range of tumors for imaging diagnosis and interventional treatment. MRI is the best approach for scrutinizing pathological changes of rat livers in the period of observation.展开更多
采用二乙基亚硝胺(DENA)诱发大鼠肝细胞癌的动物模型,应用新生血管抑制药物β环糊精十四硫酸酯(β CD 14S)联合肝动脉结扎的方法对其进行治疗.实验共分为5组:(1)阴性对照组;(2)β CD 14S(0.5g/kg)门静脉给药组;(3)肝动脉结扎组;(4)β ... 采用二乙基亚硝胺(DENA)诱发大鼠肝细胞癌的动物模型,应用新生血管抑制药物β环糊精十四硫酸酯(β CD 14S)联合肝动脉结扎的方法对其进行治疗.实验共分为5组:(1)阴性对照组;(2)β CD 14S(0.5g/kg)门静脉给药组;(3)肝动脉结扎组;(4)β CD 14S(0.5g/kg)肝动脉给药+肝动脉结扎组;(5)β CD 14S(0.5g/kg)门静脉给药+肝动脉结扎组.实验结果表明,β CD 14S+肝动脉结扎治疗组较单纯用药或肝动脉结扎组术后30d生存率明显提高.影象学和病理学的观察表明大鼠肝细胞癌的血供受到抑制,证实了β CD 14S对肝细胞癌诱导的新生血管有较好的抑制作用,它与血管栓塞疗法的联合应用可望为肝细胞癌的治疗提供一种更为有效的新方法.展开更多
文摘BACKGROUND: OCI-5, the rat homologene of human glypican 3 ( GPC3), is confirmed upregulated in hepatocellular carcinoma (HCC). The present study was undertaken to detect gene expression change of OCI-5 during occurrence and progression of rat HCC. METHODS: Male Sprague-Dawley rats were given diethyl-nitrosamine ( DENA) to induce HCC. Three DENA-induced rats and one control rat were sacrificed every week for 18 weeks during the development of HCC. Tissues specimens were snap-frozen in liquid nitrogen and total RNA was isolated. Sk-Hepl cells were treated with DENA at different concentrations. The gene expression levels of OCI-5 and GPC3 were detected with the RT-PCR method. RESULTS: OCI-5 was not expressed in normal rat liver tissues. When HCC occurred and aggravated, OCI-5 expression was gradually elevated to a very high level. GPC3 was not expressed in the DENA-treated Sk-Hepl cells. CONCLUSIONS: OCI-5 was not expressed in normal rat liver tissues but in rat HCC tissues. High-expression of OCI-5 in DENA-induced rat HCC model was the gene expression change of HCC not the DENA-induced gene expression. The expression level of OCI-5 was not only elevated in rat HCC but also gradually along the occurrence and progression of HCC, indicating that GPC3 might serve as a sensitive marker of early stage HCC.
文摘BACKGROUND: Rat hepatocellular carcinoma ( HCC ) model which has a high analogy to clinical liver cancer is of great value in understanding the pathogenesis and evolution of liver cancer, in searching effective anti-cancer treat- ments ( drug, hepatectomy and liver transplantation ), and designing cancer prevention strategies. In this study we es- tablished a modified rat model of hepatocellular carcinoma to enhance rats' physique and surgical endurance. METHODS: Wistar rats were fed with diethylnitrosamine (DENA) by three methods for evaluation of general condi- tions for 130 days: Doppler ultrasonographic measurement, laparotomy and histopathological examination. RESULTS: No rat died in control group ( group A) and modified DENA-induction-HCC group ( group C), but 6 deaths in classical DENA-induction-HCC group (group B) (survival rate 80%). All survived rats in groups B and C de- veloped diffusive hepatocellular carcinoma and liver cirrho- sis. General appearance of rats in the group C was better than that in the group B. CONCLUSION: With good general conditions for surgery, the modified rat model for hepatocellular carcinoma has a high carcinogenic rate and a high survival rate.
基金This study was supported by grants from specialized Research Fund for the Doctoral Program of Higher Education (SRFDP) (20030b10090)China Medical Board of New York (CMB 82-412) the TCM Administration Bureau of Sichuan Province (TCM 2004 B03).
文摘Diethylnitrosamine (DENA) is able to induce various benign and malignant liver lesions in rats with a high success rate and a low mortality rate. It provides a more appropriate model that better simulates the various lesions occurring in humans than the usual model of tumor implantations. The aim of the present study was to evaluate MRI liver examination in Sprague-Dawley(SD) rats as a routine method to detect hepatocellular carcinoma (HCC) nodules induced by DENA and to follow up their growth. METHODS:Hepatic carcinogenesis was induced in 80 male SD rats using oral DENA solution. All animals were imaged for liver tumor detection with a 1.5 Tesla magnet (Siemens Sonata,Erlangen, Germany) using correspondence scan parameters and a radio-frequency knee coil. Macroscopic examinations were performed along the axial MRI sections to evaluate magnetic resonance imaging (MRI) findings, and histopathological assessment was also performed. RESULTS:No false negative results were obtained on MR images. Hepatic tumors in 72 rats were confirmed macro-scopically and 68 rats were detected by MRI till the 20th week. The smallest and the largest nodules detected by MRI were 2 mm and 37 mm in diameter respectively. The agreement rate of MRI with macroscopic observation was 39. 1% and 97. 4% respectively for 2 mm to 5 mm and more than 5 mm nodules. CONCLUSIONS:The hepatic tumor induced by DENA provides a more representative range of tumors for imaging diagnosis and interventional treatment. MRI is the best approach for scrutinizing pathological changes of rat livers in the period of observation.
文摘 采用二乙基亚硝胺(DENA)诱发大鼠肝细胞癌的动物模型,应用新生血管抑制药物β环糊精十四硫酸酯(β CD 14S)联合肝动脉结扎的方法对其进行治疗.实验共分为5组:(1)阴性对照组;(2)β CD 14S(0.5g/kg)门静脉给药组;(3)肝动脉结扎组;(4)β CD 14S(0.5g/kg)肝动脉给药+肝动脉结扎组;(5)β CD 14S(0.5g/kg)门静脉给药+肝动脉结扎组.实验结果表明,β CD 14S+肝动脉结扎治疗组较单纯用药或肝动脉结扎组术后30d生存率明显提高.影象学和病理学的观察表明大鼠肝细胞癌的血供受到抑制,证实了β CD 14S对肝细胞癌诱导的新生血管有较好的抑制作用,它与血管栓塞疗法的联合应用可望为肝细胞癌的治疗提供一种更为有效的新方法.
