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Objective: To investigate the efficacy of antiangiogenesis, mechanism and timing of transcatheter arterial chemoembolization (TACE) combined with sorafenib in treatment of liver cancer in new Zealand rabbits with VX2 liver cancer model. Methods: Thirty New Zealand rabbits with VX2 liver cancer were randomly divided into normal saline control group, single TACE group, single sorafenib group, pre-TACE + sorafenib group and post-TACE + sorafenib group (n=6 in each). Serum VEGF was measured by ELISA 7 days before TACE, 1 day before TACE, 3 days after TACE, 7 days after TACE, and 14 days after TACE. All the rabbits were sacrificed 14 days after operation for MVD immunohistochemical staining, and the tumor growth rate of each group was compared. Results: Compared with that in normal saline control group, serum VEGF in TACE + sorafenib group, TACE + sorafenib group and TACE + sorafenib group increased significantly (P<0.05), but the peak value of VEGF in TACE + sorafenib group was lower than that in TACE group and TACE + sorafenib group(P<0.05). Fourteen days after TACE, the VEGF level in the group + sorafenib was the lowest and that in the group of one drug alone was the highest (P<0.05). In 14 days after TACE + sorafenib group, MVD value was higher than that in saline control group and sorafenib group, but significantly lower than that of single TACE group(P<0.05). The 14 days after TACE + sorafenib group had the smallest tumor growth(P<0.05). Conclusion: TACE combined with sorafenib can significantly inhibit the growth of VX2 liver cancer in rabbits. The effect of TACE combined with sorafenib is better than that of TACE alone or sorafenib alone. However, after TACE the level of VEGF is increased and the level of serum VEGF is decreased by combining sorafenib, which decreases the microvessel density. Moreover, the effect of TACE combined with sorafenib on anti-tumor and anti-angiogenesis is better than that after TACE.
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Objective To study the pharmacokinetics of raltitrexed using different ways of drug delivery, including femoral venous infusion, hepatic artery perfusion, hepatic artery injection of lipiodol suspension, hepatic artery perfusion followed by embolization with Gelfoam. Methods According to the administration way of raltitrexed, a total of 40 New Zealand rabbit models with VX2 liver tumor were randomly divided into group A (femoral venous perfusion), group B (hepatic arterial perfusion), group C (hepatic artery injection of lipiodol suspension), and group D(hepatic artery perfusion followed by embolization with Gelfoam). Drug concentration in plasma were determined by using LC-MS/MS method and the pharmacokinetic parameters were calculated. Results After administration of raltitrexed, the Tmax was 5 minutes in all 4 groups. In group A, B, C and D, the values were (5.88±1.39), (7.31±2.60), (9.86±5.10) and (7.19±2.27) respectively, with group C having the longest t1/2 value, which was significantly different with that of group A (P＜0.05); the (ng·ml-1·h-1) values were (2 056.40± 139.17), (1 389.21±180.28), (911.84±105.62) and (1 133.41±181.42)respectively, with the value of group A being obviously higher than that of group B, C and D (P＜0.05) and the value of group C being the lowest; the AUC0-t(ng· ml-1·h-1) values were (5 482.72±1 007.07), (4 156.99±1 475.77), (2 785.13±1 107.36) and (3 903.64±947.25) respectively, with the value of group A being remarkably higher than that of group B, C and D (P＜0.05) and the value of group C being the lowest. Conclusion Compared with the femoral vein infusion way, the ways of hepatic artery infusion, hepatic artery lipiodol suspension injection and hepatic artery perfusion followed by embolization with Gelfoam may promote more raltitrexed to deposit in the tumor area, thus, the curative effect is enhanced, the drug concentration in plasma is lowered and the side effects are alleviated.
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Objective To establish animal models facilitating observation of the process of epithelial-mesenchymal transition between liver cirrhosis and liver cancer. Methods Liver cirrhosis and liver cancer models were established in mouse and subsequently assessed using HE and immunohistochemical staining. Results The success rate of the liver cirrhosis model was 100％ and the fatality rate was 30％. The success rate of the liver cancer model was also 100％ and the fatality rate was 40％. In the liver cirrhosis and liver cancer models,the positive expression rates were,respectively,46. 7％ and 7. 1％ for E-cadherin,40. 0％ and 7. 1％ for β3-integrin,13. 6％ and 40. 0％ for vimentin,and 20. 0％ and 57. 1％ for fibronectin. Conclusion In mouse models of liver cirrhosis and liver cancer,low expression levels of E-cadherin and β3-integrin in addition to high expression levels of fibronectin and vimentin are related to the epithelial-mesenchymal transition between liver cancer and cirrhosis,and may be important indicators for clinical detection.
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[ Objective] To explore the variation features of contrast enhanced ultrasound ( CEUS) quantitative parameters and its correlation with tumor microvessel density ( MVD ) , after the treatment of living liver cancer using high intensity focused ultrasound ( HIFU ) . [ Methods ] A group of 30 New Zealand white rabbits were made into VX2 liver cancer models, that were randomly divided into control group ( n =15, not HIFU treatment) and treatment group ( n =15, HIFU treatment).CEUS was performed, then obtaining ascending slope(AS),arrival time(AT),time-to-peak(TTP),peak intensity ( PI) ,area under curve ( AUC ) .And correlation analysis was performed with MVD obtained by immune histochemical method. [ Results ] Compared with those in the control group, AS, PI, AUC were significantly decreased in treatment group (P <0.05) and so was MVD (P <0.05).AT,TTP were significantly delayed than those in the control group (P<0.05).The AS, PI, AUC of CEUS quantitative parameters were positively correlated with MVD (P<0.05).The AT, TTP respectively showed a negative correlation with MVD ( P<0.05) . [ Conclusion] CEUS quantitative parameters of liver cancer tissue have high correlation with MVD.It can reflect the microvessel structure change of the liver cancer tissue and help to judge the curative effect and prognosis of HIFU for liver cancer.
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Background and purpose:Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive system in our country, with high fatality, development of HCC and the machine system research and treatment is a primary issue in current study of HCC. To explore the expression ofβ-catenin at different stages in the process of hepatocellular carcinoma carcinogenisis for SD rats induced by chemicals. Methods: The experimental group included 48 male SD rats mice with primary liver cancer induced by diethylnirtosamine/carbon tetrachloride/Ethanol, while 48 normal male SD rats mice were used as the control group. The rats were killed every 3 weeks to collect the specimens and observe the pathological changes by HE staining. The changes ofβ-catenin protein expressions were detected by immunohistochemistry and Western blot respectively. Results:SD rats liver cancer was conifrmed by HE staining after 21 weeks DEN/CCl4/Ethanol induction. Immunohistochemistry showed thatβ-catenin expression level was obviously higher in the experimental group(0.27±0.01) than that of the control group(0.21±0.02) after 3 weeks induction(P<0.05). As time progresses, the expression levels ofβ-catenin kept on rising, and at the 18th(0.30±0.02) and 21th weeks(0.32±0.02), it was significantly higher than that of the earlier liver tissues of the experimental group(P<0.05), Western blot consistent with immunohistochemical results. Conclusion:β-catenin protein expression is different in the normal liver tissue, cirrhosis, liver cancer,β-catenin and the occurrence of liver carcinoma development had close relationship.β-catenin protein in the cell with further accumulation, may active a series of target gene, leading to the formation of liver cancer..