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Purpose: The purpose of this study is to evaluate the feasibility of percutaneous transauricular artery access for hepatic artery catheterization using a peripherally inserted central catheter (PICC) device and hepatic artery catheterization through auricular approach. Methods: Ten New Zealand White rabbits were used to establish a VX2 liver tumor model. Hepatic artery angiography and embolization were performed 3 weeks after inoculation. The rabbits were restrained in supine position under anesthesia. Intra-arterial access was accomplished with percutaneous Seldinger technique through the auricular artery using a PICC device. The hepatic artery catheterization was performed with a microcatheter and guide wire. The rate of technical success and procedure time was investigated. Results: Two rabbits failed initial percutaneous transauricular arterial access, with success in a contralateral attempt. Thus, percutaneous transauricular arterial access was achieved in 10 of 12 auricular arteries, with a technical success rate of 83.3%. The time needed to obtain intra-auricular access was 7.2 ± 3.1 min. Hepatic artery catheterization, angiography, and embolization were accomplished through the auricular approach in all 10 rabbits. Conclusion: Arterial access in rabbits can be achieved through the auricular artery. Hepatic artery catheterization, angiography, and embolization can be performed through auricular arterial access
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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 effects of the treatment for rabbit VX-2 tongue cancer with paclitaxel or paclitaxel liposome infusion through rabbit lingual artery or ear vein infusion.Methods:24 rabbits with VX-2 tongue cancer were divided into 6 groups(n =40) randomly.The rabits in 3 groups were respectively treated by intra-arterial infusion with paclitaxel,paclitaxel liposome and 5％ glucose,and those in other 3 groups by ear vein infusion with the same materials.After 7 days of treatment,the lesion volumes were measured for response evaluation,cells apotosis in the cancer tissure was detected by llowcytometry,P53 protein expression was examined by immunohistochemical staining,respectively.The data was analyzed by SPSS 20.0 software package.Results:The response rate and apotosis of the tumor cells in intra-arterial infusion with paclitaxel liposome group were higher than those in the other groups(P ＜ 0.05),P53 protein expression was lower than that of the other groups (P ＜ 0.05).Conclusion:Intra-arterial infusion through tongue artery with paclitaxel liposome is more effective than the other methods in the treatment of rabbit VX-2 tongue cancer.
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Objective To discuss the value of diffusion-weighted MRI (DWI) and 18F-FDG-PET/CT in assessing the early therapeutic effect of radiofrequency ablation (RFA) for VX2 sarcomas in experimental rabbits. Methods VX2 sarcoma was inoculated at bilateral hind limbs in 14 New Zealand white rabbits to establish the animal models. The implanted VX2 tumor on one hind leg was treated with ultrasound-guided percutaneous RFA (study group), while no RFA was given to the VX2 tumor on the contralateral hind leg (control group). DWI-MRI was performed at 2 days after RFA, and 18F-FDG-PET/CT examination was employed at 3 days after RFA. The mean apparent diffusion coefficient (ADC) values and standard uptake value (SUV) of the untreated tumor and the ablated tumor were separately calculated. Taking the pathologic result as the gold standard, the consistency of DWI-MRI, PET/CT as well as the combination of DWI-MRI and PET/CT with the clinical diagnosis was separately evaluated by Kappa test. Results Before RFA, DWI-MRI demonstrated that the VX2 tumor was characterized by hypo-intensity signal on T1 and hyper-intensity signal on T2 with ring-shaped enhancement on T1-weighted image; PET/CT showed that the tumor had nodular or ring-shaped 18F-FDG accumulation. After RFA, DWI-MRI revealed that the VX2 tumor was manifested as hyper-intensity signal on T1 and slight higher density on T1 with slight enhancement on contrast-enhanced T1-weighted image; PET/CT showed lowered accumulation of 18F-FDG. The mean ADC value of the ablated tumor was (1.52 ± 0.24) × 10-3 mm2/s, which was obviously higher than that of the un-ablated tumor, that was (1.09 ± 0.12) × 10-3 mm2/s, the difference was statistically significant(P0.05). The Kappa value of the consistency between combination of DWI-MRI with PET/CT and pathology was 0.786, which was significantly different from the result by simple DWI-MRI or simple PET/CT evaluation (P< 0.05). Conclusion Both ADC value of DWI-MRI and SUV value of PET/CT are useful indexes for evaluating the early therapeutic effect of RFA. Both DWI-MRI and PET/CT have their respective advantages, nevertheless, combination use of both can effectively improve the evaluation of curative effect for VX2 tumor after RFA in experimental rabbits.
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Objective To evaluate the effectiveness and safety of interventional thermochemotherapy for VX2 transplanted hepatic tumor model in experimental rabbits.Methods The hepatic tumor model was established in 20 New Zealand rabbits by implanting VX2 tumor cells into the right hepatic lobes of the rabbits.The rabbits were randomly and equally divided into two groups with 10 rabbits in each group:group A (study group)and group B(control group).Via the femoral access,the catheter was placed into the tumorfeeding artery,which was confirmed by DSA.The rabbits in group A received an infusion of 100 ml 5% glucose plus 5-Fu(20 mg/kg)at 60℃ temperature,while the rabbits in group B received an infusion of 100 ml 5% glucose plus 5-Fu(20 mg/kg)at normal room temperature(22-25℃).Before and after the procedure,the tumor size was measured by means of B ultrasonography and the serum ALT was estimated to assess the liver function.The results were statistically compared between two groups.Results After the treatment,the tumor size in group A(study group)became much smaller than that in group B(control group),with P＜0.05.And no significant difference in the serum ALT level existed between group A and group B.Conclusion The interventional thermochemotherapy is superior to interventional chemotherapy in inhibiting VX2 transplanted hepatic tumor in experimental rabbits.
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Objective To establish a rabbit VX2 liver tumor model by transplanting tumor tissue mass into the rabbit's liver,to analyze and observe the growing features of the liver tumor.Methods The tumor tissue mass(about 106-108 VX2 liver tumor cells)was inoculated into the left hepatic labe in 20 rabbits to establish rabbit VX-2 hepatic carcinoma model.The observation included the following two respects.(1)The tumor's volume at 7,10,14,17 and 21 days after the procedure was measured by ultrasonography and the growth rate of tumor was calculated.(2)The morphological feature of the tumor was inspected both macroscopically and microscopically.Results The growing pattern of the tumor was compatible with the exponential curve.Seventeen days after transplantation the increase rate of the tumor volume was much higher than that of the tumor diameter. Histopathologjcally,the growing pattern of the tumor took the form of infiltrative way,with its appearance being quite similar to the VX2 squamous cell carcinoma.Conclusion Transplantation of tumor tissue mass is the technique of first choice to establish the VX2 liver carcinoma model in rabbits.This experimental model is a very ideal animal form for both clinical and fundamental studies of liver carcinoma.
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Objective To establish a suitable and stable metastatic rabbit VX2 liver tumor model for the use in experimental study,to discuss the successful rate of different tumor transplanting methods,and to analyze the digital subtract angiography(DSA)imagining features of the transplanted liver tumor.Methods Sixty male New Zealand white rabbits were randomly and equally divided into 3 groups with 20 rabbits in each group.For the rabbits of two groups,receiving injection methods and used as control groups,VX2 carcinoma particle(containing about 5×107 carcinoma cells) was inoculated into the left hepatic lobe through injection via hepatic artery or through direct injection with a syringe needle.For the rabbits in the retrofit group tumor tissue particle(containing about 106-108 carcinoma cells)was directly transplanted into liver through puncturing of the Glisson's capsule.The observation included the following two respects. (1)The tumor's survival rate of the three groups was evaluated.(2)The DSA imaging feature of the transplanted tumor was observed.Results The survival rate of the transplanted tumor in three groups was 7/20,10/20 and 19/20 respectively,with the survival rate of the retrofit group being the highest in 3 groups(P＜0.05).On DSA the transplanted tumors were rich in blood supplying.Conclusion For the establishment of rabbit VX2 liver carcinoma model,the direct transplantation of the tumor tissue particle is obviously superior to the injection method(direct injection or through hepatic arterial injection)in obtaining higher successful rate.This technique provides clinical and fundamental liver cancer studies with a reliable,stable and mature tumor animal model.
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Objective To evaluate the effects of interventional thermotherapy(60℃)via hepatic artery on the vascular permeability of hepatic tumor tissue and normal liver tissue in VX2 tumor-bearing rabbits.Methods Thirty white rabbits were used in this experiment,Thirty VX2 tumor-bearing rabbits models were established by direct injection of VX2 tissue particle into the liver parenchyma and were randomly and equally divided into three groups:(1)non-perfusion group(n=10),used as control group; (2)normal thermal perfusion group(n=10),a perfusion of 30ml saline at 37 4±0.5℃ via hepatic artery in 15 minutes was used;(3)hyper-thermai perfusion group(n=10),a perfusion of 30ml saline at 60±0.5℃via hepatic artery in 15 minutes was used.The vascular permeability of the tumor tissue and the normal liver tissue was estimated with Evan's blue method.Results In all three groups the vascular permeability was significantly incleased in tumor tissue than that in normal liver tissue(P＜0.05).Normal thermal perfusion resulted in a significant increase in the permeability of vasculature(JP＞0.05).Hyper-thermal peffusion resulted in a significant increase in vascular permeability of tumor tissue (P＜0.05),and vascular permeability was increased in tumor tissue mole markedly than that in normal tissue(P＜0.05).Conclusion Hyperthermia hepatic arterial perfusion can increase vascular permeability for both tumor tissue and normal tissue in VX2 tumor-bearing rabbits.
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Objective To study the inhibitory effects of hydroxyapatite nanoparticles on liver VX2 tumor in rabbits after intratumoral injection. Methods 40 rabbits with implantation of liver VX2 tumors were randomly divided into 4 groups and intratumorally injected with different preparations.Group A: (control group), 1 ml nomal saline containing 0.2% CMC-Na; Group B: ( 5-Fu group),20 mg/ml 5-Fu 1 ml; Group C: (Nano HAP), 20 mg/ml Nano HAP 1 ml; Group D: (5-Fu+Nano HAP), 20 mg/ml 5-Fu 1 ml and 20 mg/ml Nano HAP 1 ml. Ultrasonography was performed to measure liver tumor volume 7, 14, 21 d after treatment. Survival durations of the animals were recorded. Tumor tissues and liver tissues close to tumor were obtained and examined histologically.Results The average tumor volumes 7, 14 and 21 d after treatment were (4.93 ±0.76)cm3,(15. 67±2.75)cm3 and (52. 36±10. 57)cm3 in group A, (4. 16±0. 33)cm3 , (10. 26± 1.60)cm3 and (18. 89±4.65)cm3 in group B, (1.43±0.13)cm3 , (3.69±0.77)cm3 and (9.51±2.09)cm3 in group C, (2. 80±0.46)cm3 , (3. 77±0. 91)cm3 and (8. 46±0.95)cm3 in group D respectively. The average tumor volumes of groups B, C and D were significantly smaller than that of group A in the same time phases after treatment. The life span of group C was longer than that of other three groups, and there was no statistically significant difference between group B and group D, although the two groups were significantly longer than group A. Blood flow was not detected by color Doppler or power Doppler in group C and group D. Pathological examination showed that there was obvious intratumoral necrosis in group C and D. Tumor in group B exhibited thoroughgoing necrosis. Conclusion Hydroxyapatite nanoparticles intratumoral injection is safe and feasible for treatment of liver tumor. Hydroxyapatite nanoparticles can exert a significant inhibitory effect on liver VX2 tumor growth in rabbits without liver toxicity.
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This study investigated the inhibitory effect of the extract of fungi of Huaier (EFH) on the growth of hepatocellular carcinoma (HCC) cells.Hep-G2 cells,a human HCC cell line,were cultured in DMEM containing 10% fetal bovine serum and treated with EFH of different concentrations (1,2,4,8 mg/mL) for 24,48 and 72 h respectively.The apoptosis rate of the cells was flow cytometrically measured.Thirty-six tumor-bearing New Zealand rabbits were randomly divided into 3 groups:group A (control group),in which the rabbits were infused with 0.2 mL/kg normal saline via the hepatic artery;group B (transhepatic artery chemoembolization [TACE] group),in which the rabbits were given lipiodol at 0.2 mL/kg plus MMC at 0.5 mg/kg via the hepatic artery;group C (TACE +EFH group),in which EFH (500 mg/kg) were orally administered after TACE.Two weeks after TACE,the rabbits were sacrificed and the implanted tumors were sampled.The tumor volume and the necrosis rate were determined.The tumor tissues were immunohistochemically detected for the expressions of factor Ⅷ,VEGF,P53,Bax and Bcl-2.The microvessel density (MVD) was calculated by counting the factor Ⅷ-positive endothelial cells.Our results showed that after treatment with EFH,the apoptosis rate of Hep-G2 cells was enhanced in a concentration- and time-dependent manner.Two weeks after the treatment,the average tumor volume,the necrosis rate and the growth rate of the implanted tumor in group C were significantly different from those in groups A and B (P<0.05).MVD and VEGF expressions were significantly decreased in the group C when compared with those in groups B (P<0.05 for all).The Bax expression was weakest in group A and strongest in group C.The expressions of P53 and Bcl-2 were minimal in group C and maximal in group A.There were significant differences in the expressions of P53,Bax and Bcl-2 among the 3 groups (P<0.05 for all) and there was significant difference between group B and group C (P<0.05).It was concluded that EFH could suppress not only the growth of HCC cells but also tumor angiogenesis and it can induce the apoptosis of HCC cells.EFH serves as an alternative for the treatment of HCC.
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Objective To investigate the effects of low dosage of β-elemene on the radiosensitivity of rabbit VX2 renal transplant carcinoma model. Methods We took the rabbit VX2 renal transplant carcinoma as the model. Experimental rabbits were divided into three groups: the control group, the radiation group, and the radiation +β-elemene (radiosensitivity) group. The change of tumor was observed by Spiral CT and B ultrasound to compare its regrowth period. The tumor was measured by light microscopy and electron microscopy. Results The tumor in radiosensitivity group was restrained obviously and the sensitization enhancement ratio (SER) of β-elemene was 1.89. Different apoptosis was observed under transmission electron microscopy. Conclusion Low dosage β-elemene can enhance the radiosensitivity of rabbit VX2 renal transplant carcinoma model and induce the apoptosis of tumor cells, but the mechanism needs further study. It promotes apoptosis in mechanisms in vitro.
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Objective:To investigate the influence of Bifidobacterium adolescence on the expression of HIF-1?and VEGF in rabbit VX2 tumor.Methods:Rabbit VX2 tumor models were established and were divided into two groups(n= 10).Animals in the experimental group were injected with Bifidobacterium adolescence and those in the control group received normal saline via ear vein.Animals were sacrificed and the liver,kidney,spleen,heart,lung and tumor tissues were removed,cultured and Gram stained.The changes of tumor tissue were observed by H-E staining;immunohistochemistry was used to detect the expression of HIF-1?and VEGF in tumor tissues.Results:Bifidobacterium adolescence could target the tumor tissue.H-E staining showed the necrotic area was obviously enlarged after treatment with Bifidobacterium. Immunohistochemistry demonstrated that the positive rates of HIF-1?and VEGF in the experimental group were significantly lower than those of the control group(P