Establishment of Rabbit Liver VX2 Tumor Model Using Percutaneous Puncture Inoculation of Tumor Fragment Guided and Evaluated by Ultrasonography

The aim of the present study is to evaluate a method of establishing model of rabbit liver VX2 tumor using percutaneous puncture inoculation of tumor fragment guided by ultrasonography.VX2 tumor fragments were implanted into the liver of 13 New Zealand white rabbits flushed by 1 mL normal saline through percutaneous puncture needle guided by ultrasonography.Conventional ultrasonography and contrast-enhanced ultrasonography(CEUS)were performed 14 days after inoculation,and then the rabbits were sacrificed and pathologically examined.The success rate of inoculation was 100%.The average size of liver VX2 tumor was 1.7 cm×1.3 cm,CEUS of VX2 liver tumors showed the"rapid wash-in and wash-out"vascular pattern.There were significant differences between VX2 tumors and liver parenchyma in quantitative parameters of A,k and A×k(P<0.05),which meant that VX2 liver tumors were characterized by more blood flow volume and faster blood velocity than liver parenchyma.Tumor fragment flushed by normal saline into the liver through a needle may be a promising method for the induction of a hepatic tumor.And CEUS can be used for accurately assessing angiogenesis and blood perfusion of VX2 tumors.

Adriamycin Thermotherapy through the Hepatic Artery Using VX2 Carcinoma in Rabbit Liver as a Model

OBJECTIVE It has been reported that heating can enhance sensitivity of rabbit VX2 cells to adriamycin and increase the intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effect of interventional hyperthermia and interventional thermochemotherapy on VX2 carcinoma in rabbit liver. METHODS VX2 carcinoma cells were surgically implanted into the right liver lobe of 60 male New Zealand white rabbits, which were randomly divided into 4 groups (15 per group). The 4 groups (designated as 1, 2, 3, 4 respectively) were injected with 10 ml of the following via the hepatic artery: physiological saline (37℃); adriamycin (37℃); physiological saline (60℃); adriamycin (60℃). One week later, the tumor volume, serum level of aspartate transaminase (AST) and the survival of the rabbits bearing VX2 were observed and compared among the different treated groups. RESULTS The tumor growth rate in group 4 (ADM 60℃) (0.53±0.21)% was significantly lower than that in group 1 (3.48±1.17)%, in group 2 (1.09±0.26)% and group 3 (3.32±1.28)% (P<0.05, P<0.05, P<0.01, respectively). The days of survival days for group 4 (87.0±2.0) were significantly more than that in group 1 (40.0±3.0). Group 4 showed a significantly higher increase in serum AST compared to group 1 (P<0.05), but without significant differences compared to the other groups (P>0.05). CONCLUSION Adriamycin treatment at 60℃ significantly deceased the tumor growth, prolonged the survival period and resulted in reversible liver damage.

Feasibility of hyperspectral analysis for discrimination of rabbit liver VX2 tumor

BACKGROUND Hepatocellular carcinoma is one of the most common malignant tumors worldwide. Currently, the most accurate diagnosis imaging modality for hepatocellular carcinoma is enhanced magnetic resonance imaging. However, it is still difficult to distinguish cirrhosis lesions, and novel diagnosis modalities are still needed.AIM To investigate the feasibility of hyperspectral analysis for discrimination of rabbit liver VX2 tumor.METHODS In this study, a rabbit liver VX2 tumor model was established. After laparotomy,under direct view, VX2 tumor tissue and normal liver tissue were subjected to hyperspectral analysis.RESULTS The spectral signature of the liver tumor was clearly distinguishable from that of the normal tissue, simply from the original spectral curves. Specifically, two absorption peaks at 600-900 nm wavelength in normal tissue disappeared but a new reflection peak appeared in the tumor. The average optical reflection at the whole waveband of 400-1800 nm in liver tumor was higher than that of the normal tissue.CONCLUSION Hyperspectral analysis can differentiate rabbit VX2 tumors. Further research will continue to perform hyperspectral imaging to obtain more information for differentiation of liver cancer from normal tissue.

Expression of MMP-2 in residual VX2 liver tumor after transcatheter arterial embolization combined with portal venous embolization in an animal model

Objective:This study aimed to analyze the effects of transcatheter arterial embolization(TAE)combined with portal venous embolization(PVE)on the expression of MMP-2 in residual VX2 liver tumor tissues,liver function and non-embolic lobe regeneration.Methods:A total of 72 rabbits were randomly divided into Sham,TAE,PVE and TAE+PVE groups(n=18/group).The tissue samples from each group were taken at 6 h,3 days and 7 days after interventional operation,respectively.MMP-2 expression was detected by immunohistochemistry,Real-time PCR,and Western-blotting.The main indicators(such as AST,ATL,and TBIL)of liver function and the volume of non-embolized hepatic lobes were measured in each group after operation.One-way ANOVA and Kruskal-wallis method were used for statistical analysis.Results:The expression of MMP-2 mRNA and protein remained the highest in the Sham group,and the expression of MMP-2 mRNA and protein in TAE,PVE and TAE+PVE groups were successively increased,and the expression of MMP-2 in TAE+PVE group was always significantly higher than TAE group.The AST and ALT levels in each group on day 7 after operation showed a significant declination,and all groups have recovered to the preoperative baseline level and TBIL has a slight fluctuation in each group after operation with no statistical difference.On day 7 after operation,the increasing volume of non-embolized liver lobes in TAE+PVE group showed a more significant effect than those in PVE group,but there was no statistical significance(37.62±1.54 ml VS 36.18±1.15 ml,P=0.881),and its volume was significantly higher than those in the sham group(27.03±1.11 ml).Conclusion:TAE+PVE is considered to be an efficient and safe approach for treating rabbit VX2 liver transplantation tumor,but the expression of MMP-2 increased fastest after TAE+PVE,which might promote tumor cell invasion and metastasis.

A Correlative Study between CT Perfusion Parameters and Angiogenesis in Rabbit VX2 Liver Tumors

Objective: The purpose of this study was to evaluate the correlation between CT perfusion parameters and the hypoxia-inducible factor-1 alpha (HIF-1α), vascular en-dothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and microvessel density (MVD) marked by CD34 molecular of rabbit VX2 liver tumors and to investigate the value of CT perfusion imaging in evaluating tumor angiogenesis. Material and methods: Twenty-four cases of rabbit VX2 liver tumor were performed by CT perfusion scanning. Hepatic artery perfusion (HAP), portal vein perfusion (PVP), total hepatic blood flow (THBF) and hepatic perfusion index (HPI) were measured by perfusion software. HIF-1α, VEGF and MMP-2 expression and MVD were detected in the 24 rabbit VX2 liver tumor tissue samples using immunohistochemical method. The correlation between the HIF-1α, VEGF, MMP-2 expression and MVD and CT perfusion parameters were analyzed. Results: Correlation analysis revealed that the expression of HIF-1α, MMP-2, MVD were positively related to the HAP, THBF, HPI (p < 0.01), but no relations with PVP (p > 0.05);and correlation analysis revealed that the expression of VEGF was positively related to the HAP, HPI (p 0.05). There was a positive relationship between the expression of HIF-1α, VEGF, MMP-2 and MVD (p < 0.01). Conclusions: CT perfusion imaging can reflect the blood perfusion of the rabbit VX2 liver tumors and evaluate the information of angiogenesis about tumors.

射频消融治疗对兔肝VX2肿瘤VEGF表达的影响

目的:探讨射频消融(RFA)对兔肝VX2肿瘤血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的影响.方法:建立日本大耳白兔肝VX2肿瘤模型,随机分为3组:对照组直接处死取肝脏标本;RFA治疗(4h和24h)组于射频消融后4h和24h处死取出肝脏组织.并以正常兔肝脏组织为正常对照,通过免疫组织化学方法和逆转录聚合酶链式反应(RT-PCR)方法检测VEGF的蛋白和基因表达.结果:VX2肿瘤浸润性生长,射频后中央消融区呈现大片坏死,周围见炎性反应带,外围癌组织残留.免疫组化和RT-PCR示对照组肿瘤组织VEGF的蛋白和基因表达均高于正常组(VEGF/GAPDH基因灰度比:1.3048±0.1936vs0.8993±0.1107,P<0.05),射频消融后4h和24h表达明显下降(VEGF/GAPDH基因灰度比:0.7388±0.1503,0.8935±0.1936,均P<0.05),但不同时间段并无明显差异.结论:RFA治疗能下调肿瘤VEGF基因和蛋白水平的表达,抑制血管生成,减少血供,进而降低了复发和转移几率.

兔Vx-2移植性肝癌模型的建立及其影像学表现

目的 用 3种不同植瘤方式建立稳定的兔Vx 2移植性肝癌模型 ,分析移植性肝肿瘤的DSA影像特征。方法 6 0只新西兰白兔随机分成 3组 ,每组 2 0只。第 1组 ,将Vx 2瘤细胞 (约 5× 10 7个 )经肝动脉灌注入兔的肝脏 ;第 2组 ,将Vx 2瘤细胞 (约 5× 10 7个 )经剖腹途径接种于兔的肝左叶 ;第3组 ,将瘤组织块 (约含 10 6～ 10 8个瘤细胞 )经剖腹途径植入兔肝左叶。之后 ,对 3组兔比较观察 :1.不同方式植瘤的成活率 ;2 .肝内肿瘤体积变化和肿瘤生长率 ;3.大体及镜下 (光镜和电镜 )瘤组织形态特征 ;4 .成熟模型的DSA表现。结果 1.3组植瘤成活率分别为 7/ 2 0、10 / 2 0、19/ 2 0 ,第 3组植瘤成活率最高 (P <0 .0 5 ) ,其瘤体呈指数性生长 ;2 .病理学及CT表明该瘤在肝组织中呈浸润式生长 ,其性状与移植于兔其它部位的Vx 2鳞状细胞癌特征相似 ;3.DSA影像示移植性肝肿瘤具有丰富的血供。结论 成功建立了兔Vx 2移植性肝癌模型 ,瘤组织块种植方式成功率明显高于其他两种方法 。

兔肝Vx-2移植癌改良模型的建立

目的 建立稳定的兔Vx 2移植性肝癌模型 ,探讨不同植瘤方式的成功率。方法 将 60只新西兰白兔随机分 3组 ,每组 2 0只。观察 :①不同方式的成活率 ;②B超监测肿瘤生长 ,并计算肿瘤生长率 ;③瘤组织形态特征。结果 ①改良组植瘤成活率最高 (P <0 .0 5 ) ,瘤体呈指数性生长 ;②该瘤在肝组织中呈浸润式生长 ,其性状与移植于兔其他部位的Vx 2鳞状细胞癌特征相似。结论 成功建立了兔Vx 2移植性肝癌模型 ,瘤组织块种植方式成功率明显高于其他方法。

兔VX_2肝癌模型的建立及超声评价

目的 探讨不同方法制作兔VX2 移植性肝癌模型的特点 ,评价超声检查在监测VX2 肝癌中的价值。方法 将VX2 细胞滤液、VX2 瘤株小块及VX2 瘤株小块 +明胶海绵分别注射或接种于 2 8只新西兰大白兔的肝脏内 ,一周后不同时间行超声检查。结果 A组滤液注射法 :平均成瘤时间约 2 1天 ,肝的原位成瘤率为 75 %。B组包块埋植法 :平均成瘤时间14天 ,肝的原位成瘤率为 83 %。C组包块埋植 +明胶海绵法 :平均成瘤时间 14天 ,肝的原位成瘤率 88%。三组成瘤率统计学无显著差异 ( χ2 =1.118,P >0 .0 5 )。肝脏内的移植瘤在超声上均表现为低回声伴声晕的肿块 ,彩色多普勒血流成像表现为周边血供丰富 ,中央血供稀少。结论 三种方法均能制成肝癌模型 ,超声检查是一种监测肝癌模型的有效手段。

兔肝Vx-2移植癌改良模型的建立

目的 培养、建立稳定的兔肝 ＶＸ－２移植癌模型，探讨不同植瘤方式的成功率。方法 ６０只新西兰白兔随机分 ３组，每组 ２０只。分别以不同的方式将 Ｖｘ－２瘤细胞植入兔的肝脏。观察：１．不同方式植瘤的成活率；２．Ｂ超测定肝内肿瘤 ７ｄ、１０ｄ、１４ｄ、１７ｄ、２１ｄ时的大小，并计算肿瘤生长率；３．大体及镜下（光镜和电镜）瘤组织形态特征。结果 １．三组植瘤成活率分别为 ７／２０、１０／２０、１９／２０，改良组植瘤成活率最高（Ｐ＜０．０５），瘤体呈指数性生长；２．病理学及ＣＴ表明该瘤在肝组织中呈浸润式生长，其性状与移植于兔其它部位的Ｖｘ－２鳞状细胞癌特征相似。结论 成功建立了兔肝Ｖｘ－２移植癌模型，瘤组织块种植方式成功率明显高于其它两组方式，为肝癌介入治疗的基础及临床研究，提供了成熟的大型实验动物模型。

兔肝脏、肌肉、皮下VX2肿瘤模型的建立和对比研究

目的通过对肝脏、肌肉及皮下不同部位兔VX2肿瘤模型的建立和比较,寻求更适合于肿瘤经皮介入治疗的荷瘤动物模型。方法将54只新西兰白兔按VX2肿瘤接种部位不同随机分为肝脏组、肌肉组和皮下组,每组18只。三组动物术后12、16、20 d均进行CT灌注扫描,测量肿瘤大小,每次各组分别处死6只兔进行病理观察,并对三组模型的建模手术时间、肿瘤体积及并发症等情况进行比较。结果皮下组肿瘤生长最慢,肌肉组其次,肝脏组生长最快,组间差异有统计学意义(P<0.05)。接种第12天,肝脏组肿块长径已约1 cm,而皮下组则需20 d肿块长径才达1 cm左右,肌肉组肿块生长速度介于二者之间。三组建模所用时间分别为肝脏组(5.54±0.51)min,肌肉组(1.02±0.20)min,皮下组(0.98±0.21)min,肝脏组明显较长。除了肝脏组出现腹水、肝内转移及腹壁种植外,皮下组、肌肉组均无明显影响模型的情况。结论与肝脏和皮下建模相比,兔肌肉内VX2肿瘤模型具有操作简单,成瘤稳定,肿瘤生长速度适中的优点,更适合作为兔VX2瘤的经皮介入治疗模型。

建立兔移植性Vx-2肝癌模型的改进

目的 建立Vx 2兔移植性肝癌改良模型。方法 将Vx 2瘤粒经剖腹直接种植于肝实质内 ,依观察时间不同分成 3组 ,每组 10只 ,种植后分别观察 2、3、4周 ,对比观察其病理形态学和影像学表现。结果 15只种植成功 ,种植 2周组各项观察指标最为满意。结论 以瘤粒肝内种植方式、2周后可成功建立Vx 2兔移植性肝癌模型。

光敏剂-磁性纳米粒子螯合剂对磁性纳米粒子在VX2肝转移癌细胞内靶向性分布的影响

目的:研究光敏剂-磁性纳米粒子螯合物促进磁性纳米粒子在VX2肝转移癌细胞内的靶向性分布.方法:取健康新西兰大白兔40只,体质量2.5-3.0kg.建立VX2肝转移癌模型,随机分成空白对照组、光敏剂组、磁性纳米粒子组和光敏剂-磁性纳米粒子螯合物组,在成瘤后的第16、18和20d,经兔耳缘静脉分别注射生理盐水、光敏剂、磁性纳米粒子和螯合物.于第22d处死试验兔,剖腹观察肿瘤生长情况,取正常肝组织和癌结节,作普鲁氏蓝铁染色、透射电镜检查和原子光谱吸收半定量检测.结果:(1)普鲁氏蓝染色后,在螯合剂组癌结节内见到大量蓝染铁颗粒,明显多于其他各组,而肝细胞内少见蓝染铁颗粒;(2)电镜检查,螯合剂组癌细胞内有大量散在的黑色细小颗粒,主要分布在溶酶体、内质网、线粒体和细胞核内;而肝细胞内只有少量黑色细小颗粒;(3)原子光谱吸收半定量检测显示,在癌结节内,螯合剂组铁含量(9.09mg/L)明显高于空白对照组、光敏剂组和磁性纳米粒子组(P<0.01),癌组织内铁含量也明显高于正常肝组织的铁含量(P<0.01).结论:光敏剂-磁性纳米粒子螯合剂能够促进磁性纳米粒子在肝转移癌结节内的聚集.

不同粒径ContourSe微球栓塞肝动脉治疗兔VX-2移植性肝癌的实验研究

目的:研究不同粒径ContourSe微球对兔VX-2移植性肝癌的栓塞作用及对正常肝组织的影响,初步确定ContourSe微球肝动脉栓塞治疗肝癌的最佳粒径范围。方法:经剖腹途径将VX-2瘤粒悬液直接注入兔肝实质内建立兔VX-2移植性肝癌模型,共30只兔。用不同粒径的ContourSe微球对兔VX-2移植性肝癌模型行肝动脉栓塞治疗,根据使用ContourSe微球粒径的不同分为5组,第1组(n=6):注入1mL0.9%氯化钠液,作为对照组;第2组(n=6):用ContourSe微球(100～300μm)栓塞;第3组(n=6):用ContourSe微球(300～500μm)栓塞;第4组(n=6):用ContourSe微球(500～700μm)栓塞;第5组(n=6):用ContourSe微球(700～900μm)栓塞。栓塞术前行CT扫描了解兔肝肿瘤大小,栓塞术后定期处死作肝脏大体标本观察和组织学检查,了解肿瘤大小及坏死程度、正常肝组织损害情况和腹腔脏器并发症。结果:兔肝肿瘤种植成功率达100%。各组兔肝肿瘤生长率的平均值分别为,第1组:2.5450;第2组:1.3711;第3组:1.5263;第4组:1.9431;第5组:2.1699。第2组与第3组比较无明显差异(P=0.195),此2组与其余3组比较均有显著差异(P<0.001)。第2组及第3组肿瘤坏死均以重度坏死为主,尤其第2组坏死率最高。第2组兔肝可见多发灶状坏死,汇管区可见胆管壁坏死,肝纤维结缔组织间隔亦可见坏死溶解改变。结论:(1)小于500μm的ContourSe微球能较有效地阻断肿瘤血供,抑制肿瘤生长;(2)100～300μm ContourSe微球组虽然肿瘤坏死最明显,但可以引起正常肝组织胆道及肝内结缔组织坏死,临床使用须在超选择插管的前提下谨慎使用;(3)300～500μm ContourSe微球最适于临床肝肿瘤的栓塞治疗。

MMP-2/PCNA在模拟介入治疗后的兔VX_2肝癌中的表达及意义

目的 研究MMP 2 PCNA在兔VX2 肝癌中表达的意义以及模拟介入治疗对其表达的影响。方法 建立兔VX2 肝癌的动物模型,将实验动物分为介入组和对照组,比较两组的肝功能变化、肿瘤生长率,用原位杂交和免疫组化法研究各组的MMP 2 PCNA表达情况。结果 介入组在1、2、3、4周的门冬氨酸转氨酶(AST :IU L)分别为(13±2 )、(96±2 5 )、(68±13 )、(4 8±10 ) ,而同时间段对照组分别为(16±3 )、(10 3±2 3 )、(13 1±3 4)、(14 6±3 6) ;介入组在1、2、3、4周的丙氨酸转氨酶(ALT :IU L)分别为(3 6±5 )、(13 0±3 1)、(78±18)、(64±13 ) ,而同时间段对照组分别为(3 3±5 )、(14 5±2 6)、(160±3 2 )、(186±42 )。对照组的AST和ALT分别高于同一时间段介入组。各组肿瘤随着时间延长体积均增大,介入组和对照组在术后1、2、3周的肿瘤生长率分别为(10 2±88) %、(2 3 8±96) %、(2 85±94) %、(164±88) %、(5 68±12 0 ) %、(886±45 5 ) %。其中介入组在术后2、3周的肿瘤生长率明显低于同期对照组,差异有显著性(P <0 0 5 )。介入组MMP 2mRNA及蛋白表达的阳性率分别为66 7%、5 4 2 % ,较对照组(4 1 7% ,3 3 3 % )明显减少(P <0 0 5 ) ,转移组MMP 2mRNA及蛋白表达的阳性率分别为68 9%、5 1 7% ,较无转移组(

兔肝Vx-2移植癌改良模型的建立

【目的】建立稳定的兔Vx-2移植性肝癌模型,探讨不同植瘤方式的成功率。【方法】60只新西兰白兔随机分3组,每组20只。第1组,将Vx-2瘤细胞(5×107个)经肝动脉灌注入兔的肝脏;第2组,将Vx-2瘤细胞(5×107个)经肝包膜接种于2组兔的肝左叶;第3组,将瘤组织块(约含106-108个瘤细胞)经肝包膜植入肝左叶。观察:1.不同方式植瘤的成活率;2.B超测定肝内肿瘤7、10、14、17、21 d时的大小,并计算肿瘤生长率;3.大体及镜下(光镜和电镜)瘤组织形态特征。【结果】3组植瘤成活率分别为7/20、10/20、19/20,改良组植瘤成活率最高(P<0.05),瘤体呈指数性生长。病理学表明该瘤在肝组织中呈浸润式生长,其性状与移植于兔其它部位的Vx-2鳞状细胞癌特征相似。【结论】成功建立了兔Vx-2移植性肝癌模型,瘤组织块种植方式成功率明显高于动脉途径和细胞液注射方式,为肝癌介入治疗的基础及临床研究提供了成熟的大型实验动物模型。

超声导向法建立VX_2兔肝癌模型

为研制适合于超声等影像学监测和介入治疗研究的肝癌动物模型 ,将兔后腿肌肉内的 VX2 肿瘤组织剪成 1 mm× 1 mm× 3 mm条状瘤块 ,在超声引导下将 VX2 肿瘤块接种60只新西兰白兔肝脏 ,2周后测定新西兰白兔肝肿瘤接种成功率。结果显示 ,兔肝 VX2 肿瘤接种成功 ,在超声表现为接种部位的圆形或类圆形低回声结节 ,无包膜回声 ,肿瘤有液化坏死时呈不等回声。肿瘤切面呈灰白色 ,鱼肉样 ,质硬。操作熟练后模型接种成功率 90 .5%。9只模型的自然生存期为 43 .3± 5.7d。结果提示超声引导下穿刺接种制作兔 VX2 肝癌动物模型的方法是一种操作方便简单、成功率高。

经肝动脉化疗栓塞术联合姜黄素对兔VX-2肝癌VEGF表达的影响

目的探讨经肝动脉化疗栓塞术(TACE)联合姜黄素治疗兔VX-2肝癌对血管内皮生长因子VEGF表达的影响。方法建立兔VX-2肝癌模型40只,按随机数字表法分成生理盐水组(对照组)、姜黄素灌注组(HA组)、碘化油栓塞组(TAE组)和姜黄素碘化油乳剂栓塞组(TACE组),每组10只。对照组:经肝动脉缓慢注入1 mL生理盐水;HA组:经肝动脉缓慢注入姜黄素5 mg.kg-1;TAE组:经肝动脉缓慢栓塞碘化油1 mL;TACE组:经肝动脉缓慢栓塞姜黄素碘化油乳剂1 mL。治疗后2周处死实验兔,取出肿瘤标本。采用免疫组织化学法和Western印迹杂交法测定新生灶中VEGF蛋白的表达。结果免疫组织化学法VEGF蛋白的表达水平:对照组为0.582±0.181,HA组为0.524±0.277,TAE组为0.874±0.199,TACE组为0.581±0.190;Western印迹杂交法VEGF蛋白的表达水平:对照组为46.49±12.78,HA组为47.54±14.51,TAE组为83.40±18.02,TACE组为54.21±15.70。TAE组中VEGF蛋白的表达明显高于对照组、HA组和TACE组(P<0.05),对照组、HA组、TACE组之间VEGF蛋白的表达差异无统计学意义(P>0.05)(2种测定方法结果相一致)。结论姜黄素联合碘化油栓塞兔VX-2肝癌模型后能有效地降低VEGF蛋白的表达,而单纯姜黄素经肝动脉灌注不能有效地降低VEGF蛋白的表达。

兔VX-2肝移植肿瘤的制作方法研究

目的探索应用不同方法制作VX-2兔移植性肝癌模型,评价原位成瘤率。方法新西兰白兔38只,采用VX-2瘤株动物自身接种传代。A组15只采用超声引导瘤组织混悬液注射法;B组13只采用开腹瘤组织混悬液注射法;C组10只采用瘤组织块包埋法,均接种于肝左叶。各组分别于接种后1周、2周、3周、4周、5周行CT平扫、增强扫描及MR I平扫。计算各组的原位成瘤率。结果A、B组各种植成功10只,C组种植成功7只,分别为66.7%、76.9%、70%,无统计学意义。结论三组制作方法都有较高的原位成瘤率,实验周期短,均可用于兔VX-2肝癌模型的制作。

Effect of hydroxyapatite nanoparticles on the growth and p53/c-Myc protein expression of implanted hepatic VX_2 tumor in rabbits by intravenous injection

AIM： To evaluate the effect of hydroxyapatite nano- particles （Nano HAP） by intravenous injection on the inhibition of implanted hepatic VX2 tumor growth in rabbits and cell p53/c-Myc protein expression. METHODS： 60 hepatic VX2 tumor-bearing rabbits was randomly divided into five groups. Nano HAP collosol 20 mglkg, 40 mg/kg, 5-FU solutions 20 mg/mL, mixed liquor of 5-FU solution 20 mg/mL and Nano HAP collosol 20 mg/kg were infused by vein, normal saline conducted as the control. The general state, weight, liver function and gross tumor volume were detected dynamically. The expression of p53 and c-Myc gene protein in tumor tissue was detected by immunohistochemistry methods. RESULTS： The growth of implanted hepatic VX2 tumors was significantly inhibited in all therapy groups, 3 wk after the injection, the tumor control rates in Nano HAP collosol groups were 25.5% and 32.5% respectively, and the gross tumor volumes were obviously less than that of control group. （24.81 ± 5.17 and 22.73 ± 4.23 vs 33.32 ± 5.26, P 〈 0.05）. The tumor control rate of 5-FU group was 43.7% （18.74 4± 4.40 vs 33.32 ± 5.26, P 〈 0.05）, but the general state of the animals after injection aggravated; and the adverse reaction in the drug combination group obviously decreased. Due to the effect of Nano HAP, the positive expression of tumor associated the mutated p53 and c-Myc in tumor tissue was decreased obviously compared with the control group. CONCLUSION： Nano HAP has evident inhibitory action on rabbit implanted hepatic VX2 tumor in vivo, which may be the result of decreasing the expression of the mutated p53 and c-myc, and drug combination can obviously decrease the adverse reaction of 5-FU.