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1.
Creation of a VX2 tumor model has traditionally required a laparotomy and surgical implantation of tumor fragments. Open surgical procedures are invasive and require long procedure times and recovery that can result in post-operative morbidity and mortality. The purpose of this study is to report the results of a percutaneous ultrasound guided method for creation of a VX2 model in rabbit livers. A total of 27 New Zealand white rabbits underwent a percutaneous ultrasound guided approach, where a VX2 tumor fragment was implanted in the liver. Magnetic resonance imaging was used to assess for tumor growth and necropsy was performed to determine rates of tract seeding and metastatic disease. Ultrasound guided tumor implantation was successful in all 27 rabbits. One rabbit died 2 days following the implantation procedure. Two rabbits had no tumors seen on follow-up imaging. Therefore, tumor development was seen in 24/26 (92%) rabbits. During the follow-up period, tract seeding was seen in 8% of rabbits and 38% had extra-hepatic metastatic disease. Therefore, percutaneous ultrasound guided tumor implantation safely provides reliable tumor growth for establishing hepatic VX2 tumors in a rabbit model with decreased rates of tract seeding, compared to previously reported methods.  相似文献   

2.

Purpose

Based on practice guideline of “management of hepatocellular carcinoma (HCC): update” published by American Association for the Study of Liver Diseases (AASLD) and “Barcelona Clinic Liver Cancer staging system (BCLC),” this study investigated how to enroll the optimal VX2 liver tumor model for HCC researches by dynamically observing the biological progression of the tumor.

Materials

Thirty-two healthy New Zealand white rabbits were implanted VX2 liver tumor by cell suspension method (n=24) and tissue fragment method (n=8). All the rabbits underwent CT scans on day 7, 14, 21 and 28 after implantation to observe the size of the tumors, the time when metastases and ascites occurred and the survival time. Appropriate intervention times were estimated corresponding to different clinical HCC stages by using tumor diameter-time curve.

Results

The VX2 liver tumors grew rapidly within 28 days after implantation. And the tumors in the cell suspension group grew faster than those of the tissue fragment group. The appropriate intervention time corresponding to very early stage, early stage and intermediate stage were <11 days, 11–16.9 days and >16.9 days, respectively in the cell suspension group, and <19.9 days, 19.9–25.5 days and >25.5 days, respectively in the tissue fragment group.

Conclusion

Preclinical animal research needs to improve on different levels to yield best predictions for human patients. Researchers should seek for an individualized proposal to select optimal VX2 liver tumor models for their experiments. This approach may lead to a more accurate determination of therapeutic outcomes.  相似文献   

3.
张元国  任为  张彦  孙婧 《四川动物》2012,31(3):474-477,514
目的建立VX2肿瘤侵犯新西兰兔下腔静脉(IVC)的动物模型,并观察相应的生物学行为。方法经腹直视下,将VX2肿瘤组织块分别种植在28只兔肾以下IVC附近的软组织内,然后随机分为A、B两组。A组术后每周在超声下观察肿瘤的大小、IVC和腹主动脉(AA)管径大小;DSA观察侧支循环建立。B组每周随机解剖4只,取IVC和AA做病理和免疫组化(PCNA)检查,并观察转移情况。结果 1.超声显示:所有肿瘤均种植成功,肿瘤面积大小与生长时间呈明显正相关(r=0.879),IVC管径与肿瘤面积大小显著负相关(r=-0.8295);4周时25%的IVC管腔闭塞,5周时达到91.7%。2.病理和免疫组化显示:3周时IVC管壁中见大量肿瘤细胞;5周时AA管壁中未见肿瘤细胞。3.DSA显示:IVC慢性受侵犯过程中侧枝循环建立良好。4.解剖观察:模型动物在第4周开始出现肝、肺和腹腔转移。结论 VX2肿瘤成瘤率高,其生长变化、对IVC的侵犯和远处器官转移均随生长时间而变化明显。  相似文献   

4.
目的:通过研究不同活度的125I粒子以及联合TACE治疗兔VX2肝移植癌的疗效及其病理基础,探讨125I粒子组织间植入治疗肝癌的有效性。方法:建立兔VX2肝癌模型。60只肝癌模型兔随机分成5组,对照组(A组)植入空白剂量(0mCi)125I粒子,B组植入1.0mCi125I粒子,C组植入0.7mCi125I粒子,D组植入0.4mCi125I粒子,E组植入0.7mCi125I粒子+TACE。观察植入前后各组肿瘤体积并计算抑瘤率,切除肿瘤组织及周围正常组织进行常规病理检查。结果:各治疗组肿瘤大小在治疗前后比较具有统计学差异(P<0.01),均小于同期对照组(A组)(P<0.01)。在不同观察时期抑瘤率差别均有统计学意义(P<0.05),各个组间抑瘤率差异在治疗后2周最为明显(P<0.01),但均高于D组(P<0.01)。治疗后6周病理提示D组部分组织内仍可见少量肿瘤细胞,而其余各治疗组均未见明显的肿瘤细胞残存,B组对周围肝组织损伤较大,C组、E组适中。总体疗效E组优于其余各治疗组。结论:125I粒子联合TACE治疗肝癌效果明显优于单一的治疗方案,是肝癌目前较为理想的治疗方案,其中单个粒子活度以0.7mCi左右较为适宜。  相似文献   

5.
目的 对兔VX2 肝癌模型制作进行改良,以用于介入治疗学研究,同时探讨瘤灶的CT 表现及CT 在检测瘤灶中的作用.方法 将VX2瘤细胞接种于兔皮下使其成瘤并传代;新西兰兔24只,以改良嵌插法建立移植性肝癌模型,于建模后7、14、21 d分别行超声、CT及血管造影检查,用于检测兔肝VX2 瘤灶,评估瘤灶生长变化;随后处死动物,进行尸解,评估影像检查结果.结果 24只(100%) 动物以改良嵌插法建立移植性肝癌模型全部成功.瘤灶以种植后2周CT显示最清楚和典型,直径1 cm~2 cm 左右,平扫呈低密度或等密度,动脉早期明显强化,门脉期呈低密度,与周围肝组织分界较清楚.肝动脉造影显示肿瘤富血供.而种植后超过3 周的肿瘤大部分发生坏死.结论 嵌插改良法是一种值得推广的建立移植性肝癌模型的方法;在对瘤灶进行影像学评价上应尽量选择CT检查,接种后1 周左右的瘤灶较小而难以观察;2 周左右呈肝动脉源性血供丰富的约1 cm~2 cm的实体瘤,造影征像为肿瘤血管与肿瘤染色;3 周以上瘤灶大多出现明显示坏死;因此对1~2cm大小的兔VX2 肝癌瘤体,最适合行血管造影检查.  相似文献   

6.
It is possible to arterially embolize liver tumours in small animal models with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. The aim of this study was to determine the response of hepatic tissue to arterial infusion of ferromagnetic particles. Eight rabbits containing hepatic VX2 carcinomas received a hepatic arterial infusion of ferromagnetic particles suspended in lipiodol. Four rabbits were sacrificed after 60 min to determine the acute tissue response, and the other four rabbits were sacrificed after 14 days to determine the longer-term tissue response. The tumour, normal hepatic parenchyma (NHP), lungs and gallbladder of each subject were examined using light microscopy, and chemically analysed for iron concentration. Large aggregates of particles embolized within the tumour vasculature. There was only a sparse distribution of particles in the NHP, with no acute tissue response. The tumour to NHP iron concentration ratio was 4.9. Particles also lodged in blood vessels of the gallbladder wall. Two weeks after infusion there were isolated foci of necrosis in the NHP, and macrophages were associated with particle aggregates, which were also observed within multinucleated giant cells. There was no evidence that particles embolized in the lungs. Hepatic arterial infusion of ferromagnetic particles suspended in lipiodol resulted in excellent tumour targeting with no acute tissue reaction in the NHP, and no evidence of pulmonary embolization. After 14 days there was evidence of phagocytosis of the particles in NHP, but not in the tumour tissue. However, the suspension caused multiple foci of infarction in NHP, probably due to occlusion of larger arteries.  相似文献   

7.
OBJECTIVE: To explore a method of establishing a rabbit model of superior vena cava obstruction (SVCO) by injecting VX2 tumor cell suspension transcutaneously under ultrasound guidance. METHODS: A suspension of VX2 tumor cells was prepared under sterile conditions. Fifteen adult healthy New Zealand White rabbits were enrolled in the experiment. Under ultrasound guidance, about 0.1 ml of the living tumor cell suspension was transcutaneously injected in front of the anterior wall of the right superior vena cava (SVC). The lumen, wall, blood flow of SVCs and adjacent tissues were examined with gray-scale and color Doppler ultrasonography, every 3 days starting from the 9th day after injection. Meanwhile, CT scanning and digital subtraction angiography (DSA) were also performed. The rabbits were dissected immediately after death and tissue samples were collected for pathologic examination. RESULTS: Fourteen out of 15 rabbits developed tumors that were located close to SVCs and/or SVCs cavity, which was shown by ultrasonography. The diameters of the tumors were 80.7 +/- 4.3 mm. These tumors grew close to SVCs area and resulted in compression and infiltration of SVCs. CT scanning and DSA confirmed the establishment of the SVCO model. The achievement rate of the SVCO model was 93.3%. No rabbit died of complications. CONCLUSION: A method of establishing a rabbit SVCO model by injecting VX2 tumor cell suspension under ultrasonographic guidance was established successfully, and it proved to be simple, effective and repeatable. The imaging characteristics of this model are in good accordance with those of SVCO in patients.  相似文献   

8.
目的:探讨兔肝脏VX2肿瘤射频消融术(radio-frequency ablation,RFA)后残余肿瘤组织中基质金属蛋白酶9(MMP-9)表达。方法:超声引导下将VX2肿瘤组织块接种于23只新西兰大白兔肝脏中,造模成功后随机分为5组,对照组(A组,n=3),不行RFA治疗;余20只为实验组行RFA治疗,在超声引导下射频针插入肿瘤偏心位置,展开电极致损毁范围最大为肿瘤总体积的2/3,人为造成残存肿瘤组织。根据治疗结束后不同时间点分为4组:0小时组(B组,n=5)、术后1周组(C组,n=5)、术后2周组(D组,n=5)、术后4周组(E组,n=5),行超声检查结束后处死大白兔,取肿瘤组织采取免疫组化法观察残存肿瘤组织中及未治疗肿瘤组中MMP-9的表达情况。结果:RFA术后0小时、1周、2周、4周残存肿瘤组织中MMP-9的表达均较对照组明显降低(P0.05)。结论:RFA治疗后残存肿瘤细胞中MMP-9水平表达减低。  相似文献   

9.
A head and neck cancer model is developed using the VX2 carcinoma cell line injected s.c. in both ears of New Zealand White (NZW) rabbits. The study is focused on the effects of intraarterial embolization of the carcinomas with a new type of dextran hydrogel microspheres. During the phase of exponential growth the tumour-surface doubling-time was 7.1+/-2.0 days. Standard deviation in growth of the tumours was significantly larger between separate animals than between tumours growing in the left and right auricle of each individual animal (2.0 versus 0.65 days). A fresh cell suspension containing at least 10 x 10(6) vital tumour cells was necessary to yield a tumour-take of 85%. The caudal auricular artery perfuses the caudal half of the external ear and is very suitable for macroscopic cannulation. Histological evaluation shows, that the use of dextran hydrogel microspheres of at least 25 microm in combination with ligation of non-tumour perfusing branches of the central auricular artery yields diffuse embolization of the VX2 carcinoma. This tumour model can be of use in further studies to optimize particle size and dosage for embolization as well as to evaluate the effect of different anti-neoplastic drugs, slowly released by controlled degradation of dextran microspheres.  相似文献   

10.
11.
目的:研究MRI对血源性脑及脑膜转移瘤动物模型转移灶的检出效果。方法:18只新西兰大白兔随机分为3组,分别从左颈总动脉内接种VX2瘤细胞,A组:20%甘露醇注入5min后接种VX2瘤细胞:B组:20%甘露醇注入5min后,加入肝素再接种VX2瘤细胞;C组,对照组,单纯注入等量生理盐水。术后2周后行MRI检查。病理取材HE染色光镜下观察。结果:平扫:A组,1只(1/6)发现脑内结节并脑膜结节样增厚,T1WI为等信号,T2WI为稍高信号。B组,2只(2/6)为脑内多发结节,T1WI为等信号,TM为稍高信号。2只(2/6)脑膜结节样增厚。增强扫描:A组,2只(2/6)脑内见强化结节灶;直径在1.5mm-7.0mm之间。4K(4/6)脑膜线样增厚或结节样增厚强化。B组,6只(6/6)脑内见直径在1.5mm-5.0mm的高信号结节,其中5只为脑内多发结节灶;4只(4/6)脑膜线样或结节样增厚强化,左侧为主,其中2只(2/6)为双侧脑膜增厚。增强扫描A、B组问脑内病灶差异有统计学意义(Fisher’s确切概率值为0.04)。C组平扫及增强扫描均未见异常信号。结论:上述方法制成的动物模型可为医学影像学研究提供可靠的动物模型,加入肝素可提高瘤灶的形成几率,并证实血脑屏障对脑转移瘤的形成起重要作用。MRI增强检查是检出脑内及脑膜转移瘤的首选方法。  相似文献   

12.
目的建立VX2肿瘤侵犯下腔静脉(inferior vena cava,IVC)的动物模型,观察3种不同手术方式对实验动物预后的影响。方法成功建立VX2肿瘤侵犯IVC的动物模型,彩超下证实;将实验动物随机均分为A、B、C三组,分别予以彻底切除IVC和肿瘤、不予重建、彻底切除后人工血管进行重建处理,切下的IVC均送病检。分别于手术后每周彩超观察IVC,出现闭塞的IVC在DSA(digtal subtraction angiography,DSA)下观察侧枝循环建立情况。观察实验动物自然死亡时间,并解剖。结果超声发现3周时所有实验动物均有肿瘤生长(2.75±0.91cm2),IVC管腔无明显狭窄(2.53±0.23 mm);DSA显示,人工血管中长期通畅率低,随时间变化实验组可见侧支循环建立和腹壁浅静脉增粗逆流;A、B两实验组生存时间显著高于对照组C组(P1〈0.05;P2=0.036〈0.05);两实验组中A组生存时间显著高于B组(P3=0.04〈0.05)。两实验组远处转移无差异,均显著低于对照组。结论彻底切除肿瘤可以提高实验动物的术后生存时间和生存率;兔IVC人工血管重建中长期通畅率低,且围手术期死亡率高,生存时间也较不重建组低。  相似文献   

13.
目的:介绍一种兔VX2肿瘤的传代和接种方法及其应用经验和体会,从而更好的利用此模型进行生物医学研究。方法:从荷瘤新西兰大白兔取活性良好的肿瘤组织块,制备肿瘤细胞悬液,过滤后接种于健康成年新西兰兔左后肢肌肉内。通过一般观察、MRI和大体及病理学切片对肿瘤进行验证。结果:肿瘤传代和接种后生长良好,MRI、大体及组织学验证保持了VX2的肿瘤特点。结论:本研究介绍的兔VX2肿瘤的传代与接种方法稳定、可靠,值得大家推广和应用。  相似文献   

14.

Objectives

This study aimed to observe the changes in tumor angiogenesis after heated lipiodol (60°C) infusion via the hepatic artery in a rabbit model of VX2 liver cancer.

Materials and Methods

Twenty rabbits with VX2 hepatic tumors were randomly divided into 2 groups (10 rabbits in each group). Under anesthesia, a trans-catheter hepatic arterial infusion was performed, and lipiodol (37°C; control group) or heated lipiodol (60°C; treated group) was injected into the hepatic arteries of the animals. Then, changes in tumor angiogenesis were assessed using the following markers and methods. 1. Vascular endothelial growth factor receptor (VEGFR) and vascular endothelial growth factor (VEGF) expression levels in the tumor were assessed using western blotting and real-time quantitative polymerase chain reaction (PCR). 2. Proliferating cell nuclear antigen (PCNA) expression in the tumor was assessed through immunohistochemical staining. 3. The morphological changes in tumor vascular endothelial cells were observed using transmission electron microscopy (TEM).

Results

VEGFR and VEGF mRNA and protein expression levels were reduced in the treated group compared to the control group. PCNA protein showed reduced expression levels in the treated group compared to the control group. TEM indicated that the endothelial cell endoplasmic reticulum expanded, the chondriosome was swollen, and the endothelial cell microvilli were decreased after heated lipiodol infusion.

Conclusions

The tumor angiogenesis of rabbits with VX2 cancer was inhibited after arterial heated lipiodol infusion compared to lipiodol infusion.  相似文献   

15.
王冬冬  曹秀峰  吕进  朱斌  李苏卿 《生物磁学》2011,(3):452-455,492
目的:通过研究不同活度的125I粒子以及联合TACE治疗兔VX2肝移植癌的疗效及其病理基础,探讨125I粒子组织间植入治疗肝癌的有效性。方法:建立兔VX2肝癌模型。60只肝癌模型兔随机分成5组,对照组(A组)植入空白剂量(0mCi)125I粒子,B组植入1.0mCi125I粒子,C组植入0.7mCi125I粒子,D组植入0.4mCi125I粒子,E组植入0.7mCi125I粒子+TACE。观察植入前后各组肿瘤体积并计算抑瘤率,切除肿瘤组织及周围正常组织进行常规病理检查。结果:各治疗组肿瘤大小在治疗前后比较具有统计学差异(P〈0.01),均小于同期对照组(A组)(P〈0.01)。在不同观察时期抑瘤率差别均有统计学意义(P〈0.05),各个组间抑瘤率差异在治疗后2周最为明显(P〈0.01),但均高于D组(P〈0.01)。治疗后6周病理提示D组部分组织内仍可见少量肿瘤细胞,而其余各治疗组均未见明显的肿瘤细胞残存,B组对周围肝组织损伤较大,C组、E组适中。总体疗效E组优于其余各治疗组。结论:125I粒子联合TACE治疗肝癌效果明显优于单一的治疗方案,是肝癌目前较为理想的治疗方案,其中单个粒子活度以0.7mCi左右较为适宜。  相似文献   

16.
Lymph node topography of the head and neck in New Zealand White rabbits   总被引:1,自引:0,他引:1  
Investigations of the lymphogenic metastatic spread of VX2 carcinomas in New Zealand White rabbits require an exact knowledge of the topography of cervical and facial lymph nodes. The topography of neck lymph nodes was evaluated from 16 rabbits macroscopically, histologically and by lymphographic investigations, and the possibility of their surgical removal (neck dissection) was examined. The upper aerodigestive tract and the ear of New Zealand White rabbits drain via four consistent groups of 12-18 lymph nodes. Except for the paratracheal lymph node, they are all easily accessible to surgery. The data presented in this study encourage the use of induced VX2 carcinomas in New Zealand White rabbits as an animal model to study the lymphogenic metastatic spread of squamous cell carcinomas of the head and neck. Such investigations could lead to an improvement of surgical and pharmaceutical treatment of this tumour entity.  相似文献   

17.
兔脑种植VX2肿瘤动物模型的建立   总被引:5,自引:0,他引:5  
目的建立兔VX2肿瘤脑内种植动物模型,观察其生长特性。方法采用兔脑内VX2肿瘤组织块种植法将VX2肿瘤组织块种植入24只成年New Zealand大白兔右侧大脑皮质内,用B超检测肿瘤的生长情况,在实验兔在肿瘤种植后第13、171、9、21、232、5天取材,进行组织学观察。并观察实验兔在种植VX2肿瘤后的生存期及出现厌食、偏瘫等神经系统体征和死亡的时间。结果VX2肿瘤组织块种植入脑内后荷瘤兔的中位生存期为24.5 d,平均生存期为24.8 d,肿瘤体积随种植后的时间在对数坐标中接近一条直线。VX2肿瘤种植入兔脑17 d后血供较丰富、呈鱼肉状生长,与正常脑组织边缘界限不清楚,第17~19天肿瘤中心出现坏死并出现腹腔内转移。光镜下从VX2肿瘤种植后第17天开始肿瘤细胞向正常脑组织浸润,并形成瘤巢,瘤周脑组织形成水肿带。结论在缺乏兔源性脑肿瘤的情况下,采用兔VX2肿瘤组织块颅内种植能较好模拟颅内肿瘤生长,为对脑肿瘤的某些实验研究提供条件。  相似文献   

18.
Fluorescence-guided resection (FGR) and photodynamic therapy (PDT) have previously been investigated separately with the objectives, respectively, of increasing the extent of brain tumour resection and of selectively destroying residual tumour post-resection. Both techniques have demonstrated trends towards improved survival, pre-clinically and clinically. We hypothesize that combining these techniques will further delay tumour re-growth. In order to demonstrate technical feasibility, we here evaluate fluorescence imaging and PDT treatment techniques in a specific intracranial tumour model. The model was the VX2 carcinoma grown by injection of tumour cells into the normal rabbit brain. An operating microscope was used for white light imaging and a custom-built fluorescence imaging system with co-axial excitation and detection was used for FGR. PDT treatment light was applied by intracranially-implanted light emitting diodes (LED). The fluorescent photosensitizer used for both FGR and PDT was ALA-induced PpIX. For PDT, ALA (100 mg kg(-1)) and low light doses (15 and 30 J) were administered over extended periods, which we refer to as metronomic PDT (mPDT). Eighteen tumour bearing rabbits were divided equally into three groups: controls (no resection); FGR; and FGR followed by mPDT. Histological whole brain sections (H&E stain) showed primary and recurrent tumours. No bacteriological infections were found by Gram staining. Selective tumour cell death through mPDT-induced apoptosis was demonstrated by TUNEL stain. These results demonstrate that the combined treatment is technically feasible and this model is a candidate to evaluate it. Further optimization of mPDT treatment parameters (drug/light dose rates) is required to improve survival.  相似文献   

19.

Background

Brain metastasis is a common disease with a poor prognosis. The purpose of this study is to test feasibility and safety of the animal models for brain metastases and to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to enhance detection of brain metastases.

Methods

With approval from the institutional animal ethics committee, 18 New Zealand rabbits were randomly divided into three groups: Group A received an intra-carotid infusion (ICI) of mannitol followed by VX2 cells; group B received successive ICI of mannitol and heparin followed by VX2 cells; and group C received an ICI of normal saline. The survival rate and clinical symptoms were recorded after inoculation. After two weeks, conventional MRI and DCE-MRI were performed using 3.0 Tesla scanner. The number of tumors and detection rate were analyzed. After MRI measurements, the tumors were stained with hematoxylin-eosin.

Results

No rabbits died during the procedure. The rabbits had common symptoms, including loss of appetite, lassitude and lethargy, etc. at 10.8±1.8 days and 8.4±1.5 days post-inoculation in group A and B, respectively. Each animal in groups A and B re-gained the lost weight within 14 days. Brain metastases could be detected by MRI at 14 days post-inoculation in both groups A and B, with metastases manifesting as nodules in the brain parenchyma and thickening in the meninges. DCE-MRI increased the total detection of tumors compared to non-contrast MRI (P<0.05). The detection rates of T1-weighted image, T2-weighted image and DCE-MRI were 12%, 32% and 100%, respectively (P<0.05). Necropsy revealed nodules or thickening meninges in the gross samples and VX2 tumor cytomorphologic features in the slides, which were consistent with the MRI results.

Conclusions

The VX2 rabbit model of brain metastases is feasible, as verified by MRI and pathologic findings, and may be a suitable platform for future studies of brain metastases. Functional DCE-MRI can be used to evaluate brain metastases in a rabbit model.  相似文献   

20.
兔VX2肝癌模型制作技术改良   总被引:1,自引:0,他引:1  
目的探讨制作兔VX2肝癌模型的新技术、新方法。方法将新西兰兔30只随机等分为3组,分别为嵌插组、改良嵌插组和经皮穿剌组。分别按不同方法建立肝癌模型,于建模后第1、2、3周分别进行CT扫描,评估肿瘤大小。3周后处死动物进行解剖,观察肝脏成瘤及转移情况,比较各组转移率,并行常规病理组织学检查。结果 30只动物建模成功28只,成功率93%,经皮穿剌组有2只肝脏未见种植灶,嵌插组和改良嵌插组全部种植成功。改良嵌插组腹壁转移率显著低于嵌插组和经皮接种组。结论改良嵌插法3周内不会形成接种部位腹壁以及远处的转移,是一种理想的移植性肝癌模型建模方法。  相似文献   

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