Rabbit Tumor Research Articles

Evaluation of efficacy of anti-angiogenesis therapy for VX2 hepatic tumors in rabbits by spectral CT and CT perfusion imaging

Evaluation of efficacy of anti-angiogenesis therapy for VX2 hepatic tumors in rabbits by spectral CT and CT perfusion imaging

Local hyperthermia for esophageal cancer in a rabbit tumor model: Magnetic stent hyperthermia versus magnetic fluid hyperthermia

Magnetic-mediated hyperthermia (MMH) is a promising local thermotherapy approach for cancer treatment. The present study investigated the feasibility and effectiveness of MMH in esophageal cancer using a rabbit tumor model. The therapeutic effect of two hyperthermia approaches, magnetic stent hyperthermia (MSH), in which heat is induced by the clinical stent that is placed inside the esophagus, and magnetic fluid hyperthermia (MFH), where magnetic nanoparticles are applied as the agent, was systematically evaluated. A rabbit esophageal tumor model was established by injecting VX2 carcinoma cells into the esophageal submucosa. The esophageal stent was deployed perorally into the tumor segment of the esophagus. For the MFH, magnetic nanoparticles (MNPs) were administered to the rabbits by intratumoral injection. The rabbits were exposed under a benchtop applicator using an alternative magnetic field (AMF) with 300 kHz frequency for the hyperthermia treatment. The results demonstrated that esophageal stents and MNPs had ideal inductive heating properties upon exposure under an AMF of 300 kHz. MSH, using a thermal dose of 46°C with a 10-min treatment time, demonstrated antitumor effects on the rabbit esophageal cancer. However, the rabbit esophageal wall is not heat-resistant. Therefore, a higher temperature or longer treatment time may lead to necrosis of the rabbit esophagus. MFH has a significant antitumor effect by confining the heat within the tumor site without damaging the adjacent normal tissues. The present study indicates that the two hyperthermia procedures have therapeutic effects on esophageal cancer, and that MFH may be more specific than MSH in terms of temperature control during the treatment.

Correction: Noninvasive Assessment of Gene Transfer and Expression by In Vivo Functional and Morphologic Imaging in a Rabbit Tumor Model

Correction: Noninvasive Assessment of Gene Transfer and Expression by In Vivo Functional and Morphologic Imaging in a Rabbit Tumor Model

Hepatic Parenchymal Changes following Transcatheter Embolization and Chemoembolization in a Rabbit Tumor Model

ObjectiveTo compare the effects of transcatheter arterial chemoembolization (TACE) with transcatheter arterial embolization (TAE) on liver function, hepatic damage, and hepatic fibrogenesis in a rabbit tumor model.Materials and MethodsThirty-nine New Zealand white rabbits implanted with VX2 tumors in the left liver lobes were randomly divided into three groups: TAE, TACE, and control group. In the TAE group (n = 15), polyvinyl alcohol particles (PVAs) were used for left hepatic artery embolization. In the TACE group (n = 15), the tumors were treated with left hepatic arterial infusions of a suspension of 10-hydroxycamptothecin and lipiodol, followed by embolization with PVAs. In the control group (n = 9), the animals received sham treatment with distilled water. Serum and liver samples were collected at 6 hours, 3 days and 7 days after treatment. Liver damage was measured using a liver function test and histological analyses. Liver fibrogenesis and hepatic stellate cell (HSC) activation were evaluated using Sirius Red and anti-alpha-smooth muscle actin (α-SMA) immunohistochemical stains.ResultsTACE caused liver injury with greater increases in serum alanine aminotransferase and aspartate aminotransferase levels on day 3 (P<0.05). Histological analyses revealed increased hepatic necrosis in adjacent non-tumorous liver tissue from day 3 compared to the TAE group (Suzuki score of 2.33±1.29 versus 1.13±1.18, P = 0.001). HSC activation and proliferation were significantly increased in the TACE group compared to the control group at 3 and 7 days after treatment (0.074±0.014 vs. 0.010±0.006, and 0.088±0.023 vs. 0.017±0.009, P<0.05). Sirius Red staining demonstrated a statistically significant increase in collagen deposition in the livers in the TACE group 7 days after embolization compared to the control group (0.118±0.012 vs. 0.060±0.017, P = 0.05).ConclusionThe results of this animal study revealed that TACE induced prominent hepatocellular damage and hepatic fibrogenesis, which compromised liver function and may be responsible for chronic liver decompensation.

Hepatic arterial embolization with glycolic acid-ethylcellulose microspheres in treatment of hepatic tumor in rabbits

Objective To evaluate the therapeutic effects of glycolic acid-ethylcellulose microspheres infused via hepatic artery on hepatocarcinoma in rabbits.Methods Thirty New Zealand white rabbits were implanted with VX2 liver tumor and received CT examination after 13 days.The tumor volumes were calculated;the tumors were numbered according to volume and were divided into 3 groups by random number table.3 F catheters were inserted via right femoral artery to hepatic artery in all animals;the nutrition arteries of the tumor were observed by injecting contrast media;and then therapeutic agents were given through the catheter.Group A(n=10) was given glycolic acid-ethylcellulose microspheres(0.023 g/1 ml),Group B(n=10) was given lipiodol(1 ml),and Group C(n=10) was given normal saline(1 ml).The liver function and tumor growth were observed before and after treatment;the pathological changes of tumor tissues and the survival of rabbits were observed with 5 randomly selected animals in each group.Results The liver function and the tumor volumes were not significantly different among groups.One week after treatment,AST and ALT levels were significantly higher in Group A and B compared with those in Group C(P0.05).CT results showed that the tumor growth rates in group A and B were significantly smaller than that in Group C(P0.01),and that in group A was significantly smaller than that in Group B(P0.01).Pathological examination showed greatly thickened tumor fibrous capsule and large necrotic area in tumors in Group A and B,with loosely arranged tumor cells,pyknosis and greatly decreased pathologic mitosis.VEGF expression and proliferation activity in Group A were weaker than those in Group B.Compared with Group B and C,animals in Group A had a significantly longer survival time compared with group B and C(P0.05,P0.01).Conclusion Transcatheter infusion of glycolic acid-ethylcellulose microspheres is a safe and effective chemoembolization agent for treatment of rabbit hepatic tumors.

Noninvasive Assessment of Gene Transfer and Expression by In Vivo Functional and Morphologic Imaging in a Rabbit Tumor Model

PurposeTo evaluate the importance of morphology in quantifying expression after in vivo gene transfer and to compare gene expression after intra-arterial (IA) and intra-tumoral (IT) delivery of adenovirus expressing a SSTR2-based reporter gene in a large animal tumor model.Materials and MethodsTumor directed IA or IT delivery of adenovirus containing a human somatostatin receptor type 2A (Ad-CMV-HA-SSTR2A) gene chimera or control adenovirus (Ad-CMV-GFP) was performed in VX2 tumors growing in both rabbit thighs. Three days later, 111In-octreotide was administered intravenously after CT imaging using a clinical scanner. 111In-octreotide uptake in tumors was evaluated the following day using a clinical gamma-camera. Gene expression was normalized to tumor weight with and without necrosis. This procedure was repeated on nine additional rabbits to investigate longitudinal gene expression both 5 days and 2 weeks after adenovirus delivery. CT images were used to evaluate tumor morphology and excised tissue samples were analyzed to determine 111In-octreotide biodistribution ex vivo.ResultsVX2 tumors infected with Ad-CMV-HA-SSTR2 had greater 111In-octreotide uptake than with control virus (P<0.05). Intra-arterial and intra-tumoral routes resulted in similar levels of gene expression. Longitudinally, expression appeared to wane at 2 weeks versus 5 days after delivery. Areas of necrosis did not demonstrate significant uptake ex vivo. Morphology identified areas of necrosis on contrast enhanced CT and upon excluding necrosis, in vivo biodistribution analysis resulted in greater percent injected dose per gram (P<0.01) and corresponded better with ex vivo biodistribution(r = 0.72, P<0.01, Coefficient of the x-variable = .72) at 2 weeks than without excluding necrosis (P<0.01).ConclusionTumor specificity and high transgene expression can be achieved in tumors via both tumor directed intra-arterial and intra-tumoral delivery in a large animal tumor model. Using clinical machines, morphologic imaging contributes to functional imaging for quantifying SSTR2-based reporter expression in vivo.

The study of in vivo acute effect of two different delivery modalities of iron oxide core with titanium dioxide shell nanoparticles in rabbits liver tumor.

e22204 Background: To compare intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core with titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits and detect the NPs distribution and effect of NPs presence on the target tumor and other rabbit’s organs. Methods: After obtaining the IACUC approval, liver tumors were obtained by implantation of tumor tissue obtained from a hind limb VX2 tumor of donor rabbits. NPs were delivered either IV or IC. After rabbit termination, 2 hours post NPs injection, tumor, liver, kidney, lung and spleen were harvested, split in half and a part of it was frozen while the remainder was formalin fixed and paraffin embedded. To assess the NPs distribution in 2D we stained 5um thick paraffin tissue sections using Dopamine-Biotin-DHS histochemical (HC) staining followed by Nanozoomer microscopy analysis. H and E staining, TUNEL assay and Ki67 immunohistochemistry were also done. X-ray Fluorescence Microscopy (XFM) was used to quantify the NPs. Frozen tissue was used for bulk NPs concentration analysis using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Results: This study included ten rabbits; 3 rabbits had IV NPs injections, 3 had IC NPs injection, 2 control and 2 donors. ICP-MS analysis showed statistically significant higher NPs concentration in tumors of IC arm vs. IV arm (p= 0.0356), while there was higher concentration of NPs in liver (p=0.00077) and spleen (p = 0.01356) of IV vs. IC arms but no difference in kidneys or lungs. These findings were consistent with results from HC and XFM analyses. HC 2D analysis of NPs distribution showed that the RES have taken up the NPs non-specifically. There were no statistically significant differences between the treatment groups regarding the Ki67 proliferation or the TUNEL apoptosis indices or when control rabbits were compared to NPs treated rabbits. Conclusions: Both IV and IC NPs injection are feasible modalities for delivering NPs to tumors with acceptable acute systemic effects and comparable tumor effect. IV delivery increased sequestration of the NPs by RES and their accumulation in spleen and liver.

Prevalence of Tumours in Domestic Animals in the Lower Silesia (Poland) in 2009–2011

Abstract The study aimed at the analysis of prevalence frequency and localisation of tumours in domestic animals. The research material comprised 4,212 tumours developed in dogs, cats, horses, and exotic animals, isolated during surgery, autopsy or biopsy, performed for the purpose of histopathological diagnosis. The most numerous group involved canine tumours, including 3,585 cases (85.1%), followed by tumours in cats (532 cases, 12.6%), ferrets (34 cases, 0.81%), rats (19 cases, 0.45%), horses (15 cases, 0.36%), and rabbits (14 cases, 0.33%). A significant increase in incidence of tumours was noted, as compared to studies performed in the same region of Poland in 1957-1995 and 2000-2004 or in 2005-2008. This was particularly evident in exotic animals, in which 80 cases (1.9%) were detected in 2009-2011 but only 20 cases (1.2%) in 2005-2008. The most frequent localisation of neoplasia involved the skin, subcutaneous tissue, and mammary gland.

Radiofrequency Ablation and Immunostimulant OK-432: Combination Therapy Enhances Systemic Antitumor Immunity for Treatment of VX2 Lung Tumors in Rabbits

To evaluate whether antitumor immunity is enhanced systemically by combining radiofrequency ablation (RFA) and local injection of an immunostimulant, OK-432. Experiments were approved by the institutional animal care committee. Experimental Japanese rabbits inoculated with VX2 tumors in the lung and the auricle were randomized into four groups of eight: control (supportive care), RFA (RFA of lung tumor), OK-432 (direct injection of OK-432 into lung tumor), and combination therapy (lung RFA and direct OK-432 injection into lung tumor). All procedures were performed 1 week after implantation of VX2 tumors (week 1). In addition, a VX2 tumor rechallenge test was performed in the RFA and combination therapy groups. Survival time was evaluated by means of the Kaplan-Meier method and by using the log-rank test for intergroup comparison. Mean auricle tumor volumes were calculated every week. Specific growth rates (SGRs) were calculated and compared by using the Mann-Whitney test. The median survival times of the control, RFA, OK-432, and combination therapy groups were 23, 36.5, 46.5, and 105 days, respectively. Survival was significantly prolonged in the combination therapy group when compared with the other three groups (P <.05). The mean auricle tumor volume decreased only in the combination therapy group. The mean auricle tumor volumes of the combination therapy group from week 1 to week 7 were 205, 339, 264, 227, 143, 127, and 115 mm(3). SGR in the combination therapy group became significantly smaller than those in the other three groups (P < .05). In the rechallenge test, the volume of all reimplanted tumors decreased. Combining RFA with local injection of immunostimulant OK-432 may lead to indirectly activation of systemic antitumor immunity.

In vivoassessment of intratumoral aspirin injection to treat hepatic tumors

To study the antineoplastic efficacy of 10% aspirin intralesional injection on VX2 hepatic tumors in a rabbit model. Thirty-two male rabbits (age: 6-9 wk; body weight: 1700-2500 g) were inoculated with VX2 hepatic tumor cells (10(4) cells/rabbit) via supra-umbilical median laparotomy. On day 4 post-implantation, when the tumors were about 1 cm in diameter, the rabbits were randomly divided into the following groups (n = 8 each group) to assess early (24 h) and late (7 d) antineoplastic effects of intratumoral injection of 10% bicarbonate aspirin solution (experimental groups) in comparison to intratumoral injection of physiological saline solution (control groups): group 1, 24 h control; group 2, 24 h experimental; group 3, 7 d control; group 4, 7 d experimental. The serum biochemistry profile (measurements of glycemia, alkaline phosphatase, gamma-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase) and body weight measurements were obtained for all animals at the following time points: D0, before tumor implant; D4, day of treatment; D5, day of sacrifice for groups 1 and 2; D11, day of sacrifice for groups 3 and 4. Gross assessments of the abdominal and thoracic cavities were carried out upon sacrifice. The resected liver tissues, including hepatic tumors, were qualitatively (general morphology, signs of necrosis) and quantitatively (tumor area) assessed by histopathological analysis. Gross examination showed no alterations, besides the left hepatic lobe tumors, had occurred in the thoracic and abdominal cavities of any animal at any time point evaluated. However, the features of the tumor foci were distinctive between the groups. Compared to the control groups, which showed normal unabated tumor progression, the aspirin-treated groups showed imprecise but limited tumor boundaries and a general red-white coloration (indicating hemorrhaging) at 24 h post-treatment, and development of yellow-white areas of a cicatricial aspect at 7 d after treatment. At all time points evaluated, all except one biochemical parameters tested within the reference range (P > 0.05); a significant increase was detected in the alkaline phosphatase level of the control group 3 on D11 (P < 0.05). At 24 h post-treatment, the aspirin-treated groups showed extensive coagulation necrosis accompanied by a remarkable absence of viable tumor foci; at 7 d after treatment, the tumors had completely disappeared in these animals and fibrous necrotic nodules had developed. In contrast, throughout the study course, the tumors of the control groups remained unchanged, showing tumor nodules without necrosis at the time point corresponding to 24 h post-treatment and increased amounts of tumor nodules at the time point corresponding to 7 d post-treatment. Quantitative analysis of the remaining tumor area revealed that the aspirin-treated groups had significantly smaller tumor foci at 24 h post-treatment (8.5% ± 0.7%) and at 7 d after treatment (11.0% ± 4.2%), compared to those in the control groups (24 h: 98.5% ± 1.5% and 7 d: 94.0% ± 2.7%; both, P < 0.005). Intralesional injection of a 10% aspirin solution causes destruction of VX2 hepatic tumors in rabbits without evidence of relapse at 7 d after treatment administration.

Accumulation of phase-shift nanoemulsions to enhance MR-guided ultrasound-mediated tumor ablation in vivo.

Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is being explored as a non-invasive technology to treat solid tumors. However, the clinical use of HIFU for tumor ablation applications is currently limited by the long treatment times required. Phase-shift nanoemulsions (PSNE), consisting of liquid perfluorocarbon droplets that can be vaporized into microbubbles, are being developed to accelerate HIFU-mediated heating. The purpose of this study was to examine accumulation of PSNE in intramuscular rabbit tumors in vivo. MR images were acquired before and after intravenous injection of gadolinium-containing PSNE. MR signal enhancement was observed in rabbit tumors up to six hours after injection, indicating that PSNE accumulated in the tumors. In addition, PSNE vaporization was detected in the tumor with B-mode ultrasound imaging, and MR thermometry measurements indicated that PSNE accelerated the rate of HIFU-mediated heating. These results suggest that PSNE could dramatically improve the efficiency and clinical feasibility of MRgHIFU.

Spontaneous Extraskeletal Osteosarcoma in a Rabbit (&lt;i&gt;Oryctolagus cuniculus&lt;/i&gt;): Histopathological and Immunohistochemical Findings

A spontaneously occurring subcutaneous mass in the left forelimb of a nine-year-old rabbit (Oryctolagus cuniculus) was examined histopathologically and immunohistochemically. Clinically, edema and hemorrhage were seen around the mass. No connection of the tumor mass to the appendicular skeleton was found. The tumor was arranged in a solid growth pattern and irregular bundles, and neoplastic cells were polygonal to spindle-shape. Osteoid (positive for osteocalcin) and multinucleated giant cells were diffusely or focally seen. Neoplastic cells were positive for vimentin, osterix and Ki-67, indicating the nature of osteoblasts with proliferating activity, but negative for α-smooth muscle actin, desmin or CD204. Based on these findings, a diagnosis of extraskeletal osteosarcoma was made, a very rare tumor both in laboratory and pet rabbits.

Enhanced drug delivery in rabbit VX2 tumours using thermosensitive liposomes and MRI-controlled focused ultrasound hyperthermia

Purpose: The efficacy of anticancer drugs in solid tumours is impaired by their inability to reach all cancer cells in sufficient concentration to cause cytotoxicity. Hyperthermia-triggered release of drugs from thermosensitive liposomes can increase tumour drug concentration, but tumour-specific drug delivery requires precise temperature control, and effects on microregional distribution of anticancer drugs in tumours are unknown. Here we evaluate thermally triggered release of doxorubicin in a rabbit tumour model by comparing free versus thermosensitive liposomal doxorubicin administered systemically during magnetic resonance imaging (MRI)-controlled focused ultrasound hyperthermia.Materials and methods: Twelve rabbits with a transplanted VX2 tumour in each thigh had a 10 mm diameter region in one tumour heated to 43°C using focused ultrasound with temperature control by MRI thermometry. Delivery of doxorubicin to tumours and normal tissues was quantified by fluorescence in tissue homogenates, and by fluorescence microscopy.Results: Using thermosensitive liposomal doxorubicin (2.5 mg/kg), doxorubicin concentrations in heated tumours were 26.7 times higher than in unheated tumours (n = 7, p = 0.017, two-sided Wilcoxon signed-rank test). There was no significant enhancement with free doxorubicin in heated versus unheated tumours (n = 3, p = 0.5). With thermosensitive liposomes (8.3 mg/kg), fluorescence microscopy demonstrated increased doxorubicin fluorescence in heated versus unheated tumours, co-localised with nuclear staining throughout the tumour.Conclusions: Localised image-guided delivery of high concentrations of doxorubicin to cancer cells was achieved non-invasively in implanted tumours with temperature-sensitive drug carriers and a preclinical MRI-controlled focused ultrasound hyperthermia system.

Enhanced tumor growth after portal vein embolization in a rabbit tumor model

BackgroundPreoperative portal vein embolization (PVE) is used to increase future remnant liver volume through induction of hepatocellular regeneration. This event, however, potentially enhances tumor growth. The aim of our study was to assess tumor growth and liver regeneration after PVE in a rabbit hepatic tumor model. The VX2 carcinoma is derived from a virus-induced papilloma tumor in rabbits. The tumor grows rapidly, and its blood supply is similar to that of human hepatocellular carcinoma. Materials and methodsTwo weeks after subcapsular implantation of a VX2 carcinoma in the cranial liver lobe, New Zealand White rabbits were allocated to a control or PVE group (n = 5 per group). In the PVE group, the portal vein branch to the cranial liver lobes (80%) was embolized using particles and coils, leaving the caudal liver lobe (20%) free. In the tumor control group, the liver was mobilized. Computed tomography volumetry was performed on days 3, 7, 10, and 14. Tumor growth rate (TGR), hepatocellular proliferation rate, and liver damage parameters were assessed before PVE and on days 1, 3, 7, 10, and 14. ResultsPortography confirmed complete occlusion of the portal vein branch to the cranial liver lobes in all PVE rabbits. The hypertrophy response and proliferation rate in the nonembolized liver lobes were significantly higher in the PVE group, which was confirmed by liver-to-body weight index assessment. TGR was increased in both groups, with a significantly larger increase in the PVE group over time (day 14: mean, 34.4 ± 4.3 mL/d versus control: mean, 24.1 ± 7.2 mL/d; P < 0.05). ConclusionsTGR was significantly increased after PVE in the rabbit tumor model. This finding supports the notion that PVE potentially enhances tumor growth, along with the regeneration of the nonembolized liver lobe.

The effect of different one lung ventilation time on rabbit tumor necrosis factor-a and interleukin-8 in alveolar lavage fluid and surfactant protein-A in lung tissue

Objective To investigate the effect of different one-lung ventilation （OLV） time on TNF-a and IL-8 in rabbit bronchoalveolar lavage fluid, and the surfactant protein-A（SP-A） in lung tissue. Methods 60 male rabbits were randomly divided into group C, group O1, O2, O3, O4 and O5. GroupO1-O5 were established the fight lung ventilation and given l, 2, 3, 4 and 5 hours ventilation. Five rabbits in each group were made execution after completing ventilation, the other five rabbits were executed after feeding 24 h. TNF-a, IL-8 concentrations and SP-A of all rabbits were measured. Results When compared with group C during OLV, cell number in left and right lung of group O3-O5 increased over 4.6d±0.79（P〈0.01 ）, PaCO2 in group O4-O5 increased over 43.6±5.7 （P〈0.01）; TNF-a and IL-8 in left lung of group O3-O5 increased over 1O1.90±18.65（P〈0.01 ）, and TNF-a and IL-8 in right lung of group O4-O5 increased 256.16±30.32（P〈0.01 ）. 24 h later, cell number in left lung was still higher than 7.5±1.9 （P〈 0.01）; IL-8 in left lung of group O5 was still higher than 214.60±76.74 （P〈0.01）. TNF-a and IL-8 in left and fight lung had no difference during OLV and 24 h later（P〉0.05）. When compared with group C, SP-A in left lung of group O1-O3 increased over than 13.84±3.47 （P〈0.01）, and SP-A in right lung of group O1-O5 increased over than 5.51±1.48 （P〈0.01）, but SP-A decreased expression in group O4-O5. SP-A in left and fight lung of group O1-O5 increased expression more than 12.17±4.75 in 24 h later （P〈 0.01 ）. Conclusions Lung inflammatory response increases and SP-A decreases with prolonged OLV; especially when OLV is longer than 3 h, lung injury is difficult to repair even after 24 h. It should be avoided to have long time one-lung ventilation. Key words: One-lung ventilation; Inflammatory cytokines; Bronchoalveolar lavage; Surfactant protein-A

Histotripsy of Renal Implanted VX-2 Tumor in a Rabbit Model: Investigation of Metastases

To compare the number and density of lung metastases in histotripsy-treated and control subjects. Histotripsy is a noninvasive, nonthermal, pulsed ultrasound technology that produces targeted mechanical tissue fractionation. Histotripsy ablation of renal implanted VX-2 tumor has been previously demonstrated; however, concerns have been raised that mechanical forces associated with histotripsy might result in unwanted metastatic dissemination of tumor. VX-2 tumor was implanted into the left kidneys of New Zealand White rabbits. Twenty rabbits were treated with histotripsy on day 13; 8 were maintained as controls. All rabbits underwent left nephrectomy on day 14. Lungs were harvested and processed for histopathologic inspection on day 19. Whole-mount coronal lung sections were examined to determine the number of metastases and metastatic density. Tumors grew after implantation in all 28 cases and were localized with ultrasound in 19 of 20 subjects before treatment. Histology confirmed fractionation of tumor in all treatment rabbits. The number of lung metastases (88.7 vs 72.5; P = .29) and the metastatic density (8.9 vs 7.0 mets/cm(2); P = .22) were not statistically different between treatment and control rabbits. Histotripsy of renal implanted VX-2 tumor in an in-vivo rabbit model did not produce a statistically significant increase in number or density of lung metastasis. Data suggesting a trend toward increased metastases after histotripsy are overwhelmed by the high baseline rate of metastases in this aggressive tumor model. Further investigation using less aggressive tumor models is indicated to clarify this relationship.

Effects of transcatheter arterial chemoembolization with pingyangmycin-lipiodol emulsion on VX2 liver tumors in rabbits

To evaluate the changes induced in tumor tissue, the feeding artery, and neovascularization upon pingyangmycin-lipiodol emulsion treatment via transcatheter arterial chemoembolization (TACE) using the rabbit VX2 liver cancer model. The VX2 liver tumor model was established in 28 rabbits, and baseline tumor volume (V1, in mm3) was measured by spiral scan computed tomography (CT). Then, the rabbits were randomly divided into four groups (n = 7 each) and administered intraarterial therapies of: ultrafluid lipoidol embolization (group A); pingyangmycin (group B); pingyangmycin-lipiodol emulsion (group C); or saline (group D). All rabbits were sacrificed seven days later, and the response to therapy was determined by measuring the tumor volume (V2, in mm3), calculating the tumor growth rate, detecting expression of the vascular endothelial growth factor (VEGF) tumor biomarker, and performing histological analysis of the microvessel density (MVD) in the liver. Prior to therapy, the average V1 of the groups was statistically similar (A: 389.8+/-167.3, B: 404.1+/-184.9, C: 355.1+/-158.3, D: 378.1+/-189.0; (F = 0.257, P more than 0.05). In contrast, after therapy the average V2 of the groups was significantly different (A: 922.6+/-32.9, B: 665.9+/-99.9, C: 349.5+/-177.8, D: 1403.5+/-411.2; F = 26.23, P less than 0.05), as was the tumor growth ratio (A: 1.4, B: 0.6, C: -0.02, D: 2.7) and the mean positive ratio of VEGF (A: 57.1%, B: 42.9%, C: 28.6%, D: 100%; F = 8.407, P less than 0.05). MVD was highest in group D and lowest in group C (all, P less than 0.05). Bivariate correlation analysis revealed a positive correlation between VEGF expression and MVD (r = 0.743, P less than 0.01). Pingyangmycin exerts anti-tumor effects in the rabbit VX2 liver cancer model, but is more effective when administered as the combination therapy of pingyangmycin-lipiodol emulsion with TACE.

Contrast-enhanced ultrasonography of the rabbit VX2 tumor model: Analysis of vascular pathology

The accuracy of diagnosing tumors may be improved significantly by detecting the microvascular distribution. Indeed, contrast-enhanced ultrasonography (CEUS) has shown a distinct advantage in detecting microvasculature. This study aimed to determine the angiogenic characteristics of VX2 tumors in rabbits using CEUS. A total of 17 rabbits were injected with 0.5 ml VX2 cell suspension into the muscles of both hind legs to prepare the VX2 tumor models. At 14, 21, 28 and 35 days after tumor inoculation, CEUS was performed on the rabbits with 0.3 ml SonoVue following a local anesthesia. The pathological findings of the tumors were compared. A total of 12 rabbits survived after being inoculated with the tumor cells and developed a total of 38 tumors. The size of the tumors ranged from 1.12 to 10.85 cm. Using CEUS, all tumors demonstrated rim enhancement with some unenhanced regions. Enhancement began from the peripheral region and quickly showed internal reticular vessels. Regardless of the tumor size or the presence of necrosis, no complete enhancement of the tumors was observed. On microscopic examination, VX2 tumor cells were detected in striated muscles, immature blood capillaries and fibrosis tissues scattered in tumor nests. Immunohistochemical examination revealed that CD34+ cells appeared mainly in the muscles adjacent to vessels. In conclusion, CEUS may be an efficient method to evaluate angiogenesis and blood perfusion in VX2 tumors.

Combination of high-intensity focused ultrasound with nanoscale ultrasound contrast agent in treatment of rabbit breast VX2 tumors: a pilot study

To demonstrate ultrasound contrast agents to be important potentiators of high-intensity focused ultrasound (HIFU), we prospectively assessed the effectiveness of HIFU combined with nanoscale ultrasound contrast agents for the treatment of breast VX2 tumors in rabbits. We found that the change of grayscale value in the target area in the HIFU+nanobubble group was significantly higher than that in the HIFU+phosphate-buffered saline (PBS) group after irradiation (P<.01). The size of coagulation necrosis was also significantly larger in the HIFU+nanobubble group when compared to that in the HIFU+PBS group (P<.001). In conclusion, our study suggested that adding nanoscale ultrasound contrast agents may improve the treatment efficacy of HIFU for breast VX2 tumors in rabbits.

Abstract No. 380: Organ specific VX2 rabbit tumor models in interventional oncology

VX2 carcinoma is an anaplastic squamous cell carcinoma derived from a virus-induced papilloma in rabbits. The VX2 rabbit tumor model, originally proposed by Shope and Hurst in 1933 is one of the most commonly used model by interventional radiologists for studies involving liver, kidney, head and neck, uterine, lung, bowel, bone and pancreatic tumors. We present an educational exhibit summarizing the preferred and alternative organ specific methods/techniques and their advantages and disadvantages for inoculating VX2 tumors in New Zealand White Rabbits.