• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.291-300
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• 2018

The purpose of the present work is to establish an ultra-minimal invasive percutaneous puncture inoculation method for a VX2 orthotopic lung cancer rabbit model with fewer technical difficulties, lower mortality of rabbits, a higher success rate and a shorter operation time, to evaluate the growth, metastasis and apoptosis of tumor by CT scans, necropsy, histological examination, flow cytometry and immunohistochemistry. The average inoculation time was 10-15 min per rabbit. The tumorbearing rate was 100%. More than 90% of the tumor-bearing rabbits showed local solitary tumor with 2-10 mm diameters after two weeks post-inoculation, and the rate of chest seeding was only 8.3% (2/24). The tumors diameters increased to 4-16 mm, and irregularly short thorns were observed 3 weeks after inoculation. Five weeks post-inoculation, the liquefaction necrosis and a cavity developed, and the size of tumor grew further. Before natural death, the CT images showed that the tumors spread to the chest. The flow cytometry and immunohistochemistry indicated that there was less apoptosis in VX2 orthotopic lung cancer rabbit model compared to chemotherapy drug treatment group. Minimal invasive percutaneous puncture inoculation is an easy, fast and accurate method to establish the VX2 orthotopic lung cancer rabbit model, an ideal in situ tumor model similar to human malignant tumor growth.

• Journal of the Korean Society of Radiology
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• v.84 no.2
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• pp.441-453
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• 2023

Purpose To evaluate the development, location, and volume of a VX2 carcinoma using four inoculation methods in a rabbit brain. Materials and Methods Inoculation of a VX2 cell suspension was performed 1) on the appointed day, 2) seven days after storing a VX2 carcinoma in a freezer or 3) seven days after storing a VX2 carcinoma in a deep freezer after sacrificing the donor rabbits. 4) Without sacrificing the rabbits, the VX2 cell suspension was obtained using a gun biopsy, inoculation was performed on the appointed day. MR imaging was performed 10 days after inoculation. Brain tissues were obtained the day after. The development, location, and volume of the tumor were evaluated. Results Seventeen of the 18 rabbits inoculated on the appointed day developed tumors (average tumor volume, 106.32 mm³). One of five inoculated seven days after storing the VX2 tumor in the freezer, and three of five inoculated seven days after storing the VX2 tumor in the deep freezer developed tumors. Inoculation with a VX2 cell suspension obtained with a gun biopsy from five rabbits revealed development of tumors in only two rabbits. The tumors mostly developed in the superficial cortex. Conclusion TVX2 rabbit brain tumor model is easy to develop and revealed variable reproducibility. This model can be applicable in radiologic imaging, treatment planning, interventional treatment and drug delivery research. VX2 cell can be successfully innoculated into the brain using variable methods under researcher's variable conditions.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1191-1196
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• 2015

Background: Epidermal growth factor-like domain multiple 7 (EGFL7), recently identified as a secreted protein regulated by oxygen exposure, plays a critical role in promoting metastasis of hepatocellular carcinoma (HCC). Transcatheter arterial embolization (TAE) is widely used for treatment of HCC, resulting in hypoxia in tumors and surrounding liver tissues. Accordingly, we proposed the hypothesis that there could be a relationship between expression of EGFL7 and response to TAE. Materials and Methods: We established a rabbit VX2 liver tumor model using percutaneous puncture technique guided by computed tomography. TAE and sham embolization were performed and the results were confirmed by MRI 3 weeks after inoculation. We investigated the EGFL7 expression of the two groups at 6h and 3 days after intervention by means of immunohistochemistry and Western blotting. Results: Immunohistochemical staining demonstrated that the levels of EGFL7 protein significantly increased in the TAE-treated tumors compared with the control group at 6 hours (P=0.031) and 3 days (P=0.020) after intervention. Meanwhile, the relative EGFL7 protein detected in TAE group also up-regulated compared with the control group at 6 hours (P=0.020) and 3 days (P=0.024) after intervention. Conclusions: This study reveals an increase of EGFL7 expression in rabbit VX2 liver tumors after TAE. The role of EGFL7 in HCC, especially its biological behavior after TAE, needs further investigation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5089-5093
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• 2013

Objective: This study aimed to investigate the effects of BCRP expression on tumor recurrence, metastasis and treatment tolerability. Methods: A VX2 rabbit liver tumor model was established. Division was randomly into 4 groups: namely saline control group; A group, given hydration lipiodol; B group, Ad-p53; and C group, Ad-p53+hydration lipiodol. After the intervention, samples were collected to detect the BCRP, MMP-2, VEGF and PCNA. Results: The expression of BCRP, MMP-2, PCNA and VEGF in tumors in Group A had no significant difference when compared with the control group, while in B and C group, the values were significantly lower (P<0.05). BCRP positive expression in metastatic lesions significantly increased (P<0.05), and was correlated with MMP-2 ($X^2=6.172$, P=0.0131). Conclusions: BCRP may play an important role in mediating liver cancer multidrug resistance to chemotherapy, and may be correlated with tumor recurrence and metastasis, which leads to weakened treatment effect. Ad-P53 can down-regulate the expression of related genes, playing a role in multidrug resistance reversal and increased sensitivity in liver cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5799-5804
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• 2014

Background: Radiofrequency ablation (RFA) is the most widely used and studied method internationally for the local treatment of liver tumors. However, the extension of coagulation necrosis in one RFA procedure is limited and incomplete coverage of the damaged area can lead to a high local recurrence rate. Objective: In this study, we compared the effects of different solutions in enhancing hepatic radiofrequency by establishing a rabbit VX2 liver cancer model. We also determined the optimal solution to maximise effects on the extent of RFA-induced coagulation necrosis. Methods: Thirty VX2 tumor rabbits were randomly assigned to five groups: group A, RFA alone; group B, RFA with anhydrous ethanol injection; group C, RFA with 5% hypertonic saline injection; group D, RFA with lidocaine injection; and group E, RFA with a mixed solution. Routine ultrasound examinations and contrast-enhanced ultrasound (CEUS) of the ablation areas were performed after RFA. Then, we measured the major axis and transverse diameter and compared the areas of coagulation necrosis induced by RFA. Results: The mean ablation area range increased in groups B, C and especially E, and the scopes were greater compared with group A. Preoperative application of anhydrous ethanol, hypertonic saline, lidocaine and the mixed solution (groups B, C, D and E, respectively) resulted in larger coagulation necrosis areas than in group A (p<0.05). Among the groups, the coagulation necrosis areas in group E was largest, and the difference was statistically significant compared with other groups (p<0.05). Pathological findings were consistent with imaging results. Conclusions: A mixture of dehydrated alcohol, hypertonic saline and lidocaine injected with RFA increases the extent of coagulation necrosis in the liver with a single application, and the mixed solution is more effective than any other injection alone.

• Journal of radiological science and technology
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• v.35 no.2
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• pp.165-172
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• 2012

We investigated the vascular characteristics of tumors and normal tissue using perfusion CT in the rabbit brain tumor model. The VX2 carcinoma concentration of $1{\times}10^7$ cells/ml(0.1ml) was implanted in the brain of nine New Zealand white rabbits (weight: 2.4kg-3.0kg, mean: 2.6kg). The perfusion CT was scanned when the tumors were grown up to 5mm. The tumor volume and perfusion value were quantitatively analyzed by using commercial workstation (advantage windows workstation, AW, version 4.2, GE, USA). The mean volume of implanted tumors was $316{\pm}181mm^3$, and the biggest and smallest volumes of tumor were 497 $mm^3$ and 195 $mm^3$, respectively. All the implanted tumors in rabbits are single-nodular tumors, and intracranial metastasis was not observed. In the perfusion CT, cerebral blood volume (CBV) were $74.40{\pm}9.63$, $16.08{\pm}0.64$, $15.24{\pm}3.23$ ml/100g in the tumor core, ipsilateral normal brain, and contralateral normal brain, respectively ($p{\leqq}0.05$). In the cerebral blood flow (CBF), there were significant differences between the tumor core and both normal brains ($p{\leqq}0.05$), but no significant differences between ipsilateral and contralateral normal brains ($962.91{\pm}75.96$ vs. $357.82{\pm}12.82$ vs. $323.19{\pm}83.24$ ml/100g/min). In the mean transit time (MTT), there were significant differences between the tumor core and both normal brains ($p{\leqq}0.05$), but no significant differences between ipsilateral and contralateral normal brains ($4.37{\pm}0.19$ vs. $3.02{\pm}0.41$ vs. $2.86{\pm}0.22$ sec). In the permeability surface (PS), there were significant differences among the tumor core, ipsilateral and contralateral normal brains ($47.23{\pm}25.45$ vs. $14.54{\pm}1.60$ vs. $6.81{\pm}4.20$ ml/100g/min)($p{\leqq}0.05$). In the time to peak (TTP) were no significant differences among the tumor core, ipsilateral and contralateral normal brains. In the positive enhancement integral (PEI), there were significant differences among the tumor core, ipsilateral and contralateral brains ($61.56{\pm}16.07$ vs. $12.58{\pm}2.61$ vs. $8.26{\pm}5.55$ ml/100g). ($p{\leqq}0.05$). In the maximum slope of increase (MSI), there were significant differences between the tumor core and both normal brain($p{\leqq}0.05$), but no significant differences between ipsilateral and contralateral normal brains ($13.18{\pm}2.81$ vs. $6.99{\pm}1.73$ vs. $6.41{\pm}1.39$ HU/sec). Additionally, in the maximum slope of decrease (MSD), there were significant differences between the tumor core and contralateral normal brain($p{\leqq}0.05$), but no significant differences between the tumor core and ipsilateral normal brain($4.02{\pm}1.37$ vs. $4.66{\pm}0.83$ vs. $6.47{\pm}1.53$ HU/sec). In conclusion, the VX2 tumors were implanted in the rabbit brain successfully, and stereotactic inoculation method make single-nodular type of tumor that was no metastasis in intracranial, suitable for comparative study between tumors and normal tissues. Therefore, perfusion CT would be a useful diagnostic tool capable of reflecting the vascularity of the tumors.

• Journal of Veterinary Clinics
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• v.23 no.4
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• pp.388-392
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• 2006

To verify the solitary nodular hepatocellular tumor model induced by intraparenchymal VX2 tumor cell injection and assess the diagnostic imaging character by computed tomography in rabbits. The tumor cell fragment ($1{\sim}2mm^3$) was loaded in Seldinger needle and directly implanted into the livers of 80 New Zealand white rabbits. The tumor size and patterns of tumor growth were evaluated using spiral computed tomography (CT) at 1, 2, and 3 weeks after tumor implantation. A solitary nodular tumor was successfully created in 82.5% (66/80). The mortality rate was 5% (4/80). The tumor sizes measured were 7.46.3, 14.210.8, 16.212.6 cm at 1, 2, and 3 weeks after tumor implantation on arterial phase CT images. The tumors were round to oval shape with peripheral enhancement and central hypoattenuation on arterial phase, and hypoatteuated wash-out pattern on portal phase. It is considered that inoculation of tumor fragment loaded in Seldinger needle is useful and practical method for creating a solitary hepatic tumor. And CT scanning are valuable to investigate the hepatic tumor and compatible to the observations on macro-and microscopic findings.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.2
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• pp.123-129
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• 2015

$^{64}Cu$-labeled diacetyl-bis($N^4$-methylthiosemicarbazone) is a promising agent for internal radiation therapy and imaging of hypoxic tissues. In the study, we confirmed hypoxia regions in VX2 tumor implanted rabbits with injection $^{64}Cu$-ATSM and $^{18}F$-FDG using positron emission tomography (PET)/computed tomography (CT). PET images with $^{18}F$-FDG and $^{64}Cu$-ATSM were obtained for 40 min by dynamic scan and additional delayed PET images of $^{64}Cu$-ATSM the acquired up to 48 hours. Correlation between intratumoral $O_2$ level and $^{64}Cu$-ATSM PET image was analyzed. $^{64}Cu$-ATSM and $^{18}F$-FDG were intravenously co-injected and the tumor was dissected and cut into slices for a dual-tracer autoradiographic analysis. In the PET imaging, $^{64}Cu$-ATSM in VX2 tumors displayed a specific uptake in hypoxic region for48 h. The uptake pattern of $^{64}Cu$-ATSM in VX2 tumor at 24 and 48 h did not match to the $^{18}F$-FDG. Through ROI analysis, in the early phase (dynamic scan), $^{18}F$-FDG has positive correlation with $^{64}Cu$-ATSM but late phase (24 and 48 h) of the $^{64}Cu$-ATSM showed negative correlation with $^{18}F$-FDG. High uptake of $^{64}Cu$-ATSM in hypoxic region was responded with significant decrease of oxygen pressure, which confirmed by $^{64}Cu$-ATSM PET imaging and autoradiographic analysis. In conclusion, $^{64}Cu$-ATSM can utilize for specific targeting of hypoxic region in tumor, and discrimination between necrotic- and viable hypoxic tissue.

• Korean Journal of Radiology
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• v.19 no.6
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• pp.1099-1109
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• 2018

Objective: In a proof of concept study, we compared no-touch radiofrequency ablation (NtRFA) in bipolar mode with conventional direct tumor puncture (DTP) in terms of local tumor control (LTC), peritoneal seeding, and tumorigenic factors, in the rabbit VX2 subcapsular hepatic tumor model. Materials and Methods: Sixty-two rabbits with VX2 subcapsular hepatic tumors were divided into three groups according to the procedure: DTP-RFA (n = 25); NtRFA (n = 25); and control (n = 12). Each of the three groups was subdivided into two sets for pathologic analysis (n = 24) or computed tomography (CT) follow-up for 6 weeks after RFA (n = 38). Ultrasonography-guided DTP-RFA and NtRFA were performed nine days after tumor implantation. LTC was defined by either achievement of complete tumor necrosis on histopathology or absence of local tumor progression on follow-up CT and autopsy. Development of peritoneal seeding was also compared among the groups. Serum hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) were measured via ELISA (Elabscience Biotechnology Co.) after RFA for tumorigenic factor evaluation. Results: Regarding LTC, there was a trend in NtRFA (80%, 20/25) toward better ablation than in DTP-RFA (56%, 14/25) (p = 0.069). Complete tumor necrosis was achieved in 54.5% of DTP-RFA (6/11) and 90.9% of NtRFA (10/11). Peritoneal seeding was significantly more common in DTP-RFA (71.4%, 10/14) than in NtRFA (21.4%, 3/14) (p = 0.021) or control (0%). Elevations of HGF, VEGF or IL-6 were not detected in any group. Conclusion: No-touch radiofrequency ablation led to lower rates of peritoneal seeding and showed a tendency toward better LTC than DTP-RFA.