Pharmacokinetic study of conventional sorafenib chemoembolization in a rabbit VX2 liver tumor model

Parvinian, Ahmad; Casadaban, Leigh C.; Hauck, Zane; Breemen, Richard B. van; Gaba, Ron C.

doi:10.5152/dir.2014.14394

Cited by 13 publications

(14 citation statements)

References 27 publications

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“…In contrast to previous study results that indicated that sorafenib transarterial chemoembolization is safe and that there is no or minimal deterioration of hepatic function (9)(10)(11), the AST and ALT levels were signifi- cantly higher in the TAE-S group at 24 hours after treatment in the present study. There were no statistically significant differences, but other hepatic enzymes, including alkaline phosphatase and total bilirubin, were also higher in the TAE-S group at 24 hours after treatment.…”

Section: Discussioncontrasting

confidence: 85%

“…We delivered 10 mg sorafenib per rabbit, which was a much higher dose than the dose used in the study by Chatziioannou et al (9) and which was similar to the dose (3 mg/kg) used in other studies (8,10,11). To prepare the sorafenib, we sonicated the mixture of sorafenib powder and Lipiodol following Chatziioannou's method.…”

Section: Discussionmentioning

confidence: 97%

“…Only a few studies using a normal liver model have investigated the feasibility of transarterial administration of sorafenib (8,9). Only a few reports have described pharmacokinetics, safety, and degree of tumor growth after administration of sorafenib in VX2 tumor models (10,11).…”

mentioning

confidence: 99%

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Transarterial Chemoembolization Using Sorafenib in a Rabbit VX2 Liver Tumor Model: Pharmacokinetics and Antitumor Effect

Kim

et al. 2016

Journal of Vascular and Interventional Radiology

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Section: Discussioncontrasting

confidence: 85%

Section: Discussionmentioning

confidence: 97%

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Transarterial Chemoembolization Using Sorafenib in a Rabbit VX2 Liver Tumor Model: Pharmacokinetics and Antitumor Effect

Kim

et al. 2016

Journal of Vascular and Interventional Radiology

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“…Previous reports have indicated that the combination of embolic agents and angiogenesis inhibitors (e.g., sorafenib, apatinib and sunitinib) via arterial administration to the liver is effective. [16][17][18] It can increase intratumoral drug concentration and reduce systemic toxicity. The aim of present study was to investigate the feasibility, safety and effects on angiogenesis and immune response after TAE combined with donafenib in rabbit VX2 liver tumor model.…”

Section: Introductionmentioning

confidence: 99%

Transcatheter Arterial Embolization Containing Donafenib Induces Anti-Angiogenesis and Tumoricidal CD8+ T-Cell Infiltration in Rabbit VX2 Liver Tumor

Shi¹,

Li²,

Huang³

et al. 2021

CMAR

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To evaluate the effect and immune response of transcatheter arterial embolization (TAE) combined with donafenib in rabbit VX2 liver tumor model. Materials and Methods: Thirty-six New Zealand white rabbits with VX2 liver tumor were randomly divided into three groups. The LD group was treated with the emulsion of 0.5 mL lipiodol and 4 mg donafenib via hepatic arterial administration. The LE group was treated with the emulsion of 0.5 mL lipiodol and 4 mg epirubicin. The control group was treated with the equal volume of saline. Four rabbits were euthanized in each group on day 1, 3 and 7 after treatment. The tumor growth, histological markers associated with angiogenesis and immune response were assessed by imaging and histopathology. In addition, immune modulatory cytokines included interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and biochemical hepatorenal function were measured. Results: Compared to other groups, LD group achieved lower tumor growth rate, fewer metastatic lesions, and higher tumor necrosis rate on day 7 after treatment. The percentage of CD31-positive area in the LD group was significantly lower than that in the LE group on day 3 and 7 after treatment. In addition, CD8 + lymphocytes infiltration was more pronounced in LD group than in LE group on day 7 after treatment, regardless of in the tumor or adjacent liver tissue. Serum cytokines including IL-6, TNF-α and IFN-γ were strongly upregulated in the LD group on day 1 after treatment. And there was no significant difference in the hepatorenal function between LD group and LE group after treatment. Conclusion:The combination of TAE and angiogenesis inhibitor donafenib resulted in a potentiated tumoricidal effect, anti-angiogenesis and antitumour T cell response in rabbit VX2 liver tumor model. This may provide a potential basis for exploring the immune-related mechanisms of embolization in liver cancer.

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“…However, clinical data on this issue so far are inconclusive (12,13). In order to enhance the adjunctive effect of sorafenib combined with TACE and to reduce the sideeffects of systemic sorafenib therapy, local application of sorafenib into the HCC, together with embolic material, is proposed and under initial preclinical research, with promising results (14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Validation of VX2 as a Hepatocellular Carcinoma Model: Comparison of the Molecular Reaction of VX2 and HepG2 Tumor Cells to Sorafenib In Vitro

Naß

Streit

Wybranski

et al. 2017

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As there is currently no superior hepatocellular carcinoma (HCC) model with percutaneous vascular access for transarterial treatments available, the VX2 rabbit model is frequently used for in vivo investigations on liver carcinoma. However, the VX2 cell line was derived from a virus-induced skin papilloma that can form carcinosarcoma in liver of rabbits and the transferability of obtained results to HCC treatment remains open. Here we compared the most frequently investigated human HCC model cell line, HepG2, with VX2 cells in vitro in terms of sensitivity towards the broad specificity kinase inhibitor sorafenib and responsiveness to the addition of platelet-derived growth factor AB (PDGF-AB), vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF), as well as insulin and interleukin-1β (IL1β). Phosphorylation of protein kinase B (AKT) the mitogen-activated protein kinases (MAPKs) p38 and p42/44 (extracellular signal-regulated kinase, ERK1/2) and inhibitor of kappa light chain gene enhancer alpha (IĸBα) was determined by western blotting as these events are associated with early signaling cascades. Additionally, the inhibition of phosphorylation under sorafenib treatment was investigated. Sorafenib was equally toxic to both cell lines, but only in HepG2 was activation of caspase 3/7 activity, as a sign of apoptosis, observed. VX2 cells exhibited generally more intense phosphorylation signals in response to the growth factors and also serum. In contrast to VX2, HepG2 cells showed no response to PDGF-AB or VEGF as determined by kinase phosphorylation. In both cell lines, sorafenib inhibited growth factor-induced phosphorylation of ERK and p38-MAPK. AKT phosphorylation was only inhibited in VX2 cells and IĸBα phosphorylation was not influenced by this kinase inhibitor in either cell type. Taken together, the two cellular models for HCC share several features related to sorafenib application, but differed in their responsiveness towards growth factors. Therefore, results obtained with the VX2 model cannot be extended to human HCC without appropriate caution.

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Pharmacokinetic study of conventional sorafenib chemoembolization in a rabbit VX2 liver tumor model

Cited by 13 publications

References 27 publications

Transarterial Chemoembolization Using Sorafenib in a Rabbit VX2 Liver Tumor Model: Pharmacokinetics and Antitumor Effect

Transarterial Chemoembolization Using Sorafenib in a Rabbit VX2 Liver Tumor Model: Pharmacokinetics and Antitumor Effect

Transcatheter Arterial Embolization Containing Donafenib Induces Anti-Angiogenesis and Tumoricidal CD8+ T-Cell Infiltration in Rabbit VX2 Liver Tumor

Validation of VX2 as a Hepatocellular Carcinoma Model: Comparison of the Molecular Reaction of VX2 and HepG2 Tumor Cells to Sorafenib In Vitro

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