Transcatheter arterial embolization followed by octreotide and celecoxib synergistically prolongs survival of rabbits with hepatic <scp>VX2</scp> allografts

Tong, Huan; Li, Xiao; Zhang, Chun Le; Gao, Jin; Wen, Shi; Huang, Zifeng; Wen, Fu Qiang; Fu, Ping; Tang, Chaowei

doi:10.1111/1751-2980.12001

Cited by 11 publications

(17 citation statements)

References 27 publications

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“…Previous studies have demonstrated that the majority of rabbits underwent metastasis ~40 days after tumor implantation (8,14). Distal metastasis and abdominal implantation occurring at a late stage of liver carcinoma were usually accompanied by either intrahepatic metastasis or large primary implantation foci (8). Conversely, in the present study, rabbits in group A, whose peritoneum was scattered with nodules, possessed hepatic allograft diameters of <5 cm at 14 days after tumor implantation, without concomitant intrahepatic or lung metastasis.…”

Section: Discussioncontrasting

confidence: 42%

Section: Discussionmentioning

confidence: 99%

“…Surgical implantation of the tumor fragment into the liver is a common conventional method; however the risk of tumor leakage and atopic seeding cannot be avoided, and negatively impacts sequential evaluation of the efficacy of this therapeutic modality in treating VX2 carcinoma (8 ). All the rabbits used in the present study were kept under a 12-h light-dark cycle at 26˚C, 0.03% carbon dioxide and one atmosphere with free access to food and water prior to preoperative fasting.…”

Section: Introductionmentioning

confidence: 99%

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Modification of the method to establish a hepatic VX2 carcinoma model in rabbits

et al. 2018

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Abstract.The hepatic VX2 carcinoma model in rabbits is widely used for the preclinical study of hepatocellular carcinoma. In the present study, a modification was made to the conventional method to establish the animal model, as the conventional method gives rise to frequent tumor seeding due to the drop-out of tumor fragments. In order to evaluate each distinct method of establishing the model, the rabbits were divided into two groups: Group A (the conventional method; n=20) and group B (the modified method; n=20). All surgical details were recorded for reference. At 14 days post-surgery, contrast-enhanced computed tomography (CECT) and autopsy were conducted. Microscopic morphology of tumor cells was observed using hematoxylin and eosin (H&E) and transmission electron microscopy (TEM). Vascular endothelial growth factor (VEGF) and cluster of differentiation (CD)31 were detected via immunochemistry and reverse transcription-polymerase chain reaction. In total, 19 rabbits in each group succeeded in model establishment. Throughout the surgery, group A experienced a longer surgery time compared with group B (group A vs. group B, 22.57±1.34 vs. 20.17±1.50 min; P<0.001), an increased tumor fragment drop-out frequency (group A vs. group B, 1.84±0.96 vs. 1.16±0.38; P=0.008) and an increased peritoneal nodule incidence (group A vs. group B, 35 vs. 5%, P=0.042).As for CECT, H&E and TEM, hepatic VX2 allografts in the two groups demonstrated similar imaging presentations and tumor cell morphology. In addition, VEGF and CD31 levels did not differ between the two groups. In conclusion, the modified method for the establishment of hepatic VX2 carcinoma model in rabbits may decrease tumor fragment drop-out frequency during surgery and incidence of tumor seeding without affecting the properties of VX2 carcinoma.

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Section: Discussioncontrasting

confidence: 42%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modification of the method to establish a hepatic VX2 carcinoma model in rabbits

et al. 2018

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“…The establishment of VX2 hepatic allografts in rabbits, TAE procedure and experimental grouping were the same as in our previous study (14). Briefly, 72 rabbits were randomly assigned into four groups.…”

Section: Methodsmentioning

confidence: 99%

“…Somatostatin (SST) is one of the regulatory peptides for arresting the growth of HCC and the overexpression of SST receptors has also been identified in HCC (12). Our previous studies demonstrated that a combination of a COX-2 inhibitor with an SST analogue not only had an enhanced anti-proliferative effect and suppressed the metastasis of HCC in nude mice (13) but also prolonged the survival of rabbits with liver cancer that received TAE (14). …”

Section: Introductionmentioning

confidence: 99%

Octreotide and celecoxib synergistically encapsulate VX2 hepatic allografts following transcatheter arterial embolisation

Tong

Xiao

Gao

et al. 2013

Experimental and Therapeutic Medicine

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To evaluate the encapsulation of VX2 hepatic allografts in rabbits induced by octreotide and celecoxib administration following transcatheter arterial embolisation (TAE), rabbits with hepatic VX2 allografts were divided into four groups: control, TAE, octreotide + celecoxib (O+C) and the multimodality therapy (TAE+O+C). Allograft metastasis, capsule thickness and percentage of clear cells were measured and vascular endothelial growth factor (VEGF) and CD31 were detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis. The extrahepatic metastases of each intervention group were significantly fewer than those of the control group, with the TAE+O+C group exhibiting the fewest extrahepatic metastases. The TAE+O+C group had the greatest proportion of clear cells and thickest capsule on day 30. Increased capsule thickness was negatively correlated with tumour metastasis. In addition, VEGF expression levels assessed by immunohistochemistry and RT-PCR in the three intervention groups were significantly lower than those in the control group. Furthermore, the TAE+O+C group had a significantly reduced CD31 count induced by TAE. These results demonstrate that TAE, followed by long-term administration of octreotide and celecoxib, synergistically inhibits VX2 hepatic allograft metastasis by increasing the proportion of clear cells, promoting encapsulation and inhibiting angiogenesis.

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Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats

Gao¹,

Wen²,

Shi

et al. 2016

Angiogenesis

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Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non-cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats. A combination treatment of celecoxib and octreotide was found to relieve liver fibrosis, portal venous pressure, micro-hepatic arterioportal fistulas, intrahepatic and splanchnic angiogenesis. Celecoxib and octreotide exerted their anti-angiogenesis effect via an axis of cyclooxygenase-2/prostaglandin E2/EP-2/somatostatin receptor-2, which consequently down-regulated phosphorylation of extracellular signal-regulated kinase (p-ERK)–hypoxia-inducible factor-1α (HIF-1α)–vascular endothelial growth factor (VEGF) integrated signaling pathways. In conclusions, combination of celecoxib and octreotide synergistically ameliorated liver fibrosis and portal hypertension of the cirrhotic rats induced by TAA via the inhibition of intrahepatic and extrahepatic angiogenesis. The potential mechanisms behind the regimen may due to the inactivation of p-ERK–HIF-1α–VEGF signaling pathway.Electronic supplementary materialThe online version of this article (doi:10.1007/s10456-016-9522-9) contains supplementary material, which is available to authorized users.

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Transcatheter arterial embolization followed by octreotide and celecoxib synergistically prolongs survival of rabbits with hepatic VX2 allografts

Abstract: TAE followed by the long-term administration of octreotide and celecoxib can synergistically prolong the survival of rabbits with hepatic VX2 allografts by inhibiting potential neoangiogenesis, tumor growth and metastasis.

Cited by 11 publications

References 27 publications

Modification of the method to establish a hepatic VX2 carcinoma model in rabbits

Modification of the method to establish a hepatic VX2 carcinoma model in rabbits

Octreotide and celecoxib synergistically encapsulate VX2 hepatic allografts following transcatheter arterial embolisation

Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats

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