Hepatocellular carcinoma: Where there is unmet need

Bupathi, Manojkumar; Kaseb, Ahmed O.; Meric‐Bernstam, Funda; Naing, Aung

doi:10.1016/j.molonc.2015.06.005

Cited by 66 publications

(50 citation statements)

References 68 publications

(102 reference statements)

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“…VEGF and CD31 expression was measured in the present study. VEGF is an important and potent pro-angiogenesis factor, and CD31 represents the microvessel density in tissue (17,18). The present study did not identify any significant differences in VEGF or CD31 levels between the two groups.…”

Section: Discussioncontrasting

confidence: 44%

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: 44%

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

et al. 2018

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“…The hepatocyte growth factor receptor (HGFR) c-Met has been shown to promote all major events of human HCC evolution including tumor cell growth and survival (7). Its tumor promoting role has also been demonstrated in the DEN mouse model of liver cancer (51).…”

Section: Discussionmentioning

confidence: 99%

Effects of Wnt‑1 blockade in DEN‑induced hepatocellular adenomas of mice

et al. 2017

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Abstract. Recent evidence has suggested that downregulation of the Wnt/β-catenin signaling pathway may contribute to the development and growth of HCC. Consequently, elements of this pathway have begun to emerge as potential targets for improving outcomes of anti-HCC. Thus, the present study sought to examine the effects of Wnt-1 blockade using the classical diethylnitrosamine (DEN)-induced chemical carcinogenesis mouse model of HCC. The depletion of Wnt-1 using neutralizing antisera was done for ten consecutive days at the age of 9 months and mice were examined for the following 20 days. At that time, DEN-treated mice had multiple variably-sized hepatic cell adenomas. Anti-Wnt-1 was particularly potent in suppressing the expression of critical elements of the Wnt/β-catenin signaling pathway, such as β-catenin and Frizzled-1 receptor, however, not Dickkopf-related protein 1. This effect co-existed with the suppression of Cyclin D1, FOXM1, NF-κΒ and c-Jun commensurate with proliferation and apoptosis blockade in hepatocellular adenomas, and reduced Bcl-2 and c-Met in the serum of mice. Nonetheless, tumor size and multiplicity were found to be unaffected, suggesting that apoptosis may be equally important to proliferation in the context of counteracting DEN induced hepatocellular adenomas of mice.

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“…VEGF is a key player in the process of tumor angiogenesis and hepatocellular carcinoma development [29, 30]. The VEGF pathway is therefore an important focus for anticancer drug development.…”

Section: Discussionmentioning

confidence: 99%

Expression of VEGFR-2 during Liver Regeneration after Partial Hepatectomy in a Bioluminescence Mouse Model

et al. 2017

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Background: Liver regeneration requires the formation of new blood vessels. Endothelial cell proliferation is stimulated by vascular endothelial growth factor (VEGF) and its receptor tyrosine kinase VEGFR-2. The aim of this study was to investigate VEGFR-2 expression in vivo during liver regeneration after partial hepatectomy (PHx). Methods: Transgenic VEGFR-2-luc mice were used in which the luciferase reporter gene was under control of the VEGFR-2 promoter. Following 2/3 PHx, the mice underwent in vivo bioluminescence imaging until the 14th postoperative day. Additionally, liver tissue was analyzed by immunohistochemistry, in vitro luminescence assays, and quantitative RT-PCR. Results: In vivo bioluminescence imaging showed a significant increase in VEGFR-2 promoter activity after PHx. Maximum signal was recorded on the 3rd day; 8 days postoperatively the signal intensity decreased significantly. On the 14th day, bioluminescence signal reached almost baseline levels. Immunohistochemistry, quantitative RT-PCR, and in vitro luminescence confirmed a significant increase on the 3rd day following resection. The mRNA expression of VEGFR-2 was significantly higher on day 3 than preoperatively as well as on day 8. Conclusion: In vivo bioluminescence imaging with transgenic VEGFR-2-luc mice is feasible and provides a convenient model for noninvasively studying VEGFR-2 expression during liver regeneration. This may facilitate further experiments with modulation of angiogenesis by different substances.

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Hepatocellular carcinoma: Where there is unmet need

Cited by 66 publications

References 68 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

Effects of Wnt‑1 blockade in DEN‑induced hepatocellular adenomas of mice

Expression of VEGFR-2 during Liver Regeneration after Partial Hepatectomy in a Bioluminescence Mouse Model

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