Please use this identifier to cite or link to this item: https://doi.org/10.1158/1078-0432.CCR-08-0509
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dc.titleBrivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor tyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma
dc.contributor.authorHuynh, H
dc.contributor.authorNgo, V.C
dc.contributor.authorFargnoli, J
dc.contributor.authorAyers, M
dc.contributor.authorKhee, C.S
dc.contributor.authorHeng, N.K
dc.contributor.authorChoon, H.T
dc.contributor.authorHock, S.O
dc.contributor.authorChung, A
dc.contributor.authorChow, P
dc.contributor.authorPollock, P
dc.contributor.authorByron, S
dc.contributor.authorTran, E
dc.date.accessioned2020-10-27T06:55:28Z
dc.date.available2020-10-27T06:55:28Z
dc.date.issued2008
dc.identifier.citationHuynh, H, Ngo, V.C, Fargnoli, J, Ayers, M, Khee, C.S, Heng, N.K, Choon, H.T, Hock, S.O, Chung, A, Chow, P, Pollock, P, Byron, S, Tran, E (2008). Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor tyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma. Clinical Cancer Research 14 (19) : 6146-6153. ScholarBank@NUS Repository. https://doi.org/10.1158/1078-0432.CCR-08-0509
dc.identifier.issn10780432
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/181019
dc.description.abstractPurpose: Hepatocellular carcinoma (HCC) is the fifth most common primary neoplasm; surgery is the only curative option but 5-year survival rates are only 25% to 50%. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) are known to be involved in growth and neovascularization of HCC. Therefore, agents that target these pathways may be effective in the treatment of HCC. The aim of this study was to determine the antineoplastic activity of brivanib alaninate, a dual inhibitor of VEGF receptor (VEGFR) and FGF receptor (FGFR) signaling pathways. Experimental Design: Six different s.c. patient-derived HCC xenografts were implanted into mice. Tumor growth was evaluated in mice treated with brivanib compared with control. The effects of brivanib on apoptosis and cell proliferation were evaluated by immunohistochemistry. The SK-HEP1 and HepG2 cells were used to investigate the effects of brivanib on the VEGFR-2 and FGFR-1 signaling pathways in vitro. Western blotting was used to determine changes in proteins in these xenografts and cell lines. Results: Brivanib significantly suppressed tumor growth in five of six xenograft lines. Furthermore, brivanib-induced growth inhibition was associated with a decrease in phosphorylated VEGFR-2 at Tyr1054/1059, increased apoptosis, reduced microvessel density, inhibition of cell proliferation, and down-regulation of cell cycle regulators. The levels of FGFR-1 and FGFR-2 expression in these xenograft lines were positively correlated with its sensitivity to brivanib-induced growth inhibition. In VEGF-stimulated and basic FGF stimulated SK-HEP1 cells, brivanib significantly inhibited VEGFR-2, FGFR-1, extracellular signal-regulated kinase 1/2, and Akt phosphorylation. Conclusion: This study provides a strong rationale for clinical investigation of brivanib in patients with HCC. ©2008 American Association for Cancer Research.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectbasic fibroblast growth factor
dc.subjectbrivanib alaninate
dc.subjectcaspase 3
dc.subjectCD31 antigen
dc.subjectfibroblast growth factor receptor 1
dc.subjectKi 67 antigen
dc.subjectmitogen activated protein kinase 1
dc.subjectmitogen activated protein kinase 3
dc.subjectprotein kinase B
dc.subjectvasculotropin
dc.subjectvasculotropin receptor 2
dc.subjectalanine
dc.subjectbrivanib alaninate
dc.subjectdrug derivative
dc.subjectfibroblast growth factor receptor
dc.subjecttriazine derivative
dc.subjectvasculotropin receptor
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectantiangiogenic activity
dc.subjectantiangiogenic therapy
dc.subjectantineoplastic activity
dc.subjectapoptosis
dc.subjectarticle
dc.subjectcancer inhibition
dc.subjectcancer model
dc.subjectcell proliferation
dc.subjectcell strain HepG2
dc.subjectcontrolled study
dc.subjectdown regulation
dc.subjectdrug mechanism
dc.subjectdrug sensitivity
dc.subjectenzyme inhibition
dc.subjecthuman
dc.subjecthuman cell
dc.subjecthuman tissue
dc.subjectliver cell carcinoma
dc.subjectmale
dc.subjectmicrovasculature
dc.subjectmouse
dc.subjectneovascularization (pathology)
dc.subjectnonhuman
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectprotein phosphorylation
dc.subjectsignal transduction
dc.subjecttumor vascularization
dc.subjecttumor xenograft
dc.subjectweight change
dc.subjectanimal
dc.subjectcancer transplantation
dc.subjectchemical model
dc.subjectdrug antagonism
dc.subjectliver tumor
dc.subjectmetabolism
dc.subjecttumor cell line
dc.subjectAlanine
dc.subjectAnimals
dc.subjectApoptosis
dc.subjectCarcinoma, Hepatocellular
dc.subjectCell Line, Tumor
dc.subjectCell Proliferation
dc.subjectHumans
dc.subjectLiver Neoplasms
dc.subjectMale
dc.subjectMice
dc.subjectModels, Chemical
dc.subjectNeoplasm Transplantation
dc.subjectNeovascularization, Pathologic
dc.subjectReceptors, Fibroblast Growth Factor
dc.subjectReceptors, Vascular Endothelial Growth Factor
dc.subjectTriazines
dc.typeArticle
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1158/1078-0432.CCR-08-0509
dc.description.sourcetitleClinical Cancer Research
dc.description.volume14
dc.description.issue19
dc.description.page6146-6153
dc.published.statePublished
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