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Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma

BACKGROUND: To evaluate the inhibitory effects of aflibercept on the growth and subretinal invasion of retinoblastoma. METHODS: Xenotransplantation and orthotopic mouse models were created by injecting Y-79 cells subcutaneously and intravitreally, respectively. After induction of retinoblastoma, ani...

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Autores principales: Kim, Dong Yoon, Choi, Jeong A, Koh, Jae-Young, Yoon, Young Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097437/
https://www.ncbi.nlm.nih.gov/pubmed/27814771
http://dx.doi.org/10.1186/s13046-016-0451-7
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author Kim, Dong Yoon
Choi, Jeong A
Koh, Jae-Young
Yoon, Young Hee
author_facet Kim, Dong Yoon
Choi, Jeong A
Koh, Jae-Young
Yoon, Young Hee
author_sort Kim, Dong Yoon
collection PubMed
description BACKGROUND: To evaluate the inhibitory effects of aflibercept on the growth and subretinal invasion of retinoblastoma. METHODS: Xenotransplantation and orthotopic mouse models were created by injecting Y-79 cells subcutaneously and intravitreally, respectively. After induction of retinoblastoma, animals were intraperitoneally injected with aflibercept (25 mg/kg body weight) or saline twice a week for 3 weeks. Tumor size was measured weekly and compared between the two groups. At 4 weeks, animals were sacrificed and an immunohistochemical examination was conducted to compare the microvascular density and degree of apoptosis between groups. In addition, the degree of choroidal invasion was also analyzed in the orthotopic xenotransplantation model. A co-culture system of Y-79 or WERI-Rb-1 cells and human umbilical vein endothelial cells (HUVECs) was used for in vitro experiments, and the anti-angiogenic effect of aflibercept was evaluated by analyzing cell numbers. RESULTS: In the Y-79 xenotransplantation model, aflibercept treatment significantly inhibited tumor growth at 4 weeks versus baseline compared with saline-injected mice (188.53 ± 118.53 mm(3) vs. 747.87 ± 118.83 mm(3), respectively, P < 0.001). Tumors isolated from aflibercept-treated mice contained fewer blood vessels (8.59 % ± 7.60 % vs. 14.91 % ± 4.53 %, respectively, P < 0.05) and an increased number of apoptotic cells (15.10 ± 9.13 vs. 4.44 ± 2.24, respectively, P < 0.05). In the orthotopic model, the degree of subretinal invasion of tumor cells was significantly reduced after aflibercept treatment (0.07 ± 0.06 vs. 0.15 ± 0.10, P < 0.05). And addition of aflibercept to co-cultures of HUVECs and Y-79, WERI-Rb-1 cells significantly reduced HUVEC proliferation. CONCLUSIONS: Aflibercept reduced retinoblastoma angiogenesis in association with a significant reduction in tumor growth and invasion. These findings suggest that aflibercept could be used in an adjuvant role together with systemic chemotherapy to reduce tumor size and angiogenesis in retinoblastoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-016-0451-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-50974372016-11-08 Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma Kim, Dong Yoon Choi, Jeong A Koh, Jae-Young Yoon, Young Hee J Exp Clin Cancer Res Research BACKGROUND: To evaluate the inhibitory effects of aflibercept on the growth and subretinal invasion of retinoblastoma. METHODS: Xenotransplantation and orthotopic mouse models were created by injecting Y-79 cells subcutaneously and intravitreally, respectively. After induction of retinoblastoma, animals were intraperitoneally injected with aflibercept (25 mg/kg body weight) or saline twice a week for 3 weeks. Tumor size was measured weekly and compared between the two groups. At 4 weeks, animals were sacrificed and an immunohistochemical examination was conducted to compare the microvascular density and degree of apoptosis between groups. In addition, the degree of choroidal invasion was also analyzed in the orthotopic xenotransplantation model. A co-culture system of Y-79 or WERI-Rb-1 cells and human umbilical vein endothelial cells (HUVECs) was used for in vitro experiments, and the anti-angiogenic effect of aflibercept was evaluated by analyzing cell numbers. RESULTS: In the Y-79 xenotransplantation model, aflibercept treatment significantly inhibited tumor growth at 4 weeks versus baseline compared with saline-injected mice (188.53 ± 118.53 mm(3) vs. 747.87 ± 118.83 mm(3), respectively, P < 0.001). Tumors isolated from aflibercept-treated mice contained fewer blood vessels (8.59 % ± 7.60 % vs. 14.91 % ± 4.53 %, respectively, P < 0.05) and an increased number of apoptotic cells (15.10 ± 9.13 vs. 4.44 ± 2.24, respectively, P < 0.05). In the orthotopic model, the degree of subretinal invasion of tumor cells was significantly reduced after aflibercept treatment (0.07 ± 0.06 vs. 0.15 ± 0.10, P < 0.05). And addition of aflibercept to co-cultures of HUVECs and Y-79, WERI-Rb-1 cells significantly reduced HUVEC proliferation. CONCLUSIONS: Aflibercept reduced retinoblastoma angiogenesis in association with a significant reduction in tumor growth and invasion. These findings suggest that aflibercept could be used in an adjuvant role together with systemic chemotherapy to reduce tumor size and angiogenesis in retinoblastoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-016-0451-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-11-04 /pmc/articles/PMC5097437/ /pubmed/27814771 http://dx.doi.org/10.1186/s13046-016-0451-7 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kim, Dong Yoon
Choi, Jeong A
Koh, Jae-Young
Yoon, Young Hee
Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma
title Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma
title_full Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma
title_fullStr Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma
title_full_unstemmed Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma
title_short Efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma
title_sort efficacy and safety of aflibercept in in vitro and in vivo models of retinoblastoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097437/
https://www.ncbi.nlm.nih.gov/pubmed/27814771
http://dx.doi.org/10.1186/s13046-016-0451-7
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