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Bevacizumab is an Efficient Therapeutic Approach with Low Side Effects in Patient-Derived Xenografts of Adenoid Cystic Carcinoma of the Lacrimal Gland

PURPOSE: Adenoid cystic carcinoma (ACC) of the lacrimal gland (LGACC) is an aggressive malignant lacrimal gland tumor with a generally poor prognosis. Survival rates for LGACC are 56% at 5 years and 49% at 10 years. Recent studies have indicated that anti-vascular endothelial growth factor (VEGF) th...

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Autores principales: Zhang, Jingxue, Yan, Xuejing, Liu, Rui, Wu, Shen, Liu, Qian, Li, Jing, Ma, Jianmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912937/
https://www.ncbi.nlm.nih.gov/pubmed/35283648
http://dx.doi.org/10.2147/CMAR.S352623
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author Zhang, Jingxue
Yan, Xuejing
Liu, Rui
Wu, Shen
Liu, Qian
Li, Jing
Ma, Jianmin
author_facet Zhang, Jingxue
Yan, Xuejing
Liu, Rui
Wu, Shen
Liu, Qian
Li, Jing
Ma, Jianmin
author_sort Zhang, Jingxue
collection PubMed
description PURPOSE: Adenoid cystic carcinoma (ACC) of the lacrimal gland (LGACC) is an aggressive malignant lacrimal gland tumor with a generally poor prognosis. Survival rates for LGACC are 56% at 5 years and 49% at 10 years. Recent studies have indicated that anti-vascular endothelial growth factor (VEGF) therapy can inhibit angiogenesis in ACC cells. This study was designed to explore the efficacy of the antiangiogenic drug bevacizumab in a LGACC patient-derived xenograft (PDX) animal model. METHODS: The histological structure of PDX was determined by hematoxylin-eosin staining to confirm successful xenografting. Immunohistochemistry (IHC) was used to detect the expression of neovascularization-related genes in LGACC patients and in the PDX model, including VEGF, VEGFR1, and FGFR. In order to compare the efficacy of antiangiogenic drug and traditional chemotherapy drug, PDX models were treated with bevacizumab and cisplatin respectively, and body weight was evaluated. Subsequently, the neovascularization-related proteins VEGF, VEGFR2, and CD34, tumor suppressor P53 and proliferation-related protein Ki67 were analyzed by IHC. Quantitative real-time PCR was employed to examine the mRNA expression of apoptosis-related genes BAD and Caspase 9, and of HIF1α. RESULTS: VEGF, VEGFR1, and FGFR were highly expressed in patients with LGACC and PDX models. Both bevacizumab and cisplatin treatment inhibited PDX tumor growth. The body weight of PDX models treated with cisplatin significantly decreased from day 15, while those treated with bevacizumab did not markedly change. Bevacizumab reduced the expression of VEGF, CD34, and Ki67 in PDX tumors; whereas, bevacizumab upregulated P53 and downregulated HIF1α levels. CONCLUSION: The present study indicates that antiangiogenic drugs may be a promising treatment strategy for LGACC.
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spelling pubmed-89129372022-03-11 Bevacizumab is an Efficient Therapeutic Approach with Low Side Effects in Patient-Derived Xenografts of Adenoid Cystic Carcinoma of the Lacrimal Gland Zhang, Jingxue Yan, Xuejing Liu, Rui Wu, Shen Liu, Qian Li, Jing Ma, Jianmin Cancer Manag Res Original Research PURPOSE: Adenoid cystic carcinoma (ACC) of the lacrimal gland (LGACC) is an aggressive malignant lacrimal gland tumor with a generally poor prognosis. Survival rates for LGACC are 56% at 5 years and 49% at 10 years. Recent studies have indicated that anti-vascular endothelial growth factor (VEGF) therapy can inhibit angiogenesis in ACC cells. This study was designed to explore the efficacy of the antiangiogenic drug bevacizumab in a LGACC patient-derived xenograft (PDX) animal model. METHODS: The histological structure of PDX was determined by hematoxylin-eosin staining to confirm successful xenografting. Immunohistochemistry (IHC) was used to detect the expression of neovascularization-related genes in LGACC patients and in the PDX model, including VEGF, VEGFR1, and FGFR. In order to compare the efficacy of antiangiogenic drug and traditional chemotherapy drug, PDX models were treated with bevacizumab and cisplatin respectively, and body weight was evaluated. Subsequently, the neovascularization-related proteins VEGF, VEGFR2, and CD34, tumor suppressor P53 and proliferation-related protein Ki67 were analyzed by IHC. Quantitative real-time PCR was employed to examine the mRNA expression of apoptosis-related genes BAD and Caspase 9, and of HIF1α. RESULTS: VEGF, VEGFR1, and FGFR were highly expressed in patients with LGACC and PDX models. Both bevacizumab and cisplatin treatment inhibited PDX tumor growth. The body weight of PDX models treated with cisplatin significantly decreased from day 15, while those treated with bevacizumab did not markedly change. Bevacizumab reduced the expression of VEGF, CD34, and Ki67 in PDX tumors; whereas, bevacizumab upregulated P53 and downregulated HIF1α levels. CONCLUSION: The present study indicates that antiangiogenic drugs may be a promising treatment strategy for LGACC. Dove 2022-03-06 /pmc/articles/PMC8912937/ /pubmed/35283648 http://dx.doi.org/10.2147/CMAR.S352623 Text en © 2022 Zhang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Zhang, Jingxue
Yan, Xuejing
Liu, Rui
Wu, Shen
Liu, Qian
Li, Jing
Ma, Jianmin
Bevacizumab is an Efficient Therapeutic Approach with Low Side Effects in Patient-Derived Xenografts of Adenoid Cystic Carcinoma of the Lacrimal Gland
title Bevacizumab is an Efficient Therapeutic Approach with Low Side Effects in Patient-Derived Xenografts of Adenoid Cystic Carcinoma of the Lacrimal Gland
title_full Bevacizumab is an Efficient Therapeutic Approach with Low Side Effects in Patient-Derived Xenografts of Adenoid Cystic Carcinoma of the Lacrimal Gland
title_fullStr Bevacizumab is an Efficient Therapeutic Approach with Low Side Effects in Patient-Derived Xenografts of Adenoid Cystic Carcinoma of the Lacrimal Gland
title_full_unstemmed Bevacizumab is an Efficient Therapeutic Approach with Low Side Effects in Patient-Derived Xenografts of Adenoid Cystic Carcinoma of the Lacrimal Gland
title_short Bevacizumab is an Efficient Therapeutic Approach with Low Side Effects in Patient-Derived Xenografts of Adenoid Cystic Carcinoma of the Lacrimal Gland
title_sort bevacizumab is an efficient therapeutic approach with low side effects in patient-derived xenografts of adenoid cystic carcinoma of the lacrimal gland
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912937/
https://www.ncbi.nlm.nih.gov/pubmed/35283648
http://dx.doi.org/10.2147/CMAR.S352623
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