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Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model

Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare t...

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Autores principales: Carra, Silvia, Gaudenzi, Germano, Dicitore, Alessandra, Saronni, Davide, Cantone, Maria Celeste, Plebani, Alice, Ghilardi, Anna, Borghi, Maria Orietta, Hofland, Leo J., Persani, Luca, Vitale, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002338/
https://www.ncbi.nlm.nih.gov/pubmed/33809722
http://dx.doi.org/10.3390/ijms22063031
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author Carra, Silvia
Gaudenzi, Germano
Dicitore, Alessandra
Saronni, Davide
Cantone, Maria Celeste
Plebani, Alice
Ghilardi, Anna
Borghi, Maria Orietta
Hofland, Leo J.
Persani, Luca
Vitale, Giovanni
author_facet Carra, Silvia
Gaudenzi, Germano
Dicitore, Alessandra
Saronni, Davide
Cantone, Maria Celeste
Plebani, Alice
Ghilardi, Anna
Borghi, Maria Orietta
Hofland, Leo J.
Persani, Luca
Vitale, Giovanni
author_sort Carra, Silvia
collection PubMed
description Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti-tumor activity of VAN and CAB in MTC. The effects of VAN and CAB on viability, cell cycle, and apoptosis of TT and MZ-CRC-1 cells are evaluated in vitro using an MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the anti-angiogenic potential of VAN and CAB is evaluated in Tg(fli1a:EGFP)(y1) transgenic fluorescent zebrafish embryos by analyzing the effects on the physiological development of the sub-intestinal vein plexus and the tumor-induced angiogenesis after TT and MZ-CRC-1 xenotransplantation. VAN and CAB exert comparable effects on TT and MZ-CRC-1 viability inhibition and cell cycle perturbation, and stimulated apoptosis with a prominent effect by VAN in MZ-CRC-1 and CAB in TT cells. Regarding zebrafish, both drugs inhibit angiogenesis in a dose-dependent manner, in particular CAB shows a more potent anti-angiogenic activity than VAN. To conclude, although VAN and CAB show comparable antiproliferative effects in MTC, the anti-angiogenic activity of CAB appears to be more relevant.
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spelling pubmed-80023382021-03-28 Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model Carra, Silvia Gaudenzi, Germano Dicitore, Alessandra Saronni, Davide Cantone, Maria Celeste Plebani, Alice Ghilardi, Anna Borghi, Maria Orietta Hofland, Leo J. Persani, Luca Vitale, Giovanni Int J Mol Sci Article Medullary thyroid carcinoma (MTC) is a tumor deriving from the thyroid C cells. Vandetanib (VAN) and cabozantinib (CAB) are two tyrosine kinase inhibitors targeting REarranged during Transfection (RET) and other kinase receptors and are approved for the treatment of advanced MTC. We aim to compare the in vitro and in vivo anti-tumor activity of VAN and CAB in MTC. The effects of VAN and CAB on viability, cell cycle, and apoptosis of TT and MZ-CRC-1 cells are evaluated in vitro using an MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the anti-angiogenic potential of VAN and CAB is evaluated in Tg(fli1a:EGFP)(y1) transgenic fluorescent zebrafish embryos by analyzing the effects on the physiological development of the sub-intestinal vein plexus and the tumor-induced angiogenesis after TT and MZ-CRC-1 xenotransplantation. VAN and CAB exert comparable effects on TT and MZ-CRC-1 viability inhibition and cell cycle perturbation, and stimulated apoptosis with a prominent effect by VAN in MZ-CRC-1 and CAB in TT cells. Regarding zebrafish, both drugs inhibit angiogenesis in a dose-dependent manner, in particular CAB shows a more potent anti-angiogenic activity than VAN. To conclude, although VAN and CAB show comparable antiproliferative effects in MTC, the anti-angiogenic activity of CAB appears to be more relevant. MDPI 2021-03-16 /pmc/articles/PMC8002338/ /pubmed/33809722 http://dx.doi.org/10.3390/ijms22063031 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Carra, Silvia
Gaudenzi, Germano
Dicitore, Alessandra
Saronni, Davide
Cantone, Maria Celeste
Plebani, Alice
Ghilardi, Anna
Borghi, Maria Orietta
Hofland, Leo J.
Persani, Luca
Vitale, Giovanni
Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model
title Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model
title_full Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model
title_fullStr Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model
title_full_unstemmed Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model
title_short Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model
title_sort vandetanib versus cabozantinib in medullary thyroid carcinoma: a focus on anti-angiogenic effects in zebrafish model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002338/
https://www.ncbi.nlm.nih.gov/pubmed/33809722
http://dx.doi.org/10.3390/ijms22063031
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