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Intra-individual comparison of therapeutic responses to vascular disrupting agent CA4P between rodent primary and secondary liver cancers

AIM: To compare therapeutic responses of a vascular-disrupting-agent, combretastatin-A4-phosphate (CA4P), among hepatocellular carcinomas (HCCs) and implanted rhabdomyosarcoma (R1) in the same rats by magnetic-resonance-imaging (MRI), microangiography and histopathology. METHODS: Thirty-six HCCs wer...

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Autores principales: Liu, Ye-Wei, De Keyzer, Frederik, Feng, Yuan-Bo, Chen, Feng, Song, Shao-Li, Swinnen, Johan, Bormans, Guy, Oyen, Raymond, Huang, Gang, Ni, Yi-Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034151/
https://www.ncbi.nlm.nih.gov/pubmed/29991876
http://dx.doi.org/10.3748/wjg.v24.i25.2710
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author Liu, Ye-Wei
De Keyzer, Frederik
Feng, Yuan-Bo
Chen, Feng
Song, Shao-Li
Swinnen, Johan
Bormans, Guy
Oyen, Raymond
Huang, Gang
Ni, Yi-Cheng
author_facet Liu, Ye-Wei
De Keyzer, Frederik
Feng, Yuan-Bo
Chen, Feng
Song, Shao-Li
Swinnen, Johan
Bormans, Guy
Oyen, Raymond
Huang, Gang
Ni, Yi-Cheng
author_sort Liu, Ye-Wei
collection PubMed
description AIM: To compare therapeutic responses of a vascular-disrupting-agent, combretastatin-A4-phosphate (CA4P), among hepatocellular carcinomas (HCCs) and implanted rhabdomyosarcoma (R1) in the same rats by magnetic-resonance-imaging (MRI), microangiography and histopathology. METHODS: Thirty-six HCCs were created by diethylnitrosamine gavage in 14 rats that were also intrahepatically implanted with one R1 per rat as monitored by T2-/T1-weighted images (T2WI/T1WI) on a 3.0T clinical MRI-scanner. Vascular response and tumoral necrosis were detected by dynamic contrast-enhanced (DCE-) and CE-MRI before, 1 h after and 12 h after CA4P iv at 10 mg/kg (treatment group n = 7) or phosphate-buffered saline at 1.0 mL/kg (control group n = 7). Tumor blood supply was calculated by a semiquantitative DCE parameter of area under the time signal intensity curve (AUC30). In vivo MRI findings were verified by postmortem techniques. RESULTS: On CE-T1WIs, unlike the negative response in all tumors of control animals, in treatment group CA4P caused rapid extensive vascular shutdown in all R1-tumors, but mildly or spottily in HCCs at 1 h. Consequently, tumor necrosis occurred massively in R1-tumors but patchily in HCCs at 12 h. AUC30 revealed vascular closure (66%) in R1-tumors at 1 h (P < 0.05), followed by further perfusion decrease at 12 h (P < 0.01), while less significant vascular clogging occurred in HCCs. Histomorphologically, CA4P induced more extensive necrosis in R1-tumors (92.6%) than in HCCs (50.2%) (P < 0.01); tumor vascularity heterogeneously scored +~+++ in HCCs but homogeneously scored ++ in R1-tumors. CONCLUSION: This study suggests superior performance of CA4P in metastatic over primary liver cancers, which could guide future clinical applications of vascular-disrupting-agents.​
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spelling pubmed-60341512018-07-11 Intra-individual comparison of therapeutic responses to vascular disrupting agent CA4P between rodent primary and secondary liver cancers Liu, Ye-Wei De Keyzer, Frederik Feng, Yuan-Bo Chen, Feng Song, Shao-Li Swinnen, Johan Bormans, Guy Oyen, Raymond Huang, Gang Ni, Yi-Cheng World J Gastroenterol Basic Study AIM: To compare therapeutic responses of a vascular-disrupting-agent, combretastatin-A4-phosphate (CA4P), among hepatocellular carcinomas (HCCs) and implanted rhabdomyosarcoma (R1) in the same rats by magnetic-resonance-imaging (MRI), microangiography and histopathology. METHODS: Thirty-six HCCs were created by diethylnitrosamine gavage in 14 rats that were also intrahepatically implanted with one R1 per rat as monitored by T2-/T1-weighted images (T2WI/T1WI) on a 3.0T clinical MRI-scanner. Vascular response and tumoral necrosis were detected by dynamic contrast-enhanced (DCE-) and CE-MRI before, 1 h after and 12 h after CA4P iv at 10 mg/kg (treatment group n = 7) or phosphate-buffered saline at 1.0 mL/kg (control group n = 7). Tumor blood supply was calculated by a semiquantitative DCE parameter of area under the time signal intensity curve (AUC30). In vivo MRI findings were verified by postmortem techniques. RESULTS: On CE-T1WIs, unlike the negative response in all tumors of control animals, in treatment group CA4P caused rapid extensive vascular shutdown in all R1-tumors, but mildly or spottily in HCCs at 1 h. Consequently, tumor necrosis occurred massively in R1-tumors but patchily in HCCs at 12 h. AUC30 revealed vascular closure (66%) in R1-tumors at 1 h (P < 0.05), followed by further perfusion decrease at 12 h (P < 0.01), while less significant vascular clogging occurred in HCCs. Histomorphologically, CA4P induced more extensive necrosis in R1-tumors (92.6%) than in HCCs (50.2%) (P < 0.01); tumor vascularity heterogeneously scored +~+++ in HCCs but homogeneously scored ++ in R1-tumors. CONCLUSION: This study suggests superior performance of CA4P in metastatic over primary liver cancers, which could guide future clinical applications of vascular-disrupting-agents.​ Baishideng Publishing Group Inc 2018-07-07 2018-07-07 /pmc/articles/PMC6034151/ /pubmed/29991876 http://dx.doi.org/10.3748/wjg.v24.i25.2710 Text en ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Basic Study
Liu, Ye-Wei
De Keyzer, Frederik
Feng, Yuan-Bo
Chen, Feng
Song, Shao-Li
Swinnen, Johan
Bormans, Guy
Oyen, Raymond
Huang, Gang
Ni, Yi-Cheng
Intra-individual comparison of therapeutic responses to vascular disrupting agent CA4P between rodent primary and secondary liver cancers
title Intra-individual comparison of therapeutic responses to vascular disrupting agent CA4P between rodent primary and secondary liver cancers
title_full Intra-individual comparison of therapeutic responses to vascular disrupting agent CA4P between rodent primary and secondary liver cancers
title_fullStr Intra-individual comparison of therapeutic responses to vascular disrupting agent CA4P between rodent primary and secondary liver cancers
title_full_unstemmed Intra-individual comparison of therapeutic responses to vascular disrupting agent CA4P between rodent primary and secondary liver cancers
title_short Intra-individual comparison of therapeutic responses to vascular disrupting agent CA4P between rodent primary and secondary liver cancers
title_sort intra-individual comparison of therapeutic responses to vascular disrupting agent ca4p between rodent primary and secondary liver cancers
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6034151/
https://www.ncbi.nlm.nih.gov/pubmed/29991876
http://dx.doi.org/10.3748/wjg.v24.i25.2710
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