Cargando…

Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P

We sought to investigate anticancer efficacy of a vascular disrupting agent (VDA) combretastatin A-4 phosphate (CA4P) in relation to tumor size among hepatocellular carcinomas (HCCs) in rats using magnetic resonance imaging (MRI) and postmortem techniques. Nineteen rats with 43 chemically-induced HC...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Yewei, Yin, Ting, Keyzer, Frederik De, Feng, Yuanbo, Chen, Feng, Liu, Jianjun, Song, Shaoli, Yu, Jie, Vandecaveye, Vincent, Swinnen, Johan, Bormans, Guy, Himmelreich, Uwe, Oyen, Raymond, Zhang, Jian, Huang, Gang, Ni, Yicheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589653/
https://www.ncbi.nlm.nih.gov/pubmed/28903414
http://dx.doi.org/10.18632/oncotarget.19339
_version_ 1783262376351498240
author Liu, Yewei
Yin, Ting
Keyzer, Frederik De
Feng, Yuanbo
Chen, Feng
Liu, Jianjun
Song, Shaoli
Yu, Jie
Vandecaveye, Vincent
Swinnen, Johan
Bormans, Guy
Himmelreich, Uwe
Oyen, Raymond
Zhang, Jian
Huang, Gang
Ni, Yicheng
author_facet Liu, Yewei
Yin, Ting
Keyzer, Frederik De
Feng, Yuanbo
Chen, Feng
Liu, Jianjun
Song, Shaoli
Yu, Jie
Vandecaveye, Vincent
Swinnen, Johan
Bormans, Guy
Himmelreich, Uwe
Oyen, Raymond
Zhang, Jian
Huang, Gang
Ni, Yicheng
author_sort Liu, Yewei
collection PubMed
description We sought to investigate anticancer efficacy of a vascular disrupting agent (VDA) combretastatin A-4 phosphate (CA4P) in relation to tumor size among hepatocellular carcinomas (HCCs) in rats using magnetic resonance imaging (MRI) and postmortem techniques. Nineteen rats with 43 chemically-induced HCCs of 2.8–20.9 mm in size on liver cirrhosis received CA4P intravenously at 10 mg/kg. Tumor-diameter was measured by T2-weighted imaging (T2WI) to define microcancers (< 5 mm) versus larger HCCs. Vascular responses and tissue necrosis were detected by diffusion-weighted imaging (DWI), contrast-enhanced T1-weighted imaging (CE-T1WI) and dynamic contrast enhanced (DCE-) MRI, which were validated by microangiography and histopathology. MRI revealed nearly complete necrosis in 5 out of 7 micro-HCCs, but diverse therapeutic necrosis in larger HCCs with a positive correlation with tumor size. Necrosis in micro-HCCs was 36.9% more than that in larger HCCs. While increased diffusion coefficient (ADC(diff)) suggested tumor necrosis, perfusion coefficient (ADC(perf)) indicated sharply decreased blood perfusion in cirrhotic liver together with a reduction in micro-HCCs. DCE revealed lowered tumor blood flow from intravascular into extravascular extracellular space (EES). Microangiography and histopathology revealed hypo- and hypervascularity in 4 and 3 micro-HCCs, massive, partial and minor degrees of tumoral necrosis in 5, 1 and 1 micro-HCCs respectively, and patchy necrotic foci in cirrhotic liver. CD34-PAS staining implicated that poorly vascularized micro-HCCs growing on liver cirrhosis tended to respond better to CA4P treatment. In this study, more complete CA4P-response occurred unexpectedly in micro-HCCs in rats, along with CA4P-induced necrotic foci in cirrhotic liver. These may help to plan clinical applications of VDAs in patients with HCCs and liver cirrhosis.
format Online
Article
Text
id pubmed-5589653
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-55896532017-09-12 Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P Liu, Yewei Yin, Ting Keyzer, Frederik De Feng, Yuanbo Chen, Feng Liu, Jianjun Song, Shaoli Yu, Jie Vandecaveye, Vincent Swinnen, Johan Bormans, Guy Himmelreich, Uwe Oyen, Raymond Zhang, Jian Huang, Gang Ni, Yicheng Oncotarget Research Paper We sought to investigate anticancer efficacy of a vascular disrupting agent (VDA) combretastatin A-4 phosphate (CA4P) in relation to tumor size among hepatocellular carcinomas (HCCs) in rats using magnetic resonance imaging (MRI) and postmortem techniques. Nineteen rats with 43 chemically-induced HCCs of 2.8–20.9 mm in size on liver cirrhosis received CA4P intravenously at 10 mg/kg. Tumor-diameter was measured by T2-weighted imaging (T2WI) to define microcancers (< 5 mm) versus larger HCCs. Vascular responses and tissue necrosis were detected by diffusion-weighted imaging (DWI), contrast-enhanced T1-weighted imaging (CE-T1WI) and dynamic contrast enhanced (DCE-) MRI, which were validated by microangiography and histopathology. MRI revealed nearly complete necrosis in 5 out of 7 micro-HCCs, but diverse therapeutic necrosis in larger HCCs with a positive correlation with tumor size. Necrosis in micro-HCCs was 36.9% more than that in larger HCCs. While increased diffusion coefficient (ADC(diff)) suggested tumor necrosis, perfusion coefficient (ADC(perf)) indicated sharply decreased blood perfusion in cirrhotic liver together with a reduction in micro-HCCs. DCE revealed lowered tumor blood flow from intravascular into extravascular extracellular space (EES). Microangiography and histopathology revealed hypo- and hypervascularity in 4 and 3 micro-HCCs, massive, partial and minor degrees of tumoral necrosis in 5, 1 and 1 micro-HCCs respectively, and patchy necrotic foci in cirrhotic liver. CD34-PAS staining implicated that poorly vascularized micro-HCCs growing on liver cirrhosis tended to respond better to CA4P treatment. In this study, more complete CA4P-response occurred unexpectedly in micro-HCCs in rats, along with CA4P-induced necrotic foci in cirrhotic liver. These may help to plan clinical applications of VDAs in patients with HCCs and liver cirrhosis. Impact Journals LLC 2017-07-18 /pmc/articles/PMC5589653/ /pubmed/28903414 http://dx.doi.org/10.18632/oncotarget.19339 Text en Copyright: © 2017 Liu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Liu, Yewei
Yin, Ting
Keyzer, Frederik De
Feng, Yuanbo
Chen, Feng
Liu, Jianjun
Song, Shaoli
Yu, Jie
Vandecaveye, Vincent
Swinnen, Johan
Bormans, Guy
Himmelreich, Uwe
Oyen, Raymond
Zhang, Jian
Huang, Gang
Ni, Yicheng
Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P
title Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P
title_full Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P
title_fullStr Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P
title_full_unstemmed Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P
title_short Micro-HCCs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent CA4P
title_sort micro-hccs in rats with liver cirrhosis: paradoxical targeting effects with vascular disrupting agent ca4p
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589653/
https://www.ncbi.nlm.nih.gov/pubmed/28903414
http://dx.doi.org/10.18632/oncotarget.19339
work_keys_str_mv AT liuyewei microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT yinting microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT keyzerfrederikde microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT fengyuanbo microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT chenfeng microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT liujianjun microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT songshaoli microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT yujie microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT vandecaveyevincent microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT swinnenjohan microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT bormansguy microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT himmelreichuwe microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT oyenraymond microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT zhangjian microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT huanggang microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p
AT niyicheng microhccsinratswithlivercirrhosisparadoxicaltargetingeffectswithvasculardisruptingagentca4p