Cargando…
Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy
Antiangiogenic agents transiently normalize tumor vessel structure and improve vessel function, thereby providing a window of opportunity for enhancing the efficacy of chemotherapy or radiotherapy. Currently, there are no reliable predictors or markers reflecting this vessel normalization window dur...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724822/ https://www.ncbi.nlm.nih.gov/pubmed/26475217 http://dx.doi.org/10.1111/cas.12836 |
_version_ | 1782411589354258432 |
---|---|
author | Zhang, Li Takara, Kazuhiro Yamakawa, Daishi Kidoya, Hiroyasu Takakura, Nobuyuki |
author_facet | Zhang, Li Takara, Kazuhiro Yamakawa, Daishi Kidoya, Hiroyasu Takakura, Nobuyuki |
author_sort | Zhang, Li |
collection | PubMed |
description | Antiangiogenic agents transiently normalize tumor vessel structure and improve vessel function, thereby providing a window of opportunity for enhancing the efficacy of chemotherapy or radiotherapy. Currently, there are no reliable predictors or markers reflecting this vessel normalization window during antiangiogenic therapy. Apelin, the expression of which is regulated by hypoxia, and which has well‐described roles in tumor progression, is an easily measured secreted protein. Here, we show that apelin can be used as a marker for the vessel normalization window during antiangiogenic therapy. Mice bearing s.c. tumors resulting from inoculation of the colon adenocarcinoma cell line HT29 were treated with a single injection of bevacizumab, a mAb neutralizing vascular endothelial growth factor. Tumor growth, vessel density, pericyte coverage, tumor hypoxia, and small molecule delivery were determined at four different times after treatment with bevacizumab (days 1, 3, 5, and 8). Tumor growth and vessel density were significantly reduced after bevacizumab treatment, which also significantly increased tumor vessel maturity, and improved tumor hypoxia and small molecule delivery between days 3 and 5. These effects abated by day 8, suggesting that a time window for vessel normalization was opened between days 3 and 5 during bevacizumab treatment in this model. Apelin mRNA expression and plasma apelin levels decreased transiently at day 5 post‐treatment, coinciding with vessel normalization. Thus, apelin is a potential indicator of the vessel normalization window during antiangiogenic therapy. |
format | Online Article Text |
id | pubmed-4724822 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-47248222016-02-03 Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy Zhang, Li Takara, Kazuhiro Yamakawa, Daishi Kidoya, Hiroyasu Takakura, Nobuyuki Cancer Sci Original Articles Antiangiogenic agents transiently normalize tumor vessel structure and improve vessel function, thereby providing a window of opportunity for enhancing the efficacy of chemotherapy or radiotherapy. Currently, there are no reliable predictors or markers reflecting this vessel normalization window during antiangiogenic therapy. Apelin, the expression of which is regulated by hypoxia, and which has well‐described roles in tumor progression, is an easily measured secreted protein. Here, we show that apelin can be used as a marker for the vessel normalization window during antiangiogenic therapy. Mice bearing s.c. tumors resulting from inoculation of the colon adenocarcinoma cell line HT29 were treated with a single injection of bevacizumab, a mAb neutralizing vascular endothelial growth factor. Tumor growth, vessel density, pericyte coverage, tumor hypoxia, and small molecule delivery were determined at four different times after treatment with bevacizumab (days 1, 3, 5, and 8). Tumor growth and vessel density were significantly reduced after bevacizumab treatment, which also significantly increased tumor vessel maturity, and improved tumor hypoxia and small molecule delivery between days 3 and 5. These effects abated by day 8, suggesting that a time window for vessel normalization was opened between days 3 and 5 during bevacizumab treatment in this model. Apelin mRNA expression and plasma apelin levels decreased transiently at day 5 post‐treatment, coinciding with vessel normalization. Thus, apelin is a potential indicator of the vessel normalization window during antiangiogenic therapy. John Wiley and Sons Inc. 2015-11-12 2016-01 /pmc/articles/PMC4724822/ /pubmed/26475217 http://dx.doi.org/10.1111/cas.12836 Text en © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Zhang, Li Takara, Kazuhiro Yamakawa, Daishi Kidoya, Hiroyasu Takakura, Nobuyuki Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy |
title | Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy |
title_full | Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy |
title_fullStr | Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy |
title_full_unstemmed | Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy |
title_short | Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy |
title_sort | apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724822/ https://www.ncbi.nlm.nih.gov/pubmed/26475217 http://dx.doi.org/10.1111/cas.12836 |
work_keys_str_mv | AT zhangli apelinasamarkerformonitoringthetumorvesselnormalizationwindowduringantiangiogenictherapy AT takarakazuhiro apelinasamarkerformonitoringthetumorvesselnormalizationwindowduringantiangiogenictherapy AT yamakawadaishi apelinasamarkerformonitoringthetumorvesselnormalizationwindowduringantiangiogenictherapy AT kidoyahiroyasu apelinasamarkerformonitoringthetumorvesselnormalizationwindowduringantiangiogenictherapy AT takakuranobuyuki apelinasamarkerformonitoringthetumorvesselnormalizationwindowduringantiangiogenictherapy |