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Antitumor activity of gemcitabine against high-grade meningioma in vitro and in vivo
Currently, there is no established therapeutic option for high-grade meningioma recurring after surgery and radiotherapy, and few chemotherapeutic agents are in development for the treatment of high-grade meningioma. Here in this study, we screened a panel of chemotherapeutic agents for their possib...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710900/ https://www.ncbi.nlm.nih.gov/pubmed/29207619 http://dx.doi.org/10.18632/oncotarget.18827 |
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author | Takeda, Hiroyuki Okada, Masashi Kuramoto, Kenta Suzuki, Shuhei Sakaki, Hirotsugu Sanomachi, Tomomi Seino, Shizuka Yoshioka, Takashi Hirano, Hirofumi Arita, Kazunori Kitanaka, Chifumi |
author_facet | Takeda, Hiroyuki Okada, Masashi Kuramoto, Kenta Suzuki, Shuhei Sakaki, Hirotsugu Sanomachi, Tomomi Seino, Shizuka Yoshioka, Takashi Hirano, Hirofumi Arita, Kazunori Kitanaka, Chifumi |
author_sort | Takeda, Hiroyuki |
collection | PubMed |
description | Currently, there is no established therapeutic option for high-grade meningioma recurring after surgery and radiotherapy, and few chemotherapeutic agents are in development for the treatment of high-grade meningioma. Here in this study, we screened a panel of chemotherapeutic agents for their possible antitumor activity in high-grade meningioma and discovered that high-grade meningioma cells show a preferential sensitivity to antimetabolites, in particular, to gemcitabine. In vitro, gemcitabine inhibited the growth of high-grade meningioma cells effectively by inducing S-phase arrest and apoptotic cell death. In vivo, systemic gemcitabine chemotherapy suppressed not only tumor initiation but also inhibited the growth and achieved a long-term control of established tumors in xenograft models of high-grade meningioma. Histological analysis indicated that systemic gemcitabine blocks cell cycle progression and promotes apoptotic cell death in tumor cells in vivo. Together, our data demonstrate that gemcitabine exerts potent antitumor activity against high-grade meningioma through cytostatic and cytotoxic mechanisms. We therefore propose gemcitabine is a promising chemotherapeutic agent that warrants further investigation as a treatment option for high-grade meningioma. |
format | Online Article Text |
id | pubmed-5710900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57109002017-12-04 Antitumor activity of gemcitabine against high-grade meningioma in vitro and in vivo Takeda, Hiroyuki Okada, Masashi Kuramoto, Kenta Suzuki, Shuhei Sakaki, Hirotsugu Sanomachi, Tomomi Seino, Shizuka Yoshioka, Takashi Hirano, Hirofumi Arita, Kazunori Kitanaka, Chifumi Oncotarget Research Paper Currently, there is no established therapeutic option for high-grade meningioma recurring after surgery and radiotherapy, and few chemotherapeutic agents are in development for the treatment of high-grade meningioma. Here in this study, we screened a panel of chemotherapeutic agents for their possible antitumor activity in high-grade meningioma and discovered that high-grade meningioma cells show a preferential sensitivity to antimetabolites, in particular, to gemcitabine. In vitro, gemcitabine inhibited the growth of high-grade meningioma cells effectively by inducing S-phase arrest and apoptotic cell death. In vivo, systemic gemcitabine chemotherapy suppressed not only tumor initiation but also inhibited the growth and achieved a long-term control of established tumors in xenograft models of high-grade meningioma. Histological analysis indicated that systemic gemcitabine blocks cell cycle progression and promotes apoptotic cell death in tumor cells in vivo. Together, our data demonstrate that gemcitabine exerts potent antitumor activity against high-grade meningioma through cytostatic and cytotoxic mechanisms. We therefore propose gemcitabine is a promising chemotherapeutic agent that warrants further investigation as a treatment option for high-grade meningioma. Impact Journals LLC 2017-06-29 /pmc/articles/PMC5710900/ /pubmed/29207619 http://dx.doi.org/10.18632/oncotarget.18827 Text en Copyright: © 2017 Takeda 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/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Takeda, Hiroyuki Okada, Masashi Kuramoto, Kenta Suzuki, Shuhei Sakaki, Hirotsugu Sanomachi, Tomomi Seino, Shizuka Yoshioka, Takashi Hirano, Hirofumi Arita, Kazunori Kitanaka, Chifumi Antitumor activity of gemcitabine against high-grade meningioma in vitro and in vivo |
title | Antitumor activity of gemcitabine against high-grade meningioma in vitro and in vivo |
title_full | Antitumor activity of gemcitabine against high-grade meningioma in vitro and in vivo |
title_fullStr | Antitumor activity of gemcitabine against high-grade meningioma in vitro and in vivo |
title_full_unstemmed | Antitumor activity of gemcitabine against high-grade meningioma in vitro and in vivo |
title_short | Antitumor activity of gemcitabine against high-grade meningioma in vitro and in vivo |
title_sort | antitumor activity of gemcitabine against high-grade meningioma in vitro and in vivo |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710900/ https://www.ncbi.nlm.nih.gov/pubmed/29207619 http://dx.doi.org/10.18632/oncotarget.18827 |
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