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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...

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Autores principales: Takeda, Hiroyuki, Okada, Masashi, Kuramoto, Kenta, Suzuki, Shuhei, Sakaki, Hirotsugu, Sanomachi, Tomomi, Seino, Shizuka, Yoshioka, Takashi, Hirano, Hirofumi, Arita, Kazunori, Kitanaka, Chifumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
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.
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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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