Chronic pathophysiological changes in the normal brain parenchyma caused by radiotherapy accelerate glioma progression

Abstract Radiation therapy is one of standard treatment for malignant glioma after surgery. The microenvironment after irradiation is considered not to be suitable for the survival of tumor cells (tumor bed effect). This study investigated whether the effect of changes in the microenvironment of par...

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Autores principales: Yuichiro Tsuji, Naosuke Nonoguchi, Daisuke Okuzaki, Yusuke Wada, Daisuke Motooka, Yuki Hirota, Taichiro Toho, Nobuhiko Yoshikawa, Motomasa Furuse, Shinji Kawabata, Shin-Ichi Miyatake, Hiroyuki Nakamura, Ryohei Yamamoto, Shota Nakamura, Toshihiko Kuroiwa, Masahiko Wanibuchi
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:0d7b40efdd7d417caacb63654302e46c2021-11-14T12:22:41ZChronic pathophysiological changes in the normal brain parenchyma caused by radiotherapy accelerate glioma progression10.1038/s41598-021-01475-02045-2322https://doaj.org/article/0d7b40efdd7d417caacb63654302e46c2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01475-0https://doaj.org/toc/2045-2322Abstract Radiation therapy is one of standard treatment for malignant glioma after surgery. The microenvironment after irradiation is considered not to be suitable for the survival of tumor cells (tumor bed effect). This study investigated whether the effect of changes in the microenvironment of parenchymal brain tissue caused by radiotherapy affect the recurrence and progression of glioma. 65-Gy irradiation had been applied to the right hemisphere of Fisher rats. After 3 months from irradiation, we extracted RNA and protein from the irradiated rat brain. To study effects of proteins extracted from the brains, we performed WST-8 assay and tube formation assay in vitro. Cytokine production were investigated for qPCR. Additionally, we transplanted glioma cell into the irradiated and sham animals and the median survival time of F98 transplanted rats was also examined in vivo. Immunohistochemical analyses and invasiveness of implanted tumor were evaluated. X-ray irradiation promoted the secretion of cytokines such as CXCL12, VEGF-A, TGF-β1 and TNFα from the irradiated brain. Proteins extracted from the irradiated brain promoted the proliferation and angiogenic activity of F98 glioma cells. Glioma cells implanted in the irradiated brains showed significantly high proliferation, angiogenesis and invasive ability, and the post-irradiation F98 tumor-implanted rats showed a shorter median survival time compared to the Sham-irradiation group. The current study suggests that the microenvironment around the brain tissue in the chronic phase after exposure to X-ray radiation becomes suitable for glioma cell growth and invasion.Yuichiro TsujiNaosuke NonoguchiDaisuke OkuzakiYusuke WadaDaisuke MotookaYuki HirotaTaichiro TohoNobuhiko YoshikawaMotomasa FuruseShinji KawabataShin-Ichi MiyatakeHiroyuki NakamuraRyohei YamamotoShota NakamuraToshihiko KuroiwaMasahiko WanibuchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yuichiro Tsuji
Naosuke Nonoguchi
Daisuke Okuzaki
Yusuke Wada
Daisuke Motooka
Yuki Hirota
Taichiro Toho
Nobuhiko Yoshikawa
Motomasa Furuse
Shinji Kawabata
Shin-Ichi Miyatake
Hiroyuki Nakamura
Ryohei Yamamoto
Shota Nakamura
Toshihiko Kuroiwa
Masahiko Wanibuchi
Chronic pathophysiological changes in the normal brain parenchyma caused by radiotherapy accelerate glioma progression
description Abstract Radiation therapy is one of standard treatment for malignant glioma after surgery. The microenvironment after irradiation is considered not to be suitable for the survival of tumor cells (tumor bed effect). This study investigated whether the effect of changes in the microenvironment of parenchymal brain tissue caused by radiotherapy affect the recurrence and progression of glioma. 65-Gy irradiation had been applied to the right hemisphere of Fisher rats. After 3 months from irradiation, we extracted RNA and protein from the irradiated rat brain. To study effects of proteins extracted from the brains, we performed WST-8 assay and tube formation assay in vitro. Cytokine production were investigated for qPCR. Additionally, we transplanted glioma cell into the irradiated and sham animals and the median survival time of F98 transplanted rats was also examined in vivo. Immunohistochemical analyses and invasiveness of implanted tumor were evaluated. X-ray irradiation promoted the secretion of cytokines such as CXCL12, VEGF-A, TGF-β1 and TNFα from the irradiated brain. Proteins extracted from the irradiated brain promoted the proliferation and angiogenic activity of F98 glioma cells. Glioma cells implanted in the irradiated brains showed significantly high proliferation, angiogenesis and invasive ability, and the post-irradiation F98 tumor-implanted rats showed a shorter median survival time compared to the Sham-irradiation group. The current study suggests that the microenvironment around the brain tissue in the chronic phase after exposure to X-ray radiation becomes suitable for glioma cell growth and invasion.
format article
author Yuichiro Tsuji
Naosuke Nonoguchi
Daisuke Okuzaki
Yusuke Wada
Daisuke Motooka
Yuki Hirota
Taichiro Toho
Nobuhiko Yoshikawa
Motomasa Furuse
Shinji Kawabata
Shin-Ichi Miyatake
Hiroyuki Nakamura
Ryohei Yamamoto
Shota Nakamura
Toshihiko Kuroiwa
Masahiko Wanibuchi
author_facet Yuichiro Tsuji
Naosuke Nonoguchi
Daisuke Okuzaki
Yusuke Wada
Daisuke Motooka
Yuki Hirota
Taichiro Toho
Nobuhiko Yoshikawa
Motomasa Furuse
Shinji Kawabata
Shin-Ichi Miyatake
Hiroyuki Nakamura
Ryohei Yamamoto
Shota Nakamura
Toshihiko Kuroiwa
Masahiko Wanibuchi
author_sort Yuichiro Tsuji
title Chronic pathophysiological changes in the normal brain parenchyma caused by radiotherapy accelerate glioma progression
title_short Chronic pathophysiological changes in the normal brain parenchyma caused by radiotherapy accelerate glioma progression
title_full Chronic pathophysiological changes in the normal brain parenchyma caused by radiotherapy accelerate glioma progression
title_fullStr Chronic pathophysiological changes in the normal brain parenchyma caused by radiotherapy accelerate glioma progression
title_full_unstemmed Chronic pathophysiological changes in the normal brain parenchyma caused by radiotherapy accelerate glioma progression
title_sort chronic pathophysiological changes in the normal brain parenchyma caused by radiotherapy accelerate glioma progression
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/0d7b40efdd7d417caacb63654302e46c
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