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The blockade of interleukin‐33 released by hepatectomy would be a promising treatment option for cholangiocarcinoma

Interleukin‐33 (IL‐33), an alarmin released during tissue injury, facilitates the development of cholangiocarcinoma (CCA) in a murine model. However, it is unclear whether IL‐33 is associated with human CCA. The aim of this study was to support the following hypothesis: IL‐33 is released during hepa...

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Autores principales: Nagaoka, Satoshi, Yamada, Daisaku, Eguchi, Hidetoshi, Yokota, Yuki, Iwagami, Yoshifumi, Asaoka, Tadafumi, Noda, Takehiro, Kawamoto, Koichi, Gotoh, Kunihito, Kobayashi, Shogo, Miyoshi, Eiji, Doki, Yuichiro, Mori, Masaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780022/
https://www.ncbi.nlm.nih.gov/pubmed/33098728
http://dx.doi.org/10.1111/cas.14709
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author Nagaoka, Satoshi
Yamada, Daisaku
Eguchi, Hidetoshi
Yokota, Yuki
Iwagami, Yoshifumi
Asaoka, Tadafumi
Noda, Takehiro
Kawamoto, Koichi
Gotoh, Kunihito
Kobayashi, Shogo
Miyoshi, Eiji
Doki, Yuichiro
Mori, Masaki
author_facet Nagaoka, Satoshi
Yamada, Daisaku
Eguchi, Hidetoshi
Yokota, Yuki
Iwagami, Yoshifumi
Asaoka, Tadafumi
Noda, Takehiro
Kawamoto, Koichi
Gotoh, Kunihito
Kobayashi, Shogo
Miyoshi, Eiji
Doki, Yuichiro
Mori, Masaki
author_sort Nagaoka, Satoshi
collection PubMed
description Interleukin‐33 (IL‐33), an alarmin released during tissue injury, facilitates the development of cholangiocarcinoma (CCA) in a murine model. However, it is unclear whether IL‐33 is associated with human CCA. The aim of this study was to support the following hypothesis: IL‐33 is released during hepatectomy for CCA, subsequently facilitating the development of subclinical CCA and eventually leading to recurrent disease. IL‐33 expression was assessed in various samples from both humans and mice including resected liver and paired plasma samples collected at hepatectomy and after surgery, and its influences on recurrent disease and patient prognosis were determined. Homogenized human liver samples with high or low IL‐33 expression were added to the culture medium of human CCA cells, and the changes in proliferation and migration were evaluated. To examine the effects of inhibiting the IL‐33 release induced by hepatectomy, syngraft transplantation of murine CCA cells was performed in C57BL/6J mice with or without IL‐33 blockade. The amount of IL‐33 released into the plasma during hepatectomy correlated with the background liver expression. High expression of IL‐33 in the liver was an independent risk factor for recurrence. Homogenized liver tissue strongly expressing IL‐33 increased both the proliferation and migration of tumor cells. Mice who underwent hepatectomy exhibited CCA progression in the remnant liver, whereas blockade of IL‐33 during hepatectomy inhibited tumor progression. Thus, we concluded that surgery for CCA with curative intent paradoxically induced IL‐33 release, which facilitated CCA recurrence, and anti–IL‐33 therapy during hepatectomy might reduce the risk of CCA recurrence.
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spelling pubmed-77800222021-01-08 The blockade of interleukin‐33 released by hepatectomy would be a promising treatment option for cholangiocarcinoma Nagaoka, Satoshi Yamada, Daisaku Eguchi, Hidetoshi Yokota, Yuki Iwagami, Yoshifumi Asaoka, Tadafumi Noda, Takehiro Kawamoto, Koichi Gotoh, Kunihito Kobayashi, Shogo Miyoshi, Eiji Doki, Yuichiro Mori, Masaki Cancer Sci Clinical Research Interleukin‐33 (IL‐33), an alarmin released during tissue injury, facilitates the development of cholangiocarcinoma (CCA) in a murine model. However, it is unclear whether IL‐33 is associated with human CCA. The aim of this study was to support the following hypothesis: IL‐33 is released during hepatectomy for CCA, subsequently facilitating the development of subclinical CCA and eventually leading to recurrent disease. IL‐33 expression was assessed in various samples from both humans and mice including resected liver and paired plasma samples collected at hepatectomy and after surgery, and its influences on recurrent disease and patient prognosis were determined. Homogenized human liver samples with high or low IL‐33 expression were added to the culture medium of human CCA cells, and the changes in proliferation and migration were evaluated. To examine the effects of inhibiting the IL‐33 release induced by hepatectomy, syngraft transplantation of murine CCA cells was performed in C57BL/6J mice with or without IL‐33 blockade. The amount of IL‐33 released into the plasma during hepatectomy correlated with the background liver expression. High expression of IL‐33 in the liver was an independent risk factor for recurrence. Homogenized liver tissue strongly expressing IL‐33 increased both the proliferation and migration of tumor cells. Mice who underwent hepatectomy exhibited CCA progression in the remnant liver, whereas blockade of IL‐33 during hepatectomy inhibited tumor progression. Thus, we concluded that surgery for CCA with curative intent paradoxically induced IL‐33 release, which facilitated CCA recurrence, and anti–IL‐33 therapy during hepatectomy might reduce the risk of CCA recurrence. John Wiley and Sons Inc. 2020-11-24 2021-01 /pmc/articles/PMC7780022/ /pubmed/33098728 http://dx.doi.org/10.1111/cas.14709 Text en © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Clinical Research
Nagaoka, Satoshi
Yamada, Daisaku
Eguchi, Hidetoshi
Yokota, Yuki
Iwagami, Yoshifumi
Asaoka, Tadafumi
Noda, Takehiro
Kawamoto, Koichi
Gotoh, Kunihito
Kobayashi, Shogo
Miyoshi, Eiji
Doki, Yuichiro
Mori, Masaki
The blockade of interleukin‐33 released by hepatectomy would be a promising treatment option for cholangiocarcinoma
title The blockade of interleukin‐33 released by hepatectomy would be a promising treatment option for cholangiocarcinoma
title_full The blockade of interleukin‐33 released by hepatectomy would be a promising treatment option for cholangiocarcinoma
title_fullStr The blockade of interleukin‐33 released by hepatectomy would be a promising treatment option for cholangiocarcinoma
title_full_unstemmed The blockade of interleukin‐33 released by hepatectomy would be a promising treatment option for cholangiocarcinoma
title_short The blockade of interleukin‐33 released by hepatectomy would be a promising treatment option for cholangiocarcinoma
title_sort blockade of interleukin‐33 released by hepatectomy would be a promising treatment option for cholangiocarcinoma
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780022/
https://www.ncbi.nlm.nih.gov/pubmed/33098728
http://dx.doi.org/10.1111/cas.14709
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