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Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation

Inflammatory bowel diseases (IBDs), such as Crohn’s disease or ulcerative colitis, can be treated with anti TNF-alpha (TNF-α) antibodies (Abs), but they also put patients with IBDs at risk of cancer. We aimed to determine whether the anti TNF-α Ab induces colon cancer development in vitro and in viv...

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Autores principales: Wang, Dan-Yang, Ohnuma, Shinobu, Suzuki, Hideyuki, Ishida, Masaharu, Ishii, Kentaro, Hirosawa, Takashi, Hirashima, Tomoaki, Murakami, Megumi, Kobayashi, Minoru, Kudoh, Katsuyoshi, Haneda, Sho, Musha, Hiroaki, Naitoh, Takeshi, Unno, Michiaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136890/
https://www.ncbi.nlm.nih.gov/pubmed/37185713
http://dx.doi.org/10.3390/cimb45040189
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author Wang, Dan-Yang
Ohnuma, Shinobu
Suzuki, Hideyuki
Ishida, Masaharu
Ishii, Kentaro
Hirosawa, Takashi
Hirashima, Tomoaki
Murakami, Megumi
Kobayashi, Minoru
Kudoh, Katsuyoshi
Haneda, Sho
Musha, Hiroaki
Naitoh, Takeshi
Unno, Michiaki
author_facet Wang, Dan-Yang
Ohnuma, Shinobu
Suzuki, Hideyuki
Ishida, Masaharu
Ishii, Kentaro
Hirosawa, Takashi
Hirashima, Tomoaki
Murakami, Megumi
Kobayashi, Minoru
Kudoh, Katsuyoshi
Haneda, Sho
Musha, Hiroaki
Naitoh, Takeshi
Unno, Michiaki
author_sort Wang, Dan-Yang
collection PubMed
description Inflammatory bowel diseases (IBDs), such as Crohn’s disease or ulcerative colitis, can be treated with anti TNF-alpha (TNF-α) antibodies (Abs), but they also put patients with IBDs at risk of cancer. We aimed to determine whether the anti TNF-α Ab induces colon cancer development in vitro and in vivo, and to identify the genes involved in colitis-associated cancer. We found that TNF-α (50 ng/mL) inhibited the proliferation, migration, and invasion of HCT8 and COLO205 colon cancer cell lines and that anti TNF-α Ab neutralized TNF-α inhibition in vitro. The effects of anti TNF-α Ab, infliximab (10 mg/kg) were investigated in mouse models of colitis-associated cancer induced by intraperitoneally injected azoxymethane (AOM: 10 mg/kg)/orally administered dextran sodium sulfate (DSS: 2.5%) (AOM/DSS) in vivo. Infliximab significantly attenuated the development of colon cancer in these mice. Microarray analyses and RT-qPCR revealed that mast cell protease 1, mast cell protease 2, and chymase 1 were up-regulated in cancer tissue of AOM/DSS mice; however, those mast cell related genes were downregulated in cancer tissue of AOM/DSS mice with infliximab. These results suggested that mast cells play a pivotal role in the development of cancer associated with colitis in AOM/DSS mice.
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spelling pubmed-101368902023-04-28 Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation Wang, Dan-Yang Ohnuma, Shinobu Suzuki, Hideyuki Ishida, Masaharu Ishii, Kentaro Hirosawa, Takashi Hirashima, Tomoaki Murakami, Megumi Kobayashi, Minoru Kudoh, Katsuyoshi Haneda, Sho Musha, Hiroaki Naitoh, Takeshi Unno, Michiaki Curr Issues Mol Biol Article Inflammatory bowel diseases (IBDs), such as Crohn’s disease or ulcerative colitis, can be treated with anti TNF-alpha (TNF-α) antibodies (Abs), but they also put patients with IBDs at risk of cancer. We aimed to determine whether the anti TNF-α Ab induces colon cancer development in vitro and in vivo, and to identify the genes involved in colitis-associated cancer. We found that TNF-α (50 ng/mL) inhibited the proliferation, migration, and invasion of HCT8 and COLO205 colon cancer cell lines and that anti TNF-α Ab neutralized TNF-α inhibition in vitro. The effects of anti TNF-α Ab, infliximab (10 mg/kg) were investigated in mouse models of colitis-associated cancer induced by intraperitoneally injected azoxymethane (AOM: 10 mg/kg)/orally administered dextran sodium sulfate (DSS: 2.5%) (AOM/DSS) in vivo. Infliximab significantly attenuated the development of colon cancer in these mice. Microarray analyses and RT-qPCR revealed that mast cell protease 1, mast cell protease 2, and chymase 1 were up-regulated in cancer tissue of AOM/DSS mice; however, those mast cell related genes were downregulated in cancer tissue of AOM/DSS mice with infliximab. These results suggested that mast cells play a pivotal role in the development of cancer associated with colitis in AOM/DSS mice. MDPI 2023-04-01 /pmc/articles/PMC10136890/ /pubmed/37185713 http://dx.doi.org/10.3390/cimb45040189 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Dan-Yang
Ohnuma, Shinobu
Suzuki, Hideyuki
Ishida, Masaharu
Ishii, Kentaro
Hirosawa, Takashi
Hirashima, Tomoaki
Murakami, Megumi
Kobayashi, Minoru
Kudoh, Katsuyoshi
Haneda, Sho
Musha, Hiroaki
Naitoh, Takeshi
Unno, Michiaki
Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation
title Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation
title_full Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation
title_fullStr Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation
title_full_unstemmed Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation
title_short Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation
title_sort infliximab inhibits colitis associated cancer in model mice by downregulating genes associated with mast cells and decreasing their accumulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136890/
https://www.ncbi.nlm.nih.gov/pubmed/37185713
http://dx.doi.org/10.3390/cimb45040189
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