caa a22 4500 605491496 CHVBK 20210128100510.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s10147-015-0791-x doi (NATIONALLICENCE)springer-10.1007/s10147-015-0791-x Gastrointestinal toxicities of 5-fluorouracil increase the proportion of regulatory T cells in intestinal tract: advantages of alternate-day S-1 administration [Elektronische Daten] [Taiki Kajiwara, Koh Miura, Shinobu Ohnuma, Miki Shimada, Toshihiro Komura, Masahide Toshima, Atsushi Kohyama, Katsuyoshi Kudoh, Sho Haneda, Hiroaki Musha, Takeshi Naitoh, Tetsuhiko Shirasaka, Michiaki Unno] Background: 5-Fluorouracil (5-FU), a core anticancer agent for malignancies, induces gastrointestinal (GI) toxicities. Despite recent advances in tumor immunology, it still remains unknown how GI toxicities affect antitumor immunity. S-1 is a tegafur-based oral 5-FU prodrug which has been widely introduced in Japan and other countries. The alternate-day S-1 administration has been proposed to minimize its GI and other toxicities without reducing its anticancer efficacy. Methods: In this study, two S-1 administration regimens were compared in mice to evaluate their impact of GI toxicities on immunity. In the daily group as a standard administration model, S-1 was administered for 14days on and 14days off, and in the alternate-day group as a non-GI toxicity model, S-1 was administered every other day for 28days. As well as physical findings, regulatory T cells, Th1 cells and other cells in murine lymphoid tissues were analyzed with flow cytometry. Results: Only the daily group exhibited body weight loss and GI toxicities. In the daily group, a proportion of regulatory T cells in the intestinal lymphoid tissue were demonstrated to be six-fold higher than in the control without S-1, and the proportion of Th1 cells showed a decreasing trend. However, the alternate-day group exhibited almost no change in T-cell subsets. Conclusion: GI toxicities of 5-FU may have a negative influence on antitumor immunity due to increased proportions of regulatory T cells and decreased proportions of Th1 cells. The alternate-day S-1 administration may be a useful regimen with its minimal influence on T-cell subsets. Japan Society of Clinical Oncology, 2015 5-FU nationallicence Gastrointestinal toxicity nationallicence Regulatory T cell nationallicence S-1 nationallicence Alternate-day administration nationallicence 5-FU : 5-Fluorouracil nationallicence GI : Gastrointestinal nationallicence FT : Tegafur nationallicence CDHP : 5-Chloro-2,4-dihydroxypyridine nationallicence Oxo : Potassium oxonate nationallicence Tregs : Regulatory T cells nationallicence MLN : Mesenteric lymph node nationallicence GALT : Gut-associated lymphoid tissue nationallicence HPMC : Hydroxypropyl methylcellulose nationallicence PP : Peyer's patch nationallicence LP : Lamina propria nationallicence IE : Intraepithelial nationallicence CTL : Cytotoxic T lymphocyte nationallicence NO : Nitric oxide nationallicence Kajiwara Taiki Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut Miura Koh Department of Surgery, Miyagi Cancer Center, 47-1 Nodayama, Medeshima-Shiote, 981-1293, Natori, Miyagi, Japan aut Ohnuma Shinobu Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut Shimada Miki Pharmaceutical Department, Tottori University Hospital, 683-8504, Yonago, Tottori, Japan aut Komura Toshihiro Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut Toshima Masahide Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut Kohyama Atsushi Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut Kudoh Katsuyoshi Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut Haneda Sho Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut Musha Hiroaki Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut Naitoh Takeshi Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut Shirasaka Tetsuhiko Kitasato Institute for Life Science, Kitasato University, 5-9-1 Shirokane, 108-8641, Minato-ku, Tokyo, Japan aut Unno Michiaki Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut International Journal of Clinical Oncology Springer Japan 20/5(2015-10-01), 913-921 1341-9625 20:5<913 2015 20 10147 https://doi.org/10.1007/s10147-015-0791-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10147-015-0791-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kajiwara Taiki Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut NATIONALLICENCE 700 1- Miura Koh Department of Surgery, Miyagi Cancer Center, 47-1 Nodayama, Medeshima-Shiote, 981-1293, Natori, Miyagi, Japan aut NATIONALLICENCE 700 1- Ohnuma Shinobu Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut NATIONALLICENCE 700 1- Shimada Miki Pharmaceutical Department, Tottori University Hospital, 683-8504, Yonago, Tottori, Japan aut NATIONALLICENCE 700 1- Komura Toshihiro Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut NATIONALLICENCE 700 1- Toshima Masahide Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut NATIONALLICENCE 700 1- Kohyama Atsushi Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut NATIONALLICENCE 700 1- Kudoh Katsuyoshi Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut NATIONALLICENCE 700 1- Haneda Sho Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut NATIONALLICENCE 700 1- Musha Hiroaki Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut NATIONALLICENCE 700 1- Naitoh Takeshi Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut NATIONALLICENCE 700 1- Shirasaka Tetsuhiko Kitasato Institute for Life Science, Kitasato University, 5-9-1 Shirokane, 108-8641, Minato-ku, Tokyo, Japan aut NATIONALLICENCE 700 1- Unno Michiaki Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan aut NATIONALLICENCE 773 0- International Journal of Clinical Oncology Springer Japan 20/5(2015-10-01), 913-921 1341-9625 20:5<913 2015 20 10147