Gastrointestinal toxicities of 5-fluorouracil increase the proportion of regulatory T cells in intestinal tract: advantages of alternate-day S-1 administration
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| 024 | 7 | 0 | |a 10.1007/s10147-015-0791-x |2 doi |
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| 245 | 0 | 0 | |a Gastrointestinal toxicities of 5-fluorouracil increase the proportion of regulatory T cells in intestinal tract: advantages of alternate-day S-1 administration |h [Elektronische Daten] |c [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] |
| 520 | 3 | |a 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. | |
| 540 | |a Japan Society of Clinical Oncology, 2015 | ||
| 690 | 7 | |a 5-FU |2 nationallicence | |
| 690 | 7 | |a Gastrointestinal toxicity |2 nationallicence | |
| 690 | 7 | |a Regulatory T cell |2 nationallicence | |
| 690 | 7 | |a S-1 |2 nationallicence | |
| 690 | 7 | |a Alternate-day administration |2 nationallicence | |
| 690 | 7 | |a 5-FU : 5-Fluorouracil |2 nationallicence | |
| 690 | 7 | |a GI : Gastrointestinal |2 nationallicence | |
| 690 | 7 | |a FT : Tegafur |2 nationallicence | |
| 690 | 7 | |a CDHP : 5-Chloro-2,4-dihydroxypyridine |2 nationallicence | |
| 690 | 7 | |a Oxo : Potassium oxonate |2 nationallicence | |
| 690 | 7 | |a Tregs : Regulatory T cells |2 nationallicence | |
| 690 | 7 | |a MLN : Mesenteric lymph node |2 nationallicence | |
| 690 | 7 | |a GALT : Gut-associated lymphoid tissue |2 nationallicence | |
| 690 | 7 | |a HPMC : Hydroxypropyl methylcellulose |2 nationallicence | |
| 690 | 7 | |a PP : Peyer's patch |2 nationallicence | |
| 690 | 7 | |a LP : Lamina propria |2 nationallicence | |
| 690 | 7 | |a IE : Intraepithelial |2 nationallicence | |
| 690 | 7 | |a CTL : Cytotoxic T lymphocyte |2 nationallicence | |
| 690 | 7 | |a NO : Nitric oxide |2 nationallicence | |
| 700 | 1 | |a Kajiwara |D Taiki |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Miura |D Koh |u Department of Surgery, Miyagi Cancer Center, 47-1 Nodayama, Medeshima-Shiote, 981-1293, Natori, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Ohnuma |D Shinobu |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Shimada |D Miki |u Pharmaceutical Department, Tottori University Hospital, 683-8504, Yonago, Tottori, Japan |4 aut | |
| 700 | 1 | |a Komura |D Toshihiro |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Toshima |D Masahide |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Kohyama |D Atsushi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Kudoh |D Katsuyoshi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Haneda |D Sho |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Musha |D Hiroaki |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Naitoh |D Takeshi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Shirasaka |D Tetsuhiko |u Kitasato Institute for Life Science, Kitasato University, 5-9-1 Shirokane, 108-8641, Minato-ku, Tokyo, Japan |4 aut | |
| 700 | 1 | |a Unno |D Michiaki |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 773 | 0 | |t International Journal of Clinical Oncology |d Springer Japan |g 20/5(2015-10-01), 913-921 |x 1341-9625 |q 20:5<913 |1 2015 |2 20 |o 10147 | |
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| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kajiwara |D Taiki |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Miura |D Koh |u Department of Surgery, Miyagi Cancer Center, 47-1 Nodayama, Medeshima-Shiote, 981-1293, Natori, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Ohnuma |D Shinobu |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Shimada |D Miki |u Pharmaceutical Department, Tottori University Hospital, 683-8504, Yonago, Tottori, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Komura |D Toshihiro |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Toshima |D Masahide |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kohyama |D Atsushi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kudoh |D Katsuyoshi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Haneda |D Sho |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Musha |D Hiroaki |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Naitoh |D Takeshi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Shirasaka |D Tetsuhiko |u Kitasato Institute for Life Science, Kitasato University, 5-9-1 Shirokane, 108-8641, Minato-ku, Tokyo, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Unno |D Michiaki |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t International Journal of Clinical Oncology |d Springer Japan |g 20/5(2015-10-01), 913-921 |x 1341-9625 |q 20:5<913 |1 2015 |2 20 |o 10147 | ||