FullText URL blood_119_1_285.pdf
Author Nishimori, Hisakazu| Maeda, Yoshinobu| Teshima, Takanori| Sugiyama, Haruko| Kobayashi, Koichiro| Yamasuji, Yoshiko| Kadohisa, Sachiyo| Uryu, Hidetaka| Takeuchi, Kengo| Tanaka, Takehiro| Yoshino, Tadashi| Iwakura, Yoichiro| Tanimoto, Mitsune|
Abstract Chronic GVHD (cGVHD) is a main cause of late death and morbidity after allogeneic hematopoietic cell transplantation, but its pathogenesis remains unclear. We investigated the roles of Th subsets in cGVHD with the use of a well-defined mouse model of cGVHD. In this model, development of cGVHD was associated with up-regulated Th1, Th2, and Th17 responses. Th1 and Th2 responses were up-regulated early after BM transplantation, followed by a subsequent up-regulation of Th17 cells. Significantly greater numbers of Th17 cells were infiltrated in the lung and liver from allogeneic recipients than those from syngeneic recipients. We then evaluated the roles of Th1 and Th17 in cGVHD with the use of IFN-γ-deficient and IL-17-deficient mice as donors. Infusion of IFN-γ(-/-) or IL-17(-/-) T cells attenuated cGVHD in the skin and salivary glands. Am80, a potent synthetic retinoid, regulated both Th1 and Th17 responses as well as TGF-β expression in the skin, resulting in an attenuation of cutaneous cGVHD. These results suggest that Th1 and Th17 contribute to the development of cGVHD and that targeting Th1 and Th17 may therefore represent a promising therapeutic strategy for preventing and treating cGVHD.
Note This research was originally published in Blood. 2012. © the American Society of Hematology.
Published Date 2012-01-05
Publication Title Blood
Volume volume119
Issue issue1
Start Page 285
End Page 295
Content Type Journal Article
language 英語
OAI-PMH Set 岡山大学
Copyright Holders https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
File Version publisher
PubMed ID 22077062
DOI 10.1182/blood-2011-01-332478
Web of Sience KeyUT 000299012400035
Related Url https://doi.org/10.1182/blood-2011-01-332478
FullText URL Int_J_Hematol_105_6_812.pdf
Author Nishimori, Hisakazu| Fujii, Nobuharu| Fujii, Keiko| Ikeda, Tohru| Asano, Naomi| Ogo, Hiroaki| Yamakawa, Miwa| Takagi, Naoe| Otsuka, Fumio| Ikeda, Kazuma|
Abstract Studies examining risk factors associated with vasovagal reactions (VVRs) during autologous blood donations, especially in younger subjects, have been limited. The aim of the present study was to define risk factors for VVRs during preoperative autologous blood donation in patients, including those younger than 18 years old. We retrospectively analyzed 4192 autologous, preoperative blood donations between 2007 and 2015 at Okayama University Hospital. Eighty-seven (2.08%) of the patients experienced VVRs. VVRs occurred approximately three times as often in patients 0-17 years old (16/320, 5.0%) than in patients 18 years and older (71/3872, 1.8%). In particular, VVRs occurred more frequently in those 10-13 years old, and decreased with older age (P = 0.006). In a univariate analysis, younger age, lower body mass index, lower systolic blood pressure, lower body weight, lower total blood volume, female gender, first-time collection, and higher heart rate were associated with a higher incidence of VVRs. In a multivariate analysis, lower systolic blood pressure (P < 0.001), higher heart rate (P = 0.007), and first-time collection (P = 0.015), remained independent predictors of VVRs. These results emphasize the need for careful attention during blood collection.
Keywords Autologous blood donation Vasovagal reactions
Note This is an Accepted Manuscript of an article published by Springer
Published Date 2017-06
Publication Title International Journal of Hematology
Volume volume105
Issue issue6
Publisher Elsevier Science
Start Page 812
End Page 818
ISSN 0925-5710
NCID AA10797094
Content Type Journal Article
language 英語
OAI-PMH Set 岡山大学
Copyright Holders https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
File Version author
PubMed ID 28271415
DOI 10.1007/s12185-017-2204-6
Web of Sience KeyUT 000401324100014
Related Url isVersionOf https://doi.org/10.1007/s12185-017-2204-6
FullText URL s12885-017-3295-4.pdf
Author Yokota, T.| Ogawa, T.| Takahashi, S.| Okami, K.| Fujii, T.| Tanaka, K.| Iwae, S.| Ota, I.| Ueda, T.| Monden, N.| Matsuura, K.| Kojima, H.| Ueda, S.| Sasaki, K.| Fujimoto, Y.| Hasegawa, Y.| Beppu, T.| Nishimori, Hisakazu| Hirano, S.| Naka, Y.| Matsushima, Y.| Fujii, M.| Tahara, M.|
Abstract BACKGROUND: Recent preclinical and phase I studies have reported that rebamipide decreased the severity of chemoradiotherapy-induced oral mucositis in patients with oral cancer. This placebo-controlled randomized phase II study assessed the clinical benefit of rebamipide in reducing the incidence of severe chemoradiotherapy-induced oral mucositis in patients with head and neck cancer (HNC). METHODS: Patients aged 20-75 years with HNC who were scheduled to receive chemoradiotherapy were enrolled. Patients were randomized to receive rebamipide 2% liquid, rebamipide 4% liquid, or placebo. The primary endpoint was the incidence of grade ≥ 3 oral mucositis determined by clinical examination and assessed by central review according to the Common Terminology Criteria of Adverse Events version 3.0. Secondary endpoints were the time to onset of grade ≥ 3 oral mucositis and the incidence of functional impairment (grade ≥ 3) based on the evaluation by the Oral Mucositis Evaluation Committee. RESULTS: From April 2014 to August 2015, 97 patients with HNC were enrolled, of whom 94 received treatment. The incidence of grade ≥ 3 oral mucositis was 29% and 25% in the rebamipide 2% and 4% groups, respectively, compared with 39% in the placebo group. The proportion of patients who did not develop grade ≥ 3 oral mucositis by day 50 of treatment was 57.9% in the placebo group, whereas the proportion was 68.0% in the rebamipide 2% group and 71.3% in the rebamipide 4% group. The incidences of adverse events potentially related to the study drug were 16%, 26%, and 13% in the placebo, rebamipide 2%, and rebamipide 4% groups, respectively. There was no significant difference in treatment compliance among the groups. CONCLUSIONS: The present phase II study suggests that mouth washing with rebamipide may be effective and safe for patients with HNC receiving chemoradiotherapy, and 4% liquid is the optimal dose of rebamipide. TRIAL REGISTRATION: ClinicalTrials.gov under the identifier NCT02085460 (the date of trial registration: March 11, 2014).
Keywords Chemoradiotherapy Head and neck cancer Oral mucositis Placebo-controlled Randomized Rebamipide liquid
Published Date 2017-05-05
Publication Title BMC cancer
Volume volume17
Issue issue1
Publisher BioMed Central
Start Page 314
End Page 322
ISSN 1471-2407
NCID AA12034763
Content Type Journal Article
language 英語
OAI-PMH Set 岡山大学
Copyright Holders https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
File Version publisher
PubMed ID 28476132
DOI 10.1186/s12885-017-3295-4
Web of Sience KeyUT 000401614700001
Related Url https://doi.org/10.1186/s12885-017-3295-4
JaLCDOI 10.18926/AMO/54603
FullText URL 70_5_409.pdf
Author Maeda, Yoshinobu| Nishimori, Hisakazu| Inamoto, Yoshihiro| Nakamae, Hirohisa| Sawa, Masashi| Mori, Yasuo| Ohashi, Kazuteru| Fujiwara, Shin-ichiro| Tanimoto, Mitsune|
Abstract Chronic graft-versus-host disease (GVHD) is a major cause of late death and morbidity following allogeneic hematopoietic cell transplantation (HSCT). Retinoic acid (tamibarotene) exerts multiple effects on cell differentiation and is clinically used for the treatment of acute promyelocytic leukemia. Tamibarotene down-regulates both Th1 and Th17 differentiation in donor T cells after allogeneic HSCT, resulting in attenuation of experimental chronic GVHD. Based on preclinical data, we have launched a phase II study of tamibarotene in patients with steroid-refractory chronic GVHD. This study will clarify whether tamibarotene can exert beneficial effects in patients with steroid-refractory chronic GVHD.
Keywords Am80 tamibarotene retinoid chronic GVHD steroid-refractory GVHD
Amo Type Clinical Study Protocols
Published Date 2016-10
Publication Title Acta Medica Okayama
Volume volume70
Issue issue5
Publisher Okayama University Medical School
Start Page 409
End Page 412
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2016 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 27777437
Web of Sience KeyUT 000388098700014
Title Alternative An investigator initiated phase II clinical trial of tamibarotene (AM80G) for chronic graft-versus-host disease
FullText URL 127_133.pdf
Author Nishimori, Hisakazu| Maeda, Yoshinobu|
Keywords 臨床研究中核病院 慢性GVHD タミバロテン 同種造血幹細胞移植 Th17
Publication Title 岡山医学会雑誌
Published Date 2015-08-03
Volume volume127
Issue issue2
Start Page 133
End Page 137
ISSN 0030-1558
Related Url isVersionOf https://doi.org/10.4044/joma.127.133
language 日本語
Copyright Holders Copyright (c) 2015 岡山医学会
File Version publisher
DOI 10.4044/joma.127.133
NAID 130005096255
Author Sugiyama, Haruko| Maeda, Yoshinobu| Nishimori, Hisakazu| Yamasuji, Yoshiko| Matsuoka, Ken-ichi| Fujii, Nobuharu| Kondo, Eisei| Shinagawa, Katsuji| Tanaka, Takehiro| Takeuchi, Kengo| Teshima, Takanori| Tanimoto, Mitsune|
Published Date 2014-02
Publication Title Biology of Blood and Marrow Transplantation
Volume volume20
Issue issue2
Content Type Journal Article
Author Kurimoto, Etsuko| Miyahara, Nobuaki| Kanehiro, Arihiko| Waseda, Koichi| Taniguchi, Akihiko| Ikeda, Genyo| Koga, Hikari| Nishimori, Hisakazu| Tanimoto, Yasushi| Kataoka, Mikio| Iwakura, Yoichiro| Gelfand, Erwin W.| Tanimoto, Mitsune|
Published Date 2013-01-20
Publication Title Respiratory Research
Volume volume14
Content Type Journal Article
Sort Key 1
Title Alternative Cholecystokinin plays a novel protective role in diabetic kidney through anti-inflammatory actions on macrophages
FullText URL 126_1.pdf
Author Miyamoto, Satoshi| Shikata, Kenichi| Miyasaka, Kyoko| Okada, Shinichi| Sasaki, Motofumi| Kodera, Ryo| Hirota, Daisho| Kajitani, Nobuo| Takatsuka, Tetsuharu| Kataoka Usui, Hitomi| Nishishita, Shingo| Horiguchi Sato, Chikage| Funakoshi, Akihiro| Nishimori, Hisakazu| Uchida, Haruhito Adam| Ogawa, Daisuke| Makino, Hirofumi|
Keywords cholecystokinin 糖尿病性腎症 抗炎症作用 腎保護効果
Note 平成24年度岡山医学会賞総合研究奨励賞(結城賞)受賞論文 (The 2012 Okayama Medical Association Award)
Publication Title 岡山医学会雑誌
Published Date 2014-04-01
Volume volume126
Issue issue1
Publisher 岡山医学会
Publisher Alternative Okayama Medical Association
Start Page 1
End Page 6
ISSN 0030-1558
NCID AN00032489
Content Type Journal Article
Related Url http://www.okayama-u.ac.jp/user/oma/
language 日本語
Copyright Holders Copyright (c) 2014 岡山医学会
File Version publisher
Refereed True
DOI 10.4044/joma.126.1
Eprints Journal Name joma
References 1) Sugimoto H, Shikata K, Hirata K, Akiyama K, Matsuda M, Kushiro M, Shikata Y, Miyatake N, Miyasaka M, Makino H : Increased expression of intercellular adhesion molecule-1 (ICAM-1) in diabetic rat glomeruli : glomerular hyperfiltration is a potential mechanism of ICAM-1 upregulation. Diabetes (1997) 46, 2075-2081. 2) Okada S, Shikata K, Matsuda M, Ogawa D, Usui H, Kido Y, Nagase R, Wada J, Shikata Y, Makino H : Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes. Diabetes (2003) 52, 2586-2593. 3) Miyamoto S, Shikata K, Miyasaka K, Okada S, Sasaki M, Kodera R, Hirota D, Kajitani N, Takatsuka T, Kataoka HU, Nishishita S, Sato C, et al. : Cholecystokinin plays a novel protective role in diabetic kidney through anti-inflammatory actions on macrophage : anti-inflammatory effect of cholecystokinin. Diabetes (2012) 61, 897-907. 4) Rehfeld JF : Clinical endocrinology and metabolism. Cholecystokinin. Best Pract Res Clin Endocrinol Metab (2004) 18, 569-586. 5) Crawley JN, Corwin RL : Biological actions of cholecystokinin. Peptides (1994) 15, 731-755. 6) Meng AH, Ling YL, Zhang XP, Zhang JL : Anti-inflammatory effect of cholecystokinin and its signal transduction mechanism in endotoxic shock rat. World J Gastroenterol (2002) 8, 712-717. 7) Li S, Ni Z, Cong B, Gao W, Xu S, Wang C, Yao Y, Ma C, Ling Y : CCK-8 inhibits LPS-induced IL-1beta production in pulmonary interstitial macrophages by modulating PKA, p38, and NF-kappaB pathway. Shock (2007) 27, 678-686. 8) Lacourse KA, Lay JM, Swanberg LJ, Jenkins C, Samuelson LC : Molecular structure of the mouse CCK-A receptor gene. Biochem Biophys Res Commun (1997) 236, 630-635. 9) de Weerth A, Jonas L, Schade R, Schoneberg T, Wolf G, Pace A, Kirchhoff F, Schulz M, Heinig T, Greten H, von Schrenck T : Gastrin/cholecystokinin type B receptors in the kidney : molecular, pharmacological, functional characterization, and localization. Eur J Clin Invest (1998) 28, 592-601. 10) Xu SJ, Gao WJ, Cong B, Yao YX, Gu ZY : Effect of lipopolysaccharide on expression and characterization of cholecystokinin receptors in rat pulmonary interstitial macrophages. Acta Pharmacol Sin (2004) 25, 1347-1353. 11) Sanchez AP, Sharma K : Transcription factors in the pathogenesis of diabetic nephropathy. Expert Rev Mol Med (2009) 11, e13. 12) Takano Y, Yamauchi K, Hayakawa K, Hiramatsu N, Kasai A, Okamura M, Yokouchi M, Shitamura A, Yao J, Kitamura M : Transcriptional suppression of nephrin in podocytes by macrophages : roles of inflammatory cytokines and involvement of the PI3K/Akt pathway. FEBS Lett (2007) 581, 421-426. 13) Leon-Tamariz F, Verbaeys I, Van Boven M, De Cuyper M, Buyse J, de Witte P, Verbruggen A, Cokelaere M : Biodistribution and pharmacokinetics of PEG-10kDa-cholecystokinin-10 in rats after different routes of administration. Curr Drug Deliv (2010) 7, 137-143.
JaLCDOI 10.18926/AMO/49251
FullText URL 67_1_1.pdf
Author Nishimori, Hisakazu| Maeda, Yoshinobu| Tanimoto, Mitsune|
Abstract Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. Chronic GVHD often presents with clinical manifestations that resemble those observed in autoimmune diseases. Standard treatment is 1-2mg/kg/day of prednisone or an equivalent dose of methylprednisolone, with continued administration of a calcineurin inhibitor for steroid sparing. However, the prognosis of steroid-refractory chronic GVHD remains poor. Classically, chronic GVHD was said to involve predominantly Th2 responses. We are now faced with a more complex picture, involving possible roles for thymic dysfunction, transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF), B cells and autoantibodies, and Th1/Th2/Th17 cytokines, as well as regulatory T cells (Tregs), in chronic GVHD. More detailed research on the pathophysiology of chronic GVHD may facilitate the establishment of novel strategies for its prevention and treatment.
Keywords chronic GVHD Th17 Am80 regulatory T cell (Treg) steroid-refractory
Amo Type Review
Published Date 2013-02
Publication Title Acta Medica Okayama
Volume volume67
Issue issue1
Publisher Okayama University Medical School
Start Page 1
End Page 8
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2013 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 23439503
Web of Sience KeyUT 000316829900001
Author Nishimori, Hisakazu| Maeda, Yoshinobu| Tanimoto, Mitsune|
Published Date 2012-12-03
Publication Title 岡山医学会雑誌
Volume volume124
Issue issue3
Content Type Journal Article