American Society of Hematology Acta Medica Okayama 2473-9529 2 15 2018 Outcomes of patients who developed subsequent solid cancer after hematopoietic cell transplantation 1901 1903 EN Yoshihiro Inamoto National Cancer Center Hospital Tomohiro Matsuda National Cancer Center Hospital Ken Tabuchi Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Saiko Kurosawa National Cancer Center Hospital Hideki Nakasone Saitama Medical Center, Jichi Medical University Hisakazu Nishimori Okayama University Hospital Satoshi Yamasaki National Hospital Organization Kyushu Medical Center Noriko Doki Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital Koji Iwato Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital Takehiko Mori Keio University School of Medicine Satoshi Takahashi The Institute of Medical Science, The University of Tokyo Hiromasa Yabe Tokai University Hospital, Akio Kohno JA Aichi Konan Kosei Hospital Hirohisa Nakamae Osaka City University Toru Sakura Saiseikai Maebashi Hospital Hisako Hashimoto Kobe City Medical Center General Hospital Junichi Sugita Hokkaido University Hospital Hiroatsu Ago Shimane Prefectural Central Hospital Takahiro Fukuda National Cancer Center Hospital Tatsuo Ichinohe Research Institute for Radiation Biology and Medicine, Hiroshima University Yoshiko Atsuta Japanese Data Center for Hematopoietic Cell Transplantation Takuya Yamashita St. Luke's International Hospital Japan Society for Hematopoietic Cell Transplantation Late Effects and Quality of Life Working Group To characterize the outcomes of patients who developed a particular subsequent solid cancer after hematopoietic cell transplantation (HCT), age at cancer diagnosis, survival, and causes of death were compared with the respective primary cancer in the general population, using data from the national HCT registry and population-based cancer registries in Japan. Among 31 867 patients who underwent a first HCT between 1990 and 2013 and had progression-free survival at 1 year, 713 patients developed subsequent solid cancer. The median age at subsequent solid cancer diagnosis was 55 years, which was significantly younger than the 67 years for primary cancer patients in the general population (P < .001). The overall survival probability was 60% at 3 years after diagnosis of subsequent solid cancer and differed according to cancer type. Development of most solid cancers was associated with an increased risk of subsequent mortality after HCT. Subsequent solid cancers accounted for 76% of causes of death. Overall survival probabilities adjusted for age, sex, and year of diagnosis were lower in the HCT population than in the general population for colon, bone/soft tissue, and central nervous system cancers and did not differ statistically for other cancers. In conclusion, most subsequent solid cancers occurred at younger ages than primary cancers, emphasizing the need for cancer screening at younger ages. Subsequent solid cancers showed similar or worse survival compared with primary cancers. Biological and genetic differences between primary and subsequent solid cancers remain to be determined. No potential conflict of interest relevant to this article was reported.
Acta Medica Okayama 119 1 2012 Synthetic retinoid Am80 ameliorates chronic graft-versus-host disease by down-regulating Th1 and Th17. 285 295 EN Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takanori Teshima Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Haruko Sugiyama Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Koichiro Kobayashi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiko Yamasuji Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sachiyo Kadohisa Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hidetaka Uryu Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kengo Takeuchi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tadashi Yoshino Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yoichiro Iwakura Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mitsune Tanimoto Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences 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. No potential conflict of interest relevant to this article was reported.
Elsevier Science Acta Medica Okayama 0925-5710 105 6 2017 Predictors of vasovagal reactions during preoperative autologous blood donation: a single-institution analysis 812 818 EN Hisakazu Nishimori Department of Transfusion Medicine, Okayama University Hospital Nobuharu Fujii Department of Transfusion Medicine, Okayama University Hospital Keiko Fujii Department of Transfusion Medicine, Okayama University Hospital Tohru Ikeda Department of Transfusion Medicine, Okayama University Hospital Naomi Asano Department of Transfusion Medicine, Okayama University Hospital Hiroaki Ogo Department of Transfusion Medicine, Okayama University Hospital Miwa Yamakawa Department of Nursing, Okayama University Hospital Naoe Takagi Department of Nursing, Okayama University Hospital Fumio Otsuka Department of Transfusion Medicine, Okayama University Hospital Kazuma Ikeda Department of Transfusion Medicine, Okayama University Hospital 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. No potential conflict of interest relevant to this article was reported. Autologous blood donation Vasovagal reactions
BioMed Central Acta Medica Okayama 1471-2407 17 1 2017 Efficacy and safety of rebamipide liquid for chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II study 314 322 EN T. Yokota Division of Gastrointestinal Oncology, Shizuoka Cancer Center T. Ogawa Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine S. Takahashi Department of Medical Oncology, The Cancer Institute Hospital of JFCR K. Okami Department of Otolaryngology, Center of Head and Neck Surgery, Tokai University T. Fujii Department of Otolaryngology, Head and Neck Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases K. Tanaka Department of Medical Oncology, Kindai University Faculty of Medicine S. Iwae Department of Head and Neck Cancer, Hyogo Cancer Center I. Ota Department of Otolaryngology-Head and Neck Surgery, Nara Medical University T. Ueda Department of Otorhinolaryngology-Head and Neck Surgery, Hiroshima University Hospital N. Monden Department of Head and Neck Surgery, Shikoku Cancer Center K. Matsuura Department of Head and Neck Surgery, Miyagi Cancer Center H. Kojima Department of Otorhinolaryngology, Jikei University School of Medicine S. Ueda Medical Oncology, Nara Hospital, Kindai University School of Medicine K. Sasaki Head and Neck, Chiba Cancer Center Y. Fujimoto Department of Otorhinolaryngology, Nagoya University, Graduate School of Medicine Y. Hasegawa Department of Head and Neck Surgery, Aichi Cancer Center Hospital and Research Institute T. Beppu Division of Head and Neck Surgery, Saitama Cancer Center Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital S. Hirano Department of Otolaryngology-Head and Neck Surgery, Kyoto University Hospital Y. Naka Headquarters of New Product Evaluation and Development, Otsuka Pharmaceutical Co., Ltd. Y. Matsushima Headquarters of New Product Evaluation and Development, Otsuka Pharmaceutical Co., Ltd. M. Fujii Department of Otolaryngology, Eiju General Hospital M. Tahara Department of Head and Neck Medical Oncology, National Cancer Center Hospital East 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). No potential conflict of interest relevant to this article was reported. Chemoradiotherapy Head and neck cancer Oral mucositis Placebo-controlled Randomized Rebamipide liquid
Okayama University Medical School Acta Medica Okayama 0386-300X 70 5 2016 An Open-labeled, Multicenter Phase II Study of Tamibarotene in Patients with Steroid-refractory Chronic Graft-versus-Host Disease 409 412 EN Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Hisakazu Nishimori Department of Hematology and Oncology, Okayama University Hospital Yoshihiro Inamoto Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital Hirohisa Nakamae Department of Hematology, Osaka City University Hospital Masashi Sawa Department of Hematology and Oncology, Anjo Kosei Hospital Yasuo Mori Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences Kazuteru Ohashi Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center Shin-ichiro Fujiwara Division of Hematology, Department of Medicine, Jichi Medical University Mitsune Tanimoto Department of Hematology and Oncology, Okayama University Hospital Clinical Study Protocols 10.18926/AMO/54603 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. No potential conflict of interest relevant to this article was reported. Am80 tamibarotene retinoid chronic GVHD steroid-refractory GVHD
岡山医学会 Acta Medica Okayama 0030-1558 127 2 2015 慢性移植片対宿主病に対するタミバロテン(AM80G)の医師主導臨床第U相試験 133 137 EN Hisakazu Nishimori Yoshinobu Maeda No potential conflict of interest relevant to this article was reported. 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
Acta Medica Okayama 1083-8791 20 2 2014 Mammalian Target of Rapamycin Inhibitors Permit Regulatory T Cell Reconstitution and Inhibit Experimental Chronic Graft-versus-Host Disease 183 191 EN Haruko Sugiyama Yoshinobu Maeda Hisakazu Nishimori Yoshiko Yamasuji Ken-ichi Matsuoka Nobuharu Fujii Eisei Kondo Katsuji Shinagawa Takehiro Tanaka Kengo Takeuchi Takanori Teshima Mitsune Tanimoto Chronic graft-versus-host disease (GVHD) remains a major late complication of allogeneic bone marrow transplantation (BMT). In a previous study, impaired thymic negative selection of the recipients permitted the emergence of pathogenic T cells that cause chronic GVHD using MHC class II-deficient (H2-Ab1 KO) B6 into OH model and CD4(+) T cells isolated from chronic GVHD mice caused chronic GVHD when administered into the secondary recipients. In this study, we evaluated the kinetics of regulatory T cell (Treg) reconstitution in wild type B6 into C3H model. After myeloablative conditioning, host Tregs disappeared rapidly, followed by expansion of Tregs derived from the donor splenic T cell inoculum. However, the donor splenic T cell derived Treg pool contracted gradually and was almost completely replaced by newly generated donor bone marrow (BM)-derived Tregs in the late post-transplantation period. Next, we compared the effects of cyclosporine (CSA) and mammalian target of rapamycin (mTOR) inhibitors on Treg reconstitution. Administration of CSA significantly impaired Treg reconstitution in the spleen and thymus. In contrast, BM-derived Treg reconstitution was not impaired in mTOR inhibitor-treated mice. Histopathological examination indicated that mice treated with GSA, but not mTOR inhibitors, showed pathogenic features of chronic GVHD on day 120. Mice treated with CSA until day 60, but not mTOR inhibitors, developed severe chronic GVHD followed by adoptive transfer of the pathogenic CD4(+) T cells isolated from H2-Ab1 KO into C3H model. These findings indicated that long-term use of CSA impairs reconstitution of BM-derived Tregs and increases the liability to chronic GVHD. The choice of immunosuppression, such as calcineurin inhibitor-free GVHD prophylaxis with mTOR inhibitor, may have important implications for the control of chronic GVHD after BMT. No potential conflict of interest relevant to this article was reported. Chronic graft-versus-host disease (GVHD) Cyclosporine Mammalian target of rapamycin (mTOR) inhibitor Regulatory T cell
Biomed Central Ltd Acta Medica Okayama 1465-993X 14 2013 IL-17A is essential to the development of elastase-induced pulmonary inflammation and emphysema in mice EN Etsuko Kurimoto Nobuaki Miyahara Arihiko Kanehiro Koichi Waseda Akihiko Taniguchi Genyo Ikeda Hikari Koga Hisakazu Nishimori Yasushi Tanimoto Mikio Kataoka Yoichiro Iwakura Erwin W. Gelfand Mitsune Tanimoto Background: Pulmonary emphysema is characterized by alveolar destruction and persistent inflammation of the airways. Although IL-17A contributes to many chronic inflammatory diseases, it's role in the inflammatory response of elastase-induced emphysema remains unclear. Methods: In a model of elastase-induced pulmonary emphysema we examined the response of IL-17A-deficient mice, monitoring airway inflammation, static compliance, lung histology and levels of neutrophil-related chemokine and pro-inflammatory cytokines in bronchoalveolar lavage (BAL) fluid. Results: Wild-type mice developed emphysematous changes in the lung tissue on day 21 after elastase treatment, whereas emphysematous changes were decreased in IL-17A-deficient mice compared to wild-type mice. Neutrophilia in BAL fluid, seen in elastase-treated wild-type mice, was reduced in elastase-treated IL-17A-deficient mice on day 4, associated with decreased levels of KC, MIP-2 and IL-1 beta. Elastase-treated wild-type mice showed increased IL-17A levels as well as increased numbers of IL-17A+ CD4 T cells in the lung in the initial period following elastase treatment. Conclusions: These data identify the important contribution of IL-17A in the development of elastase-induced pulmonary inflammation and emphysema. Targeting IL-17A in emphysema may be a potential therapeutic strategy for delaying disease progression. No potential conflict of interest relevant to this article was reported. IL-17 Elastase Emphysema Chronic obstructive pulmonary disease
岡山医学会 Acta Medica Okayama 0030-1558 126 1 2014 糖尿病の腎臓においてcholecystokininはマクロファージに対する抗炎症作用を介した新規の保護効果を発揮する 1 6 EN Satoshi Miyamoto Kenichi Shikata Kyoko Miyasaka Shinichi Okada Motofumi Sasaki Ryo Kodera Daisho Hirota Nobuo Kajitani Tetsuharu Takatsuka Hitomi Kataoka Usui Shingo Nishishita Chikage Horiguchi Sato Akihiro Funakoshi Hisakazu Nishimori Haruhito Adam Uchida Daisuke Ogawa Hirofumi Makino No potential conflict of interest relevant to this article was reported. cholecystokinin 糖尿病性腎症 抗炎症作用 腎保護効果
Okayama University Medical School Acta Medica Okayama 0386-300X 67 1 2013 Chronic Graft-versus-Host Disease: Disease Biology and Novel Therapeutic Strategies 1 8 EN Hisakazu Nishimori Yoshinobu Maeda Mitsune Tanimoto Review 10.18926/AMO/49251 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. No potential conflict of interest relevant to this article was reported. chronic GVHD Th17 Am80 regulatory T cell (Treg) steroid-refractory
岡山医学会 Acta Medica Okayama 0030-1558 124 3 2012 合成レチノイドAm80はTh1とTh17を抑制することにより慢性移植片対宿主病を改善する 197 201 EN Hisakazu Nishimori Yoshinobu Maeda Mitsune Tanimoto No potential conflict of interest relevant to this article was reported. 慢性移植片対宿主病 同種造血幹細胞移植 Th17細胞 Th1細胞 Am80