Mechanism of choreito, a formula from Japanese Kampo medicine, for hemorrhagic cystitis

• Project/Area Number: 16K19311
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Nagoya University
• Principal Investigator: KAWASHIMA NOZOMU 名古屋大学, 医学部附属病院, 助教 (30772264)
• Research Collaborator: OKUNO Yusuke ; ITO Masafumi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 漢方医学 / 猪苓湯 / 小児血液・悪性腫瘍 / 造血細胞移植 / 出血性膀胱炎 / BKウイルス / アデノウイルス / アルキル化剤 / 漢方薬 / 東洋医学 / 造血幹細胞移植

Outline of Final Research Achievements

Hemorrhagic cystitis is a severe, intractable complication in children treated with alkylating agents for hematological and solid malignancies or for posttransplant infections, such as BK virus or adenovirus. Choreito, a Japanese Kampo medicine prescription, can significantly shorten the interval from the start of treatment to hemostasis of macroscopic hematuria. Evidence from imaging studies indicates that choreito promotes hemostasis by reducing inflammation in the bladder and perivesical connective tissue. The Kampo pattern also indicates decreased inflammation in the urinary system after taking choreito. Based on the clinical findings, animal models were established to investigate the mechanism of action of choreito. Unfortunately, the hemostatic effects of choreito were not observed, which precluded further investigation of the mechanism.

Academic Significance and Societal Importance of the Research Achievements

アルキル化剤誘発性あるいは造血細胞移植後ウイルス性出血性膀胱炎には確立した治療法がなく対症療法がおこなわれるのみであるため、その治療選択として安価で安全性の高い猪苓湯がその原因を問わず広く出血性膀胱炎に有効であることが証明されたのは社会に貢献したものと思われる。猪苓湯治療による漢方医学的投与目標の改善は客観的画像所見では膀胱周囲組織の炎症所見の改善として表現できうるということが示され、伝統医学と現代医学を結びつける学術的な新知見が得られたことでも意義深いと考えられる。

Research Products

• [Journal Article] Allogeneic stem cell transplantation with reduced intensity conditioning for patients with adrenoleukodystrophy (2019)
  • Author(s): Kato Koji、Maemura Ryo、Wakamatsu Manabu、Yamamori Ayako、Hamada Motoharu、Kataoka Shinsuke、Narita Atsushi、Miwata Shunsuke、Sekiya Yuko、Kawashima Nozomu、Shimozawa Nobuyuki、Yoshida Nao、et al
  • Journal Title: Molecular Genetics and Metabolism Reports Volume: 18 Pages: 1-6
  • DOI: 10.1016/j.ymgmr.2018.11.001
  • Peer Reviewed / Open Access
• [Journal Article] Prophylaxis and treatment with mycophenolate mofetil in children with graft-versus-host disease undergoing allogeneic hematopoietic stem cell transplantation: a nationwide survey in Japan (2019)
  • Author(s): Kawashima Nozomu、Iida Minako、Suzuki Ritsuro、Fukuda Takahiro、Atsuta Yoshiko、Hashii Yoshiko、Inoue Masami、Kobayashi Masao、Yabe Hiromasa、Okada Keiko、Adachi Souichi、Yuza Yuki、Kawa Keisei、Kato Koji
  • Journal Title: International Journal of Hematology Volume: 109 Issue: 4 Pages: 491-498
  • DOI: 10.1007/s12185-019-02601-5
  • NAID: 120006652420
  • Peer Reviewed
• [Journal Article] Whole-exome analysis to detect congenital hemolytic anemia mimicking congenital dyserythropoietic anemia (2018)
  • Author(s): Hamada Motoharu、Doisaki Sayoko、Okuno Yusuke、Muramatsu Hideki、Hama Asahito、Kawashima Nozomu、Narita Atsushi、Nishio Nobuhiro、Yoshida Kenichi、Kanno Hitoshi、Manabe Atsushi、Taga Takashi、Takahashi Yoshiyuki、Miyano Satoru、Ogawa Seishi、Kojima Seiji
  • Journal Title: International Journal of Hematology Volume: 108 Issue: 3 Pages: 306-311
  • DOI: 10.1007/s12185-018-2482-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Integration Mapping of piggyBac-Mediated CD19 Chimeric Antigen Receptor T Cells Analyzed by Novel Tagmentation-Assisted PCR (2018)
  • Author(s): Hamada Motoharu、Nishio Nobuhiro、Okuno Yusuke、Suzuki Satoshi、Kawashima Nozomu、Nakazawa Yozo、Takahashi Yoshiyuki、et al
  • Journal Title: EBioMedicine Volume: 34 Pages: 18-26
  • DOI: 10.1016/j.ebiom.2018.07.008
  • Peer Reviewed / Open Access
• [Journal Article] Integrated molecular profiling of juvenile myelomonocytic leukemia (2018)
  • Author(s): Murakami N, Okuno Y, Yoshida K, Shiraishi Y, Nagae G, Suzuki K, Narita A, Sakaguchi H, Kawashima N, Wang X, Xu Y, Chiba K, Tanaka H, Hama A, Sanada M, Ito M, Hirayama M, Watanabe A, Ueno T, Kojima S, Aburatani H, Mano H, Miyano S, Ogawa S, Takahashi Y, Muramatsu H
  • Journal Title: Blood Volume: 131 Issue: 14 Pages: 1576-1586
  • DOI: 10.1182/blood-2017-07-798157
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enhanced Expression of Anti-CD19 Chimeric Antigen Receptor in piggyBac Transposon-Engineered T Cells (2018)
  • Author(s): Morita Daisuke、Nishio Nobuhiro、Saito Shoji、Tanaka Miyuki、Kawashima Nozomu、Okuno Yusuke、Suzuki Satoshi、Matsuda Kazuyuki、Maeda Yasuhiro、Wilson Matthew H.、Dotti Gianpietro、Rooney Cliona M.、Takahashi Yoshiyuki、Nakazawa Yozo
  • Journal Title: Molecular Therapy - Methods & Clinical Development Volume: 8 Pages: 131-140
  • DOI: 10.1016/j.omtm.2017.12.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Development of clinical paroxysmal nocturnal haemoglobinuria in children with aplastic anaemia (2017)
  • Author(s): Narita Atsushi、Muramatsu Hideki、Okuno Yusuke、Sekiya Yuko、Suzuki Kyogo、Hamada Motoharu、Kataoka Shinsuke、Ichikawa Daisuke、Taniguchi Rieko、Murakami Norihiro、Kojima Daiei、Nishikawa Eri、Kawashima Nozomu、Nishio Nobuhiro、Hama Asahito、Takahashi Yoshiyuki、Kojima Seiji
  • Journal Title: British Journal of Haematology Volume: 178 Issue: 6 Pages: 954-958
  • DOI: 10.1111/bjh.14790
  • Peer Reviewed / Open Access
• [Journal Article] Danaparoid reduces transplant-related mortality in stem cell transplantation for children (2017)
  • Author(s): Kato Koji、Sakaguchi Hirotoshi、Muramatsu Hideki、Sekiya Yuko、Kawashima Nozomu、Narita Atsushi、Doisaki Sayoko、Watanabe Nobuhiro、Yoshida Nao、Matsumoto Kimikazu
  • Journal Title: Pediatric Transplantation Volume: 22 Issue: 2
  • DOI: 10.1111/petr.13099
  • Peer Reviewed / Open Access
• [Journal Article] 夜啼・驚啼に対する甘麦大棗湯の起源 医史学的考察 (2017)
  • Author(s): 川島希、山口英明
  • Journal Title: 日本小児東洋医学会誌 Volume: 30 Pages: 43-50
  • NAID: 120006501191
  • Peer Reviewed
• [Journal Article] Clinical utility of next-generation sequencing-based minimal residual disease in paediatric B-cell acute lymphoblastic leukaemia. (2017)
  • Author(s): Sekiya Y, Xu Y, Muramatsu H, Okuno Y, Narita A, Suzuki K, Wang X, Kawashima N, Sakaguchi H, Yoshida N, Hama A, Takahashi Y, Kato K, Kojima S.
  • Journal Title: Br J Haematol. Volume: 176 Issue: 2 Pages: 248-257
  • DOI: 10.1111/bjh.14420
  • Peer Reviewed
• [Journal Article] Kampo patterns and radiology in children receiving choreito for hemorrhagic cystitis after hematopoietic stem cell transplantation. (2016)
  • Author(s): Kawashima N, Sekiya Y, Narita A, Kamei M, Muramatsu H, Nishio N, Hama A, Ito Y, Takahashi Y, Kojima S.
  • Journal Title: 3451 Volume: 3 Issue: 2 Pages: 136-144
  • DOI: 10.1002/tkm2.1053
  • Peer Reviewed
• [Journal Article] Abnormal urinalysis on day 7 in patients with IgA vasculitis (Henoch–Schönlein purpura) (2016)
  • Author(s): Kawashima N, Kawada J, Nishikado Y, Kitase Y, Ito S, Muramatsu H, Sato Y, Kato T, Natsume J,Kojima, S.
  • Journal Title: Nagoya Journal of Medical Science Volume: 78 Issue: 4 Pages: 359-367
  • DOI: 10.18999/nagjms.78.4.359
  • NAID: 120005889990
  • ISSN: 2186-3326
  • URL: https://nagoya.repo.nii.ac.jp/records/22936
  • Peer Reviewed / Open Access
• [Journal Article] 【子どもの味方・漢方処方箋】 小柴胡湯(ショウサイコトウ)と柴胡桂枝湯(サイコケイシトウ) くり返す上気道炎 (2016)
  • Author(s): 川島希
  • Journal Title: チャイルドヘルス Volume: 19 Pages: 415-419
• [Journal Article] JAK2, MPL, and CALR mutations in children with essential thrombocythemia. (2016)
  • Author(s): Sekiya Y, Okuno Y, Muramatsu H, Ismael O, Kawashima N, Narita A, Wang X, Xu Y, Hama A, Fujisaki H, Imamura T, Hasegawa D, Kosaka Y, Sunami S, Ohtsuka Y, Ohga S, Takahashi Y, Kojima S, Shimada A.
  • Journal Title: Int J Hematol. Volume: 104 Issue: 2 Pages: 266-267
  • DOI: 10.1007/s12185-016-2022-2
  • Peer Reviewed
• [Journal Article] Successful T-cell reconstitution after unrelated cord blood transplantation in a patient with complete DiGeorge syndrome. (2016)
  • Author(s): Kojima D, Muramatsu H, Okuno Y, Kataoka S, Murakami N, Tanahashi Y, Suzuki K, Kato T, Sekiya Y, Kawashima N, Narita A, Nishio N, Hama A, Imai K, Nonoyama S, Takahashi Y, Kojima S.
  • Journal Title: J Allergy Clin Immunol. Volume: 138 Issue: 5 Pages: 1471-1473
  • DOI: 10.1016/j.jaci.2016.04.048
  • NAID: 120005981223
  • Peer Reviewed
• [Journal Article] A Cytokine-Based Diagnostic Program in Pediatric Aplastic Anemia and Hypocellular Refractory Cytopenia of Childhood. (2016)
  • Author(s): Elmahdi S, Hama A, Manabe A, Hasegawa D, Muramatsu H, Narita A, Nishio N, Ismael O, Kawashima N, Okuno Y, Xu Y, Wang X, Takahashi Y, Ito M, Kojima S.
  • Journal Title: Pediatr Blood Cancer Volume: 63 Issue: 4 Pages: 652-658
  • DOI: 10.1002/pbc.25799
  • Peer Reviewed
• [Journal Article] Correlation of rabbit antithymocyte globulin serum levels and clinical outcomes in children who received hematopoietic stem cell transplantation from an alternative donor. (2016)
  • Author(s): Elmahdi S, Muramatsu H, Narita A, Torii Y, Ismael O, Kawashima N, Okuno Y, Sekiya Y, Xu Y, Wang X, Hama A, Ito Y, Takahashi Y, Kojima S.
  • Journal Title: Pediatr Transplant. Volume: 20 Issue: 1 Pages: 105-113
  • DOI: 10.1111/petr.12620
  • Peer Reviewed / Open Access
• [Journal Article] MEF2D-BCL9 Fusion Gene Is Associated With High-Risk Acute B-Cell Precursor Lymphoblastic Leukemia in Adolescents. (2016)
  • Author(s): Suzuki K, Okuno Y, Kawashima N, Muramatsu H, Okuno T, Wang X, Kataoka S, Sekiya Y, Hamada M, Murakami N, Kojima D, Narita K, Narita A, Sakaguchi H, Sakaguchi K, Yoshida N, Nishio N, Hama A, Takahashi Y, Kudo K, Kato K, Kojima S.
  • Journal Title: J Clin Oncol. Volume: 34 Issue: 28 Pages: 3451-3459
  • DOI: 10.1200/jco.2016.66.5547
  • Peer Reviewed
• [Presentation] 伝統小児医学の現代小児科学への応用 (2019)
  • Author(s): 川島希
  • Organizer: 第43回「漢方研究」イスクラ奨励賞受賞記念講演
  • Invited
• [Presentation] Overviewing Japanese Traditional medicine, Kampo medicine (2018)
  • Author(s): Kawashima Nozomu
  • Organizer: 1st International Traditional and Complementary Medicine Congress
  • Int'l Joint Research / Invited
• [Presentation] Overviewing Japanese Traditional medicine, Kampo medicine (2018)
  • Author(s): Kawashima Nozomu
  • Organizer: 2nd Kampo Symposium at the Clinic for Gastroenterology and Gastrointestinal Oncology at the University Medicine, Goettingen
  • Invited
• [Presentation] 集中治療領域での漢方の底力 ショックと大量胸水に対して漢方エキス製剤が治療奏効した一例 (2018)
  • Author(s): 川島希
  • Organizer: 第69回日本東洋医学会学術総会
  • Invited
• [Presentation] 小児漢方エッセンス２ 「小児漢方医学史」 (2018)
  • Author(s): 川島希
  • Organizer: 第2回日本小児漢方懇話会フォーラム
  • Invited
• [Presentation] The History of Japanese Pediatric Kampo Medicine and its Application to Modern Medicine (2018)
  • Author(s): Kawashima Nozomu
  • Organizer: 天津中医薬大学建学60周年記念式典及び学術フォーラム
  • Int'l Joint Research / Invited
• [Presentation] 明治期皇子女と漢方医 なぜ漢方医が皇子女の主治医となり最終的に罷免に至ったか？ (2018)
  • Author(s): 川島希
  • Organizer: 第46回日本小児東洋医学会学術集会
• [Presentation] 小児がん拠点病院単一施設における漢方診療の患者ニーズ調査 (2018)
  • Author(s): 川島希、三輪田俊介、成田幸太郎、片岡伸介、濱田太立、村上典寛、市川大輔、鈴木喬悟、北澤宏展、西川英里、奥野友介、谷口理恵子、成田敦、村松秀城、西尾信博、小島勢二、高橋義行
  • Organizer: 第60回日本小児血液・がん学会学術集会
• [Presentation] Overviewing Japanese Traditional medicine, Kampo medicine: Examples of Integrated Medicine for Children Undergoing Stem Cell Transplantation for Hematological and Oncological Disease (2018)
  • Author(s): Nozomu Kawashima
  • Organizer: 1st International Traditional and Complementary Medicine Congress
  • Int'l Joint Research / Invited
• [Presentation] Choreito for Intractable Hemorrhagic Cystitis after Stem Cell Transplant (2017)
  • Author(s): Nozomu Kawashima
  • Organizer: 4th International Kampo Symposium Berlin
  • Int'l Joint Research
• [Presentation] Successful Treatment of Intractable Hemorrhagic Cystitis with Japanese Traditional Kampo Medicine, Choreito in Children Undergoing Stem Cell Transplantation for Hematological and Oncological Disease (2017)
  • Author(s): Nozomu Kawashima
  • Organizer: 14th International Conference of the Society for Integrative Oncology
  • Int'l Joint Research
• [Presentation] 『幼幼家則』方剤からみる小児漢方の変遷 (2017)
  • Author(s): 川島希
  • Organizer: 第68回日本東洋医学会学術総会
• [Presentation] 『幼幼家則』にみる疾医が記載する小児の鍼灸・外科的治療 (2017)
  • Author(s): 川島希
  • Organizer: 第45回日本小児東洋医学会学術集会
• [Presentation] 円形脱毛症に対して漢方エキス製剤による湯液療法と梅花鍼を含む鍼灸療法とを併用した一例 (2017)
  • Author(s): 川島希、胡暁晨、石川寿子、佐藤寿一
  • Organizer: 第47会日本東洋医学会東海支部学術総会
• [Presentation] 小児血液・悪性疾患の支持療法から考えるこどもの診療 (2017)
  • Author(s): 川島希
  • Organizer: 第54回北九州小児血液・腫瘍懇話会
  • Place of Presentation: リーガロイヤルホテル小倉（福岡県北九州市）
  • Invited
• [Presentation] 猪苓湯は小児血液・腫瘍疾患患者にみられる出血性膀胱炎を止血する (2016)
  • Author(s): 川島希, 片岡伸介, 濱田太立, 市川大輔, 小島大英, ,鈴木喬悟, 村上典寛, 谷口理恵子, 関屋由子, 西川英里, 成田敦, 村松秀城, 西尾信博, 濱麻人,小島勢二, 高橋義行
  • Organizer: 第58回日本小児血液・がん学会学術集会
  • Place of Presentation: 品川プリンスホテル（東京都品川区）
  • Year and Date: 2016-12-15
• [Presentation] 小児長期入院患者の夜泣き・夜驚症に対する甘麦大棗湯 (2016)
  • Author(s): 川島希
  • Organizer: 第67回日本東洋医学会学術総会
  • Place of Presentation: サンポートホール高松（香川県高松市）
  • Year and Date: 2016-06-03
• [Presentation] 夜啼・驚啼に対する甘麦大棗湯の起源：医史学的考察 (2016)
  • Author(s): 川島希
  • Organizer: 第44回日本小児東洋医学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター（大阪府豊中市）
• [Presentation] 造血細胞移植関連血栓性微小血管障害症に対して漢方診療の併用が奏効したと考えられた急性白血病の一例 (2016)
  • Author(s): 川島希
  • Organizer: 第46回日本東洋医学会東海支部学術総会
  • Place of Presentation: 名古屋大学医学部附属病院（愛知県名古屋市）
• [Book] 小児疾患の身近な漢方治療 14 (2016)
  • Author(s): 日本小児漢方交流会（企画・編集）
  • Total Pages: 96
  • Publisher: メジカルビュー社