Herbal medicine for radiation enteritis and the development of radiation-biopsy

• Project/Area Number: 19K17205
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Nagoya City University
• Principal Investigator: Murai Taro 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (00747602)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 放射線治療 / 放射線腸炎 / 半夏瀉心湯 / 多施設臨床試験 / リキッドバイオプシー / 多施設共同試験 / 放射線生検

Outline of Research at the Start

骨盤部放射線治療に伴う急性期放射線腸炎は、患者の生活の質を下げ、治療期間の延長により臨床成績を低下させる。①本研究では二重盲検ランダム化比較試験（半夏瀉心湯 vs 従来型治療（ロペラミド））を行い、半夏瀉心湯が急性期放射線腸炎に対する標準治療となることを示す。②加えて、試験に参加した子宮頸癌症例のデータを活用し、新しい診断技術「放射線生検」の開発を試みる。子宮頸癌への放射線治療前、治療後、小線源治療後に腫瘍より放出される微量なDNA断片を測定する。DNA検出率を向上させる照射法を明らかにすることにより、あたかも生検術のように特定病変の腫瘍遺伝子変異を検出する診断技術「放射線生検」を開発する。

Outline of Final Research Achievements

This grant project aims to establish the efficacy of the herbal medicine TJ-14 for acute radiation-induced enteritis (ARE). We conducted the multi-institutional randomized controlled Phase III trial study and registered on jRCT-registry. Despite these preparations, case enrolment was not sufficient and we were obliged to abort this trial, due to 1) the COVID-19 pandemic and 2) the improvement of radiation techniques which results in ARE reduction. We published other preliminary clinical research data and fundamental examinations in radiation biology or radiation physics. Preliminary clinical phase II trial results were published as well.

Academic Significance and Societal Importance of the Research Achievements

放射線腸炎は、腹部への放射線治療により発生する腸炎である。頻回の下痢を引き起こすことにより、患者の生活の質を大幅に低下させる。本研究により、漢方薬の一つである半夏瀉心湯が有効である可能性が明らかになった。
しかし、近年、放射線治療技術の発達により、放射線腸炎の頻度は著明に下がっている。従来の止痢薬との比較ため多施設共同無作為化比較試験を開始したが、症例数の関係から現実的ではないかもしれない。従って、実臨床においては、半夏瀉心湯は、治療薬として選択肢として良いと考えられる。

Research Products

• [Journal Article] Biological effects of prostaglandin E2-EP4 antagonist (AAT-008) in murine colon cancer in vivo: enhancement of immune response to radiotherapy and potential as a radiosensitizer (2023)
  • Author(s): Manabe Y, Takahashi Y, Sugie C, Wang Z, Katsuki S, Kondo T, Murai T, Nakashima M, Takaoka T, Ogawa K, Shibamoto Y
  • Journal Title: Transl Cancer Res Volume: 12(2) Issue: 2 Pages: 351-358
  • DOI: 10.21037/tcr-22-1857
  • Peer Reviewed / Open Access
• [Journal Article] Definitive radiotherapy with stereotactic or IMRT boost with or without radiosensitization strategy for operable breast cancer patients who refuse surgery (2022)
  • Author(s): Shibamoto Yuta、Takano Seiya、Iida Masato、Urano Misugi、Ohta Kengo、Oguri Masanosuke、Murai Taro
  • Journal Title: Journal of Radiation Research Volume: 63 Issue: 6 Pages: 849-855
  • DOI: 10.1093/jrr/rrac047
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of intensity-modulated radiotherapy with the 5-field technique, helical tomotherapy and volumetric modulated arc therapy for localized prostate cancer (2022)
  • Author(s): Kita Nozomi、Shibamoto Yuta、Takemoto Shinya、Manabe Yoshihiko、Yanagi Takeshi、Sugie Chikao、Tomita Natsuo、Iwata Hiromitsu、Murai Taro、Hashimoto Shingo、Ishikura Satoshi
  • Journal Title: Journal of Radiation Research Volume: 63 Issue: 4 Pages: 666-674
  • DOI: 10.1093/jrr/rrac027
  • Peer Reviewed / Open Access
• [Journal Article] Helical tomotherapy for asymptomatic chemotherapy-refractory or -unfit multiple (3 or more) metastases (2022)
  • Author(s): Yamada Yuki、Shibamoto Yuta、Kishi Kazushi、Kita Nozomi、Kondo Takuhito、Murai Taro、Sugie Chikao
  • Journal Title: Reports of Practical Oncology and Radiotherapy Volume: 27 Issue: 1 Pages: 125-133
  • DOI: 10.5603/rpor.a2022.0016
  • Peer Reviewed / Open Access
• [Journal Article] Survey of malignant pleural mesothelioma treatment in Japan: Patterns of practice and clinical outcomes in tomotherapy facilities (2022)
  • Author(s): Nakanishi-Imai Mikiko、Murai Taro、Onishi Masahiro、Mouri Atsuto、Komiyama Takafumi、Omura Motoko、Kudo Shigehiro、Miyamoto Akihiko、Hoshino Masaru、Ogawa Shinichi、Ohashi Shizuko、Koizumi Masahiko、Omagari Junichi、Mayahara Hiroshi、Karasawa Katsuyuki、Okumura Toshiyuki、Shibamoto Yuta
  • Journal Title: Journal of Radiation Research Volume: 63 Issue: 2 Pages: 281-289
  • DOI: 10.1093/jrr/rrab127
  • Peer Reviewed / Open Access
• [Journal Article] Combination therapy with radiation and hyperthermia‐induced clinical complete response of small cell carcinoma of prostate (2022)
  • Author(s): Kawai Noriyasu、Nagai Takashi、Naiki‐Ito Aya、Iida Keitaro、Etani Toshiki、Naiki Taku、Hamamoto Shuzo、Okada Atsushi、Murai Taro、Yasui Takahiro
  • Journal Title: IJU Case Reports Volume: 5 Issue: 2 Pages: 113-116
  • DOI: 10.1002/iju5.12413
  • Peer Reviewed / Open Access
• [Journal Article] Role of stereotactic body radiotherapy for early‐stage non‐small‐cell lung cancer in patients borderline for surgery due to impaired pulmonary function (2022)
  • Author(s): Tomita Natsuo、Okuda Katsuhiro、Kita Nozomi、Niwa Masanari、Hashimoto Shingo、Murai Taro、Ishikura Satoshi、Nakanishi Ryoichi、Shibamoto Yuta
  • Journal Title: Asia-Pacific Journal of Clinical Oncology Volume: In press Issue: 6 Pages: 634-641
  • DOI: 10.1111/ajco.13731
  • Peer Reviewed
• [Journal Article] Effects of a combined treatment regimen consisting of Hsp90 inhibitor DS-2248 and radiation in vitro and in a tumor mouse model. (2021)
  • Author(s): Kondo T, Shibamoto Y, Kawai T, Sugie C, Wang Z, Nakamura K, Murai T, Manabe Y, Nakashima M, Matsuo M
  • Journal Title: Translational Cancer Reseach Volume: 6 Issue: 6 Pages: 2767-2776
  • DOI: 10.21037/tcr-21-71
  • Peer Reviewed
• [Journal Article] The importance of choosing the right strategy to treat small cell carcinoma of the cervix: a comparative analysis of treatments. (2021)
  • Author(s): Kawamura M, Koide Y, Murai T, Ishihara S, Takase Y, Murao T, Okazaki D, Yamaguchi T, Uchiyama K, Itoh Y, Kodaira T, Shibamoto Y, Mizuno M, Kikkawa F, Naganawa S.
  • Journal Title: BMC Cancer Volume: 21(1) Issue: 1 Pages: 1046-1046
  • DOI: 10.1186/s12885-021-08772-x
  • Peer Reviewed / Open Access
• [Journal Article] CyberKnife for Recurrent Malignant Gliomas: A Systematic Review and Meta- Analysis. (2021)
  • Author(s): De Maria L, Terzi di Bergamo L, Conti A, Hayashi K, Pinzi V, Murai T, Lanciano R, Burneikiene S, Buglione di Monale M, Magrini SM, Fontanella MM.
  • Journal Title: Frontiers in Oncology Volume: 11 Pages: 652646-652646
  • DOI: 10.3389/fonc.2021.652646
  • Peer Reviewed / Open Access
• [Journal Article] Changes in pulmonary function and their correlation with dose-volume parameters in patients undergoing stereotactic body radiotherapy for lung cancer. (2021)
  • Author(s): Takemoto S, Shibamoto Y, Hashizume C, Miyakawa A, Murai T, Yanagi T, Sugie C, Nagai A.
  • Journal Title: Journal of Radiatiion Research Volume: 62(2) Pages: 338-345
  • Peer Reviewed / Open Access
• [Journal Article] Intensity-modulated radiation therapy for multiple targets with tomotherapy using multiple sets of static ports from different angles (2020)
  • Author(s): Manabe Yoshihiko、Shibamoto Yuta、Murai Taro、Torii Akira、Niwa Masanari、Kondo Takuhito、Okazaki Dai、Sugie Chikao
  • Journal Title: Journal of Applied Clinical Medical Physics Volume: - Issue: 6 Pages: 132-138
  • DOI: 10.1002/acm2.12874
  • Peer Reviewed / Open Access
• [Journal Article] Definitive chemoradiotherapy for squamous cell carcinoma of the esophagus: outcomes for borderline-resectable disease. (2020)
  • Author(s): Ishikura S, Kondo T, Murai T, Ozawa Y, Yanagi T, Sugie C, Miyakawa A, Shibamoto Y.
  • Journal Title: Journal of Radiatiion Research. Volume: 61(3) Pages: 464-469
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy of herbal medicine TJ-14 for acute radiation-induced enteritis: a multi-institutional prospective Phase II trial (2019)
  • Author(s): Murai Taro、Matsuo Masayuki、Tanaka Hidekazu、Manabe Yoshihiko、Takaoka Taiki、Hachiya Kae、Yamaguchi Takahiro、Otsuka Shinya、Shibamoto Yuta
  • Journal Title: Journal of Radiation Research Volume: 61 Issue: 1 Pages: 140-145
  • DOI: 10.1093/jrr/rrz025
  • Peer Reviewed / Open Access
• [Journal Article] Helical tomotherapy for chemo‐refractory multiple liver metastases (2019)
  • Author(s): Takaoka Taiki、Shibamoto Yuta、Murai Taro、Kobayashi Masanori、Sugie Chikao、Manabe Yoshihiko、Kondo Takuhito、Okazaki Dai、Yamada Yuki、Torii Akira
  • Journal Title: Cancer Medicine Volume: 8 Issue: 18 Pages: 7594-7602
  • DOI: 10.1002/cam4.2651
  • Peer Reviewed / Open Access
• [Journal Article] Organ-preserving approach via radiotherapy for small cell carcinoma of the bladder: an analysis based on the Japanese Radiation Oncology Study Group (JROSG) survey. (2019)
  • Author(s): Akamatsu H, Nakamura K, Ebara T, Inaba K, Itasaka S, Jingu K, Kosaka Y, Murai T, Nagata K, Soejima T, Takahashi S, Toyoda T, Toyoshima S, Nemoto K, Akimoto T.
  • Journal Title: J Radiat Res. Volume: 60 Issue: 4 Pages: 509-516
  • DOI: 10.1093/jrr/rrz018
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Evaluation of Onrad, A New Low-cost Version of TomoTherapy that Uses Only Static Beams (2018)
  • Author(s): MURAI TARO、TAMURA TAKESHI、NAKABAYASHI TADASHI、ITO HIROYA、MANABE YOSHIHIKO、MURATA RUMI、NIWA MASANARI、SHIBAMOTO YUTA
  • Journal Title: The Kurume Medical Journal Volume: 65 Issue: 4 Pages: 129-136
  • DOI: 10.2739/kurumemedj.MS654004
  • NAID: 130007789169
  • ISSN: 0023-5679, 1881-2090
  • Year and Date: 2018-12-31
  • Peer Reviewed / Open Access