プロフィラクティック食品の消化管有害反応低減によるメタボロミック放射線療法

2016 Fiscal Year Research-status Report

• Project/Area Number: 15K09996
• Research Institution: Kobe University
• Principal Investigator: 岡本 欣晃 神戸大学, 医学研究科, 非常勤講師 (20362791)
• Co-Investigator(Kenkyū-buntansha): 赤坂 浩亮 神戸大学, 医学部附属病院, 特命助教 (20707161) ; 佐々木 良平 神戸大学, 医学部附属病院, 特命教授 (30346267) ; 江島 泰生 神戸大学, 医学部附属病院, 特命准教授 (70423233) ; 椋本 成俊 神戸大学, 医学部附属病院, 特命技術員 (70634278) ; 吉田 賢史 神戸大学, 医学部附属病院, 特命講師 (80351906)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: メタボロミクス / 放射線防護

Outline of Annual Research Achievements

プロフィラクティック食品の消化管有害反応低減によるメタボロミック放射線療法を研究の目的としている。Sterotactic body radiotherapy(SBRT)の主眼は、肺癌から肝細胞癌や膵臓癌などの上腹部の悪性腫瘍に移行しつつあるが、腹部への照射では主として近接する消化管の有害反応がDose limiting factorとなる。消化管を防護することによる有害反応の軽減は新規がん放射線治療の成否に繋がるが、食欲低下や下痢等の腹部放射線療法に関連する消化器症状に関しては、その分子機序や標的細胞が不明なことが多い。我々はこれまでレドックス制御に着目し、放射線照射に対する消化管の標的細胞とその機序、防護法を見出してきた。本申請では放射線療法による消化管有害反応の標的細胞の評価方法を確立し、腹部悪性腫瘍に対する放射線療法にて消化管症状を有する患者血液をメタボロミクス解析し、その改善のためのプロフィラクティック食品化合物の絞り込みを行うが、現時点では還元型Coenzyme Q10（以下CoQ10）が非常に有効であるとの実験結果を得ている。有効な化合物の評価するための動物実験モデルは我々の先行研究で既に確立しており、今回は更に自家発癌モデル動物を用いて候補化合物が放射線療法を軸とする抗がん治療の有効性を保持したまま消化管防護効果を発揮することを確認する。
今回の申請では、①放射線照射後の正常組織と腫瘍細胞での細胞死に関与するROSの関与と分子機序を検討し、②メタボロミクス解析による放射線消化管障害の代謝産物の同定と有害反応軽減する候補物質の同定、③プロフィラクティック食品を投与し、担癌ラットを用いた放射線照射による消化管防護と抗腫瘍効果の増加効果を確認する。④プロフィラクティック食品を併用メタボロミック放射線療法の臨床試験と、臨床検体を用いたメタボロミクス解析を目標とする。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

これまでプロフィラクティック食品の第一の候補として還元型コエンザイムQ10の投与における、放射線線防護効果を確認できており、さらにその分子機序の解明に取り組んでいるが、照射後のメタボロミクス解析から、放射線照射に関連する代謝変動を確認できており、その足掛かりを得ている。

Strategy for Future Research Activity

メタボロミクス解析から得られた知見をもとに、質量分析などによる確認を実施していく予定である。

Causes of Carryover

プロフィラクテック食品を用いた放射線防護効果に関してメタボロミクス解析と質量分析に検討を実施したが、代謝物の同定とその確認の時間を要し、最適な質量分析方法に関しての検討に時間が必要であったため。

Expenditure Plan for Carryover Budget

今回の検討において、有益な代謝物の同定がほぼ確定しており、今後は更なる質量分析を実施していく予定である。

Research Products

• [Journal Article] Particle Therapy Using Protons or Carbon Ions for Unresectable or Incompletely Resected Bone and Soft Tissue Sarcomas of the Pelvis (2017)
  • Author(s): Yusuke Demizu, Dongcun Jin, Nor Shazrina Sulaiman, Fumiko Nagano, Kazuki Terashima, Sunao Tokumaru, Takashi Akagi, Osamu Fujii, Takashi Daimon, Ryohei Sasaki, Nobukazu Fuwa, Tomoaki Okimoto,
  • Journal Title: Int J Radiat Oncol Biol Physc Volume: 98(2 Pages: 367e374,
  • DOI: doi.org/10.1016/j.ijrobp.2017.02.030
  • Peer Reviewed
• [Journal Article] Relationship between the uptake of 18F-borono-L-phenylalanine and L-[methyl-11C] methionine in head and neck tumors and normal organs, (2017)
  • Author(s): Yoshiaki Watanabe, Hiroaki Kurihara, Jun Itami, Ryohei Sasaki, Yasuaki Arai, Kazuro Sugimura,
  • Journal Title: Radiat Oncol Volume: 12(1) Pages: 17
  • DOI: doi: 10.1186/s13014-017-0763-6.
  • Peer Reviewed / Open Access
• [Journal Article] [18F]Fluorodeoxyglucose uptake by positron emission tomography predicts outcomes for oropharyngeal and hypopharyngeal cancer treated with definitive radiotherapy. (2017)
  • Author(s): Takeaki Ishihara, Kazuhiro Kitajima, Yuko Suenaga, Yasuyuki Shimizu, Saki Osuga, Yasuo Ejima, Hirokazu Komatsu, Naoki Otsuki, Kenichi Nibu, Naomi kiyota, Satoru Takahashi, and Ryohei Sasaki,
  • Journal Title: Nagoya Journal of Medical Science Volume: 79(1) Pages: 27-36
  • DOI: doi: 10.18999/nagjms.79.1.27.
  • Peer Reviewed
• [Journal Article] Sparing of tissue minimizes neurotoxicity when using micro-slit beam versus broad beam radiation therapy, (2017)
  • Author(s): Naritoshi Mukumoto, Masao Nakayama, Hiroaki Akasaka, Yasuyuki Shimizu, Saki Osuga, Daisuke Miyawaki, Kenji Yoshida, Yasuo Ejima, Yasushi Miura, Keiji Umetani, Takeshi Kondoh, Ryohei Sasaki,
  • Journal Title: J Radiat Res Volume: 58(1) Pages: 17-23
  • DOI: doi: 10.1093/jrr/rrw065.
  • Peer Reviewed / Open Access
• [Journal Article] MGDG extracted from spinach enhances the cytotoxicity of radiation in pancreatic cancer cells (2016)
  • Author(s): Akasaka H, Mizushina Y, Yoshida K, Ejima Y, Mukumoto N, Wang T, Inubushi S, Nakayama M, Wakahara Y, Sasaki R.
  • Journal Title: Radiat Oncol. Volume: 11(1) Pages: 153
  • DOI: DOI 10.1186/s13014-016-0729-0
  • Peer Reviewed / Open Access
• [Journal Article] Dosimetric factors predicting radiation pneumonitis after CyberKnife stereotactic body radiotherapy for peripheral lung cancer. (2016)
  • Author(s): Nakamura M, Nishimura H, Nakayama M, Mayahara H, Uezono H, Harada A, Hashimoto N, Ejima Y, Ishihara T, Sasaki R.
  • Journal Title: Br J Radiol. Volume: - Pages: 20160560
  • DOI: doi.org/10.1259/bjr.20160560
  • Peer Reviewed
• [Journal Article] Characterization of titanium dioxide nanoparticles modified with polyacrylic acid and H2O2 for use as a novel Radiosensitizer (2016)
  • Author(s): Morita K, Miyazaki S, Numaki C, Ikeno S, Sasaki R, Nishimura Y, Ogino C, Kondo A,
  • Journal Title: Free Radical Research, Volume: 50(12) Pages: 1319-1328
  • DOI: DOI:10.1080/10715762.2016.1241879
  • Peer Reviewed
• [Journal Article] Cause and occurrence timing of osteoradionecrosis of the jaw: a retrospective study focusing on prophylactic tooth extraction, (2016)
  • Author(s): Satoshi Wanifuchi, Masaya Akashi, Yasuo Ejima, Hirotaka Shinomiya, Tsutomu Minamikawa, Shungo Furudoi, Naoki Otsuki, Ryohei Sasaki, Ken-ichi Nibu, Takahide Komori,
  • Journal Title: Oral and Maxillofacial Surgery, Volume: 20(4) Pages: 337-342
  • DOI: DOI: 10.1007/s10006-016-0570-5
  • Peer Reviewed
• [Journal Article] Prospective Cohort Study of Performance Status and Activities of Daily Living after Surgery for Spinal Metastasis, (2016)
  • Author(s): Kakutani K, Sakai Y, Maeno Y, Takada T, Yurube T, Kurakawa T, Miyazaki S, Terashima Y, Ito M, Hara H, Kawamoto T, Ejima Y, Sakashita A, Kizawa Y, Sasaki R, Akisue T, Minami H, Kuroda R, Kurosaka R, Nishida K,
  • Journal Title: Clin Spine Surgery, Volume: - Pages: -
  • DOI: DOI:10.1097/BSD.0000000000000456
  • Peer Reviewed
• [Journal Article] Titanium peroxide nanoparticles enhanced cytotoxic effects of X-ray irradiation against pancreatic cancer model through reactive oxygen species generation in vitro and in vivo, (2016)
  • Author(s): Masao Nakayama, Ryohei Sasaki, Chiaki Ogino, Tsutomu Tanaka, Kenta Morita, Mitsuo Umetsu, Satoshi Ohara, Zhenquan Tan, Yuya Nishimura, Hiroaki Akasaka, Kazuyoshi Sato, Chiya Numako, Seiichi Takami, Akihiko Kondo,
  • Journal Title: Radiat Oncol. Volume: 11(1) Pages: 91
  • DOI: doi: 10.1186/s13014-016-0666-y.
  • Peer Reviewed / Open Access
• [Journal Article] Diagnostic value of glutamate with 2-hydroxyglutarate in magnetic resonance spectroscopy for IDH1 mutant glioma. (2016)
  • Author(s): Nagashima H, Tanaka K, Sasayama T, Irino Y, Sato N, Takeuchi Y, Kyotani K, Mukasa A, Mizukawa K, Sakata J, Yamamoto Y, Hosoda K, Itoh T, Sasaki R, Kohmura E.
  • Journal Title: Neuro Oncol. Volume: 18(11) Pages: 1559-1568
  • DOI: DOI:10.1093/neuonc/now090
  • Peer Reviewed
• [Journal Article] Hypofractionated stereotactic radiotherapy for brain metastases from lung cancer : Evaluation of indications and predictors of local control. (2016)
  • Author(s): Ishihara T, Yamada K, Harada A, Isogai K, Tonosaki Y, Demizu Y, Miyawaki D, Yoshida K, Ejima Y, Sasaki R.
  • Journal Title: Strahlenther Onkol. Volume: 192(6) Pages: 386-393
  • DOI: doi: 10.1007/s00066-016-0963-2.
  • Peer Reviewed
• [Journal Article] Efficacy of Stereotactic Body Radiotherapy for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis / Inferior Vena Cava Tumor Thrombosis: Evaluation by Comparison with Conventional Three-Dimensional Conformal Radiotherapy, (2016)
  • Author(s): Yoshiro Matsuo, Kenji Yoshida, Hideki, Nishimura, Yasuo Ejima, Daisuke Miyawaki, Haruka Uezono, Takeaki Ishihara, Hiroshi Mayahara, Takumi Fukumoto, Yonson Ku, Masato Yamaguchi, Koji Sugimoto, and Ryohei Sasaki,
  • Journal Title: J Radiat Res, Volume: 57(5) Pages: 512-523
  • DOI: doi.org/10.1093/jrr/rrw028
  • Peer Reviewed / Open Access
• [Journal Article] Radiotherapy for brainstem gliomas in children and adults: A single-institution experience and literature review. (2016)
  • Author(s): Yoshida K, Sulaiman NS, Miyawaki D, Ejima Y, Nishimura H, Ishihara T, Matsuo Y, Nishikawa R, Sasayama T, Hayakawa A, Kohmura E, Sasaki R.
  • Journal Title: Asia Pac J Clin Oncol. Volume: 13(2) Pages: e153-e160
  • DOI: doi: 10.1111/ajco.12451
  • Peer Reviewed
• [Journal Article] Randomized Trial of Standard Pain Control with or without Gabapentin for Pain Related to Radiation-induced Mucositis in Head and Neck Cancer. (2016)
  • Author(s): Tomoko Kataoka, Naomi Kiyota, Takanobu Shimada, Yohei Funakoshi, Naoko Chayahara, Masanori Toyoda, Yutaka Fujiwara, Kenichi Nibu, Takahide Komori, Ryohei Sasaki, Toru Mukohara, and Hironobu Minami,
  • Journal Title: Auris Nasus Larynx, Volume: 43(6) Pages: 677-84
  • DOI: doi: 10.1016/j.anl.2016.02.012.
  • Peer Reviewed
• [Journal Article] FDG-PET/contrast-enhanced CT as a post-treatment tool in head and neck squamous cell carcinoma: comparison with FDG-PET/non-contrast-enhanced CT and contrast-enhanced CT. (2016)
  • Author(s): Suenaga Y, Kitajima K, Ishihara T, Sasaki R, Otsuki N, Nibu KI, Minamikawa T, Kiyota N, Sugimura K.
  • Journal Title: Eur Radiol. Volume: 26(4) Pages: 1018-30
  • DOI: doi: 10.1007/s00330-015-3902-1.
  • Peer Reviewed
• [Journal Article] [(18)F]-FDG PET/CT imaging for detection of nodal metastases in patients with squamous cell carcinoma of the pharynx and larynx: comparison with CT. (2016)
  • Author(s): Suenaga Y, Kitajima K, Kanda T, Otsuki N, Nibu KI, Sasaki R, Itoh T, Sugimura K.
  • Journal Title: Jpn J Radiol. Volume: 34(3) Pages: 203-10
  • DOI: doi: 10.1007/s11604-015-0510-6.
  • Peer Reviewed
• [Journal Article] Concomitant chemoradiotherapy for advanced squamous cell carcinoma of temporal bone. (2016)
  • Author(s): Shinomiya H, Hasegawa S, Yamashita D, Ejima Y, Kenji Y, Otsuki N, Kiyota N, Sakakibara S, Nomura T, Hashikawa K, Kohmura E, Sasaki R, Nibu KI.
  • Journal Title: Head Neck. Volume: 38 Suppl 1 Pages: E949-53.
  • DOI: DOI: 10.1002/hed.24133
  • Peer Reviewed
• [Presentation] 73.Assessment of the threshold dose for radiation fibrosis in thoracic esophageal cancer patients. (2016)
  • Author(s): Yasuo Ejima, Kenji Yoshida, Daisuke Miyawaki, Takeaki Ishihara, Ryo Nishikawa, Hiroki Kawaguchi, Yoshiro Matsuo, Atsuki Ikeda, Masanori Toyoda, Tetsu Nakamura, Ryohei Sasaki,
  • Organizer: The 1st Meeting of the Federation of Asisan Organizations for Radiation Oncology (FARO),
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2016-11-25 – 2016-11-27
  • Int'l Joint Research
• [Presentation] 76.Assessment of Parametrial Response in stage IIB/IIIB Cervical Cancer Patients from EMBRACE, (2016)
  • Author(s): Kenji Yoshida, Ryohei Sasaki,
  • Organizer: the 4th Taiwan-Japan Radiation Oncology Symposium.
  • Place of Presentation: Taipei Taiwan
  • Year and Date: 2016-06-04 – 2016-06-05
  • Int'l Joint Research
• [Presentation] 77.Space Modulated Particle Therapy with Newly Invented Bio-absorbable Spacer. (2016)
  • Author(s): Ryohei Sasaki, Hiroaki Akasaka, Sachiko Inubushi, Tianyuan Wang, Yasuyuki Shimizu, Saki Osuga, Yusuke Demizu, Takumi Fukumoto,
  • Organizer: the 4th Taiwan-Japan Radiation Oncology Symposium.
  • Place of Presentation: Taipei Taiwan
  • Year and Date: 2016-06-04 – 2016-06-05
  • Int'l Joint Research
• [Book] Non-woven Fabrics (2016)
  • Author(s): Ryohei Sasaki, Hiroaki Akasaka, Yusuke Demizu, Sachiko Inubushi, Tianyuan Wang, Takumi Fukumoto.
  • Total Pages: 324
  • Publisher: Intech
• [Book] 耳鼻咽喉科・頭頸部外科研修ノート 改訂第2版、 (2016)
  • Author(s): 佐々木良平
  • Total Pages: -
  • Publisher: 診断と治療社