Development of chronoradiobiology model in combination of immune cells and radiosensitizer

• Project/Area Number: 15K09998
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Okayama University
• Principal Investigator: Oita Masataka 岡山大学, ヘルスシステム統合科学研究科, 准教授 (10380023)
• Co-Investigator(Kenkyū-buntansha): 宇都 義浩 徳島大学, 大学院社会産業理工学研究部(生物資源産業学域), 教授 (20304553) ; 中田 一弥 東京理科大学, 理工学部応用生物科学科, 准教授 (70514115) ; 吉見 陽児 山陽小野田市立山口東京理科大学, 薬学部, 講師 (70609362)
• Research Collaborator: TOMINAGA masahide ; KATSUI kuniaki ; KATAYAMA Norihisa
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 時間放射線生物学 / 免疫放射線療法 / 生物物理学的計算モデル / 放射線感受性 / 最適化 / 生物物理理学計算モデル

Outline of Final Research Achievements

In this study, we evaluated cellular radiosensitivity and radiosensitizing properties to hypoxic cells in the combination of immune cells and radiosensitizers, and created clinically applicable immunoradiosensitizers based on temporal radiation biology models Dose evaluation and treatment plan optimization were constructed. First, we examined the co-culture conditions in case of adding immune cells to tumor cells and the tumoricidal effect of ultraviolet light on the sensitizer (titanium oxide particles). On the basis of those results, it was useful in performing calculation simulation with chronoradiobiology model, examining clinical treatment plan combined with detailed influence factor of biological parameter, and predicting and evaluating treatment effect.

Academic Significance and Societal Importance of the Research Achievements

本研究では，免疫細胞と放射線増感剤併用における細胞放射線感受性および低酸素細胞への放射線増感特性について評価し，臨床応用が可能な免疫放射線増感剤の創出ならびに時間放射線生物学モデルに基づく線量評価と治療計画最適化の構築を行った．
これらの結果については，国際学会発表および論文にて報告し，抗がん剤や免疫療法で利用される物質と放射線治療の併用時に生じる腫瘍と正常組織の感受性変化に対応可能とし、副作用発現のリスク軽減に向けたプロトコルの個別化（分子標的型の放射線治療計画）に向けた対応の実現性を示し、将来の発展に向けて提唱することができたと考える。

Research Products

• [Journal Article] Comparisonof Head Scatter Factor by Different Ion-Chambers in Flattened and Unflattened Beams (2018)
  • Author(s): Miwa T, Oita M, Aoyama H
  • Journal Title: Medical Physics Volume: 6
  • Peer Reviewed
• [Journal Article] Immunologicalaspects of Improved Tumor and Normal Tissue Responses Using Biophysical modelling (2018)
  • Author(s): Oita M, Udaka M, Aoyama H, Sasaki M, Tominaga M, Uto Y
  • Journal Title: Medical Physics Volume: 6
  • Peer Reviewed
• [Journal Article] 前立腺患者の陽子線スポットスキャニングと従来法との線量分布比較 (2018)
  • Author(s): 冨永 裕樹, 笈田 将皇, 張 智凱, 平井 諒太, 山中 将史, 多田 光寿, 春名 孝泰, 田村 瑞希, 山本 崇裕, 伊田 和司, 綱澤 勝之, 松田 哲典, 黒田 昌宏, 金 東村, 脇 隆博, 丹羽 康江, 藤島 護
  • Journal Title: 津山中央病院医学雑誌 Volume: 32 Pages: 41-52
• [Journal Article] Evaluation of Setup Errors at the Skin Surface Position for Whole Breast Radiotherapy of Breast Cancer Patients (2018)
  • Author(s): Miyahara K, Kuroda M, Yoshimura Y, Aoyama H, Oita M, Sugianto I, Matsuzaki H, Ihara H, Katayama N, Katsui K, Kanazawa S, Asaumi J.
  • Journal Title: Acta Medica Okayama Volume: 72 Issue: 4 Pages: 331-336
  • DOI: 10.18926/AMO/56167
  • NAID: 120006501277
  • URL: https://ousar.lib.okayama-u.ac.jp/56167
• [Journal Article] Effect of dose rate on antitumor activity in hypoxic cells by using flattening filter free beams (2018)
  • Author(s): Hara T, Tominaga M, Yajyu K, Kouzaki R, Yamada H, Sasaki M, Azane S, Uto Y
  • Journal Title: International Journal of Radiation Research Volume: 掲載予定
  • Peer Reviewed
• [Journal Article] Both triazolyl ester of ketorolac (15K) and YM155 inhibit the embryonic angiogenesis <i>in ovo</i> (fertilized eggs) <i>via</i> their common PAK1-survivin/VEGF signaling pathway (2017)
  • Author(s): Ahn MR, Bae JY, Jeong DH, Takahashi H, Uto Y, Maruta H.
  • Journal Title: Drug Discoveries & Therapeutics Volume: 11 Issue: 6 Pages: 300-306
  • DOI: 10.5582/ddt.2017.01058
  • NAID: 130006308126
  • ISSN: 1881-7831, 1881-784X
  • Peer Reviewed
• [Journal Article] Development of a novel Schiff base derivative for enhancing the anticancer potential of 5-aminolevulinic acid-based photodynamic therapy. (2017)
  • Author(s): Shinohara Y, Endo Y, Abe C, Shiba I, Ishizuka M, Tanaka T, Yonemura Y, Ogura SI, Tominaga M, Yamada H, Uto Y.
  • Journal Title: Photodiagnosis Photodyn Ther Volume: 20 Pages: 182-188
  • DOI: 10.1016/j.pdpdt.2017.10.014
  • Peer Reviewed
• [Journal Article] Design and Synthesis of Novel Anti-metastatic Hypoxic Cytotoxin TX-2137 Targeting AKT Kinase. (2017)
  • Author(s): Shiba I, Kouzaki R, Yamada H, Endo Y, Takino T, Sato H, Kitazato K, Kageji T, Nagahiro S, Uto Y.
  • Journal Title: Anticancer Res Volume: 37 Pages: 3877-3883
  • Peer Reviewed
• [Journal Article] Interactive Analysis of TX-1123 with Cyclo-oxygenase: Design of COX2 Selective TX Analogs. (2017)
  • Author(s): Ohkura K, Tatematsu Y, Kawaguchi Y, Uto Y, Hori H.
  • Journal Title: Anticancer Res Volume: 37 Pages: 3849-3854
  • Peer Reviewed
• [Journal Article] 1,2,3-Triazolyl esterization of PAK1-blocking propolis ingredients, artepillin C (ARC) and caffeic acid (CA), for boosting their anti-cancer/anti-PAK1 activities along with cell-permeability. (2017)
  • Author(s): Takahashi H, Nguyen BCQ, Uto Y, Shahinozzaman M, Tawata S, Maruta H.
  • Journal Title: Drug Discov Ther Volume: 11 Pages: 104-109
  • NAID: 130007040206
  • Peer Reviewed
• [Journal Article] Photodynamic Therapy Mediated by a Novel Chlorin Derivative, TONS 501-Na, in EMT6 cells. (2017)
  • Author(s): Osaki T, Sakata I, Uto Y, Azuma K, Murahata Y, Tsuka T, Itoh N, Imagawa T, Okamoto Y.
  • Journal Title: Anticancer Res Volume: 37 Pages: 1723-1728
  • Peer Reviewed
• [Journal Article] Does the biophysical modelling for immunological aspects in radiotherapy precisely predict tumor and normal tissue responses? (2016)
  • Author(s): M.Oita, K.Nakata, H.Aoyama, M.Sasaki, M.Tominaga, H.Hoda, Y.Uto
  • Journal Title: Medical Physics Volume: 43 Issue: 6Part24 Pages: 3621-3621
  • DOI: 10.1118/1.4956867
  • Peer Reviewed
• [Journal Article] Air-kerma strength and dose rate constant by the full monte carlo simulations (2016)
  • Author(s): S.Tsuji, M.Oita, N.Narihiro
  • Journal Title: Medical Physics Volume: 43 Issue: 6Part13 Pages: 3469-3469
  • DOI: 10.1118/1.4956168
  • Peer Reviewed
• [Journal Article] Characterization of stochastic noise and post-irradiation density growth for reflective-type radiochromic film in therapeutic photon beam dosimetry. (2016)
  • Author(s): Takeshi Kamomae, Masataka Oita, Naoki Hayashi, Motoharu Sasaki, Hideki Aoyama, Hiroshi Oguchi, Mariko Kawamura, Hajime Monzen, Yoshiyuki Itoh, Shiniji Naganawa
  • Journal Title: Phys Med. Volume: 32 Issue: 10 Pages: 1314-1320
  • DOI: 10.1016/j.ejmp.2016.07.091
  • Peer Reviewed / Open Access
• [Journal Article] Case Report: GcMAF Treatment in a Patient with Multiple Sclerosis (2016)
  • Author(s): Inui T, Katsuura G, Kubo K, Kuchiike D, Chenery L, Uto Y, Nishikata T, Mette M
  • Journal Title: Anticancer Research Volume: 36 Pages: 3771-74
  • Peer Reviewed / Open Access
• [Journal Article] Case Report: A Non-small Cell Lung Cancer Patient Treated with GcMAF, Sonodynamic Therapy and Tumor Treating Fields. (2016)
  • Author(s): Inui T, Amitani H, Kubo K, Kuchiike D, Uto Y, Nishikata T, Mette M
  • Journal Title: Anticancer Research Volume: 36 Pages: 3767-70
  • Peer Reviewed / Open Access
• [Journal Article] Macrophages Exhibit a Large Repertoire of Activation States via Multiple Mechanisms of Macrophage-activating Factors. (2016)
  • Author(s): Sumiya YU, Inoue T, Ishikawa M, Inui T, Kuchiike D, Kubo K, Uto Y, Nishikata T
  • Journal Title: Anticancer Research Volume: 36 Pages: 3619-23
  • Peer Reviewed / Open Access
• [Journal Article] Application of biophysical modelling for normal tissue response with immunological aspects in radiotherapy (2016)
  • Author(s): M.Oita, H.Aoyama, M.Sasaki, M.Tominaga, H.Hoda, Y.Uto
  • Journal Title: Radiotherapy & Oncology Volume: 118 Pages: S79-S80
  • DOI: 10.1016/s0167-8140(16)30162-1
  • Peer Reviewed
• [Journal Article] Macrophage Activation Mechanisms in Human Monocytic Cell Line-derived Macrophages. (2015)
  • Author(s): Yu Sumiya, Mami Ishikawa, Takahiro Inoue, Toshio Inui, Daisuke Kuchiike, Kentaro Kubo, Yoshihiro Uto and Takahito Nishikata
  • Journal Title: Anticancer Research Volume: 35 Pages: 4447-4451
  • Peer Reviewed
• [Journal Article] Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production. (2015)
  • Author(s): Yoshihiro Uto, Tomohito Kawai, Toshihide Sasaki, Ken Hamada, Hisatsugu Yamada, Daisuke Kuchiike, Kentaro Kubo, Toshio Inui, Martin Mette, Ken Tokunaga, Akio Hayakawa, Akiteru Go and Tomohiro Oosaki
  • Journal Title: Anticancer Research Volume: 35 Pages: 4487-4492
• [Presentation] Comparisonof Head Scatter Factor by Different Ion-Chambers in Flattened and Unflattened Beams (2018)
  • Author(s): Miwa T, Oita M, Aoyama H
  • Organizer: AAPM 2018 60th Annual Meeting
  • Int'l Joint Research
• [Presentation] Immunologicalaspects of Improved Tumor and Normal Tissue Responses Using Biophysical modelling (2018)
  • Author(s): Oita M, Udaka M, Aoyama H, Sasaki M, Tominaga M, Uto Y
  • Organizer: AAPM 2018 60th Annual Meeting
  • Int'l Joint Research
• [Presentation] 膵臓癌陽子線治療におけるAdaptive Radiotherapyの検討 (2018)
  • Author(s): 今江 達哉, 谷口 真悟, 二ノ丸 雄也, 清水 勝一, 笈田 将皇
  • Organizer: 第74回日本放射線技術学会秋季学術大会
• [Presentation] マクロファージ活性化因子GcMAFの貪食活性化作用に関する受容体の同定と作用機序の解明 (2017)
  • Author(s): 桑田 依洋，濱田 健，井亀 沙紀，青野 ゆかり，山田 久嗣，Martin Mette，久保 健太郎，乾 利夫，宇都 義浩
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 慶應義塾大学 日吉キャンパス（神奈川県横浜市）
  • Year and Date: 2017-03-16
• [Presentation] ウシ初乳由来マクロファージ活性化剤の創製と抗炎症作用機序の解明 (2017)
  • Author(s): 桑田 依洋，濱田 健，井亀 沙紀，青野 ゆかり，山田 久嗣，Martin Mette，久保 健太郎，乾 利夫，宇都 義浩
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 慶應義塾大学 日吉キャンパス（神奈川県横浜市）
  • Year and Date: 2017-03-16
• [Presentation] 前立腺VMAT治療計画プロトコルと生物学的線量評価に関する基礎的検討 (2017)
  • Author(s): 宇髙昌弘, 笈田将皇, 青山英樹, 佐々木幹治, 川下徹也, 原康男, 富永正英, 生島仁史
  • Organizer: 第13回中四国放射線医療技術フォーラム CSFRT2017
• [Presentation] Comparison of head scatter factor using different ionization chambers in flattened and unflattenned beams (2017)
  • Author(s): Taira Miwa, Masataka Oita, Hideki Aoyama
  • Organizer: 第45回日本放射線技術学会秋季学術大会
• [Presentation] Feasibility of dose delivery error detection by a transmission detector for patient - specific QA (2017)
  • Author(s): H Honda, K Kubo, R Yamamoto, Y Ishii, H Kanzaki, Y Hamamoto, T Mochizuki, M Oita, M Sasaki, M Tominaga, Y Uto
  • Organizer: ESTRO 36
  • Int'l Joint Research
• [Presentation] Does the biophysical modelling for immunological aspects in radiotherapy precisely predict tumor and normal tissue responses? (2016)
  • Author(s): M.Oita, K.Nakata, H.Aoyama, M.Sasaki, M.Tominaga, H.Hoda, Y.Uto
  • Organizer: 58th AAPM Annual Meeting
  • Place of Presentation: Walter E. Washington Convention Center（ワシントンDC，アメリカ合衆国）
  • Year and Date: 2016-07-31
  • Int'l Joint Research
• [Presentation] Air-kerma strength and dose rate constant by the full monte carlo simulations (2016)
  • Author(s): S.Tsuji, M.Oita, N.Narihiro
  • Organizer: 58th AAPM Annual Meeting
  • Place of Presentation: Walter E. Washington Convention Center（ワシントンDC，アメリカ合衆国）
  • Year and Date: 2016-07-31
  • Int'l Joint Research
• [Presentation] Application of biophysical modelling for normal tissue response with immunological aspects in radiotherapy (2016)
  • Author(s): M.Oita, H.Aoyama, M.Sasaki, M.Tominaga, H.Hoda, Y.Uto
  • Organizer: International Conference on Translational Research in Radio-Oncology | Physics for Health in Europe (ICTR-PHE) 2016
  • Place of Presentation: Centre International de Conferences Geneve (CICG, ジュネーブ)
  • Year and Date: 2016-02-15
  • Int'l Joint Research
• [Presentation] 多次元化する放射線治療技術～放射線生物物理学の基礎と応用～ (2015)
  • Author(s): 笈田将皇
  • Organizer: 第43回日本放射線技術学会秋季学術大会
  • Place of Presentation: 金沢市文化ホール（金沢市）
  • Year and Date: 2015-10-09
  • Invited