An attempt to achieve both controlling local tumors and repressing distant metastases through exploiting analytical findings concerning characteristics of intratumor microenvironment
Project/Area Number |
15H04295
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Tumor biology
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Research Institution | Kyoto University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
永澤 秀子 岐阜薬科大学, 薬学部, 教授 (90207994)
田野 恵三 京都大学, 複合原子力科学研究所, 准教授 (00183468)
真田 悠生 京都大学, 複合原子力科学研究所, 助教 (50738656)
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Research Collaborator |
TAKEDA Shun-ichi
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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Keywords | 休止期腫瘍細胞 / 腫瘍内微小環境 / 中性子捕捉療法 / 転移 / ゲノム改変操作 / 放射線治療生物学 / 硼素中性子捕捉療法 / CBE値 / 線量率効果 / がん微小環境 / 局所腫瘍制御 / 転移能抑制 / ゲノム編集技術 / HIF-1α / メトフォルミン / 低グルコース環境 / ティラパザミン / ピモニダゾール / 急性低酸素領域 / 遠隔転移抑制能 |
Outline of Final Research Achievements |
The p53 status of tumor cells in the local tumor influenced the distribution efficiency of 10B from 10B compounds, which are essential for neutron capture therapy, and the sensitivity to gamma-ray irradiation. The effect on the sensitivity to gamma-rays were efficiently suppressed by irradiation using high linear energy transfer radiation or reactor neutron beams. In addition, large recovery capacity from gamma-ray-induced damage in oxygenated quiescent tumor cells was efficiently suppressed with antidiabetic drug metformin. Hypoxia-inducible factor 1-alpha deficiency in tumor cells increased the metformin sensitivity under glucose deprivation or hypoxia, and the sensitivity to gamma-ray irradiation in combination with metformin. On the other hand, the higher the operation power of the reactor at the time of neutron capture therapy for the tumors implanted in the experimental animal, the higher the therapeutic effect.
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Academic Significance and Societal Importance of the Research Achievements |
腫瘍細胞のp53 statusや低酸素誘導因子の欠損の有無などゲノム特性によって、癌治療効果が変化し、悪性腫瘍に多いp53変異型腫瘍細胞では、その効果が低下する。高線エネルギー付与放射線照射はこの低下を効率よく抑制し、中性子捕捉療法では、全腫瘍細胞と休止期腫瘍細胞との間の10B分布量の差が、p53 statusの変異によってp53野生型より小さくなるために、腫瘍全体としてより均一な線量の付与が可能となり病変部全体としての制御可能性が高まる。さらには、中性子捕捉療法施行時に用いる原子炉の運転出力は高い方が、殺腫瘍細胞効果も高まるので、治療に必要な照射時間は短くても十分な治療効果を期待できる。
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Report
(4 results)
Research Products
(114 results)
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[Journal Article] Development of proton beam irradiation system for small animals using FFAG accelerator2019
Author(s)
Tanaka, H., Takata, T., Ishi, Y., Uesugi, T., Kuriyama, Y., Watanabe, T., Sakurai, Y., Kawabata, S., Masunaga, S.-I., Suzuki, M.
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Journal Title
Nuclear Instruments and Methods in Physics Research, Section A
Volume: 922
Pages: 230-234
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effect of Tirapazamine, Metformin or Mild Hyperthermia on Recovery from Radiation-Induced Damage in Pimonidazole-Unlabeled Quiescent Tumor Cells2017
Author(s)
Masunaga S, Tano K, Sanada Y, Sakurai Y, Tanaka H, Suzuki M, Kondo N, Watanabe T, Takata T, Maruhashi A and Ono K
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Journal Title
World J. Oncol.
Volume: 8
Issue: 5
Pages: 137-146
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Selective cytotoxicity of the anti-diabetic drug, metformin, in glucose-deprived chicken DT40 cells2017
Author(s)
Kadoda K, Moriwaki T, Tsuda M, Sasanuma H, Ishiai M, Takata M, Ide H, Masunaga S, Takeda S and Tano K
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Journal Title
PLOS ONE
Volume: 12
Issue: 9
Pages: e0185141-e0185141
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] NOTE:Development of real-time epithermal neutron detector for boron neutron capture therapy.2017
Author(s)
Tanaka H, Sakurai Y, Takata T, Watanabe T, Kawabata S, Suzuki M, Masunaga S, Taki K, Akabori K, Watanabe K, Ono K.
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Journal Title
Review of Scientific Instruments
Volume: 88
Issue: 5
Pages: 56101-56101
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Selective Boron Delivery by Intra-arterial Injection of BSH-WOW Emulsion in Hepatic Cancer Model for Neutron Capture Therapy.2017
Author(s)
Yanagie H, Dewi N, Higashi S, Ikushima I, Seguchi K, Mizumachi R, Murata Y, Morishita Y, Shinohara A, Mikado S, Yasuda N, Fujihara M, Sakurai Y, Mouri K, Yanagawa M, Iizuka T, Suzuki M, Sakurai Y, Masunaga S, Ono K, et al.
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Journal Title
Br J Radiol
Volume: 90
Issue: 1074
Pages: 20170004-20170004
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Effect of oxygen pressure during incubation with a 10B-carrier on 10B uptake capacity of cultured p53 wild-type and mutated tumor cells: dependency on p53 status of tumor cells and types of 10B-carriers2016
Author(s)
Masunaga S, Tatebe H, Nishimura Y, Tano K, Sanada Y, Moriwaki T, Sakurai Y, Tanaka H, Suzuki M, Kondo N, Maruhashi A and Ono K
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Journal Title
International Journal of Radiation Biology
Volume: 92
Issue: 4
Pages: 187-194
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Detection of γH2AX foci in mouse normal brain and brain tumor after boron neutron capture therapy.2016
Author(s)
Kondo N, Michiue H, Sakurai Y, Tanaka H, Nakagawa Y, Watanabe T, Narabayashi M, Kinashi Y, Suzuki M, Masunaga S, Ono K.
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Journal Title
Rep Pract Oncol Radiother.
Volume: 21(2)
Issue: 2
Pages: 108-12
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] DNA damage induced by boron neutron capture therapy is partially repaired by DNA ligase IV2016
Author(s)
Kondo N, Sakurai Y, Hirota Y, Tanaka H, Watanabe T, Nakagawa Y, Narabayashi M, Kinashi Y, Miyatake S, Hasegawa M, Suzuki M, Masunaga S, Ohnishi T, Ono K.
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Journal Title
Radiat Environ Biophys
Volume: 55(1)
Issue: 1
Pages: 89-94
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Proteomic analysis of cellular response induced by boron neutron capture reaction in human squamous cell carcinoma SAS cells2015
Author(s)
Sato A., Itoh T., Imamichi S., Kikuhara S., Fujimori H., Hirai T., Saito S., Sakurai Y., Tanaka H., Nakamura H., Suzuki M., Murakami Y., Baiseitov D., Berikkhanova K., Zhumadilov Z., Imahori Y., Itami J., Ono K., Masunaga S., Masutani M.
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Journal Title
Applied Radiation and Isotopes
Volume: 106
Pages: 113-219
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Improvement of depth dose distribution using multiple-field irradiation in boron neutron capture therapy2015
Author(s)
N. Fujimoto, H. Tanaka, Y. Sakurai, T. Takata, N. Kondo, M. Narabayashi, Y. Nakagawa, T. Watanabe, Y. Kinashi, S. Masunaga, A. Maruhashi, K. Ono, M. Suzuki,
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Journal Title
Applied Radiation and Isotopes
Volume: 106
Pages: 134-138
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Localized radiation necrosis model in mouse brain using proton ion beams.2015
Author(s)
Kondo N, Sakurai Y, Takata T, Takai N, Nakagawa Y, Tanaka H, Watanabe T, Kume K, Toho T, Miyatake S, Suzuki M, Masunaga S, Ono K.
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Journal Title
Applied Radiation and Isotopes
Volume: 106
Pages: 242-246
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Advances in boron neutron capture therapy (BNCT) at kyoto university - From reactor-based BNCT to accelerator-based BNCT.2015
Author(s)
Sakurai Y, Tanaka H, Takata T, Fujimoto N, Suzuki M, Masunaga S, Kinashi Y, Kondo N, Narabayashi M, Nakagawa Y, Watanabe T, Ono K, Maruhashi A.
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Journal Title
Journal- Korean Physical Society
Volume: 67
Issue: 1
Pages: 76-81
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Study on application of BNCT to synovial sarcoma. Poster Presentation.2018
Author(s)
Fujimoto T, Suzuki M, Kuratsu S, Sudo T, Sakuma T, Sakurai Y, Takata T, Tamari Y, Tanaka H, Masunaga S, Kinashi Y, Kondo N, Igaki H, Fujita I, Andoh T, Morishita M, Yahiro S, Shigemoto R, Kawamoto T, Akisue T, Ichikawa H, Kuroda R, Hirose T.
Organizer
18th International Congress on Neutron Capture Therapy
Related Report
Int'l Joint Research
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[Presentation] Pilot study of gadolinium accumulation in tumour with intra-arterial administration of gadoteridol-entrapped water-in-oil-in-water emulsion in VX-2 rabbit hepatic cancer model for neutron capture therapy.2018
Author(s)
Yanagawa M, Yanagie H, Fujino T, Matsukawa T, Kubota A, Morishita Y, Sakurai Y, Mouri K, Fujihara M, Mizumachi R, Murata Y, Nonaka Y, Novraina D, Hirata T, Shinohara A, Yokoyama K, Sugihara T, Suzuki M, Masunaga S, Sakurai Y, Tanaka H, Ono K, Nishimura R, Ono M, Nakajima J, Takahashi H.
Organizer
18th International Congress on Neutron Capture Therapy
Related Report
Int'l Joint Research
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[Presentation] Effect of the Change in a Reactor Power on the Response of Murine Solid Tumors in Vivo, Referring to that in Intratumor Quiescent Cells and Its Clinical Significance in Boron Neutron Capture Therapy (BNCT).2018
Author(s)
Masunaga S, Sakurai Y, Tanaka H, Takata T, Tano K, Sanada Y, Suzuki M, Maruhashi A, Ono K.
Organizer
104th Scientific Assembry and Annual Meeting, Radiological Society of North America
Related Report
Int'l Joint Research
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[Presentation] Present status and future plan for physical engineering and medical physics for BNCT in KURRI.2017
Author(s)
Yoshinori Sakurai, Hiroki Tanaka, Takushi Takata, Minoru Suzuki, Shinichiro Masunaga, Yuko Kinashi, Natsuko Kondo, Tsubasa Watanabe, Yuki Tamari, Yu Sanada, Koji Ono, Akira Maruhashi.
Organizer
9th Young Researchers' BNCT Meeting
Related Report
Int'l Joint Research
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[Presentation] Radiosensitivity of Pimonidazole -Unlabeled Intratumor Quiescent Cells to Gamma-Rays, Accelerated Carbon Ion Beams and Boron Neutron Capture Reaction (BNCR).2017
Author(s)
Shin-ichiro Masunaga, Yoshinori Sakurai, Hiroki Tanaka, Roichi Hirayama, Yoshitaka Matsumoto, Akiko Uzawa, Keizo Tano, Yu Sanada, Minoru Suzuki, Natsuko Kondo, Takushi Takata, Tsubasa Watanabe, Yuki Tamari, Akira Maruhashi, Koji Ono.
Organizer
9th Young Researchers' BNCT Meeting
Related Report
Int'l Joint Research
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[Presentation] Evaluation of Boron Neutron Capture Therapy for Leiomyosarcoma.2017
Author(s)
T. Fujimoto, N. Kamitani, T. Sudo, T. Sakuma, T. Aihara, M. Uno, N. Kanomata, Y. Sakurai, H. Tanaka, S. Masunaga, Y. Kinashi, N. Kondo, I. Fujita, T. Andoh, M. Morishita, S. Yahiro, T. Kawamoto, T. Akisue, H. Ichikawa, J. Hiratsuka, A. Maruhashi, K. Ono, R. Kuroda, M. Suzuki, T. Hirose.
Organizer
9th Young Researchers' BNCT Meeting
Related Report
Int'l Joint Research
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[Presentation] The effect of fractionated administration of thalidomide at γ-ray irradiation on tumor response and lung metastasis.2016
Author(s)
S. Masunaga, K. Tano, Y. Sanada, Y. Sakurai, H. Tanaka, M. Suzuki, N. Kondo, M. Narabayashi, T. Watanabe, Y. Nakagawa, A. Maruhashi, and K. Ono.
Organizer
The International Conference on Translational Research in Radiation Oncology - Physics for Health in Europe 2016
Place of Presentation
International Center for Conference in Geneva, Geneva, Switzerland
Year and Date
2016-02-15
Related Report
Int'l Joint Research
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[Presentation] ホウ素‐中性子捕捉療法に用いる次世代型ホウ素薬剤の開発2016
Author(s)
服部 能英,石村 美紀,大田 洋一,竹中 宏誌,上原 幸樹, 浅野 智之, 鈴木 実, 増永慎一郎, 小野 公二,切畑 光統
Organizer
第18回癌治療増感研究シンポジウム、変貌する放射線治療法~物理・化学・生物学増感法のリミックスと免疫学のコラボレーション~
Place of Presentation
奈良県文化会館、(奈良県、奈良市)
Year and Date
2016-02-05
Related Report
Invited
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[Presentation] Usefulness of fractionated administrations of thalidomide combined with gamma-ray irradiation in terms of local tumor response and lung metastasis.2015
Author(s)
Masunaga S, Sanada Y, Tano K, Sakurai Y, Tanaka H, Suzuki M, Narabayashi M, Watanabe T, Takata T, Maruhashi A, Ono K.
Organizer
日本放射線腫瘍学会第28回学術大会
Place of Presentation
ベイシア文化ホール、(群馬県、前橋市)
Year and Date
2015-11-19
Related Report
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[Presentation] New protocol for a phase I study on boron neutron capture therapy (BNCT) for malignant pleural mesothelioma2015
Author(s)
Suzuki M, Sakurai Y, Ono K, Nakagawa Y, Narabayashi M, Kondo N, Kinashi Y, Masunaga S, Tanaka H, Takata T, Maruhashi A.
Organizer
日本放射線腫瘍学会第28回学術大会
Place of Presentation
ベイシア文化ホール、(群馬県、前橋市)
Year and Date
2015-11-19
Related Report
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[Presentation] The effect of oxygen pressure during incubation with a 10B-carrier on 10B uptake capacity of cultured p53 wild-type and mutated tumor cells.2015
Author(s)
Masunaga S, Tatebe H, Nishimura Y, Tano K, Sanada Y, Moriwaki T, Sakurai Y, TanakaH, Suzuki M, Maruhashi A,Ono K.
Organizer
The 15th International Congress of Radiation Research (ICRR)
Place of Presentation
国立京都国際会館(京都府、京都市)
Year and Date
2015-05-25
Related Report
Int'l Joint Research
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[Presentation] Development of Real Time Neutron Monitors for BNCT.2015
Author(s)
Tanaka H, Sakurai Y, Suzuki M, Masunaga S, Kinashi Y, Taki K, Fijimoto N, Takata T, Watanabe T, Nakagawa Y, Narabayashi M, Kondo N, Maruhashi A, Ono K.
Organizer
The 15th International Congress of Radiation Research (ICRR)
Place of Presentation
国立京都国際会館(京都府、京都市)
Year and Date
2015-05-25
Related Report
Int'l Joint Research / Invited
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[Presentation] The Usefulness of Heavy-ion Beam to the Radioresistance and the Metastatic Potential Enhanced by Cyclic Hypoxia Condition.2015
Author(s)
Matsumoto Y, Yamashita K, Li H, Kaneko Y, Sun L, Moritake T, Uzawa A, Hirayama R, Ando K, Masunaga S, Shirai T, Furusawa Y, Sakurai H.
Organizer
The 15th International Congress of Radiation Research (ICRR)
Place of Presentation
国立京都国際会館(京都府、京都市)
Year and Date
2015-05-25
Related Report
Int'l Joint Research
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[Presentation] Experiences of Tumour Growth Suppression with Boron Delivery Systems in Rabbit Hepatic Cancer Model for Neutron Capture Therapy.2015
Author(s)
Yanagie H, Higashi S, Nakamura H, Morishita Y, Shinohara A, Fujihara M, Yanagawa M, Yui S, Suzuki M, Sakurai Y, Tanaka M, Masunaga S, Devi N, Ono K, Eriguchi M, Takahashi H.
Organizer
The 15th International Congress of Radiation Research (ICRR)
Place of Presentation
国立京都国際会館(京都府、京都市)
Year and Date
2015-05-25
Related Report
Int'l Joint Research / Invited
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[Presentation] The Response of Cancer Cells to Boron Neutron Capture Reaction.2015
Author(s)
Imamichi S, Itoh T, Sato A, Kikuhara S, Fujimori H, Hirai T, Arai Y, Murakami Y, Imahori Y, Itami J, Ono K, Sakurai Y, Tanaka H, Masunaga S, Masutani M.
Organizer
The 15th International Congress of Radiation Research (ICRR)
Place of Presentation
国立京都国際会館(京都府、京都市)
Year and Date
2015-05-25
Related Report
Int'l Joint Research
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[Presentation] Cyclotron-based epithermal neutron source (C-BENS) for boron neutron capture therapy.2015
Author(s)
Tanaka H, Sakurai Y, Suzuku M, Masunaga S, Mitsumoto T, Maruhashi A, Ono K.
Organizer
Asian Forum for Accelerators and Detectors 2015
Place of Presentation
Lecture Hall, Activity Center , National Synchrotron Radiation Research Center, Hsinchu, Taiwan
Year and Date
2015-04-26
Related Report
Int'l Joint Research / Invited
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