光子線と粒子線のがん転移への影響の比較

2015 Fiscal Year Annual Research Report

• Project/Area Number: 26290055
• Research Institution: Osaka University
• Principal Investigator: 小泉 雅彦 大阪大学, 医学(系)研究科(研究院), 教授 (90186594)
• Co-Investigator(Kenkyū-buntansha): 松浦 成昭 大阪大学, 医学(系)研究科(研究院), 教授 (70190402) ; 出水 祐介 神戸大学, 医学(系)研究科(研究院), 准教授 (50452496)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 炭素イオン線 / 陽子線 / がん移転 / がん幹細胞 / 細胞遊走 / 浸潤能

Outline of Annual Research Achievements

本研究の目的は、異なる線質である3種の放射線（光子線：X線、粒子線：炭素イオン線、陽子線）が、がん転移に関わる因子に対してどのような影響が生じるか検討し、遠隔転移抑制を視野に入れた放射線治療を行う為の生物学的な因子を定量的に提供することである。本年度は、細胞機能に関する実験を主に進めた。昨年に引き続き、ヒト肺がん細胞A549、ヒト乳がん細胞MDAMB-231、ヒト前立腺癌細胞PC-3及び、本年からヒト子宮頚がん細胞HeLaに対してX線、陽子線、炭素イオン線照射後、がん転移に関わる細胞遊走能ならびに浸潤能を比較検討した。
その結果、低線量（0.5 Gy、2 Gy）X線を照射されたがん細胞の遊走、浸潤能が亢進する結果がこれまで同様に、確認された。炭素イオン線の場合、X線でがん転移能の亢進が認められた線量と同等の生物学的効果を有する線量を照射しても、遊走能、浸潤能は抑制され、線量依存的に更に抑制されることがわかった。本結果より、粒子線は光子線に比べがん転移の抑制効果がみられることが示された。また、その結果はがん種によらず汎用的な事象であることが分かった。
次にヒト膵がん細胞AsPC-1を用いて放射線照射後の膵がんがん幹細胞のマーカーであるCD24、CD44のバリアントの発現を検討した。その結果、CD24、CD44sのmRNA levelがX線照射により亢進することが分かった。本マーカーを使いがん幹細胞と非がん幹細胞に分離し、X線を照射後の細胞の遊走能、浸潤能を比較すると非がん幹細胞は、線量依存的に細胞遊走能が抑制されることも確認された。

Current Status of Research Progress

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

Reason

X線照射により膵がん幹細胞マーカーであるCD44のバリアントの遺伝子発現が変化することを見出した。

Strategy for Future Research Activity

得られた結果を元に動物実験を行う。また、標的遺伝子のノックダウンにより、X線照射で亢進する転移能が抑制できるか否か検討する。

Causes of Carryover

実験計画の内容を見直した為、実験試薬の購入を１つ見送った。

Expenditure Plan for Carryover Budget

次年度に見送った実験を行う為、必要な実験試薬を購入する。

Research Products

• [Journal Article] VMAT-SBRT planning based on an average intensity projection for lung tumors located in close proximity to the diaphragm: a phantom and clinical validity study. (2016)
  • Author(s): Ohira S, Ueda Y, Hashimoto M, Miyazaki M, Isono M, Kamikaseda H, Masaoka A, Takashina M, Koizumi M, Teshima T.
  • Journal Title: J Radiat Res. Volume: 57(1) Pages: 91-97
  • DOI: 10.1093/jrr/rrv058.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Couch height-based patient setup for abdominal radiation therapy. (2016)
  • Author(s): Ohira S, Ueda Y, Nishiyama K, Miyazaki M, Isono M, Tsujii K, Takashina M, Koizumi M, Kawanabe K, Teshima T.
  • Journal Title: Med Dosim. Volume: 41(1) Pages: 59-63
  • DOI: 10.1016/j.meddos.2015.08.003.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Long-term results of intraoperative extracorporeal irradiation of autogenous bone grafts on primary bone and soft tissue malignancies. (2015)
  • Author(s): Hayashi K, Araki N, Koizumi M, Suzuki O, Seo Y, Naka N, Isohashi F, Myoui A, Yoshioka Y, Teshima T, Ueda T, Yoshikawa H, Ogawa K.
  • Journal Title: Acta Oncol. Volume: 54(1) Pages: 138-141
  • DOI: 10.3109/0284186X.2014.930172.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Hypofractionated Radiotherapy for Localized Prostate Cancer: A Challenging Accelerated Hypofractionated Radiotherapy. (2015)
  • Author(s): Yamazaki H, Nakamura S, Suzuki G, Yoshida K, Yoshioka Y, Koizumi M, Ogawa K.
  • Journal Title: Anticancer Res. Volume: 35(10) Pages: 5167-5177
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Effects of Injecting Calcium or Calcium Chelator on Bone Mineral Density in Ovariectomized Mice (2016)
  • Author(s): Minami K, Andy B. Chen, Matsuura N, Koizumi M, Yokota H
  • Organizer: ORS Annual Meeting
  • Place of Presentation: Florida, USA
  • Year and Date: 2016-03-05 – 2016-03-06
  • Int'l Joint Research
• [Presentation] The Sensitizing Effect of PARP Inhibitors with High-dose Irradiation in colorectal cancer cell lines (2016)
  • Author(s): Yoshizaki K, Seo Y, Minami K, Tamari K, Takashina M, Isohashi F, Ogawa K, Koizumi M
  • Organizer: The 4th International Symposium of Training Plan for Oncology Professionals
  • Place of Presentation: 奈良県文化会館(奈良県、奈良市)
  • Year and Date: 2016-02-27 – 2016-02-28
  • Int'l Joint Research
• [Presentation] Assess the Shielding of Secondary Neutron from Patient Collimator in Proton Therapy Considering Secondary Photons Generated in the Shielding Process with Monte Carlo Simulation (2015)
  • Author(s): Yamanaka M, Takashina M, Kurosu K, Moskvin V, Das I.J., Koizumi M
  • Organizer: 57th AAPM Annual Meeting
  • Place of Presentation: Anaheim, USA
  • Year and Date: 2015-07-12 – 2015-07-16
  • Int'l Joint Research
• [Presentation] Development of a System to Verify for Connection Consistency in a Brachytherapy (2015)
  • Author(s): Otani Y, Sumida I, Yagi M, Mizuno H, Takashina M, Koizumi M, Ogawa K
  • Organizer: 57th AAPM Annual Meeting
  • Place of Presentation: Anaheim, USA
  • Year and Date: 2015-07-12 – 2015-07-16
  • Int'l Joint Research
• [Presentation] Treatment Plannning Study of Prostate Cancer by CyberKnife with Respected to the Urethral Dose (2015)
  • Author(s): Mizuno H, Sumida I, Otani Y, Yagi M, Takashina M, Suzuki O, Yoshioka Y, Koizumi M, Ogawa K
  • Organizer: 57th AAPM Annual Meeting
  • Place of Presentation: Anaheim, USA
  • Year and Date: 2015-07-12 – 2015-07-16
  • Int'l Joint Research
• [Presentation] Four-Dimensional Treatment Planning for Lung VMAT-SBRT” (2015)
  • Author(s): Hashimoto M, Oohira S, Ueda Y, Miyazaki M, Isono M, Masaoka A, Takashina M, Koizumi M, Teshima T
  • Organizer: 57th AAPM Annual Meeting
  • Place of Presentation: Anaheim, USA
  • Year and Date: 2015-07-12 – 2015-07-16
  • Int'l Joint Research
• [Presentation] Overview of the JSPS Core-to-Core Program, JSPS Core-to-Core Program Training Plan for Cancer Professionals (2015)
  • Author(s): Koizumi M
  • Organizer: Pre-AAPM Scientific Symposium
  • Place of Presentation: Anaheim, USA
  • Year and Date: 2015-07-11
  • Int'l Joint Research / Invited
• [Presentation] Collaborative researches in the JSPS Core-to-Core Program, JSPS Core-to-Core Program & Training Plan for Cancer Professionals (2015)
  • Author(s): Takashina M
  • Organizer: Pre-AAPM Scientific Symposium
  • Place of Presentation: Anaheim, USA
  • Year and Date: 2015-07-11
  • Int'l Joint Research / Invited
• [Presentation] Accuracy of radionuclide generation simulation using Antisymmetrized Molecular Dynamics (AMD) (2015)
  • Author(s): Takashina M, Sakurai Y, Fukunaga K, Matsumoto M, Koizumi M, Ono A
  • Organizer: World Congress on Medical Physics and Biomedical Engineering
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2015-06-07 – 2015-06-12
  • Int'l Joint Research
• [Presentation] Simulation of radionuclide generation using Antisymmetrized Molecular Dynamics (AMD) (2015)
  • Author(s): Takashina M, Sakurai Y, Matsumoto M, Koizumi M, Ono A
  • Organizer: 54th Annual Conference of Proton Therapy Co-Operative Group
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-05-18 – 2015-05-23
  • Int'l Joint Research
• [Presentation] Optimization of Arrangements of Degrader for Carbon Ion Beam Therapy from the Viewpoint of Biological Equivalent Dose (2015)
  • Author(s): Yamada R, Kurosu K, Takashina M, Koizumi M
  • Organizer: 54th Annual Conference of Proton Therapy Co-Operative Group
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-05-18 – 2015-05-23
  • Int'l Joint Research
• [Presentation] Shielding of the secondary neutrons from patient collimator in proton therapy (2015)
  • Author(s): Yamanaka M, Takashina M, Kurosu K, Moskvin V, Das I, Koizumi M
  • Organizer: 54th Annual Conference of Proton Therapy Co-Operative Group
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-05-18 – 2015-05-23
  • Int'l Joint Research
• [Presentation] Limited impact of breathing motion, interplay effect and set-up/range uncertainties in IMPT for advanced stage NSCLC (2015)
  • Author(s): Inoue T, van Dijk L.V., Widder J, Takegawa H, Koizumi M, Takashina M, Saito A.I., Sasai K, van’t Veld A.A., Langendijk J.A., Korevaar E.W.
  • Organizer: 54th Annual Conference of Proton Therapy Co-Operative Group
  • Place of Presentation: San Diego, USA
  • Year and Date: 2015-05-18 – 2015-05-23
  • Int'l Joint Research