がんに対する重粒子線治療法高度化の為の基礎的・臨床的研究

2015 Fiscal Year Annual Research Report

• Project/Area Number: 24390288
• Research Institution: Gunma University
• Principal Investigator: 中野 隆史 群馬大学, 医学(系)研究科(研究院), 教授 (20211427)
• Co-Investigator(Kenkyū-buntansha): 清原 浩樹 群馬大学, 医学部附属病院, 助教 (10344920) ; 白井 克幸 群馬大学, 医学(系)研究科(研究院), 講師 (10400748) ; 野田 真永 群馬大学, 医学部附属病院, 講師 (60396645) ; 齋藤 淳一 群馬大学, 医学(系)研究科(研究院), 准教授 (70572816)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 重粒子線 / 放射線治療 / 放射線生物 / 粒子線治療 / 放射線腫瘍学

Outline of Annual Research Achievements

1.ヒトのNSCLC細胞株、EGFR変異を有する細胞株、KRAS変異を有する細胞株、EGFR/KRAS野生型NSCLC細胞株の3細胞株を用いて炭素イオン線の生物効果を検討した。
EGFR変異型細胞株のRBEはEGFR野生型細胞株と比較して有意に低値であった。変異型EGFR発現A549細胞は野生型EGFR発現A549細胞株と比較して有意なX線高感受性およびRBE低値を示した。一方、KRAS変異ステイタスによるX線感受性、炭素イオン線感受性およびRBEの差は認められなかった。EGFR変異型細胞株H1650、HCC827、Ma-24におけるX線誘導DSBの修復能は、EGFR野生型細胞株H1299、H1703、A549のそれと比較して有意に低かった。X線照射EGFR変異型細胞株において、NHEJ活性阻害剤併用によるγH2AX foci数の上乗せ効果は明らかでなかった。
このことから、EGFR変異型細胞株ではDSB修復の主要経路のひとつであるNHEJの活性が低いことが示唆された。一方、上記6細胞株における炭素イオン線誘導DSBの修復能は、EGFR変異ステイタスに関わらず全ての細胞株においてX線誘導DSBの修復能より有意に低かった。
EGFR変異型NSLCL細胞株はEGFR野生型NSCLC細胞株と比較してNHEJ活性が低く、X線高感受性と炭素イオン線RBE低値を示した。
2. 脳腫瘍の放射線感受性を考慮して、神経幹細胞および神経膠芽腫細胞増殖率を指標とした放射線感受性について比較検討した。その結果、増殖率を指標とした放射線感受性はA172と比べてNSCの方が約4倍高く、両細胞ともにRBEは約2であった。また、両放射線による細胞死型は、NSCでアポトーシスが主であったのに対し、A172ではアポトーシスもネクローシスも顕著に検出されず、誘発される細胞死型も異なることが明らかとなった。

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Causes of Carryover

27年度が最終年度であるため、記入しない。

Expenditure Plan for Carryover Budget

27年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Concurrent chemoradiotherapy for T3–4 and N0–1 nasopharyngeal cancer: Asian multicenter trial of the Forum for Nuclear Cooperation in Asia (2016)
  • Author(s): Tatsuya Ohno, Masaru Wakatsuki, Dang Huy Quoc Thinh, Ngo Thanh Tung, Dyah Erawati, Nana Supriana, C.R. Beena Devi, Shingo Kato, Kullathorn Thephamongkhol, Yaowalak Chansilpa, Miriam Joy C. Calaguas, Xu Xiaoting, Cao Jianping, Parvin Akhter Banu, Chul-Koo Cho, Kumiko Karasawa, Takashi Nakano and Hirohiko Tsujii
  • Journal Title: J Radiat Res Volume: 57 Pages: 44-49
  • DOI: 10.1093/jrr/rrv046
• [Journal Article] Incidence, risk factors, and dose-volume relationship of radiation-induced rib fracture after carbon ion radiotherapy for lung cancer (2016)
  • Author(s): Takanori Abe, Katsuyuki Shirai, Jun-Ichi Saitoh, Takeshi Ebara, Hirofumi Shimada, Mutsumi Tashiro, Naoko Okano, Tatsuya Ohno & Takashi Nakano
  • Journal Title: Acta Oncologica Volume: 55 Pages: 163-166
  • DOI: 10.3109/0284186X.2015.1088169
• [Journal Article] Leptomeningeal metastasis of uterine cervical cancer 17 years after primary tumor treatment (2016)
  • Author(s): Takahiro Oike, Tatsuya Ohno, Shin-Ei Noda, Tomomi Murata, Takashi Hirakawa, Junko Hirato, Mio Furuya, Hiro Sato, Yuka Hirota, Takashi Minegishi & Takashi Nakano
  • Journal Title: CLINICAL CASE REPORTS Volume: 4 Pages: 54-61
  • DOI: 10.1002/ccr3.445
• [Journal Article] Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy (2016)
  • Author(s): Takahiro Oike, Atsuko Niimi, Noriyuki Okonogi, Kazutoshi Murata, Akihiko Matsumura, Shin-Ei Noda, Daijiro Kobayashi, Mototaro Iwanaga, Keisuke Tsuchida, Tatsuaki Kanai, Tatsuya Ohno, Atsushi Shibata & Takashi Nakano
  • Journal Title: Sci Rep Volume: 6 Pages: 22275
  • DOI: 10.1038/srep22275
• [Journal Article] Difference in distant failure site between locally advanced squamous cell carcinoma and adenocarcinoma of the uterine cervix after C-ion RT (2015)
  • Author(s): Wakatsuki M, Kato S, Ohno T, Kiyohara H, Karasawa K, Tamaki T, Ando K, Irie D, Shiba S, Tsujii H, Nakano T, Kamada T, Shozu M; The Working Group of the Gynecological Tumor
  • Journal Title: J Radiat Res Volume: 56 Pages: 523-528
  • DOI: 10.1093/jrr/rru117
• [Journal Article] Carbon-ion beams induce production of an immune mediator protein, high mobility group box 1, at levels comparable with X-ray irradiation (2015)
  • Author(s): Yuya Yoshimoto, Takahiro Oike, Noriyuki Okonogi, Yoshiyuki Suzuki, Ken Ando, Hiro Sato, Shin-ei Noda, Mayu Isono, Kousaku Mimura, Koji Kono and Takashi Nakano
  • Journal Title: Journal of Radiation Research Volume: 56 Pages: 509-514
  • DOI: 10.1093/jrr/rrv007
• [Journal Article] Topics in Chemotherapy, Molecular-targeted Therapy, and Immunotherapy for Newly-diagnosed Glioblastoma Multiforme. (2015)
  • Author(s): Okonogi N, Shirai K, Oike T, Murata K, Noda SE, Suzuki Y, Nakano T
  • Journal Title: Anticancer Res. Volume: 35 Pages: 1229-1235
• [Journal Article] Radiosensitizing effect of carboplatin and paclitaxel to carbon-ion beam irradiation in the non-small-cell lung cancer cell line H460. (2015)
  • Author(s): Kubo N, Noda SE, Takahashi A, Yoshida Y, Oike T, Murata K, Musha A, Suzuki Y, Ohno T, Takahashi T, Nakano T
  • Journal Title: J Radiat Res. Volume: 56 Pages: 229-238
  • DOI: 10.1093/jrr/rru085
• [Journal Article] The EGFR mutation status affects the relative biological effectiveness of carbon-ion beams in non-small cell lung carcinoma cells (2015)
  • Author(s): Napapat Amornwichet, Takahiro Oike, Atsushi Shibata, Chaitanya S. Nirodi, Hideaki Ogiwara, Haruhiko Makino, Yuka Kimura, Yuka Hirota, Mayu Isono, Yukari Yoshida, Tatsuya Ohno, Takashi Kohno & Takashi Nakano
  • Journal Title: Scientific Reports Volume: 5 Pages: 11305
  • DOI: 10.1038/srep11305
• [Journal Article] "Polymyositis and fatal interstitial pneumonia following pelvic irradiation that led to unexpectedly severe adverse effects: a case report" (2015)
  • Author(s): Takahiro Oike, Tatsuya Ohno, Katsuyuki Shirai, Takashi Inoue & Takashi Nakano
  • Journal Title: Clinical Case Reports Volume: 3 Pages: 710-713
  • DOI: 10.1002/ccr3.322
• [Journal Article] Radio-sensitization effect of an mTOR inhibitor, temsirolimus, on lung adenocarcinoma A549 cells under normoxic and hypoxic conditions (2015)
  • Author(s): Hiroki Ushijima, Yoshiyuki Suzuki, Takahiro Oike, Mayumi Komachi, Yuya Yoshimoto, Ken Ando, Noriyuki Okonogi, Hiro Sato, Shin-ei Noda, Jun-ichi Saito and Takashi Nakano
  • Journal Title: J Radiat Res Volume: 56 Pages: 663-668
  • DOI: 10.1093/jrr/rrv021
• [Journal Article] Carbon-ion beams effectively induce growth inhibition and apoptosis in human neural stem cells compared with glioblastoma A172 cells (2015)
  • Author(s): Mayu Isono, Yukari Yoshida, Akihisa Takahashi, Takahiro Oike, Atsushi Shibata, Yoshiki Kubota, Tatsuaki Kanai, Tatsuya Ohno and Takashi Nakano
  • Journal Title: J Radiat Res Volume: 56 Pages: 856-861
  • DOI: 10.1093/jrr/rrv033
• [Journal Article] Filling the gap in central shielding: three-dimensional analysis of the EQD2 dose in radiotherapy for cervical cancer with the central shielding technique (2015)
  • Author(s): Tomoaki Tamaki, Tatsuya Ohno, Shin-ei Noda, Shingo Kato and Takashi Nakano
  • Journal Title: J Radiat Res Volume: 56 Pages: 804-810
  • DOI: 10.1093/jrr/rrv029
• [Journal Article] Development of an automatic evaluation method for patient positioning error. (2015)
  • Author(s): Kubota Y, Tashiro M, Shinohara A, Abe S, Souda S, Okada R, Ishii T, Kanai T, Ohno T, Nakano T
  • Journal Title: J Appl Clin Med Phys Volume: 16 Pages: No.4
  • DOI: 10.1120/jacmp.v16i4.5400
• [Journal Article] Clinical Trial of Prophylactic Extended-Field Carbon-Ion Radiotherapy for Locally Advanced Uterine Cervical Cancer (Protocol 0508) (2015)
  • Author(s): Masaru Wakatsuki, Shingo Kato, Hiroki Kiyohara, Tatsuya Ohno, Kumiko Karasawa, Tomoaki Tamaki, Ken Ando, Hirohiko Tsujii, Takashi Nakano, Tadashi Kamada, Makio Shozu, The Working Group of the Gynecological Tumor
  • Journal Title: PLOS ONE Volume: 10 Pages: e0127587
  • DOI: 10.1371/journal.pone.0127587
• [Journal Article] Clinical outcomes of helical tomotherapy for super-elderly patients with localized and locally advanced prostate cancer: comparison with patients under 80 years of age (2015)
  • Author(s): Noriyuki Okonogi, Hiroyuki Katoh, Hidemasa Kawamura, Tomoaki Tamaki, Takuya Kaminuma, Kazutoshi Murata, Yu Ohkubo, Yosuke Takakusagi, Masahiro Onishi, Tetsuo Sekihara, Atsushi Okazaki and Takashi Nakano
  • Journal Title: J Radiat Res Volume: 56 Pages: 889-896
  • DOI: 10.1093/jrr/rrv040
• [Journal Article] Treatment outcomes of patients with FIGO Stage I/II uterine cervical cancer treated with definitive radiotherapy: a multi-institutional retrospective research study (2015)
  • Author(s): Ariga T, Toita T, Kato S, Kazumoto T, Kubozono M, Tokumaru S, Eto H, Nishimura T, Niibe Y, Nakata K, Kaneyasu Y, Nonoshita T, Uno T, Ohno T, Iwata H, Harima Y, Wada H, Yoshida K, Gomi H, Numasaki H, Teshima T, Yamada S, Nakano T
  • Journal Title: J Radiat Res Volume: 56 Pages: 841-848
  • DOI: 10.1093/jrr/rrv036
• [Journal Article] "Pre-Exposure to Ionizing Radiation Stimulates DNA Double Strand Break End Resection, Promoting the Use of Homologous Recombination Repair" (2015)
  • Author(s): Nakako Izumi Nakajima, Yoshihiko Hagiwara, Takahiro Oike, Ryuichi Okayasu, Takeshi Murakami, Takashi Nakano, Atsushi Shibata
  • Journal Title: PLOS ONE Volume: 10 Pages: e0122582
  • DOI: 10.1371/journal.pone.0122582
• [Journal Article] "Dosimetric comparison of carbon ion radiotherapy and stereotactic body radiotherapy with photon beams for the treatment of hepatocellular carcinoma" (2015)
  • Author(s): Takanori Abe, Jun-ichi Saitoh, Daijiro Kobayashi, Kei Shibuya, Yoshinori Koyama, Hirohumi Shimada, Katsuyuki Shirai, Tatsuya Ohno and Takashi Nakano
  • Journal Title: Radiat Oncol Volume: 10 Pages: 187
  • DOI: 10.1186/s13014-015-0491-8
• [Journal Article] Carbon-ion Radiotherapy for Prostate Cancer: Analysis of Morbidities and Change in Health-related Quality of Life (2015)
  • Author(s): Ishikawa H, Katoh H, Kaminuma T, Kawamura H, Ito K, Matsui H, Hirato J, Shimizu N, Takezawa Y, Tsuji H, Suzuki K, Ohno T, Nakano T
  • Journal Title: Anticancer Res Volume: 35 Pages: 5559-5566
• [Journal Article] Prediction of Acute Radiation Mucositis using an Oral Mucosal Dose Surface Model in Carbon Ion Radiotherapy for Head and Neck Tumors (2015)
  • Author(s): Atsushi Musha, Hirofumi Shimada, Katsuyuki Shirai, Jun-ichi Saitoh, Satoshi Yokoo, Kazuaki Chikamatsu, Tatsuya Ohno, Takashi Nakano
  • Journal Title: PLOS ONE Volume: 10 Pages: e0141734
  • DOI: 10.1371/journal.pone.0141734
• [Journal Article] Combining carbon ion irradiation and non-homologous end-joining repair inhibitor NU7026 efficiently kills cancer cells (2015)
  • Author(s): Hongyu Ma, Akihisa Takahashi, Yukari Yoshida, Akiko Adachi, Tatsuaki Kanai, Tatsuya Ohno and Takashi Nakano
  • Journal Title: Radiat Oncol Volume: 10 Pages: 225
  • DOI: 10.1186/s13014-015-0536-z
• [Journal Article] Targeting of Carbon Ion-Induced G2 Checkpoint Activation in Lung Cancer Cells Using Wee-1 Inhibitor MK-1775 (2015)
  • Author(s): Ma H, Takahashi A, Sejimo Y, Adachi A, Kubo N, Isono M, Yoshida Y, Kanai T, Ohno T, Nakano T
  • Journal Title: Radiat Res Volume: 184 Pages: 660-669
  • DOI: http://dx.doi.org/10.1667/RR14171.1
• [Journal Article] Evaluation of an empirical monitor output estimation in carbon ion radiotherapy (2015)
  • Author(s): Akihiko Matsumura, Ken Yusa, Tatsuaki Kanai, Manabu Mizota, Tatsuya Ohno, and Takashi Nakano
  • Journal Title: Med Phys Volume: 42 Pages: 5188-5194
• [Journal Article] Evaluation of therapeutic gain for fractionated carbon-ion radiotherapy using the tumor growth delay and crypt survival assays (2015)
  • Author(s): Yoshida Y, Ando K, Ando K, Murata K, Yoshimoto Y, Musha A, Kubo N, Kawamura H, Koike S, Uzawa A, Takahashi T, Ohno T, Nakano T
  • Journal Title: Radiother Oncol Volume: 117 Pages: 351-357
• [Journal Article] Correction: Clinical Trial of Prophylactic Extended-Field Carbon-Ion Radiotherapy for Locally Advanced Uterine Cervical Cancer (Protocol 0508) (2015)
  • Author(s): Wakatsuki M, Kato S, Kiyohara H, Ohno T, Karasawa K, Tamaki T, Ando K, Tsujii H, Nakano T, Kamada T, Shozu M; Working Group of the Gynecological Tumor
  • Journal Title: PLOS ONE Volume: 10 Pages: e0127587
  • DOI: 10.1371/journal.pone.0127587
• [Journal Article] Monitoring bone and soft-tissue tumors after carbon-ion radiotherapy using (18)F-FDG positron emission tomography: a retrospective cohort study (2015)
  • Author(s): Yanagawa T, Saito K, Kiyohara H, Ohno T, Nakano T, Takagishi K
  • Journal Title: Radiat Oncol Volume: 10 Pages: 259
  • DOI: 10.1186/s13014-015-0571-9
• [Presentation] 放射線腫瘍学の温故知新と放射線腫瘍医養成そして国際展開へ (2015)
  • Author(s): 中野 隆史
  • Organizer: 日本放射線腫瘍学会第28回学術大会
  • Place of Presentation: 前橋市
  • Year and Date: 2015-11-19 – 2015-11-21
  • Invited