Evaluation of cell-killing effects within solid tumors by the non-invasive real-time imaging system for hypoxic cell apoptosis

• Project/Area Number: 24591849
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Kitasato University
• Principal Investigator: KAGIYA Go 北里大学, 医療衛生学部, 講師 (30524243)
• Co-Investigator(Kenkyū-buntansha): OGAWA Ryohei 富山大学大学院, 医学薬学研究部, 准教授 (60334736)
• Co-Investigator(Renkei-kenkyūsha): MATSUMOTO Hideki 福井大学, 高エネルギー医学研究センター, 准教授 (40142377)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 低酸素細胞 / アポトーシス / 非侵襲的リアルタイムイメージング / 可視化 / リアルタイム可視化 / がん幹細胞 / 低酸素領域

Outline of Final Research Achievements

The presence of hypoxic regions within solid tumors is caused by an imbalance between cell proliferation and angiogenesis. Such regions may facilitate the onset of recurrence after radiation therapy and chemotherapy, as hypoxic cells show resistance to these treatments. The non-invasive real-time imaging system to monitor hypoxic cell apoptosis is considered to be useful system for screening and evaluation of therapeutic approaches targeting the hypoxic cells. We thus started developing the imaging system for hypoxic cell apoptosis. The imaging system in which cyclic luciferase gene was expressed under the control of the hypoxic responsive promoter has successfully made it possible to visualize real-time hypoxic cell apoptosis in vitro.

Research Products

• [Journal Article] Relative biological effectiveness of therapeutic proton beams for HSG cells at Japanese proton therapy facilities. (2014)
  • Author(s): 2. Nakano M., Y. Furusawa, A. Uzawa, Y. Matsumoto, R. Hirayama, C. Tsuruoka, T. Ogino, T. Nishio, K. Kagawa, M. Murakami, G. Kagiya, K. Kume, M. Hatashita, S. Fukuda, K. Yamamoto, H. Fuji, S. Murayama, M. Hata, T. Sakae, and H. Matsumoto
  • Journal Title: J. Radiat. Res. Volume: 55 Issue: 4 Pages: 812-815
  • DOI: 10.1093/jrr/rru003
  • Peer Reviewed
• [Journal Article] Development of a therapeutically important radiation induced promoter. (2013)
  • Author(s): Ryohei Ogawa, Akihiro Morii, Akihiko Watanabe, Zheng-Guo Cui, Go Kagiya, Shigekazu Fukuda, Kyo Kume, Takashi Hasegawa, Masanori Hatashita, Hironori Izumi, Tetsuya Ishimoto, Loreto B. Feril. Jr.
  • Journal Title: Bioengineered. Volume: 4(1) Issue: 1 Pages: 44-49
  • DOI: 10.4161/bioe.21965
  • Peer Reviewed
• [Journal Article] 放射線応答性遺伝子発現制御システムの開発 (2013)
  • Author(s): Ogawa, R., A. Morii, A. Watanabe, Z. G. Cui, G. Kagiya, M. Hatashita, K. Kume, S. Fukuda, T. Hasegawa, T. Kondo.
  • Journal Title: 放射線生物研究 Volume: 48 Pages: 267-279
  • NAID: 40019814127
• [Journal Article] Regulation of gene expression in human prostate cancer cells with artificially constructed promoters that are activated in response to ultrasound stimulation (2012)
  • Author(s): Ogawa R., A. Morii, A. Watanabe, Z. G. Cui, G. Kagiya, T. Kondo, N. Doi, L. B. Feril
  • Journal Title: Ultrason Sonochem Volume: 20 Issue: 1 Pages: 460-467
  • DOI: 10.1016/j.ultsonch.2012.05.007
  • Peer Reviewed
• [Journal Article] Regulation of gene expression in retrovirus vectors by X-ray and proton beam radiation with artificially constructed promoters (2012)
  • Author(s): Ogawa, R., A. Morii, A. Watanabe, Z. G. Cui, G. Kagiya, S. Fukuda, K. Kume, T. Hasegawa, M. Hatashita, H. Izumi and T. Ishimoto
  • Journal Title: J Gene Med Volume: 14 Issue: 5 Pages: 316-327
  • DOI: 10.1002/jgm.2625
  • Peer Reviewed
• [Journal Article] An artificially constructed radiation responsive promoter is activated with doxorubicin treatment (2012)
  • Author(s): Ogawa R., A. Morii, A. Watanabe, Z. G. Cui, G. Kagiya, N. Doi, Q. L. Zhao, L. B. Feril, Jr
  • Journal Title: Cancer Gene Ther Volume: 19 Issue: 5 Pages: 345-351
  • DOI: 10.1038/cgt.2012.7
  • Peer Reviewed
• [Presentation] 低酸素細胞領域におけるアポトーシス可視化システムの構築 (2014)
  • Author(s): 1. 鍵谷 豪、小川良平、畑下昌範、田中良和、山下 慶、中村美月、福田茂一、松本英樹
  • Organizer: 第５２回日本放射線腫瘍学会生物部会学術大会
  • Place of Presentation: メルパルク京都（京都府、京都市）
  • Year and Date: 2014-07-11 – 2014-07-12
• [Presentation] 低酸素細胞アポトーシス可視化システムの構築 (2013)
  • Author(s): 鍵谷 豪、小川良平、畑下昌範、田中良和、尾崎匡邦、山下 慶、中村美月、福田茂一
  • Organizer: 第２６回北里大学バイオサイエンスファーラム
  • Place of Presentation: 北里大学（神奈川県相模原市）
• [Presentation] アポトーシス可視化システムの構築とその特性評価 –低酸素領域におけるアポトーシス細胞の可視化を目指して- (2013)
  • Author(s): 鍵谷 豪、小川良平、畑下昌範、田中良和、尾崎匡邦、山下 慶、中村美月、福田茂一、松本英樹
  • Organizer: 第５１回日本放射線腫瘍学会生物部会学術大会
  • Place of Presentation: 艮陵会館記念ホール（宮城県仙台市）
• [Presentation] ニトロオキシド化合物テンポールを用いた低酸素細胞に対する殺細胞効果の増強 -低細胞毒性ニトロキシド化合物の探索と殺細胞効果増強の評価- (2012)
  • Author(s): 1. 鍵谷 豪、小川良平、畑下昌範、田中良和、幸田華奈、尾崎匡邦、山下 慶、福田茂一、松本英樹
  • Organizer: 日本放射線腫瘍学会生物部会
  • Place of Presentation: 沖縄県宜野湾市