蛍光イメージングを用いた悪性骨軟部腫瘍の転移機序の解明と新規治療法の開発

2015 Fiscal Year Annual Research Report

• Project/Area Number: 26293333
• Research Institution: Kanazawa University
• Principal Investigator: 土屋 弘行 金沢大学, 医学系, 教授 (40227434)
• Co-Investigator(Kenkyū-buntansha): 林 克洋 金沢大学, 大学病院, 助教 (80507054) ; 山本 憲男 金沢大学, 医薬保健学総合研究科, 教授 (90332668) ; 三輪 真嗣 金沢大学, 大学病院, 医員 (40753455)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 骨 / 悪性腫瘍 / 蛍光 / イメージング / 手術

Outline of Annual Research Achievements

悪性骨軟部腫瘍に対する新規治療として、蛍光ガイド下手術（Fluorescence-guided surgery: 以下FGS）の有用性について検討した。骨転移巣から樹立されたヒト前立腺がん細胞株PC-3をヌードマウスの脛骨に移植することにより骨転移モデルを作成した。PC-3が抗CEA蛍光抗体（抗CEA DyLight 650）により蛍光標識されることをin vitroで確認したのちに骨転移モデルマウスの尾静脈に抗CEA DyLight 650を注射したところ、転移巣が蛍光を発することが確認できた。蛍光を確認しながら腫瘍を切除したところ、明視野で腫瘍を切除したグループに比べて有意に再発を抑制した。
前立腺癌骨転移の手術適応は限定されるが、同様の手技を他の癌種由来の骨転移巣にも使うことができると考えられる。

Current Status of Research Progress

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

Reason

予定の実験を行っており、学会発表、論文発表も行えているため。

Strategy for Future Research Activity

研究計画を予定通りに遂行する。

Causes of Carryover

予定よりも少ない実験動物、試薬で結果が出せたため次年度使用額が生じたが、経過は予定通りに遂行できている。

Expenditure Plan for Carryover Budget

物品費として使用する予定である。

Research Products

• [Journal Article] Fluorescence-guided surgery of human prostate cancer experimental bone metastasis in nude mice using anti-CEA DyLight 650 for tumor illumination. (2016)
  • Author(s): Miwa S, De Magalhaes N, Toneri M, Zhang Y, Cao W, Bouvet M, Tsuchiya H, Hoffman RM.
  • Journal Title: Journal of Orthopedic Research Volume: 34 Pages: 559-65
  • DOI: 10.1002/jor.22973.
  • Peer Reviewed
• [Journal Article] Repeated total en bloc spondylectomy for spinal metastases at different sites in one patient. (2015)
  • Author(s): Sugita S, Murakami H, Demura S, Kato S, Yoshioka K, Yokogawa N, Tanaka S, Tsuchiya H.
  • Journal Title: Europearn Spine Journal Volume: 24 Pages: 2196-200
  • DOI: 10.1007/s00586-015-4091-y
  • Peer Reviewed
• [Journal Article] Treatment of a Simple Bone Cyst Using a Cannulated Hydroxyapatite Pin. (2015)
  • Author(s): Shirai T, Tsuchiya H, Terauchi R, Tsuchida S, Mizoshiri N, Ikoma K, Fujiwara H, Miwa S, Kimura H, Takeuchi A, Hayashi K, Yamamoto N, Kubo T.
  • Journal Title: Medicine (Baltimore) Volume: 94 Pages: e1027
  • DOI: 10.1097/MD.0000000000001027.
  • Peer Reviewed / Open Access
• [Journal Article] Intraperitoneal administration of tumor-targeting Salmonella typhimurium A1-R inhibits disseminated human ovarian cancer and extends survival in nude mice. (2015)
  • Author(s): Matsumoto Y, Miwa S, Zhang Y, Zhao M, Yano S, Uehara F, Yamamoto M, Hiroshima Y, Toneri M, Bouvet M, Matsubara H, Tsuchiya H, Hoffman RM.
  • Journal Title: Oncotarget Volume: 6 Pages: 11369-77
  • Peer Reviewed / Open Access
• [Journal Article] Heterogeneous cell-cycle behavior in response to UVB irradiation by a population of single cancer cells visualized by time-lapse FUCCI imaging. (2015)
  • Author(s): Miwa S, Yano S, Kimura H, Yamamoto M, Toneri M, Murakami T, Hayashi K, Yamamoto N, Fujiwara T, Tsuchiya H, Hoffman RM.
  • Journal Title: Cell Cycle Volume: 14 Pages: 1932-7
  • DOI: 10.1080/15384101.2015.1033598
  • Peer Reviewed
• [Presentation] Efficacy of fluorescence-guided surgery on primary human osteosarcoma. (2016)
  • Author(s): Miwa S, Uehara Fu, Kimura H, Hayashi K, Yamamoto N, Hoffman RM, Tsuchiya H.
  • Organizer: 2016 AAOS Annual Meeting
  • Place of Presentation: Orlando, Florida
  • Year and Date: 2016-03-01 – 2016-03-05
  • Int'l Joint Research
• [Presentation] Biological reconstruction using liquid nitrogen treated tumor-bearing bone for malignant bone tumor (2015)
  • Author(s): N. Yamamoto, K. Hayashi, A. Takeuchi, S. Miwa, H. Inatani, T. Higuchi, Y. Aoki, K. Abe, A. Abdelaal, P. Suwanpramote, H. Tsuchiya
  • Organizer: 18th World Congress of International Society of Cryosurgery
  • Place of Presentation: Kanazawa
  • Year and Date: 2015-11-26 – 2015-11-28
  • Int'l Joint Research
• [Presentation] A novel method to apply adipose-derived stem cells to bone and soft tissue defects after tumor excision. (2015)
  • Author(s): Hayashi K, Yamamoto N, Shirai T, Takeuchi A, Kimura H, Miwa S, Suganuma S, Nomura I, Inatani H, Aoki Y, Fang X, Tsuchiya H
  • Organizer: International Society of Limb Salvage & Musculoskeletal Tumor Society combined meeting
  • Place of Presentation: W Marriott Orlando Grande Lakes Orlando
  • Year and Date: 2015-10-06 – 2015-10-10
  • Int'l Joint Research
• [Presentation] Development of a novel molecular-targeted therapy for osteosarcoma (2015)
  • Author(s): N. Yamamoto, S. Shimozaki, K. Hayashi, A. Takeuchi, S. Miwa, H. Inatani, Y. Aoki, T. Higuchi, K. Abe, T. Minamoto, H. Tsuchiya
  • Organizer: 2015 ISOLS/MSTS Combined Annual Meeting
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-10-06 – 2015-10-10
  • Int'l Joint Research