アクリジン色素とストロボ光を用いた骨・軟部肉腫の同時・瞬間的診断治療戦略の開発

2009 年度 研究成果報告書

• 研究課題/領域番号: 19390390
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 整形外科学
• 研究機関: 京都府立医科大学
• 研究代表者: 楠崎 克之 京都府立医科大学, 大学院・医学研究科, 教授 (30177993)
• 研究分担者: 内田 敦正 三重大学, 大学院・医学研究科, 教授 (40176681) ; 松峯 昭彦 三重大学, 医学部附属病院, 講師 (00335118) ; 熊本 忠史 三重大学, 大学院・医学研究科, 助教 (50362348) ; 若林 弘樹 三重大学, 大学院・医学研究科, 助教 (50362687) ; 里中 東彦 三重大学, 大学院・医学研究科, 医員 (60515485) ; 中村 知樹 三重大学, 医学部附属病院, 医員 (50467362) ; 松原 孝夫 三重大学, 医学部附属病院, 医員 (30422827)
• 研究期間 (年度): 2007 – 2009
• キーワード: アクリジンオレンジ / 光線力学的診断 / 光線力学的治療法 / 骨軟部腫瘍 / ストロボ光

研究概要

アクリジンオレンジ(AO)という色素はがんに特異的に集積して光が当たると蛍光を発生すると同時にがん細胞だけを瞬時に選択的に破壊します。これを利用して骨軟部腫瘍の蛍光による早期診断と治療を同時に行う方法の開発を行いました。その結果キセノン光源の青色ストロボ光を用いると皮膚に近い肉腫であれば蛍光で局在を診断でき、全光照射で強い腫瘍増殖抑制効果も得られることが分かり、この方法が肉腫の診断治療に応用できる可能性が示されました。

研究成果

• [雑誌論文] Photodynamic therapy with acridine orangein musculoskeletal sarcomas. (2010)
  • 著者名/発表者名: Matsubara T, Kusuzaki K, Matsumine A, Murata H, Marunaka Y, Hosogi S, Uchida A, Sudo A
  • 雑誌名: J Bone Joint Surg (Br) (in press)
• [雑誌論文] Clinical outcomes of minimally invasive surgery using acridine orange for musculoskeletal sarcomas around the forearm, compared with conventional limb salvage surgery after wide resection. (2010)
  • 著者名/発表者名: Matsubara T, Kusuzaki K, Matsumine A, Murata H, Nakamura T, Uchida A, Sudo A
  • 雑誌名: J Surg Oncol (in press)
• [雑誌論文] In vivo anti-tumor activity of photodynamic therapy with intravenous administration of acridine orange, followed by illumination with high-power flash wave light in a mouse osteosarcoma model. (2010)
  • 著者名/発表者名: Satonaka H, Kusuzaki K, Murata H, Matsubara T, Shintani K, Nakamura T, Matsumine A, Iino T, Uchida A
  • 雑誌名: Oncology Letters 1 ページ: 69-72
• [雑誌論文] Three-dimensional alginate spheroid culture system of murine osteosarcoma. (2009)
  • 著者名/発表者名: Akeda K, Nishimura A, Satonaka H, Shintani K, Kusuzaki K, Matsumine A, Kasai Y, Masuda K, Uchida A
  • 雑誌名: Oncol Rep 22 ページ: 997-1003
• [雑誌論文] Decorin suppresses bone metastasis in a breast cancer cell line. (2009)
  • 著者名/発表者名: Araki K, Wakabayashi H, Shintani K, Morikawa J, Matsumine A, Kusuzaki K, Sudo A, Uchida A
  • 雑誌名: Oncology (Bazel) 77 ページ: 92-99
• [雑誌論文] A new therapeutic modality involving acridine orange excitation by photon energy used during reduction surgery for rhabodomyosarcomas. (2009)
  • 著者名/発表者名: Matsubara T, Kusuzaki K, Matsumine A, Murata H, Satonaka H, Shinntani K, Nakamura T, Hosoi H, Iehara T, Sugimoto T, Uchida A
  • 雑誌名: Oncol Rep 21 ページ: 89-94
• [雑誌論文] Usefulness of limb salvage surgery for bone and soft tissue sarcomas of the distal lower leg. (2008)
  • 著者名/発表者名: Niimi R, Matsumine A, Kusuzaki K, Araki N, Aoki Y, Ueda T, Kudahara I, Myoui A, Ieguchi M, Hashimoto N, Yoshikawa H, Uchida A
  • 雑誌名: J Cancer Res Clin Oncol 134 ページ: 1087-1095
• [雑誌論文] Decorin suppresses lung metastasis of murine osteosarcoma. (2008)
  • 著者名/発表者名: Shintani K, Matsumine A, Kusuzaki K, Morikawa J, Matsubara T, Wakabayashi T, Araki K, Satonaka H, Wakabayashi H, Iino T, Uchida A
  • 雑誌名: Oncol Rep 19 ページ: 1533-1539
• [雑誌論文] A new limb salvage surgery in cases of high-grade soft tissue sarcoma using photodynamic surgery, followed by photo-and radiodynamic therapy with acridine orange. (2008)
  • 著者名/発表者名: Nakamura T, Kusuzaki K, Matsubara T, Matsumine A, Murata H, Uchida A
  • 雑誌名: J Surg Oncol 97 ページ: 523-528
• [雑誌論文] Novel hyperthermia for metastatic bone tumors magnetic materials by generating electromagnetic field. (2007)
  • 著者名/発表者名: Matsumine A, Kusuzaki K, Matsubara T, Shintani K, Satonaka H, Wakabayashi T, Miyazaki S, Morita K, Takegami K, Uchida A
  • 雑誌名: Clin Exp Metastasis 24 ページ: 191-200
• [雑誌論文] Flash wave light strongly enhanced cytocidal effect of photodynamic therapy with acridine orange on mouse osteosarcoma cell line. (2007)
  • 著者名/発表者名: Satonaka H, Kusuzaki K, Murata H, Matsubara T, Shintani K, Wakabayashi T, Matsumine A, Kimura M, Kawashima N, Uchida A
  • 雑誌名: Anticancer Res 27 ページ: 3339-3344
• [雑誌論文] Acridine orange could be an innovative anticancer agent under photon energy. (2007)
  • 著者名/発表者名: Kusuzaki K, Murata H, Matsubara T, Satonaka H, Wakabayashi T, Matsumine A, Uchida A
  • 雑誌名: In vivo 21 ページ: 205-214
• [雑誌論文] Extracorporeal photodynamic image detection of mouse osteosarcoma in soft tissues utilizing fluorovisualization effect of acridine orange. (2007)
  • 著者名/発表者名: Satonaka H, Kusuzaki K, Shintani K, Matsumine A, Matsubara T, Wakabayashi T, Uchida A
  • 雑誌名: Oncology (Bazel) 70 ページ: 465-473
• [雑誌論文] Methylene blue in place of acridine orange as a photosensitizer in photodynamic therapy of osteosarcoma.
  • 著者名/発表者名: Matsubara T, Kusuzaki K, Matsumine A, Satonaka H, Shinntani K, Nakamura T, Uchida A
  • 雑誌名: In vivo 22 ページ: 297-304
• [学会発表] In vivo antitumor activity of photodynamic therapy with intravenous administration of acridine orange followed by illumination with high-power flash wave light in a mouse osteosarcoma model. (2010)
  • 著者名/発表者名: Satonaka H, Kusuzaki K, Matsubara T, Shintani K, Nakamura T, Matsumine A, Iino T, Uchida A
  • 学会等名: 56th Annual Meeting of Orthopaedic Research Society. 2010 March
  • 発表場所: New Oreans, USA
  • 年月日: 20100311-20100314
• [学会発表] Clinical Outcomes with the KYOCERA Physio Hinge Total Knee System Type III after the Resection of a bone and soft tissue tumor of the Distal Part of the Femur: from the Japanese Musculoskeletal Oncology Group 8th. (2010)
  • 著者名/発表者名: Matsumine A, Kusuzaki K, Sugita T, Yazawa Y, Isu K, Kawai A, Abe S, Yakushiji T, Ueda T, Uchida A
  • 学会等名: Asia Pacific Musculoskeletal Tumor Society Meeting
  • 発表場所: Sebu Philippin
  • 年月日: 20100000
• [学会発表] Expression of SAP97 as a biomarker of outcome in malignant fibrous histiocytomas. (2009)
  • 著者名/発表者名: Niimi R, Matsumine A, 1Iino T, Shintani K, Nakazora S, Nakamura T, Kusuzaki K, Uchida A
  • 学会等名: 55th Annual Meeting of the Orthopaedic Research Society
  • 発表場所: Las Vegas USA
  • 年月日: 20090308-20090310
• [学会発表] Three-dimensional alginate spheroid culture system of murine osteosarcoma. (2009)
  • 著者名/発表者名: Nishimura A, Akeda K, Kusuzaki K, Matsumine A, Masuda K, Morimoto R, Okamura N, Kasai Y, 1Iino T, Uchida A
  • 学会等名: 55th Annual Meeting of the Orthopaedic Research Society
  • 発表場所: Las Vegas USA
  • 年月日: 20090308-20090310
• [学会発表] Acridine orange found in Ehrlich's era could be a "Magic Bullet" against cancer under photon energy. (2008)
  • 著者名/発表者名: Kusuzaki K, Murata H, Matsubara T, Satonaka H, Nakamura T, Matsumine A, Uchida A
  • 学会等名: The 2nd World Confererence on Magic Bullets (Ehrlich II)
  • 発表場所: Neurmberg, Germany
  • 年月日: 20081003-20081005
• [学会発表] Novel hyperthermia for metastatic bone tumors with magnetic materials. (2008)
  • 著者名/発表者名: Matsumine A, Kusuzaki K, Matsubara T, Morita K, Takegami K, Uchida
  • 学会等名: 7th Asia Pacific Musculoskeletal Tumor Society Meeting
  • 発表場所: Beijin, China
  • 年月日: 20080926-20080928
• [学会発表] new limb salvage surgery in cases of high-grade soft tissue sarcoma using photodynamic surgery, followed by photo- and radio dynamic therapy with acridine orange. (2008)
  • 著者名/発表者名: Nakamura T, Matsumine A, Kusuzaki K, Matsubara T, Niimi R, Nakazora Murata H, S, Uchida A
  • 学会等名: 7th Asia Pacific Musculoskeletal Tumor Society Meeting
  • 発表場所: Beijin, China
  • 年月日: 20080926-20080928
• [学会発表] In vivo antitumor effect of photodynamic therapy with acridine orange using flash wave light on osteosarcoma. (2008)
  • 著者名/発表者名: Satonaka H, Kusuzaki K, Matsubara T, Shintani K, Wakabayashi T, Nakamura T, Matsumine A, Uchida A
  • 学会等名: 7th Asia Pacific Musculoskeletal Tumor Society Meeting
  • 発表場所: Beijin, China
  • 年月日: 20080926-20080928
• [学会発表] Extracorporeal photodynamic image detection of mouse osteosarcoma in soft tissues utilizing fluorovisualization effect of acridine orange. (2007)
  • 著者名/発表者名: Satonaka H, Kusuzaki K, Matsubara T, Shintani K, Wakabayashi T, Matsumine A, Uchida A
  • 学会等名: The 14th International Symposium on Limb Salvage
  • 発表場所: Hamburg, Germany
  • 年月日: 20070911-20070914
• [学会発表] Novel hyperthermia for metastatic bone tumors with magnetic materials by generating an alternating electromagnetic field. (2007)
  • 著者名/発表者名: Matsumine A, Kusuzaki K, Matsubara T, Morita K, Takegami K, Uchida
  • 学会等名: The 14th International Symposium on Limb Salvage
  • 発表場所: Hamburg, Germany
  • 年月日: 20070911-20070914
• [学会発表] Acridine orange could be an innovative anticancer agent under photon energy. (2007)
  • 著者名/発表者名: Kusuzaki K, Matsubara T, Satonaka H, Wakabayashi T, Matsumine A, Uchida A
  • 学会等名: The 14th International Symposium on Limb Salvage
  • 発表場所: Hamburg, Germany
  • 年月日: 20070911-20070914