Development of rapid and simultaneous diagnosis and therapy for musculoskeletal sarcomas using acridine orange excited by high-power flash light

• Project/Area Number: 19390390
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Mie University
• Principal Investigator: KUSUZAKI Katsuyuki Mie University, 大学院・医学研究科, 教授 (30177993)
• Co-Investigator(Kenkyū-buntansha): UCHIDA Atsumasa 三重大学, 大学院・医学研究科, 教授 (40176681) ; MATSUMINE Akihiko 三重大学, 医学部附属病院, 講師 (00335118) ; KUMAMOTO Tadashi 三重大学, 大学院・医学研究科, 助教 (50362348) ; WAKABAYASHI Hiroki 三重大学, 大学院・医学研究科, 助教 (50362687) ; SATONAKA Haruhiko 三重大学, 大学院・医学研究科, 医員 (60515485) ; NAKAMURA Tomoki 三重大学, 医学部附属病院, 医員 (50467362) ; MATSUBARA Takao 三重大学, 医学部附属病院, 医員 (30422827)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2009: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2008: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2007: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
• Keywords: 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 / 安全性 / 光線力学的療

Research Abstract

To develop photodynamic diagnosis and photodynamic therapy using acridine orange excited by high-power flash light provided from xenon lamp in musculoskeletal sarcomas, we performed this study using mouse osteosarcoma model. Results showed that it was possible to brilliantly detect tumor localization through skin by PDD and to strongly inhibit tumor growth by PDT after intravenous AO injection followed by flash light illumination.

Research Products

• [Journal Article] Photodynamic therapy with acridine orangein musculoskeletal sarcomas. (2010)
  • Author(s): Matsubara T, Kusuzaki K, Matsumine A, Murata H, Marunaka Y, Hosogi S, Uchida A, Sudo A
  • Journal Title: J Bone Joint Surg (Br) (in press)
• [Journal Article] 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)
  • Author(s): Matsubara T, Kusuzaki K, Matsumine A, Murata H, Nakamura T, Uchida A, Sudo A
  • Journal Title: J Surg Oncol (in press)
• [Journal Article] 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)
  • Author(s): Satonaka H, Kusuzaki K, Murata H, Matsubara T, Shintani K, Nakamura T, Matsumine A, Iino T, Uchida A
  • Journal Title: Oncology Letters 1 Pages: 69-72
• [Journal Article] 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)
  • Author(s): Satonaka H, Kusuzaki K, Matsubara T, Murata H, Shinntani K, Nakamura T, Matsumine A, Iine T, Uchida A.
  • Journal Title: Oncology Letters 1 Pages: 69-72
  • Peer Reviewed
• [Journal Article] Three-dimensional alginate spheroid culture system of murine osteosarcoma. (2009)
  • Author(s): Akeda K, Nishimura A, Satonaka H, Shintani K, Kusuzaki K, Matsumine A, Kasai Y, Masuda K, Uchida A
  • Journal Title: Oncol Rep 22 Pages: 997-1003
• [Journal Article] Decorin suppresses bone metastasis in a breast cancer cell line. (2009)
  • Author(s): Araki K, Wakabayashi H, Shintani K, Morikawa J, Matsumine A, Kusuzaki K, Sudo A, Uchida A
  • Journal Title: Oncology (Bazel) 77 Pages: 92-99
• [Journal Article] A new therapeutic modality involving acridine orange excitation by photon energy used during reduction surgery for rhabodomyosarcomas. (2009)
  • Author(s): Matsubara T, Kusuzaki K, Matsumine A, Murata H, Satonaka H, Shinntani K, Nakamura T, Hosoi H, Iehara T, Sugimoto T, Uchida A
  • Journal Title: Oncol Rep 21 Pages: 89-94
• [Journal Article] Three-dimensional alginate spheroid culture system of murine osteosarcoma (2009)
  • Author(s): Aketa K, Nishimura A, Satonaka H , Shinntani K, Kusuzaki K, Matsumine A, Kasai Y, Masuda K, Uchida A.
  • Journal Title: Oncology Report 22 Pages: 997-1003
  • Peer Reviewed
• [Journal Article] A new therapeutic modality involving acridine orange excitation by photon energy used during reduction surgery for rhabodomyosarcomas. (2009)
  • Author(s): Matsubara T, Kusuzaki K, Matsumine A, Murata H, Satonaka H, Shinntani K, Nakamura T, Hosoi H, Iehara T, Sugimoto T, Uchida A.
  • Journal Title: Oncology Report 21 Pages: 89-94
  • Peer Reviewed
• [Journal Article] Usefulness of limb salvage surgery for bone and soft tissue sarcomas of the distal lower leg. (2008)
  • Author(s): Niimi R, Matsumine A, Kusuzaki K, Araki N, Aoki Y, Ueda T, Kudahara I, Myoui A, Ieguchi M, Hashimoto N, Yoshikawa H, Uchida A
  • Journal Title: J Cancer Res Clin Oncol 134 Pages: 1087-1095
• [Journal Article] Decorin suppresses lung metastasis of murine osteosarcoma. (2008)
  • Author(s): Shintani K, Matsumine A, Kusuzaki K, Morikawa J, Matsubara T, Wakabayashi T, Araki K, Satonaka H, Wakabayashi H, Iino T, Uchida A
  • Journal Title: Oncol Rep 19 Pages: 1533-1539
• [Journal Article] 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)
  • Author(s): Nakamura T, Kusuzaki K, Matsubara T, Matsumine A, Murata H, Uchida A
  • Journal Title: J Surg Oncol 97 Pages: 523-528
• [Journal Article] 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)
  • Author(s): Nakamura T, Kusuzaki K, Matsubara T, Matsumine A, Murata H, Uchida A.
  • Journal Title: Journal of Surgical Oncology 97 Pages: 523-528
  • Peer Reviewed
• [Journal Article] Novel hyperthermia for metastatic bone tumors magnetic materials by generating electromagnetic field. (2007)
  • Author(s): Matsumine A, Kusuzaki K, Matsubara T, Shintani K, Satonaka H, Wakabayashi T, Miyazaki S, Morita K, Takegami K, Uchida A
  • Journal Title: Clin Exp Metastasis 24 Pages: 191-200
• [Journal Article] Flash wave light strongly enhanced cytocidal effect of photodynamic therapy with acridine orange on mouse osteosarcoma cell line. (2007)
  • Author(s): Satonaka H, Kusuzaki K, Murata H, Matsubara T, Shintani K, Wakabayashi T, Matsumine A, Kimura M, Kawashima N, Uchida A
  • Journal Title: Anticancer Res 27 Pages: 3339-3344
• [Journal Article] Acridine orange could be an innovative anticancer agent under photon energy. (2007)
  • Author(s): Kusuzaki K, Murata H, Matsubara T, Satonaka H, Wakabayashi T, Matsumine A, Uchida A
  • Journal Title: In vivo 21 Pages: 205-214
• [Journal Article] Extracorporeal photodynamic image detection of mouse osteosarcoma in soft tissues utilizing fluorovisualization effect of acridine orange. (2007)
  • Author(s): Satonaka H, Kusuzaki K, Shintani K, Matsumine A, Matsubara T, Wakabayashi T, Uchida A
  • Journal Title: Oncology (Bazel) 70 Pages: 465-473
• [Journal Article] Acridine orange could be an innovative anticancer agent under photon energy (2007)
  • Author(s): Kusuzaki K, et. al.
  • Journal Title: In Vivo 21 Pages: 205-214
  • Peer Reviewed
• [Journal Article] Novel hyperthermia for metastatic bone tumors with magnetic materials by generating an alternating electromagnetic field (2007)
  • Author(s): Matsumine A, Kusuzaki K, et. al.
  • Journal Title: Clin Exp Metastasis 24 Pages: 191-200
  • Peer Reviewed
• [Journal Article] Expression of decorin,a small leucine-rich proteoglycan,as a prognostic factor in soft tissue tumors (2007)
  • Author(s): Matsumine A, Kusuzaki K, et.al.
  • Journal Title: J Surg Oncol 96 Pages: 411-418
  • Peer Reviewed
• [Journal Article] Flash wave light strongly enhanced the cytocidal effect of photodynamic therapy with acridine orange on a mouse osteosar coma cell line (2007)
  • Author(s): Satonaka H, Kusuzaki K, et. al.
  • Journal Title: Anticancer Res 27 Pages: 3339-3344
  • Peer Reviewed
• [Journal Article] Intra-osseous ganglion of the proximal humerus: a case report. (2007)
  • Author(s): Nishimura T, Kusuzaki K, et. al.
  • Journal Title: J Orthop Surg 15(1) Pages: 102-105
  • Peer Reviewed
• [Journal Article] Methylene blue in place of acridine orange as a photosensitizer in photodynamic therapy of osteosarcoma.
  • Author(s): Matsubara T, Kusuzaki K, Matsumine A, Satonaka H, Shinntani K, Nakamura T, Uchida A
  • Journal Title: In vivo 22 Pages: 297-304
• [Presentation] 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)
  • Author(s): Satonaka H, Kusuzaki K, Matsubara T, Shintani K, Nakamura T, Matsumine, A, Iino T, Uchida, A
  • Organizer: 56th Annual Meeting of Orthopaedic Research Society
  • Place of Presentation: New Orleans USA
  • Year and Date: 2010-03-08
• [Presentation] 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)
  • Author(s): Matsumine A, Kusuzaki K, Sugita T, Yazawa Y, Isu K, Kawai A, Abe S, Yakushiji T, Ueda T, Uchida A
  • Organizer: Asia Pacific Musculoskeletal Tumor Society Meeting
  • Place of Presentation: Sebu Philippin
• [Presentation] 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)
  • Author(s): Satonaka H, Kusuzaki K, Matsubara T, Shintani K, Nakamura T, Matsumine A, Iino T, Uchida A
  • Organizer: 56th Annual Meeting of Orthopaedic Research Society. 2010 March
  • Place of Presentation: New Oreans, USA
• [Presentation] Expression of SAP97 as a biomarker of outcome in malignant fibrous histiocytomas. (2009)
  • Author(s): Niimi R, Matsumine A, 1Iino T, Shintani K, Nakazora S, Nakamura T, Kusuzaki K, Uchida A
  • Organizer: 55th Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: Las Vegas USA
• [Presentation] Three-dimensional alginate spheroid culture system of murine osteosarcoma. (2009)
  • Author(s): Nishimura A, Akeda K, Kusuzaki K, Matsumine A, Masuda K, Morimoto R, Okamura N, Kasai Y, 1Iino T, Uchida A
  • Organizer: 55th Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: Las Vegas USA
• [Presentation] Fibulin-3 suppresses the synthesis cartilage matrix in chondrogenic cell line ATDC5 in vitro (2008)
  • Author(s): Wakabayashi T, Kusuzaki K, et. al.
  • Organizer: 53rd Annual Meeting Orthopaedic Research Society
  • Place of Presentation: San Diego,California
  • Year and Date: 2008-02-11
• [Presentation] Photodynamic detection of mouse osteosarcoma in the soft tissues utilizing fluorovisualization effect of acridine orange (2008)
  • Author(s): Satonaka H, Kusuzaki K, et. al.
  • Organizer: 53rd Annual Meeting Orthopaedic Research Society
  • Place of Presentation: San Diego,California
  • Year and Date: 2008-02-11
• [Presentation] Acridine orange found in Ehrlich's era could be a "Magic Bullet" against cancer under photon energy. (2008)
  • Author(s): Kusuzaki K, Murata H, Matsubara T, Satonaka H, Nakamura T, Matsumine A, Uchida A
  • Organizer: The 2nd World Confererence on Magic Bullets (Ehrlich II)
  • Place of Presentation: Neurmberg, Germany
• [Presentation] Novel hyperthermia for metastatic bone tumors with magnetic materials. (2008)
  • Author(s): Matsumine A, Kusuzaki K, Matsubara T, Morita K, Takegami K, Uchida
  • Organizer: 7th Asia Pacific Musculoskeletal Tumor Society Meeting
  • Place of Presentation: Beijin, China
• [Presentation] 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)
  • Author(s): Nakamura T, Matsumine A, Kusuzaki K, Matsubara T, Niimi R, Nakazora Murata H, S, Uchida A
  • Organizer: 7th Asia Pacific Musculoskeletal Tumor Society Meeting
  • Place of Presentation: Beijin, China
• [Presentation] In vivo antitumor effect of photodynamic therapy with acridine orange using flash wave light on osteosarcoma. (2008)
  • Author(s): Satonaka H, Kusuzaki K, Matsubara T, Shintani K, Wakabayashi T, Nakamura T, Matsumine A, Uchida A
  • Organizer: 7th Asia Pacific Musculoskeletal Tumor Society Meeting
  • Place of Presentation: Beijin, China
• [Presentation] Acridine orange found in Ehrlich's era could be a "Magic Bullet" against cancer under photon energy. (2008)
  • Author(s): Kusuzaki K, Murata H, Matsubara T, Satonaka H, Nakamura T, Matsumine A, Uchida A.
  • Organizer: The 2^<th> World Confererence on Magic Bullets (Ehrlich II)
  • Place of Presentation: Neurmberg, Germany
• [Presentation] Acridine Orenge could be an innovative anticancer agent under photon energy (2007)
  • Author(s): Kusuzaki K, et. al.
  • Organizer: 14th International Symposium on Limb Salvage
  • Place of Presentation: Hamburg,Germany
  • Year and Date: 2007-09-14
• [Presentation] Novel hyperthermia for metastasis bone tumors with magnetic materials by generating an alternating electromagnetic field (2007)
  • Author(s): Matsumine A, Kusuzaki K, et. al.
  • Organizer: 14th International Symposium on Limb Salvage
  • Place of Presentation: Hamburg,Germany
  • Year and Date: 2007-09-14
• [Presentation] Extracorporeal Photodynamin Image Detection of Mouse Osteosarcoma in Soft Tissue Utilizing Fluorovisualizatiom Effect of Acridine Orange (2007)
  • Author(s): Satonaka H, Kusuzaki K, et. al.
  • Organizer: 14th International Symposium on Limb Salvage
  • Place of Presentation: Hamburg,Germany
  • Year and Date: 2007-09-14
• [Presentation] Flash Wave Light Strongly Enhanced the Cytocidal Effect of Photodynamic Therapy with Acridine Orange on a Mouse Osteosar coma Cell Line (2007)
  • Author(s): Satonaka H, Kusuzaki K, et. al.
  • Organizer: 14th International Symposium on Limb Salvage
  • Place of Presentation: Hamburg,Germany
  • Year and Date: 2007-09-14
• [Presentation] Extracorporeal photodynamic image detection of mouse osteosarcoma in soft tissues utilizing fluorovisualization effect of acridine orange. (2007)
  • Author(s): Satonaka H, Kusuzaki K, Matsubara T, Shintani K, Wakabayashi T, Matsumine A, Uchida A
  • Organizer: The 14th International Symposium on Limb Salvage
  • Place of Presentation: Hamburg, Germany
• [Presentation] Novel hyperthermia for metastatic bone tumors with magnetic materials by generating an alternating electromagnetic field. (2007)
  • Author(s): Matsumine A, Kusuzaki K, Matsubara T, Morita K, Takegami K, Uchida
  • Organizer: The 14th International Symposium on Limb Salvage
  • Place of Presentation: Hamburg, Germany
• [Presentation] Acridine orange could be an innovative anticancer agent under photon energy. (2007)
  • Author(s): Kusuzaki K, Matsubara T, Satonaka H, Wakabayashi T, Matsumine A, Uchida A
  • Organizer: The 14th International Symposium on Limb Salvage
  • Place of Presentation: Hamburg, Germany