Study for the effect of radiation therapy amplication by acridine orange photosensitizer

• Project/Area Number: 25462328
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Mie University
• Principal Investigator: MATSUBARA TAKAO 三重大学, 医学(系)研究科(研究院), 講師 (30422827)
• Co-Investigator(Kenkyū-buntansha): MATSUMINE AKIHIKO 三重大学, 医学系研究科, 准教授 (00335118)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 放射線耐性 / アクリジンオレンジ療法 / 低酸素耐性 / CA9 / 低酸素環境 / 悪性腫瘍 / 抗がん剤耐性 / アクリジンオレンジ光線療法 / 放射線力学的療法 / アクリジンオレンジ / 光線力学的療法

Outline of Final Research Achievements

Acridine orange （AO） which is a photosensitizer accumulated to human osteosarcoma, lung cancer and breast cancer cell lines under the tumor microenvironmental condition (acidic, low oxygen and high hydrostatic pressure). There was amplification effect of about 1.5-2 times by changing tumor microenvironment, and, it was confirmed to have a higher cytotoxic effect against tumors in such specific condition. In the study of AO therapy for registrant strains. AO have a good citocydal effect for registrant strains, but there was no amplication effect in combination with AO and the protein obtained gene expression due to the tumor-specific extracellular environment analysis. While we revealed that CA9 is one of good target for osteosarcoma therapy, and that CA9 inhibitor suppressed the invasiveness and metastatic potential. In future, combination with CA9 and anti-tumor therapy can control local tumor recurrence and metastatic potential for sarcoma patients.

Research Products

• [Journal Article] Impact of plasma fibrinogen levels in benign and malignant soft tissue tumors. Cancer biomarkers (2016)
  • Author(s): Asanuma K, Matsumine A, Nakamura T, Matsubara T, Asanuma Y, Oi T, Goto M, Okuno K, Kakimoto T, Yada Y, Sudo A
  • Journal Title: section A of Disease markers Volume: 16 Issue: 3 Pages: 453-458
  • DOI: 10.3233/cbm-160584
  • Peer Reviewed
• [Journal Article] Treatment of bone defect with calcium phosphate cement subsequent to tumor curettage in pediatric patients. (2016)
  • Author(s): Nakamura T, Matsumine A, Asanuma K, Matsubara T, Sudo A
  • Journal Title: Oncology letters Volume: 11 Issue: 1 Pages: 247-252
  • DOI: 10.3892/ol.2015.3855
  • Peer Reviewed
• [Journal Article] The role of C-reactive protein in predicting post-metastatic survival of patients with metastatic bone and soft tissue sarcoma. (2015)
  • Author(s): Nakamura T, Matsumine A, Asanuma K, Matsubara T, Sudo A
  • Journal Title: Tumour Biol Volume: 36(10) Issue: 10 Pages: 7515-7520
  • DOI: 10.1007/s13277-015-3464-5
  • Peer Reviewed
• [Journal Article] Clinical characteristics of patients with large and deep soft tissue sarcomas. (2015)
  • Author(s): Nakamura T, Matsumine A, Matsubara T, Asanuma K, Uchida A, Sudo A
  • Journal Title: Oncology letters Volume: 10 Issue: 2 Pages: 841-844
  • DOI: 10.3892/ol.2015.3289
  • Peer Reviewed
• [Journal Article] Additive Influence of Extracellular pH, Oxygen Tension, and Pressure on Invasiveness and Survival of Human Osteosarcoma Cells (2013)
  • Author(s): Matsubara T, Diresta GR, Kakunaga S, Li D, Healey JH.
  • Journal Title: Front Oncol Volume: 3:199 Pages: 199-199
  • DOI: 10.3389/fonc.2013.00199
  • Peer Reviewed
• [Journal Article] Can a less radical surgery using photodynamic therapy with acridine orange be equal to a wide-margin resection? (2013)
  • Author(s): Matsubara T, Kusuzaki K, Matsumine A, Nakamura T, Sudo A.
  • Journal Title: Clin Orthop Relat Res Volume: 471(3) Issue: 3 Pages: 792-802
  • DOI: 10.1007/s11999-012-2616-9
  • Peer Reviewed
• [Presentation] A Genomic Analysis of the Effects of Acidic Extracellular pH, Low pO2, and Elevated Pressure on Human Osteosarcoma Cells (2016)
  • Author(s): Takao Matsubara, Kazuma Okuno, Akihiro Sudo, Shigeki Kakunaga, Gene R. DiResta, John H. Healey
  • Organizer: 2016 ORS Annual Meeting
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 2016-03-05
  • Int'l Joint Research
• [Presentation] Multi-institutional Study of a New Limb Salvage Surgery Using Acridine Orange in Patients with Bone Sarcomas (2016)
  • Author(s): Takao Matsubara, Katsuyuki Kusuzaki, Kyoji Okada, Takashi Tsuchiya, Takahiro Goto, Ryu Tsunoda, Hiroyuki Tsuchiya, Akihiko Matsumine, Akihiro Sudo
  • Organizer: 2015 AAOS Annual Meeting
  • Place of Presentation: Orlando, FL, USA
  • Year and Date: 2016-03-01
  • Int'l Joint Research
• [Presentation] Acridine Orange Therapy as a New Less-invasive Surgery for Recurrent or Aggressive Giant Cell Tumor of Bone (2014)
  • Author(s): Matsubara T, Kusuzaki K, Matsumine A, Nakamura T, Asanuma K, Uchida A, Sudo A
  • Organizer: 2014 Annual Meeting of American Orthopaedic Society of Surgeons
  • Place of Presentation: New Oleans, USA
• [Presentation] Tumor Microenvironmental Factors and Acridine Orange Intensity Can Predict Clinical Outcome in Soft Tissue Sarcoma Patients (2014)
  • Author(s): Matsubara T, Kusuzaki K, Matsumine A, Nakamura T, Asanuma K, Okuno K, Goto M, Oi T, Sudo A
  • Organizer: 2014 Annual Meeting of Orthopaedic Research Society
  • Place of Presentation: New Oleans, USA
• [Presentation] Carbonic Anhydrase IX Has the Potential to Predict Preoperative Chemotherapy Effect On Human Osteosarcoma Patients (2014)
  • Author(s): Okuno K, Matsubara T, Kusuzaki K, Matsumine A, Nakamura T, Asanuma K, Goto M, Oi T, Sudo A
  • Organizer: 2014 Annual Meeting of Orthopaedic Research Society
  • Place of Presentation: New Oleans, USA
• [Presentation] Hypoxia marker CA IX and VEGF expressed by Extracellular Low pH independently of hypoxia on Human Osteosarcoma Cells (2013)
  • Author(s): Matsubara T, DiResta GR, Healey JH
  • Organizer: Combined Orthopaedic Reserch Society
  • Place of Presentation: Venice, Italy
• [Presentation] The combination treatment with acridine orange photodynamic therapy and hydroxyapatite repairing to aggressive giant cell tumor of bone (2013)
  • Author(s): Matsubara T, Kusuzaki K, Matsumine A, Nakamura T, Asanuma K, Uchida A, Sudo A
  • Organizer: Connective Tissue Oncology Society
  • Place of Presentation: New York, USA