Development of novel physicochemical and molecular biological therapy for the metastatic bone tumors

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591654
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Mie University
• Principal Investigator: KATO Ko 三重大学, 大学院・医学系研究科, 教授 (20303729)
• Co-Investigator(Kenkyū-buntansha): MATSUMINE Akihiko 三重大学, 大学院・医学系研究科, 准教授 (00335118) ; NAKAMURA Tomoki 三重大学, 医学部附属病院, 助教 (50467362) ; SATONAKA Haruhiko 三重大学, 大学院・医学系研究科, リサーチアソシエイト (60515485)
• Co-Investigator(Renkei-kenkyūsha): UCHIDA Atsumasa 三重大学, 学長 (40176681)
• Project Period (FY): 2010 – 2012
• Keywords: 骨転移 / 磁性体温熱療法 / アクリジンオレンジ / ラジオ波焼灼術 / NFκB decoy

Research Abstract

We developed the novel physicochemical and molecular biological therapy for the metastatic bone tumors. First, we showed that NF-kappaB decoy suppress the cell invasion and cell growth of breast cancer cell line at the bone metastatic site, by inhibiting the expression of VCM-1and ICAM-1. Second, we demonstrated the effect of hyperthermic treatment strategy with magnetic nano-particle. Third, Photodynamic therapy(PDT) using acridine orange is proved to be effective treatment not only for the sarcoma, but also for metastatic bone tumors. Actually we started clinical application of PDT for the bone metastases. Finally, we developed the radiofrequency ablation (RFA) combined with thermo-sensitive liposome-embedding doxorubicin in an effort to safe and effective RFA treatment for the metastatic spinal tumor. Further investigation is necessary.

Research Products

• [Journal Article] Prosthetic limb salvage surgery for bone and soft tissue tumors around the knee (2012)
  • Author(s): Niimi R, Matsumine A, Hamaguchi T, Nakamura T, Uchida A, Sudo A
  • Journal Title: Oncol Rep Volume: 28 Pages: 1984-90
  • Peer Reviewed
• [Journal Article] Oncolytic virotherapy for human bone and soft tissue sarcomas using live attenuated poliovirus (2012)
  • Author(s): Atsumi S, Matsumine A, Toyoda H, Niimi R, Iino T, Nakamura T, Matsubara T, Asanuma K, Komada Y, Uchida A, Sudo A
  • Journal Title: Int J Oncol Volume: 41 Pages: 893-902
  • Peer Reviewed
• [Journal Article] Translational research of photodynamic therapy with acridine orange which targets cancer acidity (2012)
  • Author(s): Kusuzaki K, Hosogi S, Ashihara E, Matsubara T, Satonaka H, Nakamura T, Matsumine A, Sudo A, Uchida A, Murata H, Baldini N, Fais S, Marunaka Y
  • Journal Title: Curr Pharm Des Volume: 18 Pages: 141-20
  • Peer Reviewed
• [Journal Article] Clinical significance of pretreatment serum C-reactive protein level in soft tissue (2012)
  • Author(s): Nakamura T, Matsumine A, Matsubara T,Asanuma K, Uchida A, Sudo A
  • Journal Title: Cancer. Volume: 118 Pages: 1055-61
  • Peer Reviewed
• [Journal Article] Acridine orange inhibits pulmonarymetastasis of mouse osteosarcoma. (2011)
  • Author(s): Satonaka H, Kusuzaki K, Akeda K, Tsujii M, Iino T, Uemura T, Matsubara T,Nakamura T, Asanuma K, Matsumine A, Sudo A
  • Journal Title: Anticancer Res Volume: 312 Pages: 4163-8
  • Peer Reviewed
• [Journal Article] The adverse effect of an unplanned surgical excision of foot softtissue sarcoma (2011)
  • Author(s): Nishimura A, Matsumine A, Asanuma K, Matsubara T, Nakamura T, Uchida A, KatoK, Sudo A
  • Journal Title: World J Surg Oncol Volume: 9 Pages: 160
  • Peer Reviewed
• [Journal Article] Clinicalimpact of the tumor volume doubling time on sarcoma patients with lung metastases (2011)
  • Author(s): Nakamura T, Matsumine A, Matsubara T, Asanuma K, Uchida A, Sudo A
  • Journal Title: Clin Exp Metastasis Volume: 28 Pages: 819-25
  • Peer Reviewed
• [Journal Article] TNF inhibitorsuppresses bone metastasis in a breast cancer cell line (2011)
  • Author(s): Hamaguchi T, Wakabayashi H, Matsumine A, Sudo A, Uchida A
  • Journal Title: Biochem Biophys ResCommun Volume: 407 Pages: 525-30
  • Peer Reviewed
• [Journal Article] Japanese Musculoskeletal Oncology GroupMusculoskeletal Oncology Group. Clinicaloutcomes of 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 (2011)
  • Author(s): Matsumine A, Ueda T, Sugita T, Yazawa Y, Isu K, Kawai A, Abe S, Yakushiji T, Hiraga H, Sudo A, Uchida A
  • Journal Title: J Surg Oncol Volume: 103 Pages: 257-63
  • Peer Reviewed
• [Journal Article] A novel hyperthermia treatment for bone metastases using magnetic materials (2011)
  • Author(s): Matsumine A, Takegami K, Asanuma K, Matsubara T, Nakamura T, Uchida A, Sudo A
  • Journal Title: Int J Clin Oncol Volume: 16 Pages: 101-8
  • Peer Reviewed
• [Journal Article] In vino 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, Shintani K, Nakamura T, Matsumine A, Iino T, Uchida A
  • Journal Title: Oncol Lett Volume: 1 Pages: 69-72
  • Peer Reviewed
• [Journal Article] Clinical outcomes of minimally invasive surgery using acridine orange for musculskeletal 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: JSurg Oncol Volume: 102 Pages: 271-5
  • Peer Reviewed
• [Journal Article] The thrombin inhibitor, argatroban, inhibits breast cancer metastasis to bone
  • Author(s): Asanuma K, Wakabayashi H, Okamoto T,Asanuma Y, Akita N, Yoshikawa T, Hayashi T, Matsumine A, Uchida A, Sudo A
  • Journal Title: Breast Cancer
  • Peer Reviewed
• [Journal Article] Arthroscopically assisted minimally invasive plate osteosynthesis for posterior fracture-dislocation of the shoulder
  • Author(s): Fukuda A, Nishimura A, Kato K, Sudo A
  • Journal Title: J Orthop Sci Volume: (掲載決定)
  • Peer Reviewed
• [Presentation] Acridine Orange Therapy as a New Less-invasive Limb Salvage Surgery for Rhabdomyosarcomas and Synovial Sarcomas (2013)
  • Author(s): Matsubara T, Kusuzaki K, Matsumine A, Asanuma K, Nakamura T, Sudo A
  • Organizer: American Academy of Orthopaedic Surgeons
  • Place of Presentation: Chicago
  • Year and Date: 2013-03-23
• [Presentation] C-reactive Protein Level May be a Marker of Tumor Aggressiveness in Soft Tissue Sarcoma Patients (2013)
  • Author(s): Nakamura T, Matsumine A, Matsubara T, Asanuma K, Sudo A
  • Organizer: American Academy of Orthopaedic Surgeons
  • Place of Presentation: Chicago
  • Year and Date: 2013-03-23
• [Presentation] Thrombomodulin and Tissue Factor mRNA Expression in 62 Soft Tissue Sarcoma Patients (2013)
  • Author(s): Asanuma K, Matsumine A, Matsubara T, Nakamura T, Yoshikawa T, Sudo A.
  • Organizer: American Academy of Orthopaedic Surgeons
  • Place of Presentation: Chicago
  • Year and Date: 2013-03-23
• [Presentation] Analysis of Tumor Metastatic Factor Using Coagulation Activity Model in Mice (2013)
  • Author(s): Asanuma K, Matsumine A, Asanuma Y, Akita N, Yoshikawa T, Matsubara T, Nakamura T, Okamoto T, Sudo A
  • Organizer: Orthopaedic Research Society
  • Place of Presentation: San Antonio
  • Year and Date: 2013-01-29
• [Presentation] Interleukin-6 Receptor Suppresses the Bone Metastasis in Breast Cancer Cell Line (2013)
  • Author(s): Wakabayasi H, Hamaguchi T, Naito Y, Matsumine A, Sudo A
  • Organizer: Orthopaedic Research Society
  • Place of Presentation: San Antonio
  • Year and Date: 2013-01-29
• [Presentation] The inhibition of lung metastasis by inactivation of coagulation activity may lead to dissemination of tumor cells (2011)
  • Author(s): K Asanuma, A Matsumine, Y Asanuma, T Yoshikawa, K Yoshida, T Matsubara, TNakamura, A Uchida, A. Sudo
  • Organizer: EUROPEAN ORTHOPAEDIC RESEACH SOCIETY
  • Place of Presentation: Austria
  • Year and Date: 2011-09-02
• [Presentation] ovel hyperthermia for metastatic bone tumors with magnetic materials (2010)
  • Author(s): A Matsumine
  • Organizer: Connective Tissue Oncology Society Meeting
  • Place of Presentation: France
  • Year and Date: 2010-11-13