Development of oncolytic virotherapy using live attenuated poliovirus for human bone and soft tissue sarcomas.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592183
• 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: MATSUMINE Akihiko 三重大学, 医学(系)研究科(研究院), 准教授 (00335118)
• Co-Investigator(Kenkyū-buntansha): ASANUMA Kunihiro 三重大学, 大学院医学系研究科, 助教 (20378285) ; MATSUBARA Takao 三重大学, 医学系研究科, 講師 (30422827) ; NAKAMURA Tomoki 三重大学, 医学部附属病院, 助教 (50467362) ; TOYODA Hidemi 三重大学, 大学院医学系研究科, 助教 (60525327) ; KOMADA Yoshihiro 三重大学, 大学院医学系研究科, 教授 (80186791)
• Project Period (FY): 2011 – 2013
• Keywords: 弱毒化ポリオウイルス / 悪性骨軟部腫瘍 / 細胞融解療法 / CD155

Research Abstract

The poliovirus receptor CD155, is essential for poliovirus to induce cell-death in neural cells. Recently, CD155 has been shown to be selectively expressed on certain types of tumor cells originating from the neural crest. We first examined CD155 expression in sarcoma cell lines, and found the expression of CD155 in all of 10 sarcoma cell lines. Furthermore, we found that live-attenuated polio viruses (LAPV) induced apoptosis. In nude mice transplanted with HT1080, administration of live attenuated poliovirus caused growth suppression of the tumors. Next, the CD155 expression levels in 43 surgically resected soft tissue tumors were evaluated. The local recurrence free survival rate for patients with a high CD155 expression level was significantly poorer compared with that of patients with low CD155 expression levels.
These results suggest that oncolytic therapy using a LAPV may represent a new option for the treatment of sarcomas.

Research Products

• [Journal Article] Role of High-sensitivity C-reactive Protein in the Differentiation of Benign and Malignant Soft Tissue Tumors (2014)
  • Author(s): Nakamura T, Matsumine A, Iino T, Matsubara T, Asanuma K, Uchida A, Sudo A
  • Journal Title: Anticancer Res Volume: 34 Pages: 933-936
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/?term=Role+of+High-sensitivity+C-reactive+Protein+in+the+Differentiation+of+Benign+and+Malignant+Soft+Tissue+Tumors
  • Peer Reviewed
• [Journal Article] Radiofrequency ablation for the treatment of recurrent bone and soft-tissue sarcomas in non-surgical candidates (2013)
  • Author(s): Yamakado K, Matsumine A, Nakamura T, Nakatsuka A, Takaki H, Matsubara T, Asanuma K, Sudo A, Sugimura Y, Sakuma H
  • Journal Title: Int J Clin Oncol
  • DOI: 10.1007/s10147-013-0640-8
  • Peer Reviewed
• [Journal Article] Clinical outcomes of Kyocera Modular Limb Salvage system after resection of bone sarcoma of the distal part of the femur : the Japanese Musculoskeletal Oncology Group study (2013)
  • Author(s): Nakamura T, Matsumine A, Uchida A, Kawai A, Nishida Y, Kunisada T, Araki N, Sugiura H, Tomita M, Yokouchi M, Ueda T, Sudo A
  • Journal Title: Int Orthop
  • DOI: 10.1007/s00264-013-2151-7
  • Peer Reviewed
• [Journal Article] The combined use of the neutrophil-lymphocyte ratio and C-reactive protein level as prognostic predictors in adult patients with soft tissue sarcoma (2013)
  • Author(s): Nakamura T, Matsumine A, Matsubara T, Asanuma K, Uchida A, Sudo A
  • Journal Title: J Surg Oncol Volume: 108 Pages: 481-485
  • DOI: 10.1002/jso.23424
• [Journal Article] Deep-vein thrombosis after resection of musculoskeletal tumours of the lower limb (2013)
  • Author(s): Yamaguchi T, Matsumine A, Niimi R, Nakamura T, Matsubara T, Asanuma K, Hasegawa M, Sudo A
  • Journal Title: Bone Joint J Volume: 95 Pages: 1280-1284
  • DOI: 10.1302/0301-620X.95B9.30905
  • Peer Reviewed
• [Journal Article] Ewing's sarcoma with an uncommon clinical course : A case report (2013)
  • Author(s): Niimi R, Matsumine A, Nakamura T, Morimoto R, Murata T, Suzuki T, Nakashima Y, Nojima T, Uchida A, Sudo A
  • Journal Title: Oncol Lett Volume: 6 Pages: 9-12
  • DOI: 10.3892/ol.2013.1320
  • Peer Reviewed
• [Journal Article] Prognostic significance of CD155 mRNA expression in soft tissue sarcomas (2013)
  • Author(s): Atsumi S, Matsumine A, Toyoda H, Niimi R, Iino T, Sudo A
  • Journal Title: Oncol Lett Volume: 5(6) Pages: 1771-1776
  • DOI: 10.3892/ol.2013.1280
  • Peer Reviewed
• [Journal Article] Soluble Neural-cadherin as a novel biomarker for malignant bone and soft tissue tumors (2013)
  • Author(s): Niimi R, Matsumine A, Iino T, Nakazora S, Nakamura T, Uchida A, Sudo A
  • Journal Title: BMC Cancer Volume: 26 Pages: 13:309
  • DOI: 10.1186/1471-2407-13-309
  • Peer Reviewed
• [Journal Article] Clinical significance of radiofrequency ablation and metastasectomy in elderly patients with lung metastases from musculoskeletal sarcomas (2013)
  • Author(s): Nakamura T, Matsumine A, Yamakado K, Takao M, Uchida A, Sudo A
  • Journal Title: J Cancer Res Ther Volume: 9 Pages: 219-223
  • DOI: 10.4103/0973-1482.113358
  • 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 Pages: 792-802
  • DOI: 10.1007/s11999-012-2616-9
  • Peer Reviewed
• [Journal Article] The thrombin inhibitor, argatroban, inhibits breast cancer metastasis to bone (2013)
  • 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 Volume: 20 Pages: 241-246
  • DOI: 10.1007/s12282-012-0334-5.
  • Peer Reviewed
• [Journal Article] Clinical significance of pretreatment serum C-reactive protein level in soft tissue sarcoma (2012)
  • Author(s): Nakamura T, Matsumine A, Matsubara T, Asanuma K, Uchida A, Sudo A
  • Journal Title: Cancer Volume: 118 Pages: 1055-1061
  • DOI: 10.1002/cncr.26353
  • 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: 1414-1420
  • DOI: 10.2174/138161212799504812
  • Peer Reviewed
• [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: 1984-1990
  • DOI: 10.3892/or.2012.2021
  • 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
  • DOI: 10.3892/ijo.2012.1514
  • 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: 101-108
  • DOI: 10.1007/s10147-011-0217-3
  • Peer Reviewed
• [Journal Article] Clinical outcomes 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: 257263
  • DOI: 10.1002/jso.21823
  • Peer Reviewed
• [Journal Article] The adverse effect of an unplanned surgical excision of foot soft tissue sarcoma (2011)
  • Author(s): Nishimura A, Matsumine A, Asanuma K, Matsubara T, Nakamura T, Uchida A, Kato K, Sudo A
  • Journal Title: World J Surg Oncol Volume: 9 Pages: 160
  • DOI: 10.1186/1477-7819-9-160
  • Peer Reviewed
• [Journal Article] Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma (2011)
  • Author(s): Nishimura A, Akeda K, Matsubara T, Kusuzaki K, Matsumine A, Masuda K, Gemba T, Uchida A, Sudo A
  • Journal Title: Cancer Gene Ther Volume: 18 Pages: 250-259
  • DOI: 10.1038/cgt.2010.75
  • Peer Reviewed
• [Journal Article] Recurrent ankle equinus deformity due to intramuscular hemangioma of the gastrocnemius : case report (2011)
  • Author(s): Nakamura T, Matsumine A, Nishiyama M, Uchida A, Sudo A
  • Journal Title: Foot Ankle Int Volume: 32 Pages: 905-907
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/?term=Recurrent+ankle+equinus+deformity+due+to+intramuscular+hemangioma+of+the+gastrocnemius%3A+case+report
  • Peer Reviewed
• [Journal Article] Clinical impact 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: 819-825
  • DOI: 10.1007/s10585-011-9413-9
  • Peer Reviewed
• [Journal Article] The symptom-to-diagnosis delay in soft tissue sarcoma influence the overall survival and the development of distant metastasis (2011)
  • Author(s): Nakamura T, Matsumine A, Matsubara T, Asanuma K, Uchida A, Sudo A
  • Journal Title: J Surg Oncol Volume: 104 Pages: 771-775
  • DOI: 10.1002/jso.22006
• [Journal Article] Extraslkeletal subcutaneous osateosarcoma of the upper arm : A case report (2011)
  • Author(s): Nakamura T, Matsumine A, Nishimura K, Yokoyama H, Murata T, Uchida A, Sudo A
  • Journal Title: Oncology Letters Volume: 2 Pages: 75-77
  • DOI: 10.3892/ol.2010.204
  • Peer Reviewed
• [Journal Article] Retrospective analysis of metastatic sarcoma patients (2011)
  • Author(s): Nakamura T, Matsumine A, Matsubara T, Asanuma K, Niimi R, Uchida A, Sudo A
  • Journal Title: Oncology Letters Volume: 2 Pages: 315-318
  • DOI: 10.3892/ol.2011.238
  • Peer Reviewed
• [Journal Article] Acridine orange inhibits pulmonary metastasis 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: 31 Pages: 4163-4168
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/?term=Acridine+orange+inhibits+pulmonary+metastasis+of+mouse+osteosarcoma
  • Peer Reviewed
• [Journal Article] TNF inhibitor suppresses 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 Res Commun Volume: 407 Pages: 525-530
  • DOI: 10.1016/j.bbrc.2011.03.051
  • Peer Reviewed
• [Presentation] Soluble N-cadherin as a Biomarker for Malignant Bone and Soft Tissue Tumors (2014)
  • Author(s): Matsumine A, Niimi R, Iino T, Nakamura T, Matsubara T, Asanuma K, Sudo A
  • Organizer: Orthopaedic Research Society
  • Place of Presentation: New Orleans, USA
  • Year and Date: 20140315-18
• [Presentation] Soluble cd155 As A Biomarker For Malignant Bone And Soft Tissue Tumors (2014)
  • Author(s): Goto M, Matsumine A, Nakamura T, Matsubara T, Asanuma K, Oi T, Sudo A
  • Organizer: Orthopaedic Research Society
  • Place of Presentation: New Orleans, USA
  • Year and Date: 20140315-18
• [Presentation] Carbonic Anhydrase iX has the Potential to Predict Preoperative chemotherapy effect (2014)
  • Author(s): Okuno K, Matsubara T, Matsumine A, Asanuma K, Nakamura T, Goto M, Oi T, Sudo A
  • Organizer: On human Osteosarcoma Patients. Orthopaedic Research Society
  • Place of Presentation: New Orleans, USA
  • Year and Date: 20140315-18
• [Presentation] Cucurbitacin i (jsi-124) induces Apoptosis in human Osteosarcoma cells (2014)
  • Author(s): Oi T, Asanuma K, Nakamura T, Matsubara T, Matsumine A, Sudo A
  • Organizer: Orthopaedic Research Society
  • Place of Presentation: New Orleans, USA
  • Year and Date: 20140315-18
• [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, Asanuma K, Nakamura T, Okuno K, Goto M, Oi T, Sudo A
  • Organizer: Orthopaedic Research Society
  • Place of Presentation: New Orleans, USA
  • Year and Date: 20140315-18
• [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, Asanuma K, Nakamura T, Sudo A
  • Organizer: American Academy of Orthopaedic Surgeons
  • Place of Presentation: New Orleans, USA
  • Year and Date: 20140311-15
• [Presentation] The expression of Tissue Factor mRNA in bone and soft tissue sarcoma patients (2013)
  • Author(s): Asanuma K, Matsumine A, Matsubara T, Nakamura T, Ooi T, Asanuma Y, Sudo A
  • Organizer: European Musculo-Skeletal Oncolory Society
  • Place of Presentation: Gothenburg, Swedwn
  • Year and Date: 20130529-31
• [Presentation] Clinical outcomes in the oldest old patients (85 years or old) with musuculoskeletal sarcomas (2013)
  • Author(s): Ooi T, Matsumine A, Goto M, Nakamura T, Matsubara T, Asanuma K, Sudo A
  • Organizer: European Musculo-Skeletal Oncolory Society
  • Place of Presentation: Gothenburg, Swedwn
  • Year and Date: 20130529-31
• [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, USA
  • Year and Date: 20130319-23
• [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, USA
  • Year and Date: 20130319-23
• [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, USA
  • Year and Date: 20130319-23
• [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, USA
  • Year and Date: 20130126-29
• [Presentation] Tissue Factor Mrna Expression in 68 Soft Tissue Sarcoma Patients (2012)
  • Author(s): Asanuma K, Matsumine A, Matsubara T, Atsumi S, Matsui Y, Nakamura T, Uchida A, Sudo A
  • Organizer: Combined 33rd SICOT & 17th PAOA Orthopaedic World Conference
  • Place of Presentation: Dubai, United Arab Emirates
  • Year and Date: 20121128-30
• [Presentation] Soluble N-cadherin as a Biomarker for Malignant Bone and Soft Tissue Tumor (2012)
  • Author(s): Matsumine A, Niimi R, Iino T, Nakazora S, Nakamura T, Matsubara T, Asanuma K, Uchida A, Sudo A
  • Organizer: 17) 9TH ASIS PACIFIC MUSCULOSKELETAL TUMOR SOCIETY MEETING 2012 Connectine Tissue Oncology Society
  • Place of Presentation: Czech Republic, Prague
  • Year and Date: 20121114-17
• [Presentation] The Expression of Thrombomodulin Messenger RNA in 62 Soft Tissue Sarcoma Patients (2012)
  • Author(s): Asanuma K, Matsumine A, Matsubara T, Nakamura T, Uchida A, Sudo A
  • Organizer: 9TH ASIS PACIFIC MUSCULOSKELETAL TUMOR SOCIETY MEETING 2012 Connectine Tissue Oncology Society
  • Place of Presentation: Czech Republic, Prague
  • Year and Date: 20121114-17
• [Presentation] A Minimally Invasive Surgery for Bone Metastases Using the Combination of Photodynamic Therapy and Hyperthermia Treatment (2012)
  • Author(s): Matsubara T, Kusuzaki K, Matsumine A, Asanuma K, Nakamura T, Uchida A, Sudo A
  • Organizer: 9TH ASIS PACIFIC MUSCULOSKELETAL TUMOR SOCIETY MEETING 2012 Connectine Tissue Oncology Society
  • Place of Presentation: Czech Republic, Prague
  • Year and Date: 20121114-17
• [Presentation] Analysis of tumor metastatic factor using low coagulation activity model in mice (2012)
  • Author(s): Asanuma K, Matsumine A, Asanuma Y, Akita N, Yoshikawa T, Yoshida K, Matsubara T, Nakamura T, Okamoto T, Hayashi T, Uchida A, Sudo A
  • Organizer: 13) Orthopaedic Research Society
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20120204-07
• [Presentation] A Novel Oncolytic Virotherapy Using Live-attenuated Poliovirus for Soft Tissue Sarcoma (2012)
  • Author(s): Atsumi S, Matsumine A, Nakamura T, Niini R, Matsubara T, Asanuma K, Uchida A, Sudo A
  • Organizer: Orthopaedic Research Society
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20120204-07
• [Presentation] Acridine Orange Inhibits Pulmonary Metastasis and Invasion on Mouse Oseteosarcoma (2012)
  • Author(s): Satanaka H, Akeda K, Kusuzaki K, Tujii M, Iino T, Uemura T, Nakamura T, Matsubara T, Asanuma K, Matsumine A, Sudo A
  • Organizer: Orthopaedic Research Society
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20120204-07
• [Book] 先端医療シリーズ44、臨床医のための最新整形外科、軟部肉腫に対するアクリジンオレンジ療法 (2013)
  • Author(s): 松峯昭彦、松原孝夫、楠崎克之
  • Total Pages: 570
  • Publisher: 先端医療技術研究所
• [Book] がん骨転移のバイオロジーとマネージメント、Part iiがん骨転移のマネージメント、疫学～骨関連事象、予後など～ (2012)
  • Author(s): 湏藤啓広、松峯昭彦
  • Total Pages: 400
  • Publisher: 医薬ジャーナル
• [Book] Chapter VI : New concept of limb salvage surgery in musculoskeletal sarcomas with acridine orange therapy (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
  • Total Pages: 179
  • Publisher: Nova Science Publishers
• [Book] 整形外科臨床パサージュ6、軟部腫瘍プラクティカルガイド、軟部腫瘍における生検の実際 (2011)
  • Author(s): 松峯昭彦
  • Total Pages: 240
  • Publisher: 中山書店
• [Book] 薬局増刊号、病気と薬パーフェクトBOOK,骨肉腫 (2011)
  • Author(s): 松原孝夫、松峯昭彦、須藤啓広
  • Total Pages: 1928
  • Publisher: 南山堂