Development of new adjuvant therapy using nanoparticles for malignant bone and soft tumors

• Project/Area Number: 24592244
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Keio University
• Principal Investigator: MORIOKA Hideo 慶應義塾大学, 医学部, 講師 (10230096)
• Co-Investigator(Kenkyū-buntansha): SUSA Michiro 慶應義塾大学, 医学部, 助教 (90327560)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 悪性骨・軟部腫瘍 / 化学療法 / ナノ粒子 / 薬剤耐性 / 分子標的治療 / 肉腫 / 抗癌剤 / 希少がん / 骨・軟部腫瘍

Outline of Final Research Achievements

Improvements in surgical technique, chemotherapy, and radiotherapy have enhanced the prognosis of patients with malignant bone and soft tissue tumors, but have since reached a plateau in recent years. Novel approaches have been sought but with limited results. On the other hand, several varieties of nanoparticles, including multifunctional nanoparticles, are available that localize the biodistribution of conventional chemotherapeutics to the tumor site. Also, nanoparticles loaded with chemotherapeutic drugs have the ability to overcome drug resistance which is a major obstacle impeding the progress of the treatment. Multifunctional nanoparticles, which have the potential to further augment the bioavailability of drugs, are being actively investigated. The purpose of this study is to investigate in vitro and in vivo therapeutic effects of multifunctional nanoparticles in malignant bone and soft tissue tumors with drug resistance for current chemotherapy.

Research Products

• [Journal Article] MicroRNA expression and functional profiles of osteosarcoma. (2014)
  • Author(s): Kobayashi E, Satow R, Ono M, Masuda M, Honda K, Sakuma T, Kawai A, Morioka H, Toyama Y, Yamada T.
  • Journal Title: Oncology Volume: 86(2): Issue: 2 Pages: 94-103
  • DOI: 10.1159/000357408
  • Peer Reviewed / Open Access
• [Journal Article] TNFα promotes osteosarcoma progression by maintaining tumor cells in an undifferentiated state. (2013)
  • Author(s): Mori T
  • Journal Title: Oncogene Volume: Epub ahead of print Issue: 33 Pages: 4236-4241
  • DOI: 10.1038/onc.2013.545
  • Peer Reviewed
• [Journal Article] Deep infection in tumor endoprosthesis around the knee: a multi-institutional study by the Japanese musculoskeletal oncology group. (2013)
  • Author(s): Morii,T., Morioka,H., Ueda,T., Araki,N., Hashimoto,N., Kawai,A., Mochizuki,K., Ichimura,S.
  • Journal Title: BMC Musculoskelet Disord. Volume: 31 Issue: 1 Pages: 1-9
  • DOI: 10.1186/1471-2474-14-51
  • Peer Reviewed
• [Journal Article] Twist2 functions as a tumor suppressor in murine osteosarcoma cells. (2013)
  • Author(s): Ishikawa T, Shimizu T, Ueki A, Yamaguchi S, Onishi N, Sugihara E, Kuninaka S, Miyamoto T, Morioka H, Nakayama R, Kobayashi E, Toyama Y, Mabuchi Y, Matsuzaki Y, Yamaguchi R, Miyano S and Saya H
  • Journal Title: Cancer Sci Volume: (in press) Issue: 7 Pages: 880-888
  • DOI: 10.1111/cas.12163
  • Peer Reviewed
• [Journal Article] Functional analysis of cases of tumor endoprostheses with deep infection around the knee: a multi institutional study by the Japanese Musculoskeletal Oncology Group (JMOG). (2013)
  • Author(s): Morii,T., Morioka,H., Ueda,T., Araki,N., Hashimoto,N., Kawai,A., Takeuchi,K., Anazawa,U., Mochizuki,K., Ichimura,S.
  • Journal Title: Cancer Sci. Volume: 18 Issue: 4 Pages: 605-612
  • DOI: 10.1007/s00776-013-0389-y
  • Peer Reviewed
• [Journal Article] An analysis of factors related to recurrence of myxofibrosarcoma (2013)
  • Author(s): Kikuta K,Kawai A
  • Journal Title: Jpn J Clin Oncol Volume: 43(11) Issue: 11 Pages: 1093-104
  • DOI: 10.1093/jjco/hyt119
  • Peer Reviewed
• [Journal Article] Desmoplastic Fibroma Arising in the Distal Phalanx of the Great Toe: A Case Report. (2013)
  • Author(s): Koba,T., Susa,M., Nakayama,R., Watanabe,I., Horiuchi,K., Mukai,M., Yabe,H., Toyama,Y., Morioka,H.
  • Journal Title: J Foot Ankle Surg. Volume: 53 Issue: 3 Pages: 71-74
  • DOI: 10.4081/rt.2013.e43
  • Peer Reviewed
• [Journal Article] The germline TP53 mutation c.722 C>T promotes bone and liver tumorigenesis at a young age. (2012)
  • Author(s): Osumi,T., Miharu,M., Fuchimoto,Y., Morioka,H., Kosaki,K., Shimada,H.
  • Journal Title: Pediatr Blood Cancer. Volume: 59 Pages: 1332-1333
• [Journal Article] Detection of HEY1-NCOA2 fusion by fluorescence in-situ hybridization in formalin-fixed paraffin-embedded tissues as a possible diagnostic tool for mesenchymal chondrosarcoma. (2012)
  • Author(s): Nakayama R, Miura Y, Ogino J, Susa M, Watanabe I, Horiuchi K, Anazawa U, Toyama Y, Morioka H, Mukai M, Hasegawa T.
  • Journal Title: Pathol Int. Volume: 62 Pages: 823-826
• [Presentation] Stratified efficacy analysis and pharmacokinetic (PK) analysis of tarbectedin from a randomized phase II study comparing trabectedin and best supportive care (BSC) in patients (PTS) with translocation-related sarcomas (TRS). (2014)
  • Author(s): Takafumi,U., Takahashi,S., Araki,N., Sugiura,H., Yonemoto,T., Takahashi,M., Morioka,H., Hiruma,T., HIraga,H., Kunisada,T., Matsumine,A., Tanase,T., Kawai,A
  • Organizer: Connective Tissue Oncology Society, 19th Annual Meeting.
  • Place of Presentation: Berlin, Germany.
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] PhaseⅡ study of eribulin mesylate in patients with advanced soft tissue sarcoma (STS). (2014)
  • Author(s): Naito,Y., Kawai,A., Araki,N., Ozaki,T., Sugiura,H., Yazawa,Y., Morioka,H., Matsumine,A., HIraiwa,M., Asami,S., Isu,K.
  • Organizer: ASCO Annual Meeting.
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2014-05-29 – 2014-06-02
• [Presentation] Prognostic factors for high-grade soft tissue sarcomas (STS) in the extremities treated by perioperative chemotherapy with ifosfamide (IFO) and adriamycin (ADM): using the data from Japan Clinical Oncology Group trial (JCOG0304). (2014)
  • Author(s): Tanaka,K., Hasegawa,T., Mizusawa,J., Araki,N., Chuman,H., Takahashi,M., Ozaki,T., Hiruma,T., Tsuchiya,H., Morioka,H., Hatano,H., Wada,T., Hosaka,M., Yoshida,Y., Toguchida,J., Abe,S., Matsumine,A., Yokoyama,R., Fukuda,H., Iwamoto,Y.
  • Organizer: ASCO Annual Meeting.
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2014-05-29 – 2014-06-02
• [Presentation] Limb salvage surgery for malignant bone tumor of extremities in children and adolescents: long-term follow-up. (2014)
  • Author(s): Susa,M., Watanabe,I., Nishimoto,K., Horiuchi,K., Anazawa,U., Suzuki,Y., Yabe,H., Toyama,Y., Morioka,H.
  • Organizer: 10th Asia Pacific Musculoskeletal Tumour Society Meeting.
  • Place of Presentation: Melbourne, Australia.
  • Year and Date: 2014-04-09 – 2014-05-11
• [Presentation] Clinical results and prognostic factors in osteosarcoma with lung metastases. (2014)
  • Author(s): Nishimoto,K., Watanabe,I., Kikuta,K., Susa,M., Horiuchi,K., Suzuki,Y., Anazawa,U., Yabe,H., Kohno,M., Kawamura,M., Toyama,Y., Morioka,H.
  • Organizer: 10th Asia Pacific Musculoskeletal Tumour Society Meeting.
  • Place of Presentation: Melbourne, Australia.
  • Year and Date: 2014-04-09 – 2014-04-11
• [Presentation] Autophagy inhibitions suppresses therapy-induced senescence and and enhances anti-tumor effects of cisplatin on osteosarcoma cells. (2014)
  • Author(s): Hirozane,T., Horiuchi,K., Mizuno,S., Mizuochi,H., Yoda,M., Tohmonda,T., Morioka,H., Toyama,Y.
  • Organizer: 10th Asia Pacific Musculoskeletal Tumour Society Meeting.
  • Place of Presentation: Melbourne, Australia.
  • Year and Date: 2014-04-09 – 2014-04-11
• [Presentation] Clinical Outcome of Recurrent Myxofibrosarcoma. (2013)
  • Author(s): Nakayama,R., Kikuta,K., Susa,M., Kobayashi,E., Nakatani,F., Kawai,A., Chuman,H., Toyama,Y., Morioka,H.
  • Organizer: 26th European Musculoskeletal Oncology Society Meeting
  • Place of Presentation: Gothenburg, Sweden
• [Presentation] Custum-made ceramic spacer for children with osteosarcoma of lower extremities: a long follow-up. (2013)
  • Author(s): Nakatani,F., Nakayama,R., Asano,N., Kawai,A., Yamaguchi,U., Kobayashi,E., Y Tanzawa,Y., Ogura,K., Setsu,N., Fujiwara,T., Kubota,D., Watanabe,I., Susa,M., Morioka,H., Chuman,H.
  • Organizer: International Society of Limb Salvage, 17th General Meeting.
  • Place of Presentation: Bologna, Italia
• [Presentation] Surgical treatment of chondrosarcoma of the chest wall. (2013)
  • Author(s): Susa,M., Nakayama,R., Watanabe,I., Horiuchi,K., Anazawa,U., Suzuki,Y., Yabe,H., Toyama,T., Morioka,H.
  • Organizer: International Society of Limb Salvage, 17th General Meeting.
  • Place of Presentation: Bologna, Italia
• [Presentation] Clinical outcome of giant cell tumor of the mobile spine. (2013)
  • Author(s): Susa,M., Iwanami,A., Nakayama,R., Watanabe,I., Horiuchi,K., Anazawa,U., Suzuki,Y., Yabe,H., Matsumoto,M., Toyama,Y., Morioka,H.
  • Organizer: International Society of Limb Salvage, 17th General Meeting.
  • Place of Presentation: Bologna, Italia
• [Presentation] Pathologic fracture in giant cell tumor: prognostic importance and treatment implications. (2013)
  • Author(s): Watanabe,I., Horiuchi,K., Nishimoto,K., Susa,M., Nakayama,R., Toyama,Y., Yabe,H., Morioka,H.
  • Organizer: Connective Tissue Oncology Society, 18th Annual Meeting.
  • Place of Presentation: New York, USA
• [Presentation] Clinical outcome of primary malignant tumor of the mobile spine . (2013)
  • Author(s): Susa,M., Iwanami,A., Watanabe,I., Nishimoto,K., Horiuchi,K., Anazawa,U., Suzuki,Y., Yabe,H., Matsumoto,M., Toyama,Y., Morioka,H.
  • Organizer: Connective Tissue Oncology Society, 18th Annual Meeting.
  • Place of Presentation: New York, USA
• [Presentation] Establishment of novel cell lines derived from sarcoma tissues. (2013)
  • Author(s): Horiuchi,K., Nakayama,R., Susa,M., Watanabe,I., Morioka,H.
  • Organizer: Connective Tissue Oncology Society, 18th Annual Meeting.
  • Place of Presentation: New York, USA
• [Presentation] Epithelioid sarcoma: a clinicopathologic study of 44 cases. (2013)
  • Author(s): Asano,N., Yoshida,A., Ogura,K., Morioka,H., Mukai,M., Iwata,S., Ishii,T., Hiruma,T., Chuman,H., Kawai,A.
  • Organizer: Connective Tissue Oncology Society, 18th Annual Meeting.
  • Place of Presentation: New York, USA
• [Presentation] A proteomic analysis to identify nevel proteins related to mechanisms of tumor cell invasion in myxofibrosarcoma. (2013)
  • Author(s): K.,Kikuta, D.,Kubota, Y.,Suzuki, H.,Morioka, Y.,Toyama, A.,Yoshida, E.,Kobayashi, F.,Nakatani, H.,Chuman, A.,Kawai, T.Kondo
  • Organizer: The EuPA 2013 Scientific Meeting.
  • Place of Presentation: Saint Malo, France
• [Presentation] Surgical treatment of preadolescent osteosarcoma patients. (2012)
  • Author(s): Susa,M., Nakayama,R., Watanabe,I., Horiuchi,K., Anazawa,U., Suzuki,Y., Yabe,H., Toyama,Y., Morioka,H.
  • Organizer: 9th Asia Pacific Musculoskeletal Tumour Society Meeting
  • Place of Presentation: Kuala Lumpur
• [Presentation] Clinical outcome of recurrent myxofibrosarcoma. (2012)
  • Author(s): Nakayama,R., Kikuta,K., Susa,M., Watanabe,I., Horiuchi,K., Suzuki,Y., Anazawa,U., Yabe,H., Toyama,Y., Morioka,H.
  • Organizer: 9th Asia Pacific Musculoskeletal Tumour Society Meeting
  • Place of Presentation: Kuala Lumpur
• [Presentation] Detection of HEY1-NCOA2 fusion by fluorescence in situ hybridization in formalin-fixed, paraffin-embedded tissues as a possible defining diagnostic tool in mesenchymal chondrosarcoma. (2012)
  • Author(s): Nakayama,R., Ogino,J., Susa,M., Watanabe,I., Horiuchi,K., Anazawa,U., Toyama,Y., Morioka,H., Mukai,M., Hasegawa,T.
  • Organizer: 9th Asia Pacific Musculoskeletal Tumour Society Meeting
  • Place of Presentation: Kuala Lumpur
• [Presentation] Treatment of tibial adamantinoma; a study of 4 cases. (2012)
  • Author(s): Mori,T., Nakayama,R., Susa,M., Watanabe,I., Horiuchi,K., Yabe,H., Toyama,Y., Morioka,H.
  • Organizer: 9th Asia Pacific Musculoskeletal Tumour Society Meeting
  • Place of Presentation: Kuala Lumpur
• [Presentation] 17th Connective Tissue Oncology Society Annual Meeting (2012)
  • Author(s): Kobayashi,E., Sato,R., Kawai,A., Morioka,H., Toyama,Y., Yamada,T.: MicroRNA expression and functional profiles of osteosarcoma.
  • Organizer: 17th Connective Tissue Oncology Society Annual Meeting
  • Place of Presentation: Prague
• [Book] 肉腫化学療法マスタークラス (2015)
  • Author(s): 森岡秀夫
  • Total Pages: 6
  • Publisher: 南山堂
• [Remarks] 慶應義塾大学医学部整形外科学教室 腫瘍班
  • URL: http://www.keio-mog.jp/