Functional analysis of synovial sarcoma specific fusion-gene and identification of new therapeutic targets

• Project/Area Number: 26462264
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Osaka University
• Principal Investigator: Kenichiro Hamada 大阪大学, 医学系研究科, 助教 (50649043)
• Co-Investigator(Kenkyū-buntansha): 王谷 英達 大阪大学, 医学系研究科, 特任助教(常勤) (60727965) ; 中 紀文 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 整形外科主任部長 (90601964)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 滑膜肉腫 / 新規治療開発 / 融合遺伝子 / Synovial sarcoma / Targetd therapy / Xenograht model / Fusion gene / Pre-clinical study / Targeted therapy / Xenograft model / 創薬 / 抗腫瘍効果

Outline of Final Research Achievements

Synovial sarcoma is a rare aggressive disease which is characterized by a synovial sarcoma specific fusion-oncogene SS18-SSX. We examined the possibility to control the tumors by silencing SS18-SSX using doxycycline inducible system. Then, we successfully suppressed the tumor growth by silencing the fusion-oncogene SS18-SSX both in vitro and in vivo using this system. In addition, we confirmed that silencing of SS18-SSX resulted in significantly less tumor formations in vivo. These results indicated that silencing of SS18-SSX could be a treatment option for local tumors or metastases. Furthermore, we are now analyzing gene expressions regulated by SS18-SSX using this system to explore a new treatment target for synovial sarcoma.

Research Products

• [Journal Article] Clinical outcomes of patients with epithelioid sarcomas: impact and management of nodal metastasis (2018)
  • Author(s): Outani H, Imura Y, Tanaka T, Takenaka S, Oshima K, Hamada K, Kakunaga S, Joyama S, Naka N, Kudawara I, Ueda T, Araki N, Yoshikawa H.
  • Journal Title: Int J Clin Oncol Volume: 23 Pages: 181-188
  • Peer Reviewed / Open Access
• [Journal Article] Reconstruction using a constrained-type hip tumor prosthesis after resection of malignant periacetabular tumors: A study by the Japanese Musculoskeletal Oncology Group (JMOG). (2018)
  • Author(s): Ogura K, Susa M, Morioka H, Matsumine A, Ishii T, Hamada K, Ueda T, Kawai A
  • Journal Title: J Surg Oncol Volume: 印刷中 Issue: 7 Pages: 1455-1463
  • DOI: 10.1002/jso.25005
  • Peer Reviewed / Open Access
• [Journal Article] Trabectedin is a promising antitumor agent potentially inducing melanocytic differentiation for clear cell sarcoma (2017)
  • Author(s): Nakai Takaaki、Imura Yoshinori、Tamiya Hironari、Yamada Shutaro、Nakai Sho、Yasuda Naohiro、Kaneko Keiko、Outani Hidetatsu、Takenaka Satoshi、Hamada Kenichiro、Myoui Akira、Araki Nobuhito、Ueda Takafumi、Itoh Kazuyuki、Yoshikawa Hideki、Naka Norifumi
  • Journal Title: Cancer Medicine Volume: 6 Issue: 9 Pages: 2121-2130
  • DOI: 10.1002/cam4.1130
  • Peer Reviewed / Open Access
• [Journal Article] Therapeutic potential of TAS-115 via c-MET and PDGFRα signal inhibition for synovial sarcoma. (2017)
  • Author(s): Yamada S, Imura Y, Nakai T, Nakai S, Yasuda N, Kaneko K, Outani H, Takenaka S, Hamada K, Myoui A, Araki N, Ueda T, Itoh K, Yoshikawa H, Naka N.
  • Journal Title: BMC Cancer Volume: 17(1) Issue: 1 Pages: 334-334
  • DOI: 10.1186/s12885-017-3324-3
  • Peer Reviewed / Open Access
• [Journal Article] Functional and therapeutic relevance of hepatocyte growth factor/c-MET signaling in synovial sarcoma. (2016)
  • Author(s): Imura Y, Nakai T, Yamada S, Outani H, Takenaka S, Hamada K, Araki N, Itoh K, Yoshikawa H, Naka N.
  • Journal Title: Cancer Sci. Volume: 107 Issue: 12 Pages: 1867-1876
  • DOI: 10.1111/cas.13092
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Trabectedin is a promising antitumor agent for synovial sarcoma (2016)
  • Author(s): Yasui H, Imura Y, Outani H, Hamada K, Nakai T, Yamada S, Takenaka S, Sasagawa S, Araki N, Itoh K, Myoui A, Yoshikawa H, Naka N
  • Journal Title: J Chemother Volume: 28(5) Pages: 417-424
  • Peer Reviewed
• [Journal Article] Treatment outcomes of Japanese patients with Ewing sarcoma: difference between skeletal and extraskeletal Ewing sarcoma. (2016)
  • Author(s): Takenaka S, Naka N, Obata H, Joyama S, Hamada K, Imura Y, Kakunaga S, Aoki Y, Ueda T, Araki N, Yoshikawa H.
  • Journal Title: Jpn J Clin Oncol. Volume: 46(6) Issue: 6 Pages: 522-528
  • DOI: 10.1093/jjco/hyw032
  • Peer Reviewed / Open Access
• [Presentation] Ewing-like sarcoma細胞株樹立と新規癒合遺伝子の解析 (2018)
  • Author(s): 安田直弘 中井翔 王谷英達 竹中聡 濱田健一郎 中紀文 吉川秀樹
  • Organizer: 日本サルコーマ治療研究学会学術集会
• [Presentation] 淡明細胞肉腫に対するEribulin mesilateの抗腫瘍効果 (2018)
  • Author(s): 中井翔 安田直弘 王谷英達 竹中聡 濱田健一郎 中紀文 吉川秀樹
  • Organizer: 日本サルコーマ治療研究学会学術集会
• [Presentation] 初診時転移を有する軟部肉腫の治療成績 (2017)
  • Author(s): 王谷英達 中井翔 安田直弘 竹中聡 濱田健一郎 中紀文 吉川秀樹
  • Organizer: 日本整形外科学会骨軟部腫瘍学会
• [Presentation] 淡明細胞肉腫に対する trabectedin（Yondelis; ET-743）の抗腫瘍効果 (2017)
  • Author(s): 中井隆彰 王谷英達 中井翔 安田直弘 竹中聡 濱田健一郎 中紀文 吉川秀樹
  • Organizer: 日本整形外科学会骨軟部腫瘍学会
• [Presentation] 淡明細胞肉腫に対する eribulin mesilate の抗腫瘍効果 (2017)
  • Author(s): 中井翔 安田直弘 王谷英達 竹中聡 濱田健一郎 中紀文 吉川秀樹
  • Organizer: 日本整形外科学会骨軟部腫瘍学会
• [Presentation] 神経線維腫症 1 型に発症した悪性末梢神経鞘腫瘍に対する治療成績 (2017)
  • Author(s): 濱田健一郎 中井翔 安田直弘 王谷英達 竹中聡 中紀文 吉川秀樹
  • Organizer: 日本整形外科学会骨軟部腫瘍学会
• [Presentation] Clinilar resultsof Osteosarcoma patients of lower extremity under 12 years-old (2017)
  • Author(s): 濱田健一郎 中井翔 安田直弘 王谷英達 竹中聡 中紀文 吉川秀樹
  • Organizer: SICOT2017
  • Int'l Joint Research
• [Presentation] Anti-tumor effects of Eribulin mesilate on clear cell sarcoma cell lines (2017)
  • Author(s): 中井翔 安田直弘 王谷英達 竹中聡 濱田健一郎 中紀文 吉川秀樹
  • Organizer: CTOS2017
  • Int'l Joint Research
• [Presentation] Clinical outcomes and management of nodal metastasis is the patients with epithelioid sarcoma (2017)
  • Author(s): 王谷英達 中井翔 安田直弘 竹中聡 濱田健一郎 中紀文 吉川秀樹
  • Organizer: CTOS2017
  • Int'l Joint Research
• [Presentation] The Effect of SS18-SSX on TUmor growth and initiation of synovial sarcoma (2016)
  • Author(s): Hidetatsu Outani, Takaaki Tanaka, Yoshinori Imura, Kazuya Oshima, Nobuhito Araki, Takaaki Nakai, Kenichiro Hamada, Takafumi Ueda, Hideki Yoshikawa, Norifumi Naka
  • Organizer: Connective Tissue Oncology Society 2016 Annual Meeting
  • Place of Presentation: Lisbon Portugal
  • Year and Date: 2016-11-09
  • Int'l Joint Research
• [Presentation] Anti tumor effects of Trabectedin on Clear cell sarcoma cell lines (2016)
  • Author(s): Takaaki Nakai, Yoshinori Imura, Shutaro Yamada, Sho Nakai, Hidetatsu Outani, Satoshi Takenaka, Kenichiro Hamada, Akira Myoui, Nobuhito Araki, Kazuyuki Itoh, Hideki Yoshikawa, Norifumi Naka
  • Organizer: Connective Tissue Oncology Society 2016 Annual Meeting
  • Place of Presentation: Lisbon Portugal
  • Year and Date: 2016-11-09
  • Int'l Joint Research
• [Presentation] 淡明細胞肉腫に対するMET阻害剤の抗腫瘍効果 (2016)
  • Author(s): 中井隆彰 山田修太郎 濵田健一郎 金子恵子 竹中聡 名井陽 吉川秀樹 中紀文
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2016-10-13
• [Presentation] 上腕骨骨腫瘍に対する術中体外放射線照射自家骨移植を用いた再建症例の術後成績 (2016)
  • Author(s): 濵田健一郎
  • Organizer: 第89回日本整形外科骨軟部腫瘍学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-07-14
• [Presentation] TAS115は単剤でc-METまたはPS/DGFRαシグナルに依存した複数の滑膜肉腫細胞株に対して抗腫瘍効果を発揮する (2016)
  • Author(s): 山田修太郎 中井隆彰 金子恵子 竹中聡 濵田健一郎 名井陽 吉川秀樹 中紀文
  • Organizer: 第89回日本整形外科骨軟部腫瘍学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-07-14