Development of novel target therapy for metastatic organ of malignant soft tissue tumor

• Project/Area Number: 15K15560
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: 医療法人徳洲会野崎徳洲会病院(附属研究所) (2016-2017); Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses (2015)
• Principal Investigator: Itoh Kazuyuki 医療法人徳洲会野崎徳洲会病院(附属研究所), 研究所, 所長 (20301806)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 肺転移 / スフェロイド / 肉腫 / 骨肉腫 / 肺線維化 / Cachexia / metastasis / lung / CTC / Osteosarcoma / VEGF

Outline of Final Research Achievements

Prognosis of malignant soft tissue tumor clinically depended on the lung metastasis. Recently, critical roles of spheroid formation and dynamics during metastasis formation was emphasized. We herein newly developed macro-microscopy with near-infrared light. Employing this system, we could analyze the marginal zones and also intra regions of malignant soft tissue tumor spheroid with time-lapse recording.
Numerous filopodias were observed surrounding spheroid with Cdc42-dependent fashion and budding (
sprouting) formation were observed occasionally with Rho-Rho-kinase (ROCK) dependent manner. We are currently analyzing this spheroid dynamics with several compounds, which already confirmed showing the inhibitory effects for the same soft tissue tumor in vitro and also in vivo Xenograft model.

Research Products

• [Journal Article] Evidence for intrathecal sodium butyrate as a novel option for leptomeningeal metastasis. (2018)
  • Author(s): Nakagawa H, Yui Y, Sasagawa S, Itoh K.
  • Journal Title: Journal of Neuro-Oncology Volume: 印刷中 Issue: 1 Pages: 43-50
  • DOI: 10.1007/s11060-018-2852-2
  • Peer Reviewed
• [Journal Article] Sodium butyrate induces senescence and inhibits the invasiveness of glioblastoma cells. (2018)
  • Author(s): Nakagawa H, Sasagawa S, Itoh K.
  • Journal Title: Oncology letter Volume: 15(2) Pages: 1495-1502
  • DOI: 10.3892/ol.2017.7518
  • Peer Reviewed / Open Access
• [Journal Article] Development of effective tumor immunotherapy using a novel dendritic cell?targeting Toll-like receptor ligand (2017)
  • Author(s): De Silva Nadeeka H.、Akazawa Takashi、Wijewardana Viskam、Inoue Norimitsu、Oyamada Maremichi、Ohta Atsuko、Tachibana Yuki、Wijesekera Daluthgamage Patsy H.、Kuwamura Mitsuru、Nishizawa Yasuko、Itoh Kazuyuki、Izawa Takeshi、Hatoya Shingo、Hasegawa Tetsuya、Yamate Jyoji、Inaba Toshio、Sugiura Kikuya
  • Journal Title: PLOS ONE Volume: 12 Issue: 11 Pages: 0188738-0188738
  • DOI: 10.1371/journal.pone.0188738
  • 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] Trabectedin is a promising antitumour 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: Journal of Chemotherapy Volume: e-pub ahead of print Issue: 5 Pages: 1-8
  • DOI: 10.1080/1120009x.2015.1133013
  • Peer Reviewed
• [Journal Article] Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression (2016)
  • Author(s): Hiroki Fukuda, Seikou Nakamura, Yugo Chisaki, Tetsuya Takada, Yuki Toda, Hiroaki Murata, Kazuyuki Itoh, Yoshitaka Yano, Kazuyuki Takata, Eishi Ashihara
  • Journal Title: Biochem Biophys Res Commun Volume: 471 Issue: 1 Pages: 63-67
  • DOI: 10.1016/j.bbrc.2016.01.179
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ephedrae herba stimulates hepatocyte growth factor-induced MET endocytosis and downregulation via early/late endocytic pathways in gefitinib-resistant human lung cancer cells (2016)
  • Author(s): Nishimura, Y., Hyuga, S., Takiguchi, S., Hyuga, M., Itoh, K., Hanawa, T.
  • Journal Title: International Journal of Oncology Volume: 48(5) Issue: 5 Pages: 1895-1906
  • DOI: 10.3892/ijo.2016.3426
  • 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
• [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、伊村慶紀、中井翔、安田直弘、山田修太郎、金子恵子、王谷英達、竹中聡、濱田健一郎、名井陽、荒木信人、上田孝文、伊藤和幸、吉川秀樹、中紀文
  • Organizer: 第50回骨軟部腫瘍学術集会
• [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、中井隆彰、安田直弘、山田修太郎、金子恵子、竹中聡、濱田健一郎、名井陽、荒木信人、上田孝文、伊藤和幸、吉川秀樹、中紀文
  • Organizer: 第50回骨軟部腫瘍学術集会
• [Presentation] アンドロゲンとビタミンD3による前立腺癌の細胞増殖調節 (2016)
  • Author(s): 五十嵐晃、渡邉健太、由井理洋、笹川覚、平田美智子、稲田全規、宮浦千里、伊藤和幸
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] NET過剰発現非小細胞肺がんの増殖に対する麻黄及びエルロチニブの併用効果 (2016)
  • Author(s): 日向須美子、日向昌司、西村行生、伊藤和幸、小田口浩、花輪壽彦
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] 骨軟部腫瘍におけるTwist1による転移能調節 (2016)
  • Author(s): 笹川覚、由井理洋、中川秀光、伊藤和幸
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] TAS-115は単剤で、c-METまたはPDGFRαシグナルに依存した複数の滑膜肉腫細胞株に対し抗腫瘍効果を発揮する (2016)
  • Author(s): 山田修太郎、井村慶紀、中井隆彰、王谷英達、金子恵子、竹中聡、濱田健一郎、名井陽、荒木信人、上田孝文、伊藤和幸、吉川秀樹、中紀文
  • Organizer: 第49回骨・軟部腫瘍学術集会
  • Place of Presentation: 東京ドームホテル
  • Year and Date: 2016-07-14
• [Presentation] 滑膜肉腫細胞株におけるTAS-115の抗腫瘍効果：TAS-115はMET signalのみならずPDGFRα signalも抑制する (2015)
  • Author(s): 山田修太郎、伊村慶紀、中井隆彰、金子恵子、荒木信人、伊藤和幸、吉川秀樹、中紀文
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 滑膜肉腫に対する選択的c-MET阻害剤(INC280)の感受性を予知するバイオマーカーの探索 (2015)
  • Author(s): 伊村慶紀、中井隆彰、山田修太郎、王谷英達、濱田健一郎、金子恵子、名井陽、荒木信人、伊藤和幸、吉川秀樹、中紀文
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 新規マウス軟部肉腫高肺転移株樹立の試み (2015)
  • Author(s): 金子恵子、中紀文、伊村慶紀、中井隆彰、山田修太郎、濱田健一郎、王谷英達、伊藤和幸、吉川秀樹
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 淡明細胞肉腫に対するtrabectedin(Yondelis; ET-743)の抗腫瘍効果 (2015)
  • Author(s): 中井隆彰、伊村慶紀、山田修太郎、金子恵子、王谷英達、濱田健一郎、名井陽、荒木信人、伊藤和幸、吉川秀樹、中紀文
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] 日本がん転移学会と共に (2015)
  • Author(s): 伊藤和幸
  • Organizer: 第24回日本がん転移学会学術集会・総会
  • Place of Presentation: シティプラザ大阪（大阪府大阪市）
  • Year and Date: 2015-07-23
• [Presentation] 滑膜肉腫におけるMETシグナルの役割とMET阻害剤に対する感受性を予知するバイオマーカーの探索 (2015)
  • Author(s): 伊村慶紀、王谷英達、中井隆彰、山田修太郎、濱田健一郎、名井陽、荒木信人、上田孝文、伊藤和幸、吉川秀樹、中紀文
  • Organizer: 第48回日本整形外科学会 骨・軟部腫瘍学術集会
  • Place of Presentation: かがわ国際会議場（香川県高松市）
  • Year and Date: 2015-07-09
• [Presentation] 淡明細胞肉腫に対するtrabectedin (Yondelis; ET-743)の有効性 (2015)
  • Author(s): 中井隆彰、伊村慶紀、山田修太郎、金子恵子、王谷英達、濱田健一郎、名井陽、荒木信人、上田孝文、伊藤和幸、吉川秀樹、中紀文
  • Organizer: 第48回日本整形外科学会 骨・軟部腫瘍学術集会
  • Place of Presentation: かがわ国際会議場（香川県高松市）
  • Year and Date: 2015-07-09
• [Presentation] 滑膜肉腫細胞株に対するTAS-115の抗腫瘍効果の検討 (2015)
  • Author(s): 山田修太郎、伊村慶紀、中井隆彰、王谷英達、濱田健一郎、名井陽、荒木信人、上田孝文、伊藤和幸、吉川秀樹、中紀文
  • Organizer: 第48回日本整形外科学会 骨・軟部腫瘍学術集会
  • Place of Presentation: かがわ国際会議場（香川県高松市）
  • Year and Date: 2015-07-09
• [Book] Osteosarcoma A Multidisciplinary Approach to Treatment (2016)
  • Author(s): Toguchida T, Itoh K, Tsukahara T, Ogura K, Nishida Y, Kaya M, Hiraga H, Kakunaga S, Matsumine A, Futani H, Kunisada T, Morii T, Araki N, Ae K, Tsuchiya H, Matsubara H, Matsumoto S, Imai R, Iwata S, Yonemoto T. 他
  • Total Pages: 270
  • Publisher: Springer