Modeling fusion gene-associated bone and soft tissue sarcoma and its application to therapies
| Project/Area Number |
26250029
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
Nakamura Takuro 公益財団法人がん研究会, がん研究所 発がん研究部, 部長 (00180373)
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| Co-Investigator(Kenkyū-buntansha) |
森 誠一 公益財団法人がん研究会, その他部局等, 研究員 (10334814)
黒田 雅彦 東京医科大学, 医学部, 教授 (80251304)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥39,910,000 (Direct Cost: ¥30,700,000、Indirect Cost: ¥9,210,000)
Fiscal Year 2016: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2015: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2014: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
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| Keywords | 発がん / 融合遺伝子 / 骨軟部肉腫 / 動物モデル / 発生母地 / 転移 / 微小環境 / 協調遺伝子 / 胞巣状軟部肉腫 / CIC-DUX4肉腫 / 滑膜肉腫 / Ewing肉腫 / 治療評価 / CIC-DUX4 / 転移機構 |
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| Outline of Final Research Achievements |
It has been challenging to create fusion gene-associated bone and soft tissue sarcoma. We have generated mouse models for Ewing sarcoma, alveolar soft part sarcoma, CIC-DUX4 sarcoma and synovial sarcoma, and established the ex vivo model system of sarcoma. These four models recapitulate phenotypes of human sarcoma in morphology, gene expression and biological characteristics. Using the models, cell-of-origin of Ewing sarcoma, molecular mechanisms of hematogenous metastasis in alveolar soft part sarcoma, novel biomarkers for CIC-DUX4 sarcoma and cooperative genes of SYT-SSX1 in synovial sarcoma development have been clarified. Therapeutic effects of inhibitors and anti-cancer drugs were evaluated in vitro and in vivo using Ewing sarcoma and CIC-DUX4 sarcoma models.
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Report
(4 results)
Research Products
(49 results)
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[Journal Article] Transposon insertional mutagenesis in mice identifies human breast cancer susceptibility genes and signatures for stratification2017
Author(s)
Chen L, Jenjaroenpun P, Pillai AM, Ivshina AV, Ow GS, Efthimios M, Zhiqun T, Tan TZ, Lee SC, Rogers K, Ward JM, Mori S, Adams DJ, Jenkins NA, Copeland NG, Ban KH, Kuznetsov VA, Thiery JP
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Journal Title
Proceedings of the National Academy of Sciences
Volume: 114
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Combined experience of six independent laboratories attempting to create an Ewing sarcoma mouse model2016
Author(s)
Minas TZ, Surdez D, Tahereh J, Tanak M, Howarth M, Kang HJ, Han J, Han ZY, Sax B, Kream BE, Hong SH, Tirode F, Tuckermann J, Toretsky JA, Kenner L, Kovar H, Lee S, Sweet-Cordero A, Nakamura T, Moriggi R, Delattre O, Uren A
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Journal Title
Oncotarget
Volume: May 15
Pages: 15-15
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Development of novel small hairpin RNAs that do not require processing by dicer or AGO22016
Author(s)
Ohno S, Itano K, Harada Y, Asada K, Oikawa K, Kashiwazako M, Okuyama H, Kumagai K, Takanashi M, Sudo K, Ikeda N, Kuroda M.
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Journal Title
Molecular Therapy
Volume: 24
Pages: 1278-1289
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Topical Use of Angiopoietin-like Protein 2 RNAi-loaded Lipid Nanoparticles Suppresses Corneal Neovascularization.2016
Author(s)
Taketani Y, Usui T, Toyono T, Shima N, Yokoo S, Kimakura M, Yamagami S, Ohno S, Onodera R, Tahara K, Takeuchi H, Kuroda M.
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Journal Title
Mol Ther Nucleic Acids
Volume: 5
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Meis1 regulates epidermal stem cells and is required for skin tumorigenesis2014
Author(s)
Okumura K, Saito M, Isogai E, Aoto Y, Hachiya T, Sakakibara Y, Katsuragi Y, Hirose S, Kominami R, Goitsuka R, Nakamura T and Wakabayashi Y.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access
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