Novel immunological tolerance in zebrafish of human cancer cell xenotransplants and cancer immunotherapy mechanisms
| Project/Area Number |
25670127
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General pharmacology
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| Research Institution | Mie University |
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Principal Investigator |
TANAKA TOSHIO 三重大学, 医学(系)研究科(研究院), 教授 (00135443)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Yuhei 三重大学, 大学院医学系研究科・薬理ゲノミクス, 准教授 (30303720)
SHIMADA Yasuhito 三重大学, 大学院医学系研究科・薬理ゲノミクス, 助教 (40378427)
UMRMOTO Noriko 三重大学, 大学院医学系研究科・薬理ゲノミクス, 助教 (40649365)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | Zebrafish / cance / xenotransplantation / immunological tolerance / RNA-seq / システムズ薬理学 / 悪性腫瘍免疫寛容 / ヒト慢性骨髄性白血病細胞 / ヒト前立腺癌細胞 / トランスクリプトーム解析 / 免疫機構 / 異種細胞免疫寛容機構 / 免疫寛容関連遺伝子 |
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| Outline of Final Research Achievements |
Immune suppression in host animals is an essential precondition for xenograft success because the host immune system has a tendency to reject implanted cancer cells. We developed a novel zebrafish model based on two-round cancer cell xenotransplantation that achieved cancer-specific immunological tolerance without immunosuppression. We irradiated human cancer cells to abolish their proliferative abilities and implanted them into young zebrafish. These cells lasted for 2 weeks. Three months after the first xenotransplantation, the same zebrafish were implanted with nonirradiated cell lines. These cancer cells proliferated and exhibited metastasis without immune suppression. We conducted dual RNA-seq of the tumour with its surrounding tissues and identified several regulatory genes in zebrafish that are involved in immunity were altered with immunotolerance. In conclusion, this xenograft method has potential as a platform for anti-cancer drug discovery.
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Report
(3 results)
Research Products
(64 results)
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[Journal Article] In vivo selective imaging and inhibition of leukemia stem-like cells using the fluorescent carbocyanine derivative, DiOC5(3)2015
Author(s)
Beibei Zhang, Yasuhito Shimada, Junya Kuroyanagi, Michiko Ariyoshi, Tsuyoshi Nomoto, Taichi Shintou, Noriko Umemoto,Yuhei Nishimura, Takeshi Miyazaki, Toshio Tanaka
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Journal Title
Biomaterials
Volume: 52
Pages: 14-25
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Copper oxide nanoparticles reduce vasculogenesis in transgenic zebrafish throufg down-regulation of VEGF expression and induction of apoptosis2015
Author(s)
J. Chang, G. Ichihara, Y. Shimada, S. Tada-Oikawa, J. Kuroyanagi, B. Zhang, Y. Suzuki, R. Sehsah, M. Kato, T. Tanaka, S. Ichihara
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Journal Title
J Nanosci Nanotechnol
Volume: 15
Issue: 3
Pages: 2140-2147
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] S-nitrosylation regulates mitochondrial quality control via activation of2013
Author(s)
Ozawa K , Komatsubara AT, Nishimura Y, Sawada T, Kawafune H, Tsumoto H, Tsuji Y, Zhao J, Kyotani Y, Tanaka T, Takahashi R, Yoshizumi M
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Journal Title
Scientific Reports
Volume: 3: 2202
Issue: 1
Pages: 1-10
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of a novel indoline derivative for in vivo fluorescent imaging of blood-brain barrier disruption in animal models.2013
Author(s)
Nishimura Y, Yata K, Nomoto T, Ogiwara T, Watanabe K, Shintou T, Tsuboyama A, Okano M, Umemoto N, Zhang Z, Kawabata M, Zhang B, Kuroyanagi J, Shimada Y, Miyazaki T, Imamura T, Tomimoto H, Tanaka T.
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Journal Title
ACS Chem Neurosci.
Volume: 4
Issue: 8
Pages: 1183-1193
DOI
Related Report
Peer Reviewed
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[Journal Article] Fluorescent-Based Methods for Gene Knockdown and Functional Cardiac Imaging in Zebrafish.2013
Author(s)
Umemoto N, Nishimura Y, Shimada Y, Yamanaka Y, Kishi S, Ito S, Okamori K, Nakamura Y, Kuroyanagi J, Zhang Z, Zang L, Wang Z, Nishimura N, Tanaka T.
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Journal Title
Molecular Biotechnology
Volume: 55
Issue: 2
Pages: 131-142
DOI
Related Report
Peer Reviewed
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[Presentation] 希少疾患と創薬
Author(s)
田中利男
Organizer
ゲノム創薬フォーラム第33回談話会
Place of Presentation
東大医科研講堂
Related Report
Invited
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[Patent(Industrial Property Rights)] がん細胞阻害薬、がん幹細胞検出用プローブ2013
Inventor(s)
田中利男,島田康人,西村有平,新藤太一,渡邉耕平,野本毅
Industrial Property Rights Holder
田中利男,島田康人,西村有平,新藤太一,渡邉耕平,野本毅
Industrial Property Rights Type
特許
Filing Date
2013-10-25
Related Report
