Development of a novel treatment strategy to protect vascular endothelial cells with TM mutant
Project/Area Number |
18H02844
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
|
Research Institution | Fukushima Medical University |
Principal Investigator |
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2020: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
|
Keywords | トロンボモジュリン / 血管内皮細胞 / thrombomodulin / SOS / transplantation |
Outline of Final Research Achievements |
Thrombomodulin is a glycoprotein comprising several distinct structures and is mainly expressed on endothelial cell surfaces. TM negatively regulates the coagulation system and human recombinant TM consisting of an extracellular domain of TM is approved in Japan for treatment of patients with disseminated intravascular coagulation. We had recognized that rTM possesses vascular endothelial cytoprotective effects and initiated the experiments to explore the molecular mechanism by which rTM exerts cytoprotective effects and attempted to identify the minimal region of TM that produces cytoprotective function. We found that 19 amino acid structure within epidermal growth factor-like region of TM possesses angiogenic and cytoprotective function.
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Academic Significance and Societal Importance of the Research Achievements |
造血細胞移植は白血病をはじめ難治性血液がんに根治をもたらし得る画期的な治療法であるが、血管内皮細胞障害に起因する血栓性微小血管症や肝類洞閉塞症候群などによる非再発死亡が多く、その治療成績は未だ満足できるものではない。今回我々が見出した19アミノ酸を使用することで血管内皮細胞障害に起因する移植関連合併症を予防でき、移植成績の向上が期待できる。
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Report
(4 results)
Research Products
(39 results)
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[Journal Article] Aurka deficiency in the intestinal epithelium promotes age-induced obesity via propionate-mediated AKT activation.2021
Author(s)
Sun N, Meng F, Zhao J, Li X, Li R, Han J, Chen X, Cheng W, Yang X, Kou Y, Zheng K, Yang J, Ikezoe T.
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Journal Title
Int J Biol Sci.
Volume: 17
Issue: 5
Pages: 1302-14
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[Journal Article] Myeloproliferative neoplasm-driving Calr frameshift promotes the development of pulmonary hypertension in mice.2021
Author(s)
Minakawa K, Yokokawa T, Ueda K, Nakajima O, Misaka T, Kimishima Y, Wada K, Tomita Y, Miura S, Sato Y, Mimura K, Sugimoto K, Nakazato K, Nollet KE, Ogawa K, Ikezoe T, Hashimoto Y, Takeishi Y, Ikeda K.
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Journal Title
J Hematol Oncol.
Volume: 14
Issue: 1
Pages: 52-52
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[Journal Article] Aurka loss in CD19+ B cells promotes megakaryocytopoiesis via IL-6/STAT3 signaling-mediated thrombopoietin production.2021
Author(s)
Chen X, Wang C, Sun N, Pan S, Li R, Li X, Zhao J, Tong H, Tang Y, Han J, Qiao J, Qiu H, Wang H, Yang J, Ikezoe T.
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Journal Title
Theranostics.
Volume: 11
Issue: 10
Pages: 4655-71
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[Journal Article] Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells2021
Author(s)
Yusuke Azami, Naohiro Tsuyama, Yu Abe, Misaki Sugai-Takahashi, Ken-Ichi Kudo, Akinobu Ota, Karnan Sivasundaram , Moe Muramatsu, Tomonari Shigemura, Megumi Sasatani, Yuko Hashimoto, Shigehira Saji, Kenji Kamiya, Ichiro Hanamura, Takayuki Ikezoe, Masafumi Onodera, Akira Sakai.
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Journal Title
Sci Rep
Volume: 11
Issue: 1
Pages: 5216-5216
DOI
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Peer Reviewed / Open Access
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[Journal Article] Hypofibrinogenemia is associated with a high degree of risk in infectious diseases: a post-hoc analysis of post-marketing surveillance of patients with disseminated intravascular coagulation treated with thrombomodulin alfa.2021
Author(s)
Kawasugi K, Wada H, Honda G, Kawano N, Uchiyama T, Madoiwa S, Takezako N, Suzuki K, Seki Y, Ikezoe T, Iba T, Okamoto K.
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Journal Title
Thromb J.
Volume: 19
Issue: 1
Pages: 12-12
DOI
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[Journal Article] JAK2V617F Mutation Promoted IL-6 Production and Glycolysis via Mediating PKM1 Stabilization in Macrophages.2021
Author(s)
Li R, Sun N, Chen X, Li X, Zhao J, Cheng W, Hua H, Fukatsu M, Mori H, Takahashi H, Ohkawara H, Fukami M, Okamoto M, Hamazaki Y, Zheng K, Yang J, Ikezoe T.
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Journal Title
Front Immunol.
Volume: 11
Pages: 33628203-33628203
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Analysis of the Association Between Resolution of Disseminated Intravascular Coagulation (DIC) and Treatment Outcomes in Post-Marketing Surveillance of Thrombomodulin Alpha for DIC With Infectious Disease and With Hematological Malignancy by Organ Failure2020
Author(s)
Kawano N, Wada H, Uchiyama T, Kawasugi K, Madoiwa S, Takezako N, Suzuki K, Seki Y, Ikezoe T, Hattori T, Okamoto K.
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Journal Title
Thromb J.
Volume: -
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The Link Between interleukin-1β and Acute Myocardial Infarction in Chronic Myeloid Leukemia Patients Treated With Nilotinib: Cross-Sectional Study2020
Author(s)
Mori H, Sukegawa M, Fukatsu M, Sano T, Takahashi H, Harada K, Kimura S, Ohkawara H, Nakamura K, Mita M, Saito T, Hamazaki Y, Ohta M, Ikezoe T.
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Journal Title
Ann Hematol
Volume: 99
Issue: 2
Pages: 359-361
DOI
Related Report
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[Journal Article] Circulating Intranuclear Proteins May Play a Role in Development of Disseminated Intravascular Coagulation in Individuals With Acute Leukemia2020
Author(s)
Harada-Shirado K, Wang X, Mori H, Fukatsu M, Takahashi H, Shichishima-Nakamura A, Kimura S, Ohkawara H, Yamada S, Ito T, Ikezoe T.
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Journal Title
Int J Hematol.
Volume: 111
Issue: 3
Pages: 378-387
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[Journal Article] Overview2019
Author(s)
Ikezoe T
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Journal Title
Rinsho Ketsueki
Volume: 60
Issue: 6
Pages: 646-646
DOI
NAID
ISSN
0485-1439, 1882-0824
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Author(s)
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第14回 日本血栓止血学会学術標準化委員会シンポジウム
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[Presentation] 造血器腫瘍に合併するDICへの核内蛋白の関与2020
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