Effect of heme oxygenase-1 on treatment results after hematopoietic stem cell transplantation and new therapeutic strategies
| Project/Area Number |
18K07442
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52010:General internal medicine-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
谷内江 昭宏 金沢大学, 附属病院, 特任教授 (40210281)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | HO-1 / 同種造血幹細胞移植 / 移植片対宿主病 / 血栓性微小血管障害症 / 一塩基多型（SNP) / ADAMTS-13 / UNC-93 homolog B1 / 造血幹細胞移植後転帰 / 3年全生存率 / 自然免疫 / 5年全生存率 / 造血幹細胞移植 / ADAMTS13 / 一塩基置換 / 移植片対宿主病(GVHD) / ヘムオキシゲナーゼ-1 / 遺伝子一塩基多型 / 血液凝固異常 |
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| Outline of Final Research Achievements |
Life-threatening complications associated with allogeneic hematopoietic stem cell transplantation (SCT),such as severe infection, graft-versus-host disease (GVHD), and thrombotic microangiopathy, remain obstacles to overcome. We investigated the influence of the HO-1 single-nucleotide polymorphism (SNP) rs2071746 (-413A>T), ADAMTS-13 SNP rs2285489 (C>T), UNC-93 homolog B1 SNP rs308328 (T>C) on transplant outcomes in a cohort of about 600 patients undergoing unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program.
As a result, the donor HO-1 A/A or A/T genotype and donor UNC93B1 C/C genotype were associated with a better overall survival. On the other hand, the recipient ADAMTS13 C/C genotype was associated with an increased relapse rate, resulting in a lower disease-free survival rate in the patients with a recipient C/C genotype.
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| Academic Significance and Societal Importance of the Research Achievements |
同種造血幹細胞移植(SCT)は、造血器悪性腫瘍を完治する治療法として期待されているが、重症感染症や移植片対宿主病、血栓性微小血管障害症などの移植後合併症はいまだ致死率も高い。これらの病態には免疫応答や血液凝固系の関与が考えられており、今回の検討でも免疫調節性あるいは抗血栓性非HLA遺伝子多型が移植後転帰に影響を与えることが明らかになってきた。したがって、これらの因子の遺伝子型の分析は、ドナーの選択、予後の推定、および同種SCT後の治療戦略の作成に役立つ可能性が示された。
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Report
(4 results)
Research Products
(60 results)
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[Journal Article] Donor UNC-93 Homolog B1 genetic polymorphism predicts survival outcomes after unrelated bone marrow transplantation.2021
Author(s)
Uchino K, Vu Quang L, Mizuno S, Horio T, Yamamoto H, Hanamura I, Kodera Y, Luis Espinoza J, Onizuka M, Kashiwase K, Morishima Y, Fukuda T, Doki N, Miyamura K, Mori T, Morishita E, Nakao S, Takami A
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Journal Title
Genes and Immunity
Volume: 24
Issue: 1
Pages: 1-9
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Comparative evaluation of reagents for measuring protein S activity: possibility of harmonization2021
Author(s)
Ieko M, Hotta T, Watanabe K, Adachi T, Takeuchi S, Naito S, Yoshida M, Ohmura K, Takahashi N, Morishita E, Tsuda H, Kang D
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Journal Title
Int J Hematol.
Volume: 113
Issue: 4
Pages: 530-536
DOI
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Peer Reviewed / Open Access
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[Journal Article] Molecular genetic analysis of inherited protein C deficiency caused by the novel large deletion across two exons of PROC2020
Author(s)
Togashi T, Meguro-Horike M, Nagaya S, Sugihara S, Ichinohe T, Araiso Y, Yamaguchi K, Mori K, Imai Y, Kuzasa K, Horike SI, Asakura H, Watanabe A, Morishita E.
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Journal Title
Thromb Res
Volume: -
Pages: 115-118
DOI
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Peer Reviewed / Open Access
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[Journal Article] Genetic analysis of a compound heterozygous patient with congenital factor X deficiency and regular replacement therapy with a prothrombin complex concentrate2020
Author(s)
6)Togashi T, Nagaya S, Nagasawa M, Meguro-Horike M, Nogami K, Imai Y, Kuzasa K, Sekiya A, Horike SI, Asakura H, Morishita E
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Journal Title
Int J Hematol
Volume: 111
Issue: 1
Pages: 51-56
DOI
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Peer Reviewed / Open Access
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[Journal Article] Recipient ADAMTS13 Single-Nucleotide Polymorphism Predicts Relapse after Unrelated Bone Marrow Transplantation for Hematologic Malignancy.2019
Author(s)
Nomoto H, Takami A, Espinoza JL, Onizuka M, Kashiwase K, Morishima Y, Fukuda T, Kodera Y, Doki N, Miyamura K, Mori T, Nakao S, Morishita E
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Journal Title
Int J Mol Sci
Volume: Jan 8;20(1)
Issue: 1
Pages: 214-214
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Potential therapeutics for antiphospholipid antibody associated thrombocytopenia: a systematic review and meta-analysis.2018
Author(s)
Abe N, Oku K, Amengual O, Fujieda Y, Kato M, Bohgaki T, Yasuda S, Mori R, Morishita E, Suzuki-Inoue K, Atsumi T.
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Journal Title
Mod Rheumatol
Volume: Dec 17
Issue: 1
Pages: 1-21
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 性腺モザイクが原因と考えられる遺伝性プロテインS欠乏症の一家系2020
Author(s)
森下 英理子, 森 広太朗, 丸山 慶子, 小亀 浩一, 長屋 聡美, 今井 湧太, 冨樫 朋貴, 大森 健聖, 牧田 友香, 山口 浩一, 目黒 牧子, 廣島 美紀, 堀家 慎一, 朝倉 英策, 渡邉 淳
Organizer
第42回日本血栓止血学会学術集会
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