Investigation of eculizumab therapeutic response to patients with PNH
Project/Area Number |
26461447
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Osaka University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
金倉 譲 大阪大学, 医学系研究科, 教授 (20177489)
柴山 浩彦 大阪大学, 医学系研究科, 講師 (60346202)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | 発作性夜間ヘモグロビン尿症 / 溶血 / エクリズマブ / 補体 / 遺伝子多型 |
Outline of Final Research Achievements |
Approximately 550 patients in Japan with PNH were treated with eculizumab and about 3.5% of patients were found to be refractory by C5 gene polymorphism due to heterozygous base substitution (c.2654G>A, p.Arg885His). Similar polymorphisms were identified in Argentinian patient (c.2653C>T, p.Arg885Cys) and Dutch patient (c.2653C>A, p.Arg885Ser). Functional analysis proved that eculizumab could not bind to C5 due to these polymorphisms and hemolysis could not be suppressed. Thus, we have constructed and operated a system for analysis of eculizumab inadequacy.
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Report
(4 results)
Research Products
(57 results)
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[Journal Article] Interim analysis of post-marketing surveillance of eculizumab for paroxysmal nocturnal hemoglobinuria in Japan.2016
Author(s)
Ninomiya H, Obara N, Chiba S, Usuki K, Nishiwaki K, Matsumura I, Shichishima T, Okamoto S, Nishimura JI, Ohyashiki K, Nakao S, Ando K, Kanda Y, Kawaguchi T, Nakakuma H, Harada D, Akiyama H, Kinoshita T, Ozawa K, Omine M, Kanakura Y.
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Journal Title
Int J Hematol
Volume: 104
Pages: 548-558
Related Report
Peer Reviewed / Open Access
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[Journal Article] Pregnancy outcomes of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab: a Japanese experience and updated review.2016
Author(s)
Miyasaka N, Miura O, Kawaguchi T, Arima N, Morishita E, Usuki K, Morita Y, Nishiwaki K, Ninomiya H, Gotoh A, Imashuku S, Urabe A, Shichishima T, Nishimura JI, Kanakura Y.
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Journal Title
Int J Hematol.
Volume: Epub ahead of print
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] The First Follow-up Data Analysis of Patients with Acquired Bone Marrow Failure Harboring a Small Population of PNH-Type Cells in the Japanese, Multicenter, Prospective Study Optima2016
Author(s)
Ueda Y, Nishimura J, Sugimori C, Hosokawa K, Yonemura Y, Obara1 N, Noji H, Nakamura Y, Shirasugi Y, Ando K, Shichishima T, Ninomiya H, Chiba1 S, Kawaguchi T, Kanakura Y, Nakao S
Organizer
The American Society of Hematology 58th Annual Meeting
Place of Presentation
San Diego Convention Center, San Diego, USA
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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[Presentation] Paroxysmal Nocturnal Hemoglobinuria Caused By Pigt Mutations; Atypical PNH2016
Author(s)
Murakami Y, Kawamoto M, Inoue N, Osato M, Murata S, Murase S, Yoshimura H, Ueda Y, Nishimura J, Kanakura Y, Kohara N, Kinoshita T
Organizer
The American Society of Hematology 58th Annual Meeting
Place of Presentation
San Diego Convention Center, San Diego, USA
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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[Presentation] A Clinical Significance and Time-Dependent Change of Pnh Clone Size in Patients with Bone Barrow Failure Syndrome: Japanese Multi-Centre Prospective Study2016
Author(s)
Shirasugi Y, Sugimori C, Noji H, Shichishima T, Obara1 N, Chiba1 S, Ninomiya H, Nakamura Y, Ando K, Yonemura Y, Kawaguchi T, Hosokawa K, Ueda Y, Nishimura J, Kanakura Y, Nakao S
Organizer
21st Congress of the European Hematology Association
Place of Presentation
Bella Center, Copenhagen, Denmark
Year and Date
2016-06-09
Related Report
Int'l Joint Research
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[Presentation] C5 Polymorphism in a Dutch Patient with Paroxysmal Nocturnal Hemoglobinuria (PNH) and No Asian Ancestry, Resistant to Eculizumab, but in Vitro Sensitive to Coversin2015
Author(s)
Langemeijer S, Nishimura J, Weston-Davies W, Nunn MA, Kanakura Y, Mackie IJ, Muus P
Organizer
The American Society of Hematology 57th Annual Meeting
Place of Presentation
Orlando, FL, USA
Year and Date
2015-12-05
Related Report
Int'l Joint Research
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[Presentation] Clinical features and QOL evaluation of Japanese PNH patients in the International PNH Registry2015
Author(s)
Sakurai M, Okamoto S, Usuki K, Nishimura J, Kawaguchi T, Ninomiya H, Shichishima T, Okada M, Nakakuma H, Nakao S, Kanakura Y
Organizer
第77回日本血液学会学術集会
Place of Presentation
ホテル日航金沢(石川県金沢市)
Year and Date
2015-10-16
Related Report
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[Presentation] Analysis of the data from the 4th year post marketing surveillance (PMS) of eculizumab2015
Author(s)
Ninomiya H, Obara1 N, Chiba1 S, Usuki K, Nishiwaki K, Matsumura I, Shichishima T, Okamoto S, Nishimura J, Ohyashiki K, Nakao S, Ando K, Kawaguchi T, Nakakuma H, Hamada Y, Shimono A, Kinoshita T, OzawaK, Omine M, Kanakura Y
Organizer
第77回日本血液学会学術集会
Place of Presentation
ホテル日航金沢(石川県金沢市)
Year and Date
2015-10-16
Related Report
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[Presentation] The interim analysis of prospective observational study with PNH-type cells in Japanese patients with bone marrow failure (The OPTIMA study : Observation of PNH-type cells in Japanese patients with bone marrow failure syndrome and in those suspected of having PNH study).2015
Author(s)
Obara1 N, Chiba1 S, Hosokawa K, Sugimori C, Yamamoto M, Noji H, Yonemura Y, Nakamura Y, Ando K, Kawaguchi T, Shichishima T, Ninomiya H, Nishimura J, Kanakura Y, Nakao S
Organizer
20th Congress of the European Hematology Association
Place of Presentation
Vienna, Austria
Year and Date
2015-06-11
Related Report
Int'l Joint Research
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[Presentation] The Interim Analysis of the OPTIMA (Observation of GPI-Anchored Protein-Deficient [PNH-type] Cells in Japanese Patients with Bone Marrow Failure Syndrome and in Those Suspected of Having PNH).2015
Author(s)
Sugimori C, Noji H, Shichishima T, Obara1 N, Chiba1 S, Ninomiya H, Nakamura Y, Ando K, Hosokawa K, Yamamoto M, Yonemura Y, Kawaguchi T, Nishimura J, Kanakura Y, Nakao S
Organizer
The 6th JSH international symposium 2015
Place of Presentation
軽井沢プリンスホテル(長野県北佐久郡)
Year and Date
2015-05-22
Related Report
Int'l Joint Research
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[Book] 貧血学2017
Author(s)
西村純一
Total Pages
644
Publisher
日本臨床社
Related Report
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