Establish the diagnostic system for amyloidosis using modified proteomic method.

• Project/Area Number: 26860372
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Kumamoto University
• Principal Investigator: Tasaki Masayoshi 熊本大学, 大学院生命科学研究部(保), 助教 (50613402)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: アミロイドーシス / 質量分析 / 診断 / 組織診断 / プロテオミクス / 質量分析装置

Outline of Final Research Achievements

There are 36 kinds of amyloid precursor proteins that make amyloid　fibrils. Amyloidosis is classified as each disease according to type of amyloid precursor protein, and the treatment is different. For this reason, it is extremely important to accurately identify the amyloid precursor protein for typing of amyloidosis. In this study, we developed a new extraction method for amyloid and establish a system that can accurately identify amyloid precursor protein. In addition, we tried to pick up candidates as prognostic markers using mass spectrometry for AL amyloidosis.
It revealed that the analytical method using proteinase K increased the detection rate of amyloid precursor protein. In AL amyloidosis, many type of peptides derived from L chain could be detected by using mass spectrometry. In addition, candidate peptides may become a prognostic marker for AL amyloidosis.

Research Products

• [Journal Article] Clinicopathological and biochemical findings of thyroid amyloid in hereditary transthyretin amyloidosis with and without liver transplantation. (2017)
  • Author(s): Huang G, Ueda M, Tasaki M, Yamashita T, Misumi Y, Masuda T, Suenaga G, Inoue Y, Kinoshita Y, Matsumoto S, Mizukami M, Tsuda Y, Nomura T, Obayashi K, Ando Y
  • Journal Title: Amyloid Volume: 印刷中 Issue: 1 Pages: 1-6
  • DOI: 10.1080/13506129.2016.1276440
  • Peer Reviewed
• [Journal Article] Novel screening for transthyretin amyloidosis by using fat ultrasonography. (2017)
  • Author(s): Misumi Y, Ueda M, Yamashita T, Masuda T, Kinoshita Y, Tasaki M, Nagase T, Ando Y
  • Journal Title: Ann Neurol Volume: 印刷中 Issue: 4 Pages: 604-608
  • DOI: 10.1002/ana.24914
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Early skin denervation in hereditary and iatrogenic transthyretin amyloid neuropathy. (2017)
  • Author(s): Masuda T, Ueda M, Suenaga G, Misumi Y, Tasaki M, Izaki A, Yanagisawa Y, Inoue Y, Motokawa H, Matsumoto S, Mizukami M, Arimura A, Deguchi T, Nishio Y, Yamashita T, Inomata Y, Obayashi K, Ando Y.
  • Journal Title: Neurology Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Identification of amyloid precursor protein from autopsy and biopsy specimens using LMD-LC-MS/MS: the experience in Kumamoto University. (2017)
  • Author(s): Tasaki M, Ueda M, Obayashi K, Kinoshita Y, Matsumoto S, Mizukami M, Masuda T, Misumi Y, Yamashita T, Ando Y.
  • Journal Title: Amyloid Volume: 印刷中
• [Journal Article] ALアミロイドーシスにおける質量分析を用いた沈着ペプチド解析 (2017)
  • Author(s): 杉本俊哉、田崎雅義、山下太郎、植田光晴、安東由喜雄、大林光念、奥野豊、畑 裕之
  • Journal Title: 臨床血液 Volume: 印刷中
  • NAID: 130005709603
  • Peer Reviewed
• [Journal Article] Hereditary amyloidosis with cardiomyopathy caused by the novel variant transthyretin A36D. (2016)
  • Author(s): Yamashita T, Ueda M, Saga N, Nanto K, Tasaki M, Masuda T, Misumi Y, Oda S, Fujimoto A, Amano T, Takamatsu K, Yamashita S, Obayashi K, Matsui H, Ando Y.
  • Journal Title: Amyloid Volume: 23 Pages: 207-208
  • Peer Reviewed
• [Journal Article] Transthyretin-related familial amyloidotic polyneuropathy found with abnormal urinalysis at a general health checkup. (2016)
  • Author(s): Yoshimura Y, Kuwabara T, Shiraishi N, Kakizoe Y, Tasaki M, Obayashi K, Ando Y, Mukoyama M.
  • Journal Title: Nephrology Volume: 21 Issue: 4 Pages: 341-2
  • DOI: 10.1111/nep.12610
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Knee osteoarthritis associated with different kinds of amyloid deposits and the impact of aging on type of amyloid. (2016)
  • Author(s): Yanagisawa A, Ueda M, Sueyoshi T, Nakamura E, Tasaki M, Suenaga G, Motokawa H, Toyoshima R, Kinoshita Y, Misumi Y, Yamashita T, Sakaguchi M, Westermark P, Mizuta H, Ando Y.
  • Journal Title: Amyloid Volume: 23 Issue: 1 Pages: 26-32
  • DOI: 10.3109/13506129.2015.1115758
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] アミロイドーシスのプロテオーム診断 (2016)
  • Author(s): 田崎雅義
  • Journal Title: 病理と臨床 Volume: 34 Pages: 486-90
• [Journal Article] Rapid detection of wild-type and mutated transthyretins. (2015)
  • Author(s): Tasaki M, Ueda M, Obayashi K, Motokawa H, Kinoshita Y, Suenaga G, Yanagisawa A, Toyoshima R, Misumi Y, Masuda T, Yamashita T, Ando Y.
  • Journal Title: Annals of Clinical Biochemistry Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] プロテオミクスを利用した臨床検査：アミロイドーシス診断におけるプロテオーム解析法の有用性 (2015)
  • Author(s): 田崎雅義、大林光念、安東由喜雄
  • Journal Title: 臨床病理 Volume: 63 Pages: 980-5
• [Journal Article] Inhibition of insulin amyloid fibril formation by cyclodextrins. (2015)
  • Author(s): Kitagawa K, Misumi Y, Ueda M, Hayashi Y, Tasaki M, Obayashi K, Yamashita T, Jono H, Arima H, Ando Y.
  • Journal Title: Amyloid Volume: 22 Issue: 3 Pages: 181-186
  • DOI: 10.3109/13506129.2015.1064818
  • Peer Reviewed
• [Journal Article] Clinico-histopathological and biochemical analyses of corneal amyloidosis in gelatinous drop-like corneal dystrophy. (2015)
  • Author(s): Tasaki M, Ueda M, Matsumoto K, Kawaji T, Misumi Y, Eiki D, Suenaga G, Obayashi K, Yamashita T, Tanihara H, Ando Y.
  • Journal Title: Amyloid Volume: 22 Issue: 1 Pages: 67-69
  • DOI: 10.3109/13506129.2014.983222
  • Peer Reviewed
• [Journal Article] Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis. (2015)
  • Author(s): Yanagisawa A, Ueda M, Sueyoshi T, Okada T, Fujimoto T, Ogi Y, Kitagawa K, Tasaki M, Misumi Y, Oshima T, Jono H, Obayashi K, Hirakawa K, Uchida H, Westermark P, Ando Y, Mizuta H.
  • Journal Title: Mod Pathol Volume: 28 Issue: 2 Pages: 201-207
  • DOI: 10.1038/modpathol.2014.102
  • Peer Reviewed
• [Journal Article] Shikonin, dually functions as a proteasome inhibitor and a necroptosis inducer in multiple myeloma cells. (2015)
  • Author(s): Wada N, Kawano Y, Fujiwara S, Kikukawa Y, Okuno Y, Tasaki M, Ueda M, Ando Y, Yoshinaga K, Ri M, Iida S, Nakashima T, Shiotsu Y, Mitsuya H, Hata H.
  • Journal Title: International Journal of Oncology Volume: 46 Issue: 3 Pages: 963-972
  • DOI: 10.3892/ijo.2014.2804
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Myopathic phenotype of familial amyloid polyneuropathy with a rare transthyretin variant: ATTR Ala45Asp. (2014)
  • Author(s): Misumi Y, Doki T, Ueda M, Obayashi K, Tasaki M, Tamura A, Ando Y.
  • Journal Title: Amyloid Volume: 21 Issue: 3 Pages: 216-217
  • DOI: 10.3109/13506129.2014.932277
  • Peer Reviewed
• [Journal Article] パラフィン包埋ホルマリン固定組織切片を利用したLMD-LC-MS/MSシステムによる新たなアミロイドーシス診断法の構築 (2014)
  • Author(s): 田崎雅義、大林光念、植田光晴、安東由喜雄
  • Journal Title: 臨床病理 Volume: 62 Pages: 291-6
• [Journal Article] A patient with medulloblastoma in its early developmental stage. (2014)
  • Author(s): Shinojima N, Nakamura H, Tasaki M, Kameno K, Anai S, Iyama K, Ando Y, Seto H, Kuratsu J.
  • Journal Title: J Neurosurg Pediatr Volume: 14(6) Issue: 6 Pages: 615-20
  • DOI: 10.3171/2014.8.peds13590
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Concomitant accumulation of α-synuclein and TDP-43 in a patient with corticobasal degeneration. (2014)
  • Author(s): Yamashita S, Sakashita N, Yamashita T, Tawara N, Tasaki M, Kawakami K, Komohara Y, Fujiwara Y, Kamikawa M, Nakagawa T, Hirano T, Maeda Y, Hasegawa M, Takeya M, Ando Y
  • Journal Title: Journal of Neurology Volume: 261 Issue: 11 Pages: 2209-2217
  • DOI: 10.1007/s00415-014-7491-8
  • Peer Reviewed / Open Access
• [Journal Article] Hypoxia suppresses cylindromatosis (CYLD) expression to promote inflammation in glioblastoma: possible link to acquired resistance to anti-VEGF therapy. (2014)
  • Author(s): Guo J, Shinriki S, Su Y, Nakamura T, Hayashi M, Tsuda Y, Murakami Y, Tasaki M, Hide T, Takezaki T, Kuratsu J, Yamashita S, Ueda M, Li JD, Ando Y, Jono H.
  • Journal Title: Oncotarget Volume: 5 Pages: 6353-64
  • Peer Reviewed / Open Access
• [Presentation] MALDI-TOF MSを用いた簡便かつ迅速な血清異型TTR検出法の開発 (2017)
  • Author(s): 田崎雅義、大林光念、植田光晴、野村隼也、松本紗也加、水上真由美、山下太郎、安東由喜雄
  • Organizer: 第27回生物試料分析科学会年次学術集会
  • Place of Presentation: 朱鷺メッセ（新潟県、新潟市）
  • Year and Date: 2017-02-11
• [Presentation] 疾患特異的蛋白質を如何に同定し、診断および病態解析に繋げるか～臨床プロテオーム解析により試み～ (2016)
  • Author(s): 田崎雅義、大林光念、安東由喜雄
  • Organizer: 第56回日本臨床化学会年次学術集会
  • Place of Presentation: 熊本県民交流会館パレア（熊本県、熊本市）
  • Year and Date: 2016-12-02
• [Presentation] 質量分析法の基礎と応用、レーザーマイクロダイセクションを組み合わせた組織検査について (2016)
  • Author(s): 田崎雅義、大林光念、安東由喜雄
  • Organizer: 第65回日本医学検査学会
  • Place of Presentation: 神戸ポートピアホテル、神戸国際会議場（兵庫県、神戸市）
  • Year and Date: 2016-09-03
• [Presentation] Development of detection method for serum variant transthyretins using MALDI-TOF mass spectrometry (2016)
  • Author(s): Tasaki M, Ueda M, Obayashi K, Yamashita T, Ando Y.
  • Organizer: The 32nd World Congress of Biomedical laboratory Science
  • Place of Presentation: Kobe International conference center (Japan, Kobe)
  • Year and Date: 2016-08-31
  • Int'l Joint Research
• [Presentation] Identification of amyloid precursor protein from autopsy and biopsy specimens using LMD-LC-MS/MS: the experience in Kumamoto University. (2016)
  • Author(s): Tasaki M, Ueda M, Obayashi K, Kinoshita Y, Matsumoto S, Mizukami M, Masuda T, Misumi Y, Yamashita T, Ando Y.
  • Organizer: XV International Symposium on Amyloidosis
  • Place of Presentation: Uppsala Consert and Congress (Sweden, Uppsala)
  • Year and Date: 2016-07-03
  • Int'l Joint Research
• [Presentation] 新規アミロイドーシスの組織学的、生化学的解析 (2016)
  • Author(s): 田崎雅義、植田光晴、星井嘉信、大林光念、木下祐美子、水上真由美、松本紗也加、三隅洋平、山下太郎、安東由喜雄
  • Organizer: 第4回日本アミロイドーシス学会学術集会
  • Place of Presentation: KKRホテル東京（東京都、千代田区）
• [Presentation] 質量分析法を用いたアミロイドーシスの診断・病態解析における新展開 (2015)
  • Author(s): 田崎雅義、安東由喜雄
  • Organizer: 第62回日本臨床検査医学会学術集会
  • Place of Presentation: 長良川国際会議場（岐阜県、岐阜市）
  • Year and Date: 2015-11-19
• [Presentation] 各種プロテオーム解析技術を駆使して挑むアミロイドーシス ～病型診断から病態解析まで～ (2015)
  • Author(s): 田崎雅義、安東由喜雄
  • Organizer: 第55回日本臨床化学会年次学術集会
  • Place of Presentation: 大阪大学コンベンションセンター（大阪府、吹田市）
  • Year and Date: 2015-10-30
• [Presentation] レーザーマイクロダイセクション-LC-MS/MSシステムによる 病理組織切片を用いたアミロイド原因蛋白質の同定 (2015)
  • Author(s): 田崎雅義
  • Organizer: 第3回日本アミロイドーシス研究会学術集会
  • Place of Presentation: KKRホテル東京（東京都千代田区）
  • Year and Date: 2015-08-21
• [Presentation] プロテアーゼKを利用した質量分析装置によるアミロイドーシス診断 (2014)
  • Author(s): 田崎雅義、植田光晴、大林光念、本川拓誠、北川敬資、荻泰裕、三隅洋平、山下太郎、安東由喜雄
  • Organizer: 第61回日本臨床検査医学会学術集会
  • Place of Presentation: 福岡、福岡国際会議場
  • Year and Date: 2014-11-22 – 2014-11-25
• [Presentation] プロテオミクスを利用した臨床検査～アミロイドーシス診療体制構築事業におけるプロテオミクスの貢献～ (2014)
  • Author(s): 田崎雅義、安東由喜雄
  • Organizer: 第61回日本臨床検査医学会学術集会
  • Place of Presentation: 福岡、福岡国際会議場
  • Year and Date: 2014-11-22 – 2014-11-25
• [Presentation] アミロイドーシス診断事業の2年間の取り組み:血清、組織プロテオミクス解析を駆使した診断システムの貢献度 (2014)
  • Author(s): 田崎雅義、大林光念、植田光晴、荻泰裕、北川敬資、久原春代、大隈雅紀、池田勝義、安東由喜雄
  • Organizer: 第54回日本臨床化学会年次学術集会
  • Place of Presentation: 東京、東京大学本郷キャンパス
  • Year and Date: 2014-09-05 – 2014-09-07
• [Presentation] Aging accelerates wild-type transthyretin amyloid deposits in cardiac tissues of male FAP patients (2014)
  • Author(s): Masayoshi Tasak, Mitsuharu Ueda, Konen Obayashi, Haruki Koike, Yasuhiro Ogi, Keisuke Kitagawa, Genki Suenaga,Gen Sobue, Yukio Ando
  • Organizer: The XIVth International Symposium on Amyloidosis
  • Place of Presentation: インディアナ、アメリカ
  • Year and Date: 2014-04-27 – 2014-05-01