Biological markers of cancer-associated stroke

• Project/Area Number: 17K17907
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine; Neurosurgery
• Research Institution: Hiroshima University
• Principal Investigator: Nezu Tomohisa 広島大学, 医系科学研究科(医), 助教 (10457260)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2017: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
• Keywords: 悪性腫瘍関連脳梗塞 / バイオマーカー / トルーソー症候群 / マイクロRNA / CA-125 / 悪性腫瘍 / 脳梗塞 / バイオマーカー7

Outline of Final Research Achievements

Cancer-associated ischemic stroke are caused by a hypercoagulation disorder related to malignant tumors. Our prospective cohort study for acute ischemic stroke patients with cancer have revealed that younger age, increased quartile of CA-125 levels, increased D-dimer levels, and infarcts in multiple vascular lesions were independently associated with the cancer-associated stroke. The cancer-associated stroke patients with poor outcome (mortality or recurrence of stroke during hospital) had increased CA-125 levels compared to those without. Hence, increased CA-125 levels were useful for diagnosis of cancer-associated stroke and associated with its poor clinical outcomes. The CA-125 is a marker used to monitor patients with ovarian cancer, but could be also a mucinous serum marker expressed in patients with various types of cancer. Therefore, it might reflect to the condition of cancer-associated hypercoagulation caused to ischemic stroke.

Academic Significance and Societal Importance of the Research Achievements

悪性腫瘍関連脳梗塞は血液凝固異常を背景とした血栓症であり短期的に再発を繰り返し、治療に難渋することが多い。悪性腫瘍患者の深部静脈血栓症の治療には近年直接作用型経口抗凝固薬（DOAC）の有効性が示唆されつつあるが、悪性腫瘍患者がDOAC内服中に脳梗塞を起こす報告も散見され、DOACが悪性腫瘍関連脳梗塞に有効かは明らかでない。現状ではヘパリン皮下注を導入する症例が多いが、精神的・身体的苦痛を伴い障壁は大きい。悪性腫瘍患者における血栓症の一次予防、二次予防のリスク管理と最適な治療法確立が求められている。

Research Products

• [Journal Article] Effect of tooth loss and nutritional status on outcomes after ischemic stroke (2020)
  • Author(s): Shiga Yuji、Nezu Tomohisa、Hosomi Naohisa、Aoki Shiro、Nishi Hiromi、Naito Hiroyuki、Kinoshita Naoto、Ueno Hiroki、Maruyama Hirofumi
  • Journal Title: Nutrition Volume: 71 Pages: 110606-110606
  • DOI: 10.1016/j.nut.2019.110606
  • Peer Reviewed
• [Journal Article] A case of seronegative longitudinally extensive transverse myelitis with possible neuro sweet disease. (2020)
  • Author(s): Toko M, Nezu T, Ueno H, Kamimura T, Aoki S, Hosomi N, Maruyama H.
  • Journal Title: eNeurologicalSci. Volume: 18 Pages: 100227-100227
  • DOI: 10.1016/j.ensci.2020.100227
  • Peer Reviewed
• [Journal Article] Steroid-responsive Nivolumab-induced Involuntary Movement with Anti-thyroid Antibodies (2019)
  • Author(s): Maetani Y, Nezu T, Ueno H, Aoki S, Hosomi N, Maruyama H.
  • Journal Title: Internal Medicine Volume: 58 Issue: 24 Pages: 3577-3581
  • DOI: 10.2169/internalmedicine.3200-19
  • NAID: 130007761437
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2019-12-15
  • Peer Reviewed
• [Journal Article] Treatment of intractable resting tremor of spinocerebellar ataxia 42 with zonisamide. (2019)
  • Author(s): Hara N, Nezu T, Kobatake K, Morino H, Kawakami H, Maruyama H.
  • Journal Title: Journal of neurological science Volume: 15 Pages: 119-120
  • DOI: 10.1016/j.jns.2018.11.013
  • Peer Reviewed
• [Journal Article] Antithrombotic Therapy Strategy for Cancer-Associated Ischemic Stroke: A Case Series of 26 Patients (2018)
  • Author(s): Naito H, Nezu T, Hosomi N, Aoki S, Ueno H, Ochi K, Maruyama H
  • Journal Title: Journal of Stroke and Cerebrovascular Diseases Volume: 27 Issue: 9 Pages: e206-e211
  • DOI: 10.1016/j.jstrokecerebrovasdis.2018.04.021
  • Peer Reviewed
• [Journal Article] Controlling nutritional status score for predicting 3-mo functional outcome in acute ischemic stroke. (2018)
  • Author(s): Naito H, Nezu T, Hosomi N, Aoki S, Kinoshita N, Kuga J, Shimomura R, Araki M, Ueno H, Ochi K, Maruyama H
  • Journal Title: Nutrition Volume: - Pages: 55-56
  • DOI: 10.1016/j.nut.2018.02.025
  • Peer Reviewed
• [Journal Article] Alpha-2-macroglobulin as a Promising Biological Marker of Endothelial Function (2018)
  • Author(s): Shimomura Ryo、Nezu Tomohisa、Hosomi Naohisa、Aoki Shiro、Sugimoto Takamichi、Kinoshita Naoto、Araki Mutsuko、Takahashi Tetsuya、Maruyama Hirofumi、Matsumoto Masayasu
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 25 Issue: 4 Pages: 350-358
  • DOI: 10.5551/jat.41335
  • NAID: 130006602294
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed
• [Journal Article] Impact of D-dimer levels for short-term or long-term outcomes in cryptogenic stroke patients. (2018)
  • Author(s): Nezu T, Kitano T, Kubo S, Uemura J, Yamashita S, Iwanaga T, Inoue T, Hosomi N, Maruyama H, Matsumoto M, Kimura K, Yagita Y.
  • Journal Title: J Neurol Volume: 265 Pages: 628-636
  • Peer Reviewed
• [Presentation] 延髄吻側腹外側野への血管圧迫は脳梗塞患者の亜急性期血圧変動に影響する (2019)
  • Author(s): 祢津 智久、細見 直永、葛目 大輔、内藤 裕之、青木 志郎、金星 匡人、森本 優子、志賀 裕二、木下 直人、上野 弘貴、丸山 博文
  • Organizer: 第44回日本脳卒中学会学術集会
• [Presentation] 脳小血管病のバイオマーカー (2018)
  • Author(s): 祢津 智久、細見 直永
  • Organizer: 第50回日本動脈硬化学会総会・学術集会
  • Invited
• [Presentation] Controlling Nutritional Status Score Predicts 3-Month Functional Outcome in Patients With Acute Ischemic Stroke (2018)
  • Author(s): Naito H, Nezu T, Hosomi N, Aoki S, Kinoshita N, Shimomura R, Araki M, Ueno H, Ochi K, Maruyama H
  • Organizer: International Stroke Conference 2018
  • Int'l Joint Research
• [Presentation] 原因不明脳梗塞患者における右左シャント、D-dimerと再発の検討 (2017)
  • Author(s): 祢津智久、北野貴也、久保智司、城本高志、植村順一、和田裕子、細見直永、丸山博文、八木田佳樹
  • Organizer: 第42回日本脳卒中学会総会
• [Presentation] Overview: Carotid intima-media thickness (2017)
  • Author(s): Nezu T, Hosomi N, Maruyama H, Matsumoto M
  • Organizer: 第49回日本動脈硬化学会総会・学術集会
  • Invited
• [Presentation] Microbleeds evaluation study for prevention of brain hemorrhage in ischemic stroke (MB-evidence): pilot analysis for multicenter longitudinal study. (2017)
  • Author(s): Nezu T, Naka H, Hosomi N, Takamatsu K, Nomura E, Kitamura T, Torii T, Oshita T, Nakamori M, Imamura E, shimomura R, Aoki S, Maruyama H, Matsumoto M.
  • Organizer: XXIII World Congress of Neurology
  • Int'l Joint Research
• [Presentation] 血清α2マクログロブリンと炎症性サイトカインの関連：脳心血管リスク因子保有例での検討 (2017)
  • Author(s): 祢津智久、細見直永、下村怜、青木志郎、高橋哲也、林 奉権、松本昌泰、丸山博文
  • Organizer: 第60回日本脳循環代謝学会学術集会