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Faculty of Medicine School of Medicine Department of Pathology, Pathophysiology |
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Assistant Professor |
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GI Toshihiro
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Papers 【 display / non-display 】
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Histopathological Features of Cancer-Associated Venous Thromboembolism: Presence of Intrathrombus Cancer Cells and Prothrombotic Factors Reviewed International journal
Gi T., Kuwahara A., Yamashita A., Matsuda S., Maekawa K., Moriguchi-Goto S., Sato Y., Asada Y.
Arteriosclerosis, thrombosis, and vascular biology 43 ( 1 ) 146 - 159 2023.1
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Arteriosclerosis, thrombosis, and vascular biology
BACKGROUND: Cancer-associated venous thromboembolism (VTE) is a critical complication in patients with cancer. However, the pathological findings of VTE are limited. Here, we investigated the histopathological features of cancer-associated VTE in human autopsy cases. METHODS: We clinically examined the autopsy cases of VTE with (n=114) and without cancer (n=66) and immunohistochemically analyzed the expression of prothrombotic factors in intrathrombus cancer cells, the thrombus contents of erythrocytes, fibrin, platelets, citrullinated histone H3, and degree of organization. RESULTS: Vascular wall invasion or small cell clusters of cancer cells was observed in thrombi in 27.5% of deep vein thrombosis and 25.9% of pulmonary embolism cases. The majority of the cancer cells in deep vein thrombi appeared to be invading the vessel wall, whereas the majority of pulmonary thrombi had cancer cell clusters, consistent with embolization via blood flow. These cancer cells were immunohistochemically positive for TF (tissue factors) or podoplanin in up to 88% of VTE cases. The frequency of TF-positive monocyte/macrophages in thrombi was higher in cancer-associated VTE than that in VTE without cancer. Citrullinated histone H3 was predominantly observed in the early stages of organizing thrombi. There was no significant difference in thrombus components between VTE with cancer and without cancer groups. CONCLUSIONS: Vascular wall invasion or cancer cell clusters in thrombi might influence thrombogenesis of cancer-associated VTE. TF and podoplanin in cancer cells and in monocyte/macrophages may induce coagulation reactions and platelet aggregation. Neutrophil extracellular traps may play a role in the early stages of VTE, regardless of cancer status.
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Factor XI localization in human deep venous thrombus and function of activated factor XI on venous thrombus formation and hemostasis Reviewed International journal
Nobuyuki Oguri, Toshihiro Gi, Eriko Nakamura, Kazunari Maekawa, Eiji Furukoji, Hoshimi Okawa, Sho Kouyama, Saki Horiuchi, Akira Sawaguchi, Tatefumi Sakae, Minako Azuma, Yujiro Asada, Atsushi Yamashita
Research and Practice in Thrombosis and Haemostasis 2025.3
Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER
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Histological differences among thrombi in thrombotic diseases. Invited Reviewed International journal
Atsushi Yamashita, Toshihiro Gi, Yuichiro Sato
Current opinion in hematology 2025.1
Language：English Publishing type：Research paper (scientific journal)
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Expression of fibroblast activation protein-α in human deep vein thrombosis Reviewed International journal
Oguri N., Gi T., Nakamura E., Furukoji E., Goto H., Maekawa K., Tsuji A.B., Nishii R., Aman M., Moriguchi-Goto S., Sakae T., Azuma M., Yamashita A.
Thrombosis Research 241 109075 2024.9
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Thrombosis Research
Background: Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is associated with wound healing, cancer-associated fibroblasts, and chronic fibrosing diseases. However, its expression in deep vein thrombosis (DVT) remains unclear. Therefore, this study investigated FAP expression and localization in DVT. Methods: We performed pathological analyses of the aspirated thrombi of patients with DVT (n = 14), classifying thrombotic areas in terms of fresh, cellular lysis, and organizing reaction components. The organizing reaction included endothelialization and fibroblastic reaction. We immunohistochemically examined FAP-expressed areas and cells, and finally analyzed FAP expression in cultured dermal fibroblasts. Results: All the aspirated thrombi showed a heterogeneous mixture of at least two of the three thrombotic areas. Specifically, 83 % of aspirated thrombi showed fresh and organizing reaction components. Immunohistochemical expression of FAP was restricted to the organizing area. Double immunofluorescence staining showed that FAP in the thrombi was mainly expressed in vimentin-positive or α-smooth muscle actin-positive fibroblasts. Some CD163-positive macrophages expressed FAP. FAP mRNA and protein levels were higher in fibroblasts with low-proliferative activity cultured under 0.1 % fetal bovine serum (FBS) than that under 10 % FBS. Fibroblasts cultured in 10 % FBS showed a significant decrease in FAP mRNA levels following supplementation with hemin, but not with thrombin. Conclusions: The heterogeneous composition of venous thrombi suggests a multistep thrombus formation process in human DVT. Further, fibroblasts or myofibroblasts may express FAP during the organizing process. FAP expression may be higher in fibroblasts with low proliferative activity.
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Inflammatory stimuli and hypoxia on atherosclerotic plaque thrombogenicity: Linking macrophage tissue factor and glycolysis Reviewed International journal
Maekawa K., Nakamura E., Saito Y., Matsuura Y., Gi T., Nishihira K., Oguri N., Moriguchi-Goto S., Sato Y., Hatakeyama K., Shibata Y., Komohara Y., Kaikita K., Asada Y., Yamashita A.
PLoS ONE 20 ( 3 March ) e0316474 2025.3
Language：English Publishing type：Research paper (scientific journal) Publisher：PLoS ONE
Background The thrombogenic potential of cells within atherosclerotic plaques is critical in the formation of a coronary thrombus. We hypothesized that a combination of inflammatory and hypoxic stimuli enhances tissue factor (TF) expression and glycolysis in cells in atherosclerotic plaques and contributes to coronary thrombus formation. Aims To identify TF- and hexokinase (HK)-II-expressing cells in coronary atherosclerotic plaques and thrombi and determine the effects of combined inflammatory and hypoxic stimuli and glycolysis on TF expression in peripheral blood mononuclear cell-derived macrophages. Methods We immunohistochemically assessed TF and HK-II expression in stable (n = 20) and unstable (n = 24) human coronary plaques and aspirated acute coronary thrombi (n = 15). The macrophages were stimulated with tumor necrosis factor-α, interferon-γ, or interleukin-10 under normoxic (21% O2) or hypoxic (1% O2) conditions, and TF expression was assessed. Results TF and HK-II expression were increased in unstable plaques compared with stable plaques. The number of CD68- and HK-II-immunopositive cells positively correlated with the number of TF-immunopositive cells. TF- and HK-II-expressing macrophages, which expressed M1- or M2-like markers, were involved in platelet-fibrin thrombus formation in ruptured plaques. The combination of inflammatory and hypoxic conditions additively augmented TF expression and procoagulant activity in the cultured macrophages. Inhibition of glycolysis with 2-deoxyglucose reduced the augmented TF expression and procoagulant activity. Conclusion Combined inflammatory and hypoxic conditions in atherosclerotic plaques may markedly enhance procoagulant activity in macrophages and contribute to coronary thrombus formation following plaque disruption. Macrophage TF expression may be associated with glycolysis.
Books 【 display / non-display 】
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【病理診断クイックリファレンス 2023】(第1章)心・血管 心アミロイドーシス
山下 篤, 魏 峻洸（ Role： Joint author）
(株)文光堂 2023.4
Language：Japanese
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【病理診断クイックリファレンス 2023】(第1章)心・血管 感染性心内膜炎
山下 篤, 魏 峻洸（ Role： Joint author）
(株)文光堂 2023.4
Language：Japanese
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【病理診断クイックリファレンス 2023】(第1章)心・血管 心臓粘液腫
山下 篤, 魏 峻洸（ Role： Joint author）
(株)文光堂 2023.4
Language：Japanese Book type：Textbook, survey, introduction
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【徹底ガイドDICのすべて 2022-'23】病態生理と病理 病理組織
盛口 清香, 魏 峻洸（ Role： Joint author）
(株)総合医学社 2022.7 （ ISBN:9784883785742 ）
Language：Japanese Book type：Scholarly book
＜ここがポイント!＞▼播種性血管内凝固症候群(DIC)は、種々の基礎疾患によって全身の凝固線溶系が亢進した状態で、凝固系・線溶系のどちらが優位かによって、全身性に多発微小血栓が形成されることによる多臓器障害や、出血傾向をきたす病態である。▼DICの病態生理は、基礎疾患に応じて多彩で、組織所見にも多様性がある。ときに、全身の毛細血管に微小血栓が形成される。▼微小血栓は、主にフィブリンから構成され、血小板が介在する。白血球が混在する場合もある。▼剖検例の検討では、血栓形成の頻度は、主要臓器に高い傾向にある。(著者抄録)
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モデル動物の作製と利用 循環器疾患 2021 上巻
山下 篤, 魏 峻洸, 浅田 祐士郎（ Role： Contributor , 第4節 ウサギ反復傷害血栓モデル）
株式会社 エル・アイ・シー 2021.9
Language：Japanese Book type：Textbook, survey, introduction
MISC 【 display / non-display 】
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肺血栓症の病理 Invited Reviewed
魏 峻洸
病理と臨床 42 ( 9 ) 883 - 891 2024.9
Authorship：Lead author, Corresponding author Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)
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GI Toshihiro
Japanese Journal of Thrombosis and Hemostasis 35 ( 4 ) 512 - 521 2024
Authorship：Lead author, Corresponding author Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal) Publisher：The Japanese Society on Thrombosis and Hemostasis
DOI： 10.2491/jjsth.35.512
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がんの種類別に見たCATのエビデンス 癌関連静脈血栓塞栓症の病理組織学的解析
魏 峻洸, 山下 篤, 松田 俊太郎, 佐藤 勇一郎, 浅田 祐士郎
脈管学 60 ( Suppl. ) S93 - S94 2020.10
Language：Japanese Publishing type：Rapid communication, short report, research note, etc. (scientific journal) Publisher：(一社)日本脈管学会
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破裂性冠動脈プラークの血小板粘着にフィブリンやフォンウィルブランド因子が関与する
山下 篤, 西平 賢作, 前川 和也, 魏 峻洸, 畠山 金太, 柴田 剛徳, 浅田 祐士郎
日本血栓止血学会誌 31 ( 2 ) 247 - 247 2020.5
Language：Japanese Publishing type：Rapid communication, short report, research note, etc. (scientific journal) Publisher：(一社)日本血栓止血学会
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剖検例を用いた癌関連静脈血栓塞栓症の病理組織学的検討
魏 峻洸, 山下 篤, 松田 俊太郎, 佐藤 勇一郎, 浅田 祐士郎
日本血栓止血学会誌 31 ( 2 ) 247 - 247 2020.5
Language：Japanese Publishing type：Rapid communication, short report, research note, etc. (scientific journal) Publisher：(一社)日本血栓止血学会
Presentations 【 display / non-display 】
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Histopathological features of cancer-associated venous thromboembolism: presence of intrathrombus cancer cells and prothrombotic factors
魏 峻洸
第46回日本血栓止血学会学術集会
Event date： 2024.6.13 - 2024.6.15
Language：English Presentation type：Oral presentation (invited, special)
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深部静脈血栓におけるfibroblast activating protein-αの発現とその機能
大栗伸行、中村恵理子、魏 峻洸、古小路英二、前川和也、辻 厚至、西井龍一、榮 建文、東美菜子、山下 篤
第29回日本血管病理研究会
Event date： 2024.11.23 - 2024.11.24
Language：Japanese Presentation type：Oral presentation (general)
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非アルコール性脂肪性肝疾患の新規画像診断：核磁気共鳴画像による腹部大動脈硬化の検出と肝臓評価.
黒岩靖淳、内田暁子、土肥省吾、魏 峻洸、楠元寿典、古小路英二、木原 康、今村卓郎、東 美菜子、海北幸一、山下 篤
第56回日本動脈硬化学会
Event date： 2024.7.6 - 2024.7.7
Language：Japanese Presentation type：Oral presentation (general)
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Fibrin and von Willebrand factor deposition, and neutrophil extracellular traps formation during human coronary atherogenesis. International conference
Nakamura E, Horiuchi S, Maekawa K, Oguri N, Gi T, Moriguchi-Goto S, Aman M, Asada Y, Yamashita A.
32th Congress of International Society on Thrombosis and Haemostasis
Event date： 2024.6.22 - 2024.6.26
Language：English Presentation type：Oral presentation (general)
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人体病理から解析するがん関連静脈血栓塞栓症 Invited
魏 峻洸
第17回DAIICHI-SANKYO SYMPOSIUM FOR THROMBOSIS UPDATE
Event date： 2024.6.14
Language：Japanese Presentation type：Oral presentation (invited, special)
Awards 【 display / non-display 】
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Young Investigator Award
2024.6 Japanese Society of Thrombosis and Hemostasis
Toshihiro Gi
Award type：International academic award (Japan or overseas)
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日本病理学会100周年記念 病理学研究新人賞
2021.4 日本病理学会 血栓症の病態解明と新規検出法の開発
魏 峻洸
Award type：Award from Japanese society, conference, symposium, etc.
Grant-in-Aid for Scientific Research 【 display / non-display 】
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肺血栓塞栓症における非塞栓部肺動脈の変化と静脈血栓由来因子の解明
Grant number：23K06467 2023.04 - 2026.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(C)
山下 篤
Authorship：Coinvestigator(s)
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重症熱性血小板減少症候群における血小板減少と血液凝固異常の病態解明
Grant number：23K06425 2023.04 - 2026.03
独立行政法人日本学術振興会 科学研究費基金 基盤研究(C)
盛口 清香
Authorship：Coinvestigator(s)
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妊産婦死亡の主因である羊水塞栓症における血栓性病態の解明
Grant number：22K06961 2022.04 - 2025.03
独立行政法人日本学術振興会 科学研究費補助金 基盤研究(C)
阿萬 紫、
Authorship：Coinvestigator(s)
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癌関連静脈血栓症の血栓形成機序と発症予測所見の解明
Grant number：21K15403 2021.04 - 2024.03
日本学術振興会 科学研究費助成事業 若手研究 若手研究
魏 峻洸
Authorship：Principal investigator