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Affiliation |
Faculty of Medicine School of Medicine Department of Pathology, Pathophysiology |
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Assistant Professor |
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External Link |
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GIToshihiro
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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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Sugita C., Maekawa K., Gi T., Oguri N., Nakamura E., Furukoji E., Azuma M., Asada Y., Yamashita A.
Thrombosis Research 238 185 - 196 2024.6
Language：English Publishing type：Research paper (scientific journal) Publisher：Thrombosis Research
Background: Plaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII (FVIII) correlate with an increased ischemic heart disease risk. FVIII may contribute to thrombus formation on eroded plaques. Aims: We aimed to elucidate the role of elevated FVIII in arterial thrombus formation within SMC-rich neointima in rabbits. Methods and results: We assessed the effect of recombinant human FVIII (rFVIII) on blood coagulation in vitro and platelet aggregation ex vivo. An SMC-rich neointima was induced through balloon injury to the unilateral femoral artery. Three weeks after the first balloon injury, superficial erosive injury and thrombus formation were initiated with a second balloon injury of the bilateral femoral arteries 45 min after the administration of rFVIII (100 IU/kg) or saline. The thrombus area and contents were histologically measured 15 min after the second balloon injury. rFVIII administration reduced the activated partial thromboplastin time and augmented botrocetin-induced, but not collagen- or adenosine 5′-diphosphate-induced, platelet aggregation. While rFVIII did not influence platelet-thrombus formation in normal intima, it increased thrombus formation on SMC-rich neointima post-superficial erosive injury. Enhanced immunopositivity for glycoprotein IIb/IIIa and fibrin was observed in rFVIII-administered SMC-rich neointima. Neutrophil count in the arterial thrombus on the SMC-rich neointima correlated positively with thrombus size in the control group, unlike the rFVIII group. Conclusions: Increased FVIII contributes to thrombus propagation within erosive SMC-rich neointima, highlighting FVIII's potential role in plaque erosion-related atherothrombosis.
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Paratesticular cellular angiofibroma: a case report
Murashima T., Kida K., Gi T., Hida T., Fujii M., Nagai T., Takamori H., Mukai S., Sato Y., Kamoto T.
Journal of Medical Case Reports 18 ( 1 ) 170 2024.12
Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Medical Case Reports
Introduction: Paratesticular cellular angiofibroma is a rare benign mesenchymal tumor. The optimal management is surgical resection due to the difficulty of preoperative accurate diagnosis. Case presentation: A 51-year-old Japanese male visited our hospital complaining of asymptomatic left scrotal swelling. Physical examination revealed a nontender elastic paratesticular mass (5.5 cm in diameter). Although testicular germ cell tumor was ruled out clinically, the possibility of malignant potential remained for the tumor. Since the patient consented to complete resection, a transinguinal radical orchiectomy was performed. The pathological diagnosis revealed cellular angiofibroma. The patient recovered without perioperative complications, and no apparent recurrence was observed at 5 years after surgery. Conclusion: The pathological findings were compatible for cellular angiofibroma. The tumor was successfully resected, and no apparent recurrence was observed at 5 years after surgery.
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Expression of fibroblast activation protein-α in human deep vein thrombosis
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
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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杉田 千泰, 前川 和也, 魏 峻洸, 中村 恵理子, 古小路 英二, 東 美菜子, 浅田 祐士郎, 山下 篤
Thrombosis Research 238 185 - 196 2024
Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier
Background
Plaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII (FVIII) correlate with an increased ischemic heart disease risk. FVIII may contribute to thrombus formation on eroded plaques.
Aims
We aimed to elucidate the role of elevated FVIII in arterial thrombus formation within SMC-rich neointima in rabbits.
Methods and results
We assessed the effect of recombinant human FVIII (rFVIII) on blood coagulation in vitro and platelet aggregation ex vivo. An SMC-rich neointima was induced through balloon injury to the unilateral femoral artery. Three weeks after the first balloon injury, superficial erosive injury and thrombus formation were initiated with a second balloon injury of the bilateral femoral arteries 45 min after the administration of rFVIII (100 IU/kg) or saline. The thrombus area and contents were histologically measured 15 min after the second balloon injury. rFVIII administration reduced the activated partial thromboplastin time and augmented botrocetin-induced, but not collagen- or adenosine 5′-diphosphate-induced, platelet aggregation. While rFVIII did not influence platelet-thrombus formation in normal intima, it increased thrombus formation on SMC-rich neointima post-superficial erosive injury. Enhanced immunopositivity for glycoprotein IIb/IIIa and fibrin was observed in rFVIII-administered SMC-rich neointima. Neutrophil count in the arterial thrombus on the SMC-rich neointima correlated positively with thrombus size in the control group, unlike the rFVIII group.
Conclusions
Increased FVIII contributes to thrombus propagation within erosive SMC-rich neointima, highlighting FVIII's potential role in plaque erosion-related atherothrombosis.
Books 【 display / non-display 】
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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
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New Textbook of clinical Phlebology
（ Role： Contributor）
2019.10
Total pages：503 Responsible for pages：398-399 Language：Japanese Book type：Scholarly book
MISC 【 display / non-display 】
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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
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グルタミンは血管平滑筋細胞の凝固活性を抑制する
小山彰平, 山下篤, 松浦祐之介, 齋藤祐介, 前川和也, 魏峻洸, 北村和雄, 海北幸一, 浅田祐士郎
日本動脈硬化学会総会・学術集会プログラム・抄録集(Web) 54th 2022
Publishing type：Rapid communication, short report, research note, etc. (scientific journal)
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From the Winners of Freshman Researcher Award Commemorative of Japanese Society of Pathology 100th Anniversary Invited
Toshihiro Gi
Pathology and Clinical Medicine 39 ( 10 ) 2021.11
Authorship：Lead author Language：Japanese Publishing type：Article, review, commentary, editorial, etc. (scientific journal)
Presentations 【 display / non-display 】
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閉塞性細気管支炎により慢性肺移植片機能不全をきたした一剖検症例
魏 峻洸, 重草 貴文, 坪内 宏伸, 松元 信弘, 山下 篤, 前川 和也, 阿萬 紫, 佐藤 勇一郎, 鍋島 一樹, 浅田 祐士郎
日本病理学会会誌 2018.10 (一社)日本病理学会
Event date： 2018.10
Language：Japanese Presentation type：Oral presentation (general)
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深部静脈血栓症における拡散強調画像の有用性:家兎頚静脈血栓モデルを用いた検討
黒岩靖淳, 黒岩靖淳, 魏峻洸, 山下篤, 圓崎将大, 小西祐子, 宮地利明, 平井俊範, 今村卓郎, 浅沼武敏, 浅田祐士郎
日本血栓止血学会誌 2017.4.1
Event date： 2017.4.1
Language：Japanese Presentation type：Oral presentation (general)
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血管内皮細胞のPodoplanin発現はラット頸動脈におけるびらん性傷害と血栓形成を促進する
古小路英二, 山下篤, 盛口清香, 前川和也, 魏峻洸, 佐藤勇一郎, 平井俊範, 浅田祐士郎
日本血栓止血学会誌 2017.4.1
Event date： 2017.4.1
Language：Japanese Presentation type：Oral presentation (general)
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Title] Multiple coronary plaque ruptures in an autopsy case of acute myocardial infarction
2021.11.4
Event date： 2021.11.4 - 2021.11.5
Language：Japanese Presentation type：Poster presentation
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心臓 MRI での病変の不均一性を呈した AL アミロイドーシスに対して両心室心筋生検を行った一例
山村善政, 松浦祐之介, 石川哲憲, 北村和雄, 魏峻洸, 浅田祐士郎
第42回心筋生検研究会学術集会 2021.6.12
Event date： 2021.6.12
Language：Japanese Presentation type：Oral presentation (general)
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