Ueno, Akihisa

写真a

Affiliation

School of Medicine, Division of Diagnostic Pathology （Shinanomachi）

Position

Instructor
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Career 【 Display / hide 】

  • 2000.05
    -
    2002.04

    Keio University School of Medicine, Department of Radiology, Resident(Course)

  • 2002.05
    -
    2003.06

    Keio University School of Medicine, Department of Radiology, Postgraduate Training Course

  • 2003.07
    -
    2005.06

    Nippon Koukan Hospital, Department of Radiolgy, Doctor

  • 2005.07
    -
    2006.04

    Keio University School of Medicine, Department of Radiology, Postgraduate Training Course

  • 2006.05
    -
    2010.03

    Keio University School of Medicine, Department ofRadiology, Assistant

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Academic Background 【 Display / hide 】

  • 1993.04
    -
    2000.03

    Chiba University, 医学部

    University, Graduated

  • 2010.04
    -
    2014.03

    Keio University, 医学研究科, 医学研究系

    Graduate School, Withdrawal after completion of doctoral course requirements, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（医学）, Keio University, Coursework, 2015.01

    OATP1B3 expression is strongly associated with Wnt/β-catenin signalling and represents the transporter of gadoxetic acid in hepatocellular carcinoma.

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Licenses and Qualifications 【 Display / hide 】

  • Medical licence, 2000.06

  • 放射線診断専門医, 2005.10

  • 病理専門医, 2020.09

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Research Areas 【 Display / hide 】

  • Life Science / Human pathology

  • Life Science / Experimental pathology

  • Life Science / Radiological sciences

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Research Keywords 【 Display / hide 】

  • Hepatocellular carcinoma

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Research Themes 【 Display / hide 】

  • 肝細胞癌の画像病理対比, 

    2009.04
    -
    Present

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Books 【 Display / hide 】

  • 腫瘍病理鑑別診断アトラス 肝癌 第2版

    波多野まみ, 尾島英知, 上野彰久, 坂元亨宇, 文光堂, 2020.11,  Page： 313

    Scope: 第2部 組織型と診断の実際 I. 肝細胞系腫瘍 4.肝細胞癌の組織亜型,  Contact page： 54-62

  • 腹部のCT 第3版

    上野彰久　佐藤浩三 松坂陽至　上野彰久, メディカルサイエンス・インターナショナル, 2017.04

    Scope: III. 肝臓　IV.胆嚢・胆管

  • EOB-MRI/Sonazoid超音波による肝癌の診断と治療

    上野彰久　坂元亨宇, 医学書院, 2013.06

    Scope: 第7章 EOB-MRIの早期歓談と異型結節（DN)の鑑別診断能 　1. 早期肝癌の病理診断　1分子病理

  • 腹部のCT 第2版

    上野彰久　倉田忠宜, メディカルサイエンス・インターナショナル, 2010.04

    Scope: V. 胆嚢・胆管

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Papers 【 Display / hide 】

  • Immunovascular microenvironment in relation to prognostic heterogeneity of WNT/β-catenin-activated hepatocellular carcinoma

    Matsuda K., Kurebayashi Y., Masugi Y., Yamazaki K., Ueno A., Tsujikawa H., Ojima H., Kitago M., Itano O., Shinoda M., Abe Y., Sakamoto M.

    Hepatology Research （Hepatology Research)  53 （ 4 ） 344 - 356 2023.04

    ISSN  13866346

    　View Summary

    Aim: WNT/β-catenin-activated hepatocellular carcinoma (W/B subclass HCC) is considered a molecularly homogeneous entity and has been linked to resistance to immunotherapy. However, recent studies have indicated possible heterogeneity in the immunovascular microenvironment in this subclass. We set out to test the hypothesis that specific immunovascular features might stratify W/B subclass HCCs into tumors having distinct aggressive natures. Methods: In this study, we analyzed 352 resected HCCs including 78 immunohistochemically defined W/B subclass HCCs. The density of tumor-infiltrating CD3+ T cells and the area ratio of vessels encapsulating tumor clusters (VETC) were calculated on tissue specimens. The gene expressions of angiogenic factors were measured by quantitative reverse transcription–polymerase chain reaction. Disease-free survival (DFS) was assessed using multivariable Cox regression analyses. Results: The T-cell density of W/B subclass HCCs was regionally heterogenous within tumor tissues, and focally reduced T-cell density was observed in areas with VETC. VETC-positivity (defined as VETC area ratio greater than 1%) was inversely associated with T-cell infiltration in both W/B subclass and non-W/B subclass HCCs. Fibroblast growth factor 2 (FGF2) gene expression was higher in W/B subclass than in non-W/B subclass HCCs. The VETC-positivity and low T-cell density correlated with increased expression of FGF2 in W/B subclass HCCs. Additionally, VETC-positive HCCs showed significantly shorter DFS in W/B subclass HCCs. Conclusions: In conclusion, the immune and vascular microenvironments are interrelated and are also correlated with clinicopathological heterogeneity in W/B subclass HCC. These results could inform clinical practice and translational research on the development of therapeutic stratification of HCCs.

  • Eosinophilic granulomatosis with polyangiitis and severe cardiac involvement in a patient surviving for 34 years

    Tanaka M., Oshikata C., Yamashita Y., Isono R., Nakadegawa R., Masumitsu H., Motobayashi Y., Osada R., Takayasu H., Masumoto N., Manabe S., Kaneko T., Ueno A., Tsurikisawa N.

    Journal of Asthma （Journal of Asthma)   2023

    ISSN  02770903

    　View Summary

    Introduction: Many studies have reported a poor prognosis for eosinophilic granulomatosis with polyangiitis (EGPA) patients with cardiac involvement. Case study: A woman developed EGPA at 37 years of age, with weight loss, numbness in the right upper and lower extremities, muscle weakness, skin rash, abdominal pain, chest pain, an increased peripheral blood eosinophil count (4165/µL), and necrotizing vasculitis on peroneal nerve biopsy. The patient was treated with prednisolone, immunosuppressants, intravenous immune globulin, and mepolizumab, but she experienced many relapses, with chest pain, abdominal pain, numbness, and paralysis, over a long period. The patient died from aspiration pneumonia at 71 years of age after undergoing left total hip arthroplasty for left hip neck fracture. Results: Autopsy showed bronchopneumonia in the lower lung lobes on both sides, as well as infiltration of inflammatory cells, including neutrophils and lymphocytes. There was no evidence of active vasculitis in either the lung or colon. At autopsy the heart showed predominantly subendocardial fibrosis and fatty infiltration, but no active vasculitis or eosinophilic infiltration. Conclusion: To our knowledge, there have been no autopsy reports of EGPA patients who have survived for 34 years with recurrent cardiac lesions. In this case, the cardiac involvement (active vasculitis and eosinophilic infiltration) had improved by the time of death.

  • CCR9 axis inhibition enhances hepatic migration of plasmacytoid DCs and protects against liver injury

    Koda Y., Nakamoto N., Chu P.S., Teratani T., Ueno A., Amiya T., Taniki N., Chiba S., Miyamoto K., Sakamoto M., Kanai T.

    JCI Insight （JCI Insight)  7 （ 17 ）  2022.09

    　View Summary

    Plasmacytoid dendritic cells (pDCs) perform dual proinflammatory and immunosuppressive roles. We recently reported the potential of pDC therapy for treatment of intractable acute liver failure. However, establishment of efficient methods to deliver pDCs to the liver is essential for future clinical therapeutic applications. The present study demonstrates a higher abundance of liver and peripheral blood pDCs in mice lacking C-C motif chemokine receptor 9 (CCR9), a pDC gut-homing receptor, than in WT mice. Adoptive transfer of Ccr9–/– pDCs resulted in a higher efficiency of migration to the liver than WT pDCs did, while WT pDCs migrated efficiently to the original target organ, the small intestine. Further, Ccr9–/– pDCs consistently migrated efficiently to livers with concanavalin A–induced inflammation, and exerted a more effective immunosuppressive effect, resulting in better protection against acute liver inflammation than that demonstrated by WT pDCs. These findings highlight the therapeutic potential of the manipulation of the CCR9 axis as an approach to improve migration of immunosuppressive pDCs to the liver in order to exploit their beneficial effects in acute liver disease.

  • Immunovascular classification of HCC reflects reciprocal interaction between immune and angiogenic tumor microenvironments

    Kurebayashi Y., Matsuda K., Ueno A., Tsujikawa H., Yamazaki K., Masugi Y., Kwa W.T., Effendi K., Hasegawa Y., Yagi H., Abe Y., Kitago M., Ojima H., Sakamoto M.

    Hepatology （Hepatology)   2021

    ISSN  02709139

    　View Summary

    Background and Aims: Immune cells and tumor vessels constitute important elements in tumor tissue; however, their detailed relationship in human tumors, including HCC, is still largely unknown. Consequently, we expanded our previous study on the immune microenvironment of HCC and analyzed the relationship among the immune microenvironment, inflammatory/angiostatic factor expression, angiogenic factor expression, and tumor vessel findings, including vessels encapsulating tumor clusters (VETC) and macrotrabecular-massive (MTM) patterns. Approach and Results: We classified HCC into four distinct immunovascular subtypes (immune-high/angiostatic [IH/AS], immune-mid/angio-mid [IM/AM], immune-low/angiogenic [IL/AG], and immune-low/angio-low [IL/AL]). IH/AS, IM/AM, and IL/AG subtypes were associated with decreasing lymphocytic infiltration and increasing angiogenic factor expression and VETC/MTM positivity, reflecting their reciprocal interaction in the tumor microenvironment of HCC. IL/AG subtype was further characterized by CTNNB1 mutation and activation of Wnt/β-catenin pathway. IL/AL subtype was not associated with increased lymphocyte infiltration or angiogenic factor expression. Prognostically, IH/AS subtype and VETC/MTM positivity were independently significant in two independent cohorts. Increased angiogenic factor expression was not necessarily associated with VETC/MTM positivity and poor prognosis, especially when inflammatory/angiostatic milieu coexisted around tumor vessels. These results may provide insights on the therapeutic effects of immunotherapy, antiangiogenic therapies, and their combinations. The potential of evaluating the immunovascular microenvironment in predicting the clinical effect of these therapies in nonresectable HCC needs to be analyzed in the future study. Conclusions: HCC can be classified into four distinct immunovascular subtypes (IH/AS, IM/AM, IL/AG, and IL/AL) that reflect the reciprocal interaction between the antitumor immune microenvironment and tumor angiogenesis. In addition to its clinicopathological significance, immunovascular classification may also provide pathological insights on the therapeutic effect of immunotherapy, antiangiogenic therapy, and their combination.

  • Three distinct stroma types in human pancreatic cancer identified by image analysis of fibroblast subpopulations and collagen

    Ogawa, Y., Masugi, Y., Abe, T., Yamazaki, K., Ueno, A., Fujii-Nishimura, Y., Hori, S., Yagi, H., Abe, Y., Kitago, M. and Sakamoto, M.

    Clin Cancer Res （Clinical Cancer Research)  27 （ 1 ） 107 - 119 2020.10

    ISSN  1078-0432

    　View Summary

    PURPOSE: Cancer-associated fibroblasts have emerged to be highly heterogenous and can play multifaced roles in dictating pancreatic ductal adenocarcinoma (PDAC) progression, immunosuppression and therapeutic response, highlighting the need for a deeper understanding of stromal heterogeneity between patients and even within a single tumor. We hypothesized that image analysis of fibroblast subpopulations and collagen in PDAC tissues might guide stroma-based patient stratification to predict clinical outcomes and tumor characteristics. EXPERIMENTAL DESIGN: A novel multiplex immunohistochemistry-based image analysis system was established to digitally differentiate fibroblast subpopulations. Using whole-tissue slides from 215 treatment-naive PDACs, we performed concurrent quantification of principal fibroblast subpopulations and collagen and defined three stroma types: collagen-rich stroma, fibroblast activation protein a (FAP)-dominant fibroblast-rich stroma and a smooth muscle actin (ACTA2)-dominant fibroblast-rich stroma. These stroma types were assessed for the associations with cancer-specific survival by multivariable Cox regression analyses, and with clinicopathological factors including CD8(+) cell density. RESULTS: FAP-dominant fibroblasts and ACTA2-dominant fibroblasts represented the principal distinct fibroblast subpopulations in tumor stroma. Stroma types were associated with patient survival, SMAD4 status and transcriptome signatures. Compared with FAP-dominant fibroblast-rich stroma, collagen-rich stroma correlated with prolonged survival (HR, 0.57; 95% CI, 0.33-0.99), while ACTA2-dominant fibroblast-rich stroma exhibited poorer prognosis (HR, 1.65; 95% CI, 1.06-2.58). FAP-dominant fibroblast-rich stroma was additionally characterized by restricted CD8(+)-cell infiltrates and intense neutrophil infiltration. CONCLUSIONS: This study identified three distinct stroma types differentially associated with survival, immunity and molecular features, thereby underscoring the importance of stromal heterogeneity in subtyping pancreatic cancers and supporting the development of anti-stromal therapies.

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Reviews, Commentaries, etc. 【 Display / hide 】

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Presentations 【 Display / hide 】

  • 胆嚢原発の脱分化型脂肪肉腫の一例

    上野彰久　尾島英知　眞杉洋平　大島剛　紅林泰　久保田直人　阿部雄太　北川雄光　大喜多肇　坂元亨宇

    第107回日本病理学会総会, 

    2018.06
    , 

    Poster presentation

  • EOB-MRIによるWnt/β-catenin activated subtype HCCの検出能に関する検討

    上野彰久　真杉洋平　山崎剣　Effendi Kathryn　辻川華子　谷本伸弘　奥田茂男　板野理　北川雄光　陣崎雅弘　坂元亨宇

    第11回 日本肝がん分子標的治療研究会, 

    2015.01
    , 

    Poster presentation

  • 胆管疾患up-to-date　画像

    UENO AKIHISA

    第33回 画像医学会, 

    2014.02
    , 

    Public lecture, seminar, tutorial, course, or other speech

  • 肝細胞癌におけるGd-EOB-DTPAのトランスポーターの網羅的解析

    上野彰久　谷本伸弘　坂元亨宇

    第39回 肝臓学会東部会, 

    2012.12
    , 

    Symposium, workshop panel (public)

  • Reduction of Blooming Artifact of Calcification with Prototype Fine-Cell Detector Computed Tomography (0.3mm collimation): Comparison with 64-Slice MDCT

    Tanami, Yutaka, Jinzaki, Masahiro, Sato, Kozo, Ueno, Akihisa, Yamada, Minoru, Kuribayashi, Sachio

    CIRCULATION, 

    2008.10

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Elucidating the mechanism of tumor thrombotic vascular invasion in hepatocellular carcinoma

    2021.04
    -
    2025.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

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Awards 【 Display / hide 】

  • MOST VIEWS JRS ELECTRONIC EXHIBIT DURING ARRS 2015 ANUAL MEETING

    2015.06, American Roentgen Ray Society, OATP1B3 expression is strongly associated with Wnt/β-catenin signaling and represents the transporter of Gd-EOB-DTPA in hepatocellular carcinoma

    Country： United States

  • Cypos Gold Medal

    2014.04, 日本医学放射線学会, OATP1B3 expression is strongly associated with Wnt/β-catenin signaling and represents the transporter of Gd-EOB-DTPA in hepatocellular carcinoma

  • 板井悠二賞

    2010.01, 肝血流動態イメージ研究会, EOBプリモビスト造影MRIの肝細胞相で低信号を呈する乏血性結節の転帰に関する検討

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Courses Taught 【 Display / hide 】

  • GENERAL PATHOLOGY

    2021

  • GENERAL PATHOLOGY

    2020

  • 病理学各論

    2020, Laboratory work/practical work/exercise, Within own ｆaculty

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Courses Previously Taught 【 Display / hide 】

  • 病理学総論

    Keio University

    2018.04
    -
    2019.03
    , 

    Full academic year, Laboratory work/practical work/exercise

  • 病理学各論

    Keio University

    2018.04
    -
    2019.03
    , 

    Full academic year, Laboratory work/practical work/exercise

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Memberships in Academic Societies 【 Display / hide 】

  • 日本臨床細胞学会, 

    2017.04
    -
    Present

  • 日本病理学会, 

    2015.10
    -
    Present

  • 日本肝臓学会, 

    2012.12
    -
    Present

  • 日本癌学会, 

    2010.04
    -
    Present

  • 日本医学放射線学会, 

    2000.04
    -
    Present
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