Shimoda, Masayuki



School of Medicine, Department of Pathology (Shinanomachi)


Associate Professor

Academic Background 【 Display / hide

  • 1994.04

    Keio University, 医学部

    日本, University, Graduated

  • 2000.04

    Keio University, 医学研究科, 病理学

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

Academic Degrees 【 Display / hide

  • 博士(医学), Keio University, Coursework, 2007.12

    Binding of ADAM28 to P-selectin Glycoprotein Ligand-1 Enhances P-selectin-mediated Leukocyte Adhesion to Endothelial Cells

Licenses and Qualifications 【 Display / hide

  • 医師免許, 2000.05

  • 死体解剖資格認定, 2003.02

  • 日本病理学会病理専門医, 2005.07

  • 日本臨床細胞学会細胞診専門医, 2005.12

  • 日本病理学会病理専門医研修指導医, 2006.04

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Research Areas 【 Display / hide

  • Human pathology

  • Experimental pathology

Research Keywords 【 Display / hide

  • 人体病理学(主に消化管、唾液腺)

  • 実験病理学(腫瘍間質、炎症性腸疾患、プロテアーゼ、細胞外マトリックス)

Research Themes 【 Display / hide

  • 潰瘍性大腸炎関連腫瘍の臨床病理学的解析, 


  • 腫瘍間質形成機序の解析, 


  • 病的組織における組織内微小環境因子代謝解析研究, 



Papers 【 Display / hide

  • ADAM10 is indispensable for longitudinal bone growth in mice

    Mizuno S., Yoda M., Kimura T., Shimoda M., Akiyama H., Chiba K., Nakamura M., Horiuchi K.

    Bone (Bone)  134 2020.05

    ISSN  87563282

     View Summary

    © 2020 Skeletal development is a highly sophisticated process in which the expression of a variety of growth factors, signaling molecules, and extracellular matrix proteins is spatially and temporally orchestrated. In the present study, we show that ADAM10, a transmembrane protease that is critically involved in the functional regulation of various membrane-bound molecules, plays an essential role in the longitudinal growth of long bones and in skeletal development. We found that mutant mice lacking ADAM10 in osteochondroprogenitors exhibited marked growth retardation and had shorter long bones than the control mice. Histomorphometric analysis revealed that the mutant mice had a shorter hypertrophic zone and that their hypertrophic chondrocytes were smaller in size than those of the control mice. Unexpectedly, we found that the mRNA expression of the chemokine CXCL12 and its receptor CXCR4 were significantly reduced in cartilage tissues lacking ADAM10. Further, exogenous supplementation of recombinant CXCL12 rescued the defect in the ADAM10-deficient growth plate in an ex vivo culture model. Taken together, our data show a previously unknown role for ADAM10 in skeletal development that involves its regulation of the CXCL12 and CXCR4 signaling pathway.

  • Human amyloidosis, still intractable but becoming curable: The essential role of pathological diagnosis in the selection of type-specific therapeutics

    Naiki H., Sekijima Y., Ueda M., Ohashi K., Hoshii Y., Shimoda M., Ando Y.

    Pathology International (Pathology International)  70 ( 4 ) 191 - 198 2020.04

    ISSN  13205463

     View Summary

    © 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd The molecular pathogenesis of human amyloidosis has been elucidated greatly during the last 20 years. Based on the understanding of the molecular mechanisms of amyloid fibril formation and deposition, various kinds of new drugs and therapeutics have been emerging to improve the prognosis of amyloidosis and even cure this disease. In this review article, we first summarize the pathogenesis and state-of-the-art therapeutics of representative types of systemic human amyloidosis, that is, immunoglobulin light chain-related, transthyretin-related, amyloid A-associated and β2-microglobulin-related amyloidosis. Next, we describe the essential roles of pathological diagnosis, especially the typing diagnosis of amyloidosis to appropriately guide type-specific therapies of amyloidosis patients. Finally, we introduce the activities of the government-funded group for surveys and research of amyloidosis in Japan, especially the nation-wide pathology consultation system of amyloidosis, which started in April 2018. The nation-wide improvement of the typing diagnosis of amyloidosis is essential for the appropriate treatment and care of amyloidosis patients in Japan.

  • How I do it: Endoscopic diagnosis for superficial non-ampullary duodenal epithelial tumors

    Nakayama A., Kato M., Takatori Y., Shimoda M., Mizutani M., Tsutsumi K., Kiguchi Y., Akimoto T., Sasaki M., Mutaguchi M., Takabayashi K., Maehata T., Ochiai Y., Kanai T., Yahagi N.

    Digestive Endoscopy (Digestive Endoscopy)  32 ( 3 ) 417 - 424 2020.03

    ISSN  09155635

     View Summary

    © 2019 Japan Gastroenterological Endoscopy Society There are no reports on detailed endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADET) except for relatively small case series. Herein, we conducted a prospective observational study to investigate the relationship between endoscopic findings and histopathological diagnosis of SNADET. A total of 163 SNADET diagnosed using magnified endoscopic examination with image-enhanced endoscopy (IEE-ME) were prospectively registered in this study. We investigated location, size, macroscopic type, color, and IEE-ME findings including surface structure (closed- or open-loop) and presence of white opaque substance (WOS) in SNADET. We analyzed association between these findings and histopathological diagnosis of SNADET based on the Vienna classification (VCL) using logistic regression analysis. In univariate analysis, lesion size, superficial structure, and WOS deposition showed statistical significance, and the oral side of the lesion location showed statistical tendency for association with VCL C4/5. In multivariate analysis, lesion size (odds ratio [OR], 2.92; 95% CI, 1.94–4.39; P < 0.05) and negative WOS (OR, 5.59; 95% CI, 1.72–18.1; P < 0.05) were significantly associated with VCL C4/5 lesions. Superficial structures with a closed-loop pattern on the surface showed statistical tendency for predicting VCL C4/5 lesions (OR, 2.15; 95% CI, 0.86–5.37; P = 0.10). Based on these findings, we concluded that negative WOS by IEE-ME and lesion size were independent predictors of VCL C4/5 SNADET. These factors may help us to understand of pathophysiology of SNADET and to select appropriate therapeutic strategies.

  • Infiltration of tumor-associated macrophages is involved in tumor programmed death-ligand 1 expression in early lung adenocarcinoma

    Shima T., Shimoda M., Shigenobu T., Ohtsuka T., Nishimura T., Emoto K., Hayashi Y., Iwasaki T., Abe T., Asamura H., Kanai Y.

    Cancer Science (Cancer Science)  111 ( 2 ) 727 - 738 2020.02

    ISSN  13479032

     View Summary

    © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. Programmed death-ligand 1 (PD-L1) is an immune modulator that promotes immunosuppression by binding to programmed death-1 of T-lymphocytes. Although tumor cell PD-L1 expression has been shown to be associated with the clinical response to anti–PD-L1 antibodies, its concise regulatory mechanisms remain elusive. In this study, we evaluated the associations of tumor PD-L1 expression and immune cell infiltrating patterns in 146 cases of early lung adenocarcinoma (AC) to investigate the possible extrinsic regulation of tumor PD-L1 by immune cells. Using immunohistochemistry, cell surface PD-L1 expression in tumor cells was observed in 18.5% of stage 0-IA lung AC patients. Tumor PD-L1 positivity was significantly associated with stromal invasion, which was accompanied by increased tumor-associated macrophages (TAM), CD8+ cytotoxic T cells and FoxP3+ regulatory T cells. Among these immune cells, TAM and CD8+ T cells significantly accumulated in PD-L1-positive carcinoma cell areas, which showed a tumor cell nest-infiltrating pattern. Although CD8+ T cells are known to induce tumor PD-L1 expression via interferon-ɣ production, the increased TAM within tumors were also associated with tumor cell PD-L1 positivity, independently of CD8+ T cell infiltration. Our in vitro experiments revealed that PD-L1 expression in lung cancer cell lines was significantly upregulated by co–culture with M2-differentiated macrophages; expression of PD-L1 was reduced to baseline levels following treatment with a transforming growth factor-β inhibitor. These results demonstrated that tumor-infiltrating TAM are extrinsic regulators of tumor PD-L1 expression, indicating that combination therapy targeting both tumor PD-L1 and stromal TAM might be a possible strategy for effective treatment of lung cancer.

  • Hyaluronan Degradation by Cemip Regulates Host Defense against Staphylococcus aureus Skin Infection

    Dokoshi T., Zhang L.j., Li F., Nakatsuji T., Butcher A., Yoshida H., Shimoda M., Okada Y., Gallo R.L.

    Cell Reports (Cell Reports)  30 ( 1 ) 61 - 68.e4 2020.01

     View Summary

    © 2019 The Authors In this paper, Dokoshi et al. describe how the mammalian hyaluronidase Cemip is induced in the dermis during S. aureus infection. Cemip digests hyaluronan in the skin to regulate reactive adipogenesis and subsequent antimicrobial activity and skin inflammation.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • NBI併用拡大内視鏡が深達度診断に有用であった大腸側方発育型腫瘍の1例


    胃と腸  2014.11

    Introduction and explanation (commerce magazine), Joint Work

  • メタロプロテアーゼと炎症性疾患

    下田 将之;岡田 保典

    実験医学  2014.10

    Introduction and explanation (scientific journal)

  • 【colitic cancerの初期病変-遡及例の検討を含めて】 内視鏡的に遡及的検討が可能であった潰瘍性大腸炎合併大腸粘膜内腫瘍の1例

    小林 拓;岩男 泰;下田 将之;長沼 誠;金井 隆典;内野 基;池内 浩基;杉野 吉則

    胃と腸  2014.09

    Introduction and explanation (scientific journal)

  • 【小腸潰瘍の鑑別診断】 カプセル内視鏡,バルーン内視鏡で小腸炎を観察しえた好酸球性胃腸炎の1例

    細江 直樹;久松 理一;長沼 誠;柏木 和弘;下田 将之;岩男 泰;緒方 晴彦;金井 隆典

    胃と腸  2014.08

    Introduction and explanation (commerce magazine)

  • メタロプロテアーゼによる組織内微小環境因子代謝

    下田 将之;岡田 保典

    病理と臨床  2014.01

    Introduction and explanation (commerce magazine)

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Presentations 【 Display / hide

  • 低酸素刺激による血液脳関門機能破綻におけるclaudin-5の関与.


    第95回 日本病理学会総会 (東京) , 2006.05, Poster (general)

  • 脳出血を契機に診断し得たHIV-associated PMLの1剖検例―脳組織・髄液のPML型JCウィルスの多様性―

    Yasutomi Daisuke,Nogawa Shigeru,Kotou Atsuo,Fukuuchi Yasuo,Shimoda Masayuki,Yogou Yoshiaki

    第157回日本神経学会関東地方会, 2001.06

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

  • がん微小環境形成・腫瘍進展に関わるHYBID-ヒアルロン酸代謝機構の病理学的解析


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 下田 将之, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • 慶應義塾大学学事振興資金(個人研究)「ドライバー遺伝子変異特異的ながん微小環境の同定とその解析」


    慶應義塾大学, Keio Gijuku Academic Development Funds, Principal Investigator

  • 金沢大学がん進展制御研究所共同研究「線維芽細胞によるECM代謝を介した腫瘍形成・がん幹細胞維持機構の解明」


    金沢大学がん進展制御研究所, Research grant, Principal Investigator

  • 慶應義塾大学医学部JKiC学術開発プロジェクト「がん間質を制御する分子メカニズムの解析とがん関連線維芽細胞層別化に基づくがん細胞-間質細胞相互作用評価系の開発」


    慶應義塾大学医学部JKiC, Research grant, Principal Investigator

  • 基盤研究(C)「新しいガス運搬体を用いた肺移植拒絶反応軽減の基礎研究」


    Grant-in-Aid for Scientific Research, 大塚 崇, Research grant, Co-investigator

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Intellectual Property Rights, etc. 【 Display / hide

  • 抗ヒト膜型ADAM28抗体

    Application No.: PCT/JP2016/056810  2016.03 

    Patent, Joint

  • 癌治療のための抗ADAM28抗体

    Application No.: PCT/JP2013/076745  2013.10 

    Patent, Joint

Awards 【 Display / hide

  • 日本病理学会学術研究賞(A演説)

    2017.11, 日本病理学会

  • 日本結合組織学会大高賞

    2017.06, 日本結合組織学会

  • 高松宮妃癌研究基金研究助成


  • 公益信託癌臨床研究助成基金


  • 第13回日本病理学会カンファレンス優秀演題賞


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Courses Taught 【 Display / hide









Courses Previously Taught 【 Display / hide

  • 病理学各論

    Keio University, 2018, Full academic year, Major subject, Lecture

  • 病理学総論

    Keio University, 2018, Full academic year, Laboratory work/practical work/exercise


Memberships in Academic Societies 【 Display / hide

  • 日本病理学会

  • 日本臨床細胞学会

  • 日本癌学会

  • 日本がん転移学会

  • 日本結合組織学会


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Committee Experiences 【 Display / hide

  • 2020.06

    編集委員, Progress of Digestive Endoscopy

  • 2019.07

    Reviewer Board, Japanese Journal of Clinical Oncology (JJCO)

  • 2019.06

    病理コンサルテーション体制構築 協力研究者, アミロイドーシスに関する調査研究班(内木宏延班長)

  • 2018.07

    評議員, 日本がん転移学会

  • 2017.01

    編集委員, Pathology International

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