Mikami, Shuji

写真a

Affiliation

School of Medicine, Division of Diagnostic Pathology (Shinanomachi)

Position

Assistant Professor/Senior Assistant Professor

External Links

Career 【 Display / hide

  • 2017.05
    -
    Present

    Keio University Hospital, Department of Diagnostic Pathology, Deputy Medical Director

  • 2013.12
    -
    Present

    Keio University School of Medicine, Division of Diagnostic Pathology, Junior Associate Professor

  • 2019.07
    -
    Present

    腎癌取り扱い規約第5版, 規約委員

  • 2017.07
    -
    Present

    腎癌診療ガイドライン, 2017年度作成班 班員

  • 2011.03
    -
    Present

    国立がん研究センターがん対策情報センター病理診断コンサルテーションサービス コンサルタント

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Academic Background 【 Display / hide

  • 1997.03

    Tokyo Medical and Dental University, Faculty of Medicine, 医学科

    University, Graduated

  • 2001.03

    Tokyo Medical and Dental University, Graduate School, Division of Medical Sciences, 病理学

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 医学, Tokyo Medical and Dental University, Coursework, 2001.03

Licenses and Qualifications 【 Display / hide

  • 医師免許, 1997.05

  • 死体解剖資格, 2000.12

  • 日本病理学会専門医, 2002.07

  • 日本臨床細胞学会専門医, 2003.12

 

Research Areas 【 Display / hide

  • Human pathology (Human Pathology)

Research Keywords 【 Display / hide

  • Renal cell carcinoma

  • Invasion and Metastasis

  • Molecular Targeted Therapy

  • Resistant to therapy

  • Precision Medicine

 

Books 【 Display / hide

  • 腎細胞がんの核異型度の変遷

    MIKAMI SHUJI, 腎臓内科・泌尿器科 科学評論社, 2018.03

    Scope: 313-138

  • 第5回 泌尿器画像診断・治療技術研究会(JSURT)報告「腎腫瘍の画像診断と病理」 腎腫瘍のWHO分類の改定の要点と病理診断のポイント

    三上 修治, 医学開発機構, 2018.01

    Scope: 映像情報Medical50巻1号68-71

  • 第5回 泌尿器画像診断・治療技術研究会(JSURT)報告 腎腫瘍はCT/MRIでここまで鑑別できる

    秋田 大宇, 陣崎 雅弘, 三上 修治, 大家 基嗣, 医学開発機構, 2018.01

    Scope: 映像情報Medical50巻1号72-74

  • 【腎臓の腫瘍】 腎腫瘍WHO2016新分類

    MIKAMI SHUJI, 文光堂, 2017.10

    Scope: 病理と臨床35巻10号894-902

  • Pathlogy of renal cell carcinoma

    Shuji Mikami, Naoto Kuroda, Yoji Nagashima, Springer, 2017

    Scope: Renal Cell Carcinoma: Molecular Features and Treatment Updates

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Papers 【 Display / hide

  • Clinical significance of programmed death-1 and programmed death-ligand 1 expression in the tumor microenvironment of clear cell renal cell carcinoma

    Mikami S., Mizuno R., Kondo T., Shinohara N., Nonomura N., Ozono S., Eto M., Tatsugami K., Takayama T., Matsuyama H., Kishida T., Oya M.

    Cancer Science (Cancer Science)  110 ( 6 ) 1820 - 1828 2019.06

    ISSN  13479032

     View Summary

    © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. Recently, immunotherapy based on blocking immune checkpoints with programmed death-1 (PD-1) or PD-ligand 1 (PD-L1) Abs has been introduced for the treatment of advanced clear cell renal cell carcinoma (ccRCC), especially tumors resistant to vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs), but the significance of their expression in the tumor microenvironment is unclear. We investigated these immune checkpoint markers in tumor cells and tumor-infiltrating immune cells (TIIC) in the tumor microenvironment of 100 untreated and 25 VEGF-TKI-treated primary ccRCC tissues. Upregulated expression of PD-1 and PD-L1 by TIIC, and PD-L1 by tumor cells was associated with the histological grade and unfavorable prognosis of RCC patients. High PD-1 and PD-L1 expression by TIIC was associated with a poorer response to VEGF-TKI, whereas PD-L1 expression by tumor cells did not affect the efficacy of the treatment. Furthermore, increased PD-1-positive TIIC and PD-L1-positive TIIC were observed in tumors treated with VEGF-TKIs compared with those in untreated tumors. Our data suggest that PD-1 and PD-L1 expression by TIIC in the tumor microenvironment is involved in treatment resistance, and that sequential therapy with immune checkpoint inhibitors could be a promising therapeutic strategy for ccRCC resistant to VEGF-TKI treatment.

  • Sulfasalazine could modulate the CD44v9-xCT system and enhance cisplatin-induced cytotoxic effects in metastatic bladder cancer

    Ogihara K., Kikuchi E., Okazaki S., Hagiwara M., Takeda T., Matsumoto K., Kosaka T., Mikami S., Saya H., Oya M.

    Cancer Science (Cancer Science)  110 ( 4 ) 1431 - 1441 2019.04

    ISSN  13479032

     View Summary

    © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. The prognostic role of CD44v9, a variant isoform of CD44 and a new cell surface marker of cancer stem cells, remains unclear in bladder cancer (BC) patients. Furthermore, limited information is available on the functional role of sulfasalazine (SSZ), which could modulate the CD44v9-xCT system in order to enhance cisplatin (CDDP)-induced cytotoxicity and inhibit the metastatic potential of BC. CD44v9 protein expression was examined immunohistochemically in 63 muscle invasive BC (MIBC) patients who underwent radical cystectomy. CD44v9 expression was independently associated with disease recurrence and cancer-specific death in MIBC. Cytotoxic effects, glutathione levels, and reactive oxygen species production by SSZ and CD44v9 and phospho-p38 MAPK protein expression by SSZ with or without CDDP were assessed in MBT-2V cells with highly metastatic potential. Sulfasalazine exerted cytotoxic effects against MBT-2V cells by inhibiting glutathione levels and inducing the production of reactive oxygen species. Sulfasalazine in combination with CDDP appeared to exert strong cytotoxic effects against MBT-2V cells by inhibiting CD44v9 expression and upregulating phospho-p38 MAPK expression. The inhibitory effects of SSZ with or without CDDP were also investigated using an MBT-2V lung metastatic model. In the murine lung metastatic BC model, SSZ significantly prolonged animal survival. Furthermore, the combination of SSZ with CDDP exerted stronger inhibitory effects on the establishment of lung tumor nodules than SSZ or CDDP alone. CD44v9 expression could be a clinical biomarker for predicting poor outcomes in MIBC patients. Sulfasalazine in combination with CDDP has potential as a novel therapy against metastatic BC.

  • TNFAIP2 expression induces epithelial-to-mesenchymal transition and confers platinum resistance in urothelial cancer cells

    Niwa N., Tanaka N., Hongo H., Miyazaki Y., Takamatsu K., Mizuno R., Kikuchi E., Mikami S., Kosaka T., Oya M.

    Laboratory Investigation (Laboratory Investigation)   2019

    ISSN  00236837

     View Summary

    © 2019, The Author(s), under exclusive licence to United States and Canadian Academy of Pathology. Cisplatin (CDDP)-based chemotherapy is the gold standard treatment for many types of cancer. However, the phenotypic hallmark of tumors often changes after CDDP treatment, with the acquisition of epithelial-to-mesenchymal transition (EMT) and platinum resistance. Furthermore, the mechanisms by which cancer cells acquire EMT under the control of CDDP remain unclear. Following an investigation of urothelial carcinoma (UC) before and after the acquisition of platinum resistance, we offer the new target TNFAIP2, which led to EMT and tumor invasion in platinum-treated UC cells. TNFAIP2 expression in cancer was examined at the protein and transcriptional levels. A potential target for TNFAIP2 during EMT was assessed by microarray. Clinically, upregulated TNFAIP2 expression was identified as a significant predictor of mortality following surgery in three different cohorts of patients with UC (n = 156, n = 119, and n = 54). Knockdown of TNFAIP2 resulted in upregulation of E-cadherin expression and downregulation of TWIST1 expression, which decreased motile function in platinum-resistant UC cells. TNFAIP2 overexpression led to downregulation of E-cadherin expression and upregulation of TWIST1 expression in platinum-naïve UC cells. Clinical investigation of matched pre- and post-CDDP-treated UC sections confirmed upregulation of TNFAIP2 expression in CDDP-treated tumors but downregulation of E-cadherin expression. Global gene expression analysis following TNFAIP2 knockdown identified MTDH as a positive regulator of TNFAIP2-derived EMT acquisition in cancer cells. The present results suggest a relationship between TNFAIP2 and EMT in cancers under the control of CDDP, in which MTDH expression levels in cancer cells are vital for promoting TNFAIP2-derived EMT acquisition.

  • Japanese Case of Enzalutamide-Resistant Prostate Cancer Harboring a SPOP Mutation With Scattered Allelic Imbalance: Response to Platinum-Based Therapy

    Watanabe K., Kosaka T., Aimono E., Hongo H., Mikami S., Nishihara H., Oya M.

    Clinical Genitourinary Cancer (Clinical Genitourinary Cancer)   2019

    ISSN  15587673

  • Prognostic value of serum C-reactive protein level prior to second-line treatment in intermediate risk metastatic renal cell carcinoma patients

    Takamatsu K., Mizuno R., Tanaka N., Takeda T., Morita S., Matsumoto K., Kosaka T., Shinojima T., Kikuchi E., Asanuma H., Oyama M., Mikami S., Oya M.

    International Journal of Clinical Oncology (International Journal of Clinical Oncology)   2019

    ISSN  13419625

     View Summary

    © 2019, Japan Society of Clinical Oncology. Background: The later-line treatment of metastatic renal cell carcinoma (mRCC) has been drastically changing by the development of immune-oncology drugs and molecular targeted treatment in recent years. Although the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model is useful for second-line setting, this model has the problem that over 50% patients are classified as intermediate risk group. The aim of this study is to evaluate whether the serum C-reactive protein (CRP) levels prior to second-line treatment could divide intermediate risk group patients. Methods: We retrospectively reviewed 82 consequent intermediate-risk mRCC patients who received second-line molecular targeted therapy. We classified patients who had serum CRP higher than 0.5 mg/dl in elevated CRP group because the median baseline serum CRP level before second-line treatment was 0.51 mg/dl. We assessed the prognostic impact of serum CRP levels prior to second-line treatment initiation to predict overall survival (OS). Results: Thirty-three out of 82 (40%) patients demonstrated elevated baseline CRP levels. The median OS of elevated and non-elevated CRP group was 11.5 (95% CI 5.4–17.5) and 29.4 (95% CI 25.5–33.5) months, respectively (p = 0.001). The serum CRP elevation could predict prognosis in intermediate risk patients treated with second-line treatment (HR 2.5, 95% CI 1.4–4.2, p = 0.001). Conclusions: The serum CRP levels after first-line treatment termination could divide intermediate risk group mRCC patients into two prognostic subgroups in second-line targeted treatment setting.

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

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Presentations 【 Display / hide

  • 妊婦に生じた隆起性皮膚線維肉腫(DFSP)の1例

    豊島 進(慶応義塾大学), 栗原 佑一, 持丸 奈央子, 平井 郁子, 中村 善雄, 天谷 雅行, 舩越 建, 三上 修治

    日本皮膚科学会雑誌(0021-499X)127巻12号 Page2653(2017.11), 2017.11

  • 両側びまん性すりガラス陰影と気管内結節を認めた濾胞性リンパ腫の1例

    桑江 美聡(慶応義塾大学医学部附属病院 呼吸器内科), 川田 一郎, 渡辺 理沙, 入江 秀大, 奥隅 真一, 中鉢 正太郎, 鎌田 浩史, 石井 誠, 猶木 克彦, 別役 智子, 西村 瑤子, 蔵本 純子, 林 雄一郎, 三上 修治, 亀山 香織

    気管支学(0287-2137)39巻6号 Page536(2017.11), 2017.11

  • 2回肺部分切除術を施行し胃癌肺転移と考えられた1例

    森本 洋輔(日野市立総合病院 外科), 藤田 晃司, 島田 理子, 一坂 俊介, 森 克昭, 石川 啓一, 堂脇 昌一, 菊永 裕行, 熊井 浩一郎, 三浦 弘志, 森永 正二郎, 三上 修治, 山本 達也

    日本臨床外科学会雑誌(1345-2843)78巻増刊 Page738(2017.10), 2017.10

  • 細胞診で扁平上皮癌と診断し組織診との乖離があった5例の細胞像

    照井 仁美(慶応義塾大学医学部附属病院 病理診断科), 岡田 ゆり子, 蔵本 純子, 川井田 みほ, 三上 修治, 林 雄一郎, 田中 京子, 岩田 卓, 青木 大輔, 亀山 香織

    日本臨床細胞学会雑誌(0387-1193)56巻Suppl.2 Page806(2017.10), 2017.10

  • 前立腺癌における予後因子としてのバソヒビン2発現の検討(英語)

    宮崎 保匡(慶応義塾大学 医学部泌尿器科学教室), 小坂 威雄, 三上 修治, 安水 洋太, 田中 伸之, 菊地 栄次, 佐藤 靖史, 大家 基嗣

    日本癌学会総会記事(0546-0476)76回 Page P-3204(2017.09), 2017.09

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

  • 腎細胞癌の個別化医療推進を目的とした分子標的薬による癌微小環境再構築の解析

    2019.04
    -
    2021.03

    日本学術振興会, 基盤研究(C), 三上 修治, 水野 隆一、田中 伸之, 人体病理, Research grant, Principal Investigator

  • 癌微小環境に着目した腎細胞癌の進展および治療耐性機構の解明

    2017.04
    -
    2019.03

    科学研究費補助金(文部科学省・日本学術振興会) 基盤(C), Grant-in-Aid for Scientific Research, Research grant, Co-investigator

  • 腎細胞癌の分子標的薬による治療効果の病理学的解析と耐性機構の解明

    2013.04
    -
    2016.03

    Grant-in-Aid for Scientific Research, Research grant

  • 腎細胞癌における VASH1発現の病理学的検討

    2013.04
    -
    2014.03

    Keio Gijuku Academic Development Funds, Research grant

  • EMT誘導因子をターゲットとした腎細胞癌の分子標的治療

    2011.04
    -
    2013.03

    Grant-in-Aid for Scientific Research, Research grant

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Awards 【 Display / hide

  • 日本病理学会学術研究賞

    2014.11, 日本病理学会

  • 日本病理学会学術奨励賞

    2010.04, 日本病理学会

  • Pathology International High Citation Award

    2017.09

    Type of Award: Celebration by Official journal of a scientific society or Academic Journal

  • 第15回白壁賞

    岩男泰、三上修治、向井万起男、松岡克善、日比紀文、長谷川博俊、杉野吉則, 2009.09, 胃と腸, colitic cancer/dysplasiaの画像診断-拡大内視鏡を中心に

    Type of Award: Other Awards

 

Courses Taught 【 Display / hide

  • DISEASES OF ORGAN SYSTEMS

    2019

Courses Previously Taught 【 Display / hide

  • 病理診断科臨床実習

    Keio University, 2017, Full academic year, Major subject, Laboratory work/practical work/exercise, Within own faculty

  • 病理診断部臨床実習

    Keio University, 2016, Full academic year, Major subject, Laboratory work/practical work/exercise, Within own faculty

  • 病理診断部臨床実習

    Keio University, 2015, Full academic year, Major subject, Laboratory work/practical work/exercise, Within own faculty

  • 病理診断部臨床実習

    Keio University, 2014, Full academic year, Major subject, Laboratory work/practical work/exercise, Within own faculty

  • 病理診断部臨床実習

    Keio University, 2013, Full academic year, Major subject, Laboratory work/practical work/exercise, Within own faculty

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Social Activities 【 Display / hide

  • がん対策情報センター・CIS病理診断コンサルテーション・サービス

    2011.04
    -
    Present
  • 日本病理学会コンサルテーションシステム コンサルタント

    日本病理学会

    2012.04
    -
    Present
  • 腎癌研究会 世話人

    2010.04
    -
    Present
  • 中外製薬 RCC PD-L1(SP142) 病理アドバイザリーボード

    中外製薬

    2018.12
    -
    Present
  • アストラゼネカ 尿路上皮癌領域におけるPD-L1検査に関するアドバイザリーボード

    アストラゼネカ

    2018.12
    -
    Present

Memberships in Academic Societies 【 Display / hide

  • 日本病理学会, 

    1998.04
    -
    Present
  • 日本臨床細胞学会, 

    2002.04
    -
    Present
  • 日本癌学会, 

    1998.04
    -
    Present
  • 日本分子形態学会, 

    2010.10
    -
    Present

Committee Experiences 【 Display / hide

  • 2017.01
    -
    Present

    Pathology International, Editor

  • 2013.01
    -
    Present

    International Cancer Conference Journal Editorial Board

  • 2010.04
    -
    Present

    世話人, 腎癌研究会

  • 2002.04
    -
    Present

    Member, 日本臨床細胞学会

  • 1998.04
    -
    Present

    会員, 日本癌学会

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