KANAI Yae

写真a

Affiliation

School of Medicine, Department of Pathology Kanai Laboratory (Shinanomachi)

Position

Professor

Related Websites

External Links

Career 【 Display / hide

  • 1993.04
    -
    1998.06

    National Cancer Center, Pathology Division, Research member

  • 1998.07
    -
    2002.06

    National Cancer Center, Pathology Division, Head of Section

  • 2002.07
    -
    2010.03

    National Cancer Center, Pathology Division, Chief

  • 2010.04
    -
    2017.03

    National Cancer Center Research Institute, Division of Molecular Pathology, Chief

  • 2010.11
    -
    2014.03

    National Cancer Center Research Institute, Deputy Director

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Academic Background 【 Display / hide

  • 1983.04
    -
    1989.03

    Keio University, Medical School

    University, Graduated

  • 1989.04
    -
    1993.03

    Keio University, Postgraduate School, Keio University School of Medicine, Pathology Course

    Graduate School, Completed

Academic Degrees 【 Display / hide

  • 博士 (医学), Keio University, Coursework, 1993.03

Licenses and Qualifications 【 Display / hide

  • 医師免許, 1989.05

  • 死体解剖資格, 1992.02

  • 日本病理学会病理専門医, 1994.08

  • 日本臨床細胞学会細胞診専門医, 1998.12

  • 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 (Cancer epigenomics)

Research Keywords 【 Display / hide

  • Molecular pathology

  • Tumor pathology

  • DNA methylation

  • Multilayer/integrative comics analysis

  • Genitourinary Pathology

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Books 【 Display / hide

  • 解明病理学 : 病気のメカニズムを解く

    加藤 光保, 金井 弥栄, 菅野 祐幸, 青笹 克之, 医歯薬出版, 2021

  • DNA and Histone Methylation as Cancer Targets

    Arai E, Yotani T, Kanai Y., Elsevier, 2017

    Scope: Liver Cancer

  • DNA and Histone Methylation in Liver Cancer

    Arai E., Yotani T., Kanai Y., Cancer Drug Discovery and Development, 2017

     View Summary

    Epigenetic alterations, such as alterations of histone modification and DNA methylation, occur in a genome-wide manner under precancerous conditions resulting from hepatitis B virus (HBV) or hepatitis C virus (HCV) infection followed by chronic hepatitis and cirrhosis, or aberrant lipogenesis and abnormal metabolism of reactive oxygen species that characterize the pathophysiology of non-alcoholic steatohepatitis (NASH). Once DNA methylation alterations occur at the precancerous stage, they are stably preserved on DNA double strands through methylation maintenance by DNA methyltransferase 1 (DNMT1). DNA methylation alterations associated with abnormalities of DNA methyltransferase, such as overexpression of DNMT1 and splicing alterations of DNMT3B, participate in multistage hepatocarcinogenesis from the precancerous stage to the malignant progression stage and are correlated with aggressiveness of hepatocellular carcinomas (HCCs) and poorer outcome of affected patients. A number of tumor-related genes, such as ATK3, APC, BMP4, CCL20, CDH1, CDKN2A, CDKN2B, CSPG2, DAB2IP, DCC, DLC1, DPT, DPYSL3, EMILIN2, FZD7, GRASP, GSTP1, HIST1H4F, IGFALS, MGMT, MZB1, NAT2, NEFH, NFATC1, PAX4, PDSS2, PER3, PROZ, PYCARD, RASSF1A, SPDY1, RUNX3, SCGB1D1, SFN, SMPD3, SOCS1, TIMP3, TLX3, TM6SF1, TRIM33, TRIM58, WFDC6, WNK2 and ZFP41, are known to be silenced by DNA hypermethylation in human HCCs. It is believed that DNA methylation alterations could be excellent biomarkers for carcinogenetic risk estimation and prognostication. To facilitate clinical application of DNA methylation diagnosis, a scaled-down device that allows quick and accurate analysis, even in small hospitals and clinics, is now being developed. One therapeutic strategy against HCC proliferation could involve a combination of epigenetic modifiers, such as a DNA methylation inhibitor, a histone deacetylase inhibitor and an S-adenosylhomocysteine hydrolase inhibitor, to sensitize cancer cells to conventional chemotherapies, in addition to eradication of hepatitis viruses for personalized and/or pre-emptive medical care.

  • DNA Methylation Alterations in Human Cancers

    Kanai Y., Arai E., Epigenetics in Human Disease, 2012.12

  • DNA methylation alterations in human cancers. In: Epigenetics in Human Disease. ed. Tollefsbol T.

    Kanai Y, Arai E., Elsevier, Amsterdam, 2012,  Page: 29-52

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Papers 【 Display / hide

  • The Japanese Society of Pathology Practical Guidelines on the handling of pathological tissue samples for cancer genomic medicine.

    Y Hatanaka, T Kuwata, E Morii, Y Kanai, H Ichikawa, T Kubo, ...

    Pathology International (Pathology International)  71 ( 11 ) 725 - 740 2021.10

    Joint Work, Except for reviews,  ISSN  1320-5463

     View Summary

    Clinical cancer genomic testing based on next-generation sequencing can help select genotype-matched therapy and provide diagnostic and prognostic information. Pathological tissue from malignant tumors obtained during routine practice are frequently used for genomic testing. This article is aimed to standardize the proper handling of pathological specimens in practice for genomic medicine based on the findings established in “Guidelines on the handling of pathological tissue samples for genomic medicine (in Japanese)” published by The Japanese Society of Pathology (JSP) in 2018. The two-part practical guidelines are based on empirical data analyses; Part 1 describes the standard preanalytic operating procedures for tissue collection, processing, and storage of formalin-fixed paraffin-embedded (FFPE) samples, while Part 2 describes the assessment and selection of FFPE samples appropriate for genomic testing, typically conducted by a pathologist. The guidelines recommend that FFPE sample blocks be used within 3 years from preparation, and the tumor content should be ≥30% (minimum 20%). The empirical data were obtained from clinical studies performed by the JSP in collaboration with leading Japanese cancer genome research projects. The Japanese Ministry of Health, Labour, and Welfare (MHLW) recommended to comply with the JSP practical guidelines in implementing cancer genomic testing under the national health insurance system in over 200 MHLW-designated core and cooperative cancer genome medicine hospitals in Japan.

  • Molecular classification of gastric cancer predicts survival in patients undergoing radical gastrectomy based on project HOPE

    K Furukawa, K Hatakeyama, M Terashima, T Nagashima, K Urakami, ...

    Gastric Cancer, 1-11 (Gastric Cancer)   2021.09

    Joint Work, Except for reviews,  ISSN  1436-3291

     View Summary

    Background: Gastric cancer (GC) has been classified based on molecular profiling like The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG), and attempts have been made to establish therapeutic strategies based on these classifications. However, it is difficult to predict the survival according to these classifications especially in radically resected patients. We aimed to establish a new molecular classification of GC which predicts the survival in patients undergoing radical gastrectomy. Methods: The present study included 499 Japanese patients with advanced GC undergoing radical (R0/R1) gastrectomy. Whole-exome sequencing, panel sequencing, and gene expression profiling were conducted (High-tech Omics-based Patient Evaluation [Project HOPE]). We classified patients according to TCGA and ACRG subtypes, and evaluated the clinicopathologic features and survival. Then, we attempted to classify patients according to their molecular profiles associated with biological features and survival (HOPE classification). Results: TCGA and ACRG classifications failed to predict the survival. In HOPE classification, hypermutated (HMT) tumors were selected first as a distinctive feature, and T-cell-inflamed expression signature-high (TCI) tumors were then extracted. Finally, the remaining tumors were divided by the epithelial-mesenchymal transition (EMT) expression signature. HOPE classification significantly predicted the disease-specific and overall survival (p < 0.001 and 0.020, respectively). HMT + TCI showed the best survival, while EMT-high showed the worst survival. The HOPE classification was successfully validated in the TCGA cohort. Conclusions: We established a new molecular classification of gastric cancer that predicts the survival in patients undergoing radical surgery.

  • Brain Pathology of 18 Supercentenarians Aged 110 And Over

    Takao Masaki, Mihara Ban, Arai Yasumichi, Murakami Tomoyuki, Nose Soichiro, Hamaya Kazuo, Nishida Katsuya, Futamura Naonobu, Nakayama Yuji, Mizutani Masashi, Sano Terunori, Kanai Yae, Mimura Masaru, Okano Hideyuki, Hirose Nobuyoshi

    JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY 80 ( 6 ) 594 - 594 2021.06

    Joint Work, Except for reviews,  ISSN  0022-3069

  • Demarcated redness associated with increased vascular density/size: a useful marker of flat-type dysplasia in patients with ulcerative colitis.

    Ikebata A, Shimoda M, Okabayashi K, Uraoka T, Maehata T, Sugimoto S, Mutaguchi M, Naganuma M, Kameyama K, Yahagi N, Kanai T, Kitagawa Y, Kanai Y, Iwao Y

    Endoscopy international open 9 ( 4 ) E552 - E561 2021.04

    Research paper (scientific journal), Joint Work, Except for reviews,  ISSN  2364-3722

     View Summary

    Background and study aims  Recent advances in endoscopic equipment and diagnostic techniques have improved the detection of dysplasia in the inflamed mucosa of patients with ulcerative colitis (UC). However, it remains difficult to endoscopically identify flat-type dysplasia which has been formerly recognized as invisible dysplasia. Patients and methods  In this retrospective, single-center study, we endoscopically identified 10 cases of flat-type-predominant dysplasia by targeted biopsy among 38 intramucosal dysplasia lesions from patients with UC who underwent surgical or endoscopic resection from 2007 to 2017. Their endoscopic and histological features were examined, including color changes, intramucosal vascular density/size, and vascular endothelial growth factor (VEGF) expression. Results  All flat-type-predominant dysplasias were endoscopically recognized as demarcated red-colored areas and histologically diagnosed as low- (LGDs) or high-grade dysplasias (HGDs). Immunohistochemical examination using resected specimens revealed that flat-type dysplasia was characterized by significantly increased CD34-positive vascular density (LGDs, 1.7-fold, P < 0.01; HGDs, 2.2-fold, P  < 0.01) and size (LGDs, 1.03-fold, P  < 0.01; HGDs, 1.11-fold, P  < 0.01) in the mucosa, compared to adjacent non-neoplastic areas. Increased numbers of vessels were observed at the base of the mucosa in LGDs, whereas HGDs contained increased/enlarged vessels throughout the mucosa. Moreover, VEGF expression was elevated in all dysplastic epithelia. Conclusions  Demarcated red-colored areas, histologically characterized by an increased vascular density/size in the mucosa, are an endoscopic sign of formerly invisible flat-type dysplasia in patients with UC and should be considered for targeted biopsy. Prospective studies focusing on the mucosal color change for their early detection would be desirable in the future.

  • Alterations of protein glycosylation and DNA methylation in urothelial carcinoma

    Fujimoto Mao, Arai Eri, Matsuda Atsushi, Maeshima Akiko, Fujimoto Hiroyuki, Kuno Atsushi, Yoshida Teruhiko, Kanai Yae

    CANCER SCIENCE 112   670 - 670 2021.02

    Joint Work, Except for reviews,  ISSN  1347-9032

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

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Reviews, Commentaries, etc. 【 Display / hide

  • 【病理医が知っておくべき法令や指針】Q&A 剖検

    若狹 朋子, 木ノ元 直樹, 種井 善一, 金井 弥栄, 柴原 純二

    病理と臨床 ((株)文光堂)  39 ( 9 ) 904 - 908 2021.09

    Other article, Joint Work,  ISSN  0287-3745

  • 【病理医が知っておくべき法令や指針】研究に関わる指針と法令

    金井 弥栄

    病理と臨床 ((株)文光堂)  39 ( 9 ) 889 - 895 2021.09

    Other article, Single Work,  ISSN  0287-3745

  • IBD発癌の諸問題・基礎〜臨床まで 血管増生を背景とした境界のある発赤は潰瘍性大腸炎関連平坦型dysplasia発見の有用なマーカーである

    池端 昭慶, 下田 将之, 岡林 剛史, 茂田 浩平, 清島 亮, 松井 信平, 杉本 真也, 矢作 直久, 金井 隆典, 北川 雄光, 金井 弥栄, 岩男 泰

    日本大腸肛門病学会雑誌 ((一社)日本大腸肛門病学会)  74 ( 9 ) A80 - A80 2021.09

    Other article, Joint Work,  ISSN  0047-1801

  • 喫煙マウスモデルを用いたロフルミラストの気腫・肺癌発症予防効果の検討

    中山 真吾, 中鉢 正太郎, 櫻井 香, 入江 秀大, 堤 昭宏, 大竹 史朗, 和田 祥佳, 加川 志津子, 下田 将之, 金井 弥栄, Hegab Ahmed E, 福永 興壱

    日本呼吸器学会誌 ((一社)日本呼吸器学会)  10 ( 増刊 ) 204 - 204 2021.04

    Other article, Joint Work,  ISSN  2186-5876

  • 喫煙マウスモデルを用いたCelecoxibの肺気腫・肺癌発症予防効果の検討

    櫻井 香, 中鉢 正太郎, 入江 秀大, 中山 真吾, 加川 志津子, 和田 祥佳, 宮田 純, 下田 将之, 金井 弥栄, Hegab Ahmed E, 福永 興壱

    日本呼吸器学会誌 ((一社)日本呼吸器学会)  10 ( 増刊 ) 204 - 204 2021.04

    Other article, Joint Work,  ISSN  2186-5876

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Presentations 【 Display / hide

  • Intratumor DNA methylation heterogeneity reflects differentiation plasticity and malignant progression of human glioblastoma: a methylome analysis using microdissected specimens.

    Kentaro Ohara, Eri Arai, Hikaru Sasaki, Masashi Nakatsukasa, Kazunari Yoshida, Yae Kanai.

    11th AACR-JCA Joint Conference on Breakthroughs in Cancer. (Hawaii) , 2019.02, Poster (general)

  • Genome-wide DNA methylation analysis in non-alcoholic steatohepatitis-related hepatocellular carcinomas.

    Ying Tian, Eri Arai, Junko Kuramoto, Satomi Makiuchi, Noboru Tsuda, Hidenori Ojima, Yukihiro Fukamachi, Yoriko Takahashi, Nobuyoshi Hiraoka, Teruhiko Yoshida, Yae Kanai.

    11th AACR-JCA Joint Conference on Breakthroughs in Cancer. (Hawaii) , 2019.02, Poster (general)

  • Epigenome-wide association study of whole blood from kidney cancer patients indicates hypomethylation of a PCBD2 intronic region.

    Hideki Ohmomo, Shohei Komaki, Yuh Shiwa, Ryo Otomo, Yoichi Sutoh, Tsuyoshi Hachiya, Kanako Ono, Mamoru Satoh, Makoto Sasaki, Eri Arai, Hiroyuki Fujimoto, Teruhiko Yoshida, Yae Kanai, Atsushi Shimizu.

    70th American Society of Human Genetics (Houstonm) , 2019, Poster (general)

  • Integrated analysis of genetic and epigenetic alterations in gastric carcinomas.

    Menghan Yang, Eri Arai, Hiromi Sakamoto, Hirohiko Totsuka, Hirokazu Taniguchi, Hitoshi Katai, Teruhiko Yoshida, Yae Kanai.

    AACR Annual Meeting 2019 (Atlanta) , 2019, Poster (general)

  • Genome-wide DNA methylation analysis during non-alcoholic steatohepatitis-related multistage hepatocarcinogenesis: Comparison with hepatitis virus-related carcinogenesis.

    Junko Kuramoto, Eri Arai, Ying Tian, Nobuaki Funahashi, Masaki Hiramoto, Takao Nammo, Yuichi Nozaki, Yoriko Takahashi, Nanako Ito, Ayako Shibuya, Hidenori Ojima, Aoi Sukeda, Yosuke Seki, Kazunori Kasama, Kazuki Yasuda, Yae Kanai.

    AACR Annual Meeting 2018 (Chicago) , 2018, Poster (general)

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

  • Pathological diagnosis based on integration of morphological images and multi-layer omics data by artificial intelligence

    2021.04
    -
    2024.03

    Keio University, 金井 弥栄, 榊原 康文, 新井 恵吏, Grant-in-Aid for Scientific Research (B)

     View Summary

    本研究は、人工知能 (AI)の支援を受けて病理形態像とゲノム等オミックス情報を融合させ、がんの治療奏効性・有害事象・予後を予測する深層学習モデルを構築することを目的とする。予測時のAIの着眼点を可視化し、形態学的診断基準に翻訳して、病理医が顕微鏡で見るだけでモデルと同等の治療奏効性・有害事象・予後予測を可能にすることを目指す。悪性度が高い腎淡明細胞がんのCpGアイランドメチル化形質 (CIMP)の予測モデルを構築する過程で、病理画像とオミックスデータを統合する至適研究手法を確立し、「病理医とAIの創造的協働による、オミックス情報を統合した新しい病理診断の創出 (病理診断学の革新)」を図る。

  • NAD+およびエピゲノムの制御による老化メカニズムの解明と新たな抗加齢介入の開発

    2019.06
    -
    2021.03

    Keio University, 齋藤 義正, 金井 弥栄, Challenging Research (Exploratory)

     View Summary

    超高齢社会に突入した我が国において、抗加齢により健康寿命を延長させることは喫緊の課題となっている。カロリー制限によってニコチンアミドアデニンジヌクレオチド(NAD+)依存性のヒストン脱アセチル化酵素であるサーチュインが活性化されることにより、様々なエピゲノム変化が生じ、長寿遺伝子群が発現していることが予想されている。本研究では、組織幹細胞の3次元培養技術であるオルガノイド培養法により腸管上皮からオルガノイドを樹立し、エピゲノム変化および遺伝子発現を網羅的に解析することで老化の分子機構を解明する。さらに、NAD+前駆体の投与および領域特異的なエピゲノム制御に基づく新たな抗加齢介入の開発を目指す。

  • 化学療法抵抗性を有する転移性膀胱癌に対するエピジェネティックス治療確立

    2019.04
    -
    2022.03

    University of Toyama, 西山 直隆, 金井 弥栄, 北村 寛, 鈴木 拓, Grant-in-Aid for Scientific Research (C)

     View Summary

    セカンドライン以降の十分な治療戦略が必要とされる尿路上皮癌に対し、転移性尿路上皮癌の化学療法抵抗性へのエピジェネティクスの関与を解明し、エピジェネティクス治療を用いた2次治療を開発する。DNAメチル化の減弱を起こすDNAメチル基転移酵素(DNMT)阻害剤である5-aza-2-deoxycytidine(5-Aza-CdR)による化学療法再感受性獲得の詳細な分子機構について解析を行い、patient derived xenograftモデルを用いて5-Aza-CdR・ CDDP併用治療の安全性と有効性のPOCを確立し、5-Aza-CdR を用いた2次治療としての臨床試験を行う。

  • 免疫応答モニタリングによるがん免疫の全容理解に基づく新規層別化マーカーの開発

    2019
    -
    2022

    日本医療研究開発機構, 次世代治療・診断実現のための創薬基盤技術開発事業, 上田龍三, Co-investigator

  • NASH 肝がんの リピド・ゲノミクス 研究に基づく個別化医療の開発

    2018
    -
    2022

    日本医療研究開発機構, 肝炎等克服実用化研究事業, 考藤達哉, Co-investigator

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Intellectual Property Rights, etc. 【 Display / hide

  • 尿路上皮癌のリスク判定方法

    Application No.: PCT/JP2019/011442  2019.03 

    Patent, Joint, PCT international application

  • 子宮体癌の予後の判定方法

    Application No.: 特願2018-228276  2018.11 

    Patent, Joint, National application

  • Method for assessing risk of hepatocellular carcinoma

    Application No.: PCT/JP2018/031092  2018.08 

    Patent, Joint, PCT international application

  • 尿路上皮癌のリスク判定方法

    Application No.: 特願2018-051464  2018.03 

    Patent, Single, National application

  • 肝細胞癌のリスク評価方法

    Application No.: 特願2017-160284  2017.08 

    Patent, Joint, National application

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Awards 【 Display / hide

  • JCA Women Scientists Award

    Yae Kanai, 2018.09, Japanese Cancer Association, Molecular pathological approach ti epigenome mechanisms of multistage human carcinogenesis

    Type of Award: Awards of National Conference, Council and Symposium.  Country: Japan

  • Tamiya Prize

    2006.02, Foundation for Promotion of Cancer Research, Cancer development, invasion and metastasis: Epigenetic research based on histopathological approach

    Type of Award: Awards of Publisher, Newspaper Company and Foundation

  • Incitement Award of the Japanese Cancer Association

    2003.09, Japanese Cancer Association, DNA methylation abnormalities participating in multistage human carcinogenesis

    Type of Award: Awards of National Conference, Council and Symposium

  • Incitement Award of the Japanese Society of Pathology

    Yae Kanai, 2002.03, Japanese Society of Pathology, DNA methylation alterations during multistage human carcinogenesis

    Type of Award: Awards of National Conference, Council and Symposium

  • Baelz Prize

    Setsuo Hirohashi, Atsushi Ochiai, Yae Kanai, 2000.11, ベルツ財団, Inactivation of E-cadherin cell adhesion system in human cancer invasion and metastasis

 

Courses Taught 【 Display / hide

  • PATHOLOGY: SEMINAR

    2021

  • PATHOLOGY: PRACTICE

    2021

  • PATHOLOGY

    2021

  • GENERAL PATHOLOGY

    2021

  • DISEASES OF ORGAN SYSTEMS

    2021

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Courses Previously Taught 【 Display / hide

  • General Pathology

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

  • Diseases of organ systems

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

  • 症例検討 (基礎臨床統合医学)

    Keio University, 2018

  • 医学概論 (大学院医学研究科修士課程)

    Keio University, 2018

  • 医学特別講義 (大学院医学研究科博士課程)

    Keio University, 2018

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Memberships in Academic Societies 【 Display / hide

  • Associate member, Science Council of Japan, 

    2006
    -
    Present
  • 日本病理学会: 学術評議員 (病理専門医、病理専門医研修指導医、分子病理専門医、ゲノム病理組織取扱い規約委員会委員長、ゲノム病理診断検討委員会委員、ゲノム病理標準化講習会委員会委員、学術委員会委員、機関誌常任刊行委員会委員), 

    1989
    -
    Present
  • 日本癌学会: 評議員 (利益相反委員会委員、機関誌associate editor)

     
  • 日本臨床細胞学会

     
  • 日本エピジェネティクス研究会 (幹事)

     

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Committee Experiences 【 Display / hide

  • 2017
    -
    Present

    日本医療研究開発機構プログラムオフィサー・課題評価委員会委員・アドバイザー

  • 2015
    -
    2016

    文部科学省科学研究費補助金における評価に関する委員会生物系委員会委員

  • 2014
    -
    Present

    東北メディカルメガバンク計画試料情報分譲審査委員会小委員会委員

  • 2014
    -
    2015

    科学技術振興機構国際科学技術協力推進委員

  • 2014
    -
    2015

    科学技術振興機構研究成果展開事業研究成果最適展開支援プログラム推進アドバイザー

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