Kanai, Takanori

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Gastroenterology and Hepatology) （Shinanomachi）

Position

Professor

E-mail Address

E-mail address

Related Websites
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Other Affiliation 【 Display / hide 】

  • Dean, School of Medicine

  • School of Medicine, School of Medicine, Professor and Chairman

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Licenses and Qualifications 【 Display / hide 】

  • 日本がん治療認定機構暫定教育医

  • 日本肝臓学会認定肝臓専門医

  • 日本消化器内視鏡学会専門医

  • 日本消化器病学会指導医

  • 日本消化器病学会認定医

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Research Keywords 【 Display / hide 】

  • ディスバイオーシス

  • プロバイオティクス

  • 免疫学

  • 炎症性腸疾患

  • 神経免疫学

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Papers 【 Display / hide 】

  • Analysis of risk factors for immune-related adverse events in various solid tumors using real-world data

    Shimozaki K., Sukawa Y., Sato Y., Horie S., Chida A., Tsugaru K., Togasaki K., Kawasaki K., Hirata K., Hayashi H., Hamamoto Y., Kanai T.

    Future Oncology （Future Oncology)  17 （ 20 ） 2593 - 2603 2021.07

    ISSN  14796694

    　View Summary

    The aim of this study was to determine the risk factors for immune-related adverse events (irAEs) induced by immune checkpoint inhibitors. The authors conducted a retrospective study in which patients with malignant melanoma, non-small-cell lung cancer, gastric cancer or renal cell carcinoma who received anti-PD-1/PD-L1 antibodies were included. Of 247 patients, 118 developed a total of 182 irAEs. In the multivariate Fine-Gray regression analysis, serum albumin level ≥3.6 g/dl (hazard ratio: 1.62; 95% CI: 1.10-2.39; p = 0.015) and history of Type I hypersensitivity reactions (hazard ratio: 1.48; 95% CI: 1.02-2.14; p = 0.037) were significantly associated with the development of irAEs. High serum albumin levels and history of Type I hypersensitivity reactions are risk factors for irAEs.

  • Clinical, Endoscopic, and Pathological Characteristics of Immune Checkpoint Inhibitor-Induced Gastroenterocolitis

    Hayashi Y., Hosoe N., Takabayashi K., Limpias Kamiya K.J.L., Tsugaru K., Shimozaki K., Hirata K., Fukuhara K., Fukuhara S., Mutaguchi M., Sujino T., Sukawa Y., Hamamoto Y., Naganuma M., Takaishi H., Shimoda M., Ogata H., Kanai T.

    Digestive Diseases and Sciences （Digestive Diseases and Sciences)  66 （ 6 ） 2129 - 2134 2021.06

    ISSN  01632116

  • Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

    Shinzaki S., Matsuoka K., Tanaka H., Takeshima F., Kato S., Torisu T., Ohta Y., Watanabe K., Nakamura S., Yoshimura N., Kobayashi T., Shiotani A., Hirai F., Hiraoka S., Watanabe M., Matsuura M., Nishimoto S., Mizuno S., Iijima H., Takehara T., Naka T., Kanai T., Matsumoto T.

    Journal of Gastroenterology （Journal of Gastroenterology)  56 （ 6 ） 560 - 569 2021.06

    ISSN  09441174

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    Background: This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). Methods: Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn’s disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. Results: A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). Conclusions: Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

  • Current status of colon capsule endoscopy

    Hosoe N., Limpias Kamiya K.J.L., Hayashi Y., Sujino T., Ogata H., Kanai T.

    Digestive Endoscopy （Digestive Endoscopy)  33 （ 4 ） 529 - 537 2021.05

    ISSN  09155635

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    While both the annual incidence and mortality of colorectal cancer are slowly but steadily decreasing in the United States, the incidence of such malignancy is increasing in Japan. Thus, controlling colorectal cancer in Japan is a major concern. In 2006, colon capsule endoscopy was first introduced by Eliakim et al. First-generation colon capsule endoscopy had a moderate sensitivity for detecting polyps of more than 6 mm. Thus, second-generation colon capsule endoscopy was developed to achieve higher sensitivity. Colonoscopy is the gold standard tool for colorectal cancer surveillance. With an improvement in the imaging function, the performance of second-generation colon capsule endoscopy is almost as satisfactory as that of colonoscopy. Certain situations, such as incomplete colonoscopy and contraindication for use of sedation, can benefit from colon capsule endoscopy. Colon capsule endoscopy requires a more extensive bowel preparation than colonoscopy and computed tomography colonography because it requires laxatives not only for bowel cleansing but also for promoting the excretion of the capsule. Another problem with colon capsule endoscopy includes the burden of reading and interpretation and overlook of the lesions. Currently, the development of automatic diagnosis of colon capsule endoscopy using artificial intelligence is still under progress. Although the available guidelines do not support the use of colon capsule endoscopy for inflammatory bowel disease, the possible application of colon capsule endoscopy is ulcerative colitis. This review article summarizes and focuses on the current status of colon capsule endoscopy for colorectal cancer screening and the possibility for its applicability on inflammatory bowel disease.

  • Oncogenic KRAS–expressing organoids with biliary epithelial stem cell properties give rise to biliary tract cancer in mice

    Kasuga A., Semba T., Sato R., Nobusue H., Sugihara E., Takaishi H., Kanai T., Saya H., Arima Y.

    Cancer Science （Cancer Science)  112 （ 5 ） 1822 - 1838 2021.05

    ISSN  13479032

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    Biliary tract cancer (BTC) arises from biliary epithelial cells (BECs) and includes intrahepatic cholangiocarcinoma (IHCC), gallbladder cancer (GC), and extrahepatic cholangiocarcinoma (EHCC). Although frequent KRAS mutations and epigenetic changes at the INK4A/ARF locus have been identified, the molecular pathogenesis of BTC is unclear and the development of corresponding anticancer agents remains inadequate. We isolated epithelial cell adhesion molecule (EpCAM)–positive BECs from the mouse intrahepatic bile duct, gallbladder, and extrahepatic bile duct, and established organoids derived from these cells. Introduction of activated KRAS and homozygous deletion of Ink4a/Arf in the cells of each organoid type conferred the ability to form lethal metastatic adenocarcinoma with differentiated components and a pronounced desmoplastic reaction on cell transplantation into syngeneic mice, indicating that the manipulated cells correspond to BTC–initiating cells. The syngeneic mouse models recapitulate the pathological features of human IHCC, GC, and EHCC, and they should therefore prove useful for the investigation of BTC carcinogenesis and the development of new therapeutic strategies. Tumor cells isolated from primary tumors formed organoids in three-dimensional culture, and serial syngeneic transplantation of these cells revealed that their cancer stem cell properties were supported by organoid culture, but not by adherent culture. Adherent culture thus attenuated tumorigenic activity as well as the expression of both epithelial and stem cell markers, whereas the expression of epithelial-mesenchymal transition (EMT)–related transcription factor genes and mesenchymal cell markers was induced. Our data show that organoid culture is important for maintenance of epithelial cell characteristics, stemness, and tumorigenic activity of BTC–initiating cells.

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

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Reviews, Commentaries, etc. 【 Display / hide 】

  • Bacteriotherapy for inflammatory bowel disease

    Yoshimatsu Y., Mikami Y., Kanai T.

    Inflammation and Regeneration (Inflammation and Regeneration)  41 ( 1 )  2021.12

    　View Summary

    The number of patients with inflammatory bowel disease is rapidly increasing in developed countries. The main cause of this increase is thought not to be genetic, but secondary to rapidly modernized environmental change. Changes in the environment have been detrimental to enteric probiotics useful for fermentation, inducing an increase in pathobionts that survive by means other than fermentation. This dysregulated microbiota composition, the so-called dysbiosis, is believed to have increased the incidence of inflammatory bowel disease. Bacteriotherapy, a treatment that prophylactically and therapeutically corrects the composition of disturbed intestinal microbiota, is a promising recent development. In fact, fecal microbiome transplantation for recurrent Clostridioides difficile infection in 2013 was a significant contribution for bacteriotherapy. In this paper, we comprehensively review bacteriotherapy in an easy-to-understand format.

  • Pulmonary arterial hypertension caused by AhR signal activation protecting against colitis

    Hiraide T., Teratani T., Uemura S., Yoshimatsu Y., Naganuma M., Shinya Y., Momoi M., Kobayashi E., Hakamata Y., Fukuda K., Kanai T., Kataoka M.

    American Journal of Respiratory and Critical Care Medicine (American Journal of Respiratory and Critical Care Medicine)  203 ( 3 ) 385 - 388 2021.02

    ISSN  1073449X

  • How Can We Assess "Complete Healing" Beyond Endoscopic Remission?

    Fukuda T., Naganuma M., Kanai T.

    Inflammatory bowel diseases (Inflammatory bowel diseases)  25 ( 6 )  2019.05

    ISSN  10780998

  • Correction: Clinical utility of novel ultrathin single-balloon enteroscopy: A feasibility study (Endoscopy (2018) (50) DOI: 10.1055/a-0656-5622)

    Takabayashi K., Hosoe N., Miyanaga R., Fukuhara S., Kimura K., Mizuno S., Naganuma M., Yahagi N., Ogata H., Kanai T.

    Endoscopy (Endoscopy)  51 ( 5 )  2019

    ISSN  0013726X

    　View Summary

    © Georg Thieme Verlag KG, Stuttgart - New York. In the above-mentioned article, the name of the author Kaoru Takabayashi has been corrected. This was corrected in the online version on August 24, 2018.

  • Epigenetic regulation of T helper cells and intestinal pathogenicity

    Hagihara Y., Yoshimatsu Y., Mikami Y., Takada Y., Mizuno S., Kanai T.

    Seminars in Immunopathology (Seminars in Immunopathology)   2019

    ISSN  18632297

    　View Summary

    Inflammatory bowel diseases (IBDs) are characterized by relapsing and remitting chronic intestinal inflammation. Previous studies have demonstrated the contributions of genetic background, environmental factors (food, microbiota, use of antibiotics), and host immunity in the development of IBDs. More than 200 genes have been shown to influence IBD susceptibility, most of which are involved in immunity. The vertebrate immune system comprises a complex network of innate and adaptive immune cells that protect the host from infection and cancer. Dysregulation of the mutualistic relationship between the immune system and the gut environment results in IBD. Considering the fundamental role of epigenetic regulation in immune cells, epigenetic mechanisms, particularly in T helper (Th) cells, may play a major role in the complex regulation of mucosal immunity. Epigenetic regulation and dysregulation of Th cells are involved in the maintenance of intestinal homeostasis and its breakdown in IBD.

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Presentations 【 Display / hide 】

  • 口腔内細菌と原発性硬化性胆管炎の連関

    第6回日本心血管脳卒中学会学術集会　, 2019.06, Oral Presentation(guest/special)

  • ミクロ観察に挑戦する消化器内視鏡学 ：潰瘍性大腸炎の粘膜治癒観察から

    第108回日本消化器内視鏡学会関東支部例会, 2019.06, Oral Presentation(guest/special)

  • 腸内細菌と消化器疾患

    金井　隆典

    第116回　日本内科学会総会　教育講演, 2019.04, Oral Presentation(guest/special)

  • 粘膜下層深部への浸潤を認めたバレット腺癌の一例

    KANAI Takanori

    第106回日本消化器内視鏡学会関東支部例会, 2018.06

  • ガストリン著明上昇を伴わない自己免疫性胃炎を背景とした神経内分泌腫瘍の1例

    KANAI Takanori

    第106回日本消化器内視鏡学会関東支部例会, 2018.06

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

  • Development of genetically-designed COVID-19 mucosal immune vaccine with molecular needle platform

    2020.05
    -
    2021.03

    Takanori Kanai, Research grant, Principal Investigator

    　View Summary

    現在世界中に蔓延している新型コロナウイルス感染症(COVID-19)は全人類に対する緊急の脅威となっている。 これに対する有効なワクチンの開発はこの伝染性疾患を根絶するための公衆衛生上の最優先事項の一つである。 本申請において、我々は「分子ニードル」(特許出願 No. 2018-158128、No.2019-154360)技術を用いたCOVID-19に対する有効なワクチンの開発を提案する。同技術は免疫の標的となるエピトープを非常に効率的に免疫提示細胞に導入することを可能にし、「分子ニードル」を構成するバクテリオファージ由来の蛋白がアジュバントとして作用するため、余計なアジュバントを追加することなく、コンポーネントワクチンの欠点となる免疫原性の低さを改善することができる。エピトープとしては、コロナウイルス感染に際して抗体の主要な認識分子となっているS蛋白に加えて、重症化する高リクス群を感染から予防することが期待されるペプチドを標的としたワクチン開発を行う。
    本研究では、後者のペプチドの選択を、ゲノムワイド関連解析の手法を用いて同定する。すなわち、100例のSARS-CoV-2感染重症例と400例の軽症ないし無症候性感染者について、全ゲノムシーケンス、SNPアレイタイピング、および超高解像度HLAタイピングを行い、両群で有意にアレル頻度の異なるHLAアレルおよびその他の遺伝子座/多型を同定する。　
    次に同解析の結果に基づいて、同定されたHLAに提示される可能性のあるSARS-CoV-2ウイルス由来ペプチドを、大規模コンピュータシミュレーションによって同定し、ワクチンの標的エピトープとして用いる。また、その他のリスクアレルの機能的解析を通じて、重症例においても有効なワクチン療法の開発に資する。　
    最後に、我々は先進的なオルガノイド技術を用いたワクチンの有効性の評価系を構築する。この目的のために腸管、気道およびその他のSARS-CoV-2の標的となる上皮組織よりオルガノイドを樹立し、これを用いて新規に開発されるワクチンの性能を迅速かつ効率的に評価するシステムを開発する。　本研究を通じて開発されるこれらのワクチンは、患者とくに重症化リスクの高い患者をCOVID-19から保護し、現在の流行感染の終息とその究極的な根絶に貢献すると期待される。

  • 宿主侵入菌に対する腸管免疫応答を介した消化器免疫難病の病態解明

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 金井 隆典, Grant-in-Aid for Scientific Research (A) , Principal Investigator

  • 腸管AhRワールドの解明

    2019.02
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 金井　隆典, Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research (B)), Principal Investigator

  • 腸管上皮再生作用を特長とする『インジゴ潰瘍性大腸炎カプセル』の治験開始に向けた開発研究

    2018.09
    -
    Present

    Research grant, Principal Investigator

  • 腸内細菌-上皮細胞相互作用から読み解く疾患発症メカニズムの解明

    2016.10
    -
    2022.03

    Research grant, Principal Investigator

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Awards 【 Display / hide 】

  • 日本消化器病学会学術賞

    2021.04

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

  • 日本免疫学会ヒト免疫研究賞

    2020.12

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

  • 慶應義塾大学医学部坂口洋光記念医学研究助成賞

    2009

  • 三越医学研究助成賞

    2008

  • 慶應義塾大学医学部三師会　北島賞

    2008

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, INTERNAL MEDICINE (GASTROENTEROLOGY)

    2021

  • LECTURE SERIES, INTERNAL MEDICINE

    2021

  • INTERNAL MEDICINE: SEMINAR

    2021

  • INTERNAL MEDICINE: PRACTICE

    2021

  • INTERNAL MEDICINE

    2021

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Memberships in Academic Societies 【 Display / hide 】

  • 日本臨床免疫学会, 

    2006.01
    -
    Present

  • Society of Mucosal Immunology (SMI)

    　

  • 日本内科学会

    　

  • 日本消化器病学会

    　

  • 日本消化器内視鏡学会

    　

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Committee Experiences 【 Display / hide 】

  • 2015
    -
    Present

    評議員, 日本門脈亢進症学会

  • 2015
    -
    Present

    理事, 日本無菌生物ノートバイオロジー学会

  • 2014
    -
    Present

    評議員, 日本臨床腸内微生物学会

  • 2014
    -
    Present

    特定疾患事業 「神経難病治療薬OCH-NCNPの炎症性腸疾患を対象とした医師主導治験へ向けた製剤確保、治験プロトコール作成、治験相談の実施」, 厚生労働省

  • 2013
    -
    Present

    財団評議員, 日本消化器病学会

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