KEIO RESEARCHERS INFORMATION SYSTEM

Other Affiliation 【 Display / hide 】

Other Affiliation 【 Display / hide 】

• Dean, Graduate School of Medicine

• Dean, School of Medicine

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

Licenses and Qualifications 【 Display / hide 】

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 】

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 】

Papers 【 Display / hide 】

• Relevance of pepsinogen, gastrin, and endoscopic atrophy in the diagnosis of autoimmune gastritis

  Kishikawa H., Nakamura K., Ojiro K., Katayama T., Arahata K., Takarabe S., Sasaki A., Miura S., Hayashi Y., Hoshi H., Kanai T., Nishida J.

  Scientific Reports （Scientific Reports)  12 （ 1 ）  2022.12

  　View Summary

  Simple objective modalities are required for evaluating suspected autoimmune gastritis (AIG). This cross-sectional study aimed to examine whether pepsinogen, gastrin, and endoscopic findings can predict AIG. The diagnostic performance of endoscopic findings and serology in distinguishing AIG was evaluated. AIG was diagnosed in patients (N = 31) with anti-parietal cell antibody and/or intrinsic factor antibody positivity and histological findings consistent with AIG. Non-AIG patients (N = 301) were seronegative for anti-parietal cell antibodies. Receiver operating characteristic curve analysis of the entire cohort (N = 332) identified an endoscopic atrophic grade cutoff point of O3 on the Kimura–Takemoto classification (area under the curve [AUC]: 0.909), while those of pepsinogen-I, I/II ratio, and gastrin were 20.1 ng/mL (AUC: 0.932), 1.8 (AUC: 0.913), and 355 pg/mL (AUC: 0.912), respectively. In severe atrophy cases (≥ O3, N = 58, AIG/control; 27/31), the cutoff values of pepsinogen-I, I/II ratio, and gastrin were 9.8 ng/mL (AUC: 0.895), 1.8 (AUC: 0.86), and 355 pg/mL (AUC: 0.897), respectively. In conclusion, endoscopic atrophy is a predictor of AIG. High serum gastrin and low pepsinogen-I and I/II ratio are predictors even in the case of severe atrophy, suggesting their usefulness when the diagnosis of AIG is difficult or as serological screening tests.

  • Access to Document (DOI)

• Efficacy and safety of low-dose rifabutin-based 7-day triple therapy as a third- or later-line Helicobacter pylori eradication regimen

  Inokuchi K., Mori H., Matsuzaki J., Hirata K., Harada Y., Saito Y., Suzuki H., Kanai T., Masaoka T.

  Helicobacter （Helicobacter)  27 （ 4 ）  2022.08

  ISSN  10834389

  　View Summary

  Background: Rifabutin-based regimens are used as rescue therapy for refractory Helicobacter pylori infection; however, the duration for which treatment is required and side effects are concerning. This study assessed the efficacy and safety of 7-day rifabutin, amoxicillin, and vonoprazan triple therapy as third- or later-line treatment for H. pylori infection. Materials and Methods: Patients who did not respond to second-line therapy were enrolled. After H. pylori infection was confirmed with the culture method, the patients received rifabutin-containing triple therapy (20 mg vonoprazan b.i.d., 500 mg amoxicillin q.i.d., and 150 mg rifabutin q.d.) for 7 days. Twelve weeks after the eradication therapy, successful eradication was confirmed using a 13C urea breath test or the H. pylori stool antigen test. The results obtained from our previous study that reported a 10-day or 14-day esomeprazole based rifabutin-containing triple therapy as a third- or fourth-line rescue therapy treated patients were used as historical control. We determined the minimum inhibitory concentrations of amoxicillin and rifabutin. We also evaluated whether the patients were positive for the mutation of the rpoB gene. Results: Intention-to-treat and per-protocol analyses showed that our regimen resulted in a high eradication rate (91.2%, 95% CI: 84%–99% and 92.7%, 95% CI: 86%–100%, respectively). Adverse events occurred in 31.6% of the patients, and two patients discontinued the therapy. Conclusions: This is the first study to evaluate the efficacy and safety of a 7-day low-dose rifabutin-based triple therapy with vonoprazan and amoxicillin. Our results suggest that our regimen was effective and safe as a third- or later-line H. pylori eradication regimen. To clarify what component in this regimen are critical, subsequent studies using a factorial design (comparing vonoprazan-amoxicillin dual therapy vs. vonoprazan-rifabutin triple therapy) will be needed.

  • Access to Document (DOI)

• AJM300 (carotegrast methyl), an oral antagonist of α4-integrin, as induction therapy for patients with moderately active ulcerative colitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 study

  Matsuoka K., Watanabe M., Ohmori T., Nakajima K., Ishida T., Ishiguro Y., Kanke K., Kobayashi K., Hirai F., Watanabe K., Mizusawa H., Kishida S., Miura Y., Ohta A., Kajioka T., Hibi T., Motoya S., Maemoto A., Fujiya M., Ashida T., Goto M., Matsumoto T., Suzuki Y., Hamahata Y., Nakagawa T., Kato N., Kato J., Endo Y., Suzuki R., Matsuda K., Ohmiya N., Katsushima S., Hosomi S., Tarumi K.i., Watanabe C., Saito M., Yokoyama Y., Inaba T., Sakata Y., Hongo H., Shibuya T., Kawakami K., Kakuta Y., Irisawa A., Yoshimura N., Fukuda K., Shirai T., Ichikawa H., Nagata J., Suzuki T., Yokoyama K., Tomidokoro T., Kojima Y., Yamada M., Yamamoto H., Yamamoto T., Horiki N., Obata H., Inoue S., Tanaka S., Toyokawa T., Kunihiro M., Hisabe T., Ogata S., Takeshima F., Matsushima K., Matsuhashi N., Sakuraba H., Iwabuchi M., Tsuchiya A., Uchiyama K., Kanai T., Nakamura M., Yokoyama T., Hida N., Mitsuyama K., Osada T., Hiraoka S., Tsuzuki T., Masuo T., Hokari R., Kobayashi T., Saruta M., Araki M., Araki H., Shimizu M., Kikuchi M., Nishikawa T., Takedatsu H., Aoyagi K., Ochiai T., Toda N., Mizokami Y., Nagahori M., Matsueda K., Kino H., Kanamori A., Suzuki T., Sakurai T., Kudo M.

  The Lancet Gastroenterology and Hepatology （The Lancet Gastroenterology and Hepatology)  7 （ 7 ） 648 - 657 2022.07

  ISSN  24681253

  　View Summary

  Background: AJM300 is an oral, small-molecule α4-integrin antagonist. We assessed the efficacy and safety of AJM300 in patients with moderately active ulcerative colitis. Methods: This multicentre, randomised, double-blind, placebo-controlled, phase 3 study consisted of two phases: a treatment phase and an open-label re-treatment phase. The study was done at 82 hospitals and clinics in Japan. Patients with a Mayo Clinic score of 6–10, endoscopic subscore of 2 or more, rectal bleeding subscore of 1 or more, and an inadequate response or intolerance to mesalazine were enrolled. Patients were randomly allocated (1:1) via a website to either AJM300 (960 mg) or placebo by the minimisation method, which was adjusted centrally by dynamic assignment against the Mayo Clinic score (≥6 to ≤7, ≥8 to ≤10 points), any use of corticosteroid, anti-TNFα antibody, or immunosuppressants during the disease-active period (yes vs no), duration of induction therapy until randomisation (<4 weeks vs ≥4 weeks) as the minimisation factors. Patients, investigators, site staff, assessors, and the sponsor were masked to treatment assignments. The study drug was administered orally, three times daily, for 8 weeks, and continued for up to 24 weeks if endoscopic remission was not achieved or rectal bleeding did not stop. The primary endpoint was the proportion of patients with a clinical response at week 8, and was analysed in the full analysis set. Clinical response was defined as a reduction in Mayo Clinic score of 30% or more and 3 or more, a reduction in rectal bleeding score of 1 or more or rectal bleeding subscore of 1 or less, and an endoscopic subscore of 1 or less at week 8. The study is registered with ClinicalTrials.gov, NCT03531892, and is closed to recruitment. Findings: Between June 6, 2018, and July 22, 2020, 203 patients were randomly assigned to AJM300 (n=102) or placebo (n=101). At week 8, 46 (45%) patients in the AJM300 group and 21 (21%) patients in the placebo group had a clinical response (odds ratio 3·30, 95% CI 1·73−6·29; p=0·00028). During the 8-week treatment and 16-week extension treatment periods, adverse events occurred in 39 (39%) of 101 patients in the placebo group and 39 (38%) of 102 patients in the AJM300 group. We found no difference in the incidence of adverse events between groups or after repeated administration of AJM300. The most common adverse event was nasopharyngitis (11 [11%] of 101 patients in the placebo group and ten [10%] of 102 patients in the AJM300 group). The most common treatment-related adverse event was also nasopharyngitis (four [4%] of 101 patients in the placebo group and three [3%] of 102 patients in the AJM300 group). Most adverse events were mild-to-moderate in severity. No deaths were reported. A serious adverse event was reported in the AJM300 group (one patient with anal abscess), but this was judged to be unrelated to study drug. Interpretation: AJM300 was well tolerated and induced a clinical response in patients with moderately active ulcerative colitis who had an inadequate response or intolerance to mesalazine. AJM300 could be a novel induction therapy for the treatment of patients with moderately active ulcerative colitis. Funding: EA Pharma and Kissei Pharmaceutical. Translation: For the Japanese translation of the abstract see Supplementary Materials section.

  • Access to Document (DOI)

• Th17 cells in the liver: balancing autoimmunity and pathogen defense

  Taniki N., Nakamoto N., Chu P.S., Ichikawa M., Teratani T., Kanai T.

  Seminars in Immunopathology （Seminars in Immunopathology)  44 （ 4 ） 509 - 526 2022.07

  ISSN  18632297

  　View Summary

  In addition to carcinogenesis, T helper 17 (Th17) cells (a subtype of CD4 + T lymphocytes) are involved in the acute, chronic, and cirrhotic phases of liver diseases; however, their role in the development and progression of liver diseases remains unclear. It is difficult to elucidate the role of Th17 cells in liver diseases due to their dichotomous nature, i.e., plasticity in terms of pathogenic or host protective function depending on environmental and time phase factors. Moreover, insufficient depletion of Th17 cells by inhibiting the cytokines and transcription factors involved in their production causes difficulties in analyzing their specific role in vitro and in vivo murine models, partially due to complex interaction. This review summarizes the recent progress in understanding the plasticity and function of hepatic Th17 cells and type 3 cytokines.

  • Access to Document (DOI)

• Development of a Deep-Learning Algorithm for Small Bowel-Lesion Detection and a Study of the Improvement in the False-Positive Rate

  Hosoe N., Horie T., Tojo A., Sakurai H., Hayashi Y., Kamiya K.J.L.L., Sujino T., Takabayashi K., Ogata H., Kanai T.

  Journal of Clinical Medicine （Journal of Clinical Medicine)  11 （ 13 ）  2022.07

  　View Summary

  Deep learning has recently been gaining attention as a promising technology to improve the identification of lesions, and deep-learning algorithms for lesion detection have been actively developed in small-bowel capsule endoscopy (SBCE). We developed a detection algorithm for abnormal findings by deep learning (convolutional neural network) the SBCE imaging data of 30 cases with abnormal findings. To enable the detection of a wide variety of abnormal findings, the training data were balanced to include all major findings identified in SBCE (bleeding, angiodysplasia, ulceration, and neoplastic lesions). To reduce the false-positive rate, “findings that may be responsible for hemorrhage” and “findings that may require therapeutic intervention” were extracted from the images of abnormal findings and added to the training dataset. For the performance evaluation, the sensitivity and the specificity were calculated using 271 detectable findings in 35 cases. The sensitivity was calculated using 68,494 images of non-abnormal findings. The sensitivity and specificity were 93.4% and 97.8%, respectively. The average number of images detected by the algorithm as having abnormal findings was 7514. We developed an image-reading support system using deep learning for SBCE and obtained a good detection performance.

  • Access to Document (DOI)

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

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

• The elucidation of the world of AhR in the intestinal environment, followed by the diverse clinical applications

  Kanai, Takanori

  科学研究費補助金研究成果報告書 2020

• Mechanism of immune tolerance in the liver via gut-liver axis

  Kanai, Takanori

  科学研究費補助金研究成果報告書 2019

• Investigation of the mechanisms for inhibitory effects on colonic inflammation and cancer of indigo naturalis including indole compounds

  Kanai, Takanori

  科学研究費補助金研究成果報告書 2018

• To identify the mechanism of inflammatory bowel disease by using human microbe mono-associated mouse

  Kanai, Takanori

  科学研究費補助金研究成果報告書 2017

• Development of therapeutic strategy for identification of new markers for ulcerative colitis associated colorectal cancers.

  Kanai, Takanori

  科学研究費補助金研究成果報告書 2017

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Epithelium Replacement Contributes to Field Expansion of Squamous Epithelium and Ulcerative Colitis–Associated Neoplasia

  Sugimoto S., Iwao Y., Shimoda M., Takabayashi K., Sato T., Kanai T., Mutaguchi M., Nanki K., Okabayashi K., Kawaida M., Aoki Y., Yoshimatsu Y., Kiyohara H., Kawaguchi T., Mikami Y., Fukuhara K., Sujino T., Hosoe N., Ogata H., Yahagi N.

  Gastroenterology (Gastroenterology)  162 ( 1 ) 334 - 337.e5 2022.01

  ISSN  00165085

  • Access to Document (DOI)

• Successful transpapillary removal of a migrated percutaneous transhepatic biliary drainage tube with a digital peroral cholangioscope

  Kayashima A., Iwasaki E., Kanai T.

  Digestive Endoscopy (Digestive Endoscopy)  34 ( 1 ) e3 - e4 2022.01

  ISSN  09155635

  • Access to Document (DOI)

• 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.

  • Access to Document (DOI)

• 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

  • Access to Document (DOI)

• Early Dynamics of MELD Scores Predict Corticosteroid Responsiveness to Severe Acute-Onset Autoimmune Hepatitis

  Noguchi F., Chu P.s., Yoshida A., Taniki N., Morikawa R., Hasegawa Y., Yamataka K., Hoshi H., Kasuga R., Tabuchi T., Ebinuma H., Shinoda M., Obara H., Kitagawa Y., Kanai T., Nakamoto N.

  Clinical Gastroenterology and Hepatology (Clinical Gastroenterology and Hepatology)   2021

  ISSN  15423565

  • Access to Document (DOI)

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Presentations 【 Display / hide 】

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 (invited, 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 (invited, 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 (invited, 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 】

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

• 宿主侵入菌に対する腸肝脳相関の解明と消化器免疫難病の治療開発

  2023.04

  -

  2026.03

  基盤研究(A), Principal investigator

• 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, 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, 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

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Awards 【 Display / hide 】

Awards 【 Display / hide 】

• 日本消化器病学会学術賞

  2021.04

  Type of Award： Award from Japanese society, conference, symposium, etc.

• 日本免疫学会ヒト免疫研究賞

  2020.12

  Type of Award： Award from Japanese society, conference, symposium, etc.

• 慶應義塾大学医学部坂口洋光記念医学研究助成賞

  2009

• 慶應義塾大学医学部三師会　北島賞

  2008

• 三越医学研究助成賞

  2008

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Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• STEM CELL MEDICINE

  2024

• RESEARCH FRONTIERS IN BIOMEDICAL SCIENCE

  2024

• LECTURE SERIES, INTERNAL MEDICINE (GASTROENTEROLOGY)

  2024

• INTERNAL MEDICINE: SEMINAR

  2024

• INTERNAL MEDICINE: PRACTICE

  2024

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Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• 日本臨床免疫学会, 

  2006.01

  -

  Present

• 日本内科学会

  　

• 日本消化器病学会

  　

• 日本消化器内視鏡学会

  　

• 日本消化管学会

  　

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Committee Experiences 【 Display / hide 】

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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