Saito, Yoshimasa

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy 薬物治療学講座 (Shiba-Kyoritsu)

Position

Professor
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Research Areas 【 Display / hide 】

  • Life Science / Tumor diagnostics and therapeutics

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Books 【 Display / hide 】

  • 遺伝子診断と個別化医療.「ゲノム創薬科学」

    Saito Yoshimasa, 裳華房, 2017.10

    Scope: pp269-287

  • エピジェネティクスとアンチエイジング医学.「アンチエイジング医学の基礎と臨床」第3版.

    齋藤 義正, メジカルビュー社, 東京, 2015.09

    Scope: pp42-44

  • Advanced Glycation End-products (AGEs)阻害薬がOLEFTラットの肝および脂肪組織に及ぼす影響. 「酸化ストレスと肝疾患 8巻」.

    木村真規、南雲まい、飯田陽子、山田華名、齋藤義正、齋藤英胤., 株式会社嵯峨野, 東京, 2012.09

    Scope: pp67-72

  • 加齢と消化器系の変化.「高齢者用食品の開発と展望」.

    齋藤義正、齋藤英胤., シーエムシー出版, 東京, 2012.07

    Scope: pp7-12

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Papers 【 Display / hide 】

  • Intestinal metabolites predict treatment resistance of patients with depression and anxiety

    Matsuzaki J., Kurokawa S., Iwamoto C., Miyaho K., Takamiya A., Ishii C., Hirayama A., Sanada K., Fukuda S., Mimura M., Kishimoto T., Saito Y.

    Gut Pathogens 16 ( 1 )  2024.12

    Research paper (scientific journal), Joint Work, Last author, Accepted,  ISSN  1757-4749

    　View Summary

    Background: The impact of the gut microbiota on neuropsychiatric disorders has gained much attention in recent years; however, comprehensive data on the relationship between the gut microbiome and its metabolites and resistance to treatment for depression and anxiety is lacking. Here, we investigated intestinal metabolites in patients with depression and anxiety disorders, and their possible roles in treatment resistance. Results: We analyzed fecal metabolites and microbiomes in 34 participants with depression and anxiety disorders. Fecal samples were obtained three times for each participant during the treatment. Propensity score matching led us to analyze data from nine treatment responders and nine non-responders, and the results were validated in the residual sample sets. Using elastic net regression analysis, we identified several metabolites, including N-ε-acetyllysine; baseline levels of the former were low in responders (AUC = 0.86; 95% confidence interval, 0.69–1). In addition, fecal levels of N-ε-acetyllysine were negatively associated with the abundance of Odoribacter. N-ε-acetyllysine levels increased as symptoms improved with treatment. Conclusion: Fecal N-ε-acetyllysine levels before treatment may be a predictive biomarker of treatment-refractory depression and anxiety. Odoribacter may play a role in the homeostasis of intestinal L-lysine levels. More attention should be paid to the importance of L-lysine metabolism in those with depression and anxiety.

  • Plasma extracellular vesicle microRNAs reflecting the therapeutic effect of the CBP/β-catenin inhibitor PRI-724 in patients with liver cirrhosis

    Yoshida M., Matsuzaki J., Fujita K., Kimura M., Umezu T., Tokuda N., Yamaguchi T., Kuroda M., Ochiya T., Saito Y., Kimura K.

    Scientific Reports 14 ( 1 )  2024.12

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  2045-2322

    　View Summary

    There is an unmet need for antifibrotic therapies to prevent the progression of liver cirrhosis. Previously, we conducted an exploratory trial to assess the safety and antifibrotic efficacy of PRI-724, a selective CBP/β-catenin inhibitor, in patients with liver cirrhosis. PRI-724 was well tolerated and exerted a potential antifibrotic effect. Here, we investigated whether the profiles of circulating microRNAs packaged in extracellular vesicles (EV-miRNAs) are associated with responses to liver fibrosis treatments. Eighteen patients who received PRI-724 for 12 weeks in a phase 1/2a study were classified as responders (n = 10) or non-responders (n = 8) based on changes in liver stiffness. Plasma samples were obtained before and after PRI-724 administration and the levels of EV-miRNAs were analyzed. Three miRNAs (miR-6510-5p, miR-6772-5p, and miR-4261) were identified as predictors of response or non-response to PRI-724, and the levels of three other miRNAs (miR-939-3p, miR-887-3p, and miR-7112-5p) correlated with the efficacy of treatment. Expression of miR-887-3p was detected in hepatocytes and was decreased significantly in liver tissue following PRI-724 treatment. In addition, transfection of a miR-887-3p mimic activated hepatic stellate cells. Thus, decreases in the miR-887-3p level in blood may reflect recovery from liver fibroses in patients with liver cirrhosis treated with PRI-724, although further validation studies are warranted to confirm this.

  • A comparative study on dietary diversity and gut microbial diversity in children with autism spectrum disorder, attention-deficit hyperactivity disorder, their neurotypical siblings, and non-related neurotypical volunteers: a cross-sectional study

    Kurokawa S., Nomura K., Sanada K., Miyaho K., Ishii C., Fukuda S., Iwamoto C., Naraoka M., Yoneda S., Imafuku M., Matsuzaki J., Saito Y., Mimura M., Kishimoto T.

    Journal of Child Psychology and Psychiatry and Allied Disciplines 65 ( 9 ) 1184 - 1195 2024.09

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  00219630

    　View Summary

    Background: Previous research has shown a significant link between gut microbiota in children with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). However, much remains unknown because of the heterogeneity of disorders and the potential confounders such as dietary patterns and control group variations. Methods: Children aged 6–12 years who had been clinically diagnosed with ASD and/or ADHD, their unaffected neurotypical siblings, and non-related neurotypical volunteers were recruited cross-sectionally. The ASD diagnosis was confirmed using the Autism Diagnostic Observation Schedule-2 (ADOS-2) in all patients, including those with ADHD. Standardized DNA extraction and sequencing methods were used to compare gut microbial alpha-diversity among the groups. Dietary diversity was calculated from a standardized dietary questionnaire form. We compared the difference in gut microbiome between patients with ASD and/or ADHD with neurotypical siblings and non-related neurotypical controls. Results: Ninety-eight subjects were included in the study (18 with ASD, 19 with ADHD, 20 with both ASD and ADHD, 13 neurotypical siblings, and 28 non-related neurotypical controls). The alpha-diversity indices, such as Chao 1 and Shannon index, showed a significant difference between the groups in a Linear mixed-effect model (F(4, 93) = 4.539, p =.02), (F(4, 93) = 3.185, p =.017), respectively. In a post-hoc pairwise comparison, patients with ASD had lower alpha-diversity compared with non-related controls after Bonferroni correction. Dietary diversity shown in Shannon index did not differ among the groups (F(4, 84) = 1.494, p =.211). Conclusions: Our study indicates disorder-specific microbiome differences in patients with ASD. In future research on gut microbiota in neurodevelopmental disorders, it is necessary to consider the impact of ASD and ADHD co-occurrence, and strictly control for background information such as diet, to elucidate the gut–microbiota interaction in ASD and ADHD for exploring the potential of therapeutic interventions.

  • Criteria for preclinical models of cholangiocarcinoma: scientific and medical relevance

    Diego F. Calvisi , Luke Boulter , Javier Vaquero , Anna Saborowski , Luca Fabris , Pedro M. Rodrigues , Cédric Coulouarn , Rui E. Castro , Oreste Segatto , Chiara Raggi , Luc J. W. van der Laan , Guido Carpino , Benjamin Goepper , Stephanie Roessler , Timothy J. Kendall , Matthias Ever , Ester Gonzalez-Sanchez , Juan W. Valle , Arndt Vogel , John Bridgewater , Mitesh J. Borad , Gregory J. Gores , Lewis R. Roberts , Jose J. G. Marin , Jesper B. Andersen , Domenico Alvaro , Alejandro Forner , Jesus M. Banales , Vincenzo Cardinale , Rocio I. R. Macias , Silve Vicen , Xin Chen , Chiara Braconi , Monique M , A. Verstegen , Laura Fouassier , Lewis Roberts , Alexander Scheiter , Florin M. Selaru , Katja Ever , Kirsten Utpatel , Laura Broutier , Massimiliano Cadamuro , Meritxell Huch , Robert Goldin , Sergio A. Gradilone , Yoshimasa Saito

    Nature Reviews Gastroenterology & Hepatology 20 ( 7 ) 462 - 480 2023.02

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  17595045

    　View Summary

    Cholangiocarcinoma (CCA) is a rare malignancy that develops at any point along the biliary tree. CCA has a poor prognosis, its clinical management remains challenging, and effective treatments are lacking. Therefore, preclinical research is of pivotal importance and necessary to acquire a deeper understanding of CCA and improve therapeutic outcomes. Preclinical research involves developing and managing complementary experimental models, from in vitro assays using primary cells or cell lines cultured in 2D or 3D to in vivo models with engrafted material, chemically induced CCA or genetically engineered models. All are valuable tools with well-defined advantages and limitations. The choice of a preclinical model is guided by the question(s) to be addressed; ideally, results should be recapitulated in independent approaches. In this Consensus Statement, a task force of 45 experts in CCA molecular and cellular biology and clinicians, including pathologists, from ten countries provides recommendations on the minimal criteria for preclinical models to provide a uniform approach. These recommendations are based on two rounds of questionnaires completed by 35 (first round) and 45 (second round) experts to reach a consensus with 13 statements. An agreement was defined when at least 90% of the participants voting anonymously agreed with a statement. The ultimate goal was to transfer basic laboratory research to the clinics through increased disease understanding and to develop clinical biomarkers and innovative therapies for patients with CCA.

  • 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

    Research paper (scientific journal), Joint Work, Accepted,  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.

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

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Reviews, Commentaries, etc. 【 Display / hide 】

  • 胆道・膵臓がんオルガノイドを用いた個別化医療の実現に向けて

    齋藤義正

    医学のあゆみ 286 ( 7, 8 ) 649 - 652 2023.08

    Article, review, commentary, editorial, etc. (scientific journal), Single Work

  • がんオルガノイドー創薬・個別化医療の革新的プレクリニカルモデルとして

    齋藤義正

    医学のあゆみ 286 ( 7, 8 ) 623 2023.08

    Article, review, commentary, editorial, etc. (scientific journal), Single Work

  • 腸管上皮オルガノイドを用いたステムセルエイジング研究

    齋藤義正

    ファルマシア 56 ( 11 ) 994 - 998 2020.11

    Article, review, commentary, editorial, etc. (scientific journal), Single Work

  • Publisher Correction: Epigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging (npj Aging and Mechanisms of Disease, (2018), 4, 1, (12), 10.1038/s41514-018-0031-5)

    Uchida R., Saito Y., Nogami K., Kajiyama Y., Suzuki Y., Kawase Y., Nakaoka T., Muramatsu T., Kimura M., Saito H.

    npj Aging and Mechanisms of Disease (npj Aging and Mechanisms of Disease)  5 ( 1 )  2019.12

    　View Summary

    © 2019, The Author(s). The original version of this Article had an incorrect Article number of 1, an incorrect Volume of 5 and an incorrect Publication year of 2019. These errors have now been corrected in the PDF and HTML versions of the Article.

  • ヘリコバクター・ピロリ感染症とmicroRNA発現異常.

    齋藤義正, 鈴木秀和, 齋藤英胤.

    細胞 (ニューサイエンス社)  44(10)   6-9 2012.09

    Article, review, commentary, editorial, etc. (scientific journal), Joint Work

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Presentations 【 Display / hide 】

  • 腸管上皮オルガノイドを用いたシングルセル解析により見えてきたこと

    齋藤義正

    日本生理学会 第100回記念大会, 

    2023.03
    , 

    Oral presentation (invited, special)

  • 誘導性CRISPR/dCas9を用いたC19MCの肝内胆管癌オルガノイドの分化における役割の解明

    葉 子祥、松崎 潤太郎、及川 千尋、金井 弥栄、齋藤 義正

    第81回 日本癌学会学術総会, 

    2022.09
    -
    2022.10
    , 

    Oral presentation (general)

  • 膵がんドライバー遺伝子変異誘導による形質変化の追跡

    及川 千尋、松崎 潤太郎、落谷 孝広、齋藤 義正

    第81回 日本癌学会学術総会, 

    2022.09
    -
    2022.10
    , 

    Oral presentation (general)

  • 難治性がんオルガノイドを用いた個別化医療の開発

    齋藤義正

    第4回Cell Based Assay Workshop, 

    2022.03
    , 

    Oral presentation (invited, special)

  • 胆道がん患者由来オルガノイドの樹立と創薬研究への応用

    齋藤義正

    患者由来がんモデル研究会2021, 

    2021.12
    , 

    Oral presentation (invited, special)

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

  • 国際協力による難治性がんオルガノイドライブラリーの構築

    2024.09
    -
    2027.03

    国際共同研究加速基金（海外連携研究）, Principal investigator

  • デザイナーエクソソームとオルガノイドを用いた個別化がん免疫療法の開発

    2024.06
    -
    2026.03

    挑戦的研究（萌芽）, Principal investigator

  • 胆道がん腫瘍微小環境の再構築による次世代オルガノイドの開発

    2024.04
    -
    2027.03

    基盤研究(B), Principal investigator

  • 抗真菌薬を基盤とした胆道・膵臓がんに対する新規治療薬の創製

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Principal investigator

  • 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

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Challenging Research (Exploratory) , Principal investigator

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Intellectual Property Rights, etc. 【 Display / hide 】

  • がん幹細胞集団の調製方法、異種移植片の調製方法、スクリーニング方法、ｍｉＲ－３４ａの発現量を低下させる方法及びがん幹細胞増殖抑制剤

    Date applied： 特願2015-142164  2015.07 

    Patent, Joint

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Awards 【 Display / hide 】

  • Asian Pacific Digestive Week 2018, Emerging Leader Lectureship

    2018.11

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

  • 第18回日本抗加齢医学会総会　最優秀演題賞

    齋藤義正, 2018.05, 腸管上皮オルガノイドを用いたステムセルエイジングの検討

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

  • 日本抗加齢医学会優秀演題賞　

    木村真規、井手晴香、白井栄里奈、内田諒英、齋藤義正、齋藤英胤.　, 2016.06, 第16回 日本抗加齢医学会総会, 高脂肪食摂取時の脂肪組織における老化マーカー遺伝子の発現変化とDNAメチル化阻害薬の効果.　

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

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    プログラム・抄録集: 170, 2016/6/10/12.

  • 日本抗加齢医学会優秀演題賞　

    内田諒英、齋藤義正、中岡哉彰、村松俊英、木村真規、齋藤英胤.　, 2016.06, 第16回 日本抗加齢医学会総会　プログラム・抄録集: 174, 2016/6/10/12., オルガノイド培養法により樹立した腸管上上皮幹細胞における stem cell aging の検討.　

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    プログラム・抄録集: 174, 2016/6/10/12.

  • 慶應義塾大学薬学部学部長賞

    2015

    Type of Award： Keio commendation etc.

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Courses Taught 【 Display / hide 】

  • STUDY OF MAJOR FIELD: (PHARMACOTHERAPEUTICS)

    2024

  • SPECIAL LECTURES BY GUEST SPEAKERS

    2024

  • SPECIAL LECTURES BY GUEST SPEAKERS

    2024

  • SEMINAR:(PHARMACOTHERAPEUTICS)

    2024

  • RESEARCH FOR BACHELOR'S THESIS 1

    2024

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