慶應義塾研究者情報データベース

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• ライフサイエンス / 腫瘍診断、治療学

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• 遺伝子診断と個別化医療.「ゲノム創薬科学」

  齋藤 義正, 裳華房, 2017年10月

  担当範囲: 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年09月

  担当範囲: 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年09月

  担当範囲: 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年07月

  担当範囲: pp7-12

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• 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年12月

  研究論文（学術雑誌）, 共著, 最終著者, 査読有り,  ISSN  1757-4749

  　概要を見る

  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.

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• 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年12月

  研究論文（学術雑誌）, 共著, 査読有り,  ISSN  2045-2322

  　概要を見る

  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.

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• 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年09月

  研究論文（学術雑誌）, 共著, 査読有り,  ISSN  00219630

  　概要を見る

  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.

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

  Calvisi D.F., Boulter L., Vaquero J., Saborowski A., Fabris L., Rodrigues P.M., Coulouarn C., Castro R.E., Segatto O., Raggi C., van der Laan L.J.W., Carpino G., Goeppert B., Roessler S., Kendall T.J., Evert M., Gonzalez-Sanchez E., Valle J.W., Vogel A., Bridgewater J., Borad M.J., Gores G.J., Roberts L.R., Marin J.J.G., Andersen J.B., Alvaro D., Forner A., Banales J.M., Cardinale V., Macias R.I.R., Vicent S., Chen X., Braconi C., Verstegen M.M.A., Fouassier L., Scheiter A., Selaru F.M., Evert K., Utpatel K., Broutier L., Cadamuro M., Huch M., Goldin R., Gradilone S.A., Saito Y.

  Nature Reviews Gastroenterology and Hepatology 20 （ 7 ） 462 - 480 2023年02月

  研究論文（学術雑誌）, 共著, 査読有り,  ISSN  17595045

  　概要を見る

  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.

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• 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年08月

  研究論文（学術雑誌）, 共著, 査読有り,  ISSN  10834389

  　概要を見る

  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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• 腸管上皮オルガノイドのシングルセル解析による老化メカニズムの解明

  齋藤, 義正

  福澤諭吉記念慶應義塾学事振興基金事業報告集 （福澤基金運営委員会）  2021年

• 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

  齋藤, 義正

  科学研究費補助金研究成果報告書 2020年

• オルガノイド培養による胆道・膵臓腫瘍細胞バンクの構築と個別化治療への応用

  齋藤, 義正

  科学研究費補助金研究成果報告書 2019年

• オルガノイド培養技術を用いた胆道・膵臓がんのシステム生物学的検討

  齋藤, 義正

  学事振興資金研究成果実績報告書 （慶應義塾大学）  2017年

• 腸管上皮幹細胞における加齢に伴うエピゲノム変化に着目した老化の分子機構の解明

  齋藤, 義正

  科学研究費補助金研究成果報告書 2017年

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• 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年08月

  記事・総説・解説・論説等（学術雑誌）, 単著

• 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年08月

  記事・総説・解説・論説等（学術雑誌）, 単著

• 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年11月

  記事・総説・解説・論説等（学術雑誌）, 単著

• 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年12月

  　概要を見る

  © 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.

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• 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年09月

  記事・総説・解説・論説等（学術雑誌）, 共著

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• 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年03月

  , 

  口頭発表（招待・特別）

• 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年09月

  -

  2022年10月

  , 

  口頭発表（一般）

• 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年09月

  -

  2022年10月

  , 

  口頭発表（一般）

• 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年03月

  , 

  口頭発表（招待・特別）

• 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年12月

  , 

  口頭発表（招待・特別）

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• 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年09月

  -

  2027年03月

  齋藤 義正, 国際共同研究加速基金（海外連携研究）, 補助金,  研究代表者

• 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年06月

  -

  2026年03月

  齋藤 義正, 挑戦的研究（萌芽）, 補助金,  研究代表者

• 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年04月

  -

  2027年03月

  齋藤 義正, 基盤研究(B), 補助金,  研究代表者

• 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年04月

  -

  2023年03月

  文部科学省・日本学術振興会, 科学研究費助成事業, 齋藤 義正, 基盤研究(B), 補助金,  研究代表者

• 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年06月

  -

  2021年03月

  文部科学省・日本学術振興会, 科学研究費助成事業, 齋藤　義正, 挑戦的研究（萌芽), 補助金,  研究代表者

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• 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

  出願日： 特願2015-142164  2015年07月 

  特許権, 共同

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• Asian Pacific Digestive Week 2018, Emerging Leader Lectureship

  2018年11月

  受賞区分： 国際学会・会議・シンポジウム等の賞

• 第18回日本抗加齢医学会総会　最優秀演題賞

  齋藤義正, 2018年05月, 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

  受賞区分： 国内学会・会議・シンポジウム等の賞

• 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年06月, 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.　

  受賞区分： 国内学会・会議・シンポジウム等の賞

  　説明を見る

  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年06月, 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.　

  　説明を見る

  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年

  受賞区分： 塾内表彰等

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• 課題研究（薬物治療学）

  2024年度

• 大学院特別講義Ⅰ

  2024年度

• 大学院特別講義Ｂ

  2024年度

• 演習（薬物治療学）

  2024年度

• 卒業研究１（薬学科）

  2024年度

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