Details of a Researcher - MATSUZAKI Juntaro

Papers - MATSUZAKI Juntaro

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Third-Line and Later Susceptibility-Guided Helicobacter pylori Eradication Therapies: A Multicenter Study of Vonoprazan–Amoxicillin–Sitafloxacin/Rifabutin Regimens

Journal of Clinical Medicine 2026.01

Joint Work

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Impact of strength training of large muscle groups on quality of life.

Takahashi T, Matsuzaki J, Enomoto T, Saito Y

Journal of clinical biochemistry and nutrition 77 ( 3 ) 264 - 267 2025.11

Research paper (scientific journal), Joint Work, Corresponding author, Accepted, ISSN 0912-0009

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A Case Report of Autoimmune Gastritis Associated With Polyendocrine Syndrome Type III Mimicking Refractory H. pylori Infection.

Ubukata S, Mori H, Masaoka T, Matsuzaki J, Kanai T

Cureus 17 ( 9 ) e92659 2025.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 2168-8184

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Efficacy of Vonoprazan-Based Triple Therapy with Sitafloxacin and Amoxicillin for Third-Line Helicobacter pylori Eradication: A Multicenter Prospective Analysis on Drug Resistance and gyrA Mutations

Wasaki S, Mori H, Matsuzaki J, Suzuki H, Hirata K, Imaeda H, Yoshioka M, Nakazawa A, Okazawa A, Kanai T, Masaoka T

Digestive Diseases 43 ( 5 ) 1 - 8 2025.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 0257-2753

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Association of KRAS variants with survival and therapeutic outcomes in biliary tract cancers.

Iida K, Matsui Y, Urabe Y, Muramatsu T, Matsuzaki J, Saito Y

ESMO open 10 ( 6 ) 105306 2025.06

Research paper (scientific journal), Joint Work, Accepted

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【H.pylori感染の診断と治療のガイドライン-2024改訂版の特筆すべき点とは-】診断　臨床重要課題をシステマティックレビューで徹底検証(CQ)

豊島治, 松崎潤太郎, 太田浩良, 大崎敬子, 下山克

Helicobacter Research ((株)先端医学社) 29 ( 1 ) 34 - 38 2025.06

Joint Work, ISSN 1342-4319

2024改訂版ガイドラインでは診断領域のClinical Question(CQ)として,尿素呼気試験,血清抗H.pylori抗体検査,薬剤感受性検査,血清ペプシノゲン検査についてSystematic Review(SR)された.尿素呼気試験は除菌前・後の診断に推奨された.血清抗体はその結果のみで除菌を行わないことが推奨された.抗体測定キットの変更に留意するよう述べられた.薬剤感受性検査をおこない適切な除菌方法を選択することが推奨された.ペプシノゲンはIIとI/II比が除菌前,I/II比の上昇率が除菌後の補助診断として有用であるとされた.H.pylori感染診断は困難なケースが少なくない.内視鏡画像の整合性をはかること,複数の検査を総合的に診断することが肝要である.また,非専門医への啓発・教育も必須である.(著者抄録)

Upper gastrointestinal triple stenosis in a patient with trisomy 17p syndrome: Case report and literature review.

Ando H, Mori H, Takabayashi K, Matsuura N, Masaoka T, Matsuzaki J, Saito Y, Kato M, Kosaki K, Kanai T

DEN open 5 ( 1 ) e70043 2025.04

Research paper (scientific journal), Joint Work, Accepted

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Environmental factors in gastric carcinogenesis and preventive intervention strategies.

Tan Y, Matsuzaki J, Saito Y, Suzuki H

Genes and environment : the official journal of the Japanese Environmental Mutagen Society 47 ( 1 ) 5 2025.03

Research paper (scientific journal), Joint Work, Accepted, ISSN 1880-7046

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Circulating serum miRNAs predict response to platinum chemotherapy in high-grade serous ovarian cancer.

Suzuki K, Yokoi A, Matsuzaki J, Yoshida K, Yamamoto Y, Kato T, Ishikawa M, Ochiya T, Kajiyama H

Cancer medicine 13 ( 22 ) e70251 2024.11

Research paper (scientific journal), Joint Work, Accepted

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【細胞外小胞・エクソソームの医療応用の未来】疾患における細胞外小胞研究　膵臓がんにおける細胞外小胞

関戸愛香, 松崎潤太郎, 齋藤義正

医学のあゆみ (医歯薬出版(株)) 291 ( 9 ) 711 - 716 2024.11

Joint Work, ISSN 0039-2359

＜文献概要＞膵臓がん(PDAC)は,自覚症状が少なく画像診断のみでは早期発見が難しい.PDACを含む多くのがんにおいて初期段階の発見により,外科的治療を施すことが可能となる.そのため,早期発見に役立つバイオマーカーの発見が治癒の可能性を高める方法となる.現在使用されている血中バイオマーカーである血清糖鎖抗原19-9(CA19-9)やがん胎児性抗原(CEA)では,早期のPDAC診断性能が十分ではない.そこで,PDACおよびその前がん病変である膵上皮内腫瘍(PanIN),管内乳頭状粘液性腫瘍(IPMN),粘液性嚢胞性腫瘍(MCN)に注目し,細胞外小胞(EV)が輸送するmiRNAやタンパク質のなかで,これらの病変の早期発見のカギとなる新たなバイオマーカーについて紹介する.

食道アカラシアに合併した表在型食道癌の一例

勝海愛, 森英毅, 松浦倫子, 正岡建洋, 高取祐作, 富田英臣, 飽本哲兵, 松崎潤太郎, 安藤裕子, 齋藤義正, 加藤元彦, 金井隆典

日本消化器病学会関東支部例会プログラム・抄録集 (日本消化器病学会-関東支部) 381回 26 - 26 2024.09

Joint Work

Macrophage-depleted young mice are beneficial in vivo models to assess the translocation of Klebsiella pneumonia from the gastrointestinal tract to the liver in the elderly.

Tsugawa H, Tsubaki S, Tanaka R, Nashimoto S, Imai J, Matsuzaki J, Hozumi K

Microbes and infection 26 ( 8 ) 105371 2024.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 1286-4579

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Potential utility of pretreatment serum miRNAs for optimal treatment selection in advanced high-grade serous ovarian cancer.

Uehara T, Matsuzaki J, Yoshida H, Ogawa Y, Miura J, Fujimiya H, Yamamoto Y, Kawauchi J, Takizawa S, Yonemori K, Sakamoto H, Kato K, Ishikawa M, Ochiya T

Japanese journal of clinical oncology 54 ( 8 ) 917 - 925 2024.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 0368-2811

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Profile of miRNAs in small extracellular vesicles released from glioblastoma cells treated by boron neutron capture therapy.

Kondo N, Kinouchi T, Natsumeda M, Matsuzaki J, Hirata E, Sakurai Y, Okada M, Suzuki M

Journal of neuro-oncology 168 ( 1 ) 91 - 97 2024.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 0167-594X

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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 2024.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 0021-9630

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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 ) 6266 2024.03

Research paper (scientific journal), Joint Work, Lead author, Corresponding author, Accepted

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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 ) 8 2024.02

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

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食道狭窄に対して複数回の内視鏡的バルーン拡張を施行している複数箇所の消化管狭窄を有する染色体異常の1例

安藤裕子, 森英毅, 高林馨, 松浦倫子, 正岡建洋, 松崎潤太郎, 齋藤義正, 小崎健次郎, 加藤元彦, 金井隆典

日本内科学会関東地方会 (日本内科学会-関東地方会) 693回 18 - 18 2024.02

Joint Work

【上部消化管疾患の残された課題】バレット食道および食道腺がんの疫学と病態

鈴木志帆, 松崎潤太郎, 齋藤義正

Progress in Medicine ((株)ライフ・サイエンス) 43 ( 9 ) 761 - 765 2023.09

Joint Work, ISSN 0287-3648

長期間の経過を追うことができた胃前庭部難治性潰瘍の一例

井村友理, 森英毅, 正岡建洋, 松崎潤太郎, 齋藤義正, 金井隆典

日本消化器病学会関東支部例会プログラム・抄録集 (日本消化器病学会-関東支部) 376回 47 - 47 2023.09

Joint Work

Evidence for in vitro extensive proliferation of adult hepatocytes and biliary epithelial cells.

Katsuda T, Sussman J, Li J, Merrell AJ, Vostrejs W, Secreto A, Matsuzaki J, Ochiya T, Stanger BZ

Stem cell reports 18 ( 7 ) 1436 - 1450 2023.07

Joint Work

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Identifying high-grade serous ovarian carcinoma–specific extracellular vesicles by polyketone-coated nanowires

Yokoi A, Ukai M, Yasui T, Inokuma Y, Hyeon-Deuk K, Matsuzaki J, Yoshida K, Kitagawa M, Chattrairat K, Iida M, Shimada T, Manabe Y, Chang IY, Asano-Inami E, Koya Y, Nawa A, Nakamura K, Kiyono T, Kato T, Hirakawa A, Yoshioka Y, Ochiya T, Hasegawa T, Baba Y, Yamamoto Y, Kajiyama H

Science Advances 9 ( 27 ) eade6958 2023.07

Research paper (scientific journal), Joint Work, Accepted

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Gas6 ameliorates intestinal mucosal immunosenescence to prevent the translocation of a gut pathobiont, Klebsiella pneumoniae, to the liver.

Tsugawa H, Ohki T, Tsubaki S, Tanaka R, Matsuzaki J, Suzuki H, Hozumi K

PLoS pathogens 19 ( 6 ) e1011139 2023.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 1553-7366

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A validation study for the utility of serum microRNA as a diagnostic and prognostic marker in patients with osteosarcoma.

Araki Y, Asano N, Yamamoto N, Hayashi K, Takeuchi A, Miwa S, Igarashi K, Higuchi T, Abe K, Taniguchi Y, Yonezawa H, Morinaga S, Asano Y, Yoshida T, Hanayama R, Matsuzaki J, Ochiya T, Kawai A, Tsuchiya H

Oncology letters 25 ( 6 ) 222 2023.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 1792-1074

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Serum microRNAs as new criteria for referral to early palliative care services in treatment-naïve advanced cancer patients.

Miura T, Mitsunaga S, Matsuzaki J, Takizawa S, Kato K, Ochiai A, Ochiya T

Oncotarget 13 1341 - 1349 2022.12

Research paper (scientific journal), Joint Work, Accepted

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Response to letter regarding: development of plasma ghrelin level as a novel marker for gastric mucosal atrophy after <i>Helicobacter pylori</i> eradication.

Mori H, Matsuzaki J, Suzuki H

Annals of medicine 54 ( 1 ) 856 - 857 2022.12

Research paper (scientific journal), Joint Work, ISSN 0785-3890

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【Helicobacter Year Book 2022-Helicobacter研究はここまで進展した-】Helicobacter pylori除菌による胃がん抑制の新知見

勝田菜友, 松崎潤太郎, 齋藤義正

Helicobacter Research ((株)先端医学社) 26 ( 2 ) 166 - 170 2022.12

Joint Work, ISSN 1342-4319

Helicobacter pylori除菌による胃がん予防効果は既に世界中で確かなエビデンスが報告されているが,患者背景の差異による効果の違いなどまだ追究すべき点も多く残されている.最新のメタアナリシスでは,除菌の胃がん予防効果は症状の有無やがん既往歴とは関連がなく,また20年間に及ぶ観察研究では,長期的な効果が示された.また,一般集団に対する除菌は,有害事象を増加させず,かつ,費用対効果が高いと報告された.一方で,除菌後の胃がんリスクを層別化する方法は未だ最適化できていないが,最近ではmiR-124a-3pメチル化,血漿グレリン濃度,胃の細菌叢などを調べることにより,層別化できる可能性が報告された.プロトンポンプ阻害薬の継続使用を除菌後の胃がんリスクとする報告も多く,今後の更なるエビデンス蓄積が望まれる.(著者抄録)

Prediction of tissue-of-origin of early-stage cancers using serum miRNomes.

Matsuzaki J, Kato K, Oono K, Tsuchiya N, Sudo K, Shimomura A, Tamura K, Shiino S, Kinoshita T, Daiko H, Wada T, Katai H, Ochiai H, Kanemitsu Y, Takamaru H, Abe S, Saito Y, Boku N, Kondo S, Ueno H, Okusaka T, Shimada K, Ohe Y, Asakura K, Yoshida Y, Watanabe SI, Asano N, Kawai A, Ohno M, Narita Y, Ishikawa M, Kato T, Fujimoto H, Niida S, Sakamoto H, Takizawa S, Akiba T, Okanohara D, Shiraishi K, Kohno T, Takeshita F, Nakagama H, Ota N, Ochiya T, Project Team for Development and Diagnostic Technology for Detection of miRNA in Body Fluids

JNCI cancer spectrum 7 ( 1 ) 2022.11

Research paper (scientific journal), Joint Work, Lead author, Accepted

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Circulating microRNA profiling for prediction of oncological outcomes in prostate cancer patients following radical prostatectomy

Takamori H, Urabe F, Matsuzaki J, Kimura S, Sasaki H, Kimura T, Inaba K, Nakamura E, Matsui Y, Fujimoto H, Ochiya T

The Prostate 82 ( 16 ) 1537 - 1546 2022.08

Research paper (scientific journal), Joint Work, Accepted, ISSN 0270-4137

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Independent verification of circulating miRNA as diagnostic biomarkers for urothelial carcinoma

Urabe F, Matsuzaki J, Takeshita F, Kishida T, Ochiya T, Hirai K

Cancer Science 113 ( 10 ) 3510 - 3517 2022.08

Research paper (scientific journal), Joint Work, Accepted, ISSN 1347-9032

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Correction: Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes

Katsuda T, Matsuzaki J, Yamaguchi T, Yamada Y, Prieto-Vila M, Hosaka K, Takeuchi A, Saito Y, Ochiya T

eLife 11 2022.08

Research paper (scientific journal), Joint Work, Accepted

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Circulating microRNAs: Challenges with their use as liquid biopsy biomarkers.

Takizawa S, Matsuzaki J, Ochiya T

Cancer biomarkers : section A of Disease markers 35 ( 1 ) 1 - 9 2022.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 1574-0153

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【臨床実装が進む　次世代がんバイオマーカー　新規の検出技術、AIが加速するリキッドバイオプシーとその先の診断モダリティ】(第1章)がんのバイオロジーと新たなバイオマーカー　がんの診断・治療に向けた血中循環miRNA、エクソソーム研究の最前線

及川千尋, 松崎潤太郎, 加藤健, 落谷孝広

実験医学 ((株)羊土社) 40 ( 10 ) 1515 - 1521 2022.06

Joint Work, ISSN 0288-5514

血液中のエクソソームやmiRNAは、がんの早期診断や転移予測などの新たなバイオマーカー候補として、さかんに研究が行われている。特に血中miRNAプロファイルは、他のバイオマーカーに比べても発がん早期の段階から劇的に変動することが、臨床検体を用いた国内外の多くの研究で示されており、低侵襲ながんの一次スクリーニング検査への活用を想定した検証研究が進んでいる。またエクソソームや細胞外miRNAの生理活性を追究することは、バイオマーカーとしての応用に根拠を与えるのみならず、発がん予防やがんの転移抑制に効果的な新規治療戦略の開発に展開しうる。(著者抄録)

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 27 ( 4 ) e12900 2022.05

Research paper (scientific journal), Joint Work, Accepted, ISSN 1083-4389

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Identification of circulating microRNAs as potential biomarkers for hepatic necroinflammation in patients with autoimmune hepatitis.

Saeki C, Matsuzaki J, Kuroda M, Fujita K, Ichikawa M, Takizawa S, Takano K, Oikawa T, Nakanuma Y, Saruta M, Ochiya T, Tsubota A

BMJ open gastroenterology 9 ( 1 ) 2022.04

Research paper (scientific journal), Joint Work, Lead author, Accepted, ISSN 2054-4774

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Serum microRNA as liquid biopsy biomarker for the prediction of oncological outcomes in patients with bladder cancer.

Urabe F, Matsuzaki J, Ito K, Takamori H, Tsuzuki S, Miki J, Kimura T, Egawa S, Nakamura E, Matsui Y, Fujimoto H, Yamamoto Y, Ochiya T

International journal of urology : official journal of the Japanese Urological Association 29 ( 9 ) 968 - 976 2022.03

Research paper (scientific journal), Joint Work, Accepted, ISSN 0919-8172

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Development of plasma ghrelin level as a novel marker for gastric mucosal atrophy after Helicobacter pylori eradication

H Mori, H Suzuki, J Matsuzaki, K Kameyama, K Igarashi, T Masaoka, ...

Annals of Medicine 54 (1), 170-180 (Annals of Medicine) 54 ( 1 ) 170 - 180 2022

Research paper (scientific journal), Joint Work, Accepted

Background and aim: The severity of atrophic gastritis is significantly associated with the risk of gastric cancer. Although the current gold standard for assessing the gastric cancer risk is esophagogastroduodenoscopy with a pathological examination, the development of less-invasive biomarkers is warranted for efficient risk stratification of gastric cancer. Serum pepsinogens (PGs) are biomarkers used to predict the extent of gastric mucosal atrophy; however, they are not an accurate reflection of gastric mucosal atrophy after Helicobacter pylori eradication. The present study was conducted to investigate the usefulness of plasma ghrelin levels as a marker for gastric mucosal atrophy, and as a risk stratification marker for gastric cancer, even after H. pylori eradication. Methods: Patients who received H. pylori eradication treatment were enrolled in the study. The severity of gastric mucosal atrophy was evaluated both endoscopically and histologically. Serum pepsinogen and plasma ghrelin levels were measured before and at 1, 12, 24, and 48 weeks after treatment. The study was approved by the Research Ethics Committee of the Keio University School of Medicine (no. 20140102; 8 July 2014). Results: Eighteen patients completed the study protocol. Total and acyl plasma ghrelin levels demonstrated no significant change from before treatment to 48 weeks after eradication; however, there was a significant difference between open-type and closed-type atrophic gastritis. The PG I/II ratio increased significantly from 48 weeks after H. pylori eradication. The severity of the histological intestinal metaplasia scores correlated inversely with plasma total ghrelin levels from before to 48 weeks after H. pylori eradication. Conclusion: Plasma levels of ghrelin correlate well with the level of gastric mucosal atrophy, even after H. pylori eradication.KEY MESSAGES Ghrelin plasma levels are associated with the progression of endoscopic atrophic gastritis, even at 48 weeks after H. pylori eradication. Ghrelin plasma levels are also associated with increased severity of histological intestinal metaplasia 48 weeks after H. pylori eradication. Pepsinogen I/II ratios increased immediately after H. pylori eradication and are inappropriate for assessing atrophic gastritis after H. pylori eradication.

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Extracellular microRNA profiling for prognostic prediction in patients with high‐grade serous ovarian carcinoma

Kosuke Yoshida and Akira Yokoi and Juntaro Matsuzaki and Tomoyasu Kato and Takahiro Ochiya and Hiroaki Kajiyama and Yusuke Yamamoto

Cancer Science (Wiley) 112 ( 12 ) 4977 - 4986 2021.10

Research paper (scientific journal), Joint Work, Accepted

High-grade serous ovarian carcinoma is a leading cause of death in female patients worldwide. MicroRNAs (miRNAs) are stable noncoding RNAs in the peripheral blood that reflect a patient’s condition, and therefore, they have received substantial attention as noninvasive biomarkers in various diseases. We previously reported the usefulness of serum miRNAs as diagnostic biomarkers. Here, we investigated the prognostic impact of the serum miRNA profile. We used the GSE106817 dataset, which included preoperative miRNA profiles of patients with ovarian malignancies. Excluding patients with other malignancy or insufficient prognostic information, we included 175 patients with high-grade serous ovarian carcinoma. All patients except four underwent surgery and received chemotherapy as initial treatment. The median follow-up period was 54.6 months (range, 3.5-144.1 months). Univariate Cox regression analysis revealed that higher levels of miR-187-5p and miR-6870-5p were associated with both poorer progression-free survival (PFS) and overall survival (OS), and miR-1908-5p, miR-6727-5p, and miR-6850-5p were poor prognostic indicators of PFS. The OS and PFS prognostic indices were then calculated using the expression values of three prognostic miRNAs. Multivariate Cox regression analysis showed that both indices were significantly independent poor prognostic factors (hazard ratio for OS and PFS, 2.343 [P =.015] and 2.357 [P =.005], respectively). In conclusion, circulating miRNA profiles can potentially provide information to predict the prognosis of patients with high-grade serous ovarian carcinoma. Therefore, there is a strong demand for early clinical application of circulating miRNAs as noninvasive biomarkers.

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Challenges for Better Diagnosis and Management of Pancreatic and Biliary Tract Cancers Focusing on Blood Biomarkers: A Systematic Review

H Tominaga, J Matsuzaki, C Oikawa, K Toyoshima, H Manabe, E Ozawa, ...

Cancers 13 (16), 4220 (Cancers) 13 ( 16 ) 2021.08

Research paper (scientific journal), Joint Work, Corresponding author, Accepted, ISSN 2072-6694

Background: pancreatic cancer (PCa) and biliary tract cancer (BTC) are cancers with a poor prognosis and few effective treatments. One of the reasons for this is late detection. Many researchers are tackling to develop non-invasive biomarkers for cancer, but few are specific for PCa or BTC. In addition, genetic abnormalities occur in cancer tissues, which ultimately affect the expression of various molecules. Therefore, it is important to identify molecules that are altered in PCa and BTC. For this systematic review, a systematic review of Medline and Embase to select biomarker studies of PCa and BTC patients was conducted. Results: after reviewing 72 studies, 79 biomarker candidates were identified, including 22 nucleic acids, 43 proteins, and 14 immune cell types. Of the 72 studies, 61 examined PCa, and 11 examined BTC. Conclusion: PCa and BTC are characterized by nucleic acid, protein, and immune cell profiles that are markedly different from those of healthy subjects. These altered molecules and cell subsets may serve as cancer-specific biomarkers, particularly in blood. Further studies are needed to better understand the diagnosis and prognosis of PCa and BTC.

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Early prediction of COVID-19 severity using extracellular vesicle COPB2.

Fujita Y, Hoshina T, Matsuzaki J, Yoshioka Y, Kadota T, Hosaka Y, Fujimoto S, Kawamoto H, Watanabe N, Sawaki K, Sakamoto Y, Miyajima M, Lee K, Nakaharai K, Horino T, Nakagawa R, Araya J, Miyato M, Yoshida M, Kuwano K, Ochiya T

Journal of extracellular vesicles (Journal of Extracellular Vesicles) 10 ( 8 ) e12092 2021.06

Research paper (scientific journal), Joint Work, Lead author, Accepted, ISSN 2001-3078

The clinical manifestations of COVID-19 vary broadly, ranging from asymptomatic infection to acute respiratory failure and death. But the predictive biomarkers for characterizing the variability are still lacking. Since emerging evidence indicates that extracellular vesicles (EVs) and extracellular RNAs (exRNAs) are functionally involved in a number of pathological processes, we hypothesize that these extracellular components may be key determinants and/or predictors of COVID-19 severity. To test our hypothesis, we collected serum samples from 31 patients with mild COVID-19 symptoms at the time of their admission for discovery cohort. After symptomatic treatment without corticosteroids, 9 of the 31 patients developed severe/critical COVID-19 symptoms. We analyzed EV protein and exRNA profiles to look for correlations between these profiles and COVID-19 severity. Strikingly, we identified three distinct groups of markers (antiviral response-related EV proteins, coagulation-related markers, and liver damage-related exRNAs) with the potential to serve as early predictive biomarkers for COVID-19 severity. As the best predictive marker, EV COPB2 protein, a subunit of the Golgi coatomer complex, exhibited significantly higher abundance in patients remained mild than developed severe/critical COVID-19 and healthy controls in discovery cohort (AUC 1.00 (95% CI: 1.00-1.00)). The validation set included 40 COVID-19 patients and 39 healthy controls, and showed exactly the same trend between the three groups with excellent predictive value (AUC 0.85 (95% CI: 0.73-0.97)). These findings highlight the potential of EV COPB2 expression for patient stratification and for making early clinical decisions about strategies for COVID-19 therapy.

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A novel combination of serum microRNAs for the detection of early gastric cancer

S Abe, J Matsuzaki, K Sudo, I Oda, H Katai, K Kato, S Takizawa, ...

Gastric Cancer, 1-9 (Gastric Cancer) 24 ( 4 ) 835 - 843 2021.03

Research paper (scientific journal), Joint Work, Lead author, Accepted, ISSN 1436-3291

Background: The aim of this study was to identify serum miRNAs that discriminate early gastric cancer (EGC) samples from non-cancer controls using a large cohort. Methods: This retrospective case–control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospital in Tokyo between 2008 and 2012) and 1417 age- and gender-matched non-cancer controls. The samples were randomly assigned to discovery and validation sets and the miRNA expression profiles of whole serum samples were comprehensively evaluated using a highly sensitive DNA chip (3D-Gene ) designed to detect 2565 miRNA sequences. Diagnostic models were constructed using the levels of several miRNAs in the discovery set, and the diagnostic performance of the model was evaluated in the validation set. Results: The discovery set consisted of 708 samples from EGC patients and 709 samples from non-cancer controls, and the validation set consisted of 709 samples from EGC patients and 708 samples from non-cancer controls. The diagnostic EGC index was constructed using four miRNAs (miR-4257, miR-6785-5p, miR-187-5p, and miR-5739). In the discovery set, a receiver operating characteristic curve analysis of the EGC index revealed that the area under the curve (AUC) was 0.996 with a sensitivity of 0.983 and a specificity of 0.977. In the validation set, the AUC for the EGC index was 0.998 with a sensitivity of 0.996 and a specificity of 0.953. Conclusions: A novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations. ®

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Precision medicine approaches to prevent gastric cancer

J Matsuzaki, H Tsugawa, H Suzuki

Gut and Liver 15 (1), 3 (Gut and Liver) 15 ( 1 ) 3 - 12 2021.01

Research paper (scientific journal), Accepted

© Gut and Liver. Gastric cancer remains one of the most common causes of cancer-related death worldwide, although the incidence is declining gradually. The primary risk factor for gastric cancer is Helicobacter pylori infection. The Kyoto global consensus report recommends eradication of H. pylori in all infected patients. However, because it is difficult to stratify the risk of carcinogenesis among patients with a history of H. pylori infection, annual endoscopic surveillance is performed for everyone after eradication. This review summarizes the current approaches used to screen for novel molecules that could assist in the diagnosis of gastric cancer and reduce mortality. Most well-studied molecules are tissue protein biomarkers expressed by the gastric epithelium and associated with metaplasia-dysplasia-carcinoma sequences. Other strategies focus on the origin of cancer stem cell-related markers, such as CD44, and immune reaction-related markers, such as matrix metallopeptidases. Noninvasive methods such as blood-based approaches are more attractive. Serum pepsinogen levels predict the severity of gastric mucosal atrophy before H. pylori eradication, whereas plasma ghrelin levels are associated with atrophy even after eradication. Cell-free DNAs and RNAs are attractive tools for the early detection of cancer. These ideas could lead to the development of more personalized strategies for cancer prevention based on cutting-edge technologies.

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【大腸癌診療におけるprecision medicine】大腸癌患者の血清miRNAを用いた術前リンパ節転移予測診断能の意義について

森谷弘乃介, 松崎潤太郎, 高見澤康之, 坂本良平, 塚本俊輔, 志田大, 金光幸秀

癌の臨床 ((株)篠原出版新社) 65 ( 4 ) 345 - 351 2021.01

Joint Work, ISSN 0021-4949

Development of diagnostic models for solid cancers using circulating microRNAs

J Matsuzaki

CANCER SCIENCE 112, 203-203 2021

Research paper (international conference proceedings)

Su252 SUPERIORITY OF URGENT VS. EARLY ENDOSCOPIC HEMOSTASIS IN PATIENTS WITH UPPER GASTROINTESTINAL BLEEDING

M Horibe, E Iwasaki, J Matsuzaki, F Bazerbachi, T Kaneko, K Minami, ...

Gastroenterology 160 (6), S-655 2021

Research paper (international conference proceedings)

Comprehensive serum and tissue microRNA profiling in dedifferentiated liposarcoma

I Kohama, N Asano, J Matsuzaki, Y Yamamoto, T Yamamoto, ...

Oncology Letters 22 (2), 1-8 (Oncology Letters) 22 ( 2 ) 623 2021

Research paper (scientific journal), Accepted

Sarcoma is a rare cancer with several subtypes; therefore, our understanding of the pathogenesis of sarcoma is limited, and designing effective treatments is difficult. Circulating microRNAs (miRNAs), including exosomal miRNAs, have attracted attention as biomarkers in cancer. However, the roles of miRNAs and exosomes in sarcoma remain unclear. The present analysis of tissue and serum miRNA expression in osteosarcoma, Ewing's sarcoma and dedifferentiated liposarcoma (DDLPS) identified miR-1246, -4532, -4454, -619-5p and -6126 as biomarkers for DDLPS. These miRNAs were highly expressed in human DDLPS cell lines and exosomes, suggesting that they are secreted from DDLPS tissues. The present results suggested that specific miRNAs may be used as biomarkers for early diagnosis or treatment targets in DDLPS.

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Machine learning-based multiple cancer detections with circulating miRNA profiles in the blood.

J Matsuzaki, Y Yamamoto, O Yi, S Ayyar, R Miyajima, Y Takeda, T Nolan, ...

Journal of Clinical Oncology 39 (15_suppl), 3037-3037 2021

Research paper (international conference proceedings)

Superiority of urgent vs early endoscopic hemostasis in patients with upper gastrointestinal bleeding with high-risk stigmata

M Horibe, E Iwasaki, J Matsuzaki, F Bazerbachi, T Kaneko, K Minami, ...

Gastroenterology Report 9 ( 6 ) 543 - 551 2021

Research paper (scientific journal), Joint Work, Accepted, ISSN 2052-0034

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Circulating microRNAs: Next-generation Cancer Detection

J Matsuzaki, T Ochiya

The Keio journal of medicine 69 (4), 88-96 (Keio Journal of Medicine) 69 ( 4 ) 88 - 96 2020.12

Research paper (bulletin of university, research institution), Lead author, Corresponding author, Accepted

© 2020 by The Keio Journal of Medicine. Early detection of cancer is crucial for its ultimate control and the prevention of malignant progression. In Japan, a nationwide project was conducted between 2014 and 2019 to develop novel cancer detection tools using serum microRNAs (miRNAs). Using the National Cancer Center Biobank, we collected more than 10,000 serum samples from patients with malignant diseases, including rare cancers such as ovarian cancer, gliomas, and sarcomas. Subsequently, comprehensive miRNA microarray analyses were performed for all samples. This serum miRNA database provides insights regarding miRNA bio-marker candidates for each cancer type. Here, we summarize the major achievements of this national project. Notably, although circulating miRNAs packaged in extracellular vesicles are thought to be a cell-to-cell communication tool, the functional characteristics of the miRNAs listed in the project are still unknown. We hope that our findings will help elucidate the biological functions of circulating miR-NAs.

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Extracellular miRNAs for the Management of Barrett’s Esophagus and Esophageal Adenocarcinoma: A Systematic Review

K Inokuchi, T Ochiya, J Matsuzaki

Journal of Clinical Medicine 10 (1), 117 (Journal of Clinical Medicine) 10 ( 1 ) 1 - 16 2020.12

Research paper (scientific journal), Joint Work, Accepted, ISSN 2077-0383

Esophageal adenocarcinoma (EAC), the major histologic type of esophageal cancer (EC) in Western countries, is a disease with a poor prognosis, primarily due to usual diagnosis at an advanced stage. The prevalence of EAC has increased in recent years, both in Western countries and in Asia. Barrett’s esophagus (BE) is a precursor lesion of EAC. Therefore, early detection and proper management of BE and EAC is important to improve prognosis. Here, we systematically summarize current knowledge about the potential utility of extracellular microRNAs (miRNAs), which are thought to be non-invasive biomarkers for many diseases, for these purposes. A search of the PubMed and Embase databases identified 22 papers about extracellular miRNAs that have potential utility for management of EAC. Among them, 19 were EAC-related and ten were BE-related; some of these dealt with both conditions. The articles included studies reporting diagnosis, prognosis, and treatment responses. Multiple papers report dysregulation of miR-194-5p in BE and miR-21-5p, -25-3p, and -93-5p in EAC. Although it will take time to utilize these miRNAs in clinical practice, they are likely to be useful non-invasive markers in the future.

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Horibe GI bleeding prediction score: a simple score for triage decision-making in patients with suspected upper GI bleeding

M Horibe, E Iwasaki, F Bazerbachi, T Kaneko, J Matsuzaki, K Minami, ...

Gastrointestinal endoscopy 92 (3), 578-588. e4 (Gastrointestinal Endoscopy) 92 ( 3 ) 578 - 588.e4 2020.09

Research paper (scientific journal), Accepted

© 2020 American Society for Gastrointestinal Endoscopy Background and Aims: Although upper GI bleeding (UGIB) is a significant cause of inpatient admissions, no scoring method has proven to be accurate and simple as a standard for triage purposes. Therefore, we compared a previously described 3-variable score (1 point each for absence of daily proton pump inhibitor use in the week before the index presentation, shock index [heart rate/systolic blood pressure] ≥1, and blood urea nitrogen/creatinine ≥30 [urea/creatinine≥140]), the Horibe gAstRointestinal BleedING scoRe (HARBINGER), with the 8-variable Glasgow-Blatchford Score (GBS) and 5-variable AIMS65 to evaluate and validate the accuracy in predicting high-risk features that warrant admission and urgent endoscopy. Methods: Consecutive patients presenting with suspected UGIB between 2012 and 2015 were prospectively enrolled in 3 acute care Japanese hospitals. On presentation to the emergency setting, an endoscopy was performed in a timely fashion. The primary outcome was the prediction of high-risk endoscopic stigmata. Results: Of 1486 enrolled patients, 637 (43%) harbored high-risk endoscopic stigmata according to international consensus statements. The area under the receiver operating characteristic curve (AUC) for the HARBINGER was.76 (95% confidence interval [CI],.72-.79), which was significantly superior to both the GBS (AUC,.68; 95% CI,.64-.71; P <.001) and the AIMS65 (AUC,.54; 95% CI,.50-.58; P <.001). When the HARBINGER cutoff value was set at 1 to rule out patients who needed admission and urgent endoscopy, its sensitivity and specificity was 98.8% (95% CI, 97.9-99.6) and 15.5% (95% CI, 13.1-18.0), respectively. Conclusions: The HARBINGER, a simple 3-variable score, provides a more accurate method for triage of patients with suspected UGIB than both the GBS and AIMS65.

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【癌早期発見・早期診断のNew Era】血中マイクロRNAを用いた癌早期診断法の開発と展望

松崎潤太郎, 落谷孝広

消化器・肝臓内科 ((有)科学評論社) 8 ( 2 ) 132 - 136 2020.08

Joint Work, ISSN 2432-3446

【Helicobacter Topics!-「旬のHelicobacter」を知り、驚き、理解を深め、楽しむ-】Helicobacter pylori関連ディスペプシアの病態

松崎潤太郎

Helicobacter Research ((株)先端医学社) 24 ( 1 ) 83 - 85 2020.05

Joint Work, ISSN 1342-4319

慢性的に持続するディスペプシア症状のなかで、とくにHelicobacter pylori除菌治療によって改善するものをH.pylori関連ディスペプシアとよぶ。現在、世界中の主要なガイドラインにおいてディスペプシア診療の最も最初にH.pylori感染診断が推奨されている。H.pylori感染に伴うグレリン分泌の低下とディスペプシア症状との関連は以前より指摘されているが、胃粘膜萎縮の程度と除菌後の症状改善頻度には明確な関連性はない。最近、われわれの研究グループは、H.pyloriにおける好中球活性化因子NapAの多型によってディスペプシア症状の惹起頻度が異なることを見出し、スナネズミ感染モデルにおいて実際に胃排出遅延が生じることなどから、H.pylori関連ディスペプシアの有力な機序であることを報告した。(著者抄録)

Highly sensitive circulating microRNA panel for accurate detection of hepatocellular carcinoma in patients with liver disease

Y Yamamoto, S Kondo, J Matsuzaki, M Esaki, T Okusaka, K Shimada, ...

Hepatology communications 4 (2), 284-297 (Hepatology Communications) 4 ( 2 ) 284 - 297 2020.02

Research paper (scientific journal), Joint Work, Lead author, Accepted, ISSN 2471254X

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer deaths worldwide. The high mortality rate in HCC is largely due to the difficulty of early detection. In this study, to improve patient outcomes, serum samples from 345 patients with HCC, 46 patients with chronic hepatitis (CH), 93 patients with liver cirrhosis (LC), and 1,033 healthy individuals were analyzed with microRNA (miRNA) microarrays. We investigated the diagnostic potential of circulating miRNAs in serum and developed a detection model of HCC, including early stage. A diagnostic model was constructed based on the expression levels of a combination of miRNAs in a discovery set. We selected 52 miRNAs that had altered expressions according to disease progression status, established the diagnostic model with a combination of eight miRNAs in the discovery set, and tested the model in a validation set. The diagnostic values for discriminating cancer from HCC at-risk control samples were as follows: area under the curve, 0.99; sensitivity, 97.7%; specificity, 94.7%. With this model, 98% of stage I HCC cases were detected; these results were much better than those observed from conventional methods. Conclusion: Circulating miRNAs could serve as biomarkers for the accurate detection of HCC. Because the diagnostic accuracy was maintained even in stage I, this may represent an accurate detection method even for early stage HCC.

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Identification of serum microRNAs predicting the response of esophageal squamous-cell carcinoma to nivolumab

K Sudo, K Kato, J Matsuzaki, S Takizawa, Y Aoki, H Shoji, S Iwasa, ...

Japanese journal of clinical oncology 50 (2), 114-121 50 ( 2 ) 114 - 121 2020

Research paper (scientific journal), Joint Work, Accepted, ISSN 0368-2811

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A miRNA-based diagnostic model predicts resectable lung cancer in humans with high accuracy

K Asakura, T Kadota, J Matsuzaki, Y Yoshida, Y Yamamoto, K Nakagawa, ...

Communications biology 3 (1), 1-9 (Communications Biology) 3 ( 1 ) 134 2020

Research paper (scientific journal), Accepted

© 2020, The Author(s). Lung cancer, the leading cause of cancer death worldwide, is most frequently detected through imaging tests. In this study, we investigated serum microRNAs (miRNAs) as a possible early screening tool for resectable lung cancer. First, we used serum samples from participants with and without lung cancer to comprehensively create 2588 miRNAs profiles; next, we established a diagnostic model based on the combined expression levels of two miRNAs (miR-1268b and miR-6075) in the discovery set (208 lung cancer patients and 208 non-cancer participants). The model displayed a sensitivity of 99% and specificity of 99% in the validation set (1358 patients and 1970 non-cancer participants) and exhibited high sensitivity regardless of histological type and pathological TNM stage of the cancer. Moreover, the diagnostic index markedly decreased after lung cancer resection. Thus, the model we developed has the potential to markedly improve screening for resectable lung cancer.

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Adenosine leakage from perforin-burst extracellular vesicles inhibits perforin secretion by cytotoxic T-lymphocytes

H Tadokoro, A Hirayama, R Kudo, M Hasebe, Y Yoshioka, J Matsuzaki, ...

PloS one 15 (4), e0231430 (PLoS ONE) 15 ( 4 ) e0231430 2020

Research paper (scientific journal), Accepted

© 2020 Tadokoro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Extracellular vesicles (EVs) in the tumor microenvironment facilitate intercellular communication. Cancer cell-derived EVs act as an immunosuppressor by transporting cargos and presenting transmembrane proteins. By contrast, CD8+ cytotoxic T-lymphocytes (CTLs) exert anti-cancer cytotoxicity via the pore-forming protein perforin. Here, we hypothesize that although EVs are destroyed by perforin, cancer cell-derived EVs might possess mechanisms that enable them to avoid this destruction. We used a breast cancer cell line, MDA-MB-231luc-D3H2LN (D3H2LN), to generate EVs. Destruction of the EVs by perforin was demonstrated visually using atomic force microscopy. To investigate immunosuppressive metabolites within cancer cell-derived EVs, we performed metabolomic profiling of EVs from D3H2LN cells cultured for 48 h with or without IFN-γ, which induces metabolic changes in the cells. We found that both types of EV from IFN-γ treated D3H2LN cells and non-treated D3H2LN cells contained adenosine, which has immunosuppressive effects. When we exposed cancer cell-derived EVs to CTLs, perforin secretion by CTLs fell significantly. In addition, the decreases in perforin secretion were ameliorated by treatment with adenosine deaminase, which degrades extracellular adenosine. Taken together, these results suggest that after perforin secreted by CTLs disrupts the membrane of EVs, adenosine released from the EVs acts as an immunosuppressive metabolite by binding to the adenosine receptor on the CTL membrane. This mechanism provides a novel survival strategy using cancer cell-derived EVs.

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Efficacy and safety of immediate oral intake in patients with mild acute pancreatitis: A randomized controlled trial

M Horibe, E Iwasaki, A Nakagawa, J Matsuzaki, K Minami, Y Machida, ...

Nutrition 74, 110724 (Nutrition) 74 110724 2020

Research paper (scientific journal), Accepted

© 2020 Objectives: Early enteral nutrition is recommended for patients with severe acute pancreatitis (AP); however, nutritional management strategies for patients with mild AP have not been established. The aim of this study was to evaluate the benefits and safety of immediate oral intake of low-fat solid food in patients with mild AP who were allowed to take opioid analgesics. Methods: In this single-center randomized study, the immediate feeding (IMF) group was permitted immediate oral intake of low-fat (15 g/d) solid food. In the standard food (STF) group, patients received gradually increasing amounts of dietary fat. Twenty-six patients were randomized, with 13 allocated to each group. The primary outcome was the period between diagnosis and recovery from AP. The cost and rate of progression to severe disease were evaluated as secondary outcomes. Results: The IMF group (mean recovery days: 2 ± 1) recovered significantly earlier (mean difference in recovery days: 6.3; 95% confidence interval [CI], 4.8–7.9; P < 0.001) than the STF group (mean recovery days: 8.3 ± 2.3), with a lower overall treatment cost (mean difference in costs: −$460; 95% CI, −$880 to –$40; P = 0.034). The IMF group showed a lower rate of progression to severe AP (IMF, 0%; STF, 15.3%; P = 0.48). Conclusion: The initial treatment strategy for mild AP should be altered from the gradual introduction of oral feeding upon the absence of pain to immediate oral nutrition with opioid analgesics, to improve treatment efficacy and reduce treatment cost.

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Transcriptomic dissection of hepatocyte heterogeneity: linking ploidy, zonation, and stem/progenitor cell characteristics

T Katsuda, K Hosaka, J Matsuzaki, W Usuba, M Prieto-Vila, T Yamaguchi, ...

Cellular and molecular gastroenterology and hepatology 9 (1), 161-183 (Cellular and Molecular Gastroenterology and Hepatology) 9 ( 1 ) 161 - 183 2020

Research paper (scientific journal), Accepted

© 2019 The Authors Background & Aims: There is a long-standing debate regarding the biological significance of polyploidy in hepatocytes. Recent studies have provided increasing evidence that hepatocytes with different ploidy statuses behave differently in a context-dependent manner (eg, susceptibility to oncogenesis, regenerative ability after injury, and in vitro proliferative capacity). However, their overall transcriptomic differences in a physiological context is not known. Methods: By using microarray transcriptome analysis, we investigated the heterogeneity of hepatocyte populations with different ploidy statuses. Moreover, by using single-cell quantitative reverse-transcription polymerase chain reaction (scPCR) analysis, we investigated the intrapopulational transcriptome heterogeneity of 2c and 4c hepatocytes. Results: Microarray analysis showed that cell cycle–related genes were enriched in 8c hepatocytes, which is in line with the established notion that polyploidy is formed via cell division failure. Surprisingly, in contrast to the general consensus that 2c hepatocytes reside in the periportal region, in our bulk transcriptome and scPCR analyses, the 2c hepatocytes consistently showed pericentral hepatocyte-enriched characteristics. In addition, scPCR analysis identified a subpopulation within the 2c hepatocytes that co-express the liver progenitor cell markers Axin2, Prom1, and Lgr5, implying the potential biological relevance of this subpopulation. Conclusions: This study provides new insights into hepatocyte heterogeneity, namely 2c hepatocytes are preferentially localized to the pericentral region, and a subpopulation of 2c hepatocytes show liver progenitor cell–like features in terms of liver progenitor cell marker expression (Axin2, Prom1, and Lgr5).

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Su1391 EFFICACY AND SAFETY OF VONOPRAZAN, SITAFLOXACIN AND METRONIDAZOLE CONTAINING REGIMEN FOR HELICOBACTER PYLORI ERADICATION IN PATIENTS WITH PENICILLIN ALLERGY

T Masaoka, H Mori, H Suzuki, J Matsuzaki, A Okazawa, M Yoshioka, ...

Gastroenterology 158 (6), S-574 2020

Research paper (international conference proceedings)

EFFICACY AND SAFETY OF VONOPRAZAN, SITAFLOXACIN AND METRONIDAZOLE CONTAINING REGIMEN FOR HELICOBACTER PYLORI ERADICATION IN PATIENTS WITH PENICILLIN ALLERGY

T Masaoka, H Mori, H Suzuki, J Matsuzaki, A Okazawa, M Yoshioka, ...

Gastroenterology 158 (6), S574-S574 2020

Research paper (international conference proceedings)

A serum microRNA classifier for the diagnosis of sarcomas of various histological subtypes

N Asano, J Matsuzaki, M Ichikawa, J Kawauchi, S Takizawa, Y Aoki, ...

Nature communications 10 (1), 1-10 (Nature Communications) 10 ( 1 ) 1299 2019.12

Research paper (scientific journal), Joint Work, Lead author, Accepted

© 2019, The Author(s). Due to their rarity and diversity, sarcomas are difficult to diagnose. Consequently, there is an urgent demand for a novel diagnostic test for these cancers. In this study, we investigated serum miRNA profiles from 1002 patients with bone and soft tissue tumors representing more than 43 histological subtypes, including sarcomas, intermediate tumors, and benign tumors, to determine whether serum miRNA profiles could be used to specifically detect sarcomas. Circulating serum miRNA profiles in sarcoma patients were clearly distinct from those in patients with other types of tumors. Using the serum levels of seven miRNAs, we developed a molecular detector, Index VI, that could distinguish sarcoma patients from benign and healthy controls with remarkably high sensitivity (90%) and specificity (95%), regardless of histological subtype. Index VI provides an approach to the early and precise detection of sarcomas, potentially leading to curative treatment and longer survival.

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【消化管症候群(第3版)-その他の消化管疾患を含めて-】十二指腸　十二指腸乳頭炎

松崎潤太郎, 金井隆典

日本臨床 ((株)日本臨床社) 別冊 ( 消化管症候群I ) 458 - 460 2019.12

Joint Work, ISSN 0047-1852

【消化管症候群(第3版)-その他の消化管疾患を含めて-】胃　腫瘍性疾患　胃底腺ポリープ

猪口和美, 松崎潤太郎, 金井隆典

日本臨床 ((株)日本臨床社) 別冊 ( 消化管症候群I ) 207 - 211 2019.12

Joint Work, ISSN 0047-1852

クローン病経過中に急速に進行する悪性リンパ腫を発症した一例

猪口和美, 三上洋平, 福原佳代子, 松崎潤太郎, 筋野智久, 牟田口真, 高林馨, 南木康作, 神谷高博, 岡山幹夫, 菊池拓, 林雄一郎, 長沼誠, 緒方晴彦, 岩男泰, 清水隆之, 金井隆典

日本消化器病学会関東支部例会プログラム・抄録集 (日本消化器病学会-関東支部) 357回 23 - 23 2019.12

Joint Work

慢性偽性腸閉塞の経過観察中に食道アカラシアを発症した1例

猪口和美, 正岡建洋, 松崎潤太郎, 川久保博文, 亀山香織, 北川雄光, 金井隆典

日本消化器病学会関東支部例会プログラム・抄録集 (日本消化器病学会-関東支部) 355回 37 - 37 2019.07

Joint Work

Establishment of patient-derived organoids and drug screening for biliary tract carcinoma

Y Saito, T Muramatsu, Y Kanai, H Ojima, A Sukeda, N Hiraoka, E Arai, ...

Cell reports 27 (4), 1265-1276. e4 (Cell Reports) 27 ( 4 ) 1265 - 1276.e4 2019.04

Research paper (scientific journal), Accepted

© 2019 The Author(s) Biliary tract carcinomas (BTCs) are among the most aggressive malignancies and have a poor prognosis. Here, we successfully established organoid lines derived from intrahepatic cholangiocarcinoma, gallbladder cancer, and neuroendocrine carcinoma of the ampulla of Vater. These organoids derived from BTCs were cultured stably for >1 year and closely recapitulated the histopathology, gene expression, and genetic alterations evident in the primary tumors. Gene expression profiling of the organoids revealed that SOX2 could be a potential prognostic biomarker for patients with BTC. We screened a compound library consisting of drugs used clinically for their ability to suppress organoids derived from BTCs and found that the antifungal drugs amorolfine and fenticonazole significantly suppressed the growth of organoids derived from BTCs with minimal toxicity to normal biliary epithelial cells. Patient-derived organoids may be a powerful research tool for the clarification of molecular pathogenesis and the discovery of biomarkers and therapeutic drugs for refractory cancers.

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Clinical and endoscopic findings to assist the early detection of duodenal adenoma and adenocarcinoma

J Matsuzaki, H Suzuki, M Shimoda, H Mori, S Fukuhara, S Miyoshi, ...

United European gastroenterology journal 7 (2), 250-260 (United European Gastroenterology Journal) 7 ( 2 ) 250 - 260 2019.03

Research paper (scientific journal), Lead author, Accepted

© Author(s) 2018. Background: Sporadic nonampullary duodenal adenocarcinoma is a rare malignant neoplasm in which poor prognosis is often associated with delayed diagnosis. Objective: A case-control study was designed to evaluate the clinical and endoscopic characteristics of patients with nonampullary duodenal epithelial tumours (NADETs). Methods: Patients with NADETs were chronologically divided into a discovery and a validation sets. Two age- and sex-matched control individuals for each case in the discovery set were randomly selected from individuals without NADET. A prediction model for the presence of NADET, constructed in the discovery set, was evaluated in the validation set. Results: In total, 368 adenomas, 81 adenocarcinomas, and 314 controls were analysed. Current smoking, Barrett oesophagus, fundic gland polyps, history of malignant disease, and absence of dyslipidaemia were independently associated with the presence of NADET. The combination of these five factors enabled significant discrimination for NADET in the bulb with a sensitivity of 0.81 in the validation set. We also showed that duodenal adenocarcinomas in the bulb had greater invasive potential than adenocarcinomas in the second portion. Conclusion: The presence of a duodenal tumour in the bulb could be predicted by clinical and endoscopic findings, which helps improve the prognosis and quality of life of patients.

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CAPZA1 determines the risk of gastric carcinogenesis by inhibiting Helicobacter pylori CagA-degraded autophagy

H Tsugawa, H Mori, J Matsuzaki, A Sato, Y Saito, M Imoto, M Suematsu, ...

Autophagy 15 (2), 242-258 (Autophagy) 15 ( 2 ) 242 - 258 2019.02

Research paper (scientific journal), Accepted

© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. Helicobacter pylori-derived CagA, a type IV secretion system effector, plays a role as an oncogenic driver in gastric epithelial cells. However, upon delivery into gastric epithelial cells, CagA is usually degraded by macroautophagy/autophagy. Hence, the induction of autophagy in H. pylori-infected epithelial cells is an important host-protective ability against gastric carcinogenesis. However, the mechanisms by which autophagosome-lysosome fusion is regulated, are unknown. Here, we report that enhancement of LAMP1 (lysosomal associated membrane protein 1) expression is necessary for autolysosome formation. LAMP1 expression is induced by nuclear translocated LRP1 (LDL receptor related protein 1) intracellular domain (LRP1-ICD) binding to the proximal LAMP1 promoter region. Nuclear translocation of LRP1-ICD is enhanced by H. pylori infection. In contrast, CAPZA1 (capping actin protein of muscle Z-line alpha subunit 1) inhibits LAMP1 expression via binding to LRP1-ICD in the nuclei. The binding of CAPZA1 to LRP1-ICD prevents LRP1-ICD binding to the LAMP1 proximal promoter. Thus, in CAPZA1-overexpressing gastric epithelial cells infected with H. pylori, autolysosome formation is inhibited and CagA escapes autophagic degradation. These findings identify CAPZA1 as a novel negative regulator of autolysosome formation and suggest that deregulation of CAPZA1 expression leads to increased risk of gastric carcinogenesis. Abbreviations: CagA: cytotoxin-associated gene A; CAPZA1: capping actin protein of muscle Z-line alpha subunit 1; ChIP: chromatin immunoprecipitation; GTF2I: general transcription factor IIi; HDAC: histone deacetylase; LAMP1: lysosomal associated membrane protein 1; LRP1: LDL receptor related protein 1; LRP1-ICD: CagA intracellular domain; qPCR: quantitative polymerase chain reaction; VacA: vacuolating cytotoxin.

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Circulating miRNA panels for specific and early detection in bladder cancer

W Usuba, F Urabe, Y Yamamoto, J Matsuzaki, H Sasaki, M Ichikawa, ...

Cancer science 110 (1), 408-419 (Cancer Science) 110 ( 1 ) 408 - 419 2019.01

Research paper (scientific journal), Accepted

© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. Bladder cancer is the 9th leading cause of cancer death worldwide. The major problem in bladder cancer is primarily the high recurrence rate after drug treatment and resection. Although conventional screening methods, such as cystoscopy, urinary cytology and ultrasound sonography, have become widely used in clinical settings, the diagnostic performance of these modalities is unsatisfactory due to low accuracy or high invasiveness. Because circulating micro RNA (miRNA) profiles have recently been reported as an attractive tool for liquid biopsy in cancer screening, here, we performed global miRNA profiling of 392 serum samples of bladder cancer patients with 100 non-cancer samples and 480 samples of other types of cancer as controls. We randomly classified the bladder cancer and control samples into 2 cohorts, a training set (N = 486) and a validation set (N = 486). By comparing both controls, we identified specific miRNA, such as miR-6087, for diagnosing bladder cancer in the training and validation sets. Furthermore, we found that a combination of 7 miRNA (7-miRNA panel: miR-6087, miR-6724-5p, miR-3960, miR-1343-5p, miR-1185-1-3p, miR-6831-5p and miR-4695-5p) could discriminate bladder cancer from non-cancer and other types of tumors with the highest accuracy (AUC:.97; sensitivity: 95%; specificity: 87%). The diagnostic accuracy was high, regardless of the stage and grade of bladder cancer. Our data demonstrated that the 7-miRNA panel could be a biomarker for the specific and early detection of bladder cancer.

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Neutrophil-activating protein polymorphism of Helicobacter pylori determines the host risk of dyspepsia

J Matsuzaki, H Tsugawa, Y Kashiwazaki, H Mori, Y Yamamoto, ...

Cellular and molecular gastroenterology and hepatology 8 (2), 295 (Cellular and Molecular Gastroenterology and Hepatology) 8 ( 2 ) 295 - 297.e6 2019

Research paper (scientific journal), Lead author, Accepted

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Serum miRNA–based prediction of axillary lymph node metastasis in breast cancer

S Shiino, J Matsuzaki, A Shimomura, J Kawauchi, S Takizawa, ...

Clinical Cancer Research 25 (6), 1817-1827 (Clinical Cancer Research) 25 ( 6 ) 1817 - 1827 2019

Research paper (scientific journal), Accepted

© 2018 American Association for Cancer Research. Purpose: Sentinel lymph node biopsy (SLNB) is the gold-standard procedure for evaluating axillary lymph node (ALN) status in patients with breast cancer. However, the morbidity of SLNB is not negligible, and the procedure is invasive for patients without ALN metastasis. Here, we developed a diagnostic model for evaluating ALN status using a combination of serum miRNAs and clinicopathologic factors as a novel less-invasive biomarker. Experimental Design: Preoperative serum samples were collected from patients who underwent surgery for primary breast cancer or breast benign diseases between 2008 and 2014. A total of 958 serum samples (921 cases of primary breast cancer, including 630 cases in the no ALN metastasis group and 291 cases in the ALN metastasis group, and 37 patients with benign breast diseases) were analyzed by miRNA microarray. Samples were randomly divided into training and test sets. Logistic LASSO regression analysis was used to construct diagnostic models in the training set, which were validated in the test set. Results: An optimal diagnostic model was identified using a combination of two miRNAs (miR-629-3p and miR-4710) and three clinicopathologic factors (T stage, lymphovascular invasion, and ultrasound findings), which showed a sensitivity of 0.88 (0.84–0.92), a specificity of 0.69 (0.61–0.76), an accuracy of 0.818, and an area under the receiver operating characteristic curve of 0.86 in the test set. Conclusions: Serum miRNA profiles may be useful for the diagnosis of ALN metastasis before surgery in a less-invasive manner than SLNB.

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Development and validation of an esophageal squamous cell carcinoma detection model by large-scale microRNA profiling

K Sudo, K Kato, J Matsuzaki, N Boku, S Abe, Y Saito, H Daiko, ...

JAMA network open 2 (5), e194573-e194573 (JAMA network open) 2 ( 5 ) e194573 2019

Research paper (scientific journal), Joint Work, Accepted

Importance: Patients with late-stage esophageal squamous cell carcinoma (ESCC) have a poor prognosis. Noninvasive screening tests using serum microRNAs (miRNAs) to accurately detect early-stage ESCC are needed to improve mortality. Objective: To establish a model using serum miRNAs to distinguish patients with ESCC from noncancer controls. Design, Setting, and Participants: In this case-control study, serum miRNA expression profiles of patients with ESCC (n = 566) and control patients without cancer (n = 4965) were retrospectively analyzed to establish a diagnostic model, which was tested in a training set and confirmed in a validation set. Patients histologically diagnosed as having ESCC who did not receive prior therapy or have a past or concurrent cancer other than ESCC were enrolled from the National Cancer Center Hospital in Tokyo, Japan. Between October 2010 and November 2015, control samples were collected from the National Cancer Center Biobank, the Biobank of the National Center for Geriatrics and Gerontology, and the general population undergoing routine health examination. Data analysis was performed between August 2015 and October 2018. Serum samples were randomly divided into discovery and validation sets. Main Outcomes and Measures: The expression of 2565 miRNAs was assessed in each sample. The discriminant model (named the EC index) was evaluated in the training set using Fisher linear discriminant analysis with a greedy algorithm. Receiver operating characteristic curve analysis evaluated the diagnostic ability of the model in the validation set. Results: In the training set, 283 patients with esophageal cancer (median age, 67 years [range, 37-90 years]; 83.4% male) were compared with 283 control patients (median age, 54 years [range, 22-100 years]; 43.1% male), and the EC index was constructed using 6 miRNAs (miR-8073, miR-6820-5p, miR-6794-5p, miR-3196, miR-744-5p, and miR-6799-5p). The area under the receiver operating characteristic curve was 1.00, with sensitivity of 1.00 and specificity of 0.98. The validation set included 283 patients (median age, 66 years [range, 42-87 years]; 83.0% male) and 4682 control patients (median age, 68 years [range, 20-98 years]; 44.7% male), and the area under the receiver operating characteristic curve for the EC index was 1.00, with sensitivity of 0.96 and specificity of 0.98. Conclusions and Relevance: What appears to be novel serum miRNA discriminant model was developed for the diagnosis of ESCC. A multicenter prospective study is ongoing to confirm the present observations.

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Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma

Chuma, M. and Toyoda, H. and Matsuzaki, J. and Saito, Y. and Kumada, T. and Tada, T. and Kaneoka, Y. and Maeda, A. and Yokoo, H. and Ogawa, K. and Kamiyama, T. and Taketomi, A. and Matsuno, Y. and Yazawa, K. and Takeda, K. and Kunisaki, C. and Ogushi, K. and Moriya, S. and Hara, K. and Nozaki, A. and Kondo, M. and Fukuda, H. and Numata, K. and Tanaka, K. and Maeda, S. and Sakamoto, N.

Hepatology Research (Hepatology Research) 49 ( 7 ) 810 - 822 2019

Research paper (scientific journal), Accepted

© 2019 The Japan Society of Hepatology Aims: Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. Methods: We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription–polymerase chain reaction (PCR). Results: Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR-1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR-1246 was associated with aggressive tumor characteristics, including tumor–node–metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR-1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528–5.071; P = 0.0008). Conclusion: Circulating miR-1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.

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10-Year trends in Helicobacter pylori eradication rates by Sitafloxacin-based third-line rescue therapy

H Mori, H Suzuki, J Matsuzaki, T Masaoka, T Kanai

Digestion 101 (5), 644-650 (Digestion) 101 ( 5 ) 644 - 650 2019

Research paper (scientific journal), Joint Work, Accepted, ISSN 0012-2823

© 2020 S. Karger AG. All rights reserved. Background/Aims: Sitafloxacin (STFX)-containing regimens were shown to be useful options for third-line Helicobacter pylori eradication therapy. It is reported that resistance to quinolone is also increasing globally. Therefore, we conducted an analysis of the current efficacy of a 10-day-STFX-containing third-line rescue therapy and the changes of antibiotic resistance to H. pylori compared to 2 historical controls. Methods: Patients in whom eradication treatment using both first-and second-line triple therapies failed were enrolled from 2014 to 2015. The minimum inhibitory concentrations of STFX, clarithromycin (CLR), amoxicillin (AMX), metronidazole (MTZ) and the gyrA mutation status of the H. pylori strains were determined before treatment. After that, the patients received a 10-day triple therapy containing esomeprazole (20 mg, b.i.d.), AMX (500 mg, q.i.d.) and STFX (100 mg, b.i.d.; 10-day EAS). The eradication rate and the rate of antibiotic resistance to H. pylori were compared with 2 previous reports about STFX-containing third-line rescue therapies in 2009-2011 and 2012-2013. To explore the association between the eradication rates of regimens containing STFX, AMX and proton pump inhibitors and the location of gyrA mutation or AMX resistance, a meta-Analysis was attempted. Results: The overall eradication rates, the eradication rate for gyrA mutation negative-and positive-strains were 81.6% (31/38), 94.7% (18/19) and 68.4% (13/19) respectively. These rates were not significantly different from 2 previous reports. The resistant rates to STFX, CLR, AMX, MTZ and the rate of presence of mutation in gyrA were 50.0, 81.6, 36.8, 78.9 and 50.0%, respectively, which was also not significantly different from 2 previous reports. A meta-Analysis showed that the relative risk of the eradication failure is significantly lower in gyrA mutation negative strains compared to gyrA mutation positive strains, and that the relative risk of the eradication failure is significantly lower in gyrA mutation at D91 compared to gyrA mutation at N87 (p < 0.001 and p = 0.022, respectively). Moreover, a meta-Analysis showed that the relative risk of the eradication failure is significantly lower in AMX-sensitive strains compared to AMX-resistant ones. Conclusion: Changes in the rate of antibiotic resistance to H. pylori were not observed from 2009 to 2015. The status of gyrA mutation is a superior marker for predicting successful eradication in STFX/AMX-containing triple regimen as a third-line rescue therapy.

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A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Teprenone in Patients with Alzheimer’s Disease

S Yokoyama, T Yoshinaga, J Matsuzaki, H Suzuki

Journal of Alzheimer's Disease 71 (4), 1187-1199 (Journal of Alzheimer's Disease) 71 ( 4 ) 1187 - 1199 2019

Research paper (scientific journal), Accepted

© 2019 - IOS Press and the authors. All rights reserved. Teprenone (geranylgeranylacetone), an anti-ulcer agent, has been reported to inhibit amyloid-β increase, senile plaque formation, and neuronal degeneration, and improve memory in mouse models of Alzheimer's disease (AD). Objective: We conducted a randomized, double-blind, placebo-controlled study to ascertain teprenone's therapeutic ability for AD. Methods: Patients with mild to moderate AD, with a Mini-Mental State Examination (MMSE) score of 13 to 26, were randomly allocated into two groups depending on the administered drug: donepezil+ placebo (placebo group) and donepezil+teprenone (teprenone group). The primary and secondary endpoints included changes in scores of the Japanese version of the AD Assessment Scale-cognitive subscale (ADAS-J cog) and other evaluations, respectively, including MMSE scores, during a 12-month period after the first administration. Results: Forty-two and thirty-seven patients were allocated to the teprenone and placebo groups, respectively. ADAS-J cog score changes were not different between groups (placebo, 0.6±0.8; teprenone, 0.4±0.8; p=0.861). However, MMSE scores significantly improved in the teprenone group (placebo, - 1.2±0.5; teprenone, 0.2±0.5; p=0.044). Subgroup analysis considering the severity of medial temporal area atrophy revealed that this improvement by teprenone was significant in patients with mild (p=0.013) but not with severe atrophy (p=0.611). Adverse events were observed in 17.8 and 10.4% of patients in the placebo and teprenone group, respectively. Conclusion: Teprenone may be effective for AD when administered before atrophy progression in the medial temporal areas. Trial Registration: UMIN ID: UMIN000016843

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Assessment of the diagnostic utility of serum microRNA classification in patients with diffuse glioma

M Ohno, J Matsuzaki, J Kawauchi, Y Aoki, J Miura, S Takizawa, K Kato, ...

JAMA network open 2 (12), e1916953-e1916953 (JAMA network open) 2 ( 12 ) e1916953 2019

Research paper (scientific journal), Lead author, Accepted

Importance: A blood-based screening tool for detecting diffuse glioma is necessary to improve clinical outcomes. Objectives: To establish models using serum microRNAs to distinguish patients with diffuse glioma from control individuals without cancer (the Glioma Index) and to differentiate glioblastoma (GBM), primary central nervous system lymphoma (PCNSL), and metastatic brain tumors (the 3-Tumor Index). Design, Setting, and Participants: This retrospective, case-control diagnostic study included 157 patients with diffuse glioma and 109 patients with central nervous system (CNS) diseases other than diffuse glioma diagnosed from August 1, 2008, through May 1, 2016, and 314 sex- and age-matched controls without cancer. Samples of patients with diffuse glioma and controls were randomly divided into training and validation set 1, and those of patients with CNS diseases other than diffuse glioma were allocated to an exploratory set. Samples of patients with GBM, PCNSL, and metastatic brain tumors were randomly divided into training and validation set 2. Data were analyzed from April 1, 2018, to March 31, 2019. Main Outcomes and Measures: The expression of 2565 microRNAs was assessed, and the diagnostic performance was evaluated by calculating the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, and accuracy. Results: A total of 580 patients were included in the analysis (309 [53.3%] male; median age, 57 years [range, 10-87 years]). In training set 1, 100 patients with diffuse glioma (median age, 56 years [range, 14-87 years]; 55 male [55.0%]) were compared with 200 control patients (median age, 56 years [range, 14-87 years]; 105 male [52.5%]), and the Glioma Index was constructed using 3 microRNAs (miR-4763-3p, miR-1915-3p, and miR-3679-5p). In validation set 1, the AUC was 0.99 (95% CI, 0.99-1.00); sensitivity, 0.95 (95% CI, 0.89-1.00); and specificity, 0.97 (95% CI, 0.93-1.00). The Glioma Index classified 39 of 42 PCNSL samples (92.9%) and 25 of 28 metastatic brain tumor samples (89.3%) as positive and 2 of 2 spinal tumors (100%) as negative in the exploratory set. In training set 2, 68 patients with GBM, 34 with PCNSL, and 23 with metastatic brain tumor were compared, and the 3-Tumor Index was constructed using 48 microRNAs. The 3-Tumor Index had an accuracy of 0.80, positively detecting 16 of 17 GBM samples (94.1%), 4 of 5 metastatic brain tumor samples (80.0%), and 4 of 8 PCNSL samples (50.0%) in validation set 2. Conclusions and Relevance: This study appears to have identified promising serum microRNA combinations for detecting diffuse glioma and for assessing histologic features of brain tumors.

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Brain metastasis-related microRNAs in patients with advanced breast cancer

J Sato, A Shimomura, J Kawauchi, J Matsuzaki, Y Yamamoto, S Takizawa, ...

Plos one 14 (10), e0221538 (PLoS ONE) 14 ( 10 ) e0221538 2019

Research paper (scientific journal), Accepted

© 2019 Sato et al. © 2019 by the authors. Licensee MDPI, Basel, Switzerland. Brain metastasis is a major distant metastasis occurring in patients with advanced breast cancer, and is associated with poor prognosis. MicroRNAs (miRNAs) have a strong influence on various oncological functions and have been reported as potential biomarkers for detecting distant metastasis. Specific biomarkers and unique miRNAs for brain metastasis have yet to be reported. The aim of this study was to identify novel miRNAs in serum, to assist in the diagnosis of brain metastasis in patients with advanced breast cancer. We retrospectively analyzed the medical records of patients with breast cancer and collected clinical data. In addition, we evaluated serum miRNA profiles in patients with breast cancer, with and without brain metastasis, using high-sensitivity microarrays. All patients underwent computed tomography or magnetic resonance imaging brain imaging tests. A total of 51 serum samples from patients with breast cancer and brain metastasis, stored in the National Cancer Center Biobank, were used, and 28 serum samples were obtained from controls without brain metastasis. Two miRNAs, miR-4428 and miR-4480, could significantly distinguish patients with brain metastasis, with area under the receiver operating characteristic curve (AUC) values of 0.779 and 0.781, respectively, while a combination of miR-4428 and progesterone receptor had an AUC value of 0.884. No significant correlations were identified between the expression levels of these two miRNAs in serum and clinical data. We conclude that serum miR-4428 and miR-4480 may be useful as biomarkers for predicting brain metastasis in patients with breast cancer.

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Serum microRNA-based risk prediction for stroke

T Sonoda, J Matsuzaki, Y Yamamoto, T Sakurai, Y Aoki, S Takizawa, ...

Stroke 50 (6), 1510-1518 (Stroke) 50 ( 6 ) 1510 - 1518 2019

Research paper (scientific journal), Accepted

© 2019 American Heart Association, Inc. Background and Purpose-Numerous studies have shown that circulating microRNAs (miRNAs) can be used as noninvasive biomarkers of various diseases. This study aimed to identify serum miRNAs that predict the risk of stroke. Methods-The cases were individuals who had been diagnosed with cerebrovascular disorder by brain imaging. The controls were individuals with no history of stroke who had undergone a medical checkup. Serum miRNA profiling was performed for all participants using microarray analysis. Samples were divided into discovery, training, and validation sets. In the discovery set, which consisted of control samples only, serum miRNAs that correlated with the predicted risk of stroke, as calculated using 7 clinical risk factors, were identified by Pearson correlation analysis. In the training set, a discriminant model between cases and controls was constructed using the identified miRNAs, Fisher linear discrimination model with leave-one-out cross-validation and DeLong test. In the validation set, the predictive accuracy of the constructed model was calculated. Results-First, in 1523 control samples (discovery set), we identified 10 miRNAs that correlated with a predicted risk of stroke. Second, in 45 controls and 87 cases (training set), we identified 7 of 10 miRNAs that significantly associated with cerebrovascular disorder (miR-1228-5p, miR-1268a, miR-1268b, miR-4433b-3p, miR-6090, miR-6752-5p, and miR-6803-5p). Third, a 3-miRNA combination model (miR-1268b, miR-4433b-3p, and miR-6803-5p) was constructed in the training set with a sensitivity of 84%, a specificity of 98%, and an area under the receiver operating characteristic curve of 0.95 (95% CI, 0.92-0.98). Finally, in 45 controls and 86 cases (validation set), the 3-miRNA model achieved a sensitivity of 80%, a specificity of 82%, and an area under the receiver operating characteristic of 0.89 (95% CI, 0.83-0.95) for cerebrovascular disorder. Conclusions-We identified 7 serum miRNAs that could predict the risk of cerebrovascular disorder before the onset of stroke.

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Serum microRNA-based prediction of responsiveness to eribulin in metastatic breast cancer

N Satomi-Tsushita, A Shimomura, J Matsuzaki, Y Yamamoto, J Kawauchi, ...

PloS one 14 (9), e0222024 (PLoS ONE) 14 ( 9 ) e0222024 2019

Research paper (scientific journal), Accepted

© 2019 Satomi-Tsushita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The identification of biomarkers for predicting the responsiveness to eribulin in patients with metastatic breast cancer pretreated with an anthracycline and a taxane remains an unmet need. Here, we established a serum microRNA (miRNA)-based prediction model for the emergence of new distant metastases after eribulin treatment. Serum samples were collected from metastatic breast cancer patients prior to eribulin treatment and comprehensively evaluated by miRNA microarray. The prediction model for estimating eribulin efficacy was established using the logistic LASSO regression model. Serum samples were collected from 147 patients, of which 52 developed at least one new distant metastasis after eribulin monotherapy and 95 did not develop new distant metastases. A combination of eight serum miRNAs (miR-4483, miR-8089, miR-4755-3p, miR-296-3p, miR-575, miR-4710, miR-5698 and miR-3160-5p) predicted the appearance of new distant metastases with an area under the curve of 0.79, sensitivity of 0.69 and specificity of 0.82. The serum levels of miR-8089 and miR-5698 were significantly associated with overall survival after the initiation of eribulin treatment. The present study provides evidence that serum miRNA profiling may serve as a biomarker for the responsiveness to eribulin and for predicting the development of new distant metastases in metastatic breast cancer.

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Serum microRNA profile enables preoperative diagnosis of uterine leiomyosarcoma

A Yokoi, J Matsuzaki, Y Yamamoto, K Tate, Y Yoneoka, H Shimizu, ...

Cancer science 110 (12), 3718 (Cancer Science) 110 ( 12 ) 3718 - 3726 2019

Research paper (scientific journal), Lead author, Accepted

© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. Uterine leiomyosarcoma (ULMS) is the major subtype of uterine sarcoma (US) and contributes to uterine cancer deaths. Although preoperative diagnosis of US remains challenging, frequent application of laparoscopic surgery for benign uterine leiomyomas (ULM) requires precise exclusion of US. MicroRNAs are stably present in the bloodstream, and the application of circulating miRNAs as disease biomarkers has been recognized. In the present study, we aimed to identify diagnostic biomarkers for distinguishing US from ULM by focusing on circulating miRNAs. All serum samples were collected preoperatively between 2009 and 2017, and all cases were histopathologically diagnosed. Whole miRNA profiles were obtained using a miRNA microarray. By analyzing expression levels of the miRNAs, candidate miRNAs were selected based on diagnostic performance in discriminating US from ULM, and a diagnostic model was then constructed. A total of 90 serum samples were analyzed, and clustering analyses revealed that the profiles of ULMS were distinct from those of controls. Based on leave-one-out cross-validation, seven miRNAs were selected as biomarker candidates. Based on model construction, the optimal model consisted of two miRNAs (miR-1246 and miR-191-5p), with an area under the receiver operating characteristic curve (AUC) for identifying ULMS of 0.97 (95% confidence interval [CI], 0.91-1.00). In contrast, serum lactate dehydrogenase had an AUC of only 0.64 (95% CI, 0.34-0.94). Seven serum miRNAs with high diagnostic performance for preoperative US screening were detected, and a promising diagnostic model for ULMS was generated.

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Peripheral neuropathy from paclitaxel: risk prediction by serum microRNAs

S Noda-Narita, A Shimomura, Y Tanabe, J Kawauchi, J Matsuzaki, ...

BMJ supportive & palliative care (BMJ Supportive and Palliative Care) 2019

Research paper (scientific journal), Accepted

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objectives: MicroRNAs (miRNAs) have recently been reported as useful diagnostic markers in cancer; however, relationships of miRNAs with adverse events during chemotherapy have yet to be fully described. In this study, we examined the relationship between serum miRNA and the risk of peripheral neuropathy (PN), a common and persistent adverse event induced by paclitaxel, in patients with breast cancer. Methods: A total of 84 serum samples from patients with breast cancer, who received paclitaxel as neoadjuvant or adjuvant chemotherapy, were obtained between January 2011 and September 2013 at National Cancer Center Hospital. Samples were divided, 2:1, into a training cohort and a test cohort, respectively; both cohorts included specimens from patients with severe PN (≥grade 2, PN group) and non-severe PN controls (non-PN group). The training cohort was used to identify miRNAs, and combinations thereof, that could predict PN, which then were validated in the test cohort. Results: Eighty-four patients received paclitaxel: 38 and 46 patients in the PN and non-PN groups, respectively. We identified 15 discriminatory miRNAs with |fold change|>0.5, and 14 combinations of three miRNAs showed the ability to discriminate, with sensitivity, specificity and accuracy of >50%. The most discriminatory miRNA, with the highest |fold change|, was miR-451a, which regulates the expression of the drug-transporter protein P-glycoprotein, potentially promoting paclitaxel resistance. Conclusion: MiR-451a could be a predictive marker for PN caused by paclitaxel-containing chemotherapy; however, further investigation of the underlying mechanism is required to determine the role of miR-451a.

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Large-scale circulating microRNA profiling for the liquid biopsy of prostate cancer

F Urabe, J Matsuzaki, Y Yamamoto, T Kimura, T Hara, M Ichikawa, ...

Clinical Cancer Research 25 (10), 3016-3025 (Clinical Cancer Research) 25 ( 10 ) 3016 - 3025 2019

Research paper (scientific journal), Lead author, Accepted

© 2019 American Association for Cancer Research. Purpose: The high false-positive rate of prostate-specific antigen (PSA) may lead to unnecessary prostate biopsies. Therefore, the United States Preventive Services Task Force recommends that decisions regarding PSA-based screening of prostate cancer should be made with caution in men ages 55–69 years, and that men 70 years should not undergo PSA screening. Here, we investigated the potential of serum miRNAs as an accurate diagnostic method in patients with suspected prostate cancer. Experimental Design: Serum samples of 809 patients with prostate cancer, 241 negative prostate biopsies, and 500 patients with other cancer types were obtained from the National Cancer Center, Japan. Forty-one healthy control samples were obtained from two other hospitals in Japan. Comprehensive microarray analysis was performed for all samples. Samples were divided into three sets. Candidate miRNAs for prostate cancer detection were identified in the discovery set (n ¼ 123). A diagnostic model was constructed using combinations of candidate miRNAs in the training set (n ¼ 484). The performance of the diagnostic model was evaluated in the validation set (n ¼ 484). Results: In the discovery set, 18 candidate miRNAs were identified. A robust diagnostic model was constructed using the combination of two miRNAs (miR-17-3p and miR-1185-2-3p) in the training set. High diagnostic performance with a sensitivity of 90% and a specificity of 90% was achieved in the validation set regardless of the Gleason score and clinical tumor–node–metastasis stage. Conclusions: The model developed in this study may help improve the diagnosis of prostate cancer and reduce the number of unnecessary prostate biopsies.

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Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes

T Katsuda, J Matsuzaki, T Yamaguchi, Y Yamada, M Prieto-Vila, ...

Elife 8, e47313 (eLife) 8 2019

Research paper (scientific journal), Joint Work, Accepted

© Katsuda et al. Hepatocytes are regarded as the only effective cell source for cell transplantation to treat liver diseases; however, their availability is limited due to a donor shortage. Thus, a novel cell source must be developed. We recently reported that mature rodent hepatocytes can be reprogrammed into progenitor-like cells with a repopulative capacity using small molecule inhibitors. Here, we demonstrate that hepatic progenitor cells can be obtained from human infant hepatocytes using the same strategy. These cells, named human chemically induced liver progenitors (hCLiPs), had a significant repopulative capacity in injured mouse livers following transplantation. hCLiPs redifferentiated into mature hepatocytes in vitro upon treatment with hepatic maturation-inducing factors. These redifferentiated cells exhibited cytochrome P450 (CYP) enzymatic activities in response to CYP-inducing molecules and these activities were comparable with those in primary human hepatocytes. These findings will facilitate liver cell transplantation therapy and drug discovery studies.

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Generation of functional human hepatocytes in vitro: current status and future prospects

T Yamaguchi, J Matsuzaki, T Katsuda, Y Saito, H Saito, T Ochiya

Inflammation and regeneration 39 (1), 1-9 (Inflammation and Regeneration) 39 ( 1 ) 13 2019

Research paper (scientific journal), Accepted

© 2019 The Author(s). Liver and hepatocyte transplantation are the only effective therapies for late-stage liver diseases, in which the liver loses its regenerative capacity. However, there is a shortage of donors. As a potential alternative approach, functional hepatocytes were recently generated from various cell sources. Analysis of drug metabolism in the human liver is important for drug development. Consequently, cells that metabolize drugs similar to human primary hepatocytes are required. This review discusses the current challenges and future perspectives concerning hepatocytes and hepatic progenitor cells that have been reprogrammed from various cell types, focusing on their functions in transplantation models and their ability to metabolize drugs.

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Cancer stem-cell marker CD44v9-positive cells arise from Helicobacter pylori–infected CAPZA1-overexpressing cells

H Tsugawa, C Kato, H Mori, J Matsuzaki, K Kameyama, H Saya, ...

Cellular and molecular gastroenterology and hepatology 8 (3), 319-334 (Cellular and Molecular Gastroenterology and Hepatology) 8 ( 3 ) 319 - 334 2019

Research paper (scientific journal), Accepted

© 2019 The Authors Background & Aims: CD44 variant 9 (CD44v9)-positive cancer stem-like cells strongly contribute to the development and recurrence of gastric cancer. However, the origin of CD44v9-positive cells is uncertain. Methods: CD44v9, β-catenin, and epithelial splicing regulatory protein 1 signals were assessed by real-time reverse-transcription polymerase chain reaction, immunoblot analysis, or immunofluorescence microscopy. Capping actin protein of muscle Z-line α subunit 1 (CAPZA1) expression was assessed by immunoblot analysis or immunohistochemical analysis of Mongolian gerbils' gastric mucosa or human biopsy specimens. Levels of oxidative stress were assessed by measuring malondialdehyde and protein carbonylation. Histone H3 acetylation levels in the CAPZA1 proximal promoter region were measured by using chromatin immunoprecipitation analysis with an antibody against the acetylated histone H3 in human gastric carcinoma cell line (AGS) cells. Results: CD44v9 is expressed in CAPZA1-overexpressing cells in human gastric cancer tissues. CAPZA1 overexpression enhanced expression of β-catenin, which is a transcription factor for CD44, and epithelial splicing regulatory protein 1, which increases alternative splicing of CD44 to generate CD44v9. CAPZA1-overexpressing cells after cytotoxin-associated gene A accumulation showed CD44v9 expression by inducing nuclear accumulation of β-catenin, concomitant with the enhancement of expression of Sal-like protein 4 and Krüppel-like factor 5, which encode reprogramming factors. Oxidative stress increased the CAPZA1 expression in AGS cells through the enhancement of histone H3 acetylation of CAPZA1 promoter. CAPZA1 expression was increased depending on oxidative stress in H pylori–infected gastric mucosa. Conclusions: CD44v9 expression is evoked from CAPZA1-overexpressing cells after accumulation of cytotoxin-associated gene A. Our findings provide important insights into the mechanisms underlying the development of CD44v9-positive cells.

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Molecular characterization of the gastric commensal bacteria progressing gastric carcinogenesis in H. pylori-infected gastric mucosa

H TsugaWa, J Matsuzaki, H Mori, M Suematsu, H Suzuki

HELICOBACTER 24 2019

Research paper (international conference proceedings)

P1. 11-10 Serum MicroRNA Biomarkers for Screening of Resectable Lung Cancer

K Asakura, T Kadota, J Matsuzaki, Y Yoshida, K Nakagawa, H Asamura, ...

Journal of Thoracic Oncology 14 (10), S519 2019

Research paper (international conference proceedings)

MP13-09 NOVEL COMBINATION OF CIRCULATING MIRNAS FOR SPECIFIC DETECTION IN PROSTATE CANCER

F Urabe*, J Matsuzaki, Y Yamamoto, T Kimura, T Hara, S Egawa, ...

The Journal of Urology 201 (Supplement 4), e180-e180 2019

Research paper (international conference proceedings)

ACTR-17. DIAGNOSTIC UTILITY OF SERUM microRNA CLASSIFICATION IN DIFFUSE GLIOMA

M Ohno, J Matsuzaki, J Kawauchi, Y Aoki, J Miura, S Takizawa, K Kato, ...

Neuro-Oncology 21 (Suppl 6), vi16 2019

Research paper (international conference proceedings)

Integrated extracellular microRNA profiling for ovarian cancer screening

A Yokoi, J Matsuzaki, Y Yamamoto, Y Yoneoka, K Takahashi, H Shimizu, ...

Nature communications 9 (1), 1-10 (Nature Communications) 9 ( 1 ) 4319 2018.12

Research paper (scientific journal), Joint Work, Lead author, Accepted

© 2018, The Author(s). A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers that could lead to clinical applications. Here, to develop an optimal detection method, we use microarrays to obtain comprehensive miRNA profiles from 4046 serum samples, including 428 patients with ovarian tumors. A diagnostic model based on expression levels of ten miRNAs is constructed in the discovery set. Validation in an independent cohort reveals that the model is very accurate (sensitivity, 0.99; specificity, 1.00), and the diagnostic accuracy is maintained even in early-stage ovarian cancers. Furthermore, we construct two additional models, each using 9–10 serum miRNAs, aimed at discriminating ovarian cancers from the other types of solid tumors or benign ovarian tumors. Our findings provide robust evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer.

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Helicobacter pylori eradication failure may have confounded the recent large-scale health database study that showed proton pump inhibitors increase gastric cancer risk

H Suzuki, J Matsuzaki

Gut 67 (11), 2071-2072 (Gut) 67 ( 11 ) 2071 - 2072 2018.11

Research paper (scientific journal), Last author, Accepted

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Inhibiting xCT improves 5-fluorouracil resistance of gastric cancer induced by CD44 variant 9 expression

S Miyoshi, H Tsugawa, J Matsuzaki, K Hirata, H Mori, H Saya, T Kanai, ...

Anticancer research 38 (11), 6163-6170 (Anticancer Research) 38 ( 11 ) 6163 - 6170 2018.11

Research paper (scientific journal), Accepted

© 2018 International Institute of Anticancer Research.All right reserved. Background/Aim: Cancer stem cells (CSCs) play a critical role in resistance to chemotherapy. CD44 is a cell surface marker of CSCs. CD44 variant 9 (CD44v9) interacts with a cystine-glutamate antiporter (xCT) and is an unfavorable predictive factor in gastric cancer. We investigated the impact of CD44v9 expression on 5-fluorouracil (5-FU) resistance and the efficacy of the xCT inhibitor, sulfasalazine (SASP), in improving drug resistance. Materials and Methods: The human gastric cancer cell line MKN28 was transfected with pRc/CMV plasmids encoding human CD44 or CD44v9, which were used for in vitro and in vivo experiments. Results: CD44v9 expression results in 5-FU resistance by increasing intracellular glutathione and suppressing the drug-induced production of reactive oxygen species (ROS). SASP improved the drug sensitivity of CD44v9-expressing cells. Conclusion: Inhibition of xCT improved the clinical efficacy of chemotherapy against gastric cancer. CD44v9 expression can be a novel biomarker to predict resistance against 5-FU in gastric cancer.

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Gastric cancer: evidence boosts Helicobacter pylori eradication

H Suzuki, J Matsuzaki

Nature Reviews Gastroenterology & Hepatology 15 (8), 458-460 (Nature Reviews Gastroenterology and Hepatology) 15 ( 8 ) 458 - 460 2018.08

Research paper (scientific journal)

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【がんはどこまでわかるようになったか】血液中miRNA検査

松崎潤太郎, 藏田隼也, 落谷孝広

医療と検査機器・試薬 (ラボ・サービス) 41 ( 4 ) 334 - 336 2018.08

Joint Work, ISSN 1347-0434

Extracellular microRNAs and oxidative stress in liver injury: a systematic mini review

J Matsuzaki, T Ochiya

Journal of clinical biochemistry and nutrition, 17-123 (Journal of Clinical Biochemistry and Nutrition) 63 ( 1 ) 6 - 11 2018.07

Research paper (scientific journal), Lead author, Corresponding author, Accepted

© 2018 JCBN. Recent evidence has suggested that extracelluar microRNAs crucial roles in intercellular communications and are promising as minimally invasive biomarkers for various diseases including cancers. Oxidative stress also plays an essential role in homeostasis and disease development. This systematic review aims to clarify the current evidence on the interaction between oxidative stress and extracellular microRNAs. We identified 32 studies that provided information regarding the association between oxidative stress and extracellular microRNAs: 9 focused on the central nervous system, 11 focused on cardiovascular diseases, and 4 focused on liver injury. Endothelial cell-specific miR-126-3p was the most studied extracellular miRNA associated with oxidative stress. In addition, we highlight some reports that describe the mechanisms of how oxidative stress affects extracellular microRNA profiles in liver injury. In liver injury, the levels of miR-122-5p, miR-192-5p, miR-223-3p, and miR-1224-5p were reported to be elevated in the sera. The release of miR-122-5p, miR-192-5p, and miR-1224-5p from hepatocytes may be attributed to oxidative stress. miR-223-3p could be released from neutrophils and suppress oxidative stress in the liver. Elucidation of the mechanisms of the interaction between extracellular microRNAs and oxidative stress would improve our pathophysiological understanding as well as future medical practice.

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【上部消化管疾患の現況と今後の展望-病態・診断から治療を探る】バレット食道・食道腺癌

松崎潤太郎

カレントテラピー ((株)ライフメディコム) 36 ( 7 ) 639 - 644 2018.07

Joint Work, ISSN 0287-8445

Absence of high-risk stigmata predicts good prognosis even in severely anemic patients with suspected acute upper gastrointestinal bleeding

M Horibe, Y Ogura, J Matsuzaki, T Kaneko, T Yokota, O Okawa, ...

United European gastroenterology journal 6 (5), 684-690 (United European Gastroenterology Journal) 6 ( 5 ) 684 - 690 2018.06

Research paper (scientific journal), Accepted

© 2018, Author(s) 2018. Background: The need for a blood transfusion, defined as hemoglobin < 70 g/L, is the measure for assessing the risk levels in patients with upper gastrointestinal bleeding (UGIB). However, not all patients with a low hemoglobin level have a poor prognosis. Objective: We assessed the clinical predictive factors associated with poor short-term prognosis in patients with a low hemoglobin level. Methods: In this prospective cohort study, all consecutive patients with suspected acute UGIB at Tokyo Metropolitan Tama Medical Center were enrolled between 2008 and 2015. Then, we extracted those who needed a blood transfusion (hemoglobin < 70 g/L) and explored the variables associated with all-cause mortality within 28 days after presentation. Results: Among 1307 patients, 311 needed a blood transfusion and 13 (4.2%) died from all causes. The presence of high-risk stigmata requiring endoscopic treatment (peptic ulcers; Forrest scores Ia, Ib and IIa; varices with current bleeding or signs of recent bleeding; and spurting or gushing bleeding or visible vessel in other diseases), diagnosed by emergency endoscopy, was a unique factor affecting mortality (odds ratio: 8.47, 95% confidence interval: 1.45–160, P = 0.01). Patients without high-risk stigmata neither died from UGIB nor had rebleeding, irrespective of the hemoglobin levels. Conclusions: Patients without high-risk stigmata showed a good prognosis even if they needed a blood transfusion. This result could facilitate triage of patients with suspected acute UGIB who only need a blood transfusion.

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【Liquid biopsyへの期待と限界】miRNAによるliquid biopsy

松崎潤太郎

医学のあゆみ (医歯薬出版(株)) 265 ( 6 ) 499 - 503 2018.05

Joint Work, ISSN 0039-2359

血中マイクロRNA(miRNA)は、悪性腫瘍を含む体内のさまざまな異常を反映して固有のプロファイルを示すことがわかりつつあり、最適医療時代における次世代型のバイオマーカーとして注目されている。とくにがんの早期診断については、きわめて優れた診断性能が国内外から報告されている。加えて、がんの治療効果モニタリングや再発予測、予後予測によるハイリスク集団の層別化など、がん診断において広い応用範囲をもつと考えられている。またエクソソームなどの細胞外小胞に内包されて分泌されたmiRNAは、他の細胞に移行してその機能を発揮することができ、細胞間シグナル伝達ツールとしての役割を担っている。そのため血中miRNAプロファイルと疾患の関係を追究することにより、腫瘍の浸潤や転移に重要なあらたな治療標的の同定に寄与する可能性も期待できる。現在著者らの研究グループでは、バイオバンク保存血清を用いた大規模な血中miRNAデータベースを作成しており、がんの超早期診断の実用化をめざしている。(著者抄録)

Acquisition of double mutation in gyrA caused high resistance to sitafloxacin in Helicobacter pylori after unsuccessful eradication with sitafloxacin-containing regimens

Mori H., Suzuki H., Matsuzaki J., Masaoka T., Kanai T.

United European Gastroenterology Journal (United European Gastroenterology Journal) 6 ( 3 ) 391 - 397 2018.04

Research paper (scientific journal), Accepted

© 2017, © Author(s) 2017. Background and aim: Although sitafloxacin (STFX)-containing regimens are effective rescue treatments for Helicobacter pylori infection, prevalence of fluoroquinolone resistance in H. pylori has increased rapidly worldwide. The change in resistance levels and gyrA mutations, a major cause of fluoroquinolone resistance, after unsuccessful STFX-containing treatment has not been investigated. Methods: We conducted a retrospective, non-randomized study to compare the minimum inhibitory concentrations (MICs) of STFX and the location of gyrA mutations in H. pylori before and after unsuccessful eradication with STFX-containing regimens at Keio University Hospital between December 2011 and March 2015. Results: A total of 266 patients treated with STFX-containing regimens for third-line H. pylori eradication were evaluated. Double mutations in gyrA were acquired by 20.8% of strains that exhibited seven-fold increased STFX MICs, compared to pre-treatment MICs. The STFX MICs did not increase, however, when the location of the gyrA mutations did not change after treatment. Double mutations in gyrA developed in 60.0% of the strains in which eradication failed, which exhibited a baseline mutation at position D91, and in 11.1% of strains with baseline mutations at position N87. Conclusion: Acquisition of double mutations in gyrA evoked high-level resistance to STFX in H. pylori after unsuccessful eradication with STFX-containing regimens.

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Burden of impaired sleep quality on work productivity in functional dyspepsia

J Matsuzaki, H Suzuki, K Togawa, T Yamane, H Mori, T Komori, ...

United European gastroenterology journal 6 (3), 398-406 (United European Gastroenterology Journal) 6 ( 3 ) 398 - 406 2018.04

Research paper (scientific journal), Lead author, Accepted

© 2017, © Author(s) 2017. Background: Impaired sleep quality is common, and can reduce work productivity in patients with functional dyspepsia (FD). Objective: The objective of this article is to evaluate whether there is a direct association between the presence of FD and the severity of impaired sleep quality, and to calculate the economic loss due to the decreased work productivity associated with sleep quality. Methods: In Study 1, using a web-based survey completed by workers with and without FD, we evaluated impaired sleep quality, work and daily productivity, and the severity of reflux and bowel symptoms. In Study 2, the association between the presence of FD and the severity of impaired sleep quality was validated in a hospital-based cohort. Results: In both Study 1 and 2, although impaired sleep quality was more frequent in participants with FD than in those without FD, the independent association between the presence of FD and the severity of impaired sleep quality was not observed after adjustment for the severity of reflux and bowel symptoms. FD participants with impaired sleep quality reported additional economic loss of 53,500 Japanese yen/month. Conclusion: Although the association between impaired sleep quality and FD was indirect, concomitant impaired sleep quality could worsen economic loss.

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【Precision medicineをめざした胆道・膵悪性腫瘍ゲノム医療の最前線】血中マイクロRNA測定による膵癌・胆道癌の早期診断

松崎潤太郎, 落谷孝広

胆と膵 (医学図書出版(株)) 39 ( 4 ) 323 - 326 2018.04

Joint Work, ISSN 0388-9408

マイクロRNAとは17～25塩基ほどで構成される小さな一本鎖non-coding RNAである。マイクロRNAは細胞内で遺伝子発現の調節機能を有しているのみならず、細胞外へ分泌され、細胞間コミュニケーションツールとしての機能を有している。がん細胞の多くが早期段階から能動的にマイクロRNAを含む小胞(エクソソーム)を分泌するため、血中マイクロRNAプロファイルを用いたがんの早期診断が可能と考えられている。膵癌、胆道癌においてもその実例は多く報告されており、またマイクロRNAが診断マーカーのみならず予後予測マーカーとしても使用可能であることが示されている。現在われわれは、『体液中マイクロRNA測定技術基盤開発プロジェクト』と称して血清中マイクロRNAの大規模データベース構築を進めており、この技術によるがん早期診断の実現にむけて前向き検証を開始している。(著者抄録)

【プレシジョンメディシンの現状と未来】癌のリキッドバイオプシーによるプレシジョンメディシン

松崎潤太郎, 落谷孝広

The Lipid ((株)メディカルレビュー社) 29 ( 2 ) 185 - 190 2018.04

Joint Work, ISSN 0915-6607

リキッドバイオプシーとは、血液などの体液の採取によって癌組織採取(バイオプシー)に匹敵する、あるいはそれを上回る情報を入手しうるものと期待される新技術である。その解析標的には、細胞外DNA、miRNA、血中循環腫瘍細胞、エクソソームなどがあげられる。治療方針の最適化や治療後のモニタリングには細胞外DNAや血中循環腫瘍細胞の有用性がよく報告されている。一方、癌の早期診断の領域ではマイクロRNAやエクソソームの有用性が期待される。いずれの標的も検出方法や評価方法が十分には成熟しておらず、今後ますます学問的理解が深まるとともに、早い段階での実用化に向けて技術開発が進められている。(著者抄録)

【「早期発見」をめぐる課題】がん早期診断に変革をもたらす新技術の可能性と課題

松崎潤太郎, 落谷孝広

公衆衛生 ((株)医学書院) 82 ( 2 ) 120 - 125 2018.02

Joint Work, ISSN 0368-5187

【上部消化管疾患　ピロリ菌陰性時代への過渡期をむかえて】治療　実地医家が知っておくべき治療の進歩とその着目点　FD治療薬の使い方

松崎潤太郎, 鈴木秀和

Medical Practice ((株)文光堂) 35 ( 1 ) 123 - 127 2018.01

Joint Work, ISSN 0910-1551

Predicting the risk of peripheral neuropathy by the combination of four serum microRNAs

S Narita, A Shimomura, Y Tanabe, J Kawachi, J Matsuzaki, S Takizawa, ...

Annals of Oncology 29, vii57-vii58 29 vii57 - vii58 2018

Research paper (international conference proceedings)

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A tissue microRNA signature that predicts breast cancer recurrence in young women

HM Ai, J Matsuzaki, RT Takahashi, M Yoshida, Y Nezu, Y Yamamoto, ...

CANCER SCIENCE 109, 656-656 2018

Research paper (international conference proceedings)

A serum microRNA classifier for the diagnosis of bone and soft tissue sarcomas of various histological subtypes

N Asano, J Matsuzaki, J Kawauchi, S Takizawa, E Kobayashi, ...

CANCER SCIENCE 109, 503-503 2018

Research paper (international conference proceedings)

302-The Efficacy and Safety of Immediate Versus Gradually Increasing Oral Intake of Low-Fat Solid Food after Fasting in the Recovery Phase of Mild Acute Pancreatitis: A Single …

M Horibe, E Iwasaki, A Nakagawa, J Matsuzaki, K Minami, H Tamagawa, ...

Gastroenterology 154 (6), S-73 2018

Research paper (international conference proceedings)

117 THE MULTICENTER VALIDATION STUDY OF THE SIMPLE SCORE, WHICH PREDICTS NEED FOR AN URGENT ENDOSCOPIC INTERVENTION FOR SUSPECTED UPPER GASTROINTESTINAL BLEEDING

M Horibe, Y Ogura, J Matsuzaki, K Minami, S Fukuhara, E Iwasaki, ...

Gastrointestinal Endoscopy 87 (6), AB53 2018

Research paper (international conference proceedings)

Circulating microRNA classifiers to distinguish among gastric, esophageal, and colorectal cancers

J Matsuzaki, S Abe, H Takamaru, K Sudo, H Katai, Y Kanemitsu, H Daiko, ...

CANCER SCIENCE 109, 549-549 2018

Research paper (international conference proceedings), Lead author

Serum microRNAs as a potential biomarker for evaluating axillary lymph nodes metastasis in breast cancer

S Shiino, J Matsuzaki, A Shimomura, J Kawauchi, S Takizawa, ...

European Journal of Cancer 92, S127 2018

Research paper (international conference proceedings)

Prediction of response to trasutuzumab/pertuzumab/taxane therapy by microRNA in HER2 positive advanced breast cancer

A Kawachi, A Shimomura, J Matsuzaki, J Kawauchi, S Takizawa, ...

Annals of Oncology 29, iii27-iii28 2018

Research paper (international conference proceedings)

Prediction of pathological complete response by microRNA in breast cancer patients treated with neoadjuvant chemotherapy

A Shimomura, S Shiino, J Kawauchi, S Takizawa, M Ichikawa, ...

CANCER SCIENCE 109, 394-394 2018

Research paper (international conference proceedings)

PLASMA GHRELIN IS A USEFUL MARKER OF GASTRIC MUCOSAL ATROPHY AFTER HELICOBACTER PYLORI ERADICATION: A PROSPECTIVE CLINICAL STUDY

H Mori, H Suzuki, J Matsuzaki, T Masaoka, K Igarashi, T Kanai

Gastroenterology 154 (6), S925-S926 2018

Research paper (international conference proceedings)

Overexpression of CAPZA1, a novel negative regulator of autophagy, develops CD44v9-expressing cancer stem-like cells in Helicobacter pylori-infected gastric mucosa

H Tsugawa, J Matsuzaki, C Kato, H Mori, M Suematsu, H Suzuki

HELICOBACTER 23 2018

Research paper (international conference proceedings)

NapA polymorphism determine the risk of Helicobacter pylori-associated dyspepsia

J Matsuzaki, H Tsugawa, H Suzuki

HELICOBACTER 23 2018

Research paper (international conference proceedings), Lead author

Investigating serum microRNAs predicting new lesions after eribulin for patients with metastatic breast cancer

NT Kitamura, S Akihiko, J Kawauchi, S Takizawa, J Matsuzaki, ...

CANCER SCIENCE 109, 469-469 2018

Research paper (international conference proceedings)

Identification of serum microRNAs predicting the response to nivolumab in patients with advanced gastric cancer

T Miyamoto, K Kato, J Matsuzaki, S Takizawa, K Sudo, H Shoji, S Iwasa, ...

Annals of Oncology 29, x3 2018

Research paper (international conference proceedings)

Development of diagnostic method for bone and soft tissue sarcomas of various histological subtypes using serum microRNA profiles.

N Asano, J Matsuzaki, J Kawauchi, S Takizawa, E Kobayashi, ...

Journal of Clinical Oncology 36 (15_suppl), 12019-12019 2018

Research paper (international conference proceedings)

Circulating microRNA classifiers to distinguish digestive cancers

J Matsuzaki, K Kato, Y Saito, H Daiko, H Katai, Y Kanemitsu, T Okusaka, ...

CANCER SCIENCE 109, 648-648 2018

Research paper (international conference proceedings), Lead author

SPECIFIC PREDICTION OF DUODENAL TUMOR USING DEMOGRAPHIC AND ENDOSCOPIC CHARACTERISTICS: AN AGE-AND SEX-MATCHED CASE-CONTROL STUDY

H Suzuki, J Matsuzaki, M Shimoda, H Mori, S Fukuhara, Y Kanai, T Kanai

Gastroenterology 154 (6), S664-S665 2018

Research paper (international conference proceedings)

The role of extracellular RNAs in ovarian cancer

A Yokoi, Y Yoshioka, Y Yamamoto, J Matsuzaki, T Kato, K Kato, ...

CANCER SCIENCE 109, 351-351 2018

Research paper (international conference proceedings)

【成人領域における医療の進歩】マイクロRNAを用いたがん診断の進歩と現状

松崎潤太郎, 落谷孝広

東京小児科医会報 (東京小児科医会) 36 ( 2 ) 16 - 19 2017.11

Joint Work, ISSN 0287-3613

マイクロRNAとは18～25塩基ほどで構成される小さな一本鎖non-coding RNAである。がん組織中のマイクロRNAは多彩な機能を有し、各がん組織内のマイクロRNAプロファイルは、がんの始原細胞の形質を保有しており、各臓器によって異なるプロファイルを示していることが知られている。また近年、マイクロRNAがエクソソームに内包されて細胞外へ分泌された後、他の細胞へと送達され、受け取った細胞内でも機能しうる可能性が指摘され、エクソソームを介した核酸の授受が新たな細胞間コミュニケーションツールであることが明らかとなった。そのため血中マイクロRNAのプロファイルは生体内の状況を反映する多様な情報を有しており、特にがん診断はその実現可能性が高いと考えられる。現在我々は、『体液中マイクロRNA測定技術基盤開発プロジェクト』と称して血清中マイクロRNAの大規模データベース構築を進めており、この技術によるがん診断の実現に向けて前向き検証を開始している。(著者抄録)

Gender difference of gastric emptying in healthy volunteers and patients with functional dyspepsia

H Mori, H Suzuki, J Matsuzaki, K Taniguchi, T Shimizu, T Yamane, ...

Digestion 95 (1), 72-78 95 ( 1 ) 72 - 78 2017

Research paper (scientific journal), Accepted

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A tissue microRNA signature that predicts the prognosis of breast cancer in young women

A Hironaka-Mitsuhashi, J Matsuzaki, R Takahashi, M Yoshida, Y Nezu, ...

PLoS One 12 (11), e0187638 12 ( 11 ) e0187638 2017

Research paper (scientific journal), Accepted

Access to Document (DOI)

Circulating microRNAs as potential biomarkers to detect transformation of Barrett’s oesophagus to oesophageal adenocarcinoma

J Matsuzaki, H Suzuki

BMJ open gastroenterology 4 (1) 4 ( 1 ) e000160 2017

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Enteric glial dysfunction evoked by apolipoprotein E deficiency contributes to delayed gastric emptying

S Fukuhara, T Masaoka, S Nishimura, M Nakamura, J Matsuzaki, ...

Digestive diseases and sciences 62 (12), 3359-3369 62 ( 12 ) 3359 - 3369 2017

Research paper (scientific journal), Accepted

Access to Document (DOI)

Circulating microRNAs and extracellular vesicles as potential cancer biomarkers: a systematic review

J Matsuzaki, T Ochiya

International journal of clinical oncology 22 (3), 413-420 22 ( 3 ) 413 - 420 2017

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Antibiotic resistance and gyrA mutation affect the efficacy of 10-day sitafloxacin-metronidazole-esomeprazole therapy for Helicobacter pylori in penicillin allergic …

H Mori, H Suzuki, J Matsuzaki, T Masaoka, T Kanai

United European gastroenterology journal 5 (6), 796-804 2017

Research paper (scientific journal), Accepted

Serum microRNAs to predict the response to nivolumab in patients with esophageal squamous cell carcinoma.

K Sudo, K Kato, J Matsuzaki, J Kawauchi, S Takizawa, T Miyamoto, ...

Journal of Clinical Oncology 35 (15_suppl), e14511-e14511 2017

Research paper (international conference proceedings)

Serum Micrornas can Detect Colorectal Cancer; two Validation Study after In-Silico Analysis

H Takamaru, Y Saito, T Sakamoto, S Abe, M Yamada, T Nakajima, ...

Gastroenterology 152 (5), S1018 2017

Research paper (international conference proceedings)

Novel serum microRNAs that enable liquid biopsy for colorectal cancer: validation study of large cohort

H Takamaru, Y Saito, T Sakamoto, S Abe, M Yamada, T Nakajima, ...

Cancer Research 77 (13 Supplement), 5678-5678 2017

Research paper (international conference proceedings)

Impact of Functional Dyspepsia and ITS Concomitant Symptoms on the Loss of Work Productivity

H Suzuki, K Togawa, J Matsuzaki

Gastroenterology 152 (5), S940 2017

Research paper (international conference proceedings)

Eradication of Helicobacter pylori with Sitafloxacin Plus Metronidazole Based Triple Therapy for Penicillin Allergy Patients

H Mori, H Suzuki, J Matsuzaki, T Masaoka, T Kanai

Digestion 95 (1), 93-93 2017

Research paper (international conference proceedings)

Detection of esophageal cancer patients using circulating serum microRNA from the result of comprehensive analysis

K Kato, K Sudo, N Boku, S Abe, Y Saito, K Koyanagi, H Daiko, J Kawauchi, ...

Annals of Oncology 28, v35-v36 2017

Research paper (international conference proceedings)

Brain metastases-related microRNAs in the advanced breast cancer patients

J Sato, A Shimomura, J Kawauchi, J Matsuzaki, S Takizawa, H Sakamoto, ...

Annals of Oncology 28, x11 2017

Research paper (international conference proceedings)

Trends of plasma lipid, glucose, insulin, adiponectin and ghrelin in patients after H. pylori eradication

H Mori, H Suzuki, J Matsuzaki, T Masaoka, K Kameyama, T Uraoka, ...

HELICOBACTER 22 2017

Research paper (international conference proceedings)

【病態バイオマーカーの"いま"】がん　血中マイクロRNAによるリキッドバイオプシー

松崎潤太郎, 落谷孝広

生体の科学 ((公財)金原一郎記念医学医療振興財団) 67 ( 5 ) 450 - 451 2016.10

Joint Work, ISSN 0370-9531

近年の免疫療法や分子標的治療薬などの化学療法を含めた集学的治療の発展により延命効果は著しいが,進行再発がんの治癒は依然として一部の症例に限られる。一方,早期に診断ができれば少ない負担でがんを根治できる時代を迎えている。そのため,がん死亡の減少に確実に寄与し得る新たな早期診断技術の開発が注目されている。将来のがん早期診断のためのバイオマーカーの有力な候補として期待されているのが血中マイクロRNAである。研究レベルでの血中マイクロRNAの診断精度は各国で良好な成績を挙げており,一刻も早い前向きな検証と臨床現場での実用化が望まれる。(著者抄録)

Influence of regular exercise on gastric emptying in healthy men: a pilot study.

2016.09

Joint Work

【胆汁酸研究の進歩と展望-これからのbreakthroughを目指して-】胆汁酸代謝と発癌　食道への胆汁酸の影響と食道癌発癌機序

松崎潤太郎

肝胆膵 ((株)アークメディア) 72 ( 5 ) 833 - 838 2016.05

Joint Work, ISSN 0389-4991

【消化器疾患の病態生理】Helicobacter pyloriの三次除菌、四次除菌

森英毅, 松崎潤太郎, 正岡建洋, 津川仁, 三好佐和子, 福原誠一郎, 岩崎栄典, 西澤俊宏, 柏崎有紀, 金井隆典, 鈴木秀和

Progress in Medicine ((株)ライフ・サイエンス) 36 ( 3 ) 319 - 321 2016.03

Joint Work, ISSN 0287-3648

Rifabutin-based 10-day and 14-day triple therapy as a third-line and fourth-line regimen for Helicobacter pylori eradication: A pilot study

H Mori, H Suzuki, J Matsuzaki, H Tsugawa, S Fukuhara, S Miyoshi, ...

United European gastroenterology journal 4 (3), 380-387 4 ( 3 ) 380 - 387 2016

Research paper (scientific journal), Accepted

Access to Document (DOI)

A prospective study on symptom generation according to spicy food intake and TRPV 1 genotypes in functional dyspepsia patients

SY Lee, T Masaoka, HS Han, J Matsuzaki, MJ Hong, S Fukuhara, ...

Neurogastroenterology & Motility 28 (9), 1401-1408 28 ( 9 ) 1401 - 1408 2016

Research paper (scientific journal), Accepted

Access to Document (DOI)

A simple scoring system to assess the need for an endoscopic intervention in suspected upper gastrointestinal bleeding: a prospective cohort study

M Horibe, T Kaneko, N Yokogawa, T Yokota, O Okawa, Y Nakatani, ...

Digestive and Liver Disease 48 (10), 1180-1186 48 ( 10 ) 1180 - 1186 2016

Research paper (scientific journal), Accepted

Access to Document (DOI)

Association of baseline plasma des-acyl ghrelin level with the response to rikkunshito in patients with functional dyspepsia

Togawa, K. and Matsuzaki, J. and Kobayakawa, M. and Fukushima, Y. and Suzaki, F. and Kasugai, K. and Nishizawa, T. and Naito, Y. and Hayakawa, T. and Kamiya, T. and Andoh, T. and Yoshida, H. and Tokura, Y. and Nagata, H. and Mori, M. and Kato, K. and Hosoda, H. and Takebayashi, T. and Miura, S. and Uemura, N. and Joh, T. and Hibi, T. and Suzuki, H.

Journal of Gastroenterology and Hepatology (Australia) 31 ( 2 ) 334 - 341 2016

Research paper (scientific journal), Accepted

Access to Document (DOI)

Efficacy of 10-day Sitafloxacin-Containing Third-Line Rescue Therapies for Helicobacter pylori Strains Containing the gyrA Mutation

Mori, H. and Suzuki, H. and Matsuzaki, J. and Tsugawa, H. and Fukuhara, S. and Miyoshi, S. and Hirata, K. and Seino, T. and Matsushita, M. and Masaoka, T. and Kanai, T.

Helicobacter 21 ( 4 ) 286 - 294 2016

Research paper (scientific journal), Accepted

Access to Document (DOI)

Novel combination of serum microRNA for detecting breast cancer in the early stage

A Shimomura, S Shiino, J Kawauchi, S Takizawa, H Sakamoto, ...

Cancer science 107 (3), 326-334 107 ( 3 ) 326 - 334 2016

Research paper (scientific journal), Accepted

Access to Document (DOI)

Questionnaire-based survey on diagnostic and therapeutic endoscopies and H. pylori eradication for elderly patients in East Asian countries

J Matsuzaki, R Hayashi, T Arakawa, F Ueno, Y Kinoshita, T Joh, Y Naito, ...

Digestion 93 (1), 93-102 93 ( 1 ) 93 - 102 2016

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Efficacy of 10‐day Sitafloxacin‐Containing Third‐Line Rescue Therapies for Helicobacter pylori Strains Containing the gyrA Mutation

H Mori, H Suzuki, J Matsuzaki, H Tsugawa, S Fukuhara, S Miyoshi, ...

Helicobacter 21 (4), 286-294 2016

Research paper (international conference proceedings)

Sa1711 The Presence of Sleep Disorders Was Independently Associated With Delayed Gastric Emptying, But Not With the Presence of Functional Dyspepsia

T Yamane, T Masaoka, J Matsuzaki, H Mori, T Komori, T Shimizu, ...

Gastroenterology 150 (4), S354 2016

Research paper (international conference proceedings)

Relationship between Bone Mineral Density and Metabolic Biomarkers in Postmenopausal Women who Underwent a Comprehensive Health Check-up

M Takayama, H Hirose, R Shimizu, K Makino, J Matsuzaki, N Takata, ...

Ningen Dock International 3 (1), 7-12 2016

Research paper (scientific journal), Accepted

H. pylori infection enhanced cell invasion and proliferation via CagA accumulation in CD44v9-expressing cancer stem-like cells

H Mori, H Tsugawa, J Matsuzaki, Y Kashiwazaki, T Masaoka, T Uraoka, ...

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 31, 46-47 2016

Research paper (international conference proceedings)

【機能性消化管障害-気のせいでない科学の裏付けと最新治療-】機能性胃腸症(FD)　上部不定愁訴の鑑別診断と進め方

松崎潤太郎, 鈴木秀和

診断と治療 ((株)診断と治療社) 103 ( 8 ) 1000 - 1004 2015.08

Joint Work, ISSN 0370-999X

＜Headline＞ 1 機能性ディスペプシア(FD)を診断するためには、症状の原因となりうる器質的疾患を除外することが必要である。2 鑑別すべき器質的疾患として、特に胃癌、食道癌、肝臓癌、膵癌などの悪性腫瘍は確実に除外する必要があり、上部消化管内視鏡検査や腹部超音波検査が有用である。3 そのほかにも鑑別すべき疾患は多数あり(表1)、丁寧な問診や診察を含めたきめ細かい外来診療が求められる。(著者抄録)

【バレット食道研究の最前線】バレット食道の成因

松崎潤太郎, 鈴木秀和

The GI Forefront ((株)メディカルレビュー社) 11 ( 1 ) 27 - 29 2015.07

Joint Work, ISSN 1349-9629

バレット食道の臨床的な危険因子として、胃食道逆流症の症状があることに加えて、男性、加齢、喫煙、および中心性肥満が挙げられる。またHelicobacter pylori感染者はバレット食道が進展しづらい。また胃内容物の逆流成分のなかでも特に胆汁の逆流は、発がんとの関わりが深い。これらの情報は食道腺がん発症リスクの高い患者の効率的な拾い上げ、発がん予防となり得る生活習慣介入のあり方、および新規治療の開発に有用である。(著者抄録)

壊死性膵炎後のWalled-off necrosis(WON)に対するネクロセクトミー施行中に穿孔をきたした一例

町田雄二郎, 岩崎栄典, 片山正, 清原裕貴, 上田真裕, 南一洋, 川崎慎太郎, 清野隆史, 松下美紗子, 堀部昌靖, 松崎潤太郎, 山岸由幸, 樋口肇, 鈴木秀和, 緒方晴彦, 金井隆典

Progress of Digestive Endoscopy ((一社)日本消化器内視鏡学会-関東支部) 87 ( Suppl. ) s110 - s110 2015.06

Joint Work, ISSN 1348-9844

中高年者の薬剤耐性ピロリ菌(H.pylori)の細菌学的、分子論的調査と三次・四次除菌レジメンの開発

鈴木秀和, 森英毅, 三好佐和子, 福原誠一郎, 松崎潤太郎, 西澤俊宏, 正岡建洋

大和証券ヘルス財団研究業績集 ((公財)大和証券ヘルス財団) ( 38 ) 64 - 68 2015.03

Joint Work

ピロリ菌除菌治療を受ける40歳以上の患者に対し上部消化管内視鏡検査を行い、ピロリ菌を分離培養した。分離菌株の抗菌薬に対する最小発育阻止濃度を寒天平板希釈法で測定し、各菌株の耐性率を検討した。また、薬剤耐性遺伝子を同定し、一次・二次除菌不成功患者のピロリ菌に対する薬剤耐性と除菌率を調べた。中高年の二次除菌不成功患者におけるピロリ菌株はクラリスロマイシンに対する耐性菌の割合が90.9%、メトロニダゾールに対する耐性菌の割合が68.9%と高率であった。シタフロキサシン(STFX)に対する耐性菌株の割合は58.3%と比較的高率であったが、STFX含有レジメンの全体の除菌率は80.0%であり、DNA gyrase subunit A遺伝子変異のない株には93.9%と非常に高い除菌率を示した。STFX感受性株での三次除菌の第一選択薬はSTFXを含む除菌レジメンを使用すべきである。リファブチンを含む三次除菌レジメンの除菌率も高かった。

【機能性消化管疾患-病態の解明と新たな治療】機能性消化管疾患と発症機序　機能性ディスペプシアとヘリコバクターピロリ感染症

鈴木秀和, 松崎潤太郎

臨床消化器内科 ((株)日本メディカルセンター) 30 ( 2 ) 211 - 215 2015.01

Joint Work, ISSN 0911-601X

Helicobacter pylor(H.pylori)除菌治療によりディスペプシア症状が消失し,その後12ヵ月経過しても症状再発がみられない場合は,H.pylori関連ディスペプシア(H.pylori-associated dyspepsia;HpD)という用語で機能性ディスペプシアは明確に区別することが,2014年1月末の京都の会議で,最終的に国際的なコンセンサスとなった.H.pylori感染により生じる胃粘膜中の酸化ストレスはディスペプシア症状と相関があり,グレリン分泌や胃平滑筋層での筋特異的マイクロRNAの発現変化などを介して胃運動障害を引き起こす.ただしH.pylori陽性ディスペプシア患者のうち除菌治療によって症状改善を達成しうるのは13人に1人と限定的効果である点に留意する必要がある.(著者抄録)

Nordihydroguaiaretic acid disrupts the antioxidant ability of Helicobacter pylori through the repression of SodB activity in vitro

H Tsugawa, H Mori, J Matsuzaki, T Masaoka, T Hirayama, H Nagasawa, ...

BioMed research international 2015 2015 734548 2015

Research paper (scientific journal), Accepted

Access to Document (DOI)

Association of visceral fat area, smoking, and alcohol consumption with reflux esophagitis and Barrett's esophagus in Japan

J Matsuzaki, H Suzuki, M Kobayakawa, JM Inadomi, M Takayama, ...

PLoS One 10 (7), e0133865 10 ( 7 ) e0133865 2015

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Role of MicroRNAs-221/222 in digestive systems

J Matsuzaki, H Suzuki

Journal of clinical medicine 4 (8), 1566-1577 4 ( 8 ) 1566 - 77 2015

Research paper (scientific journal), Joint Work, Lead author, Accepted, ISSN 2077-0383

Access to Document (DOI)

Aging, Smoking, Dyslipidemia, and Obesity Are Independently Associated With the Prevalence of Colorectal Neoplasia in Japan: Analyses of Comprehensive Health Checkup Data: 1392

N Inoue, M Takayama, K Makino, J Matsuzaki, E Shiomi, R Shimizu, ...

American Journal of Gastroenterology 110, S601 2015

Research paper (international conference proceedings)

Smoking, a Previous History of Malignancy, and the Presence of Barrett's Esophagus As Risk Factors for Adenoma and Carcinoma of the Duodenum

J Matsuzaki, T Masaoka, S Fukuhara, S Okada, H Mori, T Kanai, Y Sugino, ...

Gastroenterology 148 (4), S219-S219 2015

Research paper (international conference proceedings), Lead author

Sa1887 Adiponectin Ameliorates Carcinogenic Pathway Depending on miR-221/222 in Esophageal Adenocarcinoma Cells

J Matsuzaki, H Tsugawa, T Masaoka, H Mori, M Watanabe, T Kanai, ...

Gastroenterology 148 (4), S-347 2015

Research paper (international conference proceedings), Lead author

Prokinetics, Mosapride Citrate, Is Useful Adjunction in a Morning-Only Bowel Preparation Using Polyethylene Glycol and Electrolyte Solution (PEG-ELS) Plus Ascorbic Acid for …

N Inoue, J Matsuzaki, T Yoshida, K Kashiwagi, Y Sugino, Y Iwao

Official journal of the American College of Gastroenterology| ACG 110, S640-S641 2015

Research paper (international conference proceedings)

Overexpression of CD44v9 in Gastric Cancer Cells Confers Resistance to Trastuzumab by Inducing Antioxidant Enzymes That Inhibit Tumor Cell Death Induced by Oxidative Stress

H Mori, H Suzuki, J Matsuzaki, H Tsugawa, S Okada, T Masaoka, T Kanai

Gastroenterology 148 (4), S359-S360 2015

Research paper (international conference proceedings)

Mo1405 The Aberrant Shape of Main Pancreatic Duct Increases the Risk of the Post ERCP Pancreatitis

S Kawasaki, J Matsuzaki, H Ogata, E Iwasaki, T Kanai

Gastrointestinal Endoscopy 81 (5), AB408-AB409 2015

Research paper (international conference proceedings)

Impairment of Apolipoprotein E Evokes Delayed Gastric Emptying Through Nitrergic Dysfunction

S Fukuhara, H Suzuki, T Masaoka, H Tsugawa, S Okada, H Mori, K Hirata, ...

Digestion 91 (1), 87-87 2015

Research paper (international conference proceedings)

Eradication of Helicobacter pylori with 10-day and 14-day Rifabutin-based Triple Therapy as a Third-or Fourth-line Rescue Therapy: An Open-label Randomized Pilot Trial: 2469

H Mori, J Matsuzaki, H Tsugawa, Y Kashiwazaki, T Masaoka, T Kanai, ...

American Journal of Gastroenterology 110, S1023 2015

Research paper (international conference proceedings)

Adiponectin ameliorates carcinogenic pathway depending on miR-221/222 in esophageal adenocarcinoma cells

J Matsuzaki, H Tsugawa, T Masaoka, H Mori, M Watanabe, T Kanai, ...

Gastroenterology 148 (4), S347-S347 2015

Research paper (international conference proceedings), Lead author

急性膵炎後感染性膵壊死に対して超音波内視鏡下経胃的ドレナージ施行後、遅発性に結腸瘻を形成した1例

武田果林, 三宅麗, 川崎慎太郎, 南一洋, 松下美紗子, 清野隆史, 堀部昌靖, 松崎潤太郎, 岩崎栄典, 山岸由幸, 樋口肇, 鈴木秀和, 日比泰造, 北郷実, 北川雄光, 緒方晴彦, 金井隆典

Progress of Digestive Endoscopy ((一社)日本消化器内視鏡学会-関東支部) 86 ( Suppl. ) s120 - s120 2014.12

Joint Work, ISSN 1348-9844

【機能性ディスペプシアと過敏性腸症候群の実地診療　器質的疾患を否定しても残る症状にどう対処するか】治療　機能性消化管疾患の治療とその着目点　ヘリコバクター・ピロリの除菌療法と機能性ディスペプシア

松崎潤太郎, 鈴木秀和

Medical Practice ((株)文光堂) 31 ( 8 ) 1307 - 1310 2014.08

Joint Work, ISSN 0910-1551

【バレット食道腺癌の診断と治療】食道腺癌発癌における転写因子CDX2の制御システム

松崎潤太郎

消化器内科 ((有)科学評論社) 59 ( 1 ) 7 - 10 2014.07

Joint Work, ISSN 1884-2895

高Ca血症を伴ったPTHrP産生食道小細胞癌の1剖検例

渥美義大, 岩崎栄典, 星野舞, 瀧田麻衣子, 石山由佳, 松崎潤太郎, 岸野竜平, 泉谷幹子, 中澤敦, 塚田信廣

日本内科学会雑誌 ((一社)日本内科学会) 103 ( 3 ) 741 - 743 2014.03

Research paper (other academic), Joint Work, ISSN 0021-5384

79歳男。1ヵ月前より食欲低下、嚥下困難感を自覚し近医を受診、造影CTで多発転移性肝腫瘍、食道・胃透視検査で上部食道に5cmの陰影欠損を認め、著者らの施設で精査を予定していたが、意識障害が出現したため緊急入院となった。意識レベルはJCSII-10、腹部は平坦軟で圧痛なく、肝を正中に5cm触知された。また、Intact-PTHは正常であったが、PTHrPとCaの高値がみられ、血液検査で意識障害に肝性脳症と高Ca血症の関与が疑われた。そこで、肝不全用アミノ酸製剤、補液と利尿剤、エルシトニンが使用されたが入院6日目にCaは悪化して昏睡状態となり、ゾレドロン酸を投与するも意識状態および血清Caは改善せず肝不全も増悪、患者は入院8日目に死亡となった。尚、病理解剖では上部食道に28×44cm大、type 2病変を認め、食道内分泌細胞癌、小細胞型ほか、肝臓、肺、リンパ節への多発転移がみられ、肝臓はほぼ転移腫瘍で置換され、免疫組織化学染色で原発巣および転移巣でPTHrP産生が証明された。

Randomized clinical trial: Rikkunshito in the treatment of functional dyspepsia-a multicenter, double-blind, randomized, placebo-controlled study

Suzuki, H. and Matsuzaki, J. and Fukushima, Y. and Suzaki, F. and Kasugai, K. and Nishizawa, T. and Naito, Y. and Hayakawa, T. and Kamiya, T. and Andoh, T. and Yoshida, H. and Tokura, Y. and Nagata, H. and Kobayakawa, M. and Mori, M. and Kato, K. and Hosoda, H. and Takebayashi, T. and Miura, S. and Uemura, N. and Joh, T. and Hibi, T. and Tack, J. and Kasugai, K. and Nishizawa, T. and Naito, Y. and Joh, T. and Miura, S. and Uemura, N. and Fukushima, Y. and Suzaki, F. and Hayakawa, T. and Ando, T. and Yoshida, H. and Tokura, Y. and Nagata, H. and Kobayakawa, M. and Mori, M. and Kato, K. and Tsuzuki, Y. and Iwata, A. and Kobayashi, K. and Imaeda, H. and Yamaguchi, Y. and Iwasaki, E. and Komatsu, H. and Serizawa, H. and Oyamada, Y. and Yagou, Y. and Yoshida, T. and Nishida, J. and Yamamoto, S. and Tokita, K.

Neurogastroenterology and Motility 26 ( 7 ) 950 - 961 2014

Research paper (scientific journal), Accepted

Access to Document (DOI)

Greater loss of productivity among Japanese workers with gastro-esophageal reflux disease (GERD) symptoms that persist vs resolve on medical therapy

Suzuki, H. and Matsuzaki, J. and Masaoka, T. and Inadomi, J.M.

Neurogastroenterology and Motility 26 ( 6 ) 764 - 771 2014

Research paper (scientific journal), Accepted

Access to Document (DOI)

Mucosal expression of aquaporin-4 in the stomach of histamine type 2 receptor knockout mice and Helicobacter pylori-infected mice

Fukuhara, S. and Matsuzaki, J. and Tsugawa, H. and Masaoka, T. and Miyoshi, S. and Mori, H. and Fukushima, Y. and Yasui, M. and Kanai, T. and Suzuki, H.

Journal of Gastroenterology and Hepatology (Australia) 29 ( S4 ) 53 - 59 2014

Research paper (scientific journal), Accepted

Access to Document (DOI)

Propofol versus traditional sedative agents for endoscopic submucosal dissection

Nishizawa, T. and Suzuki, H. and Matsuzaki, J. and Kanai, T. and Yahagi, N.

Digestive Endoscopy 26 ( 6 ) 701 - 706 2014

Research paper (scientific journal), Accepted

Access to Document (DOI)

Neural Stem Cell Transplantation Restored the Delayed Gastric Emptying in Apolipoprotein E-Knockout Mice

S Fukuhara, H Suzuki, T Masaoka, J Matsuzaki, H Tsugawa, S Okada, ...

Gastroenterology 146 (5), S19-S19 2014

Research paper (international conference proceedings)

Accumulation of Helicobacter pylori-Derived CagA Oncoprotein in CD44-Variant Expressing Cancer Stem-Like Cells by Escaping Autophagy

H Tsugawa, H Suzuki, H Saya, M Hatakeyama, T Hirayama, K Hirata, ...

DIGESTION 89 (1), 83-83 2014

Research paper (international conference proceedings)

66 Neural Stem Cell Transplantation Restored the Delayed Gastric Emptying in Apolipoprotein E-Knockout Mice

S Fukuhara, H Suzuki, T Masaoka, J Matsuzaki, H Tsugawa, S Okada, ...

Gastroenterology 146 (5), S-19 2014

Research paper (international conference proceedings)

MicroRNAs in Barrett's esophagus: future prospects

J Matsuzaki, H Suzuki

Frontiers in genetics 5, 69 5 ( APR ) 69 2014

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Differences of lifestyle factors between erosive esophagitis and Barrett's esophagus: PP176

J Matsuzaki, H Suzuki, Y Sugino

Neurogastroenterology & Motility 26 2014

Research paper (international conference proceedings), Lead author, Accepted

Sa1900 CD44v9 Results in Resistance to Trastuzumab via Induction of ROS Resistance

H Mori, H Suzuki, J Matsuzaki, H Tsugawa, S Okada, S Fukuhara, ...

Gastroenterology 5 (146), S-324 2014

Research paper (international conference proceedings)

Sa1331 Efficacy and Safety of Rikkunshito, a Japanese Herbal Medicine, on the Treatment of Functional Dyspepsia: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study

H Suzuki, J Matsuzaki, Y Fukushima, F Suzaki, K Kasugai, T Nishizawa, ...

Gastroenterology 146 (5), S-265 2014

Research paper (international conference proceedings)

P266 Chronic inflammatory bowel disorders diagnosed by screening colonoscopy for health check-up

N Inoue, Y Iwao, J Matsuzaki, N Takada, E Shiomi, R Shimizu, T Yoshida, ...

Journal of Crohn's and Colitis 8 (Supplement_1), S174-S174 2014

Research paper (international conference proceedings)

NNUCLEAR-TRANSLOCATED LRP1-ICD IS RELATED TO THE FORMATION OF AUTOPHAGOLYSOSOME ASSOCIATED WITH CAGA DEGRADATION IN GASTRIC EPITHELIAL CELLS INFECTED WITHH. PYLORIVIA INDUCTION …

H Tsugawa, J Matsuzaki, H Mori, T Masaoka, A Sato, M Imoto, T Hirayama, ...

Helicobacter 19 2014

Research paper (international conference proceedings)

Neural Stem Cell Transplantation Improved Delayed Gastric Emptying in Apolipoprotein E-Knockout Mice

S Fukuhara, H Suzuki, T Masaoka, J Matsuzaki, H Tsugawa, S Miyoshi, ...

Digestive Diseases And Sciences 59 (9), 2019-2019 2014

Research paper (international conference proceedings)

Mucosal expression of aquaporin‐4 in the stomach of histamine type 2 receptor knockout mice and Helicobacter pylori‐infected mice

S Fukuhara, J Matsuzaki, H Tsugawa, T Masaoka, S Miyoshi, H Mori, ...

Journal of gastroenterology and hepatology 29, 53-59 2014

Research paper (scientific journal), Accepted

ENHANCED MIGRATION AND PROLIFERATION IN CD44V9-EXPRESSING CANCER STEM-LIKE CELLS WITH H. PYLORIINFECTION: Abstract no.: P18. 23

H Mori, S Miyoshi, H Tsugawa, J Matsuzaki, S Fukuhara, T Masaoka, ...

Helicobacter 19 2014

Research paper (international conference proceedings)

Endoplasmic reticulum chaperone, 78 kDa glucose-regulated protein regulates neuronal nitric oxide expression

T Masaoka, H Tsugawa, J Matsuzaki, H Mori, S Fukuhara, S Miyoshi, ...

Neurogastroenterology And Motility 26, 26-26 2014

Research paper (international conference proceedings)

Differences of lifestyle factors between erosive esophagitis and Barrett's esophagus

J Matsuzaki, H Suzuki, Y Sugino

NEUROGASTROENTEROLOGY AND MOTILITY 26, 67-67 2014

Research paper (international conference proceedings), Lead author, Accepted

NNUCLEAR-TRANSLOCATED LRP1-ICD IS RELATED TO THE FORMATION OF AUTOPHAGOLYSOSOME ASSOCIATED WITH CAGA DEGRADATION IN GASTRIC EPITHELIAL CELLS INFECTED WITH H. PYLORI VIA …

H Tsugawa, J Matsuzaki, H Mori, T Masaoka, A Sato, M Imoto, T Hirayama, ...

HELICOBACTER 19, 97-97 2014

Research paper (international conference proceedings)

ENHANCED MIGRATION AND PROLIFERATION IN CD44V9-EXPRESSING CANCER STEM-LIKE CELLS WITH H. PYLORI INFECTION

H Mori, S Miyoshi, H Tsugawa, J Matsuzaki, S Fukuhara, T Masaoka, ...

HELICOBACTER 19, 165-165 2014

Research paper (international conference proceedings)

Endoscopic transluminal drainage and necrosectomy for walled off pancreatic necrosis after severe necrotizing pancreatitis: report of 3 cases

E Iwasaki, Y Yamagishi, S Kawasaki, T Seino, M Matsuchita, H Higuchi, ...

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 29, 215-215 2014

Research paper (international conference proceedings)

上部消化管出血を契機に発見された胃脂肪腫の2例

星野舞, 中澤敦, 瀧田麻衣子, 石山由佳, 岸野竜平, 松崎潤太郎, 酒井元, 岩崎栄典, 泉谷幹子, 塚田信廣, 向井清

Progress of Digestive Endoscopy ((一社)日本消化器内視鏡学会-関東支部) 84 ( Suppl. ) s107 - s107 2013.12

Joint Work, ISSN 1348-9844

経肝的に挿入されたSEMSの逸脱に対してAPCによるトリミングを施行した2症例

瀧田麻衣子, 岩崎栄典, 星野舞, 石山由佳, 岸野竜平, 松崎潤太郎, 泉谷幹子, 中澤敦, 塚田信廣

Progress of Digestive Endoscopy ((一社)日本消化器内視鏡学会-関東支部) 84 ( Suppl. ) s114 - s114 2013.12

Joint Work, ISSN 1348-9844

【消化器疾患の病態生理】慶應義塾大学病院でのHelicobacter pylori診療の現況

森英毅, 鈴木秀和, 松崎潤太郎, 津川仁, 平田賢郎, 岡田佐和子, 福原誠一郎, 日比紀文

Progress in Medicine ((株)ライフ・サイエンス) 33 ( 3 ) 391 - 393 2013.03

Joint Work, ISSN 0287-3648

Erratum: Enhancement of amoxicillin resistance after unsuccessful helicobacter pylori eradication (Antimicrobial Agents and Chemotherapy (2011) 55: 6 (3012-3014)

T Nishizawa, H Suzuki, H Tsugawa, H Muraoka, J Matsuzaki, K Hirata, ...

Antimicrobial Agents and Chemotherapy 57 (2), 1106 57 ( 2 ) 1106 2013

Research paper (scientific journal), Accepted

Access to Document (DOI)

Validation of the gerdQ questionnaire for the management of gastro-oesophageal reflux disease in Japan

Suzuki, H. and Matsuzaki, J. and Okada, S. and Hirata, K. and Fukuhara, S. and Hibi, T.

United European Gastroenterology Journal 1 ( 3 ) 175 - 183 2013

Research paper (scientific journal), Accepted

Access to Document (DOI)

Bile acids increase levels of microRNAs 221 and 222, leading to degradation of CDX2 during esophageal carcinogenesis

J Matsuzaki, H Suzuki, H Tsugawa, M Watanabe, S Hossain, E Arai, ...

Gastroenterology 145 (6), 1300-1311 145 ( 6 ) 1300 - 1311 2013

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Biliary findings assist in predicting enlargement of intraductal papillary mucinous neoplasms of the pancreas

J Matsuzaki, H Suzuki, S Okuda, A Tanimoto, K Asakura, S Fukuhara, ...

Clinical Gastroenterology and Hepatology 11 (5), 548-554 11 ( 5 ) 548 - 554 2013

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence

K Hirata, H Suzuki, H Imaeda, J Matsuzaki, H Tsugawa, O Nagano, ...

British journal of cancer 109 (2), 379-386 109 ( 2 ) 379 - 386 2013

Research paper (scientific journal), Accepted

Access to Document (DOI)

Correction: Overexpression of miR-142-5p and miR-155 in gastric mucosa-associated lymphoid tissue (MALT) lymphoma resistant to Helicobacter pylori eradication (PLoS ONE)

Saito, Y. and Suzuki, H. and Tsugawa, H. and Imaeda, H. and Matsuzaki, J. and Hirata, K. and Hosoe, N. and Nakamura, M. and Mukai, M. and Saito, H. and Hibi, T.

PLoS ONE 8 ( 7 ) 2013

Research paper (scientific journal)

Access to Document (DOI)

Effect of lansoprazole on the epigastric symptoms of functional dyspepsia (ELF study): a multicentre, prospective, randomized, double-blind, placebo-controlled clinical trial

H Suzuki, H Kusunoki, T Kamiya, S Futagami, Y Yamaguchi, T Nishizawa, ...

United European gastroenterology journal 1 (6), 445-452 1 ( 6 ) 445 - 452 2013

Research paper (scientific journal), Accepted

Access to Document (DOI)

Improvement of reflux symptom related quality of life after Helicobacter pylori eradication therapy

K Hirata, H Suzuki, J Matsuzaki, T Masaoka, Y Saito, T Nishizawa, ...

Journal of clinical biochemistry and nutrition 52 (2), 172-178 52 ( 2 ) 172 - 178 2013

Research paper (scientific journal), Accepted

Access to Document (DOI)

The tumor suppressor microRNA-29c is downregulated and restored by celecoxib in human gastric cancer cells

Saito, Y. and Suzuki, H. and Imaeda, H. and Matsuzaki, J. and Hirata, K. and Tsugawa, H. and Hibino, S. and Kanai, Y. and Saito, H. and Hibi, T.

International Journal of Cancer 132 ( 8 ) 1751 - 1760 2013

Research paper (scientific journal), Accepted

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Expression of CD44 Variant 9 Contributes to 5-Fluorouracil Resistance in Gastric Cancer Through Anti-Oxidative Stress Mechanism

S Okada, H Suzuki, T Masaoka, H Tsugawa, J Matsuzaki, S Fukuhara, ...

DIGESTIVE DISEASES AND SCIENCES 58 (9), 2433-2433 2013

Research paper (international conference proceedings)

Mo1849 Bile Acids Enhance Oncogenic miR-221/222 in the Transformation From Barrett's Esophagus to Adenocarcinoma

J Matsuzaki, H Suzuki, H Tsugawa, Y Saito, S Hossain, E Arai, S Sekine, ...

Gastroenterology 144 (5), S-674 2013

Research paper (international conference proceedings), Lead author

Su1724 Expression of CD44 Variant 9 Contributes to 5-Fluorouracil Resistance in Gastric Cancer Through Anti-Oxidative Stress Mechanism

S Okada, H Suzuki, T Masaoka, H Tsugawa, J Matsuzaki, S Fukuhara, ...

Gastroenterology 5 (144), S-460-S-461 2013

Research paper (international conference proceedings)

Tu2095 Application of 13C-Acetic Acid Breath Test for Animals With Impaired Gastric Motility

S Fukuhara, H Suzuki, T Masaoka, S Suemasu, J Matsuzaki, H Tsugawa, ...

Gastroenterology 144 (5), S-927-S-928 2013

Research paper (international conference proceedings)

Tu1797 The Loss of Work Productivity Associated With Gastroesophageal Reflux Disease (GERD) in a Japanese Working Population

H Suzuki, J Matsuzaki, T Masaoka, S Okada, JM Inadomi, T Hibi

Gastroenterology 5 (144), S-847-S-848 2013

Research paper (international conference proceedings)

The tumor suppressor microRNA‐29c is downregulated and restored by celecoxib in human gastric cancer cells

Y Saito, H Suzuki, H Imaeda, J Matsuzaki, K Hirata, H Tsugawa, S Hibino, ...

International journal of cancer 132 (8), 1751-1760 2013

Research paper (scientific journal), Accepted

アルコール性慢性膵炎仮性嚢胞破裂後の腹腔内出血・膵液瘻に内視鏡治療併用の保存加療が有効であった一例

福原誠一郎, 中村雄二, 山岸由幸, 石橋由佳, 松崎潤太郎, 碓井真吾, 樋口肇, 鈴木秀和, 日比紀文

Progress of Digestive Endoscopy ((一社)日本消化器内視鏡学会-関東支部) 82 ( Suppl. ) s89 - s89 2012.12

Joint Work, ISSN 1348-9844

【喫煙、アルコールと消化器疾患】喫煙とアルコールについてどのように患者に説明するべきか

鈴木秀和, 松崎潤太郎, 日比紀文

G.I.Research ((株)先端医学社) 20 ( 4 ) 325 - 329 2012.08

Joint Work, ISSN 0918-9408

禁煙や節酒といった生活習慣改善を促す指導は、悪性腫瘍・心疾患・糖尿病などでの死亡率を改善させることが示されており、医師の責任のもとにおいて、コメディカルと連携し適切に遂行されることが求められている。禁酒や節酒指導の場面では、丁寧な問診や共感、および成功時の称賛などを駆使した精神心理学的サポートがとくに重要である点が、他疾患の治療とは異なる大きな特徴といえる。それに加え、適切な薬剤療法の介入も成功率を上昇させる。(著者抄録)

【消化器疾患の病態生理】GERDにおける日本語版GerdQ問診票の有用性

岡田佐和子, 鈴木秀和, 松崎潤太郎, 平田賢郎, 福原誠一郎, 斉藤義正, 日比紀文

Progress in Medicine ((株)ライフ・サイエンス) 32 ( 3 ) 560 - 562 2012.03

Joint Work, ISSN 0287-3648

【逆流性食道炎とBarrett食道】バレット食道、食道腺癌に関わるmicroRNA

松崎潤太郎, 鈴木秀和, 日比紀文

消化器内科 ((有)科学評論社) 54 ( 2 ) 197 - 201 2012.02

Joint Work, ISSN 1884-2895

Reduced ghrelin production induced anorexia after rat gastric ischemia and reperfusion

S Mogami, H Suzuki, S Fukuhara, J Matsuzaki, K Kangawa, T Hibi

American Journal of Physiology-Gastrointestinal and Liver Physiology 302 (3 … 302 ( 3 ) G359 - 64 2012

Research paper (scientific journal), Accepted

Access to Document (DOI)

Reactive oxygen species-induced autophagic degradation of Helicobacter pylori CagA is specifically suppressed in cancer stem-like cells

H Tsugawa, H Suzuki, H Saya, M Hatakeyama, T Hirayama, K Hirata, ...

Cell host & microbe 12 (6), 764-777 12 ( 6 ) 764 - 777 2012

Research paper (scientific journal), Accepted

Access to Document (DOI)

Overexpression of miR-142-5p and miR-155 in gastric mucosa-associated lymphoid tissue (MALT) lymphoma resistant to Helicobacter pylori eradication

Y Saito, H Suzuki, H Tsugawa, H Imaeda, J Matsuzaki, K Hirata, N Hosoe, ...

PloS one 7 (11), e47396 7 ( 11 ) e47396 2012

Research paper (scientific journal), Accepted

Access to Document (DOI)

High frequency of overlap between functional dyspepsia and overactive bladder

J Matsuzaki, H Suzuki, Y Fukushima, K Hirata, S Fukuhara, S Okada, ...

Neurogastroenterology & Motility 24 (9), 821-827 24 ( 9 ) 821 - 827 2012

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Development of a novel microRNA promoter microarray for ChIP-on-chip assay to identify epigenetically regulated microRNAs

Y Saito, H Suzuki, T Taya, M Nishizawa, H Tsugawa, J Matsuzaki, ...

Biochemical and biophysical research communications 426 (1), 33-37 426 ( 1 ) 33 - 37 2012

Research paper (scientific journal), Accepted

Access to Document (DOI)

Efficacy of sitafloxacin-based rescue therapy for Helicobacter pylori after failures of first-and second-line therapies

J Matsuzaki, H Suzuki, T Nishizawa, K Hirata, H Tsugawa, Y Saito, ...

Antimicrobial agents and chemotherapy 56 (3), 1643-1645 56 ( 3 ) 1643 - 1645 2012

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Efficacy of solifenacin on irritable bowel syndrome with diarrhea: open-label prospective pilot trial

Y Fukushima, H Suzuki, J Matsuzaki, A Kiyosue, T Hibi

Journal of neurogastroenterology and motility 18 (3), 317 18 ( 3 ) 317 - 323 2012

Research paper (scientific journal), Accepted

Access to Document (DOI)

FecA1, a bacterial iron transporter, determines the survival of Helicobacter pylori in the stomach

H Tsugawa, H Suzuki, J Matsuzaki, K Hirata, T Hibi

Free Radical Biology and Medicine 52 (6), 1003-1010 52 ( 6 ) 1003 - 1010 2012

Research paper (scientific journal), Accepted

Access to Document (DOI)

Classification of functional dyspepsia based on concomitant bowel symptoms

J Matsuzaki, H Suzuki, K Asakura, Y Fukushima, JM Inadomi, ...

Neurogastroenterology & Motility 24 (4), 325-e164 24 ( 4 ) 2012

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Are solifenacin and ramosetron really ideal to treat irritable bowel syndrome?: Author's reply

H Suzuki, J Matsuzaki

Journal of neurogastroenterology and motility 18 (4), 459 18 ( 4 ) 459 2012

Research paper (scientific journal)

Access to Document (DOI)

616 Specific Amino Acid Mutation of p53 Enhanced the Stability of Intracellular CagA by Inhibiting Autophagy Induction

H Tsugawa, H Suzuki, M Hatakeyama, T Hirayama, J Matsuzaki, K Hirata, ...

Gastroenterology 142 (5), S-120-S-121 2012

Research paper (international conference proceedings)

Eradication ofHelicobacter pyloriwith 10-Day Sitafloxacin-based Triple Therapy as a Third-or Fourth-Line Rescue Therapy: Preliminary Results of Open-Label Randomized Trial: 132

H Mori, H Suzuki, J Matsuzaki, S Fukuhara, S Okada, K Hirata, ...

American Journal of Gastroenterology 107, S56-S57 2012

Research paper (international conference proceedings)

Predictive Factors for the Increase in Size of Branch Duct-type Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Retrospective Cohort Study with a 6-year Follow-Up: 197

H Suzuki, J Matsuzaki, S Okuda, A Tanimoto, K Asakura, S Fukuhara, ...

American Journal of Gastroenterology 107, S85 2012

Research paper (international conference proceedings)

Oncogenic microRNA-221/222 Promotes Proteasomal Degradation of CDX2 and Hyperproliferation in the Carcinogenesis of Barrett's Esophagus

J Matsuzaki, H Suzuki, H Tsugawa, Y Saito, S Hossain, K Mukaisho, ...

DIGESTIVE DISEASES AND SCIENCES 57 (11), 2729-2729 2012

Research paper (international conference proceedings), Lead author

Mo1569 MicroRNA-21 Expression Causes Nuclear Loss of the Tumor Suppressor PDCD4 in Precancerous Gastric Adenomas

K Hirata, H Suzuki, Y Saito, H Tsugawa, J Matsuzaki, S Fukuhara, ...

Gastroenterology 142 (5), S-631 2012

Research paper (international conference proceedings)

Improvement in the quality of life related to reflux symptoms after Helicobacter pylori eradication therapy: 443

K Hirata, H Suzuki, J Matsuzaki, T Masaoka, Y Saito, T Nishizawa, ...

Neurogastroenterology & Motility 24 2012

Research paper (international conference proceedings)

High frequency of overlap between functional dyspepsia, irritable bowel syndrome and overactive bladder: 493

H Suzuki, J Matsuzaki, Y Fukushima, K Hirata, S Fukuhara, S Okada, ...

Neurogastroenterology & Motility 24 2012

Research paper (international conference proceedings)

FXR Activation Promotes CDX2 Degradation via the Ubiquitin-Proteosome System with Upregulation of microRNA-221/222 in Human Esophageal Cells

J Matsuzaki, H Suzuki, H Tsugawa, Y Saito, S Hossain, T Akaike, ...

DIGESTION 85 (2), 151-151 2012

Research paper (international conference proceedings), Lead author

Su1082 GERDQ is Superior Tool for the Evaluation of GERD Symptoms and Unmet Medical Needs to the Carlsson-Dent Questionnaire-a Large Scale Survey

H Suzuki, J Matsuzaki, S Okada, H Tsugawa, S Fukuhara, K Hirata, T Hibi

Gastroenterology 5 (142), S-420 2012

Research paper (international conference proceedings)

Tu1155 The Extension of Mucosal Lesions, Helicobacter pylori Infection Status and API2-MALT1 Positivity are Associated With the Therapeutic Response for Gastric MALT Lymphoma

S Okada, H Suzuki, J Matsuzaki, H Tsugawa, S Fukuhara, K Hirata, ...

Gastroenterology 5 (142), S-760 2012

Research paper (international conference proceedings)

The Gerd-Q is a useful tool for evaluating the patients' satisfaction and identifying the patients with “unmet medical needs”: 422

S Okada, H Suzuki, J Matsuzaki, S Fukuhara, K Hirata, T Hibi

Neurogastroenterology & Motility 24 2012

Research paper (international conference proceedings)

Su1612 Dynamics of Aquaporin-4 in Gastric Parietal Cells in the Hyperplastic Gastric Fundic Mucosa of Histamine Type 2 Receptor Knockout Mice

S Fukuhara, H Suzuki, J Matsuzaki, H Tsugawa, K Hirata, S Okada, Y Abe, ...

Gastroenterology 5 (142), S-464 2012

Research paper (international conference proceedings)

Su1097 GERDQ is an Easy and Useful Tool for Assessing the Severity of Gastroesophageal Reflux Disease and Identifying Patients With “Unmet Medical Needs”

S Okada, H Suzuki, J Matsuzaki, H Tsugawa, S Fukuhara, K Hirata, T Hibi

Gastroenterology 142 (5), S-423 2012

Research paper (international conference proceedings)

High frequency of overlap between functional dyspepsia, irritable bowel syndrome and overactive bladder

H Suzuki, J Matsuzaki, Y Fukushima, K Hirata, S Fukuhara, S Okada, ...

NEUROGASTROENTEROLOGY AND MOTILITY 24, 186-186 2012

Research paper (international conference proceedings)

The Gerd-Q is a useful tool for evaluating the patients' satisfaction and identifying the patients with" unmet medical needs"

S Okada, H Suzuki, J Matsuzaki, S Fukuhara, K Hirata, T Hibi

NEUROGASTROENTEROLOGY AND MOTILITY 24, 165-165 2012

Research paper (international conference proceedings)

Improvement in the quality of life related to reflux symptoms after Helicobacter pylori eradication therapy

K Hirata, H Suzuki, J Matsuzaki, T Masaoka, Y Saito, T Nishizawa, ...

NEUROGASTROENTEROLOGY AND MOTILITY 24, 171-171 2012

Research paper (international conference proceedings)

Enhancement of Amoxicillin Resistance after Unsuccessful Helicobacter pylori Eradication

T Nishizawa, H Suzuki, H Tsugawa, H Muraoka, J Matsuzaki, K Hirata, ...

Antimicrobial agents and chemotherapy 57 (2), 1106 55 ( 6 ) 3012 - 4 2011.06

Research paper (scientific journal), Joint Work, Accepted, ISSN 0066-4804

Access to Document (DOI)

【IBSの病態生理】IBSとFDのオーバーラップ

鈴木秀和, 松崎潤太郎, 日比紀文

G.I.Research ((株)先端医学社) 19 ( 2 ) 137 - 141 2011.04

Joint Work, ISSN 0918-9408

機能性ディスペプシア(FD)は過敏性腸症候群(IBS)とともに、機能性消化管障害(FGIDs)を代表する非常に頻度の高い疾患である。最近この2疾患が高頻度にオーバーラップすることが、Fordらのシステマティックレビューによって明示され、その意義や背景に存在する機序についての研究が盛んにおこなわれている。とくに心理的因子(ストレスなど)、中枢神経系の異常、さらに消化管粘膜の炎症がFDとIBSのオーバーラップにおいて重要である可能性が示唆されている。消化管粘膜の炎症は、何らかの感染性胃腸炎を契機に生じたFDやIBS症例でとくに強く、FGIDs発症の要因として感染症の存在は無視できない。このようにIBSとFDのオーバーラップは、FGIDsの治療戦略や新たな診断基準にも影響を及ぼす可能性のある新しい概念といえる。(著者抄録)

【消化器疾患の病態生理】Helicobacter pylori除菌後の逆流症状とQOLの変化に対する検討　患者記入式アンケートを用いて

平田賢郎, 鈴木秀和, 松崎潤太郎, 岡田佐和子, 福原誠一郎, 斎藤義正, 日比紀文

Progress in Medicine ((株)ライフ・サイエンス) 31 ( 3 ) 822 - 824 2011.03

Joint Work, ISSN 0287-3648

【機能性消化管障害を診るコツ　NERD/FD/IBSを中心に】機能性ディスペプシア(FD)の診断・治療のコツ　FDの薬物治療の実際

鈴木秀和, 松崎潤太郎, 日比紀文

消化器の臨床 ((株)ヴァンメディカル) 14 ( 1 ) 53 - 58 2011.02

Joint Work, ISSN 1344-3070

FDの治療法として、H.pylori除菌療法とPPI投与は一定のエビデンスが得られている。消化管運動機能賦活薬も有効とされているが、現在までのエビデンスの多くはシサプリドによるものである。抗うつ薬はプラセボを上回る効果があるかはっきりはしていないが、一般的に使用されている。Acotiamide(Z-338)はアセチルコリンエステラーゼ阻害作用を有する新規の胃運動機能改善薬であり、その有用性が期待されている。また、近年FDとIBSなどその他の機能性消化管障害とのオーバーラップが注目されており、上部消化管だけでなく消化管全体に対して治療を施していくことによるFD症状の改善効果の検証が望まれる。(著者抄録)

Two amino acids mutation of ferric uptake regulator determines Helicobacter pylori resistance to metronidazole

H Tsugawa, H Suzuki, K Satoh, K Hirata, J Matsuzaki, Y Saito, ...

Antioxidants & redox signaling 14 (1), 15-23 14 ( 1 ) 15 - 23 2011

Research paper (scientific journal), Accepted

Access to Document (DOI)

Helicobacter pylori resistance to rifabutin in the last 7 years

T Nishizawa, H Suzuki, J Matsuzaki, H Muraoka, H Tsugawa, K Hirata, ...

Antimicrobial agents and chemotherapy 55 (11), 5374-5375 55 ( 11 ) 5374 - 5375 2011

Research paper (scientific journal), Accepted

Access to Document (DOI)

Dysfunctional gastric emptying with down-regulation of muscle-specific microRNAs in Helicobacter pylori-infected mice

Y Saito, H Suzuki, H Tsugawa, S Suzuki, J Matsuzaki, K Hirata, T Hibi

Gastroenterology 140 (1), 189-198 140 ( 1 ) 189 - 198 2011

Research paper (scientific journal), Accepted

Access to Document (DOI)

Enhanced bacterial efflux system is the first step to the development of metronidazole resistance in Helicobacter pylori

H Tsugawa, H Suzuki, H Muraoka, F Ikeda, K Hirata, J Matsuzaki, Y Saito, ...

Biochemical and biophysical research communications 404 (2), 656-660 404 ( 2 ) 656 - 660 2011

Research paper (scientific journal), Accepted

Access to Document (DOI)

Etiological difference between ultrashort-and short-segment Barrett’s esophagus

J Matsuzaki, H Suzuki, K Asakura, Y Saito, K Hirata, T Takebayashi, T Hibi

Journal of gastroenterology 46 (3), 332-338 46 ( 3 ) 332 - 338 2011

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Ghrelin and oxidative stress in gastrointestinal tract

H Suzuki, J Matsuzaki, T Hibi

Journal of clinical biochemistry and nutrition, 1004280030-1004280030 48 ( 2 ) 122 - 125 2011

Research paper (scientific journal), Accepted

Access to Document (DOI)

What is the difference between Helicobacter pylori-associated dyspepsia and functional dyspepsia?

H Suzuki, J Matsuzaki, T Hibi

Journal of neurogastroenterology and motility 17 (2), 124 17 ( 2 ) 124 - 130 2011

Research paper (scientific journal), Accepted

Access to Document (DOI)

Metronidazole-based quadruple versus standard triple therapy: which is better as first-line therapy for Helicobacter pylori eradication?

H Suzuki, J Matsuzaki, T Hibi

Expert review of clinical pharmacology 4 (5), 579-582 4 ( 5 ) 579 - 582 2011

Research paper (scientific journal), Accepted

Access to Document (DOI)

Activation of the Tumor Suppressor MicroRNA-29c by the Selective Cyclooxygenase-2 Inhibitor, Celecoxib in Human Gastric Cancer

H Suzuki, Y Saito, H Imaeda, J Matsuzaki, K Hirata, H Tsugawa, Y Kanai, ...

Gastroenterology 5 (140), S-121-S-122 2011

Research paper (international conference proceedings)

Smoking Increases the Risk of Onset of the Epigastric Pain Syndrome in Males and Worsens the Symptoms of Postprandial Distress Syndrome in Females

S Okada, H Suzuki, J Matsuzaki, Y Fukushima, K Asakura, T Takebayashi, ...

Gastroenterology 140 (5), S-884 2011

Research paper (international conference proceedings)

Reduced Ghrelin Production Induced Anorexia After Gastric Ischemia and Reperfusion in the Rat

S Mogami, H Suzuki, H Tsugawa, J Matsuzaki, Y Kase, T Hibi

Gastroenterology 140 (5), S-481 2011

Research paper (international conference proceedings)

Rebamipide Normalized the Gastric Emptying Through the Protection Against Gastric Oxidative Stress

S Fukuhara, H Suzuki, J Matsuzaki, S Mogami, H Tsugawa, K Hirata, ...

Gastroenterology 140 (5), S-600-S-601 2011

Research paper (international conference proceedings)

Quality of Life Related to Reflux Symptoms Showed Improvement AfterH. pylori Eradication Therapy

K Hirata, H Suzuki, J Matsuzaki, Y Saito, S Fukuhara, S Okada, T Hibi

Gastroenterology 5 (140), S-302-S-303 2011

Research paper (international conference proceedings)

Iron-Uptake System for the Antioxidant Ability of Helicobacter pylori Regulated by Ferric Uptake Regulator (FUR)

H Tsugawa, H Suzuki, K Hirata, J Matsuzaki, S Okada, S Fukuhara, ...

Gastroenterology 5 (140), S-468 2011

Research paper (international conference proceedings)

Impaired Heme Oxygenase-1 Induction in the Gastric Antrum Induced Disruption of the Interstitial Cells of Cajal Network in a Rat Model of Streptozotocin-Induced Diabetes

S Mogami, H Suzuki, H Tsugawa, J Matsuzaki, Y Kase, T Hibi

Gastroenterology 5 (140), S-374 2011

Research paper (international conference proceedings)

H. pylori-Derived Oncoprotein, CagA, is Degraded by Autophagy in Human Gastric Epithelial Cells

H Tsugawa, H Suzuki, M Hatakeyama, J Matsuzaki, K Hirata, S Okada, ...

Gastroenterology 140 (5), S-10 2011

Research paper (international conference proceedings)

H. pylori Infection Induced Internalization of Duodenal Cellular Iron Exporter FPN1

K Hirata, H Suzuki, H Tsugawa, Y Saito, J Matsuzaki, S Fukuhara, ...

Gastroenterology 140 (5), S-311 2011

Research paper (international conference proceedings)

Frequent Overlap of Overactive Bladder with Functional Dyspepsia and/or Irritable Bowel Syndrome: 1332

H Suzuki, J Matsuzaki, K Asakura, Y Fukushima, S Okada, T Takebayashi, ...

Official journal of the American College of Gastroenterology| ACG 106, S510 2011

Research paper (international conference proceedings)

Evidence of Overlap Between Overactive Bladder (OAB), FD and IBS in a Web-Survey Responder Population

J Matsuzaki, H Suzuki, Y Fukushima, K Hirata, S Okada, S Fukuhara, ...

Gastroenterology 140 (5), S-710 2011

Research paper (international conference proceedings), Lead author

Enhanced Expression of MicroRNA-142-5p and MicroRNA-155 and Suppressed Expression of Tp53inp1 Would Be Novel Molecular Biomarkers for Gastric Mucosa-Associated Lymphoid Tissue …

H Suzuki, Y Saito, H Imaeda, H Tsugawa, S Okada, K Hirata, J Matsuzaki, ...

Gastroenterology 140 (5), S-40 2011

Research paper (international conference proceedings)

Enhanced Expression of Aquaporin-4 and KCNQ1 in the Gastric Parietal Cells in Histamine Type 2 Receptor Knockout Mice

S Fukuhara, H Suzuki, J Matsuzaki, Y Saito, H Tsugawa, K Hirata, ...

Gastroenterology 140 (5), S-470 2011

Research paper (international conference proceedings)

Degradation of Caudal-related Homeobox 2 (Cdx2) is Enhanced by Bile Acid with Upregulation ofmicroRNA-221/222in Human Esophageal Cells During the Progression of Barrett's …

J Matsuzaki, H Suzuki, Y Saito, H Tsugawa, K Hirata, S Okada, ...

Digestive Diseases and Sciences 56 (10) 2011

Research paper (international conference proceedings), Lead author

Degradation of Caudal-Related Homeobox 2 (CDx2) is Enhanced by Bile Acid With Upregulation of MicroRNA-221/222 in Human Esophageal Cells on the Progression of Barrett's …

J Matsuzaki, H Suzuki, Y Saito, H Tsugawa, K Hirata, S Okada, ...

Gastroenterology 140 (5), S-309 2011

Research paper (international conference proceedings), Lead author

The Selective Cyclooxygenase-2 Inhibitor Celecoxib Activates the Tumor Suppressor microRNA-29c in Human Gastric Cancer

Y Saito, H Suzuki, H Tsugawa, J Matsuzaki, K Hirata, T Hibi

DIGESTION 83 (3), 229-229 2011

Research paper (international conference proceedings)

The Tumor-Suppressive Effect of MicroRNA-375 on the Differentiated Gastric Adenocarcinoma, but Not on the Undifferentiated

S Okada, H Suzuki, Y Saito, H Tsugawa, J Matsuzaki, K Hirata, ...

Gastroenterology 5 (140), S-684 2011

Research paper (international conference proceedings)

【機能性消化管異常症　消化管を一本の管としてみる】胃部不快感(機能性胃腸症の診療の実際)　FDの診断と治療の実際

鈴木秀和, 松崎潤太郎, 日比紀文

診断と治療 ((株)診断と治療社) 98 ( 9 ) 1431 - 1435 2010.09

Joint Work, ISSN 0370-999X

【消化管悪性リンパ腫診療の最前線】API2-MALT1キメラ遺伝子陽性胃MALTリンパ腫におけるマイクロRNA発現異常

斎藤義正, 鈴木秀和, 津川仁, 松崎潤太郎, 平田賢郎, 日比紀文

消化器内科 ((有)科学評論社) 51 ( 2 ) 114 - 117 2010.08

Joint Work, ISSN 1884-2895

【メタボリックシンドロームと消化器疾患】メタボリックシンドロームと胃食道逆流症

鈴木秀和, 松崎潤太郎, 日比紀文

G.I.Research ((株)先端医学社) 18 ( 3 ) 187 - 191 2010.06

Joint Work, ISSN 0918-9408

近年、Helicobacter pylori感染率の低下や疾患体系の欧米化に伴って胃食道逆流症(GERD)が急増している。欧米ではGERDが肥満と明確に関連することが示されており、その分子学的な機序も含めて研究が進んでいる。さらに脂質異常症も、肥満とは独立して胃食道逆流の増悪に寄与することがわかりつつある。胆石症はおもに胆汁の十二指腸-胃-食道逆流と関連し、Barrett食道や下部食道腺癌に関与している。一方、わが国ではメタボリックシンドロームとは関連のない胸やけ症状を訴える患者も多い。これはおもに機能性胸やけ患者であると思われ、胃食道逆流がないにもかかわらず胸やけ症状を自覚する患者群である。機能性胸やけ患者にはGERD患者とは異なった治療戦略の検討が必要である。(著者抄録)

【消化器疾患の病態生理】バレット粘膜の背景因子の検討

松崎潤太郎, 鈴木秀和, 斎藤義正, 平田賢郎, 朝倉敬子, 今枝博之, 武林享, 日比紀文

Progress in Medicine ((株)ライフ・サイエンス) 30 ( 3 ) 821 - 824 2010.03

Research paper (conference, symposium, etc.), Joint Work, ISSN 0287-3648

胆嚢運動機能障害の存在を示唆する胆石の有無が、内視鏡的パレット粘膜の頻度に影響を与えているか検討した。上部消化管内視鏡検査を行った4945例中、内視鏡的にパレット粘膜が疑われる病変(ESEM)を認める患者528例、ESEMを認めない患者528例を抽出し、症例対照研究を行った。ロジスティック回帰分析で、食道裂孔ヘルニア、重症の逆流性食道炎、広範な胃粘膜萎縮、胆石、肥満とESEMの関連性が示された。さらに、これらの因子で調整した多変量ロジスティック回帰分析で、食道裂孔ヘルニア、広範な胃粘膜萎縮、胆石が独立したESEMの危険因子であることが示唆された。胆石は胃粘膜萎縮と相乗的に作用してESEMの形成にかかわることが示唆された。ultrashort segment以外のESEMと、胆石や逆流性食道炎は強い関連性を示し、ultrashort segment病変には胃粘膜萎縮が主に関与していた。

Serum lipid levels are positively associated with non-erosive reflux disease, but not with functional heartburn

Matsuzaki, J. and Suzuki, H. and Iwasaki, E. and Yokoyama, H. and Sugino, Y. and Hibi, T.

Neurogastroenterology and Motility 22 ( 9 ) 2010

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Homology model of the DNA gyrase enzyme of Helicobacter pylori, a target of quinolone-based eradication therapy

Matsuzaki, J. and Suzuki, H. and Tsugawa, H. and Nishizawa, T. and Hibi, T.

Journal of Gastroenterology and Hepatology (Australia) 25 ( SUPPL. 1 ) S7 - 10 2010

Research paper (international conference proceedings), Lead author, Accepted

Access to Document (DOI)

Gallstones increase the prevalence of Barrett’s esophagus

J Matsuzaki, H Suzuki, K Asakura, Y Saito, K Hirata, T Takebayashi, T Hibi

Journal of gastroenterology 45 (2), 171-178 45 ( 2 ) 171 - 178 2010

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Delayed gastric emptying and disruption of the interstitial cells of Cajal network after gastric ischaemia and reperfusion

S Suzuki, H Suzuki, K Horiguchi, H Tsugawa, J Matsuzaki, T Takagi, ...

Neurogastroenterology & Motility 22 (5), 585-e126 22 ( 5 ) 2010

Research paper (scientific journal), Accepted

Access to Document (DOI)

Acid suppression by proton pump inhibitors enhances aquaporin-4 and KCNQ1 expression in gastric fundic parietal cells in mouse

J Matsuzaki, H Suzuki, Y Minegishi, E Sugai, H Tsugawa, M Yasui, T Hibi

Digestive diseases and sciences 55 (12), 3339-3348 55 ( 12 ) 3339 - 3348 2010

Research paper (scientific journal), Lead author, Accepted

Access to Document (DOI)

Clinical results of observation of the upper gastrointestinal tract by transgastrostomic endoscopy using an ultrathin endoscope

H Imaeda, N Hosoe, H Nakamizo, K Kashiwagi, H Suzuki, Y Saito, ...

Journal of gastroenterology and hepatology 25 (12), 1850-1854 25 ( 12 ) 1850 - 1854 2010

Research paper (scientific journal), Accepted

Access to Document (DOI)

Contribution of efflux pumps to clarithromycin resistance in Helicobacter pylori

K Hirata, H Suzuki, T Nishizawa, H Tsugawa, H Muraoka, Y Saito, ...

Journal of gastroenterology and hepatology 25, S75-S79 25 ( SUPPL. 1 ) S75 - 9 2010

Research paper (scientific journal), Accepted

Access to Document (DOI)

18 Overexpression of Mir-142-5p and Mir-155 and Suppression of Tumor Protein 53-Induced Nuclear Protein 1 in Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Y Saito, H Suzuki, H Tsugawa, H Imaeda, J Matsuzaki, K Hirata, N Hosoe, ...

Gastroenterology 138 (5), S-3 2010

Research paper (international conference proceedings)

884 The Role of the Ferric Uptake Regulator (Fur) in Helicobacter pylori Resistance to Metronidazole

H Tsugawa, H Suzuki, S Suzuki, K Hirata, J Matsuzaki, Y Saito, T Hibi

Gastroenterology 5 (138), S-124 2010

Research paper (international conference proceedings)

266 Chronic Infection With Helicobacter pylori Induces Downregulation of Muscle-Specific MicroRNAs and Smooth Muscle Hypertrophy of the Mouse Stomach

Y Saito, H Suzuki, H Tsugawa, S Suzuki, J Matsuzaki, K Hirata, T Hibi

Gastroenterology 5 (138), S-49 2010

Research paper (international conference proceedings)

180 Induction of H. pylori Resistance to Metronidazole Through Enhanced Expression of a Bacterial Efflux Pump

H Tsugawa, H Suzuki, H Muraoka, S Suzuki, K Hirata, J Matsuzaki, ...

Gastroenterology 138 (5), S-33 2010

Research paper (international conference proceedings)

Homology model of the DNA gyrase enzyme of Helicobacter pylori, a target of quinolone‐based eradication therapy

J Matsuzaki, H Suzuki, H Tsugawa, T Nishizawa, T Hibi

Journal of gastroenterology and hepatology 25, S7-S10 2010

Research paper (international conference proceedings), Lead author, Accepted

S2063 Impaired Heme Oxygenase-1 Induction in the Gastric Antrum of Streptozotocin-Induced Diabetic Rats

S Suzuki, H Suzuki, H Tsugawa, J Matsuzaki, Y Kase, T Hibi

Gastroenterology 5 (138), S-312 2010

Research paper (international conference proceedings)

S1630 Caudal-Related Homeobox 2 (CDx2) Suppresses Stratification of Esophageal Squamous Epithelial Cells by Down-Regulating MicroRNA-221/222

J Matsuzaki, H Suzuki, Y Saito, H Tsugawa, K Hirata, T Hibi

Gastroenterology 138 (5), S-242 2010

Research paper (international conference proceedings), Lead author

Nitric oxide involvement in gastric disorders

H Suzuki, S Suzuki, J Matsuzaki, H Tsugawa, Y Saito, K Hirata, ...

NITRIC OXIDE-BIOLOGY AND CHEMISTRY 22, S35-S35 2010

Research paper (conference, symposium, etc.)

M1909 Increased Expression of MicroRNA-21 is an Early Event in Human Gastric Carcinogenesis

K Hirata, Y Saito, H Suzuki, H Imaeda, J Matsuzaki, T Hibi

Gastroenterology 5 (138), S-437 2010

Research paper (international conference proceedings)

M1346 High Prevalence of Lower Gastrointestinal (GI) Symptoms in Functional Dyspepsia: A Factor and Cluster Analysis in the General Population

H Suzuki, J Matsuzaki, K Asakura, Y Fukushima, Y Saito, T Takebayashi, ...

Gastroenterology 138 (5), S-385 2010

Research paper (international conference proceedings)

M1139 Sitafloxacin-Based Third-Line Eradication of H. pylori

H Suzuki, J Matsuzaki, T Nishizawa, Y Saito, K Hirata, H Tsugawa, ...

Gastroenterology 138 (5), S-340 2010

Research paper (international conference proceedings)

T1700 Dyslipidemia is a Risk Factor for NERD, but Not for Functional Heartburn

J Matsuzaki, H Suzuki, E Iwasaki, Y Sugino, H Yokoyama, T Hibi

Gastroenterology 138 (5), S-560 2010

Research paper (international conference proceedings), Lead author

W1751 MicroRNA-21 Plays a Critical Role in Helicobacter pylori-Associated Gastric Cancer by Suppressing Btg2

A Ikura, Y Saito, H Suzuki, H Tsugawa, J Matsuzaki, K Hirata, T Hibi

Gastroenterology 5 (138), S-732 2010

Research paper (international conference proceedings)

W1749 Downregulation of the Tumor Suppressor MicroRNA-29c Plays a Critical Role in the Progression of Human Gastric Cancer

Y Saito, H Suzuki, H Imaeda, J Matsuzaki, K Hirata, H Tsugawa, N Hosoe, ...

Gastroenterology 5 (138), S-732 2010

Research paper (international conference proceedings)

The Selective Cyclooxygenase-2 Inhibitor Celecoxib Activates the Tumor SuppressorMicroRNA-29cin Human Gastric Cancer

Y Saito, H Suzuki, H Tsugawa, J Matsuzaki, K Hirata, T Hibi

Digestive Diseases and Sciences 55 (10) 2010

Research paper (international conference proceedings)

T1766 Transient Gastroparesis and Reduced Ghrelin After Gastric Ischemia and Reperfusion

S Suzuki, H Suzuki, H Tsugawa, J Matsuzaki, H Hosoda, K Kangawa, ...

Gastroenterology 138 (5), S-574 2010

Research paper (international conference proceedings)

【Helicobacter pylori Now　基礎・臨床の最新研究】H.pylori感染症関連疾患と除菌治療の意義　生活習慣病

鈴木秀和, 松崎潤太郎, 日比紀文

日本臨床 ((株)日本臨床社) 67 ( 12 ) 2366 - 2371 2009.12

Joint Work, ISSN 0047-1852

【バレット食道の取扱い】バレット食道のリスク要因

松崎潤太郎, 鈴木秀和, 日比紀文

消化器科 ((有)科学評論社) 49 ( 1 ) 14 - 17 2009.07

Joint Work, ISSN 0289-8756

【Helicobacter Year Book　Annual Review 2008】Helicobacter研究のレビューと今後の展望　Helicobacter pylori感染と非胃・十二指腸疾患とのかかわり

鈴木秀和, 松崎潤太郎, 日比紀文

Helicobacter Research ((株)先端医学社) 13 ( 3 ) 213 - 220 2009.06

Joint Work, ISSN 1342-4319

Helicobacter pylori(H.pylori)が胃炎や消化性潰瘍の原因であるという知見は、消化器病領域の新時代を築いた。近年、H.pyloriと非胃・十二指腸疾患との関連についての報告がなされており、消化器病領域を超えた、H.pylori感染症の病態が注目されている。特発性血小板減少性紫斑病(ITP)、鉄欠乏性貧血、動脈硬化性疾患に関してはすでに多くの報告がなされている。また肝疾患とH.pyloriおよびその他のHelicobacter属のかかわりについての報告も多くみられた。(著者抄録)

Chromatin remodeling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells

Y Saito, H Suzuki, H Tsugawa, I Nakagawa, J Matsuzaki, Y Kanai, T Hibi

Oncogene 28 (30), 2738-2744 28 ( 30 ) 2738 - 2744 2009

Research paper (scientific journal), Accepted

Access to Document (DOI)

W1953 MicroRNA-142 and-155 Are Novel Molecular Markers for Gastric MALT Lymphoma with API2-MALT1 FUSION

Y Saito, H Suzuki, I Nakagawa, J Matsuzaki, E Iwasaki, T Nishizawa, ...

Gastroenterology 136 (5), A-760 2009

Research paper (international conference proceedings)

1088 Role of MicroRNA-29c in the Chemoprevention of Gastric Cancer By a Selective COX-2 Inhibitor

Y Saito, H Suzuki, I Nakagawa, J Matsuzaki, E Iwasaki, H Tsugawa, ...

Gastroenterology 5 (136), A-167-A-168 2009

Research paper (international conference proceedings)

977 Sitafloxacin and Garenoxacin, New-Generation Quinolones, Can Overcome the Antibiotic Resistance of H. pylori with gyrA Mutations

H Suzuki, J Matsuzaki, H Muraoka, T Nishizawa, Y Saito, E Iwasaki, T Hibi

Gastroenterology 136 (5), A-150 2009

Research paper (international conference proceedings)

93 Enhanced Esophageal NADPH Oxidase 3 Expression and Free Radical Production in Response to Acid

E Iwasaki, H Suzuki, Y Saito, T Masaoka, T Nishizawa, H Tsugawa, ...

Gastroenterology 5 (136), A-16 2009

Research paper (international conference proceedings)

47 Gastric Acid Secretion Suppression Enhanced Aquaporin-4 and KCNQ1 Expressions in the Fundic Parietal Cells

J Matsuzaki, H Suzuki, Y Saito, H Tsugawa, S Suzuki, E Iwasaki, K Hirata, ...

Gastroenterology 136 (5), A-7-A-8 2009

Research paper (international conference proceedings), Lead author

129 Ferric Uptake Regulator (FUR) Mutation in Helicobacter pylori Associated with the Development of Resistance to Metronidazole: Implication of the Structural-Functional …

H Tsugawa, H Suzuki, I Nakagawa, K Hirata, T Nishizawa, Y Saito, ...

Gastroenterology 136 (5), A-23-A-24 2009

Research paper (international conference proceedings)

Efflux Pump Inhibition May Reverse the Clarithromycin Resistance ofH. pyloriwith 23S rRNA Mutation: 130

K Hirata, H Suzuki, T Nishizawa, H Tsugawa, H Muraoka, J Matsuzaki, ...

American Journal of Gastroenterology 104, S51-S52 2009

Research paper (international conference proceedings)

M1051 Efflux Pumps Contribute to Clarithromycin Resistance in H. pylori

K Hirata, H Suzuki, T Nishizawa, H Tsugawa, H Muraoka, I Nakagawa, ...

Gastroenterology 5 (136), A-339 2009

Research paper (international conference proceedings)

Link of Gallstones and Endoscopically Suspected Esophageal Metaplasia (ESEM) in Japanese Patients: Case-control study: 60

J Matsuzaki, H Suzuki, K Asakura, K Hirata, Y Saito, T Takebayashi, T Hibi

American Journal of Gastroenterology 104, S26 2009

Research paper (international conference proceedings)

H Suzuki, J Matsuzaki, T Hibi

Nihon rinsho. Japanese journal of clinical medicine 67 (12), 2366-2371 67 ( 12 ) 2366 - 2371 2009

Research paper (scientific journal)

T1779 Enhanced Ghrelin Secretion and Gastric Excitatory Neural Network in Rats with Gastric Outlet Obstruction

E Iwasaki, H Suzuki, S Suzuki, Y Saito, T Masaoka, T Nishizawa, ...

Gastroenterology 5 (136), A-578 2009

Research paper (international conference proceedings)

【胃食道逆流症(GERD)の診かた】診断　胸やけの発生機序と機能性胸やけの位置づけ

鈴木秀和, 松崎潤太郎, 日比紀文

治療 ((株)南山堂) 90 ( 6 ) 1905 - 1909 2008.06

Joint Work, ISSN 0022-5207

胸やけの症状発生には酸の逆流のほかにも、食道粘膜の知覚過敏、十二指腸液の逆流、気体の逆流、食道蠕動障害、精神的因子など複数の機序が混在している。症状は典型的な胸やけであっても胃食道逆流の関連を確認できない機能的胸やけ(functional heartburn:FH)と称される病態もある。FHは機能性ディスペプシア(functional dyspepsia:FD)との関連が示唆されている。(著者抄録)

Endoscopically Suspected Esophageal Metaplasia (Esem) Is Associated with the Complications of Hiatus Hernia, Reflux Esophagitis and Severe Gastric Mucosal Atrophy in Japanese …

J Matsuzaki, H Suzuki, K Hirata, M Ikewada, Y Saito, T Hibi

American Journal of Gastroenterology 103, S15 2008

Research paper (international conference proceedings)

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