論文 - 松崎　潤太郎

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年07月

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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年07月

研究論文（学術雑誌）, 共著, 査読有り

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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年06月

研究論文（学術雑誌）, 共著, 査読有り,  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年06月

研究論文（学術雑誌）, 共著, 査読有り,  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年12月

研究論文（学術雑誌）, 共著, 査読有り

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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年12月

研究論文（学術雑誌）, 共著,  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年12月

共著,  ISSN  1342-4319

　概要を見る

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年11月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り

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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年08月

研究論文（学術雑誌）, 共著, 査読有り,  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年08月

研究論文（学術雑誌）, 共著, 査読有り,  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年08月

研究論文（学術雑誌）, 共著, 査読有り

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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年06月

研究論文（学術雑誌）, 共著, 査読有り,  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年06月

共著,  ISSN  0288-5514

　概要を見る

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年05月

研究論文（学術雑誌）, 共著, 査読有り,  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年04月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り,  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年03月

研究論文（学術雑誌）, 共著, 査読有り,  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年

研究論文（学術雑誌）, 共著, 査読有り

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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年10月

研究論文（学術雑誌）, 共著, 査読有り

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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

Tominaga H, Matsuzaki J, Oikawa C, Toyoshima K, Manabe H, Ozawa E, Shimamura A, Yokoyama R, Serizawa Y, Ochiya T, Saito Y

Cancers （Cancers）  13 （ 16 ）  2021年08月

研究論文（学術雑誌）, 共著, 責任著者, 査読有り,  ISSN  2072-6694

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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年06月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り,  ISSN  2001-3078

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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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