九州大学 研究者情報
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基本情報 研究活動 教育活動 社会活動 病院臨床活動
森山 大樹(もりやま たいき) データ更新日:2022.06.15

准教授 /  九州大学病院 光学医療診療部 九州大学大学院 臨床・腫瘍外科


主な研究テーマ
胃癌・食道癌の臨床的研究
内視鏡外科手術
キーワード:胃癌、食道癌、内視鏡外科手術
2014.05.
膵癌における癌間質相互作用, microRNA
キーワード:膵癌, 間質細胞, マイクロRNA
2006.04.
研究業績
主要原著論文
1. Haimin Feng, Taiki Moriyama, Kenoki Ohuchida, Nan Sheng, Chika Iwamoto, Koji Shindo, Kengo Shirahane, Naoki Ikenaga, Shuntaro Nagai, Kohei Nakata, Kazuhiro Mizumoto, Masafumi Nakamura, N-acetyl cysteine induces quiescent-like pancreatic stellate cells from an active state and attenuates cancer-stroma interactions, J Exp Clin Cancer Res, 10.1186/s13046-021-01939-1, 40, 133, 1-19, 2021.04, Background: Pancreatic stellate cells (PSCs) occupy the majority of the pancreatic cancer microenvironment, contributing to aggressive behavior of pancreatic cancer cells (PCCs). Recently, anti-fibrotic agents have proven to be an effective strategy against cancer, but clinical trials have shown little efficacy, and the driving mechanism remains unknown. N-acetyl-cysteine (NAC) is often used for pulmonary cystic fibrosis. Pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, was habitually used for type II diabetes, but recently reported to inhibit metastasis of PCCs. However, few studies have focused on the effects of these two agents on cancer-stromal interactions.
Method: We evaluated the expression of α-smooth muscle actin (α-SMA) and the number of lipid droplets in PSCs cultured with or without NAC. We also evaluated changes in invasiveness, viability, and oxidative level in PSCs and PCCs after NAC treatment. Using an indirect co-culture system, we investigated changes in viability, invasiveness, and migration of PSCs and PCCs. Combined treatment effects of NAC and Pioglitazone were evaluated in PSCs and PCCs. In vivo, we co-transplanted KPC-derived organoids and PSCs to evaluate the effects of NAC and Pioglitazone's combination therapy on subcutaneous tumor formation and splenic xenografted mouse models.
Results: In vitro, NAC inhibited the viability, invasiveness, and migration of PSCs at a low concentration, but not those of PCCs. NAC treatment significantly reduced oxidative stress level and expression of α-SMA, collagen type I in PSCs, which apparently present a quiescent-like state with a high number of lipid droplets. Co-cultured PSCs and PCCs mutually promoted the viability, invasiveness, and migration of each other. However, these promotion effects were attenuated by NAC treatment. Pioglitazone maintained the NAC-induced quiescent-like state of PSCs, which were reactivated by PCC-supernatant, and enhanced chemosensitivity of PCCs. In vivo, NAC and Pioglitazone's combination suppressed tumor growth and liver metastasis with fewer stromal components and oxidative stress level.
Conclusion: NAC suppressed activated PSCs and attenuated cancer-stromal interactions. NAC induces quiescent-like PSCs that were maintained in this state by pioglitazone treatment..
2. Moriyama T, Han HS, Kudo K, Sadakari Y, Moriyama T, Nakashima N, Nakamura M, Shimizu S, Role of international tele-education with live surgery for pre-clinical medical students, Proceedings of the APAN – Research Workshop 2019, 48-53, 2019.04.
3. Moriyama T, Ohuchida K, Mizumoto K, Cui L, Ikenaga N, Sato N, Tanaka M, Enhanced cell migration and invasion of CD133+ pancreatic cancer cells cocultured with pancreatic stromal cells, Cancer, 116, 14, 3357-3368, 2010.04, BACKGROUND: Recently, cancer stem cells have been reported as a new therapeutic target in pancreatic cancer as well as other cancers, but the specific role of these cells is unknown. METHODS: The authors investigated the functional roles of CD133+ cells, 1 of the putative cancer stem cell candidates in pancreatic cancer. CD133 expression was assessed in human pancreatic cancer and cancer cell lines by quantitative real-time reverse transcriptase polymerase chain reaction and flow cytometry. Next, they compared the ability of CD133+ and CD133- cells to proliferate, migrate, and invade using 2 pancreatic cancer cell lines. In particular, they evaluated the relationship between CD133+ cells and primary pancreatic stromal cells. RESULTS: CD133 was expressed in primary human pancreatic cancer tissues and some cancer cell lines, whereas there was little expression in primary normal pancreatic epithelial cells and primary pancreatic stromal cells. CD133+ cells, isolated by flow cytometry, showed increased cell proliferation under anchorage-independent conditions (P<.01), and enhanced migration and invasion, particularly when cocultured with primary pancreatic stromal cells (P<.001). Chemokine-related receptor-4 (CXCR4), markedly overexpressed in CD133+ cells, may be responsible for the increased invasive ability of the cells cocultured with pancreatic stromal cells, which express stromal derived factor-1, the ligand to CXCR4. CONCLUSIONS: These data suggest that CD133+ cells exhibit more aggressive behavior, such as increased cell proliferation, migration, and invasion, especially in the presence of pancreatic stromal cells. The targeting therapy for the interaction between CD133+ cancer cells and stromal cells may be a new approach for the treatment of pancreatic cancer. Copyright (c) 2010 American Cancer Society..
4. Moriyama T, Ohuchida K, Mizumoto K, Yu J, Sato N, Nabae T, Takahata S, Toma H, Nagai E, Tanaka M, MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance., Mol Cancer Ther, 8, 5, 1067-1074, 2009.04, Abstract

Due to the poor prognosis of pancreatic cancer, novel diagnostic modalities for early diagnosis and new therapeutic strategy are urgently needed. Recently, microRNA-21 (miR-21) was reported to be strongly overexpressed in pancreatic cancer as well as in other solid cancers. We investigated the functional roles of miR-21, which have not been fully elucidated in pancreatic cancer. miR-21 expression was assessed in pancreatic cancer cell lines (14 cancer cell lines, primary cultures of normal pancreatic epithelial cells and fibroblasts, and a human normal pancreatic ductal epithelial cell line) and pancreatic tissue samples (25 cancer tissues and 25 normal tissues) by quantitative real-time reverse transcription-PCR amplification. Moreover, we investigated the proliferation, invasion, and chemoresistance of pancreatic cancer cells transfected with miR-21 precursor or inhibitor. miR-21 was markedly overexpressed in pancreatic cancer cells compared with nonmalignant cells, and miR-21 in cancer tissues was much higher than in nonmalignant tissues. The cancer cells transfected with the miR-21 precursor showed significantly increased proliferation, Matrigel invasion, and chemoresistance for gemcitabine compared with the control cells. In contrast, inhibition of miR-21 decreased proliferation, Matrigel invasion, and chemoresistance for gemcitabine. Moreover, miR-21 positively correlated with the mRNA expression of invasion-related genes, matrix metalloproteinase-2 and -9, and vascular endothelial growth factor. These data suggest that miR-21 expression is increased in pancreatic cancer cells and that miR-21 contributes to the cell proliferation, invasion, and chemoresistance of pancreatic cancer..
5. Moriyama T, Yamashita H, Noguchi S, Takamatsu Y, Ogawa T, Watanabe S, Uchino S, Ohshima A, Kuroki S, Tanaka M, Intraoperative Parathyroid Hormone Assay in Patients with Graves' Disease for Prediction of Postoperative Tetany, World J Surg, 29, 10, 1282-1287, 2005.04, We measured intraoperative parathyroid hormone (IOPTH) levels before and after thyroidectomy in a large group of patients to test whether changes in IOPTH can predict postoperative tetany. Subjects were 111 consecutive patients (94 females and 17 males) with Graves' disease undergoing subtotal thyroidectomy. Blood samples for IOPTH assay were obtained after anesthesia (basal) and following skin closure (postoperative). Data were compared between patients who developed tetany (n = 9) and those who did not (n = 102). There was no significant difference in sex, age, period of antithyroid drug administration, or the weight of the thyroid between the two groups. The preoperative serum calcium level was significantly lower (p < 0.05) and the basal IOPTH significantly higher (p < 0.05) in the tetany group than in the non-tetany group. The IOPTH level was significantly lower (p < 0.005) and the average percent decrease in IOPTH levels was higher (p < 0.001) in the tetany group than in the non-tetany group. A decrease in IOPTH of more than 70% was shown to be 78% sensitive, 94% specific, and 93% accurate, and it has 78% positive predictive value and 94% negative predictive value for the development of tetany. Our study shows that a postoperative decrease of IOPTH level is the most predictive of postoperative tetany of the clinical risk factors investigated. We recommend IOPTH measurement as an adjunct to postoperative management of patients with Graves' disease to assist in preventing hypocalcemia and determining the earliest time for safe discharge..
主要総説, 論評, 解説, 書評, 報告書等
主要学会発表等
学会活動
所属学会名
日本外科学会
日本消化器外科学会
日本内視鏡外科学会
日本癌治療学会
日本胃癌学会
日本食道学会
日本内分泌外科学会
日本乳癌学会
日本遠隔医療学会
日本消化器内視鏡学会
学協会役員等への就任
2018.05, 九州外科学会, 評議員.
学会大会・会議・シンポジウム等における役割
2021.03.11~2021.03.12, 第57回日本腹部救急医学会総会, プログラム委員.
2021.02.19~2021.02.20, 第57回九州外科学会・第57回九州小児外科学会・第56回九州内分泌外科学会 (セッション:胃・十二指腸3), 座長.
2020.10.28~2020.10.28, 第14回肝臓内視鏡外科研究会・ 第12回膵臓内視鏡外科研究会, 技術支援.
2020.08.28~2020.08.29, 第47回日本膵切研究会 , 技術支援.
2020.01.23~2020.01.23, 2nd Myanmar Telemedicine Workshop, Commentator.
2019.12.14~2019.12.14, 第4回国際臨床医学会, 座長.
2018.12.06~2018.12.08, 第31回日本内視鏡外科学会総会, 座長.
2018.11.09~2018.11.10, 第22回日本遠隔医療学会学術大会, 実行委員長、座長.
2018.02.10~2018.02.11, JTTA Spring Conference 2018, 座長.
2017.11.18~2017.11.18, 2nd Philippine Telemedicine Network (TNP) Workshop at the ELSA Annual Congress 2017, Commentator.
2017.09.30~2018.10.01, 第21回日本遠隔医療学会学術大会, 座長.
2017.09.13~2017.09.13, Third MIS- Asia Teleconference, Co-Chair.
2017.03.29~2017.03.29, Second MIS- Asia Teleconference, Co-Chair.
2017.03.01~2017.03.01, 第6回内視鏡外科チームテレカンファレンスセミナー, ディスカッサント.
2017.02.13~2017.02.17, The 43rd Asia-Pacific Advanced Network (APAN43) Meeting, MIS Session, Moderator.
2016.12.02~2016.12.03, The 10th Asia Telemedicine Symposium , Commentator (Day 2, Session3).
2016.08.01~2016.08.05, The 42nd Asia-Pacific Advanced Network (APAN42) Meeting JIPMER Session, Moderator.
学術論文等の審査
年度 外国語雑誌査読論文数 日本語雑誌査読論文数 国際会議録査読論文数 国内会議録査読論文数 合計
2018年度      
2014年度
その他の研究活動
海外渡航状況, 海外での教育研究歴
新ヤンゴン総合病院, ヤンゴン専門病院, Myanmar, 2020.01~2020.01.
チョーライ病院, Vietnam, 2018.04~2018.04.
セントルークス医療センター, Philippines, 2018.03~2018.03.
国立台湾大学, 台北医科大学Wanfang病院, Chang Gung Memorial Hospital, Taiwan, 2018.02~2018.02.
復旦大学中山病院, China, 2018.01~2018.01.
ヤンゴン第一医科大学, 新ヤンゴン総合病院, ヤンゴン総合病院, Myanmar, 2017.10~2017.10.
ILBS, India, 2017.02~2017.02.
マヒドン大学シリラ病院, チュラロンコン大学, ブルムングラッド国際病院, Thailand, 2017.01~2017.01.
India Habitat Centre, India, 2017.02~2017.02.
108陸軍中央病院, バックマイ病院, Vietnam, 2016.11~2016.11.
トリブバン大学, カトマンズ病院, NREN, Nepal, 2016.11~2016.11.
香港大学, Hong Kong , 2016.08~2016.08.
セントルークス医療センター, Philippines, 2016.07~2016.07.
慶尚大学, Korea, 2016.06~2016.06.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2021年度~2023年度, 基盤研究(C), 代表, scRNA-seqを用いた食道癌TME内NK細胞の化学療法による機能的変化の解析.
2021年度~2023年度, 基盤研究(C), 分担, 細胞内共生microbiomeからみた新規膵癌進展メカニズムの解明.
2019年度~2021年度, 基盤研究(C), 分担, 局所浸潤を先導する癌関連脂肪細胞(CAA)を標的とした新規膵癌制御法の開発.
2019年度~2021年度, 基盤研究(C), 分担, 膵癌の転移臓器指向性に着目した臓器特異的転移形成促進性微小環境の解明.
2019年度~2021年度, 挑戦的研究(萌芽), 分担, Drop-seqによる不均一性を伴う患者由来消化器癌微小環境の単一細胞解析.
2019年度~2021年度, 基盤研究(B), 分担, 膵癌PDXライブラリ-を用いたシングルセル解析による腫瘍内治療抵抗不均一性の解明.
2018年度~2020年度, 基盤研究(C), 代表, 3D膵癌オルガノイドモデルを用いた新たな癌細胞死形態とそれに伴う浸潤機構の解明.
2016年度~2020年度, 基盤研究(A), 分担, 中南米における早期胃癌診断率向上のための継続的遠隔医療教育システムの構築.
2019年度~2020年度, 挑戦的研究(萌芽), 分担, 膵癌オルガノイドを用いたpartialEMTによるクラスター浸潤機序の解明と制御.
2017年度~2019年度, 挑戦的萌芽研究, 分担, 3Dバイオプリンターを用いた膵癌微小環境モデルによる新たな浸潤・転移機序の可視化.
2017年度~2019年度, 挑戦的萌芽研究, 分担, 膵癌クラスター浸潤を導くPSCの機序解明と微小環境基質改変による制御.
2016年度~2018年度, 基盤研究(B), 分担, 膵癌の新たな転移・再発機序の解明;膵管内播種に着目して.
2016年度~2018年度, 基盤研究(B), 分担, 転移を導く臓器特異的リーディングセルの解明と微小転移環境リモデリングの制御.
2016年度~2018年度, 基盤研究(C), 分担, 膵癌における新たなリンパ節転移機序CCID formationの解明とその制御.
2015年度~2017年度, 基盤研究(C), 代表, 膵癌の転移・播種における間質細胞(線維芽細胞・膵星細胞)との関わり.
2015年度~2017年度, 基盤研究(C), 分担, 化合物ライブラリーを利用した膵癌間質標的新規治療薬の開発.
2013年度~2014年度, 若手研究(B), 代表, 膵癌腹膜播種を誘導する特異的間質細胞の同定および膵癌新規治療法の開発.
2013年度~2013年度, 挑戦的萌芽研究, 分担, 癌間質のnormalizationによる薬剤送達改善と新規膵癌治療への応用.
2011年度~2012年度, 若手研究(A,B), 代表, 膵癌抑制効果を有する特異的間質細胞の同定および新規膵癌治療法の開発.
2010年度~2011年度, 研究活動スタート支援, 代表, 膵癌抑制効果を有する特異的間質細胞の同定および新規膵癌治療法の開発.

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