研究者詳細 - 寺井　崇二

Treatment of hepatic diseases with bone marrow stem cell transplantation 査読

その他リンク： https://jlc.jst.go.jp/DN/JALC/00249900949?from=CiNii

Use of bone marrow cells for the development of cellular therapy in liver diseases 査読

Sakaida, I, S Terai, K Okita

HEPATOLOGY RESEARCH 31 ( 4 ) 195 - 196 2005年4月

Okita, K., Terai, S., Sakaida, I.

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 94 ( 4 ) 769 - 774 2005年4月

消化器領域における細胞増殖因子と組織再生療法を目指したニューフロンティア基礎から臨床へ骨髄細胞から肝細胞への分化過程における線維芽細胞増殖因子の促進効果

石川剛, 寺井崇二, 沖田極

日本消化器病学会雑誌 102 ( 臨増総会 ) A156 - A156 2005年3月

Percutaneous radiofrequency ablation with cooled electrodes combined with hepatic arterial balloon occlusion in hepatocellular carcinoma 査読

T Yamasaki, T Kimura, F Kurokawa, KJ Aoyama, T Ishikawa, K Tajima, Y Yokoyama, T Takami, K Omori, K Kawaguchi, M Tsuchiya, S Terai, Sakaida, I, K Okita

JOURNAL OF GASTROENTEROLOGY 40 ( 2 ) 171 - 178 2005年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

Background. We have reported that percutaneous radiofrequency ablation (RFA) with balloon occlusion of the hepatic artery (balloon-occluded RFA), using an expandable electrode, increases the coagulation area. In this study, we investigated the efficacy of balloon-occluded RFA and balloon-microcatheter-occluded RFA, using a cool RF single electrode. Methods. We studies 41 patients with 47 hepatocellular carcinoma (HCC) lesions. We treated 28 patients (32 nodules) with balloon-occluded RFA, 5 patients (6 nodules) with balloon-microcatheter-occluded RFA, and 8 patients (9 nodules) with standard RFA. Initial therapeutic efficacy was evaluated with dynamic computed tomography performed 1 week after one session of treatment. Results. One session of treatment was done for 20 nodules (62.5%) in the balloon-occluded RFA group and for 4 nodules (66.7%) in the balloon-microcatheter-occluded RFA group. We compared the coagulation diameter for balloon-occluded RFA (7 nodules), balloon-microcatheter-occluded RFA (6 nodules), and standard RFA (9 nodules) after one application cycle (12 min). The greatest dimension of the area coagulated by balloon-occluded RFA was significantly larger (greatest long-axis dimension, 47.6 +/- 7.8 mm; greatest short-axis dimension, 33.4 +/- 7.5 mm) than that coagulated by standard RFA (greatest long-axis dimension, 35.3 +/- 4.7 mm; greatest short-axis dimension, 25.9 +/- 3.7 mm; P = 0.002 for greatest long-axis dimension; P 0.041 for greatest short-axis dimension). However, there was significant difference only in the greatest short-axis dimension of the area coagulated comparing balloon-microcatheter-occluded RFA and standard RFA. Conclusions. We consider balloon-occluded RFA using a cool RF electrode to be superior to standard RFA for the treatment of HCC, especially when larger coagulation volumes are required.

DOI： 10.1007/s00535-004-15L6-5

Prognostic factors in patients with advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy 査読

T Yamasaki, T Kimura, F Kurokawa, K Aoyama, T Ishikawa, K Tajima, Y Yokoyama, T Takami, K Omori, K Kawaguchi, M Tsuchiya, S Terai, Sakaida, I, K Okita

JOURNAL OF GASTROENTEROLOGY 40 ( 1 ) 70 - 78 2005年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

Background. The prognosis of patients with advanced hepatocellular carcinoma (HCC) is poor. We aimed to clarify the prognostic factors in patients with advanced HCC receiving hepatic arterial infusion chemotherapy (HAIC). Methods. Forty-four HCC patients were treated with HAIC, using low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) with/without leucovorin (or isovorin). Of these 44 patients, 15 received low-dose CDDP and 5-FU, and 29 received low-dose CDDP, 5-FU, and leucovorin or isovorin. Prognostic factors were evaluated by univariate and multivariate analyses of patient and disease characteristics. Results. Of all patients, 5 and 12 patients respectively, exhibited a complete response (CR) and a partial response (PR) (response rate, 38%). The response rate (48.3%) in the low-dose CDDP and 5-FU with leucovorin/isovorin group was significantly better than that (20%) in the low-dose CDDP and 5-FU group (P = 0.002). The 1-, 2-, 3-, and 5-year cumulative survival rates of the 44 patients were 39%, 18%, 12%, and 9%, respectively. The regimen using low-dose CDDP and 5-FU with leucovorin/isovorin tended to improve survival rates (P = 0.097). Univariate and multivariate analyses showed the same variables' the Child-Pugh score (P = 0.013, P = 0.018), alpha-fetoprotein (AFP) level (P = 0.010, P = 0.009), and therapeutic effect after HAIC (P = 0.003, P = 0.01), respectively, to be significant prognostic factors. Conclusions. Patients who had advanced HCC with favorable hepatic reserve capacity and a lower AFP level were suitable candidates for HAIC. Moreover, the regimen using low-dose CDDP and 5-FU with leucovorin/isovorin may be suitable for advanced HCC patients, because of the improvement in the response rate and survival compared with the low-dose CDDP and 5-FU regimen without leucovorin/isovorin.

DOI： 10.1007/s00535-004-1494-7

Development of New Therapy in Fulminant Hepatitis from Glucagon-Insulin Therapy to Bone Marrow Cell Transplantation

Kiwamu Okita, Isao Sakaida, Shuji Terai, Naoki Yamamoto, Kaoru Omori, Tsuyoshi Ishikawa, Kouji Aoyama, Koh Shinoda, Yoshihiko Hamamoto

International Journal of Oncology 52 ( 3-4 ) 25 - 31 2005年

Development of cell therapy using autologous bone marrow cells for liver cirrhosis 査読

Isao Sakaida, Shuji Terai, Hiroshi Nishina, Kiwamu Okita

Medical Molecular Morphology 38 ( 4 ) 197 - 202 2005年

記述言語：英語掲載種別：研究論文（国際会議プロシーディングス）

The plasticity of bone marrow has been confirmed by the autopsy of a female recipient of bone marrow cell transplantation from a male donor. To establish new clinical cell therapies using autologous bone marrow cells for patients with liver failure, we developed a new in vivo model named the green fluorescent protein (GFP)/carbon tetrachloride (CCl4) model. Using the GFP/CCl4 model, we found that transplanted Liv8-negative cells efficiently repopulated into cirrhotic liver tissue and differentiated into albumin-producing hepatocytes under persistent liver damage induced by carbon tetrachloride. Moreover, bone marrow cell transplantation into mice with liver cirrhosis improved liver function and liver fibrosis with the strong expression of matrix metalloproteinases (MMPs), especially MMP-9 activity, resulting in an improved survival rate. Results from the GFP/CCl4 model showed that cell therapy using autologous bone marrow cells has the potential to become an effective treatment for patients with liver failure. A summary of findings from the GFP/CCl4 model is described. © The Japanese Society for Clinical Molecular Morphology 2005.

DOI： 10.1007/s00795-005-0298-z

Scopus

Lesson from the GFP/CCl4 model - Translational Research Project: the development of cell therapy using autologous bone marrow cells in patients with liver cirrhosis 査読

S Terai, Sakaida, I, H Nishina, K Okita

JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 12 ( 3 ) 203 - 207 2005年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

The plasticity of bone marrow has been confirmed by the analysis of autopsy findings in female recipients of bone marrow cells transplanted from male donors. To establish new clinical cell therapies using autologous bone marrow cells for patients with liver failure, we developed a new in vivo model, the "green fluorescent protein (GFP)/carbon tetrachloride (CCl4) model". Using the GFP/CCl4 model, we found that transplanted Liv8-negative cells efficiently repopulated into cirrhotic liver tissue and trans-differentiated into albumin-producing hepatocytes under conditions of persistent liver damage induced by CCl4. Moreover, one marrow cell transplantation into liver cirrhosis mice improved their liver function, ameliorated liver fibrosis, and improved their survival rate. Results from the GFP/CCl4 model showed that cell therapy using autologous bone marrow cells has the potential to become an effective treatment for patients with liver failure. Here we describe the findings from the GFP/CCl4 model and the scope of the translational research project.

DOI： 10.1007/s00534-005-0977-0

Molecular signature associated with plasticity of bone marrow cell under persistent liver damage by self-organizing-map-based gene expression 査読

K Omori, S Terai, T Ishikawa, K Aoyama, Sakaida, I, H Nishina, K Shinoda, S Uchimura, Y Hamamoto, K Okita

FEBS LETTERS 578 ( 1-2 ) 10 - 20 2004年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE BV

The mechanism that regulates the plasticity of bone marrow cells (BMCs) into hepatocytes is poorly understood. We developed a green fluorescent protein/carbon tetrachloride model to find that BMC transplantation recovered liver damage. Serum albumin level and liver fibrosis were recovered by BMC transplantation. To understand the mechanism, we used DNA-chip technology to profile the change of transient gene expression before and after BMC transplantation. On the basis of gene expression with self-organizing map using specific equation, genes were classified into 153 clusters. The information is useful to understand the dramatic gene activation during the process of the plasticity of BMC. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

DOI： 10.1016/j.febslet.2004.09.090

Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice 査読

Sakaida, I, S Terai, N Yamamoto, K Aoyama, T Ishikawa, H Nishina, K Okita

HEPATOLOGY 40 ( 6 ) 1304 - 1311 2004年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JOHN WILEY & SONS INC

We investigated the effect of bone marrow cell (BMC) transplantation on established liver fibrosis. BMCs of green fluorescent protein (GFP) mice were transplanted into 4-week carbon tetrachloride (CCl4)-treated C57BL6 mice through the tail vein, and the mice were treated for 4 more weeks with CCl4 (total, 8 weeks). Sirius red and GFP staining clearly indicated migrated BMCs existing along with fibers, with strong expression of matrix metalloproteinase (MMP)-9 shown by anti-MMP-9 antibodies and in situ hybridization. Double fluorescent immunohistochemistry showed the expression of MMP-9 on the GFP-positive cell surface. Film in situ zymographic analysis revealed strong gelatinolytic activity in the periportal area coinciding with the location of MMP-9-positive BMCs. Four weeks after BMC transplantation, mice had significantly reduced liver fibrosis, as assessed by hydroxyproline content of the livers, compared to that of mice treated with CCl4 alone. Subpopulation of Liv8-negative BMCs was responsible for this fibrolytic effect. In conclusion, mice with BMC transplants with continuous CCl4 injection had reduced liver fibrosis and a significantly improved survival rate after BMC transplantation compared with mice treated with CCl4 alone. This finding introduces a new concept for the therapy of liver fibrosis.

DOI： 10.1002/hep.20452

自己骨髄細胞を用いた肝硬変症に対する肝臓再生療法

寺井崇二, 大森薫, 石川剛, 青山浩司, 高見太郎, 横山雄一郎, 田島邦彦, 坂井田功, 沖田極

治療学 38 ( 10 ) 1158 - 1159 2004年10月

記述言語：日本語出版者・発行元：ライフサイエンス出版(株)

肝不全患者に対し生体肝移植が行われているが,ドナーの問題,外科侵襲の多さという問題点があり,次世代の肝臓再生療法の開発が求められている.われわれは骨髄細胞(肝幹細胞)の移植療法の有効性を評価するため,GFP/CCl4モデルを開発し解析してきた.さらに基盤研究を基に臨床研究(自己骨髄細胞を用いた肝臓再生療法)へと展開した.われわれは,肝移植が受けられない肝不全患者に対する新たな治療方法の開発を慎重に進めている(著者抄録)

肝細胞癌に対する新しいバルーンマイクロカテーテルを用いたリピオドール併用肝動脈バルーン閉塞下ラジオ波凝固療法

肝発癌機構におけるhelix-loop-helix(HLH)型転写制御分子の発現とその制御

高見太郎, 寺井崇二, 沖田極

肝臓 45 ( Suppl.2 ) A486 - A486 2004年9月

骨髄細胞の肝細胞への分化過程において変動する血清蛋白質の解析

横山雄一郎, 寺井崇二, 大森薫, 青山浩司, 石川剛, 高見太郎, 坂井田功, 沖田極

日本癌学会総会記事 63回 505 - 506 2004年9月

肝発癌早期に高発現するHHM(Human Homologue of Maid)のプロモーター解析と,肝疾患患者血清中の抗HHM抗体の検出

高見太郎, 寺井崇二, 横山雄一郎, 田島邦彦, 谷本治子, 仁科博史, 坂井田功, 沖田極

日本癌学会総会記事 63回 295 - 295 2004年9月

山崎隆弘, 木村輝昭, 浦田洋平, 丸本芳雄, 青山浩司, 石川剛, 田島邦彦, 横山雄一郎, 大森薫, 川口浩太郎, 高見太郎, 土屋昌子, 山口裕樹, 寺井崇二, 黒川典枝, 坂井田功, 沖田極

肝臓 45 ( 9 ) 505 - 506 2004年9月

記述言語：日本語出版者・発行元：(一社)日本肝臓学会

肝細胞癌4例を対象に,新しいバルーンマイクロカテーテルを用いたリピオドール併用肝動脈バルーン閉塞下ラジオ波凝固療法を施行した.通常の腹部血管造影の手技にて,5Frカテーテルを用い,精査を行い,マイクロカテーテルにてTranscatheter arterial chemoembolizationを施行し,腫瘍内にリピオドールをpoolingさせた後,Equinox occlusion balloon catheterを胆癌領域の肝動脈に留置し,バルーン閉塞後に経皮的ラジオ波凝固療法を施行した.治療効果判定として1週間後の造影CTで凝固範囲を測定した.12分間1回穿刺での凝固範囲が検討できたのは2例で,各々50×47mm,55×44mmであった.1週間後の造影CTでは,全例で治療部位の早期濃染像は認めなかったが,1例で脈管近傍のsafety marginが不足していたため,経皮的エタノール注入療法を追加した.合併症として発熱の遷延1例,肝梗塞1例を認めたが保存的に改善し,その他は全例に発熱と疼痛を認めたが対処療法で改善した.また一時的に肝機能悪化を認めたが,1週間後に前値に復した