研究者詳細 - 寺井　崇二

Therapeutic or spontaneous Helicobacter pylori eradication can obscure magnifying narrow-band imaging of gastric tumors. 査読

Kobayashi M, Hashimoto S, Mizuno K, Takeuchi M, Sato Y, Watanabe G, Ajioka Y, Azumi M, Akazawa K, Terai S

Endoscopy international open 4 ( 6 ) E665 - 72 2016年6月

Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib 査読

Naoki Yamamoto, Takahiro Yamasaki, Taro Takami, Koichi Uchida, Koichi Fujisawa, Toshihiko Matsumoto, Issei Saeki, Shuji Terai, Isao Sakaida

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION 58 ( 3 ) 202 - 209 2016年5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：JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION

Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient t-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC.

DOI： 10.3164/jcbn.15-127

Effective prevention of hand-foot syndrome by the consumption of dried bonito broth 査読

Kenya Kamimura, Yoko Shinagawa, Kohei Ogawa, Yuji Kobayashi, Hiroyuki Abe, Takeshi Yokoo, Hiroteru Kamimura, Hirokazu Kawai, Takeshi Suda, Satoshi Yamagiwa, Hiroshi Baba, Shuji Terai

Japanese Journal of Cancer and Chemotherapy 43 ( 4 ) 463 - 465 2016年4月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Journal of Cancer and Chemotherapy Publishers Inc.

To examine whether the consumption of dried bonito both is effective for the prevention of hand-foot syndrome (HFS), concentrated bonito broth was administered to 10 patients with HCC who were treated with sorafenib. Among the 10 patients, seven showed an increase in peripheral blood flow, as observed on Doppler ultrasonography. Only one patient showed Grade 1 HFS on day 14 after the initiation of sorafenib (10%)
this incidence rate of HFS was significantly lower than that obtained in our previous studies and reported data. These results suggest that consumption of dried bonito broth contributes to the prevention of HFS by maintaining peripheral blood flow.

Scopus

当院における悪性胃十二指腸狭窄に対する内視鏡的ステント留置術の有用性の検討

林和直, 山本幹, 水野研一, 本田穣, 橋本哲, 横山純二, 竹内学, 佐藤祐一, 寺井崇二

Gastroenterological Endoscopy 58 ( Suppl.1 ) 790 - 790 2016年4月

Modulation of anti-cancer drug sensitivity through the regulation of mitochondrial activity by adenylate kinase 4 査読国際誌

Fujisawa Koichi, Terai Shuji, Takami Taro, Yamamoto Naoki, Yamasaki Takahiro, Matsumoto Toshihiko, Yamaguch Kazuhito, Owada Yuji, Nishina Hiroshi, Takafumi Noma, Sakaida Isao

Journal of Experimental & Clinical Cancer Research Vol.35 ( No.1 ) 48 - 48 2016年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Adenylate kinase is a key enzyme in the high-energy phosphoryl transfer reaction in living cells. Anisoform of this enzyme, adenylate kinase 4 (AK4), is localized in the mitochondrial matrix and is believed to beinvolved in stress, drug resistance, malignant transformation in cancer, and ATP regulation. However, the molecularbasis for the AK4 functions remained to be determined.Methods: HeLa cells were transiently transfected with an AK4 small interfering RNA (siRNA), an AK4 short hairpinRNA (shRNA) plasmid, a control shRNA plasmid, an AK4 expression vector, and a control expression vector toexamine the effect of the AK4 expression on cell proliferation, sensitivity to anti-cancer drug, metabolome, geneexpression, and mitochondrial activity.Results: AK4 knockdown cells treated with short hairpin RNA increased ATP production and showed greatersensitivity to hypoxia and anti-cancer drug, cis-diamminedichloro-platinum (II) (CDDP). Subcutaneous grafting AK4knockdown cells into nude mice revealed that the grafted cells exhibited both slower proliferation and reduced thetumor sizes in response to CDDP. AK4 knockdown cell showed a increased oxygen consumption rate with FCCPtreatment, while AK4 overexpression lowered it. Metabolome analysis showed the increased levels of thetricarboxylic acid cycle intermediates, fumarate and malate in AK4 knockdown cells, while AK4 overexpressionlowered them. Electron microscopy detected the increased mitochondrial numbers in AK4 knockdown cells.Microarray analysis detected the increased gene expression of two key enzymes in TCA cycle, succinatedehydrogenase A (SDHA) and oxoglutarate dehydrogenease L (OGDHL), which are components of SDH complexand OGDH complex, supporting the metabolomic results.Conclusions: We found that AK4 was involved in hypoxia tolerance, resistance to anti-tumor drug, and theregulation of mitochondrial activity. These findings provide a new potential target for efficient anticancer therapiesby controlling AK4 expression.

DOI： 10.1186/s13046-016-0322-2

Modulation of anti-cancer drug sensitivity through the regulation of mitochondrial activity by adenylate kinase 4. 査読国際誌

Fujisawa K, Terai S, Takami T, Yamamoto N, Yamasaki T, Matsumoto T, Yamaguchi K, Owada Y, Nishina H, Noma T, Sakaida I

Journal of experimental & clinical cancer research : CR 35 48 - 48 2016年3月

Advanced diagnostic endoscopy for gastric cancers discovered after H. Pylori eradication 査読

Masaaki Kobayashi, Takahiro Hoshi, Shin-Ichi Morita, Tsutomu Kanefuji, Takeshi Suda, Ken-Ichi Mizuno, Satoru Hashimoto, Manabu Takeuchi, Yuichi Sato, Shuji Terai

Journal of Japanese Society of Gastroenterology 113 ( 2 ) 235 - 244 2016年2月

Human T-cell leukemia virus type 1 (HTLV-1) Tax1 oncoprotein but not HTLV-2 Tax2 induces the expression of OX40 ligand by interacting with p52/p100 and RelB 査読

Yosuke Motai, Masahiko Takahashi, Takayuki Takachi, Masaya Higuchi, Toshifumi Hara, Mariko Mizuguchi, Yutaka Aoyagi, Shuji Terai, Yuetsu Tanaka, Masahiro Fujii

VIRUS GENES 52 ( 1 ) 4 - 13 2016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

Human T-cell leukemia virus type 1 (HTLV-1) is a causative retrovirus of adult T-cell leukemia and HTLV-1-associated myelopathy. Unlike HTLV-1, the same group of retrovirus HTLV-2 has not been found to be associated with these diseases. HTLV-1 and HTLV-2 encode transforming proteins Tax1 and Tax2, and a few distinct activities of Tax1 from those of Tax2 have been proposed to contribute to the HTLV-1-specific pathogenesis of disease. One significant difference of Tax1 from Tax2 is the activation of transcription factor NF-kappa B2/p100/p52. We found that Tax1 but not Tax2 induces the expression of OX40 ligand (OX40L) in a human T-cell line. To induce the OX40L expression, Tax1 but not Tax2 was observed to interact with NF-kappa B2/p100/p52 and RelB and the distinct interaction activity was mediated by the Tax1 amino acid region of 225-232. In addition, Tax1 but not Tax2 or Tax1/225-232 interacted with p65, p50, and c-Rel; however, the interactions were much less than those noted with NF-kappa B2/p100/p52 and RelB. OX40L is a T-cell costimulatory molecule of the tumor necrosis factor family, and its signal plays a critical role in establishing adaptive immunity by inducing the polarized differentiation of T-cells to cells such as T helper type 2 and T follicular helper cells. Therefore, the present findings suggest that Tax1 might alter the immune response to HTLV-1 and/or differentiation of HTLV-1-infected T-cells via OX40L induction, thereby acting as a factor mediating the distinct phenotypes and pathogenesis of HTLV-1 from that of HTLV-2.

DOI： 10.1007/s11262-015-1277-7

Circadian variations in the liver metabolites of medaka (Oryzias latipes) 査読

Koichi Fujisawa, Taro Takami, Yoshitaka Kimoto, Toshihiko Matsumoto, Naoki Yamamoto, Shuji Terai, Isao Sakaida

SCIENTIFIC REPORTS 6 20916 2016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：NATURE PUBLISHING GROUP

Circadian rhythms are biological rhythms with a period of around 24 hours. In this study, we compared the metabolome of the liver of medaka during the day and night. To comprehensively analyze the circadian variations in the levels of metabolites in the liver, livers were isolated from Zeitgeber time (ZT)4 and ZT16, and the variations in metabolite levels were evaluated. Inosinemonophosphate (IMP) and uridinemonophosphate (UMP) were found to be increased at night, indicating that nucleotide synthesis is most active during the night. Furthermore, the levels of metabolites of the tricarboxylic acid cycle were also reduced at night. In addition, the levels of many amino acids were reduced during the night, suggesting that the amino acids had been degraded. Moreover, the citrulline/ornithine ratio, which is related to arginine consumption, was lower during the day than at night. This pattern suggests that the urea cycle is activated during the day, whereas large amounts of nitric oxide and citrulline may be produced from arginine via nitric oxide synthase during the night. The results of this metabolomic analysis may be useful in future fundamental research to provide insight into chronobiology as well as applied research on drug evaluations using medaka as a model species.

DOI： 10.1038/srep20916

Percutaneous transhepatic obliteration for hepatic encephalopathy accompanied with chronic renal failure in a super-elderly patient: A case report 査読

Yusuke Watanabe, Toru Ishikawa, Satoshi Abe, Ryousuke Inoue, Tomoyuki Sugano, Akito Iwanaga, Keiichi Seki, Terasu Honma, Toshiaki Yoshida, Takeo Nemoto, Keiko Takeda, Shuji Terai

Acta Hepatologica Japonica 56 ( 12 ) 668 - 674 2016年1月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Japan Society of Hepatology

We herein report the case of a super-elderly patient with hepatic encephalopathy accompanied with chronic renal failure, who successfully underwent percutaneous transhepatic obliteration (PTO). An 85-year-old man was diagnosed with non-alcoholic fatty liver cirrhosis and chronic renal failure. He had a collateral vessel from the left portal vein to the paraesophageal vein, which caused repeated hepatic encephalopathy, and medications poorly controlled his hepatic encephalopathy. PTO was performed using a half dose of contrast medium. After PTO, his portal vein pressure did not increase
however, he had respiratory discomfort with right pleural effusion on the fifth day. The pleural effusion disappeared on increasing the diuretic dose. Although the diuretic dose was increased, his renal function did not worsen and the NH3 level did not increase. Hepatic encephalopathy might be controlled by performing PTO in a super-elderly patient, with minimal reduction in renal function from contrast medium and diuretics.

DOI： 10.2957/kanzo.56.668

Scopus

Liver regeneration therapy using autologous bone marrow-derived cells for cirrhotic patients 査読

Taro Takami, Isao Sakaida, Shuji Terai

Gene Therapy and Cell Therapy Through the Liver: Current Aspects and Future Prospects 25 - 34 2016年1月

記述言語：英語掲載種別：論文集(書籍)内論文出版者・発行元：Springer Japan

In our animal studies, we have reported that bone marrow cells (BMCs) infused via a peripheral vein effi ciently repopulate the cirrhotic liver. Repopulated BMCs produce collagenases including matrix metalloproteinase-9. As a result, we observed reduced liver fi brosis, elevated serum albumin levels, and a signifi cant increase in survival. Based on these data, we have begun “autologous bone marrow cell infusion (ABM i) therapy” using non-cultured autologous whole BMCs. This therapy was offi cially approved as “advanced medical technology B” in Japan. However, ABM i therapy involves bone marrow (BM) aspiration under general anesthesia. We therefore developed a less-invasive liver regeneration therapy using cultured autologous mesenchymal stem cells (MSCs) isolated from a small amount of BM fl uid aspirated under local anesthesia. We showed that peripheral infusion of cultured human BMCs reduces hepatic fi brosis in immunodefi cient cirrhotic mice, consistent with the maintenance of redox homeostasis in hepatic stellate cells and hepatocytes. To evaluate safety using canine models, cultured autologous MSCs were administered to the same subject in approximately three times the quantity and ten times the concentration used in humans. We then constructed a cell-processing facility with a new isolator system to confer protection from hepatitis virus. Here, we summarize the current status and prospects for our liver regeneration therapy.

DOI： 10.1007/978-4-431-55666-4_3

Scopus

Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model 査読

Hiroyuki Abe, Kenya Kamimura, Yuji Kobayashi, Masato Ohtsuka, Hiromi Miura, Riuko Ohashi, Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Masanori Tsuchida, Yutaka Aoyagi, Guisheng Zhang, Dexi Liu, Shuji Terai

MOLECULAR THERAPY-NUCLEIC ACIDS 5 e276 2016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：NATURE PUBLISHING GROUP

Liver fibrosis is the final stage of liver diseases that lead to liver failure and cancer. While various diagnostic methods, including the use of serum marker, have been established, no standard therapy has been developed. The objective of this study was to assess the approach of overexpressing matrix metalloproteinase-13 gene (MMP13) in rat liver to prevent liver fibrosis progression. A rat liver fibrosis model was established by ligating the bile duct, followed by liver-targeted hydrodynamic gene delivery of a MMP13 expression vector, containing a CAG promoter-MMP13-IRES-tdTomato-polyA cassette. After 14 days, the serum level of MMP13 peaked at 71.7 pg/ml in MMP13-treated group, whereas the nontreated group only showed a level of similar to 5 pg/ml (P < 0.001). These levels were sustained for the next 60 days. The statistically lower level of the hyaluronic acids in treated group versus the nontreated group (P < 0.05) reveals the therapeutic effect of MMP13 overexpression. Quantitative analysis of tissue stained with sirius red showed a statistically larger volume of fibrotic tissue in the nontreated group compared to that of MMP13-treated rats (P < 0.05). These results suggest that the liver-targeted hydrodynamic delivery of MMP13 gene could be effective in the prevention of liver fibrosis.

DOI： 10.1038/mtna.2015.49

Training ROI selection based on MILBoost for liver cirrhosis classification using ultrasound images 査読

Fujita, Y., Mitani, Y., Hamamoto, Y., Segawa, M., Terai, S., Sakaida, I.

Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 9799 451 - 459 2016年

Improvement of Pancreatic Tumor-induced NAFLD with Pancrelipase 査読

Naosuke Kuraoka, Atsunori Tsuchiya, Takeshi Suda, Shuji Terai

INTERNAL MEDICINE 55 ( 1 ) 89 - 90 2016年

The Combination Therapy of Dissolution Using Carbonated Liquid and Endoscopic Procedure for Bezoars: Pragmatical and Clinical Review 査読

Kohei Ogawa, Kenya Kamimura, Ken-ichi Mizuno, Yoko Shinagawa, Yuji Kobayashi, Hiroyuki Abe, Yukari Watanabe, Shunsaku Takahashi, Kazunao Hayashi, Junji Yokoyama, Manabu Takeuchi, Masaaki Kobayashi, Satoshi Yamagiwa, Yuichi Sato, Shuji Terai

GASTROENTEROLOGY RESEARCH AND PRACTICE 2016 7456242 2016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：HINDAWI LTD

Bezoars are relatively rare foreign bodies of gastrointestinal tract and often cause ileus and ulcerative lesions in the stomach and subsequent bleeding and perforation due to their size and stiffness. Therefore, the removal of bezoars is essential and recent development of devices, the endoscopic removal procedure, is often applied. However, due to their stiffness, simple endoscopic removal failed in not a few cases, and surgical removal has also been used. Recently, the efficacy of a combination therapy of endoscopic procedure and dissolution using carbonated liquid has been reported. To develop the safe and effective removal procedure, we carefully reviewed a total of 55 reported cases in this study including our 3 additional cases, successfully treated with dissolution with endoscopic fragmentation. In summary, the data showed the efficiency in the combination therapy, treating the larger size of bezoar and reducing the length of hospital stay. To the best of our knowledge, this is the largest pragmatical and clinical review for the combination therapy of dissolution and endoscopic treatment for bezoars. This review should help physicians to manage bezoars more efficiently.

DOI： 10.1155/2016/7456242

Endoscopic Removal of Ingested Dentures and Dental Instruments: A Retrospective Analysis 査読

Ken-ichi Mizuno, Kazuya Takahashi, Kentaro Tominaga, Yuki Nishigaki, Hiroki Sato, Satoshi Ikarashi, Kazunao Hayashi, Takashi Yamamoto, Yutaka Honda, Satoru Hashimoto, Kenya Kamimura, Manabu Takeuchi, Junji Yokoyama, Yuichi Sato, Masaaki Kobayashi, Shuji Terai

GASTROENTEROLOGY RESEARCH AND PRACTICE 2016 3537147 2016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：HINDAWI PUBLISHING CORP

Background. Dentures and dental instruments are frequently encountered ingested foreign bodies. The aim of the present study was to assess the safety and efficacy of endoscopically removing ingested dental objects. Methods. Twenty-nine consecutive patients with 29 dental objects who were treated at the Niigata University Medical and Dental Hospital from August 2009 to December 2015 were retrospectively reviewed. Characteristics of the patients and the ingested dental objects, the clinical features and findings of radiological imaging tests, and outcomes of endoscopic removal were analyzed. Results. Patients' mean age was 62.9 + 21.0 years. The ingested dental objects included 23 dentures (13 crowns, 4 bridges, 4 partial dentures, and 2 other dentures) and 6 dental instruments. Twenty-seven upper gastrointestinal endoscopies and 2 colonoscopies were performed, and their success rates were 92.6% and 100%, respectively. There were 2 cases of removal failure; one case involved an impacted partial denture in the cervical esophagus, and this case required surgical removal. Conclusions. Endoscopic removal of ingested dentures and dental instruments is associated with a favorable success rate and acceptable complications. The immediate intervention and appropriate selection of devices are essential for managing ingested dental objects.

DOI： 10.1155/2016/3537147