研究者詳細 - 寺井　崇二

Possible involvement of mucosal-associated invariant T cells in the progression of inflammatory bowel diseases 査読

Kentaro Tominaga, Satoshi Yamagiwa, Toru Setsu, Naruhiro Kimura, Hiroki Honda, Hiroteru Kamimura, Yutaka Honda, Masaaki Takamura, Junji Yokoyama, Kenji Suzuki, Toshifumi Wakai, Shuji Terai

BIOMEDICAL RESEARCH-TOKYO 38 ( 2 ) 111 - 121 2017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：BIOMEDICAL RESEARCH PRESS LTD

munity. Recent studies have demonstrated that MAIT cells might be implicated in inflammatory bowel diseases (IBDs), but their precise function in IBD remains to be elucidated. We investigated the possible involvement of MAIT cells in the immunopathogenesis of IBDs. Heparinized peripheral blood and biopsy specimens of the colon were collected from 25 patients with ulcerative colitis (UC), 15 patients with Crohn's disease (CD), and 19 heathy individuals. Lymphocytes were isolated from the blood and colon, and then MAIT cells were analyzed by flow cytometry. The frequency of MAIT cells was significantly lower in the blood of IBD patients compared to healthy donors and significantly higher in the inflamed colons compared to healthy colons (P = 0.001). Among the IBD patients, the frequency of MAIT cells in the blood and colon was correlated with disease activities. In vitro activated MAIT cells from IBD patients secreted significantly more tumor necrosis factor-alpha and interleukin-17 than those from healthy donors. These findings indicate that MAIT cells are activated in IBD patients, and their accumulation in the inflamed mucosa is correlated with disease activities.

DOI： 10.2220/biomedres.38.111

A Mesenteric Desmoid Tumor with Rapid Progression 査読

Kazunao Hayashi, Masaaki Takamura, Hisashi Yokoyama, Yuichi Sato, Satoshi Yamagiwa, Hitoshi Nogami, Toshifumi Wakai, Go Hasegawa, Shuji Terai

INTERNAL MEDICINE 56 ( 5 ) 505 - 508 2017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：JAPAN SOC INTERNAL MEDICINE

We herein report the case of a rapidly progressive sporadic mesenteric desmoid tumor (DT). A 62-year-old woman presented with a 4-cm-diameter palpable mass in the left supraumbilical area. The mass showed an ill-defined margin with heterogeneous delayed enhancement on computed tomography and heterogeneous high intensity on T2-weighted magnetic resonance imaging. Sixteen months after the initial observation, the mass had grown in size, reaching 13 cm in diameter. The resected mass was histologically confirmed as a DT of the mesentery. Since DT often has an unpredictable clinical course, clinicians should bear in mind the need for imaging follow-up.

DOI： 10.2169/internalmedicine.56.7320

Efficacy and safety of telaprevir- and simeprevir-based triple therapies for older patients with chronic hepatitis C 査読

Satoshi Yamagiwa, Toru Ishikawa, Nobuo Waguri, Soichi Sugitani, Hiroto Wakabayashi, Shogo Ohkoshi, Takashi Tsukishiro, Toru Takahashi, Toshiaki Watanabe, Shuji Terai

World Journal of Hepatology 9 ( 5 ) 252 - 262 2017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：Baishideng Publishing Group Co

AIM To evaluate and compare the efficacy and safety of telaprevir (TVR)-and simeprevir (SMV)-based triple therapies in elderly patients, specifically patients aged 66 years or older. METHODS The present study enrolled 112 and 76 Japanese patients with chronic hepatitis C virus genotype 1b infection who were treated with a 12-wk TVR-based or SMV-based triple therapy, respectively, followed by a dual therapy that included pegylated interferon a and ribavirin (RBV) for 12 wk. The patients were categorized into two groups according to age as follows: A younger group of patients aged ≤ 65 years old and an older group of patients aged &gt
65 years old. Among the patients treated with TVR-based triple therapy, 34 patients were included in the older group. The median ages were 56 years (range: 28-65 years) in the younger group and 69 years (range: 66-81 years) in the older group. Among the patients treated with SMV-based triple therapy, 39 patients were included in the older group. The median ages were 59 years (range: 36-65 years) in the younger group and 71 years (range: 66-86 years) in the older group. The clinical, biochemical and virological data were analyzed before and during treatment. RESULTS Among the patients treated with the TVR-based triple therapy, no significant difference in the sustained virological response (SVR) was found between the younger (80.8%) and older (88.2%) groups. The SVR rates for patients with the interleukin 28B (IL28B) (rs8099917) TG/GGgenotypes (73.9% and 60.0% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (86.3% and 92.9%, respectively). The cumulative exposure to RBV for the entire 24-wk treatment period (as a percentage of the target dose) was significantly higher in the younger group than in the older group (91.7% vs 66.7%, respectively, P &lt
0.01), but the cumulative exposure to TVR was not significantly different between the younger and older groups (91.6% vs 81.9%, respectively). A multivariate analysis identified the TT-genotype of IL28B (OR = 8.160
95%CI: 1.593-41.804, P = 0.012) and the adherence of RBV ( &gt
60%) (OR = 11.052
95%CI: 1.160-105.273, P = 0.037) as independent factors associated with the SVR. Adverse events resulted in discontinuation of the treatment in 11.3% and 14.7% of the younger and older groups, respectively. Among the patients treated with the SMV-based triple therapy, no significant difference in the SVR rare was found between the younger (81.1%) and older (82.1%) groups. The SVR rates for patients with the IL28B TG/GG-genotypes (77.8% and 64.7% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (88.2% and 100%, respectively). A multivariate analysis identified the TT-genotype of IL28B as an independent factor associated with the SVR (OR = 9.677
95%CI: 1.114-84.087, P = 0.040). Adverse events resulted in discontinuation of the treatment in 7.0% and 14.3% of patients in the younger and older groups, respectively. CONCLUSION Both TVR- and SMV-based triple therapies can be successfully used to treat patients aged 66 years or older with genotype 1b chronic hepatitis C. Genotyping of the IL28B indicates a potential to achieve SVR in these difficult-to-treat elderly patients.

DOI： 10.4254/wjh.v9.i5.252

Scopus

Tumor markers for early diagnosis for brain metastasis of hepatocellular carcinoma: A case series and literature review for effective loco-regional treatment 査読

Kenya Kamimura, Yuji Kobayashi, Yoshifumi Takahashi, Hiroyuki Abe, Daisuke Kumaki, Takeshi Yokoo, Hiroteru Kamimura, Norihiro Sakai, Akira Sakamaki, Satoshi Abe, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

CANCER BIOLOGY & THERAPY 18 ( 2 ) 79 - 84 2017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：TAYLOR & FRANCIS INC

Intrahepatic lesions of hepatocellular carcinoma (HCC) have been controlled by significant advances in treatment using loco-regional therapies, including, surgery, ablative therapy, catheter-based chemotherapy, and embolization. Consequently, the number of patients with extrahepatic metastatic lesions has increased. Their prognosis remains poor with approximately <1y of survival from the time of diagnosis. A molecularly targeted drug, sorafenib, have been used to treat extrahepatic lesions and shown the prolonged survival time. However, the therapeutic benefit for the brain metastasis remains unclear, since it causes intratumor bleeding leading to the severe brain damage. No guidelines for the brain metastasis of HCC have been developed to date due to the shortage of the experiences and evidences. Therefore, the development of standard therapy for brain metastasis following the early diagnosis is essential by accumulating the information of clinical courses and evidences. For this purpose, we reviewed cases of HCC brain metastasis reported to date and analyzed additional 8 cases from our hospital, reviewing 592 advanced HCC cases to estimate the possible metastatic lesions in the brain. With careful review of cases and literature, we suggest that the cases with lung metastasis with increase tendency of tumor markers within recent 3-6months have higher risks of brain metastasis. Therefore, they should be carefully followed by imaging modalities. In addition, the loco-regional treatment, including surgical resection and radiation therapy should be performed for better prognosis by preventing re-bleeding from the tumors.

DOI： 10.1080/15384047.2016.1276134

An Unusual Case of an Extremely Large α-Fetoprotein-Producing Tumor. 査読

Takahashi K, Tsuchiya A, Terai S

Gastroenterology 151 ( 6 ) 1077 - 1080 2016年12月

Myofibroblast distribution is associated with invasive growth types of colorectal cancer 査読

Masafumi Takatsuna, Satoko Morohashi, Tadashi Yoshizawa, Hideaki Hirai, Toshihiro Haga, Rie Ota, Kensuke Saito, Yunyan Wu, Hiroko Seino, Yutaka Aoyagi, Shuji Terai, Hiroshi Kijima

ONCOLOGY REPORTS 36 ( 6 ) 3154 - 3160 2016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：SPANDIDOS PUBL LTD

Both the invasive growth types of colorectal cancer (CRC) and the number of myofibroblasts have been associated with histopathological factors such as lymph node and liver metastasis, and local recurrence. However, there are few studies, that have assessed the association between invasive growth type and myofibroblast distribution in CRC. We aimed to evaluate the relationship between the clinicopathological factors of CRC and two invasive growth types, the expanding and infiltrating types. We categorized 150 cases of pT3 CRC into the expanding and infiltrating types and measured the myofibroblast density of three histological layers: the submucosa (SM), the muscularis propria (MP) and the subserosa (SS). We compared these two invasive growth types and analyzed the relationship between clinicopathological factors and myofibroblast density. Myofibroblast density was significantly higher in the infiltrating type than that in the expanding type (P<0.05). In the lymph node metastasis-positive group of the infiltrating type, myofibroblast density in MP was significantly higher than that in the lymph node metastasis-negative group (P<0.001). In the infiltrating type, the group with the higher level of lymphatic invasion had a significantly higher density of myofibroblasts in the MP than the group with the lower level of lymphatic invasion (P<0.01). These results suggest that myofibroblasts participate more in the infiltrating type compared with the expanding type of CRC. It would appear that myofibroblasts present in the MP play an important role in the malignant potential of the infiltrating type compared to the expanding type.

DOI： 10.3892/or.2016.5202

Transhepatic arterial chemotherapy using a combination of miriplatin and CDDP powder in patients with hepatocellular carcinoma 査読

Kenya Kamimura, Hiroteru Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Nobuo Waguri, Toru Ishikawa, Takeshi Suda, Satoshi Yamagiwa, Shuji Terai

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 31 361 - 361 2016年11月

Case of severe alcoholic hepatitis treated with granulocytapheresis 査読

Yukari Watanabe, Kenya Kamimura, Tomohiro Iwasaki, Hiroyuki Abe, Shunsaku Takahashi, Ken-ichi Mizuno, Manabu Takeuchi, Atsushi Eino, Ichiei Narita, Shuji Terai

WORLD JOURNAL OF CLINICAL CASES 4 ( 11 ) 369 - 374 2016年11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：BAISHIDENG PUBLISHING GROUP INC

Severe alcoholic hepatitis (AH) has a high mortality, and it is associated with encephalopathy, acute renal failure, sepsis, gastrointestinal bleeding, and endotoxemia. The 28-d mortality remains poor (34%-40%), because no effective treatment has been established. Recently, corticosteroids (CS) have been considered effective for significantly improving the prognosis of those with AH, as it prevents the production of pro-inflammatory cytokines. However, CS are not always appropriate as an initial therapeutic option, such as in cases with an infection or resistance to CS. We describe a patient with severe AH complicated by a severe infection caused by the multidrug resistance bacteria (Pseudomonas aeruginosa), and was successfully treated with granulocytapheresis monotherapy without using CS. The experience of this case will provide understanding of the disease and information treating cases without using CS.

DOI： 10.12998/wjcc.v4.i11.369

[Series: Diagnosis at a Glance]. 査読

Kobayashi T, Tsuchiya A, Kuraoka N, Yamamoto T, Honda Y, Yokoyama J, Kawai H, Yamagiwa S, Suda T, Terai S

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 105 ( 11 ) 2263 - 2267 2016年11月

Vonoprazan 20 mg <i>vs</i> lansoprazole 30 mg for endoscopic submucosal dissection-induced gastric ulcers. 査読国際誌

Takahashi K, Sato Y, Kohisa J, Watanabe J, Sato H, Mizuno K, Hashimoto S, Terai S

World journal of gastrointestinal endoscopy 8 ( 19 ) 716 - 722 2016年11月

Significance of hepatic progenitor cell marker-positive hepatocellular carcinoma and its possible prediction by AFP-L3 査読

Atsunori Tsuchiya, Yuichi Kojima, Satoshi Seino, Yusuke Watanabe, Kenya Kamimura, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

HEPATOLOGY 64 669A - 670A 2016年10月

Liver-targeted hydrodynamic gene therapy: Recent advances in the technique 査読

Takeshi Yokoo, Kenya Kamimura, Hiroyuki Abe, Yuji Kobayashi, Tsutomu Kanefuji, Kohei Ogawa, Ryo Goto, Masafumi Oda, Takeshi Suda, Shuji Terai, Masafumi Oda

WORLD JOURNAL OF GASTROENTEROLOGY 22 ( 40 ) 8862 - 8868 2016年10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：BAISHIDENG PUBLISHING GROUP INC

One of the major research focuses in the field of gene therapy is the development of clinically applicable, safe, and effective gene-delivery methods. Since the first case of human gene therapy was performed in 1990, a number of gene-delivery methods have been developed, evaluated for efficacy and safety, and modified for human application. To date, viral-vector-mediated deliveries have shown effective therapeutic results. However, the risk of lethal immune response and carcinogenesis have been reported, and it is still controversial to be applied as a standard therapeutic option. On the other hand, delivery methods for non-viral vector systems have been developed, extensively studied, and utilized in in vivo gene-transfer studies. Compared to viral-vector mediated gene transfer, nonviral systems have less risk of biological reactions. However, the lower gene-transfer efficiency was a critical hurdle for applying them to human gene therapy. Among a number of nonviral vector systems, our studies focus on hydrodynamic gene delivery to utilize physical force to deliver naked DNA into the cells in the living animals. This method achieves a high gene-transfer level by DNA solution injections into the tail vein of rodents, especially in the liver. With the development of genome editing methods, in vivo gene-transfer therapy using this method is currently the focus in this research field. This review explains the method principle, efficiency, safety, and procedural modifications to achieve a high level of reproducibility in large-animal models.

DOI： 10.3748/wjg.v22.i40.8862

Platinum-based transhepatic arterial chemotherapy using a combination of miriplatin and CDDP powder in patients with hepatocellular carcinoma 査読

Kohei Ogawa, Kenya Kamimura, Takeshi Suda, Takeshi Yokoo, Akira Sakamaki, Satoshi Abe, Hiroteru Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Nobuo Waguri, Toru Ishikawa, Satoshi Yamagiwa, Shuji Terai

HEPATOLOGY 64 652A - 652A 2016年10月

Biological significance of a disintegrin and metalloproteinase 21 expression in hepatocellular carcinoma 査読

Masaaki Takamura, Hiroki Honda, Satoshi Yamagiwa, Naruhiro Kimura, Toru Setsu, Kentaro Tominaga, Hiroteru Kamimura, Takuya Genda, Yasunobu Matsuda, Toshifumi Wakai, Shuji Terai

HEPATOLOGY 64 639A - 639A 2016年10月

Myofibroblasts of the muscle layer stimulate the malignant potential of colorectal cancer 査読

Masafumi Takatsuna, Satoko Morohashi, Tadashi Yoshizawa, Hideaki Hirai, Toshihiro Haga, Rie Ota, Yunyan Wu, Hajime Morohashi, Kenichi Hakamada, Shuji Terai, Hiroshi Kijima

ONCOLOGY REPORTS 36 ( 3 ) 1251 - 1257 2016年9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：SPANDIDOS PUBL LTD

Myofibroblasts of colorectal cancer (CRC) have been associated with histopathological factors such as lymph node metastasis, liver metastasis and local recurrence. However, few studies have assessed the association between these malignant potentials and the myofibroblast distribution in CRC. We aimed to evaluate the relationship between clinical factors and myofibroblast distribution around CRC invasive lesions. The study included 121 cases of pT3 CRC that were diagnosed at stage II or III. Myofibroblast density of the following three histological layers was measured: the submucosa (SM), muscularis propria (MP) and subserosa (SS). We analyzed the relationship between the clinicopathological factors and myofibroblast density by studying the histopathological features of the three layers. The myofibroblast density of the MP layer was significantly higher in the groups with high-frequency lymphatic and venous invasion than the groups with low-frequency lymphatic (P<0.001) and venous (P<0.01) invasion, respectively. In the positive lymph node metastasis group, the myofibroblast density at the MP layer was significantly higher than that in the negative lymph node metastasis group (P<0.001). The high myofibroblast density group at the MP layer was significantly associated with poor overall survival (P<0.003). Our study indicated that myofibroblasts are a type of cancer-associated fibroblasts and that the myofibroblast distribution contributes to the malignant potential of CRC. Furthermore, we demonstrated that myofibroblasts present at the MP layer play an important role in the malignant potential and poor prognosis of patients with CRC.

DOI： 10.3892/or.2016.4932

Assessments of histologic changes after peroral endoscopic myotomy. 査読

Sato H, Sagara S, Suzuki K, Terai S, Yahagi N

Gastrointestinal endoscopy 84 ( 2 ) 377 - 378 2016年8月

Management of gastric and duodenal neuroendocrine tumors 査読

Yuichi Sato, Satoru Hashimoto, Ken-ichi Mizuno, Manabu Takeuchi, Shuji Terai

WORLD JOURNAL OF GASTROENTEROLOGY 22 ( 30 ) 6817 - 6828 2016年8月

記述言語：英語出版者・発行元：BAISHIDENG PUBLISHING GROUP INC

Gastrointestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, like all NETs. However, the incidence of GI-NETS has been increasing in recent years. Gastric NETs (G-NETs) and duodenal NETs (D-NETs) are the common types of upper GI-NETs based on tumor location. G-NETs are classified into three distinct subgroups: type I, II and III. Type I G-NETs, which are the most common subtype (70%-80% of all G-NETs), are associated with chronic atrophic gastritis, including autoimmune gastritis and Helicobacter pylori associated atrophic gastritis. Type II G-NETs (5%-6%) are associated with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome (MEN1-ZES). Both type I and II G-NETs are related to hypergastrinemia, are small in size, occur in multiple numbers, and are generally benign. In contrast, type III G-NETs (10%-15%) are not associated with hypergastrinemia, are large-sized single tumors, and are usually malignant. Therefore, surgical resection and chemotherapy are generally necessary for type III G-NETs, while endoscopic resection and follow-up, which are acceptable for the treatment of most type I and II G-NETs, are only acceptable for small and well differentiated type III G-NETs. D-NETs include gastrinomas (50%-60%), somatostatin-producing tumors (15%), nonfunctional serotonin-containing tumors (20%), poorly differentiated neuroendocrine carcinomas (< 3%), and gangliocytic paragangliomas (< 2%). Most D-NETs are located in the first or second part of the duodenum, with 20% occurring in the periampullary region. Therapy for D-NETs is based on tumor size, location, histological grade, stage, and tumor type. While endoscopic resection may be considered for small nonfunctional D-NETs (G1) located in the higher papilla region, surgical resection is necessary for most other D-NETs. However, there is no consensus regarding the ideal treatment of D-NETs.

DOI： 10.3748/wjg.v22.i30.6817

Effects of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery 査読

Yuji Kobayashi, Kenya Kamimura, Hiroyuki Abe, Takeshi Yokoo, Kohei Ogawa, Yoko Shinagawa-Kobayashi, Ryo Goto, Ryosuke Inoue, Masato Ohtsuka, Hiromi Miura, Tsutomu Kanefuji, Takeshi Suda, Masanori Tsuchida, Yutaka Aoyagi, Guisheng Zhang, Dexi Liu, Shuji Terai

MOLECULAR THERAPY-NUCLEIC ACIDS 5 ( 8 ) e359 2016年8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：CELL PRESS

Hydrodynamic gene delivery is a common method for gene transfer to the liver of small animals, and its clinical applicability in large animals has been demonstrated. Previous studies focused on functional analyses of therapeutic genes in animals with normal livers and little, however, is known regarding its effectiveness and safety in animals with liver fibrosis. Therefore, this study aimed to examine the effects of liver fibrosis on hydrodynamic gene delivery efficiency using a rat liver fibrosis model. We demonstrated for the first time, using pCMV-Luc plasmid, that this procedure is safe and that the amount of fibrotic tissue in the liver decreases gene delivery efficiency, resulting in decrease in luciferase activity depending on the volume of fibrotic tissue in the liver and the number of hepatocytes that are immunohistochemically stained positive for transgene product. We further demonstrate that antifibrotic gene therapy with matrix metalloproteinase-13 gene reduces liver fibrosis and improves efficiency of hydrodynamic gene delivery. These results demonstrate the negative effects of fibrotic tissue on hydrodynamic gene delivery and its recovery by appropriate antifibrotic therapy.

DOI： 10.1038/mtna.2016.63