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Expressions of sonic hedgehog, patched, smoothened and Gli-1 in human intestinal stromal tumors and their correlation with prognosis

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World Journal of Gastroenterology 2006年第35期12卷 5687-5691页

作者： Ayumi Yoshizaki Toshiyuki Nakayama shinji naito Chun-Yang Wen Ichiro Sekine Department of Molecular Pathology Nagasaki University Graduate School of Biomedical Sciences 1-12-4 Sakamoto Nagasaki 852-8523 Japan Division of Pathology Research LaboratoryNational Ureshino Medical Center Saga Japan Department of Digestive Disease Affiliated Hospital of Beihua University Jilin 132011 Jilin Province China

AIM: To investigate the role that the hedgehog (Hh) signaling pathway, which includes sonic hedgehog (Shh), Patched (Ptc), Smoothened (Smo) and Gli-1, plays in hu- man gastrointestinal stromal tumors (GISTs). METHODS: Surgically resected specimens from pa- tients with GISTs, leiomyomas and schwannomas were examined by immunohistochemical staining for aberrant expression of hedgehog signaling components, Shh, Ptc, Smo and Gli-1, respectively. RESULTS: In GISTs, 58.1% (18 of 31), 77.4% (24 of 31), 80.6% (25 of 31) and 58.1% (18 of 31) of the specimens stained positive for Shh, Ptc, Smo and Gli-1, respectively. In leiomyomas, 92.3% (12 of 13), 92.3% (12 of 13), 69.2% (9 of 13) and 92.3% (12 of 13) stained positive for Shh, Ptc, Smo and Gli-1, respectively. In schwannomas, 83.3% (5 of 6), 83.3% (5 of 6), 83.3% (5 of 6) and 100% (6 of 6) stained positive for Shh, Ptc, Smo and Gli-1, respectively. Immunohistochemistry revealed that the expressions of Shh and Gli-1 were sig- nificantly higher in leiomyomas than in GISTs (P < 0.05, respectively). Shh expression strongly correlated with the grade of tumor risk category and with tumor size (P < 0.05, respectively). However, the expressions of Ptc and Smo did not correlate with histopathological differentiation. CONCLUSION: These results suggest that the Hh sig- naling pathway may play an important role in myogenic differentiation and the malignant potential of human in-testinal stromal tumors.

关键词： Gastrointestinal stromal tumor Leiomyoma Schwannoma Hedgehog Immunohistochemistry

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Expression of vascular endothelial growth factor and its receptors VEGFR-1 and 2 in gastrointestinal stromal tumors,leiomyomas and schwannomas

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World Journal of Gastroenterology 2006年第38期12卷 6182-6187页

作者： Toshiyuki Nakayama Yang Cheul Cho Yuka Mine Ayumi Yoshizaki shinji naito Chun Yang Wen Ichiro Sekine Department of Tumor and Diagnostic Pathology Nagasaki University Graduate School of Biomedical Sciences 1-12-4 Sakamoto Nagasaki 852-8523 Japan Division of Pathology Research Laboratory National Ureshino Medical Center Saga 843-0301 Japan Department of Digestive Disease Affiliated hospital of Beihua University Jilin 132011 Jilin Province China

AIM： To investigate the role of vascular endothelial growth factor （VEGF/and its receptors VEGFR-1 and 2 in the growth and differentiation of gastrointestinal strornal tumors （GISTs）. METHODS： Thirty-three GISTs, 15 leiomyomas and 6 schwannomas were examined by immunohistochemistry in this study. RESULTS： VEGF protein was expressed in the cytoplasm of tumor cells, and VEGFRol and 2 were expressed both in the cytoplasm and on the membrane of all tumors. Irnrnunohistochernical staining revealed that 26 GISTs （78.8%）, 9 leiornyornas （60.0%） and 3 schwannornas （50.0%/were positive for VEGF; 24 GISTs （72.7%/, 12 leiornyornas （80.0%） and 4 schwannornas （66.7%） were positive for VEGFR-1; 30 GISTs （90.9%/, 5 leiornyornas （33.3%/and 4 schwannornas （66.7%） were positive for VEGFR-2. VEGFR-2 expression was statistically different between GISTs and leiomyomas （P 〈 0.0001）. However, there was no correlation between the expression of VEGF pathway componenets and the clinical risk categories. CONCLUSION： Our results suggest that the VEGF pathway may play an important role in the differentiation of GISTs, leiomyomas and schwannomas.

关键词： Gastrointestinal stromal tumor Leiomyoma Schwannoma Vascular endothelial growth factor Vascular endothelial growth factor receptors

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Expression of Ets-1 proto-oncoprotein in gastrointestinal stromal tumors, leiomyomas and schwannomas

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World Journal of Gastroenterology 2006年第11期12卷 1743-1746页

作者： Toshiyuki Nakayama Ayumi Yoshizaki shinji naito Chun Yang Wen Gabit Alipov Yuichi Yakata Ichiro Sekine Department of Molecular Pathology Nagasaki University Graduate School of Biomedical Sciences1-12-4 Sakamoto Nagasaki 852-8523 Japan Division of Pathology Research Laboratory National Ureshino Medical Center Saga 843-0301 Japan Department of Digestive Disease Nanjing Drum Tower Hospital Medical School of Nanjing UniversityNanjing 210008 Jiangsu Province China Tissue and Histopathology Section Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Sciences Nagasaki 852-8523 Japan

AIM： Gastrointestinal stromal tumors （GISTs） are rare. GISTs differ from other mesenchymal tumors of the gastrointestinal tract （e.g. leiornyomas and schwannomas）. The purpose of this study was to investigate the role of Ets-1 in the growth and differentiation of GISTs. METHODS： Twenty-eight GISTs, nine leiomyomas and six schwannomas were examined by immunohistochemical staining method for Ets-1 in this study. Specimens were selected from surgical pathology archival tissues at Nagasaki University Hospital. RESULTS： Ets-1 protein was expressed in the cytoplasm of cells in all of these tumors. Immunohistochemical staining revealed that 27 GISTs （96.4%）, six leiomyomas （66.7%）, and five schwannomas （83.3%） were positive for Ets-1. Ets-1 expression was statistically different between GISTs and leiomyomas （P〈0.005）. However, there was no correlation between Ets-1 expression and clinical risk categories. CONCLUSION： Ets-1 plays an important role in the growth and differentiation of GISTs, leiomyomas and schwannomas.

关键词： Ets-1 GISTs Leiomyoma Schwannoma Immunohistochemistry Risk category

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Expression of Angiopoietin-1, 2 and 4 and Tie-1 and 2 in gastrointestinal stromal tumor, leiomyoma and schwannoma

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World Journal of Gastroenterology 2007年第33期13卷 4473-4479页

作者： Toshiyuki Nakayama Maki Inaba shinji naito Yumi Mihara Shiro Miura Mitsuru Taba Ayumi Yoshizaki Chun-Yang Wen Ichiro Sekine Department of Tumor and Diagnostic Pathology Nagasaki University Graduate School of Biomedical Sciences 1-12-4 Sakamoto Nagasaki 852-8523 Japan Division of Pathology Research Laboratory National Ureshino Medical Center Saga 843-0301 Japan Department of Digestive Disease Affiliated hospital of Beihua University Jilin 132011 Jilin Province China

AIM: To investigate the role of angiopoietin (Ang) -1, -2 and -4 and its receptors, Tie-1 and -2, in the growth and differentiation of gastrointestinal stromal tumors (GISTs).METHODS: Thirty GISTs, seventeen leiomyomas and six schwannomas were examined by immunohistochemistry in this ***: Ang-1, -2 and -4 proteins were expressed in the cytoplasm of tumor cells, and Tie-1 and -2 were expressed both in the cytoplasm and on the membrane of all tumors. Immunohistochemical staining revealed that 66.7% of GISTs (20 of 30), 76.5% of leiomyomas (13 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-1. 83.3% of GISTs (25 of 30), 82.4% of leiomyomas (14 of 17) and 100% of schwannomas (6 of 6) were positive for Ang-2. 36.7% of GISTs (11 of 30), 58.8% of leiomyomas (10 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-4. 60.0% of GISTs (18 of 30), 82.4% of leiomyomas and 100% of schwannomas (6 of 6) were positive for Tie-1. 10.0% of GISTs (3 of 30), 94.1% of leiomyomas (16 of 17) and 33.3% of schwannomas (2 of 6) were positive for Tie-2. Tie-2 expression was statistically different between GISTs and leiomyomas (P < 0.001). However, there was no correlation between expression of angiopoietin pathway components and clinical risk ***: Our results suggest that the angiopoietin pathway plays an important role in the differentiation of GISTs, leiomyomas and schwannomas.

关键词： Gastrointestinal stromal tumors Leiomyomas Schwannomas

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Prior Somatic Stimulation Improves Performance of Acquired Motor Skill by Facilitating Functional Connectivity in Cortico-Subcortical Motor Circuits

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Journal of Behavioral and Brain Science 2012年第3期2卷 343-356页

作者： Shintaro Uehara Isao Nambu Michikazu Matsumura shinji Kakei Eiichi naito Brain ICT Laboratory Advanced ICT Research Institute National Institute of Information and Communications Technology Kyoto Japan Center for Information and Neural Networks (CiNet) National Institute of Information and Communications Technology Kyoto Japan Graduate School of Human and Environmental Studies Kyoto University Kyoto Japan Tokyo Metropolitan Institute for Neuroscience Tokyo Japan

Once people have a well-trained motor skill, their performance becomes stabilized and achieving substantial improvement is difficult. Recently, we have shown that even a plateaued hand motor skill can be upgraded with short-period electrical stimulation to the hand prior to the task. Here, we identify the neuronal substrates underlying the improvement of the plateaued skill by examining the enhanced functional connectivity in the sensory-motor regions that are associated with motor learning. We measured brain activity using functional magnetic resonance imaging and performed psychophysiological interaction analysis. We recruited seven right-handed very-well trained participants, whose motor performance of continuously rotating two balls with their right hands became stabilized at higher performance levels. We prepared two experiments, in each of which they repeated an experimental run 16 times. In each run, they performed this cyclic rotation as many times as possible in 16 s. In the thenar-stimulation experiment, we applied 60-s stimulation to the thenar muscle before each of the 5th - 12th runs, and the others were preceded by ineffective sham stimulation. In the control experiment, the sham was always provided. Thenar stimulation enabled the participants to perform the movements at higher cycles. In association with this performance improvement, we found enhanced activity couplings between the primary motor cortex and the sensorimotor territory of the putamen and between the cerebellum and the primary sensorimotor cortices, without any quantitative activity increase. Neither behavioral change nor these increased activity couplings were observed in the ***, in contrast to the stable neuronal states in the cortico-subcortical motor circuits when the well-learned task is repeated at the later stages of motor skill learning, plastic changes in the motor circuits seem to be required when the plateaued skill is upgraded, and the stimulation may entail a state

关键词： Cortico-Subcortical Motor Circuit Primary Motor Cortex Basal Ganglia Cerebellum Motor Skill Learning Somatic Stimulation Neuronal Plasticity Functional Magnetic Resonance Imaging

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Protocol for laparoscopic cholecystectomy: Is it rocket science?

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World Journal of Gastroenterology 2016年第47期22卷 10287-10303页

作者： Tomohide Hori Fumitaka Oike Hiroaki Furuyama Takafumi Machimoto Yoshio Kadokawa Toshiyuki Hata Shigeru Kato Daiki Yasukawa Yuki Aisu Maho Sasaki Yusuke Kimura Yuichiro Takamatsu Masato naito Masaya Nakauchi Takahiro Tanaka Daigo Gunji Kiyokuni Nakamura Kiyoko Sato Masahiro Mizuno Taku Iida Shintaro Yagi shinji Uemoto Tsunehiro Yoshimura Department of Gastrointestinal and General Surgery Tenriyorodusoudanjyo Hospital Department of Gastrointestinal Surgery Mitsubishi Kyoto Hospital Department of Anesthesiology Mitsubishi Kyoto Hospital Department of Gastroenterology and Hepatology Mitsubishi Kyoto Hospital Department of Hepatobiliary Pancreatic Surgery Kyoto University Hospital

Laparoscopic cholecystectomy(LC) does not require advanced techniques, and its performance has therefore rapidly spread worldwide. However, the rate of biliary injuries has not decreased. The concept of the critical view of safety(CVS) was first documented two decades ago. Unexpected injuries are principally due to misidentification of human factors. The surgeon's assumption is a major cause of misidentification, and a high level of experience alone is not sufficient for successful LC. We herein describe tips and pitfalls of LC in detail and discuss various technical ***, based on a review of important papers and our own experience, we summarize the following mandatory protocol for safe LC:(1) consideration that a high level of experience alone is not enough;(2) recognition of the plateau involving the common hepatic duct and hepatic hilum;(3) blunt dissection until CVS exposure;(4) Calot's triangle clearance in the overhead view;(5) Calot's triangle clearance in the view from underneath;(6) dissection of the posterior right side of Calot's triangle;(7) removal of the gallbladder body; and(8) positive CVS exposure. We believe that adherence to this protocol will ensure successful and beneficial LC worldwide, even in patients with inflammatory changes and rare anatomies.

关键词： Laparoscopic cholecystectomy Gallbladder Critical view of safety biliary injury Protocol

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IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions

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World Journal of Gastroenterology 2014年第29期20卷 10050-10061页

作者： Takafumi naito Katsuhiko Nosho Miki Ito Hisayoshi Igarashi Kei Mitsuhashi shinji Yoshii Hironori Aoki Masafumi Nomura Yasutaka Sukawa Eiichiro Yamamoto Yasushi Adachi Hiroaki Takahashi Masao Hosokawa Masahiro Fujita Toshinao Takenouchi Reo Maruyama Hiromu Suzuki Yoshifumi Baba Kohzoh Imai Hiroyuki Yamamoto Shuji Ogino Yasuhisa Shinomura Department of Gastroenterology Rheumatology and Clinical ImmunologySapporo Medical University School of Medicine Department of Gastroenterology Keiyukai Sapporo Hospital Center for Gastroenterology Teine-Keijinkai Hospital Department of Medical Oncolo-gy Dana-Farber Cancer InstituteBostonMA 02115United States Department of Surgery Keiyukai SapporoHospital Department of Pathology Keiyukai Sapporo Hospital Department of Molecular Biology Sapporo Medical University School of Medicine Department of Gastroenterological Surgery Graduate School of Medical ScienceKumamoto University Division of Cancer Research The Institute of Medical ScienceThe University of Tokyo Division of Gastroenterology and Hepatology Department of Internal MedicineSt.Marianna University School of Medicine

AIM: To investigate insulin-like growth factor 2 (IGF2) differentially methylated region (DMR)0 hypomethylation in relation to clinicopathological and molecular features in colorectal serrated lesions.

关键词： BRAF Colon polyp Colorectal neoplasia Colorectum Genome Insulin-like growth factor Long interspersed nucleotide element-1 Microsatellite instability Serrated pathway

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