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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

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

Enlarged accessory spleen presenting stomach submucosal tumor

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World Journal of Gastroenterology 2007年第11期13卷 1752-1754页

作者： Shunzen Chin Hajime Isomoto Yohei Mizuta chun-yang wen Saburo Shikuwa Shigeru Kohno Second Department of Internal Medicine Nagasaki University School of Medicine 1-7-1 Sakamoto Nagasaki Japan Beihua University 3999 Huashan Road Jilin City

A 62-year-old man presented with upper abdominal discomfort underwent upper gastrointestinal endoscopy. Gastroscopy and endoscopic ultrasonography revealed a submucosal tumor (SMT) with homogenous echogenicity originated from extragastric organs. An abdominal contrast-enhanced computed tomography (CT) showed that the well-marginated ovoid mass, approximately 6 cm in diameter, enhanced homogenously to a similar degree as splenic parenchyma. 99mTechnetium sulfur colloid scintigraphy revealed the splenic nature of the mass. A diagnosis of accessory spleen mimicking gastric SMT was made. Subsequent follow-up was uneventful without performing splenectomy.

关键词： Accessory spleen ^99mTechnetium sulfur colloid scintigraphy Computed tomography Gastric submucosal tumor

Expression of Interleukin-11 and Interleukin-11 receptor a in human colorectal adenocarcinoma; Immunohistochemical analyses and correlation with clinicopathological factors

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World Journal of Gastroenterology 2006年第2期12卷 317-321页

作者： Kazuyuki Yamazumi Toshiyuki Nakayama Takafumi Kusaba chun yang wen Ayumi Yoshizaki Yuichi Yakata Takeshi Nagayasu Ichiro Sekine Department of Molecular Pathology Nagasaki University Graduate School of Biomedical Sciences 1-12-4 Sakamoto Nagasaki 852-8523 Japan Division of Surgical Oncology Department of Translational Medical Sciences Nagasaki University Graduate School of Biomedical Sciences 1-12-4 Sakamoto Nagasaki 852-8523 Japan Department of Digestive Disease Nanjing Drum Tower Hospital Medical School of Nanjing University Nanjing 210008 Jiangsu Province China

AIM： There is strong evidence that interleukin-11 （IL-11） is involved in the regulation of tumor progression, cellular growth and differentiation. Recently, interleukin-11 receptor （IL-11R） has been detected on some cancer cells. In this study, we investigated the expression of IL-11 and IL-11R in colorectal adenocarcinoma. METHODS： To elucidate the involvement of IL-11 and IL-11Rα in human intestinal adenocarcinomas, we examined 115 cases of surgically resected human colonic adenocarcinoma and 11 cases of adenoma by immunohistochemistry and Western blotting. RESULTS： Among 115 cases of adenocarcinoma, 100 cases （87.0%） showed positive staining in the cytoplasm of carcinoma cells for the IL-11, and 87 cases （75.6%） were positive for the IL-11Ra. Six cases （54.5%） and four cases （36.4%） of 11 adenomas were positive for IL-11 and IL-11Ra, respectively. The expression of IL- 11Ra correlated with the histological differentiation （P=0.033503）, the depth of tumor invasion （P= 0.006395）, Dukes＇ classification （P= 0.015648） and lymphatic invasion （P= 0.003865）. However, the expression of IL- 11Rα was not correlated with the venous invasion and the presence of lymph node metastasis. The expression of IL-11 was not correlated with any clinicopathological factors. In Western blot analysis, two human colorectal carcinoma cell lines and four tissues of surgically resected human carcinoma expressed both IL-11 and IL-11Rα proteins. CONCLUSION： IL-11 and IL-11Rα are highly expressed in human colorectal adenocarcinoma and the IL-11Rα expression is correlated with clinicopathological factors, These findings suggest that the expression of IL-11Rα is an important factor for the invasion of human colorectal adenocarcinoma.

关键词： IL-11, IL-11 receptor α Colorectal cancer

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

Antibody to eosinophil cationic protein suppresses dextran sulfate sodium-induced colitis in rats

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World Journal of Gastroenterology 2005年第29期11卷 4505-4510页

作者： Kazuko Shichijo Kazuya Makiyama chun-yang wen Mutsumi Matsuu Toshiyuki Nakayama Masahiro Nakashima Makoto Ihara Ichiro Sekine Department of Molecular Pathology Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Sciences 1-12-4 Sakamoto Nagasaki 852-8523 Japan Department of Endoscopy Nagasaki University School of Medicine Hospital and Clinics 1-12-4 Sakamoto Nagasaki 852-8523 Japan Department of Digestive Disease the Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 Jiangsu Province China Tissue and Histopathology Section Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Sciences 1-12-4 Sakamoto Nagasaki 852-8523 Japan Radiation Biophysics Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Sciences 1-12-4 Sakamoto Nagasaki 852-8523 Japan

AIM： To produce an antibody against rat eosinophil cationic protein （ECP） and to examine the effects of the antibody in rats with dextran sulfate sodium （DSS）-induced colitis. METHODS： An antibody was raised against rat ECP. Rats were treated with 3% DSS in drinking water for 7 d and received the antibody or normal serum. The colons were examined histologically and correlated with clinical symptoms. Immunohistochemistry and Western blot analysis were estimated as a grade of inflammation. RESULTS： The ECP antibody stained the activated eosinophils around the injured crypts in the colonic mucosa. Antibody treatment reduced the severity of colonic ulceration and acute clinical symptoms （diarrhea and/or bloodstained stool）. Body weight gain was significantly greater and the colon length was significantly longer in anti-ECPtreated rats than in normal serum-treated rats. Expression of ECP in activated eosinophils was associated with the presence of erosions and inflammation. The number of Ki-67-positive cells in the regenerated surface epithelium increased in anti-ECP-treated rats compared with normal serum-treated rats. Western blot analysis revealed reduced expression of macrophage migration inhibitory factor （MIF） in anti-ECP-treated rats. CONCLUSION： Our results indicate that treatment with ECP antibody, improved DSS-induced colitis in rats, possibly by increasing the regenerative activity of the colonic epithelium and downregulation of the immune response, and suggest that anti-ECP may promote intestinal wound healing in patients with ulcerative colitis （UC）.

关键词： Ulcerative colitis Eosinophil cationic protein Dextran sulfate sodium

Crohn's disease in Japanese is associated with a SNP-haplotype of N-acetyltransferase 2 gene

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World Journal of Gastroenterology 2005年第31期11卷 4833-4837页

作者： Haruhisa Machida Kazuhiro Tsukamoto chun-yang wen Saburou Shikuwa Hajime Isomoto Yohei Mizuta Fuminao Takeshima Kunihiko Murase Naomichi Matsumoto Ikuo Murata Shigeru Kohno Chen-yang wen Second Department of Internal Medicine Nagasaki University School of Medicine 1-7-1 Sakamoto Nagasaki 852-8501 Japan Department of Pharmaco-therapeutics Nagasaki University Graduate School of Biomedical Sciences 1-14 Bunkyo-machi Nagasaki 852-8521 Japan Department of Molecular Pathology Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Sciences 1-12-4 Sakamoto Nagasaki 852-8523 Japan Department of DigestiveDisease The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 Jiangsu Province China Department of Gastroenterology National Hospital Organization Nagasaki Medical Center 2-1001-1 KubaraOmura 856-8562 Japan Department of Human Genetics Nagasaki University Graduate School of Biomedical Sciences 1-12-4 SakamotoNagasaki 852-8523 Japan

AIM： To investigate the frequency and distribution of /V-acetyltransferase 2 （NAT2） and uridine 5＇-diphosphate （UDP）-glucuronosyltransferase 1A7 （UGT1A7） genes in patients with ulcerative colitis （UC） and Crohn＇s disease （CD）. METHODS： Frequencies and distributions of IVAT2 and UGT1A7SNPs as well as their haplotypes were investigated in 95 patients with UC, 60 patients with CD, and 200 gender-matched, unrelated, healthy, control volunteers by PCR-restriction fragment length polymorphism （RFLP）, PCR-denaturing high-performance liquid chromatography （DHPLC）, and direct DNA sequencing. RESULTS： Multiple logistic regression analysis revealed that the frequency of haplotype, NAT2＊7B, significantly increased in CD patients, compared to that in controls （P= 0.0130, OR = 2.802, 95%CI = 1.243-6.316）. However, there was no association between NAT2 haplotypes and UC, or between any UGT1A7haplotypes and inflammatory bowel disease （IBD）. CONCLUSION： It is likely that the NAT2 gene is one ofthe determinants for CD in Japanese. Alternatively, a new CD determinant may exist in the 8p22 region, where NAT2 is located.

关键词： Crohn's disease N-acetyltransferase 2 gene Polymorphism Disease-susceptible gene Association study Japanese population

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

A Design Method of Business Application Framework Based on Software Patterns

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Wuhan University Journal of Natural Sciences 2001年第Z1期6卷 204-208页

作者： He Ke\|qing 1, yang chun wen 1, Ying Shi 2 1. School of Computer Science, Wuhan University, Wuhan 430072, China 2. State Key Laboratory of Software Engineering, Wuhan University, Wuhan 430072, China School of Computer Science Wuhan University Wuhan 430072 China

This paper discusses design and implementation method of Business Application Framework based on software patterns, and then presents MVC pattern of architecture and the method of dynamical update promulgation for Business Application Framework. We discuss adaptation of Abstract Factory for the kernel functionality of Business Application Framework, such as data creation, manipulation, composition, etc. It also presents class model and its class structure of Abstract Factory pattern. Finally, we briefly discuss the update, modification, and reconstruction method of Business Application Framework.

关键词： object oriented MVC pattern Abstract Factory pattern software framework UML role model