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Expression of pituitary tumor transforming gene in human gastric carcinoma

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World Journal of Gastroenterology 2004年第4期10卷 481-483页

作者： Chun-YangWen ToshiyukiNakayama MutsumiMatsuu KazukoShichijo IchiroSekine Ai-PingWang masahiro Nakashima Yi-Tao Ding masahiro ito Hiromi Ishibashi Department of Molecular Pathology Atomic Bomb Disease InstituteNagasaki University Graduate School of Biomedical Sciences1-12-4 SakamotoNagasaki 852-8523Japan Department of Digestive Disease Nanjing Drum Tower HospitalMedical School of Nanjing UniversityNanjing 210008Jiangsu ProvinceChina Tissue and Histopathology Section Division of Scientific Data Registry Atomic Bomb Disease InstituteNagasaki University Graduate School of Biomedical Sciences1-12-4 SakamotoNagasaki 852-8523Japan Department of Hepatobiliary Surgery Nanjing Drum Tower HospitalMedical School of Nanjing UniversityNanjing 210008Jiangsu ProvinceChina Department of Pathology National Nagasaki Medical Center2-1001-1 KubaraOmuraNagasaki 856-8562Japan Clinical Research Center National Nagasaki Medical Center2-1001-1 KubaraOmuraNagasaki 856-8562Japan

AIM:Pituitary tumor transforming gene (PTTG1) is overexpressed in a variety of tumors, including carcinomas of the lung, breast, colon, as well as in leukemia, lymphoma and pituitary ***,there is little information on its expression in gastric carcinoma. We sought to investigate the expression of PTTG1 in gastric carcinoma and to explore the relationship between its expression and clinicopathological ***:We studied 75 primary human gastric adenocarcinomas, including 17 mucosal carcinomas, 21 submucosal infiltrative carcinomas, 12 carcinomas invading proprial muscle layers, 6 carcinomas reaching the subserosa,and 19 carcinomas penetrating the serosal *** analysis was performed using paraffinembedded sections of gastric ***: PTTG1 was expressed heterogeneously in carcinomas. Positive PTTG1 staining was observed in 65.3% of the carcinomas (49 of 75). Its expression did not correlate significantly with either the histological type or the depth of infiltration of the gastric ***,a statistical analysis showed significant differences between the primary adenocarcinomas and the associated metastatic lymph ***: The results of this study demonstrate that PTTG1 expression is enhanced in metastatic lymph nodes in comparison to that in primary carcinomas. We suggest that PTTG1 may contribute to lymph node metastases in gastric carcinoma.

关键词：垂体肿瘤转化基因胃癌基因表达免疫组织化学肿瘤侵袭肿瘤病理学

Expression of β-catenin in hepatocellular carcinoma

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World Journal of Gastroenterology 2005年第16期11卷 2398-2401页

作者： Liem Thanh Tien masahiro ito Mikiko Nakao Daisuke Niino Meirmanov Serik masahiro Nakashima Chun-Yang Wen Hiroshi Yatsuhashi Hiromi Ishibashi Department of Pathology National Nagasaki Medical Center 2-1001-1 KubaraOmuraNagasaki 856-8562Japan Department of Molecular Pathology Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Science1-12-4 SakamotoNagasaki 852-8523Japan Tissue and Histopathology Section Division of Scientific Data Registry Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Science1-12-4 SakamotoNagasaki 852-8523Japan Department of Digestive Disease Nanjing Drum Tower Hospital Medical School of Nanjing UniversityNanjing 210008Jiangsu ProvinceChina Clinical Research Center National Nagasaki Medical Center 2-1001-1 KubaraOmuraNagasaki 856-8562Japan

AIM: The beta-catenin has been recognized as a critical member of the Wnt signaling pathway and plays an important role in the generation/differentiation of many tissues. Inappropriate activation of this pathway has been implicated in carcinogenesis. The mechanism underlying the development as well as its prognosis of hepatocellular carcinoma (HCC) has remained unclear. The purpose of this study is to analyze the expression of beta-catenin in HCC in relation to histological grades and viral hepatitis backgrounds. METHODS: Thirty-two sections were selected at random from autopsy and surgical cases of HCC. Immuohistologically, the location and positivity of beta-catenin expression in HCC was examined. RESULTS: Normal hepatocytes did not express beta-catenin. In 78% of HCC beta-catenin was expressed at the membrane of the cells, with or without cytoplasmic and/or nuclear expression. The tumor cells with well-and moderately-differentiated grades expressed frequently at the membrane and cytoplasm compared with poorly-differentiated type. Nuclear expression of beta-catenin was prone to occur in the tumor cells of poorly-differentiated grade. There were 15% of hepatitis C virus (HCV) backgrounds with nuclear expression. In contrast, there was 38% with nuclear expression in hepatitis B virus (HBV) backgrounds. In nonB-nonC hepatitis, no case expressed nuclear beta-catenin. CONCLUSION: The beta-catenin expression in HCC cells was heterogenous among types of hepatitis viral infection. Wnt signaling pathway might be deeply involved in less-differentiated HCC and HBV background. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.

关键词： Hepatocellular carcinoma beta-Catenin Immunohistochemistry

Production, purification and characterization of D-aspartate oxidase from the fungus <i>Trichoderma harzianum</i>SKW-36

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Advances in Bioscience and Biotechnology 2012年第1期3卷 7-13页

作者： Shigekazu Yano Hiroyuki Ozaki Shinji Matsuo masahiro ito Mamoru Wakayama Department of Biotechnology Faculty of Life Sciences Ritsumeikan University Kusatsu Shiga Japan

Trichoderma harzianum Rifai SKW-36 produced two kinds of D-amino acid oxidizing enzymes. One enzyme was D-aspartate oxidase acting on acidic D-amino acids such as D-aspartate and D-glutamate and another one was D-amino acid oxidase acting on neutral D-amino acid such as D-phenylalanine and D-methionine. These enzymes in the cell-free extract were separated by DEAE-Toyopearl ion-exchange column chromatography. Casamino acids, peptone, and yeast extract as carbon and nitrogen sources were effective for the production of the enzymes. No D-amino acid tested induced the production of the enzymes. Casamino acid (0.33%) as carbon and nitrogen source gave a highest specific activity of D-aspartate oxidase among media tested. D-Aspartate oxidase, which was purified by four-step column chromatography in addition to ammonium sulfate precipitation, exhibited a subunit molecular mass of 40 kDa by SDS-PAGE analysis. D-Aspartate, D-glutamate and N-methyl-D- aspartate were oxidized as substrates with the specific activities of 7.80 U/mg, 4.90 U/mg, and 4.22 U/mg, respectively. D-Asparagine, D-glutamine, D-alanine, and D-valine were slightly oxidized. No other D- amino acids tested were inert. The enzyme exhibited relatively wide substrate specificity compared to D-aspartate oxidases reported so far. The pH and temperature optima were 7.5 - 8.0 and 35°C, respectively. The enzyme was stable at pH 6.0 - 9.0. About 75% of the enzyme activity was retained even after treating the enzyme at 50°C for 10 min. The enzyme activity was inhibited not by benzoate and tartrate, but 60% and 24% by fumarate and malonate, respectively.

关键词： D-Aspartate Oxidase Trichoderma harzianum Purification Characterization

mPGES-1 expression in non-cancerous liver tissue impacts on postoperative recurrence of HCC

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World Journal of Gastroenterology 2010年第38期16卷 4846-4853页

作者： Koichi Nonaka Hikaru Fujioka Yasushi Takii Seigo Abiru Kiyoshi Migita masahiro ito Takashi Kanematsu Hiromi Ishibashi Clinical Research Center and Department of Surgery National Hospital Organization Nagasaki Medical Center2-1001-1 Kubara Omura 856-8652Japan Department of Hepatology Nagasaki University Graduate School of Biomedical Sciences Department of Transplant and Digestive Surgery Nagasaki University Graduate School of Biomedical Sciences Clinical Research Center and Department of Surgery National Hospital Organization Nagasaki Medical Center2-1001-1 Kubara Omura 856-8652Japan

AIM:To investigate whether microsomal prostaglandin E synthase-1 (mPGES-1) expression in hepatocellular carcinoma (HCC) and in non-cancerous liver affects HCC prognosis after hepatectomy. METHODS: The relationship between patient clinical prof iles, tumor factors, surgical determinants, and mPGES-1 expression and the recurrence-free survival rate were examined in 64 patients who underwent curative hepatectomy between March 2003 and December 2006. RESULTS: The scores for mPGES-1 expression were higher in well differentiated and moderately differentiated HCC tissues than in poorly differentiated HCC tissues (well differentiated, 5.1 ± 2.7; moderately differentiated, 5.1 ± 1.7; poorly differentiated, 3.0 ± 1.8). In noncancerous liver tissues, the mPGES-1 levels were higher in injured liver tissues than in normal tissues. Cirrhotic livers had higher mPGES-1 levels than livers with chronic hepatitis (normal livers, 3.3 ± 0.7; chronic hepatitic livers, 5.4 ± 1.9; cirrhotic livers, 6.4 ± 1.6). A univariate analysis revealed that the recurrence-free survival rate was signif icantly lower in patients with vascular invasion,a higher mPGES-1 level in non-cancerous liver tissue,a larger tumor diameter (≥5 cm), and a lower serum albumin level (≤3.7 g/dL). The mPGES-1 expression in HCC tissues did not correlate well with postoperative recurrence. A multivariate analysis demonstrated that the presence of vascular invasion and higher mPGES-1 levels were statistically significant independent predictors for early postoperative recurrence of ***: Increased mPGES-1 expression in noncancerous liver tissues is closely associated with the early recurrence of HCC after curative resection.

关键词： Curative resection Hepatocellular carcinoma Microsomal prostaglandin E synthase-1 Noncancerous liver tissue Recurrence-free survival

Concurrent systemic AA amyloidosis can discriminate primary sclerosing cholangitis from IgG4-associated cholangitis

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World Journal of Gastroenterology 2012年第2期18卷 192-196页

作者： Takehiro Kato Atsumasa Komori Sung-Kwan Bae Kiyoshi Migita masahiro ito Yasuhide Motoyoshi Seigo Abiru Hiromi Ishibashi Clinical Research Center National Hospital Organization Nagasaki Medical CenterKubara 2-1001-1OmuraNagasaki 856-8562Japan Department of Hepatology Nagasaki University Graduate School of Biomedical SciencesKubara 2-1001-1OmuraNagasaki 856-8562Japan

Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis,except epidemic *** them,primary sclerosing cholangitis (PSC) might initiate amyloid A protein deposition in diverse tissues,giving rise to systemic amyloidosis,due to a progressive and unresolved inflammatory process,and its possible association with inflammatory bowel ***,only one such case has been reported in the literature to *** report a 69-year-old Japanese woman with cirrhosis who was diagnosed with PSC complicated with systemic AA amyloidosis,without any evidence of other inflammatory *** a result of cholestasis in conjunction with biliary strictures and increased serum IgG4,the presence of IgG4 + plasma cells was examined systemically,resulting in unexpected documentation of Congo-red-positive amyloid deposits,but not IgG4 + plasma cells,in the liver,stomach and salivary *** serum IgG4 is the hallmark of IgG4-related disease,including IgG4-associated cholangitis,but it has also been demonstrated in certain patients with *** A deposits in multiple organs associated with an indolent clinical course that progresses over many years might have a diagnostic value in discriminating PSC from IgG4-associated cholangitis.

关键词： Primary sclerosing cholangitis IgG4-associ-ated cholangitis AA amyloidosis

A novel animal model for in vivo study of liver cancer metastasis

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World Journal of Gastroenterology 2012年第29期18卷 3875-3882页

作者： Shinsuke Fujiwara Hikaru Fujioka Chise Tateno Ken Taniguchi masahiro ito Hiroshi Ohishi Rie Utoh Hiromi Ishibashi Takashi Kanematsu Katsutoshi Yoshizato Clinical Research Center National Hospital Organization Nagasaki Medical Center and Division of HepatologyNagasaki University Graduate School of Biomedical SciencesNagasaki 856-8652Japan Liver Research Laboratory PhoenixBio Co.LtdHiroshima 739-8511Japan Yoshizato Project CLUSTERHiroshima Prefectural Institute of Industrial Science and TechnologyHiroshima 739-8511Japan Division of Surgery Ⅱ Nagasaki University Graduate School of Biomedical SciencesNagasaki 856-8652Japan Liver Research Center Osaka City UniversityGraduate School of MedicineOsaka 532-0025Japan

AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer ***:Cell transplantation into mouse livers was conducted using alpha-fetoprotein(AFP)-producing hu-man gastric cancer cells(h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator(uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient(SCID) mouse line(uPA/SCID mice).Host mice were divided into two groups(A and B).Group A mice were transplanted with h-GCCs alone,and group B mice were transplanted with h-GCCs and h-hepatocytes *** replacement index(RI),which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section,was estimated by measuring h-AFP and h-albumin concentrations in sera,respectively,as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological ***:The h-GCCs successfully engrafted,repopulated,and colonized the livers of mice in group A(RI = 22.0% ± 2.6%).These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures,which is a characteristics feature of gastric *** serum h-AFP level reached 211.0 ± 142.2 g/mL(range,7.1-324.2 g/mL).In group B mice,the h-GCCs and h-hepatocytes independently engrafted,repopulated the host liver,and developed colonies(RI = 12.0% ± 6.8% and 66.0% ± 12.3%,respectively).h-GCC colonies also showed typical adenocarcinomatous glandular structures around the *** mice survived for the full 56 day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational *** mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in ***:A novel animal model of human liver cancer metastas

关键词： Urokinase-type plasminogen activator/severe combined immunodeficient mouse Mouse with humanized liver Liver cancer metastasis Alpha-fetoprotein-producing gastric cancer cells

Endoscopic identification of Peyer's patches of the terminal ileum in a patient with Crohn's disease

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World Journal of Gastroenterology 2004年第18期10卷 2767-2768页

作者： Hiroshi Ishimoto Hajime Isomoto Saburo Shikuwa Chun Yang Wen Takashi Suematu masahiro ito Ikuo Murata Hiromi Ishibashi Shigeru Kohno DepartmentofInternalMedicine NationalNagasakiMediealCenter2-1001KubaraOmuraNagasaki856-8562Japan GastrointestinalUnit.MassachusettsGenerulHospital DepartmentofMedicineHarvardMedicalSchoolJackson70655FruitStreetBostonMa02114USA DepartmentofMolecularPalhology AtomicBombDiseaseInstituteNagasakiUniversitySchoolofMedicine1-7-1SakarnotoNagasnki852-8501Japan ContralElectroscopeLaboratory NagasakiUniversitySchoolofMedicineNagasaki852-8501Japan DepartmentofPathology NationalNagasakiMedicalCenterj2-1001KubaraOmuraNagasaki856-8562Japan

We presented a 20-year-old patient with Crohn's disease (CD).Colonoscopy revealed longitudinal ulceration in the terminal ileum and rectal aphtoid *** treatment with mesalamine and total parenteral nutrition,repeat colonoscopy revealed a granular elevated area in the terminal ileum,which appeared as an irregular dome-like elevation with irregularly arranged villi on magnifying *** specimens taken from the region showed microgranulomas and lymphoid hyperplasia,Scanning electron microscopy revealed the presence of M cells,confirming that the area corresponded to Peyer's ***'s patches by magnifying endoscopy and electron microscopy may provide insights into the pathogenesis of CD.

关键词： Adult Biopsy Crohn Disease Endoscopes, Gastrointestinal Humans Ileum Intestinal Mucosa Male Microscopy, Electron, Scanning Peyer's Patches

Novel serine/threonine kinase 11 gene mutations in PeutzJeghers syndrome patients and endoscopic management

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World Journal of Gastrointestinal Endoscopy 2013年第3期5卷 102-110页

作者： Hiroyuki Yajima Hajime Isomoto Hiroaki Nishioka Naoyuki Yamaguchi Ken Ohnita Tatsuki Ichikawa Fuminao Takeshima Saburo Shikuwa masahiro ito Kazuhiko Nakao Kazuhiro Tsukamoto Shigeru Kohno Department of Molecular Microbiology and Immunology Nagasaki University Graduate School of Biomedical SciencesNagasaki University School of MedicineNagasaki 852-8501Japan Department of Gastroenterology and Hepatology Nagasaki University School of MedicineNagasaki 852-8501Japan Department of Pharmacotherapeutics Nagasaki University Graduate School of Biomedical SciencesNagasaki University School of MedicineNagasaki 852-8521Japan Department of Pathology National Nagasaki Medical CenterOmuraNagasaki 856-0835Japan

AIM:To explore mutations in serine/threonine kinase 11(STK11) gene in Peutz-Jeghers syndrome(PJS) with gastrointestinal(GI) hamartomatous ***:Six Japanese PJS patients in 3 families were enrolled in this *** of the cases had hamartomatous polyposis in the gastrointestinal tract,including the small intestine,along with mucocutaneous ***-band imaging(NBI)-magnification endoscopy was employed to detect microvascular and microsurface irregularities in the GI *** magnification findings could be classified into three groups(type A,type B,or type C).Endoscopic polypectomy was performed using double-balloon enteroscopy or *** DNA was extracted from a whole blood sample from each *** of the coding exons of STK11 gene,its boundary regions,and the promoter region containing the polymorphic regions were amplified by polymerase chain reaction,and direct sequencing was performed to assess the germline ***:NBI-magnification endoscopic observation could detect the abnormalities in microvessels and microsurface structures of GI ***,we found 5 cases of type A and one case without the examination for the gastric polyps,while there were 4 cases of type B and 2 case of type A for the colorectal ***-nine small-bowel and 115 colorectal polyps over 27 sessions for each were resected endoscopically without significant *** only delayed complication included the occurrence of bleeding in a case,and this was successfully managed with *** polyps contained no malignant *** on mutation analysis,all 3 cases in Family I exhibited the +658C>T nonsense mutation in exon 5,which resulted in the production of a truncated protein(Q220X).In Family II,a case had-252C>A and-193C>A in the promoter *** Family III,a case was found to have the +1062C>G(F342L) mutation in exon ***:We found two novel mutations of STK11 in association with ***

关键词： Peutz-Jeghers syndrome Serine/threonine kinase 11 Gastrointestinal hamartomatous polyps Double-balloon enteroscopy Narrow-band imaging

Development of ulcerative colitis during the course of rheumatoid arthritis: Association with selective IgA deficiency

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World Journal of Gastroenterology 2006年第32期12卷 5240-5243页

作者： Yuki Asada Hajime Isomoto Saburo Shikuwa Chun Yang Wen Eiichiro Fukuda Masaru Miyazato, Kenta Okamoto Takashi Nakamura Hitoshi Nishiyama Yohei Mizuta Kiyoshi Migita masahiro ito Shigeru Kohno Department of Internal Medicine National Nagasaki Medical Center 1001-1 Kubara Omura Japan Second Department of Internal Medicine Nagasaki University School of Medicine 1-7-1 Sakamoto Nagasaki Japan Department of Pathology National Nagasaki Medical Center 1001-1 Kubara Omttra Japan Department of Pathology National Nagasaki Medical Center 1001-1 Kubara Omura Japan

A 56-year-old woman with a 29-year history of rheumatoid arthritis （RA） was admitted to the hospital, complaining of high fever, abdominal pain and severe bloody diarrhea. Colonoscopy revealed friable and edematous mucosa with spontaneous bleeding, diffuse erosions and ulcers extending from the rectum to the distal transverse colon. Histopathological findings of rectal biopsies were compatible with ulcerative colitis （UC）. Being diagnosed as having severe active leftside UC, she was successfully treated with intravenous methylprednisolone followed by prednisolone and leukocytapheresis. Laboratory tests revealed low serum and saliva IgA levels, which might play a role in the development of UC. To our knowledge, this is the first case of UC occurring during the course of RA, accompanied by selective IgA deficiency.

关键词： Ulcerative colitis Rheumatoid arthritis Selective IgA deficiency