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World Journal of Gastrointestinal Surgery 2023年第8期15卷 1831-1837页

作者： Renma Ito Kazuhiro miwa Yutaka Matano Internal Medicine Komatsu Municipal HospitalKomatsu 923-0961Japan

BACKGROUND Although endoscopic submucosal dissection(ESD)is becoming more common for early gastric cancer,it requires more advanced techniques and a longer treatment duration than endoscopic mucosal *** ESD using a multifunctional snare(SOUTEN)has been reported to be effective for colorectal lesions,as it can reduce treatment *** suturing of post-ESD mucosal defects has been reported to reduce the incidence of ESD-related *** SUMMARY This study reports outpatient hybrid ESD for early gastric cancer using SOUTEN,followed by endoscopic suturing of post-ESD mucosal defects in an 86-year-old *** referral for ESD,a 10-mm flat,depressed lesion was found on the posterior wall of the gastric antrum,the depth of which was expected to be *** his history of delirium,we performed outpatient endoscopic *** procedure used was hybrid ESD using SOUTEN to reduce the duration of treatment and endoscopic suturing of post-ESD mucosal ESD defects to reduce *** procedure time was 62 min and the lesion was completely resected based on histopathological examination,with no reported postoperative *** This safe and useful procedure may be especially important for outpatient endoscopic treatment.

关键词： Outpatient treatment Hybrid endoscopic submucosal dissection Multifunctional snare Early gastric cancer Endoscopic suturing Case report

Role of cyclooxygenase-2 in the carcinogenesis of gastrointestinal tract cancers: A review and report of personal experience

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World Journal of Gastroenterology 2006年第9期12卷 1336-1345页

作者： Takashi Fujimura Tetsuo Ohta Katsunobu Oyama Tomoharu Miyashita Koichi miwa Gastroenterologic Surgery Department of Oncology Division of Cancer MedicineGraduate School of Medical ScienceKanazawa UniversityKanazawaJapan

Selective cyclooxygenase （COX）-2 inhibitors （coxibs） were developed as one of the anti-inflammatory drugs to avoid the various side effects of non-steroidal anti-inflammatory drugs （NSAIDs）. However, coxibs also have an ability to inhibit tumor development of various kinds the same way that NSAIDs do. Many experimental studies using cell lines and animal models demonstrated an ability to prevent tumor proliferation of COX-2 inhibitors. After performing a randomized study for polyp chemoprevention study in patients with familial adenomatous polyposis （FAP）, which showed that the treatment with celecoxib, one of the coxibs, significantly reduced the number of colorectal polyps in 2000, the U.S. Food and Drug Administration （FDA） immediately approved the clinical use of celecoxib for FAP patients. However, some coxibs were recently reported to increase the risk of serious cardiovascular events including heart attack and stroke. In this article we review a role of COX-2 in carcinogenesis of gastrointestinal tract, such as the esophagus, stomach and colorectum, and also analyze the prospect of coxibs for chemoprevention of gastrointestinal tract tumors.

关键词： Cyclooxygenase-2 (COX-2) Selective COX-2 inhibitors Esophageal cancer Gastric-cancer Colorectal cancer

Microstructure formation and grain refinement of Mg-based alloys by electromagnetic vibration technique

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Transactions of Nonferrous Metals Society of China 2010年第7期20卷 1192-1198页

作者： M.J.LI T.TAMURA N.OMURA K.miwa National Institute of Advanced Industrial Science and Technology Materials Research Institute for Sustainable DevelopmentNagoya 463-8560Japan

The microstructure formation and grains refinement of two Mg-based alloys,***31 and AZ91D,were reported using an electromagnetic vibration(EMV) *** two alloys were solidified at various vibration frequencies and the microstructures were *** average size of grains was quantitatively measured as a function of vibration frequencies. Moreover,the grain size distribution was outlined versus number fraction.A novel model was proposed to account for the microstructure formation and grain refinement when considering the significant difference of the electrical resistivity properties of the solid and the liquid during EMV processing in the semisolid *** remarkable difference originates uncoupled movement between the mobile solid and the sluggish liquid,which can activate melt *** microstructure evolution can be well explained when the fluid flow intensity versus vibration frequency is taken into ***,the influence of the static magnetic field on texture formation is also considered,which plays an important role at higher vibration frequencies.

关键词： magnesium alloy electromagnetic vibration microstructure formation grain refinement solidification

Gene expression profiling defined pathways correlated with fibroblast cell proliferation induced by Opisthorchis viverrini excretory /secretory product

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World Journal of Gastroenterology 2006年第22期12卷 3585-3592页

作者： Chanitra Thuwajit Peti Thuwajit Kazuhiko Uchida Daoyot Daorueang Sasithorn Kaewkes Sopit Wongkham Masanao miwa Department of Biochemistry Liver Fluke and Cholangiocarcinoma Research Center Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Institute of Basic Medical Science University of Tsukuba TsukubaIbaraki 305-8575Japan Department of Parasitology Liver Fluke and Cholangiocarcinoma Research Center Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand

AIM： To investigate the mechanism of fibroblast cell proliferation stimulated by the Opisthorchis viverrini excretory/secretory （ES） product. METHODS： NIH-3T3, mouse fibroblast cells were treated with O. viverrini ES product by non-contact co-cultured with the adult parasites. Total RNA from NIH-3T3 treated and untreated with O. viverrini was extracted, reverse transcribed and hybridized with the mouse 15K complementary DNA （cDNA） array. The result was analyzed by ArrayVision version 5 and GeneSpring version 5 softwares. After normalization, the ratios of gene expression of parasite treated to untreated NIH-3T3 cells of 2-and more-fold upregulated was defined as the differentially expressed genes. The expression levels of the signal transduction genes were validated by semiquantitative SYBR-based real-time RT-PCR. RESULTS： Among a total of 15 000 genes/ESTs, 239 genes with established cell proliferation-related function were 2 fold-and more-up-regulated by O. viverrini ES product compared to those in cells without exposure to the parasitic product. These genes were classified into groups including energy and metabolism, signal transduction, protein synthesis and translation, matrix and structural protein, transcription control, cell cycle and DNA replication. Moreover, the expressions of serinethreonine kinase receptor, receptor tyrosine kinase and collagen production-related genes were up-regulated by *** ES product, The expression level of signal transduction genes, pkC, pdgfra, jak 1, eps 8, tgfβ 1/4,strap and h ras measured by real-time RT-PCR confirmed their expression levels to those obtained from cDNA array. However, only the up-regulated expression of pkC,eps 8 and tgfβ3 1/4 which are the downstream signaling molecules of either epidermal growth factor （EGF） or transforming growth factor-β （TGF-β） showed statistical significance （P 〈 0.05）.CONCLUSION： O. viverrini ES product stimulates the significant changes of gene expression in several funct

关键词： Gene expression profile Opisthorchis viverrini Excretory/secretory product cDNA array Fibroblast Cell proliferation Signal transduction Cholangiocarcinogenesis

Amplification of D22S283 as a favorable prognostic indicator in liver fluke related cholangiocarcinoma

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World Journal of Gastroenterology 2006年第27期12卷 4338-4344页

作者： Jongkonnee Thanasai Temduang Limpaiboon Patcharee Jearanaikoon Vajarabhongsa Bhudhisawasdi Narong Khuntikeo Banchob Sripa Masanao miwa Graduate School Faculty of Medical TechnologyMahidol UniversityBangkok 10700Thailand Department of Clinical Chemistry Centre for Research and Development of Medical Diagnostic LaboratoriesFaculty of Associated Medical SciencesKhon Kaen UniversityKhon Kaen 40002Thailand Department of Surgery Liver Fluke and Cholangiocarcinoma Research CenterFaculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Pathology Liver Fluke and Cholangiocarcinoma Research CenterFaculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of Biochemistry and Molecular Oncology Institute of Basic Medical SciencesUniversity of TsukubaIbaraki 3058575Japan

AIM： To analyze the DNA copy number of target genes NF2, TIMP3, ST13, TOB2, BIK, and TP and the reference microsatellite markers D22S283, D22S423, and D22S274 mapped on 22q12-qter in liver fluke related cholangiocarcinoma （CCA） and define its correlation with clinical parameters. METHODS： Quantitative real time PCR （qPCR） was used for determining allelic imbalances in 65 liver fluke related CCA tissues. Statistical correlations between allelic imbalances and clinicopathological parameters, i.e. age, sex, tumor stage, histological type, blood vessel invasion, nerve invasion and lymphatic invasion were evaluated by means of the X^2 test. Cox regression analysis was used for determining patient＇s survival. RESULTS： Amplifications of the TP （22q13.33）, TOB2 （22q13.2-13.31）, D22S283 （22q12.3）, TIMP3 （22q12.3） and NF2 （22q12.2） were found in 35 （53.8%）, 28 （43.1%）, 27 （41.5%）, 24 （36.9%）, and 24 （36.9%）, respectively. Losses at the D22S423 （22q13.1-13.2）and BIK （22q13.31） were detected in 26 （40%） and 23 （35.4%）, respectively. Significant correlations were observed between lymphatic invasion and allelic losses of BIK （P = 0.025） and D22S283 （P = 0.041）. Univariate and multivariate Cox regression analysis revealed D22S283 amplification as an independent predictor of good prognosis （P = 0.006, death hazard ratio = 0.411, 95% CI = 0.217-0.779） and blood vessel invasion as an independent poor prognostic factor （P = 0.042, death hazard ratio = 1.911, 95% CI = 1.022-3.571） in CCA patients. CONCLUSION： This study provides evidence for the involvement of gene amplification and deletion on chromosome 22q in liver fluke related CCA, This is the first report of D22S283 amplification as an independent indicator of favorable prognosis in liver fluke related CCA.

关键词： Liver fluke related cholangiocarcinoma Chromosome 22q D22S283 Allelic imbalance Quantitative real time PCR

Enzyme-digested Colla Corii Asini(E’jiao) prevents hydrogen peroxide-induced cell death and accelerates amyloid beta clearance in neuronal-like PC12 cells

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Neural Regeneration Research 2020年第12期15卷 2270-2277页

作者： Li Xiao Feng Liao Ryoji Ide Tetsuro Horie Yumei Fan Chikako Saiki Nobuhiko miwa Department of Pharmacology The Nippon Dental UniversitySchool of Life Dentistry at TokyoTokyoJapan National Engineering Research Center for Gelatin-based Traditional Chinese Medicine Dong-E-E-Jiao Co.Ltd.LiaochengShandong ProvinceChina Department of Physiology The Nippon Dental UniversitySchool of Life Dentistry at TokyoTokyoJapan Research Center The Nippon Dental UniversitySchool of Life Dentistry at TokyoTokyoJapan Department of Life Sciences Prefectural University of HiroshimaHiroshimaJapan

As an aging-associated degenerative disease,Alzheimer’s disease is characterized by the deposition of amyloid beta(Aβ),oxidative stress,inflammation,dysfunction and loss of cholinergic *** Corii Asini(CCA)is a traditional Chinese medicine which has been used for feebleness-related diseases and *** might delay aging-induced degenerative changes in *** the present study,we evaluated antioxidant activity,cytoprotective effects,and Aβremovability of enzyme-digested Colla Corii Asini(CCAD).Oxygen radical absorbance capacity(ORAC)activity assay showed that,as compared to gelatins from the skin of porcine,bovine and cold water fish,CCA exhibited the highest ORAC *** ORAC activity of CCA and CCAD was increased gradually by the length of time in *** analysis by scanning electron microscopy showed that among CCA manufactured in 2008,2013,2017 and gelatin from cold water fish skin,CCA manufactured in 2008 presented the smoothest surface *** further tested the protective effects of CCAD(manufactured in 2008)and enzyme-digested gelatin from cold water fish skin(FGD)on hydrogen peroxide(H2O2)-induced cell death in nerve growth factor-differentiated neuronal-like PC12 *** blue assay showed that both FGD and CCAD at 0.5 mg/m L increased cell viability in H2O2-treated neuronal-like PC12 *** protection of CCAD was significantly superior to that of ***(Ach E)assay showed that both FGD and CCAD inhibited Ach E activity in nerve growth factor-differentiated neuronal-like PC12 cells to 89.1%and 74.5%of that in non-treated cells,*** data suggest that CCAD might be able to increase the neurotransmitter *** CCAD inhibited Ach E activity in neuronal-like PC12 cells,CCAD prevented H2O2-induced abnormal deterioration of Ach *** and neprilysin activity assay results indicated that CCAD reduced amyloid beta accumulation and increased neprilysin activity in Aβ1–

关键词： acetylcholinesterase activity Alzheimer’s disease amyloid beta clearance antioxidant Colla Corii Asini collagen neuroprotection PC12 cells

Effects of thymidine phosphorylase on tumor aggressiveness and 5-fluorouracil sensitivity in cholangiocarcinoma

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World Journal of Gastroenterology 2010年第13期16卷 1631-1638页

作者： Jongkonnee Thanasai Temduang Limpaiboon Patcharee Jearanaikoon Banchob Sripa Chawalit Pairojkul Srisurang Tantimavanich Masanao miwa Department of Clinical Microbiology Faculty of Medical Technology Mahidol University Department of Clinical Chemistry Centre for Research and Development of Medical Diagnostic Laboratories Faculty of Associated Medical Sciences Khon Kaen University Department of Clinical Chemistry Centre for Research and Development of Medical Diagnostic Laboratories Faculty of Associated Medical SciencesKhon Kaen University Department of Pathology Liver Fluke and Cholangiocarcinoma Research Center Faculty of Medicine Khon Kaen University Nagahama Institute of Bio-Science and Technology

AIM: To evaluate the role of thymidine phosphorylase (TP) in cholangiocarcinoma using small interfering RNA (siRNA). METHODS: A human cholangiocarcinoma-derived cell line KKU-M139, which has a naturally high level of endogenous TP, had TP expression transiently knocked down using siRNA. Cell growth, migration, in vitro angiogenesis, apoptosis, and cytotoxicity were assayed in TP knockdown and wild-type cell lines. RESULTS: TP mRNA and protein expression were decreased by 87.1% ± 0.49% and 72.5% ± 3.2%, respectively, compared with control cells. Inhibition of TP significantly decreased migration of KKU-M139, and suppressed migration and tube formation of human umbilical vein endothelial cells. siRNA also reduced the ability of TP to resist hypoxia-induced apoptosis, while suppression of TP reduced the sensitivity of KKU-M139 to 5-fluorouracil. CONCLUSION: Inhibition of TP may be beneficial in decreasing angiogenesis-dependent growth and migration of cholangiocarcinoma but may diminish the response to 5-fluorouracil chemotherapy.

关键词： Liver fluke Cholangiocarcinoma Thymidine phosphorylase 5-fluorouracil siRNA Tumor aggressiveness Cell migration

Immunohistochemical expression of mismatch repair genes:A screening tool for predicting mutator phenotype in liver fluke infection-associated intrahepatic cholangiocarcinoma

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World Journal of Gastroenterology 2006年第23期12卷 3740-3745页

作者： Upama Liengswangwong Anant Karalak Yukio Morishita Masayuki Noguchi Thiravud Khuhaprema Petcharin Srivatanakul Masanao miwa Institute of Health Research Chulalongkorn University PathumwanBangkok and National Center for Genetic Engineering and BiotechnologyThailand Science ParkPathumthaniThailand National Cancer Institute BangkokThailand Department of Pathology Institute of Clinical MedicineUniversity of TsukubaIbarakiJapan National Cancer Institute BangkokThailand Department of Biochemistry and Molecular Oncology Institute of Basic Medical SciencesUniversity of TsukubaIbaraki and Faculty of BioscienceNagahama Institute of Bio-Science and TechnologyNagahamaShigaJapan

AIM： To clarify possible contributions of DNA mismatch repair （MMR） system in carcinogenesis of liver fluke infection-associated intrahepatic cholangiocarcinoma （ICC） by using immunohistochemical assay. METHODS： A total of 29 ICC samples, which had been assessed for genomic instability by a PCR-based method, were used for study. They were examined immunohistochemically to demonstrate protein expression of two MMR genes, hMSH2 and hMLH1. Results obtained were compared with their mutator phenotype assessed previously. RESULTS： Either hMSH2 or hMLH1 protein was obviously expressed in 28 of 29 （96.6%） ICC samples. Positive nuclear localization of hMSH2 or hMLH1 protein was observed in 86.2% （25/29） or 93.1% （27/29） ICC cases, respectively, while their negative nuclear reactivity was only detected in 13.8% （4/29） or 6.9% （2/29） ICC cases analyzed, respectively. CONCLUSION： Our study, probably for the first time, showed through immunohistochemical detection of hMSH2 and hMLH1 gene that DNA MMR system does not play a prominent role in liver fluke infection-associatedcholangiocarcinogenesis. These results confirm previous findings on mutational status of these genes assessed through a PCR-based method. The immunohistochemical analysis has proven to be an effective and sensitive approach for screening MMR deficiency regardless of somatic inactivation or promoter hypermethylation of hMSH2 and/or hMLH1 gene. Furthermore, immunohistochemistry is more advantageous compared to mutator phenotyping assay in terms of simplicity, less time consuming and cost effectiveness for screening possible involvements of target MMR genes in tumorigenesis.

关键词： Liver fluke infection Cholangiocarcinoma Mismatch repair hMSH2 hMLH1 Immunohistochemistry MSI Mutator phenotype

MUC1 and MUC5AC mucin expression in liver fluke-associated intrahepatic cholangiocarcinoma

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World Journal of Gastroenterology 2005年第32期11卷 4939-4946页

作者： Chanchai Boonla Banchob Sripa Peti Thuwajit Ubon Cha-On Anucha Puapairoj Masanao miwa Sopit Wongkham Department of BiochemistryLiver Fluke and Cholangiocarcinoma Research Center Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of PathologyLiver Fluke and Cholangiocarcinoma Research Center Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Department of PathologyLiver Fluke and Cholangiocarcinoma Research Center Faculty of Medicine Khon Kaen UniversityKhon Kaen 40002Thailand Institute of Basic Medical SciencesUniversity of Tskuba TsukubaIbaraki 305-8575Japan

AIM： To investigate the expressions of MUC1 and MUC5AC in intrahepatic cholangiocarcinoma （ICC）. Association of expressions of mucins MUC1 and MUC5AC with clinical findings, metastasis, and survival of the liver fluke-associated ICC patients was determined. METHODS： The expressions of MUC1 and MUC5AC mucins were examined by immunohistochemical staining in 87 cases of histologically-proven ICC. The expressions of mucins in relationship between clinicopathological significance and prognosis of the patients were evaluated. RESULTS： Fifty-two patients （60%） exhibited both MUC1 and MUCSAC expressions, whereas 31% expressed either MUC1 or MUC5AC, and 9% expressed neither. High MUC1 immunoreactivity displayed a significant correlation wibh tumor progression as reflected by vascular invasion （P〈0.001）, whereas high expression of MUC5AC significantly correlated with neural invasion （P = 0.022） and advanced ICC stage （P = 0.008）. Patients with high expression of MUC1 had a significantly shorter survival （P = 0.0002）. According to multivariate analyses, MUC1 reactivity （P = 0.026）, histological grading and stage of tumor represented the least probability of survival. CONCLUSION： MUC1 is overexpressed in liver flukeassociated cholangiocarcinoma and relates to vascular invasion and poor prognosis, whereas MUC5AC mucin is neoexpressed and relates to neural invasion and advanced ICC stage. High MUC1 expression in tumor may be useful for predicting the poor outcome of ICC patients.

关键词： Cholangiocarcinoma Mucin MUC1 MUC5AC Invasion Survival Immunohistochemistry

Clinical usefulness of endoscopic ultrasonography for the evaluation of ulcerative colitis-associated tumors

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World Journal of Gastroenterology 2015年第9期21卷 2693-2699页

作者： Kiyonori Kobayashi Kana Kawagishi Shouhei Ooka Kaoru Yokoyama miwa Sada Wasaburo Koizumi Research and Development Center for New Medical Frontiers Kitasato UniversitySchool of MedicineSagamiharaKanagawa 252-0380Japan Department of Gastroenterology Kitasato UniversitySchool of MedicineSagamihara 252-0380Japan

AIM:To evaluate the clinical usefulness of endoscopic ultrasonography(EUS) for the diagnosis of the invasion depth of ulcerative colitis-associated ***:The study group comprised 13 patients with 16 ulcerative colitis(UC)-associated tumors for which the depth of invasion was preoperatively estimated by *** lesions were then resected endoscopically or by surgical colectomy and were examined *** mean age of the subjects was 48.2 ± 17.1 years,and the mean duration of UC was 15.8 ± 8.3 *** lesions were treated by endoscopic resection and the other 14 lesions by surgical *** depth of invasion of UCassociated tumors was estimated by EUS using an ultrasonic probe and was evaluated on the basis of the deepest layer with narrowing or rupture of the colonic ***:The diagnosis of UC-associated tumors by EUS was carcinoma for 13 lesions and dysplasia for 3 *** invasion depth of the carcinomas was intramucosal for 8 lesions,submucosal for 2,the muscularis propria for 2,and subserosal for ***(69%) of the 16 lesions arose in the *** macroscopic appearance was the laterally spreading tumor-non-granular type for 4 lesions,sessile type for 4,laterally spreading tumor-granular type for 3,semipedunculated type(Isp) for 2,type 1 for 2,and type 3 for *** depth of invasion was correctly estimated by EUS for 15 lesions(94%) but was misdiagnosed as intramucosal for 1 carcinoma with high-grade submucosal *** 2 lesions treated by endoscopic resection were intramucosal carcinoma and dysplasia,and both were diagnosed as intramucosal lesions by ***:EUS provides a good estimation of the invasion depth of UC-associated tumors and may thus facilitate the selection of treatment.

关键词： Ulcerative colitis Colitis-associated tumor Diagno