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| 1 | Association of Fusobacterium nucleatum with immunity andmolecular alterations in colorectal cancer显示文摘The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum(F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6%(44/511), which was lower than that in United States cohort studies(13%). Similar to the United States studies, F. nucleatum positivityin Japanese colorectal cancers was significantly associated with microsatellite instability(MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets(i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain micro RNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. Micro RNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and micro RNA expressions in colorectal cancer. | Katsuhiko Nosho Yasutaka Sukawa Yasushi Adachi Miki Ito Kei Mitsuhashi Hiroyoshi Kurihara Shinichi Kanno Itaru Yamamoto Keisuke Ishigami Hisayoshi Igarashi Reo Maruyama Kohzoh Imai Hiroyuki Yamamoto Yasuhisa Shinomura | 2016 | World Journal of Gastroenterology2016，22，2： | 44 |
| 2 | Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma显示文摘AIM:To clarify the association of glypican-3(GPC3)expression with Wnt and other growth signaling molecules in hepatocellular carcinoma(HCC). METHODS:Expression of GPC3,Wnt,matrix metalloproteinases(MMPs),sulfatase(SULF)1,SULF2,and other growth signaling molecules was analyzed in HCC cell lines and tissue samples by real-time reverse transcriptionpolymerase chain reaction,immunoblotting,and/or immunostaining.Expression of various genes in GPC3 siRNA-transfected HCC cells was analyzed. RESULTS:GPC3 was overexpressed in most HCCs at mRNA and protein levels and its serum levels weresignificantly higher in patients with HCC than in non- HCC subjects(P<0.05).Altered expressions of various MMPs and growth signaling molecules,some of which were correlated with GPC3 expression,were observed in HCCs.Down-regulation of GPC3 expression by siRNA in GPC3-overexpressing HCC cell lines resulted in a significant decrease in expressions of MMP2,MMP14,fibroblast growth factor receptor 1,insulin-like growth factor 1 receptor.GPC3 expression was significantly correlated with nuclear/cytoplasmic localization ofβ-catenin. CONCLUSION:These results suggest that GPC3,in conjunction with MMPs and growth signaling molecules, might play an important role in the progression of HCC. | Noriyuki Akutsu Hiroyuki Yamamoto Shigeru Sasaki Hiroaki Taniguchi Yoshiaki Arimura Kohzoh Imai Yasuhisa Shinomura | 2010 | World Journal of Gastroenterology2010，16，28： | 20 |
| 3 | Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer显示文摘AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling pathway.METHODS:We analyzed 231 formalin-fixed,paraffinembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical treatment.The patients' age,sex,tumor location,depth of invasion,pathological type,lymph node metastasis,and pathological stage were determined by a review of the medical records.Expression of HER2 was analyzed by immunohistochemistry(IHC) using the HercepTest TM kit.Standard criteria for HER2 positivity(0,1+,2+,and 3+) were used.Tumors that scored 3+ were considered HER2-positive.Expression of phospho Akt(pAkt) was also analyzed by IHC.Tumors were considered pAkt-positive when the percentage of positive tumor cells was 10% or more.PI3K,catalytic,alpha polypeptide(PIK3CA) mutations in exons 1,9 and 20 were analyzed by pyrosequencing.Epstein-Barr virus(EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA(EBER) with an EBER-RNA probe.Microsatellite instability(MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and BAT26.RESULTS:HER2 expression levels of 0,1+,2+ and 3+ were found in 167(72%),32(14%),12(5%) and 20(8.7%) samples,respectively.HER2 overexpression(IHC 3+) significantly correlated with intestinal histological type(15/20 vs 98 /205,P = 0.05).PIK3CA mutations were present in 20 cases(8.7%) and significantly correlated with MSI(10/20 vs 9/211,P < 0.01).The mutation frequency was high(21%) in T4 cancers and very low(6%) in T2 cancers.Mutations in exons 1,9 and 20 were detected in 5(2%),9(4%) and 7(3%) cases,respectively.Two new types of PIK3CA mutation,R88Q and R108H,were found in exon1.All PIK3CA mutations were heterozygous missense singlebase substitutions,the most common being H1047R(6/20,30%) in exon20.Eighteen cancers(8%) were EBV-positive and this positivity significantly correlated with a diffuse histological type(13/18 vs 93/198,P = 0.04).There were 7 cases of lymphoepithelioma-like carcinomas(LELC) and 6 of those cases were EBV-positive(percent/EBV:6/18,33%;percent/all LELC:6/7,86%).pAkt expression was positive in 119(53%) cases but showed no correlation with clinicopathological characteristics.pAkt expression was significantly correlated with HER2 overexpression(16/20 vs 103/211,P < 0.01) but not with PIK3CA mutations(12/20 vs 107/211,P = 0.37) or EBV infection(8/18 vs 103/211,P = 0.69).The frequency of pAkt expression was higher in cancers with exon20 mutations(100%) than in those with exon1(40%) or exon9(56%) mutations.One case showed both HER2 overexpression and EBV infection and 3 cases showed both PIK3CA mutations and EBV infection.However,no cases showed both PIK3CA mutations and HER2 overexpression.One EBVpositive cancer with PIK3CA mutation(H1047R) was MSI-positive.Three of these 4 cases were positive for pAkt expression.In survival analysis,pAkt expression significantly correlated with a poor prognosis(hazard ratio 1.75;95%CI:1.12-2.80,P = 0.02).CONCLUSION:HER2 expression,PIK3CA mutations and EBV infection in gastric cancer were characterized.pAkt expression significantly correlates with HER2 expression and with a poor prognosis. | Yasutaka Sukawa Hiroyuki Yamamoto Katsuhiko Nosho Hiroaki Kunimoto Hiromu Suzuki Yasushi Adachi Mayumi Nakazawa Takayuki Nobuoka Mariko Kawayama Masashi Mikami Takashi Matsuno Tadashi Hasegawa Koichi Hirata Kohzoh Imai Yasuhisa Shinomura | 2012 | World Journal of Gastroenterology2012，18，45： | 19 |
| 4 | Diagnosis of autoimmune pancreatitis显示文摘Autoimmune pancreatitis(AIP) is a distinct form of chronic pancreatitis that is increasingly being reported. The presentation and clinical image findings of AIP sometimes resemble those of several pancreatic malignancies, but the therapeutic strategy differs appreciably. Therefore, accurate diagnosis is necessary for cases of AIP. To date, AIP is classified into two distinct subtypes from the viewpoints of etiology, serum markers, histology, other organ involvements, and frequency of relapse: type 1 is related to Ig G4(lymphoplasmacytic sclerosing pancreatitis) and type 2 is related to a granulocytic epithelial lesion(idiopathic duct-centric chronic pancreatitis). Both types of AIP are characterized by focal or diffuse pancreatic enlargement accompanied with a narrowing of the main pancreatic duct, and both show dramatic responses to corticosteroid. Unlike type 2, type 1 is characteristically associated with increasing levels of serum Ig G4 and positive serum autoantibodies, abundant infiltration of Ig G4-positive plasmacytes, frequent extrapancreatic lesions, and relapse. These findings have led several countries to propose diagnostic criteria for AIP, which consist of essentially similar diagnostic items; however, several differences exist for each country, mainly due to differences in the definition of AIP and the modalities used to diagnose this disease. An attempt to unite the diagnostic criteria worldwide was made with the publication in 2011 of the international consensus diagnostic criteria for AIP, established at the 2010 Congress of the International Association of Pancreatology(IAP). | Hiroyuki Matsubayashi Naomi Kakushima Kohei Takizawa Masaki Tanaka Kenichiro Imai Kinichi Hotta Hiroyuki Ono | 2014 | World Journal of Gastroenterology2014，20，44： | 17 |
| 5 | A candidate targeting molecule of insulin-like growth factor-Ⅰ receptor for gastrointestinal cancers显示文摘Advances in molecular research in cancer have brought new therapeutic strategies into clinical usage.One new group of targets is tyrosine kinase receptors,which can be treated by several strategies,including small molecule tyrosine kinase inhibitors(TKIs) and monoclonal antibodies(mAbs).Aberrant activation of growth factors/receptors and their signal pathways are required for malignant transformation and progression in gastrointestinal(GI) carcinomas.The concept of targeting specif ic carcinogenic receptors has been validated by successful clinical application of many new drugs.Type I insulin-like growth factor(IGF) receptor(IGF-IR) signaling potently stimulates tumor progression and cellular differentiation,and is a promising new molecular target in human malignancies.In this review,we focus on this promising therapeutic target,IGF-IR.The IGF/IGF-IR axis is an important modifier of tumor cell proliferation,survival,growth,and treatment sensitivity in many malignant diseases,including human GI cancers.Preclinical studies demonstrated that downregulation of IGF-IR signals reversed the neoplastic phenotype and sensitized cells to anticancer treatments.These results were mainly obtained through our strategy of adenoviruses expressing dominant negative IGF-IR(IGF-IR/dn) against gastrointestinal cancers,including esophagus,stomach,colon,and pancreas.We also summarize a variety of strategies to interrupt the IGFs/IGF-IR axis and their preclinical experiences.Several mAbs and TKIs targeting IGF-IR have entered clinical trials,and early results have suggested that these agents have generally acceptable safety profiles as single agents.We summarize the advantages and disadvantages of each strategy and discuss the merits/demerits of dual targeting of IGF-IR and other growth factor receptors,including Her2 and the insulin receptor,as well as other alternatives and possible drug combinations.Thus,IGF-IR might be a candidate for a molecular therapeutic target in human GI carcinomas. | Yasushi Adachi Hiroyuki Yamamoto Hirokazu Ohashi Takao Endo David P Carbone Kohzoh Imai Yasuhisa Shinomura | 2010 | World Journal of Gastroenterology2010，16，46： | 14 |
| 6 | Endoscopic ultrasonography guided-fine needle aspirationfor the diagnosis of solid pancreaticobiliary lesions:Clinicalaspects to improve the diagnosis显示文摘Endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA) has been applied to pancreaticobiliary lesions since the 1990 s and is in widespread use throughout the world today. We used this method to confirm the pathological evidence of the pancreaticobiliary lesions and to perform suitable therapies. Complications of EUS-FNA are quite rare, but some of them are severe. Operators should master conventional EUS observation and experience a minimum of 20-30 cases of supervised EUS-FNA on non-pancreatic and pancreatic lesions before attempting solo EUSFNA. Studies conducted on pancreaticobiliary EUSFNA have focused on selection of suitable instruments(e.g., needle selection) and sampling techniques(e.g., fanning method, suction level, with or without a stylet, optimum number of passes). Today, the diagnostic ability of EUS-FNA is still improving; the detection of pancreatic cancer(PC) currently has a sensitivity of 90%-95% and specificity of 95%-100%. In addition to PC, a variety of rare pancreatic tumors can be discriminated by conducting immunohistochemistry on the FNA materials. A flexible, large caliber needle has been used to obtain a large piece of tissue, which can provide sufficient histological information to be helpful in classifying benign pancreatic lesions. EUSFNA can supply high diagnostic yields even for biliary lesions or peri-pancreaticobiliary lymph nodes. This review focuses on the clinical aspects of EUS-FNA in the pancreaticobiliary field, with the aim of providing information that can enable more accurate and efficient diagnosis. | Hiroyuki Matsubayashi Toru Matsui Yohei Yabuuchi Kenichiro Imai Masaki Tanaka Naomi Kakushima Keiko Sasaki Hiroyuki Ono | 2016 | World Journal of Gastroenterology2016，22，2： | 12 |
| 7 | Hepatic schwannoma:Imaging findings on CT,MRI and contrast-enhanced ultrasonography显示文摘A primary benign schwannoma of the liver is extremely rare and is difficult to preoperatively discriminate from a malignant tumor.We compared the imaging and pathological findings,and examined the possibility of preoperatively diagnosing a benign liver schwannoma.A 72-year-old woman was admitted to our hospital because of a 4.6-cm mass in the liver.A malignant tumor was suspected,and a right hepatectomy was performed.After this,the diagnosis of a primary benign schwannoma of the liver was made through pathological examination.Contrast-enhanced ultrasonography(CEUS) with Sonazoid showed minute blood flows into the septum and solid areas of the tumor in the vascular phase;most likely due to increased arterial flow associated with infiltration of chronic inflammatory cells.In the postvascular phase,CEUS showed contrast defect of cystic areas and delayed enhancement of solid areas;most likely due to aggregation of siderophores.Because discriminating between a benign and malignant schwannoma of the liver is difficult,surgery is generally recommended.However,the two key findings from CEUS may be useful in discriminating ancient schwannoma by recognizing the hemorrhage involved in the secondary degeneration and aggregation of siderophores. | Yu Ota Kazunobu Aso Kenji Watanabe Takahiro Einama Koji Imai Hidenori Karasaki Ryuji Sudo Yosui Tamaki Mituyoshi Okada Yosihiko Tokusashi Toru Kono Naoyuki Miyokawa Masakazu Haneda Masahiko Taniguchi Hiroyuki Furukawa | 2012 | World Journal of Gastroenterology2012，18，35： | 11 |
| 8 | Hepatic clearance measured with ^(99m)Tc-GSA single-photon emission computed tomography to estimate liver fibrosis显示文摘AIM: To evaluate the clinical utility of hepatic clearance(HC) measured with technetium-99m-diethylenetriaminepenta-acetic acid-galactosyl human serum albumin(99mTc-GSA) single-photon emission computed tomography(SPECT) to estimate the degree of liver fibrosis.METHODS:Seventy-eight consecutive patients who underwent initial hepatectomy due to hepatocellular carcinoma were enrolled in this study.Indocyanine green clearance(ICG R15),quantitative indices estimated by 99mTc-GSA[the receptor index(LHL15 and HH15)and HC via SPECT analysis],and conventional liver function tests were performed before hepatectomy.Correlations among the quantitative indices for liver functional reserve,conventional liver function tests,andthe degree of liver fibrosis were evaluated.RESULTS:The degree of liver fibrosis was correlated with ICG R15,HH15,LHL15,and HC.HC showed the best correlation with conventional liver function tests.According to multivariate analysis,HC and LHL15 were significant independent predictors of severe fibrosis.HC was the most valuable index for predicting severe fibrosis.CONCLUSION:HC measured with 99mTc-GSA SPECT is a reliable index for assessing liver fibrosis before hepatectomy. | Masahiko Taniguchi Atsutaka Okizaki Kenji Watanabe Koji Imai Koichiro Uchida Takahiro Einama Noriyuki Shuke Naoyuki Miyokawa Hiroyuki Furukawa | 2014 | World Journal of Gastroenterology2014，20，44： | 11 |
| 9 | Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers显示文摘AIM: To clarify the expression and role of Ephrin receptor A4 (EphA4) in gastric cancer in relation to clinicopathological characteristics and the expression of fibroblast growth factor receptor 1 (FGFR1) and ephrin ligands. METHODS: Eleven gastric carcinoma cell lines, 24 paired surgical fresh specimens of gastric adenocarcinoma and adjacent nontumor tissue, 74 conventional formalin-fixed, paraffin-embedded tumor specimens, and 55 specimens spotted on tissue microarray (TMA) were analyzed. Reverse transcription-PCR (RT-PCR), real-time RT-PCR, immunohistochemistry, and cell growth assays were performed. RESULTS: Overexpression of EphA4 mRNA expres-sion was observed in 8 (73%) of 11 gastric cancer cell lines and 10 (42%) of 24 gastric cancer tissues. Over-expression of EphA4, analyzed by immunohistochemistry, was observed in 62 (48%) of 129 gastric cancer tissues. EphA4 overexpression, at the protein level, was significantly associated with depth of invasion and recurrence. EphA4 overexpression was also correlated with FGFR1 overexpression. Patients with EphA4-positive cancer had significantly shorter overall survival periods than did those with EphA4-negative cancer (P = 0.0008). The mRNAs for ephrin ligands were coexpressed in various combinations in gastric cancer cell lines and cancer tissues. Downregulation of EphA4 expression by siRNA in EphA4-overexpressing gastric cancer cell lines resulted in a significant decrease in cell growth. CONCLUSION: Our results suggest that overexpres-sion of EphA4 plays a role in gastric cancer. | Mariko Oki Hiroyuki Yamamoto Hiroaki Taniguchi Yasushi Adachi Kohzoh Imai Yasuhisa Shinomura | 2008 | World Journal of Gastroenterology2008，14，37： | 11 |
| 10 | Liver injury after aluminum potassium sulfate and tannic acid treatment of hemorrhoids显示文摘We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid(ALTA) regimen. A 41-year-old man developed a fever and liver injury after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA with lidocaine. The acute liver injury was classified clinically as hepatocellular and pathologically as cholestastic. We could not classify the mechanism of injury. High eosinophil and immunoglobulin E levels characterized the injury,and a drug lymphocyte stimulation test was negative on postoperative day 25. Fluid replacement for two weeks after hospitalization improved the liver injury. ALTA therapy involves injecting chemicals into the submucosa,from the rectum to the anus,and this is the first description of a case that developed a severe liver disorder after this treatment; hence,an analysis of future cases as they accumulate is desirable. | Kenichi Yoshikawa Reimi Kawashima Yuki Hirose Keiko Shibata Takafumi Akasu Noriko Hagiwara Takeharu Yokota Nami Imai Akira Iwaku Go Kobayashi Hirohiko Kobayashi Akiyoshi Kinoshita Nao Fushiya Hiroyuki Kijima Kazuhiko Koike Masayuki Saruta | 2017 | World Journal of Gastroenterology2017，23，27： | 5 |
| 11 | Genetic and epigenetic characteristics of gastric cancers with JC virus T-antigen显示文摘AIM:To clarify the significance of JC virus(JCV)T-antigen (T-Ag)expression in human gastric cancer. METHODS:We investigated the relationship between T-Ag detected by immunohistochemistry and Epstein- Barr virus(EBV)infection,microsatellite instability (MSI),and genetic and epigenetic alterations in gastric cancers.Mutations in the p53,β-catenin,KRAS,BRAF, PIK3CA genes were analyzed by polymerase chain reaction(PCR)-single strand conformation polymorphism and DNA sequencing.Allelic losses were determined by PCR at 7 microsatellite loci.Aberrant DNA methylation was analyzed by MethyLight assay. RESULTS:JCV T-Ag protein expression was found in 49%of 90 gastric cancer tissues.T-Ag positivity was not correlated with clinicopathological characteristics. T-Ag expression was detected in a similar percentage of EBV positive cancers(4 of 9,44%)and EBV negativecancers(35 of 73,48%).T-Ag expression was detected in a significantly lower percentage of MSI-H cancers (14%)than in non MSI-H cancers(55%,P=0.005). T-Ag expression was detected in a significantly higher percentage of cancers with nuclear/cytoplasmic localization of catenin(15 of 21,71%)than in cancers without(42%,P=0.018).p53 mutations were detected in a significantly lower percentage of T-Ag positive cancers(32%)than in T-Ag negative cancers(57%,P= 0.018).T-Ag positive gastric cancers showed a significant increase in the allelic losses and aberrant methylation compared with T-Ag negative gastric cancers(P=0.008 and P=0.003). CONCLUSION:The results suggest that JCV T-Ag is involved in gastric carcinogenesis through multiple mechanisms of genetic and epigenetic alterations. | Satoshi Yamaoka Hiroyuki Yamamoto Katsuhiko Nosho Hiroaki Taniguchi Yasushi Adachi Shigeru Sasaki Yoshiaki Arimura Kohzoh Imai Yasuhisa Shinomura | 2009 | World Journal of Gastroenterology2009，15，44： | 3 |
| 12 | Endoscopic and biopsy diagnoses of superficial, nonampullary, duodenal adenocarcinomas显示文摘AIM: To investigate the accuracy of endoscopic or biopsy diagnoses of superficial nonampullary duodenal epithelial tumors(NADETs).METHODS:Clinicopathological data were reviewed for84 superficial NADETs from 74 patients who underwent surgery or endoscopic resection between September2002 and August 2014 at a single prefectural cancer center.Superficial NADETs were defined as lesions confined to the mucosa or submucosa.Demographic and clinicopathological data were retrieved from charts,endoscopic and pathologic reports.Endoscopic reports included endoscopic diagnosis,location,gross type,diameter,color,and presence or absence of biopsy.Endoscopic diagnoses were made by an endoscopist in charge of the examination before biopsy specimens were obtained.Endoscopic images were obtained using routine,front-view,high-resolution video endoscopy,and chromoendoscopy with indigocarmine was performed for all lesions.Endoscopic images were reviewed by at least two endoscopists to assess endoscopic findings indicative of carcinoma.Preoperative diagnoses based on endoscopy and biopsy findings were compared with histological diagnoses of resected specimens.Sensitivity,specificity,and accuracy were assessed for endoscopic diagnosis and biopsy diagnosis.RESULTS:The majority(81%)of the lesions were located in the second portion of the duodenum.The median lesion diameter was 14.5 mm according to final histology.Surgery was performed for 49 lesions from 39 patients,and 35 lesions from 35 patients were endoscopically resected.Final histology confirmed 65carcinomas,15 adenomas,and 3 hyperplasias.A finaldiagnosis of duodenal carcinoma was made for 91%(52/57)of the lesions diagnosed as carcinoma by endoscopy and 93%(42/45)of the lesions diagnosed as carcinoma by biopsy.The sensitivity,specificity,and accuracy of endoscopic diagnoses were 80%,72%,and 78%,respectively,whereas those of biopsy diagnoses were 72%,80%,and 74%,respectively.Preoperative diagnoses of carcinomas were made in88%(57/65)of the carcinoma lesions via endoscopy or biopsy.Endoscopic findings associated with carcinoma were red color,depression,and mixed-type morphology.CONCLUSION:Preoperative endoscopy and biopsy showed similar accuracies in the diagnosis of carcinoma in patients with superficial NADETs. | Naomi Kakushima Hideyuki Kanemoto Keiko Sasaki Noboru Kawata Masaki Tanaka Kohei Takizawa Kenichiro Imai Kinichi Hotta Hiroyuki Matsubayashi Hiroyuki Ono | 2015 | World Journal of Gastroenterology2015，21，18： | 3 |
| 13 | Cancer detection by ubiquitin carboxyl-terminal esterase L1 methylation in pancreatobiliary fluids显示文摘AIM:To evaluate the utility of measuring epigenetic alterations in pancreatic and biliary fluids in determining molecular markers for pancreatobiliary cancers.METHODS:DNA was extracted from undiluted pancreatic and biliary fluids.As a surrogate for a genomewide hypomethylation assay,levels of long interspersed nuclear element-1(LINE-1) methylation were analyzed using bisulfite pyrosequencing.CpG island hypermethylation of 10 tumor-associated genes,aryl-hydrocarbon receptor repressor,adenomatous polyposis coli,calcium channel,voltage dependent,T type α1G subunit,insulin-like growth factor 2,O-6-methyl-guanine-DNA methyltransferase,neurogenin 1,CDKN2A,runt-related transcription factor 3(RUNX3),secreted frizzled-related protein 1,and ubiquitin carboxyl-terminal esterase L1(UCHL1),was analyzed using MethyLight.To examine the role of CpG methylation and histone deacetylation in the silencing of UCHL1,human gallbladder carcinoma cell lines and pancreatic carcinoma cell lines were treated with 2 or 5 μmol/L 5-AZA-dC for 72 h or 100 nmol/L Trichostatin A for 24 h.After the treatment,UCHL1 expression was analyzed by real-time reverse transcription-polymerase chain reaction.RESULTS:Pancreatobiliary cancers exhibited significantly lower LINE-1 methylation levels in pancreatic and biliary fluids than did noncancerous pancreatobiliary disease(58.7% ± 4.3% vs 61.7% ± 2.2%,P = 0.027;53.8% ± 6.6% vs 57.5% ± 1.7%,P = 0.007);however,LINE-1 hypomethylation was more evident in pancreatic cancer tissues than in pancreatic fluids(45.4% ± 5.5% vs 58.7% ± 4.3%,P < 0.001).CpG island hypermethylation of tumor-associated genes was detected at various frequencies,but it was not correlated with LINE-1 hypomethylation.Hypermethylation of the UCHL1 gene was cancer-specific and most frequently detected in pancreatic(67%) or biliary(70%) fluids from patients with pancreatobiliary cancer.As a single marker,hypermethylation of the UCHL1 gene in pancreatic and biliary fluids was most useful for the detection of pancreatic and pancreatobiliary cancers,respectively(100% specificity).Hypermethylation of the UCHL1 and RUNX3 genes in pancreatic and biliary fluids was the most useful combined marker for pancreatic(87% sensitivity and 100% specificity) and pancreatobiliary(97% sensitivity and 100% specificity) cancers.Treatment with a demethylating agent,5-AZA-2'-deoxycytidine,restored UCHL1 expression in pancreatobiliary cancer cell lines.CONCLUSION:Our results suggest that hypermethylation of UCHL1 and RUNX3 in pancreatobiliary fluid might be useful for the diagnosis of pancreatobiliary cancers. | Norihiro Kato Hiroyuki Yamamoto Yasushi Adachi Hirokazu Ohashi Hiroaki Taniguchi Hiromu Suzuki Mayumi Nakazawa Hiroyuki Kaneto Shigeru Sasaki Kohzoh Imai Yasuhisa Shinomura | 2013 | World Journal of Gastroenterology2013，19，11： | 3 |
| 14 | Endoscopic submucosal dissection in a patient with esophageal adenoid cystic carcinoma显示文摘We report the first use of endoscopic submucosal dissection(ESD) for the treatment of a patient with adenoid cystic carcinoma of the esophagus(EACC). An 82-year-old woman visited our hospital for evaluation of an esophageal submucosal tumor. Endoscopic examination showed a submucosal tumor in the middle third of the esophagus. The lesion partially stained with Lugol's solution,and narrow band imaging with magnification showed intrapapillary capillary loops with mild dilatation and a divergence of caliber in the center of the lesion. Endoscopic ultrasound imaging revealed a solid 8 mm × 4.2 mm tumor,primarily involving the second and third layers of the esophagus. A preoperative biopsy was non-diagnostic. ESD was performed to resect the lesion,an 8 mm submucosal tumor. Immunohistologically,tumor cells differentiating into ductal epithelium and myoepithelium were observed,and the tissue type was adenoid cystic carcinoma. There was no evidence of esophageal wall,vertical stump or horizontal margin invasion with p T1 b-SM2 staining(1800 μm from the muscularis mucosa). Further studies are needed to assess the use of ESD for the treatment of patients with EACC. | Kenichi Yoshikawa Akiyoshi Kinoshita Yuki Hirose Keiko Shibata Takafumi Akasu Noriko Hagiwara Takeharu Yokota Nami Imai Akira Iwaku Go Kobayashi Hirohiko Kobayashi Nao Fushiya Hiroyuki Kijima Kazuhiko Koike Haruka Kaneyama Keiichi Ikeda Masayuki Saruta | 2017 | World Journal of Gastroenterology2017，23，45： | 3 |
| 15 | Overexpression of β3/γ2 chains of laminin-5 and MMP7 in biliary cancer显示文摘AIM:To clarify the clinicopathological significance of laminin-5 γ2 (LNγ2) and β3 (LNβ3) chains and MMP7 expression in biliary tract cancer.METHODS: We analyzed the association between immunohistochemically detected LNγ2, LNβ3, and MMP7 expression in biliary tract cancer and clinicopathological characteristics. Activity of MMP7 was analyzed by casein zymography. An in vitro invasion assay after treatment with MMP7-specific siRNA was performed.RESULTS: LNγ2 expression was predominantly observed in carcinoma cells at the invasive front. LNγ2 expression was seen in 57% of patients with biliary tract cancer, and was associated with depth of invasion, histologic type, and advanced stage. The expression pattern of LNβ3 was classified into two types: invasive front dominant type (38%) and diffuse type (28%).The invasive front dominant type was associated with histologic type and advanced stage. MMP7 positivity was correlated with LNγ2 or LNβ3 expression but not with clinicopathological characteristics. Active MMP7 detected by casein zymography was correlated with depth of invasion and advanced stage. Downregulation of MMP7 expression by siRNA resulted in a significant decrease in biliary tract cancer cell invasion in vitro.CONCLUSION: Our results suggest that LNγ2 and LNβ3, in conjunction with MMP7, play a key role in the progression of biliary tract cancer. | Toshikuni Oka Hiroyuki Yamamoto Shigeru Sasaki Masanori Ii Keiichi Hizaki Hiroaki Taniguchi Yasushi Adachi Kohzoh Imai Yasuhisa Shinomura | 2009 | World Journal of Gastroenterology2009，15，31： | 2 |
| 16 | A new conceptualization for Mikulicz’s disease as an IgG4-related plasmacytic disease显示文摘 | Motohisa Yamamoto Hiroki Takahashi Mikiko Ohara Chisako Suzuki Yasuyoshi Naishiro Hiroyuki Yamamoto Yasuhisa Shinomura Kohzoh Imai | 2006 | Modern Rheumatology2006，，6： | 1 |
| 17 | China's Endogenous Investment Cycle显示文摘 | Imai Hiroyuki | 1994 | Journal of Comparative Economics1994，，19： | 1 |
| 18 | Targeting for insulin-like growth factor-I receptor with short hairpin RNA for human digestive/gastrointestinal cancers显示文摘 | Yu Wang Yasushi Adachi Arisa Imsumran Hiroyuki Yamamoto Wenhua Piao Hua Li Masanori Ii Yoshiaki Arimura Mi Young Park Dalrae Kim Choon-Taek Lee David P. Carbone Kohzoh Imai Yasuhisa Shinomura | 2010 | Journal of Gastroenterology2010，，2： | 1 |
| 19 | Flexural shear behavior of composite bridge girder withcorrugated steel webs around middle support显示文摘 | Hiroshi Shiratoni Hiroyuki Ikeda Yohiaki Imai | 2003 | JSECJournal2003，724，62： | 1 |
| 20 | Preoperative indicators of failure of en bloc resection or perforation in colorectal endoscopic submucosal dissection: implications for lesion stratification by technical difficulties during stepwise training显示文摘 | Kenichiro Imai Kinichi Hotta Yuichiro Yamaguchi Naomi Kakushima Masaki Tanaka Kohei Takizawa Noboru Kawata Hiroyuki Matsubayashi Tadakazu Shimoda Keita Mori Hiroyuki Ono | 2015 | Gastrointestinal Endoscopy2015，，： | 1 |
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