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1Association 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 2016World Journal of Gastroenterology2016,22,2:44
23维图像处理系统在稻米品质检测中的应用研究显示文摘利用微切片 3维图像处理系统对稻米的品质特性进行了探索性的研究。结果表明 ,借助于 3维可视化技术 ,可以对稻谷的外观品质、营养品质及蒸煮品质等进行更为直观且客观的观察与测定。尤其是在营养成分分布密度的评价、心白米内部组织的分析、蒸煮过程中组织结构变化的观测等方面 ,取得了传统研究方法难以获得的结果。利用该系统对垩白度的定量化测定 ,为食品的定量形态学研究开辟了一条新的研究途径。侯彩云 Seiichi OSHITA Yasuhisa SEO Yoshinori KAWAGOE Toru Torii Kenichi Kudoh Toshiro Higuchi Gabsoo Do 2001农业工程学报2001,17,3:30
3Atheroprotective effects of antioxidants through inhibition of mitogen-activated protein kinases显示文摘Reactive oxygen species (ROS) have been known to play an important role in the pathogenesis of atherosclerosis and several other cardiovascular diseases. It is now apparent that ROS induce endothelial cell damage and vascular smooth muscle cell (VSMC) growth and cardiac remodeling, which are associated with hypertension, atherosclerosis, heart failure, and restenosis. Several lines of evidence have indicated that ROS and mitogen-activated protein (MAP) kinases were involved in vascular remodeling under various pathological conditions. Recently, it was also reported that MAP kinases were sensitive to oxidative stress. MAP kinases play an important role in cell differentiation, growth, apoptosis, and the regulation of a variety of transcription factors and gene expressions. Bioflavonoids and polyphenolic compounds are believed to be beneficial for the prevention and treatment of athero-sclerosis and cardiovascular diseases. One of the most widely distributed bioflavonoids, 3,3',4',5,7-penta-hydroxyflavone (quercetin) and its metabolite quercetin 3-O-β-D-glucuronide (Q3GA) inhibited Angiotensin Ⅱ-stimulated JNK activation and resultant hypertrophy of VSMC. Several studies have suggested that various antioxi-dants including probucol, N-acetyl-L-cysteine, diphenylene iodonium, Trolox C (vitamin E analogue), and vitamin C inhibit VSMC growth, which is associated with pathogenesis of cardiovascular diseases. Therefore, inhibition of MAP kinases by antioxidant treatment may prove to be a therapeutic strategy for cardiovascular diseases. In contrast, some clinical studies have reported that antioxidant vitamins did not show beneficial effects in coron aryartery disease or in a number of high-risk people. Thus, further studies are needed to clarify why antioxidants showed beneficial effects in vitro, whereas less satisfactory results were obtained in some clinical conditions.Moe KYAW Masanori YOSHIZUMI Koichiro TSUCHIYA Yuki IZAWA Yasuhisa KANEMATSU Toshiaki TAMAKI 2004Acta Pharmacologica Sinica2004,25,8:24
4Association 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 2010World Journal of Gastroenterology2010,16,28:20
5Alterations 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 2012World Journal of Gastroenterology2012,18,45:19
6A 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 2010World Journal of Gastroenterology2010,16,46:14
7Interrelationship between microsatellite instability and microRNA in gastrointestinal cancer显示文摘There is an increasing understanding of the roles that microsatellite instability (MSI) plays in Lynch syndrome (by mutations) and sporadic (by mainly epigenetic changes) gastrointestinal (GI) and other cancers. Deficient DNA mismatch repair (MMR) results in the strong mutator phenotype known as MSI, which is the hallmark of cancers arising within Lynch syndrome. MSI is characterized by length alterations within simple repeated sequences called microsatellites. Lynch syndrome occurs primarily because of germline mutations in one of the MMR genes, mainly MLH1 or MSH2 , less frequently MSH6 , and rarely PMS2 . MSI is also observed in about 15% of sporadic colorectal, gastric, and endometrial cancers and in lower frequencies in a minority of other cancers where it is often associated with the hypermethylation of the MLH1 gene. miRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level and are critical in many biological processes and cellular pathways. There is accumulating evidence to support the notion that the interrelationship between MSI and miRNA plays a key role in the pathogenesis of GI cancer. As a possible new mechanism underlying MSI, overexpression of miR-155 has been shown to downregulate expression of MLH1, MSH2, and MSH6. Thus, a subset of MSI-positive (MSI+) cancers without known MMR defects may result from miR-155 overexpression. Target genes of frameshift mutation for MSI are involved in various cellular functions, such as DNA repair, cell signaling, and apoptosis. A novel class of target genes that included not only epigenetic modifier genes, such as HDAC2 , but also miRNA processing machinery genes, including TARBP2 and XPO5 , were found to be mutated in MSI+ GI cancers. Thus, a subset of MSI+ colorectal cancers (CRCs) has been proposed to exhibit a mutated miRNA machinery phenotype. Genetic, epigenetic, and transcriptomic differences exist between MSI+ and MSI cancers. Molecular signatures of miRNA expression apparently have the potential to distinguish between MSI+ and MSI CRCs. In this review, we summarize recent advances in the MSI pathogenesis of GI cancer, with the focus on its relationship with miRNA as well as on the potential to use MSI and related alterations as biomarkers and novel therapeutic targets.Hiroyuki Yamamoto Yasushi Adachi Hiroaki Taniguchi Hiroaki Kunimoto Katsuhiko Nosho Hiromu Suzuki Yasuhisa Shinomura 2012World Journal of Gastroenterology2012,18,22:14
8An updated review of gastric cancer in the next-generation sequencing era:Insights from bench to bedside and vice versa显示文摘Gastric cancer(GC)is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide.There is an increasing understanding of the roles that genetic and epigenetic alterations play in GCs.Recent studies using nextgeneration sequencing(NGS)have revealed a number of potential cancer-driving genes in GC.Whole-exome sequencing of GC has identified recurrent somatic mutations in the chromatin remodeling gene ARID1A and alterations in the cell adhesion gene FAT4,a member of the cadherin gene family.Mutations in chromatin remodeling genes(ARID1A,MLL3 and MLL)have been found in 47%of GCs.Whole-genome sequencing and whole-transcriptome sequencing analyses have also discovered novel alterations in GC.Recent studies of cancer epigenetics have revealed widespread alterations in genes involved in the epigenetic machinery,such as DNA methylation,histone modifications,nucleosome positioning,noncoding RNAs and microRNAs.Recent advances in molecular research on GC have resulted in the introduction of new diagnostic and therapeutic strategies into clinical settings.The antihuman epidermal growth receptor 2(HER2)antibody trastuzumab has led to an era of personalized therapy in GC.In addition,ramucirumab,a monoclonal antibody targeting vascular endothelial growth factor receptor(VEGFR)-2,is the first biological treatment that showed survival benefits as a single-agent therapy in patients with advanced GC who progressed after firstline chemotherapy.Using NGS to systematically identify gene alterations in GC is a promising approach with remarkable potential for investigating the pathogenesis of GC and identifying novel therapeutic targets,as well as useful biomarkers.In this review,we will summarize the recent advances in the understanding of the molecular pathogenesis of GC,focusing on the potential use of these genetic and epigenetic alterations as diagnostic biomarkers and novel therapeutic targets.Hiroyuki Yamamoto Yoshiyuki Watanabe Tadateru Maehata Ryo Morita Yoshihito Yoshida Ritsuko Oikawa Shinya Ishigooka Shun-ichiro Ozawa Yasumasa Matsuo Kosuke Hosoya Masaki Yamashita Hiroaki Taniguchi Katsuhiko Nosho Hiromu Suzuki Hiroshi Yasuda Yasuhisa Shinomura Fumio Itoh 2014World Journal of Gastroenterology2014,20,14:12
9Overexpression 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 2008World Journal of Gastroenterology2008,14,37:11
10Efficacy of multislice computed tomography for gastroenteric and hepatic surgeries显示文摘AIM: To determine the efficacy of multislice CT for gastroenteric and hepatic surgery.METHODS: Dual-phase helical computed tomography was performed in 50 of 51 patients who underwent gastroenteric and hepatic surgeries. Twenty-eight, eighteen and four patients suffering from colorectal cancer, gastric cancer,and liver cancer respectively underwent colorectal surgery (laparoscopic surgery: 6 cases), gastrectomy, and hepatectomy. Three-dimensional computed tomography imaging of the inferior mesenteric artery, celiac artery and hepatic artery was performed. And in the follow-up examination of postoperative patients, multiplanar reconstruction image was made in case of need.RESULTS: Scans in 50 patients were technically satisfactory and included in the analysis. Depiction of major visceral arteries, which were important for surgery and other treatments, could be done in all patients.Preoperative visualization of the left colic artery and sigmoidal arteries, the celiac artery and its branches, and hepatic artery was very useful to lymph node dissection,the planning of a reservoir and hepatectomy. And multiplanar reconstruction image was helpful to diagnosis for the postoperative follow-up of patients.CONCLUSION: Three-dimensional volume rendering or multiplanar reconstruction imaging performed by multislice computed tomography was very useful for gastroenteric and hepatic surgeries.Hiroshi Ohtani Hidemi Kawajiri Yuichi Arimoto Koichi Ohno Yasuhisa Fujimoto Hiroko Oba Kenji Adachi Masaya Hirano Shoichi Terakawa Mitsuo Tsubakimoto 2005World Journal of Gastroenterology2005,11,10:9
11Stapled gastro/duodenojejunostomy shortens reconstruction time during pylorus-preserving pancreaticoduodenectomy显示文摘AIM:To investigate whether a stapled technique is superior to the conventional hand-sewn technique for gastro/duodenojejunostomy during pylorus-preserving pancreaticoduodenectomy(PpPD).METHODS:In October 2010,we introduced a mechanical anastomotic technique of gastro-or duodenojejunostomy using staplers during PpPD.We compared clinical outcomes between 19 patients who underwent PpPD with a stapled gastro/duodenojejunostomy(stapled anastomosis group)and 19 patients who underwent PpPD with a conventional hand-sewn duodenojejunostomy(hand-sewn anastomosis group).RESULTS:The time required for reconstruction was significantly shorter in the stapled anastomosis group than in the hand-sewn anastomosis group(186.0±29.4 min vs 219.7±50.0 min,P=0.02).In addition,intraoperative blood loss was significantly less(391.0±212.0 mL vs 647.1±482.1 mL,P=0.03)and the time to oral intake was significantly shorter(5.4±1.7d vs 11.3±7.9 d,P=0.002)in the stapled anastomosis group than in the hand-sewn anastomosis group.There were no differences in the incidences of delayed gastric emptying and other postoperative complications between the groups.CONCLUSION:These results suggest that stapled gastro/duodenojejunostomy shortens reconstruction time during PpPD without affecting the incidence of delayed gastric emptying.Norihiro Sato Kei Yabuki Shiro Kohi Yasuhisa Mori Noritaka Minagawa Toshihisa Tamura Aiichiro Higure Koji Yamaguchi 2013World Journal of Gastroenterology2013,19,48:6
12Electrochemical behavior of [UO_2Cl_4]^(2-) in 1-ethyl-3-methylimidazolium based ionic liquids显示文摘In order to examine the chemical form of uranyl species in 1-ethyl-3-methylimidazolium(EMI) based ionic liquids,UV-visible absorption spectra of solutions prepared by dissolving [EMI] 2 [UO2Cl4] into a mixture of EMICl and EMIBF 4(50:50 mol%) were measured.As a result,it was confirmed that uranyl species in the mixture of EMICl and EMIBF 4 existed as [UO2Cl4]2-.Cyclic voltammograms(CVs) of [UO2Cl4]2-in the mixture were measured at 25 ℃ using a Pt working electrode,a Pt wire counter electrode,and an Ag/Ag + reference electrode(0.01 M AgNO 3,0.1 M tetrabutylammonium perchlorate in acetonitrile) in a glove box under an Ar atmosphere.Peaks corresponding to one redox couple were observed around-1.05 V(Epc) and-0.92 V(Epa) vs.ferrocene/ferrocenium ion(Fc/Fc +).The potential differences between two peaks(Ep) increased from 101 to 152 mV with an increase in the scan rate from 50 to 300 mV s-1,while the(Epc+Epa)/2 value was constant,-0.989 V vs.Fc/Fc + regardless of the scan rate.Furthermore,the diffusion coefficient of [UO2Cl4]2-and the standard rate constant were estimated to be 3.7 × 10-8 cm 2 s-1 and(2.7-2.8) × 10-4 cm s-1 at 25 oC.By using the diffusion coefficient and the standard rate constant,the simulation of CVs was performed based on the reaction,[UO2Cl4]2-+ e = [UO2Cl4]3-.The simulated CVs were found to be consistent with the experimental ones.From these results,it is concluded that [UO2Cl4]2-in the mixture of EMICl and EMIBF 4 is reduced to [UO2Cl4]3-quasi-reversibly at-0.989 V vs.Fc/Fc +.OGURA Toshinari SASAKI Kotoe TAKAO Koichiro ARAI Tsuyoshi IKEDA Yasuhisa 2012Science China Chemistry2012,55,9:6
13MicroRNA-31 expression in colorectal serrated pathway progression显示文摘MicroRNAs have been increasingly recognized as useful biomarkers for colorectal cancers(CRC).We have recently observed that microRNA-31(miR-31)expression is associated with BRAF mutation and prognosis in CRC.Moreover,high miR-31 expression is frequently detected in sessile serrated adenomas compared with hyperplastic polyps(HPs).These results suggest that miR-31 may contribute to the progression of serrated lesions.At a follow-up colonoscopy,we observed the case of a 75-year-old man with a 7-mm flat-elevated lesion in the cecum and diagnosed the lesion as an early invasive carcinoma with serrated features.Tissue specimens were obtained from the representative areas to compare the molecular alterations in the carcinoma component with those in the HP component.Higher miR-31 expression was observed in the carcinoma component(57-fold increase)and the HP component(8-fold increase)compared with the paired normal mucosa,suggesting that miR-31 may be one of the key molecules in serrated pathway progression.Hironori Aoki Katsuhiko Nosho Hisayoshi Igarashi Miki Ito Kei Mitsuhashi Takafumi Naito Eiichiro Yamamoto Tokuma Tanuma Masafumi Nomura Hiroyuki Maguchi Toshiya Shinohara Hiromu Suzuki Hiroyuki Yamamoto Yasuhisa Shinomura 2014World Journal of Gastroenterology2014,20,34:5
14Analysis of the fusion hindrance in mass-symmetric heavy ion reactions显示文摘The fusion hindrance,which is also denominated by the term extra-push,is studied on mass-symmetric systems by the use of the liquid drop model with the two-center parameterization.Following the idea that the fusion hindrance exists only if the liquid drop barrier(saddle point) is located at the inner side of the contact point after overcoming the outer Coulomb barrier,the reactions in which two barriers are overlapped with each other are determined.It is shown that there are many systems where the fusion hindrance does not exist for the atomic number of projectile or target nucleus Z 43,while for Z> 43,all of the mass-symmetric reactions are fusion-hindered.ABE Yasuhisa BOILLEY David 2009Science China(Physics,Mechanics & Astronomy)2009,52,10:5
15Xyloglucan for Generating Tensile Stress to Bend Tree Stem显示文摘响应环境变化,被子植物树由形成紧张木头把他们的茎弄弯,它由充满纤维素的 G 组成(凝胶状) 在纤维房间的墙中的层并且在第二等的木部产生反常张力的应力。我们生产了转基因的白杨植物 overexpressing 在房间墙中减少每特定的多糖,,的几 endoglycanases 第二等的木部由主要、第二等的墙层组成。当水平地放了时,转基因的白杨 overexpressing xyloglucanase 的茎的基础区域不能独自在木部的紧张方面由于低紧张向上弯曲。在野类型的植物, xyloglucan 在多重 layering 期间在 G 层的内部表面被发现。在 situ xyloglucan endotransglucosylase ( XET ),活动证明整个 xyloglucan 的加入,潜在地因为墙紧缩,在内部表面层 S1 和 S2 开始了并且在整个G层开发被保留,当为墙松开的 xyloglucan heptasaccharide ( XXXG )的加入发生在膨胀地区的主要的墙中时。我们建议 xyloglucan 网络被 XET 增强形成在墙界限之间的一个进一步的连接并且分泌了 xyloglucans 以便承受在纤维素 G 层 microfibrils 以内创造的张力的压力。Kei'ichi Baba Yong Woo Park Tomomi Kaku Rumi Kaida Miyuki Takeuchi Masato Yoshida Yoshihiro Hosoo Yasuhisa Ojio Takashi Okuyama Toru Taniguchi Yasunori Ohmiya Teiji Kondo Ziv Shani Oded Shoseyov Tatsuya Awano Satoshi Serada Naoko Norioka Shigemi Norioka Takahisa Hayashi 2009Molecular Plant2009,2,5:4
16Genetic 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 2009World Journal of Gastroenterology2009,15,44:3
17Risk factors for complications of endoscopic submucosal dissection in gastric tumors: analysis of 478 lesions显示文摘Kotaro Mannen Seiji Tsunada Megumi Hara Kanako Yamaguchi Yasuhisa Sakata Takehiro Fujise Takahiro Noda Ryo Shimoda Hiroyuki Sakata Shinichi Ogata Ryuichi Iwakiri Kazuma Fujimoto 2010Journal of Gastroenterology2010,,1:3
18Risk factors for complications of endoscopic submucosal dissection in gastric tumors: analysis of 478 lesions显示文摘Kotaro Mannen Seiji Tsunada Megumi Hara Kanako Yamaguchi Yasuhisa Sakata Takehiro Fujise Takahiro Noda Ryo Shimoda Hiroyuki Sakata Shinichi Ogata Ryuichi Iwakiri Kazuma Fujimoto 2010Journal of Gastroenterology2010,,1:3
19Cancer 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 2013World Journal of Gastroenterology2013,19,11:3
20How accurately can we predict synthesis cross sections of superheavy elements?显示文摘Synthesis of superheavy elements beyond oganesson is facing new challenges as new target–projectile combinations are necessary. Guidance from models is thus expected for future experiments. However, hindered fusion models are not well established and predictions in the fission barriers span few MeVs. Consequently, predictions are not reliable. Strategies to constrain both fusion hindrance and fission barriers are necessary to improve the predictive power of the models. But, there is no hope to get an accuracy better than one order of magnitude in fusion–evaporation reactions leading to superheavy elements synthesis.David Boilley Bartholome Cauchois Hongliang Lu Anthony Marchix Yasuhisa Abe Caiwan Shen 2018Nuclear Science and Techniques2018,29,12:3
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