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| 1 | Transcriptional silencing of Dickkopf gene family by CpG island hypermethylation in human gastrointestinal cancer显示文摘AIM: To clarify alterations of Dickkopfs (Dkks) and Kremen2 (Krm2) in gastrointestinal cancer. METHODS: We investigated the expression profiles and epigenetic alterations of Dkks and Krm2 genes in gastrointestinal cancer using RT-PCR, tissue microarray analysis, and methylation specific PCR (MSP). Cancer cells were treated with the demethylating agent and/or histone deacetylase inhibitor. WST-8 assays and in vitro invasion assays after treatment with specific siRNA for those genes were performed. RESULTS: Dkks and Krm2 expression levels were reduced in a certain subset of the gastrointestinal cancer cell lines and cancer tissues. This was correlated with promoter hypermethylation. There were significant correlations between Dkks over-expression levels and beta-catenin over-expression in colorectal cancer. In colorectal cancers with beta-catenin over-expression, Dkk-1 expression levels were significantly lower in those with lymph node metastases than in those without. Down-regulation of Dkks expression by siRNA resulted in a significant increase in cancer cell growth and invasiveness in vitro.CONCLUSION: Down-regulation of the Dkks associated to promoter hypermethylation appears to be frequently involved in gastrointestinal tumorigenesis. | Tadateru Maehata Hiroaki Taniguchi Hiroyuki Yamamoto Katsuhiko Nosho Yasushi Adachi Nobuki Miyamoto Chie Miyamoto Noriyuki Akutsu Satoshi Yamaoka Fumio Itoh | 2008 | World Journal of Gastroenterology2008，14，17： | 19 |
| 2 | An 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 | 2014 | World Journal of Gastroenterology2014，20，14： | 12 |
| 3 | Evaluation of magnifying colonoscopy in the diagnosis of serrated polyps显示文摘AIM:To elucidate the colonoscopic features of serrated lesions of the colorectum using magnifying colonoscopy.METHODS:Broad division of serrated lesions of the colorectum into hyperplastic polyps(HPs),traditional serrated adenomas(TSAs),and sessile serrated adenomas/polyps(SSA/Ps) has been proposed on the basis of recent molecular biological studies.However,few reports have examined the colonoscopic features of these divisions,including magnified colonoscopic findings.This study examined 118 lesions excised in our hospital as suspected serrated lesions after magnified observation between January 2008 and September 2011.Patient characteristics(sex,age),conventional colonoscopic findings(location,size,morphology,color,mucin) and magnified colonoscopic findings(pit pattern diagnosis) were interpreted by five colonoscopists with experience in over 1000 colonoscopies,and were compared with histopathological diagnoses.The pit patterns were categorized according to Kudo's classification,but a more detailed investigation was also performed using the subclassification [type Ⅱ-Open(type Ⅱ-O),type Ⅱ-Long(type Ⅱ-L),or type Ⅳ-Serrated(type Ⅳ-S)] proposed by Kimura T and Yamano H.RESULTS:Lesions comprised 23 HPs(23/118:19.5%),39 TSAs(39/118:33.1%:with cancer in one case),50 SSA/Ps(50/118:42.4%:complicated with cancer in three cases),and six others(6/118:5.1%).We excluded six others,including three regular adenomas,one hamartoma,one inflammatory polyp,and one juvenile polyp for further analysis.Conventional colonoscopy showed that SSA/Ps were characterized as larger in diameter than TSAs and HPs(SSA/P vs HP,13.62 ± 8.62 mm vs 7.74 ± 3.24 mm,P < 0.001;SSA/Ps vs TSA,13.62 ± 8.62 mm vs 9.89 ± 5.73 mm,P < 0.01);common in the right side of the colon [HPs,30.4%(7/23):TSAs,20.5%(8/39):SSA/P,84.0%(42/50),P < 0.001];flat-elevated lesion [HPs,30.4%(7/23):TSAs,5.1%(2/39):SSA/Ps,90.0%(45/50),P < 0.001];normal-colored or pale imucosa [HPs,34.8%(8/23):TSAs,10.3%(4/39):SSA/Ps,80%(40/50),P < 0.001];and with large amounts of mucin [HPs,21.7%(5/23):TSAs,17.9%(7/39):SSA/Ps,72.0%(36/50),P < 0.001].In magnified colonoscopic findings,17 lesions showed either type Ⅱ pit pattern alone or partial type Ⅱ pit pattern as the basic architecture,with 14 HPs(14/17,70.0%) and 3 SSA/Ps.Magnified colonoscopy showed the type Ⅱ-O pit pattern as characteristic of SSA/Ps [sensitivity 83.7%(41/49),specificity 85.7%(54/63)].Cancer was also present in three lesions,in all of which a type Ⅵ pit pattern was also present within the same lesion.There were four HPs and four TSAs each.The type Ⅳ-S pit pattern was characteristic of TSAs [sensitivity 96.7%(30/31),specificity 89.9%(72/81)].Cancer was present in one lesion,in which a type Ⅵ pit pattern was also present within the same lesion.In our study,serrated lesions of the colorectum also possessed the features described in previous reports of conventional colonoscopic findings.The pit pattern diagnosis using magnifying colonoscopy,particularly magnified colonoscopic findings using subclassifications of surface architecture,reflected the pathological characteristics of SSA/Ps and TSAs,and will be useful for colonoscopic diagnosis.CONCLUSION:We suggest that this system could be a good diagnostic tool for SSA/Ps using magnifying colonoscopy. | Shinya Ishigooka Masahito Nomoto Nobuyuki Obinata Yoshichika Oishi Yoshinori Sato Satoko Nakatsu Midori Suzuki Yoshiko Ikeda Tadateru Maehata Tomoaki Kimura Yoshiyuki Watanabe Takashi Nakajima Hiro-o Yamano Hiroshi Yasuda Fumio Itoh | 2012 | World Journal of Gastroenterology2012，18，32： | 11 |
| 4 | Long-term effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer显示文摘 | Yuji Maehata Shotaro Nakamura Kiyoshi Fujisawa Motohiro Esaki Tomohiko Moriyama Kouichi Asano Yuta Fuyuno Kan Yamaguchi Issei Egashira Hyonji Kim Motonobu Kanda Minako Hirahashi Takayuki Matsumoto | 2012 | Gastrointestinal Endoscopy2012，，1： | 10 |
| 5 | Cutting edge of endoscopic full-thickness resection for gastric tumor显示文摘Recently,several studies have reported local full-thickness resection techniques using flexible endoscopy for gastric tumors,such as gastrointestinal stromal tumors,gastric carcinoid tumors,and early gastric cancer(EGC). These techniques have the advantage of allowing precise resection lines to be determined using intraluminal endoscopy. Thus,it is possible to minimize the resection area and subsequent deformity. Some of these methods include:(1) classical laparoscopic and endoscopic cooperative surgery(LECS);(2) inverted LECS;(3) combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique; and(4) non-exposed endoscopic wall-inversion surgery. Furthermore,a recent prospective multicenter trial of the sentinel node navigation surgery(SNNS) for EGC has shown acceptable results in terms of sentinel node detection rate and the accuracy of nodal metastasis. Endoscopic full-thickness resection with SNNS is expected to become a treatment option that bridges the gap between endoscopic submucosal dissection and standard surgery for EGC. In the future,the indications for these procedures for gastric tumors could be expanded. | Tadateru Maehata Osamu Goto Hiroya Takeuchi Yuko Kitagawa Naohisa Yahagi | 2015 | World Journal of Gastrointestinal Endoscopy2015，7，16： | 4 |
| 6 | Endoscopic removal of foreign bodies:A retrospective study in Japan显示文摘BACKGROUND The ingestion of foreign bodies(FBs)and food bolus impaction(FBI)in the digestive tract are commonly encountered clinical problems.Methods to handle such problems continue to evolve offering advantages,such as the avoidance of surgery,reduced cost,improved visualization,reduced morbidity,and high removal success rate.However,to date,no studies have evaluated the endoscopic management of FBs in Japan.AIM To elucidate level of safety and efficacy in the endoscopic management of FBs and FBI.METHODS A total of 215 procedures were performed at Keio University Hospital between November 2007 and August 2018.Data were collected from medical charts,and endoscopic details were collected from an endoscopic reporting system.Procedures performed with a flexible gastrointestinal endoscope were only taken into account.Patients who underwent a technique involving FB or FBI from the digestive tract were only included.Data on patient sex,patient age,outpatient,inpatient,FB type,FB location,procedure time,procedure type,removal device type,success,and technical complications were reviewed and analyzed retrospectively.RESULTS Among the 215 procedures,136(63.3%)were performed in old adults(≥60 years),180(83.7%)procedures were performed in outpatients.The most common type of FBs were press-through-pack(PTP)medications[72(33.5%)cases],FBI[47(21.9%)],Anisakis parasite(AP)[41(19.1%)cases].Most FBs were located in the esophagus[130(60.5%)cases]followed by the stomach[68(31.6%)cases].AP was commonly found in the stomach[39(57.4%)cases],and it was removed using biopsy forceps in 97.5%of the cases.The most common FBs according to anatomical location were PTP medications(40%)and dental prostheses(DP)(40%)in the laryngopharynx,PTP(48.5%)in the esophagus,AP(57.4%)in the stomach,DP(37.5%)in the small intestine and video capsule endoscopy device(75%)in the colon.A transparent cap with grasping forceps was the most commonly used device[82(38.1%)cases].The success rate of the procedure was 100%,and complication were observed in only one case(0.5%).CONCLUSION Endoscopic management of FBs and FBI in our Hospital is extremely safe and effective. | Kenji JL Limpias Kamiya Naoki Hosoe Kaoru Takabayashi Yukie Hayashi Xi Sun Ryoichi Miyanaga Kayoko Fukuhara Seiichiro Fukuhara Makoto Naganuma Atsushi Nakayama Motohiko Kato Tadateru Maehata Rieko Nakamura Koichi Ueno Junichi Sasaki Yuko Kitagawa Naohisa Yahagi Haruhiko Ogata Takanori Kanai | 2020 | World Journal of Gastrointestinal Endoscopy2020，12，1： | 3 |
| 7 | Gastrointestinal stromal tumor presenting with prominent calcification显示文摘We present a rare case of a gastrointestinal stromal tumor (GIST) in the stomach with prominent calcifica-tion at presentation. A 61-year-old woman visited our hospital because of epigastric discomfort. A spherical calcified lesion with a diameter of about 30 mm was incidentally shown in the left upper quadrant on an abdominal X-ray. Computed tomography demonstrated that the tumor was growing from the upper gastric body, with calcification in the peripheral ring area. A laparoscopic partial gastrectomy was performed, and the resected specimen revealed a well-circumscribed tumor with exophytic growth from the gastric muscularis propria. Microscopic examination revealed spindle- shaped tumor cells with calcification and hemorrhage. Additionally, positive immunoreactivity of the tumor to KIT and CD34 and a low mitotic index resulted in the diagnosis of very low risk GIST. There are a few case reports of heavily calcified GIST, although solitary or punctate calcification of primary GIST has been reported in several case series. Dystrophic calcification of necrotic or degenerative tissue is the supposed cause of primary calcified GISTs. In contrast, appearance of calcification after administration of imatinib mesylate, which may be one indicator of disease response, is possibly caused by a different mechanism. | Naoki Izawa Takeshi Sawada Ryuichi Abiko Daisuke Kumon Mami Hirakawa Mika Kobayashi Nobuyuki Obinata Masahito Nomoto Tadateru Maehata Shun-ichi Yamauchi Takefumi Kouro Takashi Tsuda Satoshi Kitajima Hiroshi Yasuda Keiichi Tanaka Ichiro Tanaka Masahiro Hoshikawa Masayuki Takagi Fumio Itoh | 2012 | World Journal of Gastroenterology2012，18，39： | 2 |
| 8 | Multicenter study of the long-term outcomes of endoscopic submucosal dissection for early gastric cancer in patients 80 years of age or older显示文摘 | Nobutsugu Abe Takuji Gotoda Toshiaki Hirasawa Shu Hoteya Kenji Ishido Yosuke Ida Hiroyuki Imaeda Eiji Ishii Atsushi Kokawa Chika Kusano Tadateru Maehata Satoshi Ono Hirohisa Takeuchi Masanori Sugiyama Shinichi Takahashi | 2012 | Gastric Cancer2012，，1： | 2 |
| 9 | 辣椒SSR标记的开发和高密度遗传连锁图谱的构建显示文摘为了方便辣椒的标记辅助育种和遗传分析,我们利用辣椒基因组富集文库和公共数据库辣椒的cDNA序列,从中开发了一批非冗余的、具有2~3个碱基基序的SSR(simple sequence repeat)标记。SSR富集文库由三种限制性内切酶(AluI、HaeⅢ、RsaI)和两种生物素标记的寡核苷酸探针b(GA)15和b(CA)15共同构建而成。从6528个克隆开发了1736个基因组SSR标记,从13003个序列中获得了1344个cDNA序列来源的SSR标记。利用自交系K9-11和MZC-180的种内杂交种(K9-11×MZC-180)获得了双单倍体分离群体,并用于遗传作图。将597个标记定位到该连锁图上,其中包括265个新开发的SSR标记。将该遗传图谱命名为KL-DH,它包括12个连锁群,覆盖了2028cM的遗传距离,标记间的平均距离少于4cM。将KL-DH图谱的框架结构与已发表的COSⅡ图谱进行了比较,并利用番茄的基因组序列来整合两个图谱。COSⅡ图谱是由C.frutescens×C.annuum种间杂种的F2分离群体构建而成。本研究所建立的种内杂交KL-DH图谱和种间杂交COSⅡ图谱在图谱长度和标记分布上比较相似,表明KL-DH图谱几乎覆盖了整个辣椒基因组。 | Toru Sugita Yukari Semi Hiromasa Sawada Yumi Utoyama Yuko Hosomi Eri Yoshimoto Yuki Maehata Hiroyuki Fukuoka Ryutaro Nagata Akio Ohyama 高凌云 孔秋生 | 2013 | 辣椒杂志2013，，2： | 2 |
| 10 | Endoscopic diagnosis of superficial non‐ampullary duodenal epithelial tumors in J apan: M ulticenter case series显示文摘 | Kenichi Goda Daisuke Kikuchi Yorimasa Yamamoto Kengo Takimoto Naomi Kakushima Yoshinori Morita Hisashi Doyama Takuji Gotoda Yuji Maehata Noritsugu Abe | 2014 | Digestive Endoscopy2014，，： | 2 |
| 11 | Long-term effect of Helicobacter pylori eradication on the development of metachronous gastric cancer aRer endoscopic resection of early gastric cancer 显示文摘 | Maehata Y Nakamum S Fujisawa K | 2012 | Gastrointest Endosc2012，75，1： | 1 |
| 12 | Correlation between the asiponeetin-liptin ratio and parameters of insulin resistance in patients with type 2 dai betes显示文摘 | INOUE M MAEHATA E YANO M | 2005 | Metabolism2005，54，： | 1 |
| 13 | Both direct and collagen-mediated signals are required for active vita- min D3-elicited differentiation of human osteoblastic cells: Roles of osterix, an osteoblast-related transcription factor 显示文摘 | Maehata Y Takamizawa S Ozawa S | 2006 | Matrix Biol2006，25，1： | 1 |
| 14 | Significance of dysadherin and E-cadherin expression in differentiated-type gastric carcinoma with submucosal invasion显示文摘 | Maehata Y Hirahashi M Aishma S | 2011 | Hum Pathol2011，42，4： | 1 |
| 15 | Design chart of gas-cooled current leads made of copper of different RRR values 显示文摘 | K Maehata K Ishibashi Y Wakuta | 1994 | Cryogenics1994，34，： | 1 |
| 16 | Increased electronegative charge of serum low-density lipoprotein in patients with diabetes mellitus显示文摘 | Yano M Inoue M Maehata E | 2004 | Clin Chim Acta2004，340，12： | 1 |
| 17 | Correlation between the adiponectin- leptin ratio and parameters of insulin resistance in patients with type 2 diabetes显示文摘 | Inoue M Maehata E Yano M | 2005 | Metabolism2005，54，3： | 1 |
| 18 | Both direct and collagen-mediated signals are required for active vitamin D3-elicited differentiation of human osteoblastic cells: roles of osterix, an osteoblast-related transcription factor显示文摘 | Maehata Y Takamizawa S Ozawa S | 2006 | Matrix Biol2006，25，1： | 1 |
| 19 | Design chart of gas-cooled cur- rent leads made of copper of different RRR values 显示文摘 | Maehata K Ishibashi K Wakuta Y | 1994 | Cryogenics1994，34，： | 1 |
| 20 | Paclitaxel inhibits expression of heat shock protein 27 in ovarian and uterine eancer cells显示文摘 | Tanaka Y Maehata K Kohno I | 2004 | Int J Gynecol Cancer2004，14，4： | 1 |
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