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Alterations in the human epidermal growth factor receptor 2-phosphatidylinositol 3-kinase-v-Akt pathway in gastric cancer

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World Journal of Gastroenterology 2012年第45期18卷 6577-6586页

作者： 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 First Department of Internal Medicine Sapporo Medical University School of MedicineSapporo 60-8543Japan Department of Molecular Biology Sapporo Medical University School of MedicineSapporo 60-8543Japan First Department of Surgery Sapporo Medical University School of MedicineSapporo 60-8543Japan Department of Gastroenterology JR Sapporo HospitalSapporo 60-8543Japan Department of Surgery Sapporo Gekakinen HospitalSapporo 60-8543Japan Department of Surgical Pathology Sapporo Medical University HospitalSapporo 60-8543Japan Division of Cancer Research The Institute of Medical ScienceThe University of TokyoTokyo 108-8639Japan

AIM:To investigate human epidermal growth factor receptor 2(HER2)-phosphatidylinositol 3-kinase(PI3K)-vAkt murine thymoma viral oncogene homolog signaling ***:We analyzed 231 formalin-fixed,paraffinembedded gastric cancer tissue specimens from Japanese patients who had undergone surgical *** patients' age,sex,tumor location,depth of invasion,pathological type,lymph node metastasis,and pathological stage were determined by a review of the medical *** of HER2 was analyzed by immunohistochemistry(IHC) using the HercepTest TM *** criteria for HER2 positivity(0,1+,2+,and 3+) were *** that scored 3+ were considered *** of phospho Akt(pAkt) was also analyzed by *** were considered pAkt-positive when the percentage of positive tumor cells was 10% or ***3K,catalytic,alpha polypeptide(PIK3CA) mutations in exons 1,9 and 20 were analyzed by ***-Barr virus(EBV) infection was analyzed by in situ hybridization targeting EBV-encoded small RNA(EBER) with an EBER-RNA *** instability(MSI) was analyzed by polymerase chain reaction using the mononucleotide markers BAT25 and ***:HER2 expression levels of 0,1+,2+ and 3+ were found in 167(72%),32(14%),12(5%) and 20(8.7%) samples,***2 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 *** in exons 1,9 and 20 were detected in 5(2%),9(4%) and 7(3%) cases,*** new types of PIK3CA mutation,R88Q and R108H,were found in *** PIK3CA mutations were heterozygous missense singlebase substitutions,the most common being H1047R(6/20,30%) in *** cancers(8%) were EBV-positive and this positivity significantly correlated with a diffu

关键词： Human epidermal growth factor receptor 2 Phosphatidylinositol 3-kinase Catalytic Alpha polypep-tide Epstein-Barr virus Aid: Gastric cancer

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Cancer detection by ubiquitin carboxyl-terminal esterase L1 methylation in pancreatobiliary fluids

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World Journal of Gastroenterology 2013年第11期19卷 1718-1727页

作者： Norihiro Kato Hiroyuki Yamamoto Yasushi Adachi Hirokazu Ohashi Hiroaki Taniguchi Hiromu Suzuki mayumi nakazawa Hiroyuki Kaneto Shigeru Sasaki Kohzoh Imai Yasuhisa Shinomura First Department of Internal Medicine Sapporo Medical University School of MedicineSapporo 060-8543Japan The Section of Antibody Vaccine and Molecular Targeted Therapy ResearchThe Institute of Medical ScienceThe University of TokyoTokyo 108-8639Japan Department of Molecular Biology Sapporo Medical University School of MedicineSapporo 060-8556Japan Division of Gastroenterology Muroran City General HospitalMuroran 051-8512Japan

AIM:To evaluate the utility of measuring epigenetic alterations in pancreatic and biliary fluids in determining molecular markers for pancreatobiliary ***:DNA was extracted from undiluted pancreatic and biliary *** a surrogate for a genomewide hypomethylation assay,levels of long interspersed nuclear element-1(LINE-1) methylation were analyzed using bisulfite *** 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 *** 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 *** the treatment,UCHL1 expression was analyzed by real-time reverse transcription-polymerase chain ***: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 *** of the UCHL1 gene was cancer-specific and most frequently detected in pancreatic(67%) or biliary(70%) fluids from patients with pancreatobiliary *** a single marker,hypermethylation of the UCHL1 gene in pancreatic and biliary fluids was most useful for the de

关键词： Pancreatobiliary cancers DNA methylation Pancreatobiliary fluids Ubiquitin carboxyl-terminal esterase L1 Runt-related transcription factor 3

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