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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 | New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brainrelated diseases显示文摘Brain-derived neurotrophic factor(BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has beenreported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer's disease, Huntington's disease, depression and schizophrenia. | Naoki Adachi Tadahiro Numakawa Misty Richards Shingo Nakajima Hiroshi Kunugi | 2014 | World Journal of Biological Chemistry2014，5，4： | 30 |
| 3 | Removal of diminutive colorectal polyps: A prospective randomized clinical trial between cold snare polypectomy and hot forceps biopsy显示文摘AIM To compare the efficacy and safety of cold snare polypectomy(CSP) and hot forceps biopsy(HFB) for diminutive colorectal polyps.METHODS This prospective, randomized single-center clinical trial included consecutive patients ≥ 20 years of age with diminutive colorectal polyps 3-5 mm from December 2014 to October 2015. The primary outcome measures were en-bloc resection(endoscopic evaluation) and complete resection rates(pathological evaluation). The secondary outcome measures were the immediate bleeding or immediate perforation rate after polypectomy, delayed bleeding or delayed perforation rate after polypectomy, use of clipping for bleeding or perforation, and polyp retrieval rate. Prophylactic clipping after polyp removal wasn't routinely performed.RESULTS Two hundred eight patients were randomized into the CSP(102), HFB(106) and 283 polyps were evaluated(CSP: 148, HFB: 135). The en-bloc resection rate was significantly higher with CSP than with HFB [99.3%(147/148) vs 80.0%(108/135), P < 0.0001]. The complete resection rate was significantly higher with CSP than with HFB [80.4%(119/148) vs 47.4%(64/135), P < 0.0001]. The immediate bleeding rate was similar between the groups [8.6%(13/148) vs 8.1%(11/135), P = 1.000], and endoscopic hemostasis with hemoclips was successful in all cases. No cases of perforation or delayed bleeding occurred. The rate of severe tissue injury to the pathological specimen was higher HFB than CSP [52.6%(71/135) vs 1.3%(2/148), P < 0.0001]. Polyp retrieval failure was encountered CSP(7), HFB(2).CONCLUSION CSP is more effective than HFB for resecting diminutive polyps. Further long-term follow-up study is required. | Yoriaki Komeda Hiroshi Kashida Toshiharu Sakurai George Tribonias Kazuki Okamoto Masashi Kono Mitsunari Yamada Teppei Adachi Hiromasa Mine Tomoyuki Nagai Yutaka Asakuma Satoru Hagiwara Shigenaga Matsui Tomohiro Watanabe Masayuki Kitano Takaaki Chikugo Yasutaka Chiba Masatoshi Kudo | 2017 | World Journal of Gastroenterology2017，23，2： | 20 |
| 4 | 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 |
| 5 | 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 |
| 6 | 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 |
| 7 | Interrelationship 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 | 2012 | World Journal of Gastroenterology2012，18，22： | 14 |
| 8 | 小菜蛾对4种农药抗药性的研究显示文摘用浸叶法测定了日本关西地区小菜蛾幼虫对乙酰甲胺磷、巴丹、氯氰菊酯和Bt4种不同类型农药的抗药性。试验明确小菜蛾在当地对上述4种参试农药都已产生不同程度抗药性。小菜蛾R系幼虫在240mg/kg氯氰菊酯、200μl/LBt浓度下死亡率分别仅为37%、72%。 | 陈满盈 Adachi Toshikazu | 1999 | 植物保护1999，25，1： | 12 |
| 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 | Genomic characterization of esophageal squamous cellcarcinoma:insights from next-generation sequencing显示文摘Two major types of cancer occur in the esophagus: squamous cell carcinoma, which is associated with chronic smoking and alcohol consumption, and adenocarcinoma, which typically arises in gastric reflux-associated Barrett's esophagus. Although there is increasing incidence of esophageal adenocarcinoma in Western counties, esophageal squamous cell carcinoma(ESCC) accounts for most esophageal malignancies in East Asia, including China and Japan. Technological advances allowing for massively parallel, high-throughput next-generation sequencing(NGS) of DNA have enabled comprehensive characterization of somatic mutations in large numbers of tumor samples. Recently, several studies were published in which whole exome or whole genome sequencing was performed in ESCC tumors and compared with matched normal DNA. Mutations were validated in several genes, including in TP53, CDKN2 A, FAT1, NOTCH1, PIK3 CA, KMT2 D and NFE2L2, which had been previously implicated in ESCC. Several new recurrent alterations have also been identified in ESCC. Combining the clinicopathological characteristics of patients with information obtained from NGS studies may lead to the development of effective diagnostic and therapeutic approaches for ESCC. As this research becomes more prominent, it is important that gastroenterologist become familiar with the various NGS technologies and the results generated using these methods. In the present study, we describe recent research approaches using NGS in ESCC. | Yasushi Sasaki Miyuki Tamura Ryota Koyama Takafumi Nakagaki Yasushi Adachi Takashi Tokino | 2016 | World Journal of Gastroenterology2016，22，7： | 10 |
| 11 | Morphology Control of Anatase TiO2 by Surfactant-assisted Hydrothermal Method显示文摘由在长烃的水疗院 lysing 钛 isopropoxide 锁住包含表面活化剂的答案,有多种明确的形态学的 TiO2 好粒子被一条热水的线路在这研究综合。结构的变化被扫描电子显微镜学,传播电子显微镜学和 X 光检查衍射分析在形成过程期间监视。有象粒子,表,杆,试管和象花的形状那样的各种各样的形态学的 TiO2 被小心地控制准备条件获得。因为它能在 TiO2 表面上在解决方案和表面活化剂的吸附潜力改变表面活化剂的费用状态,试验性的结果证明 pH 值为生产 TiO2 的形状控制是关键的。锐钛矿 TiO2 的形状发展被在不同舞台熄灭反应阐明,不同塑造的 TiO2 的形成机制被建议。 | 王富民 石战胜 巩峰 酒金亭 ADACHI Motonari | 2007 | Chinese Journal of Chemical Engineering2007，15，5： | 10 |
| 12 | New anti-proliferative agent,MK615,from Japanese apricot “Prunus mume” induces striking autophagy in colon cancer cells in vitro显示文摘AIM: To investigate the anti-neoplastic effects of MK615, an extract from the Japanese apricot (Prunus mume), against colon cancer cells. METHODS: Three colon cancer cell lines, SW480, COLO, and WiDr, were cultured with MK615. Growth inhibition was evaluated by cell proliferation assay and killing activity was determined by lactate dehydrogenase assay. Induction of apoptosis was evaluated by annexin Ⅴ flow cytometry. Morphological changes were studied by light and electron microscopy, and immunofluorescence staining with Atg8. RESULTS: MK615 inhibited growth and lysed SW480, COLO and WiDr cells in a dose-dependent manner. Annexin Ⅴ flow cytometry showed that MK615 induced apoptosis after 6 h incubation, at which point the occurrence of apoptotic cells was 68.0%, 65.7% and 64.7% for SW480, COLO, and WiDr cells, respectively. Light and electron microscopy, and immunofluorescence staining with Atg8 revealed that MK615 induced massive cytoplasmic vacuoles (autophagosomes) in all three cell lines. CONCLUSION: MK615 has an anti-neoplastic effect against colon cancer cells. The effect may be exerted by induction of apoptosis and autophagy. | Shozo Mori Tokihiko Sawada Toshie Okada Tatsushi Ohsawa Masakazu Adachi Kubota Keiichi | 2007 | World Journal of Gastroenterology2007，13，48： | 9 |
| 13 | Efficacy 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 | 2005 | World Journal of Gastroenterology2005，11，10： | 9 |
| 14 | Development of 2D Temperature and Concentration Measurement Method Using Tunable Diode Laser Absorption Spectroscopy显示文摘 | Yoshihiro Deguchi Daisuke Yasui Akira Adachi | 2012 | Journal of Mechanics Engineering and Automation2012，2，9： | 7 |
| 15 | Functional interactions between steroid hormones and neurotrophin BDNF显示文摘Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS) .Though BDNF has two types of receptors,high affinity tropomyosin-related kinase(Trk) B and low affinity p75 receptors,BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogenactivated protein kinase/extracellular signal-regulated protein kinase,phospholipase Cγ,and phosphoinositide 3-kinase pathways.Notably,it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke,Parkinson's disease,Alzheimer's disease,and mental disorders.On the other hand,glucocorticoids,stress-induced steroid hormones,also putatively contribute to the pathophysiology of depression.Interestingly,in addition to the reduction in BDNF levels due to increased glucocorticoid exposure,current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones,such as estrogen,are involved in not only sexual differentiation in the brain,but also numerous neuronal events including cell survival and synaptic plasticity.Furthermore,it is well known that estrogen plays a role in the pathophysiology of Parkinson's disease,Alzheimer's disease,and mental illness,while serving to regulate BDNF expression and/or function.Here,we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones(glucocorticoids and estrogen). | Tadahiro Numakawa Daisaku Yokomaku Misty Richards Hiroaki Hori Naoki Adachi Hiroshi Kunugi | 2010 | World Journal of Biological Chemistry2010，1，5： | 7 |
| 16 | 基于模糊语言变量的动态目标无线网络选择技术(英文)显示文摘Even though various wireless Network Access Technologies(NATs)with different specifications and applications have been developed in the recent years,no single wireless technology alone can satisfy the anytime,anywhere,and any service wireless-access needs of mobile users.A real seamless wireless mobile environment is only realized by considering vertical and horizontal handoffs together.One of the major design issues in heterogeneous wireless networks is the support of Vertical Handoff(VHO).VHO occurs when a multi-interface enabled mobile terminal changes its Point of Attachment(PoA)from one type of wireless access technology to another,while maintaining an active session.In this paper we present a novel multi-criteria VHO algorithm,which chooses the target NAT based on several factors such as user preferences,system parameters,and traffic-types with varying Quality of Service(QoS)requirements.Two modules i.e.,VHO Necessity Estimation(VHONE)module and target NAT selection module,are designed.Both modules utilize several'weighted'users’and system’s parameters.To improve the robustness of the proposed algorithm,the weighting system is designed based on the concept of fuzzy linguistic variables. | Faisal Kaleem Abolfazl Mehbodniya Arif Islam Kang K.Yen Fumiyuki Adachi | 2013 | China Communications2013，10，1： | 6 |
| 17 | MK615 inhibits pancreatic cancer cell growth by dual inhibition of Aurora A and B kinases显示文摘AIM:To investigate the anti-neoplastic effect of MK615, an anti-neoplastic compound isolated from Japanese apricot, against human pancreatic cancer cells in vitro. METHODS: Three human pancreatic cancer cell lines PANC-1, PK-1, and PK45H were cultured with MK615 at concentrations of 600, 300, 150, and 0 μg/mL. Growth inhibition was evaluated by cell proliferation assay, and killing activity was determined by lactate dehydrogenase (LDH) assay. Expression of Aurora A and B kinases was detected by real-time polymerase chain reaction (PCR) and Western blotting. Cell cycle stages were evaluated by flow cytometry. RESULTS: The growth inhibitory rates of MK615 at 150, 300, and 600 μg/mL were 2.3% ± 0.9%, 8.9% ± 3.2% and 67.1% ± 8.1% on PANC1 cells, 1.3% ± 0.3%, 8.7% ± 4.1% and 45.7 ± 7.6% on PK1 cells, and 1.2 ± 0.8%, 9.1% ± 2.1% and 52.1% ± 5.5% on PK45H cells, respectively (P <0.05). The percentage cytotoxicities of MK615 at 0, 150, 300, and 600 μg/mL were 19.6% ± 1.3%, 26.7% ± 1.8%, 25.5% ± 0.9% and 26.4% ± 0.9% in PANC1 cells, 19.7% ± 1.3%, 24.7% ± 0.8%, 25.9% ± 0.9% and 29.9% ± 1.1% in PK1 cells, and 28.0% ± 0.9%, 31.2% ± 0.9%, 30.4% ± 1.1% and 35.3 ± 1.0% in PK45H cells, respectively (P < 0.05). Real-time PCR and Western blotting showed that MK615 dually inhibited the expression of Aurora A and B kinases. Cell cycle analysis revealed that MK615 increased the population of cells in G2/M phase. CONCLUSION: MK615 exerts an anti-neoplastic effect on human pancreatic cancer cells in vitro by dual inhibition of Aurora A and B kinases. | Toshie Okada Tokihiko Sawada Tatsushi Osawa Masakazu Adachi Keiichi Kubota | 2008 | World Journal of Gastroenterology2008，14，9： | 6 |
| 18 | MK615 decreases RAGE expression and inhibits TAGE-induced proliferation in hepatocellular carcinoma cells显示文摘AIM:To investigate the proliferative effect of advanced glycation end-products(AGEs) and the role of their cellular receptor(RAGE) on hepatocellular carcinoma(HCC) cells,and the inhibitory effects of MK615,an extract from Japanese apricot,against AGEs were also evaluated.METHODS:Two HCC cell lines,HuH7 and HepG2,were used.Expression of RAGE was investigated by poly-merase chain reaction,Western blotting,and flow cytemetry(FACS).The effect of MK615 on RAGE expression was also evaluated by FACS.The proliferative effects of a control(unglycated bovine serum albumin),glucosederived AGEs(Glc-AGE),and glyceraldehyde-derived AGEs(Glycer-AGE),and the anti-proliferative effect of MK615 against AGEs,were evaluated using MTT assays.RESULTS:Expression of RAGE was confirmed at both the mRNA and protein levels in both HuH7 and HepG2.FACS revealed that the level of RAGE expression was higher in HuH7 than in HepG2.Treatment with 0.1 μg/mL MK615 decreased the expression level of RAGE from 24.3% to 3.7% in HuH7 and from 6.2% to 4.8% in HepG2.The growth indices for the control,Glc-AGE,and Glycer-AGE were 1.06 ± 0.08,0.99 ± 0.04,and 1.38 ± 0.05,respectively,in HuH7(P = 0.037),and were 1.03 ± 0.04,1.04 ± 0.03,and 1.07 ± 0.05,respectively,in HepG2(P > 0.05).When the cells were cultured simultaneously with Glycer-AGE and MK615,MK615 abrogated the proliferative effect of Glycer-AGE in HuH7.CONCLUSION:Only Glycer-AGE has a proliferative effect on HuH7,which expresses a higher level of RAGE.MK615 suppresses the proliferative effect of GlycerAGE on HuH7 by decreasing the expression of RAGE. | Yuhki Sakuraoka Tokihiko Sawada Toshie Okada Takayuki Shiraki Yoshikazu Miura Katsuya Hiraishi Tatsushi Ohsawa Masakazu Adachi Jun-ichi Takino Masayoshi Takeuchi Keiichi Kubota | 2010 | World Journal of Gastroenterology2010，16，42： | 6 |
| 19 | CD1a在具有血管周上皮样细胞分化的肿瘤中的表达显示文摘 | Adachi Y Horie Y Kitamura Y 樊祥山(摘译) | 2008 | 临床与实验病理学杂志2008，24，3： | 5 |
| 20 | Proposal of criteria to select candidates with colorectal liver metastases for hepatic resection:Comparison of our scoring system to the positive number of risk factors显示文摘AIM: To select accurately good candidates of hepatic resection for colorectal liver metastasis. METHODS: Thirteen clinicopathological features, which were recognized only before or during surgery, were selected retrospectively in 81 consecutive patients in one hospital (GroupⅠ). These features were entered into a multivariate analysis to determine independent and significant variables affecting long-term prognosis after hepatectomy. Using selected variables, we created a scoring formula to classify patients with colorectal liver metastases to select good candidates for hepatic resection. The usefulness of the new scoring system was examined in a series of 92 patients from another hospital (Group Ⅱ), comparing the number of selected variables. RESULTS: Among 81 patients of GroupⅠ, multivariate analysis, i.e. Cox regression analysis, showed that multiple tumors, the largest tumor greater than 5 cm in diameter, and resectable extrahepatic metastases were significant and independent prognostic factors for poor survival after hepatectomy (P < 0.05). In addition, these three factors: serosa invasion, local lymph node metastases of primary cancers, and post- operative disease free interval less than 1 year including synchronous hepatic metastasis, were not significant, however, they were selected by a stepwise method of Cox regression analysis (0.05 < P < 0.20). Using these six variables, we created a new scoring formula to classify patients with colorectal liver metastases. Finally, our new scoring system not only classified patients in GroupⅠvery well, but also that in Group Ⅱ, according to long-term outcomes after hepatic resection. The positive number of these six variables also classified them well.CONCLUSION: Both, our new scoring system and the positive number of significant prognostic factors are useful to classify patients with colorectal liver metastases in the preoperative selection of good candidates for hepatic resection. | Ikuo Nagashima Tadahiro Takada Miki Adachi Hirokazu Nagawa Tetsuichiro Muto Kota Okinaga | 2006 | World Journal of Gastroenterology2006，12，39： | 5 |
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