トリプル ネガティブ ニュウガン ニオケル プロテアソーム カンレン インシ PAG1 ニヨル シンキ ゾウショク キコウ ノ カイメイ

Triple negative breast cancer （TNBC） is considered to be one of the most aggressive subtypes of all breast cancers. To identify novel potential therapeutic targets and clarify pathophysiological features for TNBC, we conducted Meta-gene profiling analysis based on gene-expression profiling of TNBC cases purified by lasermicrobeam microdissection, and found that proteasome-associated genes （PAGs） were commonly upregulated in various pathways including cell cycle regulation in TNBC. Depletion of PAGs with RNAi caused the upregulation of p27 and p21 proteins in MDA-MB-231 and HCC1937 cells, respectively, resulting in growth inhibition. Interestingly, immunocytochmical staining revealed that PAG1 was observed in the nucleoli and/or cytoplasm （n-PAG1 and c-PAG1） in TNBC cell line and clinical specimens. Immunohistochemical staining of 100 TNBCs showed that high level of n-PAG1 was significantly associated with poor disease free and overall survival of TNBC patients. These results indicate that n-PAG1 plays a critical role in nucleus during cell cycle progression and might be a novel prognostic indicator or an attractive molecular target of TNBC

Non-bismuth quadruple therapy for first-line Helicobacter pylori eradication: A randomized study in Japan

AIM: To find the way to improve the eradication rate of first-line therapy in Japanese patients

野生カイツブリ若鳥のEustrongylidosisによる死亡例

A young male little grebe (Tachybaptus ruficollis), caught at Kobe in Hyogo Prefecture, Japan in December 1995, died of a severe infection with Eustrongylides tubifex Jagerskiold 1909 (Nematoda:Dioctophymatoidea). Numerous nematodes were found in the lumen of the proventriculus, attaching to the mucosa, and some were penetrating into muscle layer. Histopathologically, severe inflammation was found around the nematodes. E.tubifex may be one of factors contributing to the mortality of wild little grebes. 野生カイツブリ(Tachybaptus ruficollis)一羽が兵庫県下で衰弱のために保護され死亡した。剖検により腺胃漿膜面に付着する多数の線虫(Eustrongylides tubifex)が認められ, 筋層を貫通して内腔に頭部もしくは尾部を露出していた。病理組織学的には線虫が侵入した周囲組織に炎症性細胞浸潤を伴う高度な病変が認められ, 本線虫寄生が野生における死因のひとつになっていると推察された

Helicobacter pylori Induces IκB Kinase α Nuclear Translocation and Chemokine Production in Gastric Epithelial Cells

NF-κB is an important transcriptional factor that is involved in multiple cellular responses, such as inflammation and antiapoptosis. IκB kinase α (IKKα) and IKKβ, which are critical regulators of NF-κB activity, possess various mechanisms for NF-κB activation. This variability in NF-κB signaling may be associated with distinct inflammatory responses in specific cell types. The gastric pathogen Helicobacter pylori is known to activate NF-κB. However, the role of IKK in H. pylori infection remains unclear. In this report, we show that H. pylori activates both IKKα and IKKβ in gastric cancer cells and enhances NF-κB signaling in distinct manners. We found that IKKβ acted as an IκBα kinase during H. pylori infection, whereas IKKα did not. H. pylori induced IKKα nuclear translocation in time-, multiplicity of infection-, and cag pathogenicity island-dependent manners. In contrast, p100 processing, which is a known IKKα activity induced by several cytokines, was not induced by H. pylori. Both IKKs were responsible for chemokine secretion by infected cells. However, the antiapoptotic effect of H. pylori was merely transduced by IKKβ. Microarray analysis and real-time PCR indicated that both IKKs were involved in the transcriptional activation of genes associated with inflammation, antiapoptosis, and signal transduction. Our results indicate that H. pylori activates NF-κB via both IKKα and IKKβ using distinct mechanisms. IKKα nuclear translocation induced by H. pylori is indispensable for appropriate inflammatory responses but not for antiapoptosis, which suggests a critical role for IKKα in gastritis development