Yosui Tamaki

Extracellular vesicle-encapsulated miR-30e suppresses cholangiocarcinoma cell invasion and migration via inhibiting epithelial-mesenchymal transition

Early-staged cholangiocarcinoma (CCA) is difficult to diagnose due to its high potential for invasion and metastasis. Epithelial-mesenchymal transition (EMT) is induced by transforming growth factor-β (TGF-β) in a process thought to be important for invasion and metastasis in several cancers, including CCA. Although microRNAs (miRNAs) have been implicated in the pathogenesis of several malignancies, their roles to CCA are not clearly understood. Some miRNAs were reported to be included in extracellular vesicles (EVs) and transferred from their donor cells to other cells, modulating recipient cell behaviors. In this study, the involvement and functional roles of EV-contained miRNAs during EMT in human CCA were determined. Expression profiling identified a subset of miRNAs that were reduced by TGF-β in CCA cells. Among these, miR-30e was highly downregulated by TGF-β and predicted to target Snail, which is an EMT-inducible transcription factor. MiR-30e overexpression suppressed cell invasion and migration via inhibiting EMT, whereas miR-30e inhibition promoted EMT, cell invasion and migration. Moreover, miR-30e was enriched in EVs derived from CCA cells after miR-30e overexpression, and miR-30e intercellular transfer through EVs suppressed EMT, cell invasion and migration in recipient CCA cells. Together, our results suggest that EV-mediated miR-30e transfer could inhibit EMT via directly targeting Snail, which subsequently suppresses CCA cell invasion and migration. These findings provide several new insights into regulatory mechanisms of tumor invasion and metastasis in human CCA.

Tu1052 Prognostic Value of Contrast-Enhanced Ultrasonography in Patients With Small Hepatocellular Carcinoma

Introduction: Epidemiological studies have shown that nonalcoholic fatty liver disease (NAFLD) not only is a possible precursor of cirrhosis, but also has been associated with metabolic syndrome, diabetes and cardiovascular disease. There is a need to find a biomarker which proves to be reliable, non-invasive, and easy to perform in clinical practice. Our aim was to know whether serum alanine aminotransferase (ALT) value is a reliable biomarker of liver fat content in subjects with NAFLD in the general population, and to determine if the current threshold of normality for ALT is appropriate to assess the presence of liver fat in these subjects. Methods: This is a cross-sectional, randomized, prospective, populationbased study. We studied 120 healthy subjects attending health screening centers, alcohol consumption less than 50 g/week. Subjects underwent blood tests including aminotransferases. Viral hepatitis, autoimmune, drugs and others causes of liver disease were excluded. Measurements: quantification of liver fat content by spectroscopy 1H MR with magnetic field strength of 3 tesla. We used a cut off value .5% of liver fat content as the upper limit of normal for the diagnosis of hepatic steatosis (1). Serum ALT levels by commercially available kits. Results: There was an excellent positive correlation between liver fat content and serum levels of ALT (r = 0.73, p ,0.0001). All subjects with ALT values .37 U/L had hepatic steatosis (PPV: 100%) and none of the subjects with ALT ,20 U/L had steatosis (NPV: 100%). ROC curves were created, obtaining that the cutoff value that represents the normal threshold for the diagnosis of NAFLD was ALT: 23 U / L (sensitivity: 94.67%, specificity 73.91%, PPV: 85.84%, NPV: 89.47%). Conclusion: This study shows that serum ALT levels could be a reliable biomarker of NAFLD if the upper limit of normal for ALT is set at 23 U/L.

Acute renal failure in a HCV cirrhotic patient receiving interferon therapy

症例は58歳, 女性. 当科にて慢性C型肝炎と診断され, 平成4, 6年にインターフェロン (IFN) 投与を受けるも肝機能障害は続き, 平成14年4月に施行した肝生検では前肝硬変への進展が確認された. 平成14年4月30日より天然型IFNαの少量長期投与を開始したが, 平成14年9月2日の受診時, 下腿浮腫およびBUN, Cr値の軽度上昇を認め, IFN投与を中止した. その後も副腎皮質ステロイドを始めとする治療に反応することなく急速に腎不全へと進展. 10月9日より血液透析を導入したが, DICを合併し, 11月21日に死亡した. 剖検ではC型肝硬変症に合併した肝性IgA腎症と診断された. 肝硬変症に糸球体病変が高率に合併するが, 一般にはあまり知られていない. IFNによる腎障害はその多くが可逆性であるが, 潜在的に腎機能障害が存在する場合は本症例のように急速に腎不全へと進行しうる. 肝硬変症へのIFN投与の適応拡大にあたり, 充分な注意が必要である.