Exosomal p38 Mitogen-activated Protein Kinase Promotes Tumour Repopulation in -mutated Bile Duct Cancer Cells.

Background/aim: Tumour repopulation is a major obstacle for successful cancer treatment. This study investigated whether anticancer agents contribute to tumour repopulation in TP53-mutated bile duct cancer cells.

Materials And Methods: TP53-mutated HuCCT1 and HuH28 cells were exposed to anticancer agents, and recipient cells were exposed to their conditioned media or exosomes.

[Retracted] Alteration of p53-binding protein 1 expression as a risk factor for local recurrence in patients undergoing resection for extrahepatic cholangiocarcinoma.

Following the publication of this paper, the Journal was alerted by an investigation committee of Niigata University to the fact that the paper had been identified as a duplicate publication, which had already been published. Therefore, in accordance with the rules of Niigata University Fraud Investigation committee, a request was made that the paper be retracted. After having been in contact with the authors, they agreed with the decision to retract the paper.

Dysregulation of sphingolipid metabolic enzymes leads to high levels of sphingosine-1-phosphate and ceramide in human hepatocellular carcinoma.

Aim: Sphingosine-1-phosphate (S1P) and ceramide are bioactive sphingolipids known to be important in regulating numerous processes involved in cancer progression. The aim of this study was to determine the absolute levels of sphingolipids in hepatocellular carcinoma (HCC) utilizing data obtained from surgical specimens. In addition, we explored the clinical significance of S1P in patients with HCC and the biological role of S1P in HCC cells.

Urokinase-type Plasminogen Activator Is a Therapeutic Target for Overcoming Sorafenib Resistance in Hepatoma Cells.

Background/aim: Sorafenib is a multikinase inhibitor approved as a first-line therapy for hepatocellular carcinoma. This study examined the sorafenib resistance mechanism.

Materials And Methods: Hepatoma HepG2 cells were exposed to sorafenib, and the biological activity of the conditioned media was analyzed using cell proliferation/apoptosis assays, multiplex immunoassays, ELISA, and western blot analyses.

Activin a Receptor Type 2A Mutation Affects the Tumor Biology of Microsatellite Instability-High Gastric Cancer.

Background: Activin A receptor type 2A (ACVR2A) is one of the most frequently mutated genes in microsatellite instability-high (MSI-H) gastric cancer. However, the clinical relevance of the ACVR2A mutation in MSI-H gastric cancer patients remains unclear. The aims of this study were to explore the effect of ACVR2A mutation on the tumor behavior and to identify the clinicopathological characteristics of gastric cancer patients with ACVR2A mutations.

Changes in disease characteristics of primary biliary cholangitis: An observational retrospective study from 1982 to 2016.

Aim: Disease characteristics of primary biliary cholangitis have changed recently. However, detailed studies on the subject have been limited. Therefore, we aimed to clarify disease characteristics of patients with recent primary biliary cholangitis using the cohort from Niigata University and 21 affiliated hospitals.

Epidermal growth factor receptor/heme oxygenase-1 axis is involved in chemoresistance to cisplatin and pirarubicin in HepG2 cell lines and hepatoblastoma specimens.

Purpose: To investigate the possibility that the antioxidant stress protein Heme oxygenase-1 (HO-1) is involved in the acquisition of chemoresistance in cisplatin and pirarubicin (CITA) therapy.

Methods: Human hepatoblastoma-derived cell line (HepG2) was used to generate a knockdown cell line of HO-1 by small interfering RNA (siRNA). Expression of HO-1, epidermal growth factor receptor (EGFR), Akt, and extracellular signal-regulated kinase1/2 (ERK1/2) was examined by Western blot.

Overexpression of a disintegrin and metalloproteinase 21 is associated with motility, metastasis, and poor prognosis in hepatocellular carcinoma.

Cell motility plays an important role in intrahepatic metastasis of hepatocellular carcinoma (HCC), and predicts poor prognosis in patients. The present study investigated the role of a disintegrin and metalloproteinases (ADAMs) in HCC, since these proteins are known to be associated with cell motility. We confirmed the expression of 12 ADAMs with putative metalloproteinase activity in HCC cells, and established a KYN-2 HCC cell line stably expressing short interfering RNA against ADAM21 to investigate the effect of ADAM21 deficiency on HCC cell motility and metastasis in vitro and in vivo.

Oncogenic role of p21 in hepatocarcinogenesis suggests a new treatment strategy.

A well-known tumor suppressor, p21, acts paradoxically by promoting tumor growth in some cellular conditions. These conflicting functions have been demonstrated in association with the HBx gene and in hepatocarcinogenesis. The molecular behavior of p21 depends on its subcellular localization.

DNA damage response and sphingolipid signaling in liver diseases.

Patients with unresectable hepatocellular carcinoma (HCC) cannot generally be cured by systemic chemotherapy or radiotherapy due to their poor response to conventional therapeutic agents. The development of novel and efficient targeted therapies to increase their treatment options depends on the elucidation of the molecular mechanisms that underlie the pathogenesis of HCC. The DNA damage response (DDR) is a network of cell-signaling events that are triggered by DNA damage.

Comparison of Number Versus Ratio of Positive Lymph Nodes in the Assessment of Lymph Node Status in Extrahepatic Cholangiocarcinoma.

Background: This study aimed to compare the utility of the number of positive lymph nodes with the lymph node ratio (LNR) in predicting survival after resection of extrahepatic cholangiocarcinoma.

Methods: A retrospective analysis of 142 consecutive patients who underwent radical resection of extrahepatic cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were resected.

Sphingosine-1-phosphate transporters as targets for cancer therapy.

Sphingosine-1-phosphate (S1P) is a pleiotropic lipid mediator that regulates cell survival, migration, the recruitment of immune cells, angiogenesis, and lymphangiogenesis, all of which are involved in cancer progression. S1P is generated inside cancer cells by sphingosine kinases then exported outside of the cell into the tumor microenvironment where it binds to any of five G protein coupled receptors and proceeds to regulate a variety of functions. We have recently reported on the mechanisms underlying the "inside-out" signaling of S1P, its export through the plasma membrane, and its interaction with cell surface receptors.

Alcoholic liver disease complicated by deep bleeding into the muscles or retroperitoneum: report of three cases and a review of the literature.

We herein report three cases of alcoholic cirrhosis complicated by deep bleeding. In two of the three cases, intramuscular or retroperitoneal hematomas developed spontaneously. In contrast, in the remaining case, an intramuscular hematoma developed after trauma.

Hepatitis B virus X stimulates redox signaling through activation of ataxia telangiectasia mutated kinase.

Hepatitis B virus X (HBX) protein plays a crucial role in carcinogenesis, but its mechanism is unclear. The involvement of ataxia telangiectasia mutated (ATM) kinase in the enhanced redox system was investigated by examining the phosphorylation level of ATM in HBX gene-transfected cells and in transgenic mice following redox system manipulation by treatment with hydrogen peroxide (H2O2) or antioxidant. Western blotting and immunostaining showed that phospho-ATM was significantly increased by HBX both in vitro (3.

Imbalance between CD56+bright and CD56+dim natural killer cell subsets in the liver of patients with recurrent hepatitis C after liver transplantation.

Progressive liver fibrosis remains a major problem for patients with recurrent chronic hepatitis C(CHC) after liver transplantation (LT). However, the involvement of natural killer (NK) and natural killer T (NKT) cells, which predominate in the liver, in recurrent CHC after LT remains unclear.In the present study, we investigated the status of NK and NKT cells in the liver and peripheral blood obtained from 10 patients with recurrent CHC after LT (LT-C), 15 patients with CHC, and 7 normal donors for living donor LT.

Valproic acid overcomes transforming growth factor-β-mediated sorafenib resistance in hepatocellular carcinoma.

Sorafenib is a multi-kinase inhibitor approved for hepatocellular carcinoma, but rarely causes tumor regression in patients with chronic liver diseases. To investigate whether growth factor-mediated signaling is involved in sorafenib resistance, HepG2 and PLC/PRF/5 hepatoma cells were exposed to epidermal growth factor (EGF), hepatocyte growth factor (HGF) or transforming growth factor-β (TGF-β) prior to treatment with sorafenib. Furthermore, to identify an effective combination treatment with sorafenib, growth factor-sensitized cells were treated with sorafenib alone or in combination with celecoxib, lovastatin or valproic acid (VPA).

Increase of fucosylated alpha-fetoprotein fraction at the onset of autoimmune hepatitis and acute liver failure.

Aim: Increased serum α-fetoprotein (AFP) has been associated with a good prognosis following acute liver failure (ALF), but the levels of the fucosylated fraction of AFP (Lens culinaris agglutinin-reactive fraction of AFP [AFP-L3]) following acute liver injury remain unknown. The aim of the present study was to investigate the clinical significance of AFP and AFP-L3 in patients with acute liver injury.

Methods: We investigated the serum levels of AFP and highly sensitive AFP-L3% in 27 patients with acute-onset autoimmune hepatitis (AIH), 28 patients with acute hepatitis (AH) and 22 patients with ALF at the onset using a highly sensitive immunoassay (micro-total analysis system).

p27 Is a critical prognostic biomarker in non-alcoholic steatohepatitis-related hepatocellular carcinoma.

Non-alcoholic steatohepatitis (NASH) is a recently identified chronic liver disease, which progresses to liver cirrhosis and hepatocellular carcinoma (HCC). As the number of patients studied to date has been limited, clinically useful prognostic biomarkers of NASH-related HCC have not been available. In this study, we investigated the status of a cell-cycle regulator, p27, in NASH-related HCC.

Effects of rapamycin on granulation formation in response to centrally doubled coiled stents as a tracheal substitute.

Introduction: In experiments involving tracheal wall defects in rabbits, metallic coil stents inevitably induce granulation formation in the defects. We examined the involvement of the mammalian target of rapamycin (mTOR) signaling pathway in granulation formation and examined the effects of rapamycin.

Methods: The anterior half of the tracheal wall was removed for a longitudinal length of six tracheal rings.

Mycotoxins are conventional and novel risk biomarkers for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant disease with poor prognosis. To improve the clinical outcome, early diagnosis of HCC arising from nonviral agents and hepatitis virus is important. Among several etiological factors, mycotoxins defined as carcinogens by the International Agency for Research in Cancer (IARC) might be one of the critical risk factors for nonviral HCC.

Clinical significance of cell cycle inhibitors in hepatocellular carcinoma.

It is well accepted that cell cycle regulators are strongly implicated in the progression of cancer development. p16 and p27 are potent cyclin-dependent kinase (CDK) inhibitors involved in G1 phase progression, and are regarded as adverse prognostic biomarkers for various types of cancers. It has been reported that the main mechanism for p16 inactivation is aberrant DNA methylation, while p27 is exclusively inactivated by proteasome-mediated protein degradation.

Hepatitis B virus X induces cell proliferation in the hepatocarcinogenesis via up-regulation of cytoplasmic p21 expression.

Background: Hepatitis B virus X protein (HBx) has been shown to induce hepatocarcinogenesis by disrupting the functions of intracellular molecules. Cyclin-dependent kinase inhibitor p21 (Cip1/WAF1), known as a tumour-suppressor gene, has been reported to have paradoxical function, that is, acting as an oncogene, particularly when expressed in the cytoplasm. The effects of HBx on the expression and function of p21 also remain controversial.

DNA damage sensor γ -H2AX is increased in preneoplastic lesions of hepatocellular carcinoma.

Background: Phosphorylated histone H2AX ( γ -H2AX) is a potential regulator of DNA repair and is a useful tool for detecting DNA damage. To evaluate the clinical usefulness of γ -H2AX in hepatocellular carcinoma (HCC), we measured the level of γ -H2AX in HCC, dysplastic nodule, and nontumorous liver diseases.

Methods: The level of γ -H2AX was measured by immunohistochemistry in fifty-eight HCC, 18 chronic hepatitis, 22 liver cirrhosis, and 19 dysplastic nodules.

P21-activated kinase-2 is a critical mediator of transforming growth factor-β-induced hepatoma cell migration.

Background And Aim: Transforming growth factor-β (TGF-β) has been shown to play a central role in the promotion of cell motility, but its functional mechanism has remained unclear. With the aim of investigating the diagnostic and treatment modalities for patients with hepatocellular carcinoma (HCC), the signaling pathway that may contribute to TGF-β-mediated cell invasion in hepatoma cells was evaluated.

Methods: Three hepatoma cell lines, HepG2, PLC/PRF/5, and HLF, were treated with TGF-β, and the involvement of the non-canonical TGF-β pathway was analyzed by cell migration assays.

Involvement of liver-intestine cadherin in cancer progression.

Cadherins constitute a superfamily of Ca(2+)-dependent cell adhesion molecules that play critical roles in the maintenance of tissue structure and morphogenesis. Their dysregulation is commonly observed in a variety of cancers. Liver-intestine cadherin (LI-cadherin), which was so named in view of its sole expression in the liver and intestine of the rat, is a structurally unique member of the cadherin superfamily, possessing seven cadherin repeats within the extracellular cadherin domain and only 25 amino acids in the cytoplasmic domain.