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.

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.

Blockade of ataxia telangiectasia mutated sensitizes hepatoma cell lines to sorafenib by interfering with Akt signaling.

Sorafenib is a multi-kinase inhibitor applicable to hepatocellular carcinoma (HCC), but its limited therapeutic effects are a major problem to be solved. Here, we show that blockade of ataxia telangiectasia mutated (ATM) improves the antitumor effects of sorafenib. When hepatoma cell lines HepG2 and PLC/PRF/5 were treated with sorafenib plus ATM small inhibitory RNAs, ATM inhibitor KU55933 or caffeine, Akt signaling was suppressed and the cytotoxic effects were significantly potentiated.

Multidrug resistance-associated protein 2 determines the efficacy of cisplatin in patients with hepatocellular carcinoma.

We hypothesized that expression of multidrug resistance-associated protein 2 (MRP2), a major cisplatin transporter, may determine the efficacy of cisplatin as a treatment for patients with hepatocellular carcinoma (HCC). A prospective analysis was conducted of 49 consecutive patients who underwent resection for HCC (16 patients treated with cisplatin-based neoadjuvant chemotherapy and 33 patients treated without neoadjuvant chemotherapy). Expression of MRP2 in resected specimens was assessed by immunohistochemical and Western blot analyses.