Computed tomography angiographic findings in hepatocellular carcinoma less than 2 cm detected during follow‐up in 29 patients

Iwamoto, Shozo; Sanefuji, Hayato; Okuda, Kunio

doi:10.1046/j.1440-1746.2003.03125.x

Cited by 1 publication

(1 citation statement)

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“…Even early HCC lesions are more often overt HCC that already have an arterial blood supply, rather than extremely well differentiated and supplied by the portal vein as generally believed (19). It is well known that vascular (portal) invasion portends a poor prognosis (37).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Core Protein Augments Androgen Receptor-Mediated Signaling

Kanda

Steele²,

Ray

2008

J Virol

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Hepatitis C virus (HCV) infection is frequently associated with the development of hepatocellular carcinoma (HCC), which is one of the male-dominant diseases. Androgen signaling in liver may be related to carcinogenesis. In this study, we investigated whether HCV proteins cross talk with the androgen receptor (AR) signaling pathway for promotion of carcinogenesis. We have demonstrated that HCV core protein alone or in context with other HCV proteins enhances AR-mediated transcriptional activity and further augments in the presence of androgen. Subsequent study suggested that HCV core protein activates STAT3, which in turn enhances AR-mediated transcription. This activity was blocked by a pharmacological inhibitor of the Jak/Stat signaling pathway, AG490. Vascular endothelial growth factor (VEGF) is a target gene of AR in liver and plays an important role in angiogenesis. Therefore, we examined whether HCV infection modulates VEGF expression in hepatocytes. Our results demonstrated that HCV enhances VEGF expression and facilitates tube formation in human coronary microvascular endothelial cells in the presence of AR. Together, our results suggest that HCV core protein acts as a positive regulator in AR signaling, providing further insight into oncogenic potential in the development of HCC in HCV-infected individuals.Hepatitis C virus (HCV) infection affects nearly 4 million people and is the most common cause of cirrhosis and hepatocellular carcinoma (HCC) in the United States (23). The current approved therapy for treatment for HCV is pegylated interferon in combination with ribavirin (43). Although several advances have shown promise for improving the management of HCV infection, it nevertheless remains as a major health problem (2, 7, 60). Regardless of the etiology, chronic liver diseases progress at unequal rates in the two sexes, with the major sequelae, such as cirrhosis and HCC, being more common in men than in women (16,54). The significance of androgen receptor (AR) expression in HCC and the surrounding liver has been studied extensively (18,31,33). With this background, we decided to investigate the relationship between AR and HCC after HCV infection, knowing that human liver expresses both estrogen receptors and ARs.AR is a ligand-dependent transcription factor that belongs to the nuclear receptor superfamily (14, 17). The transcriptional activation function of AR is not only essential for normal sexual development in men but is also implicated in the progression of cancer (9). AR has a modular structure containing the N terminus harboring transcriptional activation domain(s), a central DNA-binding domain, and a C-terminal ligand-binding domain. Binding of androgen to the ligand-binding domain induces conformational change in AR and leads to the shuttling of receptor from the cytoplasm to the nucleus, where it forms a homodimer and is recruited to the AR element (ARE). ARE is present in the regulatory elements on the target genes such as vascular endothelial growth factor (VEGF) and transforming growt...

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Section: Discussionmentioning

confidence: 99%