Regulation of angiogenesis by Id-1 through hypoxia-inducible factor-1alpha-mediated vascular endothelial growth factor up-regulation in hepatocellular carcinoma.

Purpose: Metastasis is commonly associated with poor prognosis of hepatocellular carcinoma (HCC). Being an important angiogenic factor, vascular endothelial growth factor (VEGF) plays a central role in HCC growth and metastasis. Recently, Id-1 (inhibitor of differentiation/DNA synthesis) has been suggested to be a key factor in cancer progression but the molecular mechanism remains unknown.

Therapeutic potential of cardiotrophin 1 in fulminant hepatic failure: dual roles in antiapoptosis and cell repair.

Hypothesis: Administration of cardiotrophin 1 (CT-1) can treat experimental fulminant hepatic failure (FHF).

Design: Rat model with FHF induced by D-galactosamine (D-gal).

Setting: Fulminant hepatic failure is a rapidly progressive disease that lacks effective nonsurgical treatment.

Significance of the serum brain-derived neurotrophic factor and platelets in hepatocellular carcinoma.

The present study investigated the significance of the serum brain-derived neurotrophic factor (BDNF) and platelets in relation to the clinicopathological features of hepatocellular carcinoma (HCC) patients. Localization of the BDNF expression in human HCC tissues was performed by immunohistochemistry. The measurement of soluble BDNF in the serum was performed by enzyme-linked immunosorbent assay.

Radiofrequency ablation for hepatocellular carcinoma and metastatic liver tumors: a comparative study.

Background: This study compared the effectiveness of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) and liver metastases.

Methods: We compared the outcomes of 240 patients with HCC and 44 patients with liver metastases treated with RFA. Data were prospectively collected and retrospectively analyzed.

Signal transducers and activators of transcription 5b activation enhances hepatocellular carcinoma aggressiveness through induction of epithelial-mesenchymal transition.

Poor prognosis of hepatocellular carcinoma (HCC) is associated with a high potential of vascular invasion and metastasis. Epithelial-mesenchymal transition (EMT) is a key event in the tumor invasion process. Recently, signal transducers and activators of transcription 5 (STAT5) has been linked to tumor progression by EMT induction.

Identification of hepatitis B virus-specific lymphocytes in human liver grafts from HBV-immune donors.

Both animal and human studies have demonstrated the adoptive transfer of immunity against hepatitis B virus (HBV) through liver transplantation that may be attributed to the presence of HBV-specific immunocompetent cells of donor origin in liver grafts. In this study, we characterized the resident lymphocytes in 41 human liver grafts by immunohistochemical staining and flow cytometry and directly identified the intragraft HBV-specific lymphocytes in relation to the donor's and subsequent recipient's immunity using enzyme-linked immunospot assay. A significant number of HBV-specific T and B cells were detectable in 59.

Significance of circulating endothelial progenitor cells in hepatocellular carcinoma.

This study evaluated the significance of circulating bone marrow-derived endothelial progenitor cells (EPCs) in patients with hepatocellular carcinoma (HCC), a solid tumor with rich neovasculature. Eighty patients with HCC were recruited for the study, and 16 patients with liver cirrhosis and 14 healthy subjects were also included for comparison. Blood samples were taken before treatment.

Live donor liver transplantation in adults.

Live donor liver transplantation (LDLT) was initiated in 1988 for children recipients. Its application to adult recipients was limited by graft size until the first right liver LDLT was performed in Hong Kong in 1996. Since then, right liver graft has become the major graft type.

Donor quality of life before and after adult-to-adult right liver live donor liver transplantation.

Donor right hepatectomy for adult-to-adult live donor liver transplantation (ALDLT) is a major surgical operation for the benefit of the recipient. Justification of procedure mandates knowledge of the possible physical and psychological negative effects on the donor. We prospectively and longitudinally quantified donor quality of life using generic and condition-specific questionnaires up to 1 year.

Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition.

Purpose: Hepatocellular carcinoma (HCC) is a rapidly growing tumor associated with a high propensity for vascular invasion and metastasis. Epithelial-mesenchymal transition (EMT) is a key event in the tumor invasion process. Recently, Twist has been identified to play an important role in EMT-mediated metastasis through the regulation of E-cadherin expression.

High doses of tyrosine kinase inhibitor PTK787 enhance the efficacy of ischemic hypoxia for the treatment of hepatocellular carcinoma: dual effects on cancer cell and angiogenesis.

The present study aimed to investigate the therapeutic efficacy of combining vascular endothelial growth factor (VEGF) receptor blockade using tyrosine kinase inhibitor PTK787 with hypoxia for the treatment of hepatocellular carcinoma (HCC). The in vivo effects of the treatments were determined in a rat orthotopic HCC model, in which hypoxia was generated by hepatic artery ligation (HAL). Compared with HAL alone, PTK787 combined with HAL significantly prolonged the animal survival, reduced the tumor size, induced more tumor tissue necrosis and apoptosis, and down-regulated the expression of von Willebrand factor.

Preoperative plasma transcript AA454543 level is an independent prognostic factor for hepatocellular carcinoma after partial hepatectomy.

Background: We have previously reported that tissue expression levels of transcript AA454543 in hepatocellular carcinoma (HCC) are significantly higher than those of normal livers, livers with cirrhosis, and livers with hepatitis. In addition, a higher level of transcript AA454543 in tumor tissues is associated with poor prognosis. We aim to examine whether quantitative measurement of preoperative plasma transcript AA454543 can provide similar prognostic information.

Liver intestine-cadherin (CDH17) haplotype is associated with increased risk of hepatocellular carcinoma.

Purpose: Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a leading cause of cancer death worldwide. We previously showed that aberrant mRNA splicing of the liver intestine-cadherin gene CDH17 in liver tissues was triggered by the specific constellation of two CDH17 single nucleotide polymorphisms (651T and IVS6+35G). CDH17 aberrant splicing was highly associated with tumor dissemination and shorter survival of HCC patients.

Rac activation is associated with hepatocellular carcinoma metastasis by up-regulation of vascular endothelial growth factor expression.

Purpose: Hepatocellular carcinoma (HCC) is associated with a propensity for vascular invasion and metastasis, which contribute to poor prognosis. Angiogenesis is a crucial process contributing to tumor growth and metastasis. Recently, Rac has been suggested to play a role in angiogenesis.

Suppression of hypoxia inducible factor-1alpha (HIF-1alpha) by YC-1 is dependent on murine double minute 2 (Mdm2).

Inhibition of HIF-1alpha activity provides an important strategy for the treatment of cancer. Recently, 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) has been identified as an anti-HIF-1alpha drug in cancer therapy with unclear molecular mechanism. In the present study, we aimed to investigate the effect and mechanism of YC-1 on HIF-1alpha in a hepatocellular carcinoma cell line under hypoxic condition, which was generated by incubating cells with 0.

Anterior approach versus conventional approach right hepatic resection for large hepatocellular carcinoma: a prospective randomized controlled study.

Objective: To evaluate whether major right hepatectomy using the anterior approach technique for large hepatocellular carcinoma (HCC) results in better operative and long-term survival outcomes when compared with the conventional approach technique.

Summary Background Data: The anterior approach technique has been advocated recently for large right liver tumors. However, its beneficial effects on the operative and survival outcomes of the patients have not been evaluated prospectively.

Molecular adsorbent recirculating system treatment for patients with liver failure: the Hong Kong experience.

Background: The molecular adsorbent recirculating system (MARS) is an extracorporeal liver dialysis system that allows selective removal of bilirubin and other albumin-bound toxins. We reported here our experience with the use of this technique for management of liver failure at Queen Mary Hospital, Hong Kong.

Methods: From December 2002 to 2004, a total of 74 MARS sessions were performed on 22 patients.

Blockage of epidermal growth factor receptor by quinazoline tyrosine kinase inhibitors suppresses growth of human hepatocellular carcinoma.

Epidermal growth factor receptor (EGFR) is highly expressed in many human tumors including hepatocellular carcinoma (HCC). Therefore, inhibition of EGF receptors could be a potential target for anticancer therapy. In this study, we investigated the effects of two EGFR tyrosine kinase inhibitors, PD153035 and its analogue 4-[[3-chloro-4-fluorophenyl]amino]-6,7-dimethoxyquinazoline hydrochloride (ANAPD) on human HCC cell lines by cell proliferation assay, flow cytometry and Western blot.

Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach.

The heterogeneity and instability of human tumors hamper straightforward identification of cancer-causing mutations through genomic approaches alone. Herein we describe a mouse model of liver cancer initiated from progenitor cells harboring defined cancer-predisposing lesions. Genome-wide analyses of tumors in this mouse model and in human hepatocellular carcinomas revealed a recurrent amplification at mouse chromosome 9qA1, the syntenic region of human chromosome 11q22.

Platelet activation during tumor development, the potential role of BDNF-TrkB autocrine loop.

Platelets are an important place for the storage of angiogenic factors, such as vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). The present study aims to investigate the interaction between BDNF-TrkB pathway and platelet activation during tumor development. In an orthotopic hepatocellular carcinoma (HCC) model, increased levels of serum and plasma BDNF were detected with tumor progression.

ATR dependent activation of Chk2.

ATM and ATR are essential regulators of DNA damage checkpoints in mammalian cells through their respective effectors, Chk2 and Chk1. Cross regulation of the ATM-Chk2 and ATR-Chk1 pathways is very limited, although ATM and ATR show overlapping function in a partnership and time-dependent manner. In this study, we report that Chk2 is a substrate of ATR in response to ionizing and ultraviolet radiation.