The anti-viral effect of sorafenib in hepatitis C-related hepatocellular carcinoma.

BACKGROUND: Sorafenib is currently the only approved systemic therapy shown to have efficacy in the treatment of advanced hepatocellular carcinoma (HCC). Recent studies suggest that hepatitis C (HCV)-related HCC patients derive more clinical benefit from sorafenib than other subgroups, but the mechanism for this effect is unknown. In vitro data suggest that sorafenib may exert anti-viral properties, and thus our aim in this study was to evaluate potential anti-viral activity of sorafenib in patients with HCV-related HCC. AIM: To evaluate potential anti-viral activity of sorafenib in patients with HCV-related HCC. METHODS: We prospectively enrolled patients with HCV-related HCC treated with sorafenib for up to 6 months. Baseline clinical, viral and oncologic data were collected. Patients' HCV viral loads were obtained at various time points, and compared with their baseline viral levels. No patients received any known anti-viral therapy during this time. RESULTS: Thirty-three patients were identified with baseline and subsequent HCV levels available for analysis. Six patients completed 6 months of full dose sorafenib, and comparisons of their HCV viral loads showed no significant change at week 24 (difference of means = 0.3500, CI: -0.1799-0.8799, P = 0.150), or the interim time points. Similarly, the HCV viral loads of all patients who received sorafenib and the viral loads of those patients who had tumour response to sorafenib showed no significant changes at any time point. CONCLUSION: Despite preclinical data and previous subgroup analyses suggesting that sorafenib has an anti-viral effect against HCV, this study suggests that sorafenib lacks significant anti-viral activity in HCV patients with HCC.

Imaging of hepatocellular carcinoma and early diagnosis.

The incidence of hepatocellular carcinoma (HCC) is steeply rising in industrialized nations, and the vast majority of patients do not qualify for curative treatment at the time of diagnosis. This phenomenon is directly related to the clinician's ability to accurately diagnose HCC at an early stage, which can be quite challenging in the setting of a cirrhotic, nodular liver. A particular difficulty arises in the differentiation of very small neoplastic lesions from hyperplastic nodules. In the past decade, technological advances have made dynamic imaging of the cirrhotic liver more feasible, which in turn improves the sensitivity and specificity of these modalities for the diagnosis of HCC. In this article we describe the typical characteristics of HCCin modalities such as ultrasound, computed tomography, and magnetic resonance imaging, discuss the recent advances in dynamic imaging in each of these modalities, and review the published guidelines for surveillance and diagnosis for HCC.

Glycogen synthase kinase 3beta and Alzheimer's disease: pathophysiological and therapeutic significance.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the serine-threonine kinase, glycogen synthase kinase beta(GSK-3beta) in the pathogenesis of AD. GSK-3beta may play an important role in the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review, we discuss the interaction between GSK-3beta and several key molecules involved in AD, including the presenilins, amyloid precursor protein, tau, and beta-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt, Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD.