Evaluation of virtual CT sonography for enhanced detection of small hepatic nodules: a prospective pilot study.

OBJECTIVE: Virtual CT sonography is a system for synchronizing multiplanar reconstructed CT scans with corresponding conventional ultrasound images in real time. The aim of this study was to prospectively evaluate the feasibility of virtual CT sonography for detection of nodules difficult to detect with conventional sonography alone. SUBJECTS AND METHODS: Fifty-nine patients with 140 nodules were included in the study. All patients underwent CT angiography then conventional sonography and finally virtual CT sonography. The number, location, and echogenicity of nodules and parenchyma were assessed. RESULTS: Among 140 nodules detected with CT angiography, 71 were detected with conventional sonography and another 46 were detected with virtual CT sonography, increasing the overall sensitivity from 50.7% to 83.57%. The average diameter of nodules detected only with virtual CT sonography (9.7 +/- 3.3 mm) was significantly smaller than that of nodules detected with conventional sonography (16.6 +/- 6.2 mm). The results of multivariate analysis suggested that nodule size (p < 0.001), echo pattern (p = 0.004), and location (p = 0.028) are associated with the difference in detection. Interestingly, 87% of the nodules 10 mm in diameter or smaller were already dysplastic or malignant. CONCLUSION: Nodules 10 mm in diameter or smaller have significant malignant potential and therefore are clinically important. Even though we do not consider virtual CT sonography a screening tool, we conclude it superior to conventional sonography for detection of small hepatic nodules, allowing bedside percutaneous ultrasound-guided biopsy and treatment that would not be possible with conventional sonography alone.

Heparin-binding EGF-like factor augments esophageal epithelial cell proliferation, migration and inhibits TRAIL-mediated apoptosis via EGFR/MAPK signaling.

OBJECTIVE: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been shown to stimulate the growth and migration of human keratinocytes in an autocrine or paracrine manner. Bearing in mind the preceding narratives, present study was designed to explore the role of HB-EGF on esophageal epithelial cell growth, migration and anti-apoptosis. MATERIAL AND METHODS: HET-1A and TTn cells were treated with recombinant HB-EGF, and cell proliferation and migration were assessed by MTT and Boyden chamber assays, respectively. Anti-apoptotic effects of HB-EGF was studied by Bcl-2/Bcl-xL gene expression and utilizing a TNF-related death apoptosis inducing ligand (TRAIL). RESULTS: Recombinant HB-EGF promotes human esophageal epithelial cell proliferation in a dose dependent manner, where 1 and 10 ng/ml doses were found to be most effective. HB-EGF induced cell migration was noted in TTn, but not in HET-1A cells. Recombinant HB-EGF induced the Bcl-2, Bcl-xL mRNA/protein expression in HET-1A and TTn cells. TRAIL induced the apoptosis in TTn, whereas it was significantly inhibited in HB-EGF treated conditions. Finally, we also revealed HB-EGF induced phosphorylation of EGFR and p38 MAPK in those cell lines, while all cellular functions were repressed by EGFR inhibitor AG1478. CONCLUSION: HB-EGF promotes esophageal epithelial cell proliferation, migration and induces anti-apoptotic gene expression via EGFR/p38 MAPK phosphorylation.

Administration of PPARß/δ agonist reduces copper-induced liver damage in mice: possible implications in clinical practice.

In this study we investigated if peroxisome proliferator-activated receptor ß/δ activation protects from copper-induced acute liver damage. Mice treated with copper had significant body weight loss, serum alanine aminotransferase increase, modest changes in liver histology, increase of tumor necrosis factor α and macrophage inflammatory protein 2 mRNA and 8-hydroxy-2'-deoxyguanosine. Mice treated with copper and peroxisome proliferator-activated receptor ß/δ agonist GW0742 had significantly less body weight loss, less serum alanine aminotransferase increase, less tumor necrosis factor α, macrophage inflammatory protein-2 and 8-hydroxy-2'-deoxyguanosine upregulation than copper treated mice. The opposite effect was observed in mice treated with copper and peroxisome proliferator-activated receptor ß/δ antagonist GSK0660. In vitro, copper induced reactive oxygen species, which was lower in cells treated with GW0742 or transfected with peroxisome proliferator-activated receptor ß/δ expression vector; together, transfection and GW0742 had an additive reactive oxygen species-reducing effect. Copper also upregulated Fas ligand and Caspase 3/7 activity, effects that were significantly lower in cells also treated with GW0742. In conclusion, peroxisome proliferator-activated receptor ß/δ activation reduced copper-induced reactive oxygen species, pro-inflammatory and acute phase reaction cytokines in mice liver. Peroxisome proliferator-activated receptor ß/δ agonists could become useful in the management of copper-induced liver damage.