RESUMEN
Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a control group consisting of sham animals implanted with Gelfoam into their livers (LG). After two weeks from implantation, liver tissue from lobes with and without tumor was obtained from experimental animals (LT+/LT-) as well as liver tissue from controls (LG+/LG-). Peaks obtained by Gas Chromatography-Mass Spectrometry were subjected to identification. 56 metabolites were identified and their profiles compared between groups using principal component analysis (PCA) and a mixed-effect two-way ANOVA model. Results. Animals recovered from surgery uneventfully. Analyses identified a metabolite profile that significantly differs in experimental conditions after controlling the False Discovery Rate (FDR). 16 metabolites concentrations differed significantly when comparing samples from (LT+/LT-) to samples from (LG+/LG-) livers. A significant difference was also shown in 20 metabolites when comparing samples from (LT+) liver lobes to samples from (LT-) liver lobes. Conclusion. Normal liver tissue harboring malignancy had a distinct metabolic signature. The role of metabolic profiles on liver biopsies for the detection of early liver cancer remains to be determined.
RESUMEN
Purpose. The incidence of liver tumors is rising in USA. The purpose of this study was to evaluate liver oxido-reductive status in the presence of chronic liver disease and hepatocellular carcinoma (HCC). Methods. Glutathione species and ophthalmate (OA) concentrations were measured by LC-MS in processed plasma and red blood cells (RBC) from infected Woodchuck with hepatitis virus (WHV). Blood samples were obtained from: (i) infected animals with tumors (WHV+/HCC+), (ii) infected animals without tumors (WHV+/HCC-) and (iii) healthy animals (WHC-/HCC-). Results. The concentration of reduced glutathione (GSH) and the ratio GSH/GSG were lower in plasma from WHV+/HCC+ animals when compared to WHV+/HCC- and WHV-/HCC- (P < 0.01). In contrast, the concentration of oxidized glutathione (GSSG) was found to be higher in plasma from WHV+/HCC+ animals when compared to WHV+/HCC- and WHV-/HCC- (P < 0.01). The Glutathione species and its ratio from the RBC compartment were similar among all groups. OA concentration in both plasma and RBC was significantly higher from WHV+/HCC+ when compared to WHV+/HCC- and WHV-/HCC- (P < 0.01). Conclusions. Disturbances of the glutathione redox buffer system and higher concentrations of OA were found in the WCV+/HCC+ animal model. The role of these compounds as biomarkers of early tumor development in patients with end stage liver disease remains to be determined.
RESUMEN
PURPOSE: Available tumor markers have low sensitivity/specificity for the diagnosis of liver tumors. The present study was designed to evaluate the oxidoreductive status of the liver as surrogates of tumor subsistence and growth. METHODS: Glutathione species (GSH:GSSG), ophthalmate (OA) concentrations, and their turnover were measured in plasma of rabbits (n = 6) in their healthy state and in the state of tumor growth after implantation of the VX2 carcinoma in their liver. Tumors were allowed to grow for a period of 14 days when rabbits were sacrificed. Livers were removed and cysteine concentration was measured in liver tissue. RESULTS: Tumor growth was found in 100% of the rabbits. Concentration and labeling of GSH/GSSG were similar in experimental animals before and after tumor implantation and to sham animals. In contrast, OA concentration increased significantly in experimental animals after tumor implantation when compared to same animals prior to tumor implantation and to sham animals (P < .05). The concentration of cysteine, a precursor of GSH, was found to be significantly lower in the liver tissue adjacent to the tumor (P < .05). CONCLUSION: Disturbances in the oxidoreductive state of livers appear to be a surrogate of early tumor growth.