ABSTRACT
Objective To compare the CLIP score, the JIS score, and the China staging system (CS) in the prediction of survival of patients with resectable hepatocellular carcinoma (HCC). Methods The Clinicopathologic and follow-up data of 224 patients who underwent hepatic resection for HCC from January 2000 to July 2005 were retrospectively studied. The patient distribution and the survival curve of each staging system were used to compare the ability to stratify and to discriminate prognosis. The likelihood ratio, chi-square test and the linear trend chi-square test were used to compare the homogeneity and the monotonicity of the relationship between stage and mortality rate of each staging system. The increase in the -2 log likelihood statistic on removal of any one staging system was in turn used as a means of ranking the individual staging systems according to their importance within the regression model. The statistical package used was SPSS version 16. 0 and Stata SE version 8.0. Results Based on the China staging system, the percentages of patients categorized as Ⅰa, Ⅰ b, Ⅱa,Ⅱb and Ⅲ a were 14. 3%, 17.4%, 21.9%, 31.7% and 14. 7% respectively, showing excellent stratification ability. However, nearly 81. 6% of the patients were classified as a CLIP score of 0-2, which showed poor stratification ability, and only 3. 1 % of the patients were classified as score 0 category of the JIS scoring system. In the follow-up period, the log-rank test and the corresponding Kaplan-Meier survival curves confirmed each staging system to be able to differentiate patient survival in the different stages. Individual pairwise comparisons revealed inconsistencies across the different staging systems. In particular, using the log-rank test, the JIS scoring system and the China staging system showed significant differences in patient survival on all pairwise comparisons. By contrast, the CLIP scoring system failed to differentiate significantly between score 2 and score 3 patients. The JIS scoring system could identify the best prognostic group who would benefit from curative and aggressive treatments, whereas the discriminatory value of the CLIP score was noted in the intermediate- and advanced-phase HCC patients. The China staging system was shown to have the best homogeneity, overall discriminatory capacity and monotonicity of gradient. The change in the -2 log likelihood statistic on removal of any staging system revealed that for this cohort of patients, the appropriate importance in the ranking of the independent contribution of each factor to the regression model was: CS> CLIP>JIS. Conclusion Among three clinical staging systems, the China staging system had the highest prognostic value, with better stratification and higher discriminatory capacity than the CLIP scoring system and the JIS scoring system for this cohort of patients who received partial hepatectomy for HCC. The CLIP scoring system performed better in identifying the worst prognostic patients.
ABSTRACT
Anaplastic thyroid carcinoma is an aggressive neoplasm and resistant to all sorts of treatment due to its rapid growth and invasive potential. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor modulating variety of biological properties, such as regulating of adipogenesis, inhibition of cancer cell proliferation or differentiation of tumor cells. The purpose of this study was to evaluate the possibility for the therapeutic effect of PPARgamma ligands against anaplastic thyroid tumor in vitro. Expressions of the PPARc gene and protein were examined in 5 human anaplastic carcinoma cell lines (MSA, IAA, ROA, K119 and KOA-2). We next evaluated the effects of PPARgamma ligands (Thiazolidinedione, Prostaglandin J2 and RS1303) on proliferation, differentiation, apoptosis and invasion. Five cell lines showed higher level of the PPARc gene and protein expression than papillary thyroid carcinoma. PPARgamma ligands inhibited cell proliferation by inducing apoptosis instead of differentiation in dose-dependent manner. PPARgamma ligands also down regulated the invasive potential of 5 cell lines. The inhibitory effect of proliferation or invasion was prominent in 3 cell lines, which exhibited higher expression level of the PPARc gene or protein. Our results indicated that PPARgamma ligands modify malignant potential of anaplastic carcinoma cell lines altering growth or invasive properties, suggesting that PPARgamma could be potentially the novel molecular target for human thyroid anaplastic carcinoma.
Subject(s)
Antineoplastic Agents/pharmacology , Prostaglandin D2/analogs & derivatives , Receptors, Cytoplasmic and Nuclear/metabolism , Transcription Factors/metabolism , Apoptosis/drug effects , Blotting, Western , Carcinoma/genetics , Carcinoma/metabolism , Carcinoma/pathology , Cell Differentiation/drug effects , Cell Division/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Dose-Response Relationship, Drug , Gene Expression Regulation, Neoplastic/drug effects , Humans , In Situ Nick-End Labeling , Ligands , Neoplasm Invasiveness , Prostaglandin D2/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Cytoplasmic and Nuclear/genetics , Thiazolidinediones/pharmacology , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Transcription Factors/geneticsABSTRACT
BACKGROUND: Cellular functions are maintained by a continuous supply of ATP, which is supplied efficiently by mitochondrial oxidative phosphorylation. Since myoglobin, found in cardiac myocytes and red skeletal muscle, but not in the liver, facilitates oxygen diffusion under low oxygen conditions and enhances oxidative phosphorylation, this study seeks to enhance hepatic ATP levels and attenuate ischemia-reperfusion injury in rodent livers by adenovirus-mediated myoglobin expression. MATERIAL AND METHODS: After infecting Hep3B and rodent livers with adenovirus carrying CMV promoter sequences linked to the human myoglobin gene (AdCMVMyo), reverse transcriptase-PCR and immunodetection for myoglobin, and cellular and hepatic ATP levels were examined. The effect of myoglobin was evaluated in a hepatic ischemia-reperfusion model in the rat. RESULTS: Myoglobin expression was confirmed in Hep3B and rat livers after AdCMVMyo infection. The ATP levels in Hep3B cells and C57BL/6 mice livers 72 h after AdCMVMyo transfection were significantly higher than control levels and those after adenovirus-mediated beta-galactosidase transfection. Finally, expression of myoglobin attenuated ischemia-reperfusion injury in the rat liver. CONCLUSION: These results indicate that myoglobin gene transfer to the liver enhanced ATP levels both in vitro and in vivo and might be a novel strategy to reduce ischemia-reperfusion injury.
Subject(s)
Liver/blood supply , Liver/metabolism , Myoglobin/genetics , Myoglobin/metabolism , Reperfusion Injury/therapy , Adenosine Triphosphate/metabolism , Adenoviridae , Animals , Cell Line , Gene Expression , Genetic Vectors , Humans , Male , Mice , Models, Animal , Rats , Reperfusion Injury/metabolism , Reperfusion Injury/prevention & control , TransfectionABSTRACT
Objective To study the effect of expression of myoglobin which mediated by adenovirus,on ATP value of liver and the protective effect on liver ischemia reperfusion injury.Methods Adenovirus carrying CMV promoter sequences linked to the human myoglobin gene(AdCMVMyo) were transfected into rats liver. Then myoglobin, hepatic ATP levels and liver function were evaluated. Results Myoglobin expression was verified in rat livers after AdCMVMyo transfection. The ATP levels in rat livers 72 hours after AdCMVMyo transfection were significantly higher than that in control group(P