AIM To investigate the associations of the genetic polymor-phisms of vascular endothelial growth factor A(VEGF-A)-1498C>T and-634G>C, with the survival of patients with colorectal cancer(CRC). METHODS A prospect...AIM To investigate the associations of the genetic polymor-phisms of vascular endothelial growth factor A(VEGF-A)-1498C>T and-634G>C, with the survival of patients with colorectal cancer(CRC). METHODS A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction(PCR) in real-time. The real-time PCR technique was used to identify the VEGF-A-1498C>T(rs833031) and-634G>C(rs2010963) polymorphisms. Genotyping was validated for VEGF-A-1498C>T polymorphism in 129 patients and for VEGF-A-634G>C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method. RESULTS In the univariate analysis there was a significant association(OR = 0.32; P = 0.048) between genotype CC of the VEGF-A-1498C>T polymorphism and the presence of CRC liver metastasis. There was no association between VEGF-A-1498C>T polymorphism and VEGF-A-634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of the VEGF-A-1498C>T polymorphism was significantly correlated with the 5-year survival(P = 0.032), but not significant difference(P = 0.27) was obtained with the VEGF-A-634G>C polymorphism with the 5-year survival in the univariate analysis. The genotype CT(HR = 2.79) and CC(HR = 4.67) of the polymorphism VEGF-A-1498C>T and the genotype CC(HR = 3.76) of the polymorphism VEGF-A-634C>G acted as an independent prognostic factor for the risk of death in CRC patients. CONCLUSION The CT and CC genotypes of the VEGF-A-1498C>T and the CC genotype of the VEGF-A-634C>G polymorphisms are prognostic factors of survival in Brazilians patients with sporadic colorectal carcinoma.展开更多
The molecular basis of the carcinogenesis of hepatocellular carcinoma(HCC) has not been adequately clarified, which negatively impacts the development of targeted therapy protocols for this overwhelming neoplasia. The...The molecular basis of the carcinogenesis of hepatocellular carcinoma(HCC) has not been adequately clarified, which negatively impacts the development of targeted therapy protocols for this overwhelming neoplasia. The aberrant activation of signaling in the HCC is primarily due to the deregulated expression of the components of the Wnt-/-β-catenin. This leads to the activation of β-catenin/T-cell factor-dependent target genes that control cell proliferation, cell cycle, apoptosis, and cell motility. The deregulation of the Wnt pathway is an early event in hepatocarcinogenesis. An aggressive phenotype was associated with HCC, since this pathway is implicated in the proliferation, migration, and invasiveness of cancer cells, regarding the cell's own survival. The disruption of the signaling cascade Wnt-/-β-catenin has shown anticancer properties in HCC's clinical evaluations of therapeutic molecules targeted for blocking the Wnt signaling pathway for the treatment of HCC, and it represents a promising perspective. The key to bringing this strategy in to clinical practice is to identify new molecules that would be effective only in tumor cells with aberrant signaling β-catenin.展开更多
文摘AIM To investigate the associations of the genetic polymor-phisms of vascular endothelial growth factor A(VEGF-A)-1498C>T and-634G>C, with the survival of patients with colorectal cancer(CRC). METHODS A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction(PCR) in real-time. The real-time PCR technique was used to identify the VEGF-A-1498C>T(rs833031) and-634G>C(rs2010963) polymorphisms. Genotyping was validated for VEGF-A-1498C>T polymorphism in 129 patients and for VEGF-A-634G>C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method. RESULTS In the univariate analysis there was a significant association(OR = 0.32; P = 0.048) between genotype CC of the VEGF-A-1498C>T polymorphism and the presence of CRC liver metastasis. There was no association between VEGF-A-1498C>T polymorphism and VEGF-A-634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of the VEGF-A-1498C>T polymorphism was significantly correlated with the 5-year survival(P = 0.032), but not significant difference(P = 0.27) was obtained with the VEGF-A-634G>C polymorphism with the 5-year survival in the univariate analysis. The genotype CT(HR = 2.79) and CC(HR = 4.67) of the polymorphism VEGF-A-1498C>T and the genotype CC(HR = 3.76) of the polymorphism VEGF-A-634C>G acted as an independent prognostic factor for the risk of death in CRC patients. CONCLUSION The CT and CC genotypes of the VEGF-A-1498C>T and the CC genotype of the VEGF-A-634C>G polymorphisms are prognostic factors of survival in Brazilians patients with sporadic colorectal carcinoma.
文摘The molecular basis of the carcinogenesis of hepatocellular carcinoma(HCC) has not been adequately clarified, which negatively impacts the development of targeted therapy protocols for this overwhelming neoplasia. The aberrant activation of signaling in the HCC is primarily due to the deregulated expression of the components of the Wnt-/-β-catenin. This leads to the activation of β-catenin/T-cell factor-dependent target genes that control cell proliferation, cell cycle, apoptosis, and cell motility. The deregulation of the Wnt pathway is an early event in hepatocarcinogenesis. An aggressive phenotype was associated with HCC, since this pathway is implicated in the proliferation, migration, and invasiveness of cancer cells, regarding the cell's own survival. The disruption of the signaling cascade Wnt-/-β-catenin has shown anticancer properties in HCC's clinical evaluations of therapeutic molecules targeted for blocking the Wnt signaling pathway for the treatment of HCC, and it represents a promising perspective. The key to bringing this strategy in to clinical practice is to identify new molecules that would be effective only in tumor cells with aberrant signaling β-catenin.
