Primary liver cancer is one of the most common cancer in the world with highest cancer mortality rate. The most common type of primary liver cancer is hepatocellular carcinoma (HCC). There are many risk factors for liver cancer and currently available treatments for HCC are largely inadequate. Gene mutation and dysfunction of p53 are common and is recognized as an important molecular event in hepatocarcinogenesis. Therefore, replacement of the aberrant p53 gene is an attractive approach in the treatment of HCC providing an alternative treatment for primary HCC. In this study, we assessed whether the transfection with wild-type p53 gene is able to restore the pro-apoptotic effects and evaluate the feasibility of gene therapy in fixing a faulty p53 molecule. We established a non-viral cationic lipid-based p53 gene delivery into two human HCC cell lines namely HLF and PLC/PRF/5 cells. Both cell lines have mutations in the p53 gene. We compared the results with the normal liver cell line, WRL68, that constitutively expresses the wild-type p53 gene. In this study, the introduction of wild-type p53 gene into HLF and PLC/PRF/5 cells resulted in an increased of p53 gene expression, protein expression and cells growth inhibition shown in MTS reduction cell viability assay, FITC-Annexin V and PI apoptosis assay, western blot and caspase activity assay. In summary, the study provides a promising therapeutic approach for p53 gene delivery into HCC patients. The p53 gene delivery can be instituted together with chemotherapy as a combination treatment to induce apoptosis.
Many studies have shown that the immune response highly depends on the inheritance of specific HLA
genes in promoting the generation of T cells for the elimination of pathogens. Loss or alteration of HLA
antigen expression in tumor cells has been observed in a variety of human malignancies leading to immune
escape or immune resistance. We investigated whether the inheritance of certain alleles of HLA class II
genes confers susceptibility or resistance towards the development of colorectal carcinoma (CRC).
Molecular typing of HLA DRB1, DQB1 and DPB1 alleles in 42 patients diagnosed with CRC and 50
ethnically matched healthy controls using the PCR-sequence based typing (PCR-SBT) was conducted. The
HLA DPB1*02:01:02 was significantly higher in CRC patients (38.1%, p=0.0189) compared to healthy
controls (16%). Also, HLA DQB1*05:02:01 was present in 28.6% of CRC patients but only 10% of healthy
controls (p=0.0278). The odds ratios for HLA DPB1*02:01:02 and HLA DQB1*05:02:01were 3.23 and 3.60,
respectively. There were no significant association observed for the DRB1 allele with CRC. Our study
suggests that the HLA DPB1*02:01:02 and HLA DQB1*05:02:01 alleles may confer a higher risk for CRC