Introduction: Liver cancer is among the main leading cause of mortality in Malaysia and the world. Therefore, there is an urgent need to understand the complex mechanisms and pathways involved in liver cancer. Methods: Microarray datasets GSE84402, GSE60502, GSE29721 and GSE19665 were downloaded from GEO database. The datasets were normalised and differentially expressed genes (DEGs) were calculated using GeneSpring software. GO and KEGG pathway enrichment analyses were then performed using DAVID. Finally, Cytoscape stringApp plugin was utilised to construct a protein-protein interaction (PPI) network. Results: A total of 1382, 714, 1038 and 1828 DEGs satisfying p value cut-off 0.01 and fold change cut-off 2.0 are identified from each dataset. 412 DEGs appeared in at least three datasets, consisting of 167 up-regulated and 245 down-regulated genes. These genes are most significantly enriched in terms related to cell division and mitotic nuclear division. Construction of PPI network produced a network with 275 nodes and 2157 edges with confidence score 0.7. Topological analysis identified CDK1, TOP2A and NDC80 as key genes. MCODE plugin extracted five modules from the network with mitotic cell cycle process being the most enriched term in module 1. Meanwhile, platelet degranulation, epoxygenase P450 pathway, cellular response to zinc ion and complement and coagulation cascade are the terms enriched in module 2, 3, 4 and 5. Conclusion: The key genes and pathways identified from this study provide information on the molecular mechanism underlying liver cancer to increase our understanding regarding liver cancer development and progression at molecular level
Liver cancer

Introduction: Curcumin is an active constituent derived from turmeric with a variety of pharmacological activities. It suppressed cell proliferation and induced apoptosis in several cancer cell lines. However, due to its poor bioavailability, derivative analogue of curcumin has been synthesized to enhance the drug-like effects. BHMC was synthesized by removing β-diketone moiety from curcumin structure and modify it into conjugated double bonds. It has been proved to exhibit stronger anticancer effects with improved bioavailability compared to curcumin. Objective: This study aims to investigate the toxicity effect of BHMC and curcumin on human liver cancer, HepG2 and non-cancer mouse fibroblast, 3T3. Methods: Both cell lines were purchased from ATCC and cultured in supplemented DMEM. Cell viability was determined via MTT assay and confirmed with trypan blue assay. Morphology hallmarks of apoptosis of both treated cells were analyzed using inverted microscope at 40X magnifications. Results: BHMC and curcumin were very potent towards HepG2 and normal 3T3. These data were further confirmed with trypan blue assay which showed that both compounds significantly reduced the percentage of HepG2 and 3T3 cells viability. Both treated cells also displayed all the morphology hallmarks of apoptosis upon treatment. Conclusion: BHMC has a greater cytotoxicity effect on HepG2 compared to curcumin despite its non-selective cytotoxicity effect on non-cancer 3T3.
Liver cancer

Liver Cancer ; Yellow color ; Rattus norvegicus

The age-adjusted incidence of primary liver cancer (PLC) has been declining in China. However, PLC cases in China account for 55% globally. The disease burden is still high and the 5-year survival rate was not improved significantly in the past two decades. This guideline outlines PLC screening in the risk populations, both in hospital and community. Liver cirrhosis and chronic hepatitis B are the main causes of PLC in China. For better PLC surveillance and screening in clinical practices, it is recommended to stratify population at the risk into 4 risk levels, namely, low-risk, intermediate-risk, high-risk, and extremely high-risk.The lifelong surveillance is suggested for those at the risk of PLC. The intervals and tools for surveillance and screening are recommended based on the risk levels. Abdominal ultrasonography combined with serum alpha-fetoprotein examination (routine surveillance) every 6 months is recommended for those at a high risk of PLC.Routine surveillance every 3 months and enhanced CT/MRI examination every 6-12 months are recommended for those at an extremely high risk of PLC. The surveillance interval can be extended every 1 year or longer for those at a low-risk or at an intermediate-risk of PLC, because their annual incidence of PLC is very low. The cost-effectiveness of these recommendations remains to be evaluated.
Carcinoma, Hepatocellular ; China/epidemiology* ; Early Detection of Cancer ; Hepatitis B, Chronic ; Humans ; Liver Cirrhosis ; Liver Neoplasms/epidemiology*

Humans ; Female ; Prevalence ; Breast Neoplasms ; Cancer Survivors ; Non-alcoholic Fatty Liver Disease ; Liver

Cancer Vaccines ; therapeutic use ; Carcinoma, Hepatocellular ; therapy ; Humans ; Liver Neoplasms ; therapy ; Vaccines, Synthetic ; therapeutic use

Cancer Vaccines ; therapeutic use ; Carcinoma, Hepatocellular ; therapy ; Humans ; Immunotherapy ; methods ; Liver Neoplasms ; therapy

Antigens, Neoplasm ; immunology ; Cancer Vaccines ; therapeutic use ; Dendritic Cells ; immunology ; Humans ; Immunotherapy ; methods ; Liver Neoplasms ; therapy

Antigens, Neoplasm ; immunology ; Cancer Vaccines ; immunology ; Carcinoma, Hepatocellular ; immunology ; therapy ; Humans ; Immunotherapy ; Liver Neoplasms ; immunology ; therapy

The association of hepatitis B virus (HBV) infection and liver cancer is well documented in epidemiological study. Patients with chronic hepatitis B have increased risk of hepatocelluar carcinoma (HCC), in particular those with active liver disease and cirrhosis. The incidence of HCC increases with age and is more common among male patients. The introduction of universal HBV vaccination program for the newborn in endemic regions has started to show beneficial impact. Taiwan introduced this program two decades ago and the incidence of liver cancer among infants and young children have declined significantly. The carcinogenic events leading to HCC are under intense research. A number of hypotheses have been proposed. HBV is not directly hepatotoxic but its interaction with the host immune system creates opportunity for HBV DNA integration into the host genome. One of the main foci of research is the HBX-encoded X protein. Its integration and protein expression impose alteration in cell proliferation cycle and apoptosis process. Many other factors may be involved including viral-induced alterations in p53 and telemerase, HBV genotypes, co-infection with HCV or delta agents, patient's lifestyle such as smoking, alcohol excesses, and genetic factors of the host patient. The processes of necroinflammation, cell proliferation and fibrosis facilitate the initial carcinogenic development. HCC surveillance with tumor markers such as alpha-foetal protein, decarboxylated prothrombin, in conjunction with imaging techniques has identified early small HCC that is amenable to curative therapy. Viral load has been correlated with increase risk of HCC. The available anti-viral agents have demonstrated clinical benefit among those with maintained and sustained response. Interferon and lamivudine therapy have demonstrated reduction of HCC among responders. However, they only constitute a minority proportion of treated patients. The mainstay of prevention should lie in prevention of HBV infection and early effective therapy of chronic hepatitis B infection.
Hepatitis B virus measurement ; seconds ; Liver Cancer ; Infection as complication of medical care ; Therapeutic procedure