Chronic liver injury (CLI) is a complex pathological process typically characterized by progressive destruction and regeneration of liver parenchymal cells due to diverse risk factors such as alcohol abuse, drug toxicity, viral infection, and genetic metabolic disorders. When the damage to hepatocytes is mild, the liver can regenerate itself and restore to the normal state; when the damage is i...

In this review, the role of NF-kappaB in the induction of hepatocarcinogenesis by peroxisome proliferators is examined. The administration of peroxisome proliferators for more than a three-day period leads to the activation of NF-kappaB in the livers of rats and mice. On the other hand, peroxisome proliferator activated receptor-alpha (PPARalpha) activation in non-hepatic tissues can lead to th...

An aldehyde dehydrogenase (ALDH) with properties identical to those of the NADP+-dependent, tumor-associated aldehyde dehydrogenase appearing during rat hepatocarcinogenesis has been identified in normal rat urinary bladder. Like the tumor-associated aldehyde dehydrogenase, bladder NADP+-ALDH is cytosolic and preferentially oxidizes benzaldehyde-like aromatic aldehydes. Bladder ALDH is also ext...

Hepatocellular carcinoma (HCC) is an aggressive primary liver cancer. However, its origin remains a debated question. Using human data and various hepatocarcinogenesis mouse models, we show that, in early stages, transformed hepatocytes, independent of their proliferation status, activate hepatic progenitor cell (HPC) expansion. Genetic lineage tracing of HPCs and hepatocytes reveals that, in a...

To examine genetic and epigenetic alterations associated with HBV integration in hepatocarcinogenesis, we compared genomic DNA profiles of primary hepatocellular carcinomas (HCCs) and cell lines that either contained or did not contain integrated HBV. To accomplish this, we carried out Restriction Landmark Genomic Scanning (RLGS), a two-dimensional system that displays 2000-3000 Not I landmark ...

Infection of Hepatitis B Virus (HBV) is a risk factor of chronic active hepatitis (CAH), hepatic cirrhosis and hepatocellular carcinoma (HCC). Infection of HBV may develop to HCC without antecedent hepatic cirrhosis. Pathogenesis of HBV causing malignant changes has not been fully understood. HBx, a protein of HBV, is an activator of transcription process involved in hepatocarcinogenesis. Most ...

We have studied the expression of insulin-like growth factor II (IGF-II) during hepatocarcinogenesis in four independent transgenic mouse lines. In all four lines liver-directed transgene expression induces a stepwise and relatively synchronized tumorigenesis. IGF-II reexpression occurs in all four lines irrespective of the mechanism of tumor induction. Reexpression is chronologically associate...

Unlike other types of cancer, hepatocellular carcinoma (HCC) is usually preceded by chronic inflammation caused by viral infection. The mutation of mitochondrial DNA (mtDNA) in hepatocarcinogenesis associated with viral infection was investigated. Compared with control liver tissue, the frequency of mtDNA mutations was markedly increased in both noncancerous and cancerous liver specimens from i...

Hepatocellular carcinoma is the most common primary malignancy of the liver in adults. It is also the fifth most common solid cancer worldwide and the third leading cause of cancer-related death. Recent research supports that liver cancer is a disease of adult stem cells. From the models of experimental hepatocarcinogenesis, there may be at least three distinct cell lineages with progenitor pro...