BACKGROUND: Dysplastic nodules (DNs) recently have been identified as @entity157 ( @entity157 ). To test an alternative hypothesis regarding DN development, in which we have suggested that DNs develop as an infiltrating clonal expansion in advance of, or parallel to @entity82 , the authors investigated the rates of apoptosis and proliferation in @entity1 hepatocarcinogenesis. METHODS: The authors performed terminal deoxynucleotidyl transferase-mediated @entity1977 - @entity1885 nick end labeling (TUNEL) assay and proliferation cell nuclear antigen (PCNA) staining in 11 low-grade DNs, 8 high-grade DNs including 3 cases with @entity157 subnodules, 10 small HCCs, and 29 cases of surrounding cirrhotic nodules. @entity157 subnodules were present in three cases of high DNs. They determined TUNEL-labeling indices (LIs) and PCNA-LIs as the percentage of positive hepatocyte nuclei per 500 randomly counted cells. RESULTS: TUNEL-LIs (mean +/- standard deviation) were 0.8 +/- 0.82 in cirrhotic nodules, 1.0 +/- 0.98 in low-grade DNs, 3.0 +/- 4.33 in high-grade DNs, 8.7 +/- 7.71 in @entity157 subnodules of high-grade DNs, and 3.2 +/- 3.58 in small HCCs. The peak values of apoptotic activity were higher in high-grade DNs and HCCs than in low-grade DNs and cirrhotic nodules. Each case of low-grade DN showed a low to medium level of apoptotic activity when compared with those of the four surrounding cirrhotic nodules. The PCNA-LIs were 2.6 +/- 1.35 in cirrhotic nodules, 4.5 +/- 2.31 in low-grade DNs, 15.3 +/- 10.50 in high-grade DNs, 25.4 +/- 5.25 in @entity157 subnodules of high-grade DNs, and 34.9 +/- 15.70 in small HCCs. The peak values gradually increased, although only @entity157 showed significantly elevated proliferation activity. The differences of @entity63869 -LIs and TUNEL-LIs, measured in each case, were 1.7 +/- 1.89 in cirrhotic nodules, 3.6 +/- 2.43 in low-grade DNs, 7.9 +/- 5.69 in high-grade DNs, 16.2 +/- 2.87 in @entity157 subnodules of high-grade DNs, 28.2 +/- 13.97 in small HCCs. At all stages of hepatocarcinogenesis, the rates of cell proliferation were higher than apoptosis, allowing a preferential net gain of (pre)neoplastic cells, and it was significantly increased in small HCCs. In regenerative cirrhotic nodules, 14% (4 cases) showed higher rates of apoptosis than proliferation. CONCLUSIONS: The regulation/dysregulation of apoptosis of (pre)neoplastic cells as well as of proliferation may play an important role in the process of hepatocarcinogenesis.

Apoptosis and proliferation in hepatocarcinogenesis related to XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity82 :: ('MESH:D005355', 'Disease') :: ['cirrhosis'] @entity1885 :: ('MESH:D001710', 'Chemical') :: ['biotin'] @entity63869 :: ('MESH:D018809', 'Chemical') :: ['PCNA'] @entity1977 :: ('CHEBI:17625', 'Chemical') :: ['dUTP'] @entity157 :: ('MESH:D006528', 'Disease') :: ['HCC', 'preneoplastic lesions of hepatocellular carcinoma', 'Hepatocellular carcinoma']
@entity82 :: (MESH:D005355,Disease) :: ['cirrhosis']
