Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of PCNA and EGFr in chemically induced hepatocellular carcinoma of liver and squamous cell carcinoma of stomach in rats were immunohistochemically observed. The results showed that the carcinoma cells of both tumors revealed a positive immunreaction to PCNA and EGFr. The histochemical observation of mast cell (MC) in both tumor tissues showed that the amount of MC in the surroundings of tumor cell nests was markedly different. According to the amount of the surrounding MCs the tumor cell nests could be divided into two groups: Group A with abundant MC infiltration and Group B with only scarce or without MC infiltration. The PCNA-positive cells in the tumor cell nests of both groups were calculated respectively. The results revealed that the amount of PCNA-positive cells in the group B was markedly more than that in the group A. The numerical ratio between two groups was 3:1 in the liver carcinoma and 2:1 in the stomach carcinoma approximately. An overexpression of EGFr was observed in tumor tissues of both groups, but there was also a marked difference in the amount of positively expressed cells and in the intensity of their staining reaction between both groups. The positively expressed cells in group B were much more and their staining intensity was much stronger than those in group A. According to the above mentioned results of observation, the expression state of both factors (PCNA and EGFr) was basically identical, suggesting that the MC may possess some inhibitory effect upon the growth rate of tumor cells of the experimental hepatocellular carcinoma of liver and the squamous cell carcinoma of stomach in rats.
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PMID:The relationship between mast cell infiltration and the expression of PCNA and EGFr in experimental hepatocellular carcinoma of liver and squamous cell carcinoma of stomach in rats. 875 35

The expression of PCNA and the protooncogenes of ras family (N-ras, H-ras and Ki-ras) in hepatocarcinoma cells and the proliferating liver cells in precancerous, hyperplastic nodules during experimental hepatocarcinogenesis, induced by diethylnitrosamine in rat liver was observed immunohistochemically and by in situ hybridization. The results indicated that there was a positive expression of PCNA in both the carcinomas cells and precancerous liver cells. The amount of PCNA-positive cells exhibited a negative correlation with the amount of infiltrating mast cells surrounding carcinoma cell nests and the hyperplastic, precancerous nodules. These results basically coincided with that of the separate observation of the expression of protooncogenes in the same study.
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PMID:[Expression of PCNA and protooncogenes during experimental hepatocarcinogenesis in rats]. 876 41

CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transcription factor that has been implicated in the regulation of cell-specific gene expression mainly in hepatocytes and adipocytes but also in several other terminally differentiated cells. It has been previously demonstrated that the C/EBPalpha protein is functionally indispensable, as inactivation of the C/EBPalpha gene by homologous recombination in mice results in the death of animals homozygous for the mutation shortly after birth (Wang, N., Finegold, M. J., Bradley, A., Ou, C. N., Abdelsayed, S. V., Wilde, M. D., Taylor, L. R., Wilson, D. R., and Darlington, G. J. (1995) Science 269, 1108-1112). Here we show that C/EBPalpha -1-mice have defects in the control of hepatic growth and lung development. The liver architecture is disturbed, with acinar formation, in a pattern suggestive of either regenerating liver or pseudoglandular hepatocellular carcinoma. Pulmonary histology shows hyperproliferation of type II pneumocytes and disturbed alveolar architecture. At the molecular level, accumulation of glycogen and lipids in the liver and adipose tissues is impaired, and the mutant animals are severely hypoglycemic. Levels of c-myc and c-jun RNA are specifically induced by several fold in the livers of the C/EBPalpha -/- animals, indicating an active proliferative stage. Furthermore, immunohistologic detection with an antibody to proliferating cell nuclear antigen/cyclin shows a 5-10 times higher frequency of positively stained hepatocytes in C/EBPalpha -/- liver. These results suggest a critical role for C/EBPalpha in vivo for the acquisition of terminally differentiated functions in liver including the maintenance of physiologic energy homeostasis.
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PMID:Increased hepatic cell proliferation and lung abnormalities in mice deficient in CCAAT/enhancer binding protein alpha. 879 45

Hepatocellular carcinoma (HCC) is a heterogeneous disease. HCC derived from different stages of cellular differentiation may have different clinical and pathobiological behavior. To test the hypothesis that HCC can be classified into two types based on its phenotypic markers (hepatocellular and biliary differentiation), liver tissues from 290 Chinese patients with HCC were studied. Expression of hepatocytic differentiation marker (HEP-PAR-reactive antigen), biliary differentiation markers (AE1-AE3, cytokeratin-19), proliferation markers (Ki-67, proliferating cell nuclear antigen), alpha-fetoprotein, p53, and transforming growth factor-alpha in the tumor tissue were assessed by immunohistochemistry. Hepatocytic differentiation marker was detected in 99.7% and biliary differentiation markers were detected in 29.3% of these tumors. Clinically, no patient with HCC with biliary markers survived for more than 27 weeks compared with a 22.6% survival rate in patients with HCC negative for biliary markers. HCCs positive for the biliary differentiation markers showed features of more aggressive disease in terms of poorer cellular differentiation (P < 0.001) and high-level expression of proliferation markers (Ki-67, P < 0.001; proliferating cell nuclear antigen, P = 0.0114) compared with HCCs without biliary markers. HCCs with biliary markers also had a higher level of expression of alpha-fetoprotein (P < 0.001) and p53 (P = 0.0077). Classification of HCCs based on its phenotypic (differentiation) markers has both clinical and pathobiological implications.
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PMID:Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications. 886 66

To assess the characteristics of intrahepatic metastatic lesions (IML) in hepatocellular carcinoma (HCC), we analysed both the histological features and proliferative activities of 15 resected cases of HCC accompanied by IML. The histological features of the IML were essentially the same as those observed in the main nodules in 12 (80%) of 15 cases. In 13 (87%) of 15 cases, the labelling index of proliferating cell nuclear antigen (PCNA) in the IML was either higher than or the same as in the main nodules. In 10 (77%) of 13 cases, the MIB-1 labelling index in the IML was either higher than or the same as in the main nodules. The results indicate that the histological features of the IML are essentially the same as those of the main nodules, while the proliferative activities in the IML were generally higher than those in the main nodules. Such characteristics may thus provide a clue to help distinguish intrahepatic metastasis from the multicentric occurrence of HCC.
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PMID:Proliferative activity in intrahepatic metastasis of hepatocellular carcinoma. 887 73

Studies of cellular proliferation may aid in elucidation of mechanisms of hepatocarcinogenesis and provide potential prognostic information in cases of hepatocellular carcinoma. Increased proliferation has been reported in the liver tissue adjacent to hepatocellular carcinoma and may be a risk factor for recurrence after tumor resection. We quantitated proliferating cell nuclear antigen (PCNA) clone PC10 and MIB-1 nuclear immunostain by image cytometry in fixed, paraffin-embedded tissue sections of normal, cirrhotic, and dysplastic livers with and without co-existent hepatocellular carcinoma and in the hepatocellular carcinoma. Fifteen high power fields were analyzed in each case using the CAS 200 image analyzer and results were expressed as the percent positive nuclear area. Cirrhotic liver showed significantly less proliferation adjacent to hepatocellular carcinoma than without hepatocellular carcinoma. There was a similar, but not significant, tendency for dysplastic liver. Increasing mean proliferation was noted from normal to cirrhotic to dysplastic liver to low grade to high grade hepatocellular carcinoma. These findings were similar using both PC10 and MIB-1. There tended to be slightly more staining with PC10 than with MIB-1, but the mean percent positive nuclear area was significantly greater with PC10 only in high grade hepatocellular carcinoma. Comparison of individual cases, however, yielded significant correlation between the two antibodies in the low grade and high grade hepatocellular carcinomas, but not in the benign livers. These findings demonstrate that image cytometric quantitation of PC10 and MIB-1 immunostain may be comparable measures of cellular proliferation and that there is no increase in proliferation in the hepatic tissue adjacent to hepatocellular carcinoma.
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PMID:Image cytometric comparison of proliferating cell nuclear antigen and MIB-1 staining in hepatocellular carcinoma and adjacent liver tissue. 888 91

There is an increased prevalence of p53 mutations in hepatocellular carcinomas (HCCs). A total of 62 HCC samples with adjacent liver tissue were analyzed immunohistochemically for the presence of p53 by two different commercial sources of Pab 1801. Polyclonal antibodies anti-HbsAg and anti-HbcAg were employed for the detection of HBV in the adjacent tissue and PC-10 for the detection of proliferating cell nuclear antigen (PCNA). Positive staining for p53 was identified in 42% and 55% of the HCC cases using each monoclonal antibody. p53 was found in 42% of the low grade and 43% of the high grade HCC. In 32% of the HCC cases, p53 was found in the adjacent liver tissue. In 52.6% of the cases with evidence of HBV infection, p53 positive expression was observed. PCNA was detected in 56% of the HCC cases (69% low grade, 57% high grade HCC). Eighty-one percent of the p53 positive tumours expressed PCNA, mostly with a high index. p53 and PCNA were not related to histologic grade. A trend for positive correlation was observed between p53 expression and HBV infection. The detection of p53 in non neoplastic tissue and the absence of a significant correlation between p53 expression and degree of differentiation support the hypothesis that the p53 gene mutation is involved in early stages of hepatocellular carcinogenesis.
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PMID:Immunohistochemical expression of p53 protein and proliferating cell nuclear antigen in hepatocellular carcinoma. 892 68

In rats with diethylnitrosamine (DENA)-induced hepatocellular carcinoma (HCC), we studied in vivo gene transfer efficiency using intraportal injections of recombinant adenovirus carrying the lacZ reporter gene (AdCMVlacZ) and the therapeutic efficacy of adenovirus-mediated transfer of the thymidine kinase gene of the herpes simplex virus (HSV-tk) followed by ganciclovir (GCV) administration. DENA was very effective in inducing HCC but also stimulated nontumor cell replication, as shown by proliferating cell nuclear antigen (PCNA) staining. The study of in vivo gene transfer efficiency in tumor-bearing rats showed that nontumor tissue and small tumor nodules were transduced effectively whereas a poor transduction rate was noted in large tumor nodules. Concerning therapeutic efficacy, three groups of rats with established HCC were studied: group A and B received intraportally recombinant adenovirus carrying HSV-tk (AdCMVtk) or AdCMVlacZ, respectively, and 2 days after GCV was given intraperitoneally for 9 days; group C received only saline. Of the rats from groups B and C, 100% and 93% respectively, exhibited multiple HCC tumor nodules at end of the study. In contrast, a complete regression of tumor was observed in 63% of animals from group A. This group showed significant elevation of serum transaminases and a diffuse hepatotoxic lesion in liver tissue; histological signs of regeneration were observed in surviving animals. Nine out of 19 rats from group A died during the treatment period. We conclude that (i) in the DENA model of HCC, tumoral cells can be destroyed in vivo by the HSV-tk/GCV system despite poor transduction of large tumor nodules, suggesting that toxic metabolites generated by nontumor cells may exert a bystander effect on tumor tissue; (ii) significant hepatoxicity and a high mortality rate occurred in HSV-tk/GCV-treated rats; these side effects appear to be due to the fact that in DENA-treated livers enhanced cell proliferation was present not only in tumor nodules but also in nontumor parenchyma, leading to GCV sensitization of both tissues; (iii) our results have implications concerning the efficacy and potential risks of the HSV-tk/GCV system in the treatment of human HCC.
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PMID:Gene transfer and therapy with adenoviral vector in rats with diethylnitrosamine-induced hepatocellular carcinoma. 904 2

We studied the relationship between hepatocyte proliferation and hepatitis delta virus (HDV) replication at the single cell level. The proliferating cell nuclear antigen (PCNA) (by immunohistochemistry) and the HDV RNA (by in situ hybridization) were stained in neoplastic and non-neoplastic liver tissues of 19 patients with chronic HDV infection, including four cases of cirrhosis with superimposed hepatocellular carcinoma (HCC). As controls, we assessed the hepatocyte proliferation of liver tissues from 16 patients with chronic hepatitis B and on three normal livers. The hepatocyte PCNA labelling index of HDV-infected tissues was comparable with that seen in chronic hepatitis B-infected livers but was significantly higher than that observed in normal livers. Although cirrhotic tissues had lower hepatocyte proliferating fractions than non-cirrhotic tissues, the difference was not statistically significant. The hepatocyte proliferation rate did not correlate with the level of intrahepatic HDV replication or with the histological activity. In double-labelling experiments, PCNA and HDV RNA staining did not co-localize, with the exception of two of three cirrhotic tissues associated with HCC, where the association between the two markers was statistically significant. This co-localization was not observed, however, in the adjacent tumorous tissues. In patients with chronic HDV infection the hepatocyte proliferation was increased with respect to normal liver tissue, but was comparable with that observed in patients with chronic hepatitis B virus infection and did not correlate with the level of HDV replication or the histological activity. In the cirrhotic tissue of patients with HCC (but not in the tumour counterpart), HDV RNA may occasionally co-localize with the marker of hepatocyte proliferation. Whether this association between viral replication and cell division is related to liver carcinogenesis remains to be established.
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PMID:Relationship between hepatocyte proliferation and hepatitis delta virus replication in neoplastic and non-neoplastic liver tissues. 909 64

Early Recurrence of Hepatoma: PCNA Labeling Index and DNA Ploidy Pattern Sixty-four cases of recurrent hepatocellular carcinoma (HCC) after hepatectomy were divided into two groups; E-group with recurrence within one year, and L-group with recurrence after 1 year. Clinicopathological features and surgical curability were the same in both groups. E-group had significantly higher positive rates of portal invasion, intrahepatic metastasis and rate of patients with more than 40% on PCNA labeling index. While the similar recurrence mode and the same treatment modalities were done, cumulative survival rates after recurrence in E-group had a poorer prognosis than L-group. These results suggest the possibility of lower response for the treatment on the recurrent lesion would be manifest in the E-group. New modalities for prevention of early recurrence of HCC after resection should be developed.
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PMID:[Clinicopathological study on early recurrent hepatoma and its treatment]. 926 14


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