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)

Determination of p21, a product of Ha-ras oncogene, and HBsAg in hepatocellular carcinoma (HCC) and liver cirrhosis etc. was carried out with ABC method. The results showed that HCC tissues exhibited enhancement of p21 expression with a positive rate of 72.4%, which was obviously higher than the expression of p21 in tissues from liver cirrhosis, chronic hepatitis and hepatoblastoma. The p21 positive rate of regenerative cirrhosis nodules close to the HCC was 87.2%. The p21 expression level in HBsAg positive regenerative nodules of cirrhosis close to the HCC was significantly high, and its positive rate reached 93.9%. The expression level of p21 protein in well-differentiated HCC was higher than that of poorly differentiated and undifferentiated HCC. Therefore, the result suggests that the expression level of p21 in liver cirrhosis is related to persistent infection of HBV. The elevated expression of p21 plays an important role in the development of regenerative nodules in liver cirrhosis towards HCC, and it is also an important factor in the early stage of HCC development.
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PMID:[Expression of p21 in hepatocellular carcinoma and liver cirrhosis and its relation with HBV infection]. 165 96

To elucidate the cell biological significance of ras oncogene, the expression of ras-p21 was analyzed in 53 cases of liver tissues including 34 cases of hepatocellular carcinoma (HCC), by using immunohistochemical method. In result, 22 (65%) cases of 34 HCC and 34 (79%) cases of 43 liver cirrhosis were positive for p21, whereas all of chronic hepatitis and normal livers were negative. Especially, comparative study between the expression of p21 and clinicopathological background of HCC revealed that p21 was prominently expressed in well differentiated form, nodular type, small liver cancer, and the cases showing AFP levels below 400 ng/ml. From these results, it was indicated that ras oncogene might play an important role in malignant transformation of hepatocytes or differentiation of HCC.
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PMID:[The expression of ras p21 product in hepatocellular carcinoma]. 170 Jan 76

Pathological diagnosis of hepatic tumors is sometimes difficult when performed with only routine examinations such as Hematoxylin and Eosin (H.E.) stain. The diagnostic usefulness of KM01 was compared to that of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), CA19-9 and ras p21 in this immunohistochemical study. AFP was positive in about half of the cases of hepatocellular carcinoma and hepatoblastoma, and AFP-positive cells were frequently found at the periphery of acini in both diseases. Absorbed CEA stain was mostly negative in hepatocellular carcinoma, but was positive in the cells of mixed hepatocellular and cholangiocellular carcinoma (MHCC) and metastatic liver cancer, especially in their cytoplasm. CA19-9 immunostaining was completely negative, and was only 3% positive in hepatocellular carcinoma. KM01 stain was positive in about half of the cases of hepatocellular carcinoma, hepatoblastoma and MHCC. It was positive in proliferated bile ducts around the capsule in the former two diseases but positive in the tumor cell of both parts of the cytoplasm in the latter. The histological positivity of ras p21 was high in all tumor cells of these three types of tumors. Negative absorbed CEA and KM01 in pseudoglandular hepatocellular carcinoma differentiated from MHCC and metastatic liver cancer. However these tumor markers were occasionally positive and nonspecific in cancer-like lesions, implying no advantage for differential diagnosis between hepatocellular carcinoma and apparent cancer-like lesions. The above results demonstrate that AFP, CEA and KM01 are effective for differentiating hepatocellular carcinoma among various hepatic tumors.
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PMID:Immunohistochemical study on hepatic tumors--KM01 stains compared with AFP, CEA, CA19-9 and RAS P21. 171 40

The expression of the c-myc gene has previously been shown to be elevated and deregulated in the human hepatoma cell line Hep G2 (B. E. Huber and S. S. Thorgeirsson, Cancer Res., 47: 3414-3420, 1987). We now report that the Hep G2 N-ras gene is activated to a dominant-acting, transforming gene by a missense mutation in codon 61. Hep G2 DNA produced transformed foci when transfected into NIH 3T3 cells. Subsequent to a secondary round of transfection, Southern blot analysis of tumorigenic NIH 3T3 foci demonstrated the presence of human N-ras sequences. Nucleotide sequence analysis of one Hep G2 N-ras allele demonstrated that codons 12, 13, and 59 were normal and that codon 61 had a missense mutation (CAA to CTA). This mutation results in the incorporation of leucine instead of glutamine at residue 61 of the N-ras gene product, p21. N-ras sequences were amplified by the polymerase chain reaction from both Hep G2 genomic DNA and Hep G2 complementary DNA. Analysis of the amplified sequences demonstrated that only one Hep G2 N-ras allele exhibited the codon 61 mutation and that both the mutant and normal alleles were transcribed. Northern blot analysis demonstrated equivalent steady-state levels of N-ras transcripts in Hep G2 cells and normal human liver. The steady-state levels of N-ras and ornithine decarboxylase transcripts were positively correlated suggesting a positive relationship between N-ras expression and the replication rate of Hep G2 cells. c-Ki-ras and c-Ha-ras transcripts were not detected in either Hep G2 cells or normal human liver. Immunoprecipitation experiments using the monoclonal antibody Y13-259 demonstrated the presence of p21 in Hep G2 cells. Expression of a dominant-acting, transforming N-ras gene, in conjunction with the altered regulation of the c-myc gene, documents two important genetic lesions that could be responsible for the transformed phenotype of Hep G2 cells.
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PMID:Characterization of a transforming N-ras gene in the human hepatoma cell line Hep G2: additional evidence for the importance of c-myc and ras cooperation in hepatocarcinogenesis. 215 25

The immunohistochemical localization of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) was studied in 44 cases with cholangiocarcinoma (CC) to determine the correlation to the expression of ras oncogene product p21 on tumor cells. HCG-immunoreactivity was found in 10 of 44 cases (23%) and AFP in only one (2.3%), whereas the expression of ras p21 was demonstrated in 39 (88.6%). The incidence of HCG-positive cells within the tumor was less than 1% in 8 of 10. The incidence of AFP-positive cells was less than 0.01%. All were histologically classified as adenocarcinoma and none of them had histologic features of trophoblastic tumors, yolk sac tumor or hepatocellular carcinoma. Nine of 10 HCG-positive and one AFP-positive CC expressed ras p21 on their tumor cells. However, one HCG-positive CC was negative for ras p21, though the incidence of HCG-positive cells within the tumor was 25%. HCG- and AFP-immunoreactivity was more frequently observed in poorly or undifferentiated tumor cells than in moderately or well-differentiated areas, whereas the expression of ras p21 was more diffuse in well-differentiated tumor and stronger in moderately differentiated areas, but rarely found in poorly and undifferentiated tumor. These results suggest that HCG production by CC of the usual adenocarcinoma variety is not rare, when compared to AFP production, and is preferentially localized in a small number of poorly differentiated and undifferentiated carcinoma cells, and there is no correlation between the production of HCG or AFP and the expression of ras p21 in CCs.
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PMID:Human chorionic gonadotropin and alpha-fetoprotein in cholangiocarcinoma in relation to the expression of ras p21: an immunohistochemical study. 247 36

Hepatitis B virus (HBV)-related antigens produced by the human hepatoma cell line (HB611 cell), which had been transfected with a cloned HBV DNA and established as a stable producer of HBV (T. Tsurimoto, A. Fujiyama, and K. Matsubara, 1987, Proc. Natl. Acad. Sci. USA 84, 444-448), were investigated immunochemically and morphologically. All HBV-related antigens, HBV surface (HBsAg), e (HBeAg), and core (HBcAg), were semiquantitatively examined by the respective reversed passive hemagglutination assay (RPHA). RPHAs for HBcAg and for HBeAg were characterized as reacting only to the core particles and to the free form of nucleocapsid proteins, respectively. The amounts of HBsAg and nucleocapsid protein in culture medium were roughly related to the number of viable cells. The amount of core particles was, instead, proportional to the number of dead cells. Relative amounts of HBsAg, core particles, and nucleocapsid proteins in culture medium, cell surface, and cell lysate were determined and it was found that HBsAg and nucleocapsid proteins were effectively secreted into culture medium but core particles were not. Molecular species of nucleocapsid proteins were identified to be p17 and p18 (HBeAg polypeptides) in the culture medium and HBeAg polypeptides and p21.5 (HBcAg polypeptide) in the cytosol fraction. The p21.5 was preferentially found in the nuclear fraction.
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PMID:Intra- and extracellular distribution and immunochemical characterization of hepatitis B virus nucleocapsid proteins produced by a human hepatoma cell line transfected with cloned viral DNA. 253 6

An immunohistochemical assay was used to assess expression of ras p21 and myc p62 oncogene products in human hepatocellular carcinoma (HCC) and non-neoplastic liver tissues. The monoclonal antibodies Y13 259 and Myc1-9E10, specific for ras p21 and myc p62 oncoproteins, were employed on paraffin-embedded sections. Most HCCs showed enhanced ras p21 and myc p62 expression, as indicated by staining intensity. Cirrhotic livers revealed increased myc p62 and occasionally increased ras p21 expression. HBsAg+ hepatocytes showed intense immunostaining for ras p21. Fibrotic, cholestatic, fetal and normal adult liver did not present enhancement of oncoprotein production. We suggest that combined over-expression of ras and myc oncoproteins may be important for the malignant phenotypic alteration in human HCC.
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PMID:Expression of ras and myc oncogenes in human hepatocellular carcinoma and non-neoplastic liver tissues. 254 35

Aberrant proto-oncogene expression has been implicated in hepatic cell proliferation, transformation and carcinogenesis using a rat model. To investigate the role of ras p21 product expression in human hepatocellular carcinoma (HCC), we have localized ras p21 in formalin fixed, paraffin-embedded normal and abnormal livers utilizing the avidin-biotin peroxidase method and a monoclonal antibody to ras-gene product p21. A semi-quantitative estimate of p21 expression was performed by serial dilutions of primary antibody. While low dilutions of anti-p21 stained normal hepatocytes, higher dilutions failed to react with normal hepatocytes and these dilutions were used for assessment of p21 enhancement. Increased p21 expression of ras oncogene in HCC occurs in fibrolamellar carcinomas and other better differentiated HCC. Tumor dedifferentiation is associated with an attenuation of p21 expression. Liver adjacent to HCC exhibits p21 enhancement, in contrast to liver surrounding metastatic carcinoma, suggesting increased p21 expression in HCC induction.
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PMID:ras oncogene p21 expression in hepatocellular carcinoma. 255 Jun

We have previously described the inhibition of glucocorticoid-dependent transcription from the mouse mammary tumor virus long terminal repeat promoter by products of the H-ras and v-mos oncogenes. We have studied the effects of conditional oncogenes on expression of glucocorticoid-dependent indicator genes. Expression of the glucocorticoid-dependent transcription of the tyrosine aminotransferase gene was monitored in FTO-2B rat hepatoma cells during Mr 21,000 protein (p21) H-ras induction. A strong transcriptional repression of the tyrosine aminotransferase gene followed p21 H-ras expression. The sequences in a glucocorticoid-dependent promoter which are responsible for the oncogene-mediated repression could be localized to the glucocorticoid response element; a construct in which a 15-base pair glucocorticoid response element was inserted 5' of the thymidine kinase promoter exhibited the oncogene-mediated repression of transcription. We observed a strong repression of glucocorticoid-dependent promoters and promoter constructs not only in the presence of p21 H-ras and p37 v-mos but also with p60 v-src. p57 v-myc, however, had no effect. Oncogene expression is not a sufficient prerequisite for an initial repression of glucocorticoid hormone-dependent gene transcription, since even in the presence of constitutively high levels of oncogene product a transient stimulation of glucocorticoid-dependent gene expression was found. Protein synthesis inhibition experiments revealed that no hormonally induced cellular protein is needed for the oncogene-mediated repression. It seemed reasonable that this phenomenon might reflect oncogene effects on the glucocorticoid receptor. We, therefore, made measurements of the glucocorticoid receptor protein. In the presence of glucocorticoid hormone the receptor translocated rapidly from the cytoplasm to the nucleus. In normal NIH 3T3 cells, after 24-h treatments the nuclear receptor levels had declined to about 50% of those determined at 2 h and in the presence of p21 H-ras they declined to 15%. The levels of cytoplasmic receptor were not affected by p21 H-ras expression.
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PMID:Oncogene mediated repression of glucocorticoid hormone response elements and glucocorticoid receptor levels. 256 9

The development of monoclonal antibodies (MAb) against ras protein has made possible to study the expression of ras oncogene by immunohistochemical methods in many human solid tumors. Using the MAb RAP-5 generated against a synthetic peptide having the sequence of amino acids 10-17 of the human T24 ras gene product and the peroxidase anti-peroxidase (PAP) technique, we have observed increased level of ras p21 protein in four human hepatoma cell lines and corresponding tumors in athymic mice. The increased level of p21 is not correlated with the grade of differentiation of tumor cells, nor with the expression of HBsAg. The continuous enhanced expression of ras gene product at the cell line level and after transplantation in athymic mice suggests that the increase in p21 level may be important in the maintenance of the transformed phenotype of the hepatoma cells.
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PMID:Immunocytochemical localization of p21 ras gene product in human hepatoma cell lines and corresponding tumors in athymic mice. 283 67


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