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)

Cellular copper metabolism and the mechanism of resistance to copper toxicity were investigated using a wild type hepatoma cell line (HAC) and a copper-resistant cell line (HAC600) that accumulates copper and has a highly elevated level of metallothionein (MT). Of the enzymes involved in reactive oxygen metabolism, only glutathionine peroxidase was elevated (3-4-fold) in resistant cells, suggestive of an increase in the cellular flux of hydrogen peroxide. A majority of the cytoplasmic copper (greater than 60%) was isolated from both cell lines as a GSH complex. Kinetic studies of 67Cu uptake showed that GSH bound 67Cu before the metal was complexed by MT. Depletion of cellular GSH with buthionine sulfoximine inhibited the incorporation of 67Cu into MT by greater than 50%. These results support a model of copper metabolism in which the metal is complexed by GSH soon after entering the cell. The complexed metal is then transferred to MT where it is stored. This study also indicates that resistance to metal toxicity in copper-resistant hepatoma cells is due to increases in both cellular GSH and MT. Furthermore, it is suggested that elevated levels of GSH peroxidase allows cells to more efficiently accommodate an increased cellular hydrogen peroxide flux that may occur as a consequence of elevated levels of cytoplasmic copper.
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PMID:The role of glutathione in copper metabolism and toxicity. 256 91

A significant increase in the molecular weights of lamin A and more so of lamin C was observed when isolated Novikoff hepatoma chromatin was incubated in the presence of Ca2+. This increase did not occur to any significant degree in similar preparations of normal rat liver nuclei. Although detectable in Coomassie Brilliant Blue stained gels, this increase to a higher molecular weight (by approximately 2000 Mr) was much more visible when the electrophoretically separated lamins were transferred to nitrocellulose sheets and stained (using peroxidase-antiperoxidase) with polyclonal antiserum to the three major lamin proteins. This modification could also be induced when whole Novikoff hepatoma cell lysates were incubated in the presence of calcium. Again, this change did not occur in normal rat liver cells treated in the same manner. Further analysis has provided evidence that this modification is most likely mediated by the transaminating activity of an intrinsic nuclear transglutaminase forming a cross-link between the affected lamins and an unknown low molecular weight (approximately equal to 2000 Mr) moiety.
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PMID:Enzymatic modification of Novikoff hepatoma lamins A and C. 257 66

Detection of RNA transcripts within individual cells by in situ hybridization provides a powerful means for identifying specific cell types actively transcribing specific genes. We have applied this technique in order to analyze expression of the alpha-fetoprotein and albumin genes in a human hepatoma cell line, HuH-7. Using either 3H- or 35S-labeled human alpha-fetoprotein complementary DNA clone as a probe, we found that essentially all HuH-7 cells contained alpha-fetoprotein mRNA, although in various amounts. This correlated well with the presence of alpha-fetoprotein in all cells as detected by the peroxidase-antiperoxidase immunoenzyme method. The intracellular concentration of albumin, on the other hand, was below the level of detection by the peroxidase-antiperoxidase method. Consistent with this observation, we could not detect albumin mRNA with 3H-labeled albumin complementary DNA probes. However, the use of 35S-labeled probes having higher specific activities and higher efficiency of grain development resulted in the detection of albumin mRNA in a small percentage of HuH-7 cells. A variety of parameters involved in the in situ hybridization technique was examined to establish conditions suitable for demonstrating the presence of high- and low-copy numbers of mRNA in various cell and tissue preparations.
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PMID:Detection of messenger RNAs of alpha-fetoprotein and albumin in a human hepatoma cell line by in situ hybridization. 257 34

The metabolism of chemical carcinogens was investigated in liver preparations from 28 captive woodchucks (Marmota monax). Of these, 23 were naturally infected with the woodchuck hepatitis virus (WHV), and eight also had primary hepatocellular carcinoma (PHC). Twenty-nine parameters were investigated in liver subcellular fractions, including cross-reactivity with HBsAg, and biochemical parameters, such as gamma-glutamyl transpeptidase, cytochrome P-450 and microsomal monooxygenases (aryl hydrocarbon hydroxylase, ethoxycoumarin and ethoxyresorufin deethylases, aminopyrine and dimethylnitrosamine demethylases, and testosterone 7 alpha-, 16 alpha- and 6 beta-hydroxylases), uridine 5'-diphosphoglucuronosyl transferase, GSH and related enzymes (peroxidase, reductase and S-transferase), as well as other cytosolic enzyme activities (glucose 6-phosphate and 6-phosphogluconate dehydrogenases, NADPH- and NADH-dependent diaphorases, and DT diaphorase). In addition, liver preparations were used in order to quantify the metabolic activation into bacterial mutagens of five procarcinogens (aflatoxin B1, the pyrolysis products Trp-P-2 and MeIQ, 2-aminofluorene and dimethylnitrosamine) and the decrease of potency of three direct-acting mutagens (sodium dichromate, ICR 191 and 4-nitroquinoline 1-oxide). WHV infection produced a significant stimulation of carcinogen metabolism, as shown by the simultaneous change in detoxification parameters (GSH depletion) and activation indices (enhancement of microsomal monooxygenases and of procarcinogen activation into mutagenic metabolites). There were no significant differences between WHV-positive samples from animals without PHC and the noncancerous tissue of PHC-bearing animals, whereas a decrease of both activation and detoxification indices was recorded in the tumorous tissue. There was a considerable interindividual variability among WHV carriers, which was tentatively ascribed to genetic factors. Pregnancy was the only known factor influencing the results in WHV carriers. However, even by excluding pregnant animals, the effects on carcinogen metabolism produced by WHV infection were still statistically significant. These results, together with previous data obtained in humans, revealed that metabolic factors may play a role in the synergism between viral hepatitis and chemical hepatocarcinogens in the etiopathogenesis of PHC.
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PMID:Enhanced metabolic activation of chemical hepatocarcinogens in woodchucks infected with hepatitis B virus. 272 Sep 3

Rabbit antiserum to Pre-S1 protein was used to establish peroxidase-antiperoxidase (PAP) and avidin-biotin-peroxidase complex (ABC) immunohistochemical techniques for detection of Pre-S1 protein in paraffin-embedded liver tissue. Pre-S1 protein could be expressed in hepatocyte cytoplasm and on membrane in some cases with chronic viral hepatitis, cirrhosis and hepatocellular carcinoma (HCC), and its expression was intimately associated with HBsAg, HBcAg in liver and HBV DNA in serum, indicating that pre-S1 protein may represent the essential component of hepatitis B virus (HBV) and also serve as one of the markers of HBV infection. The incidence of Pre-S1 protein was slightly lower in nontumorous liver of HCC than in other cases and Pre-S1 protein could not be detected in tumorous tissue of HCC suggesting that expression of pre-S1 protein may be suppressed in HCC cases.
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PMID:A preliminary study on expression and significance of pre-S1 protein in liver tissue of patients with HBV infection. 276 Sep 66

The identification and characterization of collagenous and non-collagenous glycoproteins have made it possible to use specific antibodies as tools for the topographical localization of the various connective tissue components, and thus to follow the progression of parenchymal-stromal interactions. This investigation is an approach to the study of in vivo relationships between basement membrane components (type IV collagen, laminin) and neoplastic cells of hepatocellular carcinoma. Ten cases of hepatic carcinomas were analysed and paraffin-embedded sections were immunostained with anti-laminin and anti-type IV collagen antibodies. The avidin-biotin-peroxidase complex technique was used. In well differentiated neoplasms with hepatic tumour cells organized in a trabecular pattern lined by sinusoid structures, type IV collagen was always detected at the sinusoidal level. Laminin was evident only in two cases with a prominent intraparenchymal vascular bed. In less differentiated neoplasms, sinusoids were almost absent and only large tumour vessels were positive for both laminin and type IV collagen. At the interface between tumour tissue and the surrounding stroma, some carcinomatous elements were surrounded by laminin and type IV collagen. Our data further support the hypothesis that basement membrane phenotypic expression may be influenced both by the degree of tumour differentiation and by the characteristics of the micro-environment.
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PMID:Hepatocellular carcinoma: expression of basement membrane glycoproteins. An immunohistochemical approach. 282 85

Two monoclonal antibodies, designated 4C4 and 4G1, were produced by immunization of BALB/c mice with a human esophageal carcinoma cell line, CE69T/VGH, followed by fusion of the spleen cells from an immunized mouse with myeloma cells NS-1. 4C4 showed strong binding activity to three human esophageal carcinoma cell lines and one human hepatoma cell line, but not to any other cell lines tested. 4G1 reacted with three human esophageal carcinoma cell lines and four other cell lines. By peroxidase-antiperoxidase staining, 4C4 and 4G1 detected antigens of the epithelial cells on 10 pairs of esophageal carcinoma and normal esophageal specimens. 4G1 recognized a CE69T/VGH antigen with a molecular weight of 180K. Since 4G1 also reacted with purified carcinoembryonic antigen (CEA) and immunoprecipitated 125I-CEA, 4G1 seems to be an antibody recognizing CEA produced by CE69T/VGH cells. Since 4C4 also bound to the epithelial cells of normal uterine, vaginal, breast and liver tissues, it seems to recognize an epithelial antigen, and can be used to characterize the antigen in the specialization or differentiation of epithelial cells.
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PMID:Monoclonal antibodies against human esophageal carcinoma cell lines. 282 67

GM2 ganglioside was detected in all five sera of hepatoma patients analyzed by thin-layer chromatography in conjunction with enzyme-immunostaining with rabbit anti-GM2 antibody and horseradish peroxidase-conjugated anti-rabbit IgG, and was quantitated by densitometry. The GM2 contents of these sera were 20 to 100 times higher than those of sera from normal adults. By the method used, an increased GM2 level could be detected with samples of less than 0.1 ml of sera from hepatoma patients. The elevated levels of serum GM2 in hepatoma patients were suggested to be due to elevated GM2 levels in the liver lesions, because the GM2 contents of the liver of five patients with liver cancer, including three with hepatoma, were higher than those of normal liver tissues.
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PMID:Detection of ganglioside GM2 in sera and tumor tissues of hepatoma patients. 282 93

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

Using a monoclonal antibody to bromodeoxyuridine, we studied the cell kinetics of human hepatocellular carcinoma, liver cirrhosis, chronic active hepatitis and alcoholic liver fibrosis. Specimens were taken either by biopsy or surgery and immediately incubated with 0.1% bromodeoxyuridine solution at 37 degrees C for 45 min. After in vitro labeling, the bromodeoxyuridine taken up by the nuclei of S-phase cells was determined by the avidin-biotin-peroxidase complex method, using an anti-bromodeoxyuridine monoclonal antibody as the first antibody. The number of positive nuclei in 1,000 hepatic cells was counted, and the bromodeoxyuridine labeling index was expressed per thousand. The mean bromodeoxyuridine labeling index +/- S.D. of the cancerous portion of hepatocellular carcinoma, the noncancerous portion of hepatocellular carcinoma, liver cirrhosis, chronic active hepatitis and alcoholic liver fibrosis were 64.1 +/- 31.3, 33.6 +/- 14.4, 23.2 +/- 20.8, 9.1 +/- 6.1 and 21.6 +/- 13.0, respectively. The mean bromodeoxyuridine labeling index of the hepatocellular carcinoma cancerous portion was statistically higher than that of any other group. There was no statistical difference by the t test or the Wilcoxon test between the noncancerous portion of hepatocellular carcinoma and liver cirrhosis, and these two groups were proved interdependent by chi 2 test (Fisher's exact test), whether they were subdivided by bromodeoxyuridine labeling index greater than or equal to 10 or not. Bromodeoxyuridine labeling index was not significantly correlated with the usual biochemical parameters such as serum AST, ALT, gamma-GTP, alkaline phosphatase, lactate dehydrogenase, cholinesterase, albumin, and alpha-fetoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:S-phase cells in diseased human liver determined by an in vitro BrdU-anti-BrdU method. 284 68


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