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 activity of butyrylcholinesterase (BCHE), a liver fetal isozyme (Zone L-V) of a nonspecific esterase, was studied histochemically and cytochemically in rat hepatocellular carcinomas induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). In normal adult rats, BCHE activity was very prominent in cells of the intestinal mucosa but was not detectable in the liver. On the other hand, in fetal rat liver, a few cells scattered throughout the organ were BCHE positive. 3'-Me-DAB induced poorly differentiated hepatocellular carcinomas showing an intense BCHE activity, especially in areas consisting of small tumoral cells proliferating in a sheet-like pattern. Surrounding noncancerous liver tissue was completely devoid of reaction products. Less-differentiated trabecular hepatocellular carcinomas also showed a positive reaction. On the other hand, well-differentiated hepatocellular carcinoma and hepatocellular carcinoma with an adenomatous pattern were barely stained, while areas of cholangiofibrosis were usually negative. Thus, in confirmation of a previous report, BCHE appears to be a positive marker of poorly differentiated hepatocellular carcinomas induced by 3'-Me-DAB. By electron microscopy, reaction products were demonstrated in the cisternae of the endoplasmic reticulum, in the nuclear envelopes, and sometimes on the cell surface of undifferentiated tumoral cells. The significance of the appearance of BCHE activity in hepatocellular carcinomas induced by 3'-Me-DAB is discussed.
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PMID:Histochemical and cytochemical study of butyrylcholinesterase activity in rat hepatocellular carcinomas induced by 3'-methyl-4-dimethylaminoazobenzene. 710 11

Aldose reductase and aldehyde reductase are members of the aldo-keto reductase superfamily, and participate in the reduction of a wide range of carbonyl compounds. We have purified aldose reductase from rat lens and raised antiserum against it in rabbits. Immunoblot analyses using this antibody showed that a significant amount of aldose reductase was expressed in cell lines derived from hepatomas while it was negligible in normal hepatocytes. Elevated expression of aldose reductase was also observed in cancerous lesions of 3'-methyl-4-dimethyl-aminoazobenzene (3'-Me-DAB)-induced hepatocarcinomas. Expression of aldose reductase mRNA was confirmed in these cells by Northern-blot analysis, suggesting that the induction occurred at the stage of gene transcription. The level of aldehyde reductase, however, did not change in cancerous tissue or in the cell lines. The viability of hepatoma cells in the presence of 3-deoxyglucosone and glyceraldehyde was decreased by an aldose reductase inhibitor, ONO-2235 (5-[1Z,2E)-2-methyl-3-phenylpropenylidene]-4-oxo-2-thioxo -3- thiazolidineacetic acid). Taken together, induction of aldose reductase gene expression during hepatocarcinogenesis may render cancer cells resistant to various toxic carbonyl compounds produced during metabolism or administered as anti-cancer drugs.
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PMID:Elevation of aldose reductase gene expression in rat primary hepatoma and hepatoma cell lines: implication in detoxification of cytotoxic aldehydes. 755 25

It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by such azo dye carcinogens as 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). Mammalian S-adenosylmethionine (AdoMet) synthetase exists as two isozymes, non-hepatic-type and liver-type enzymes, which are the products of two different genes. We have examined the expression of two AdoMet synthetase isozyme proteins and mRNAs in rat hepatomas induced by 3'-Me-DAB. The levels of non-hepatic-type enzyme protein and mRNA are clearly induced by 3'-Me-DAB feeding. On the other hand, the levels of liver-type enzyme protein and mRNA are nearly the same or slightly decreased during hepatocarcinogenesis. These results indicate that the expression of the non-hepatic-type isozyme gene is obviously influenced with the progression of carcinogenesis and that the non-hepatic-type isozyme is useful as a oncodevelopmental marker in the liver.
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PMID:Expression of non-hepatic-type S-adenosylmethionine synthetase isozyme in rat hepatomas induced by 3'-methyl-4-dimethylaminoazobenzene. 822 30

Whether the gene expression of hepatic Ca(2+)-binding protein regucalcin is altered in hepatomas was investigated. The change in regucalcin mRNA levels was analyzed by Northern blotting using liver regucalcin complementary DNA (0.9 kb). Rat hepatoma was induced by continuous feeding of basal diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). After 35 weeks feeding, rats were sacrificed, and the non-tumorous and tumorous tissues of the livers were removed. In individual rats, the regucalcin mRNA levels in the tumorous tissues were generally decreased in comparison with that of the non-tumorous tissues of the chemical-fed rats, although the chemical administration might decrease the mRNA expression in normal rat liver, suggesting that the chemical administration causes a suppressive effect on the mRNA expression. When the genomic DNA extracted from the liver tumorous tissues was digested with restriction enzymes (EcoRI, BamHI and HindIII) and analyzed by Southern blotting, no rear-ranged band was found in the regucalcin gene from the hepatoma. Interestingly, in the transplantable Morris hepatoma cells, the regucalcin mRNA was markedly expressed, while the albumin mRNA was expressed only slightly. The present study demonstrates that regucalcin mRNA is clearly expressed in the transformed cells (Morris hepatoma cells).
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PMID:Expression of calcium-binding protein regucalcin mRNA in hepatoma cells. 871 43

The inbred DRH rats are highly resistant to the induction of hepatocellular carcinoma (HCC) by feeding of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). Previously, we found that two quantitative trait loci (QTLs), Drh1 and Drh2, significantly reduced the number, size and area of glutathione S-transferase-placental form (GST-P)-positive foci and GST-P mRNA levels in (F344xDRH)F(2) rat livers induced by feeding 3'-Me-DAB for 8 weeks. It is unclear, however, whether these QTLs affecting pre-neoplastic lesions are also the determinants of the later stage hepatocarcinogenesis, and whether there are any additional QTLs affecting hepatocarcinogenesis in the progression stage. To answer these questions, we analyzed QTL parameters for liver tumors in 99 (F344xDRH)F(2) rats induced by feeding 3'-Me-DAB for 20 weeks. The QTL parameters examined were GST-P mRNA, ornithine decarboxylase activity, and the number and total area of HCC/nodules macroscopically detectable on the liver surface. In composite interval mapping, we observed two major QTL peaks overlapping on the map positions of Drh1 on rat chromosome 1 (RNO1) and Drh2 on RNO4, respectively. The newly mapped QTL on RNO1 affected the GST-P mRNA level at 20 weeks of 3'-Me-DAB feeding, but did not affect the number and size of tumors. The primary effect of Drh1 is, therefore, to inhibit GST-P induction and to prevent enzyme altered foci (EAF) formation. On the other hand, the QTLs on RNO4, co-mapped to Drh2, affected all parameters of liver tumors examined except for the level of GST-P mRNA. The latter QTLs influenced not only the induction of GST-P and formation of EAF but also the progression of tumors in the later stage of hepatocarcinogenesis. The GST-P induction is differentially controlled by stages of hepatocarcinogenesis and the DRH resistance to carcinogenesis is principally attributed to the QTLs on RNO4 out of two resistance QTLs identified in the pre-neoplastic stage.
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PMID:Resistance of DRH strain rats to chemical carcinogenesis of liver: genetic analysis of later progression stage. 1175 40

AIM:To determine the correlation between expression of androgen receptor (AR) gene and hepatocarcinogenesis.METHODS:Male SD rats were used as experimental animals and the animal model of experimental hepatocarcinoma was established by means of 3'-me-DAB administration. Androgen receptor mRNA was detected by a non-radioactive in situ hybridization assay in neoplastic and non-neoplastic liver tissues.RESULTS:The expression of androgen receptor mRNA was observed only in neoplastic cells and some atypical hyperplastic cells. In the liver tissue of control animal and the remaining normal liver cells adjacent to the carcinoma tissue, no positive signal was seen.CONCLUSION:Androgen has an important correlation with hepatocarcinogenesis and the expression of androgen receptor gene might be a mark event during hepatocarcinogenesis.
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PMID:In situ hybridization assay of androgen receptor gene in hepatocarcinogenesis. 1181 55

The replication time and pattern have been investigated in hepatoma cells induced by feeding 3'Me-DAB to male rats for 5 months. With the use of tritiated thymidine as a DNA label along with autoradiography, mitotic nuclear labeling has been studied 0.5 to 72 hours after the administration of the label. The following time intervals have been estimated: replication time, 31 hours; DNA synthesis, 17 hours; G(2) plus Mitosis, 2 hours; G(1), 12 hours. Only about 8 per cent of the tumor cell (interphase) population is "flash" labeled, following a single dose of 50 microC of H(3)TDR. This group of cells has been followed through three cycles of division. The repeated rhythmic passage of tumor cells through cell division is similar to that previously reported for normal liver cells in the growing rat. However, tumor cells have longer replication and DNA synthesis times. In addition, the several time intervals studied vary more in the tumor cell population than they do in the growing normal cell population.
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PMID:THE REPLICATION TIME AND PATTERN OF CARCINOGEN--INDUCED HEPATOMA CELLS. 1420 84

The carcinogen-resistant inbred rat strain DRH established from closed-colony Donryu rats by use of selective brother-sister mating over 20 generations under continuous feeding of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) maintains a highly resistant phenotype without carcinogen exposure for many years. We reported that the clonal expansion of preneoplastic glutathione S-transferase-P(GST-P)-positive foci induced by 3'-Me-DAB was less extensive in the liver of DRH rats than in the liver of susceptible strains, such as Donryu and F344, although levels of DNA adducts were comparable among these rats. Comparative studies of the events after initiation indicate that DRH rats are constitutionally less prone to cellular damage caused by continuous administration of 3'-Me-DAB than are parental Donryu rats. Consequently, the reduced growth response of the liver during the promotion stage may contribute to the low susceptibility to development of liver tumors. Genetic analysis of (F344 x DRH)F2 rats identified two quantitative trait loci, Drh1 on chromosome 1 and Drh2 on chromosome 4, which provide resistance to the development of GST-P-positive preneoplastic foci induced by 3'-Me-DAB during the early stage of its administration. The resistance to progression to hepatocellular carcinoma is affected solely by Drh2. These observations indicate that at least two genetic loci are critically involved in the steps leading to chemical hepatocarcinogenesis. The DRH rat is a useful experimental model with which to study genetic susceptibility and resistance to chemically induced liver cancers.
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PMID:Genetic resistance to chemical hepatocarcinogenesis in the DRH rat strain. 1535 16

The purpose of this study is to investigate if the EGFR-Stat3 signal pathway contributes to the carcinogenesis of hepatoma in rats. Hepatoma was induced in rats by 3'Me-DAB as a model. EGFR, TGFalpha, Stat3, p-Stat3 in different stages of carcinogenesis were detected by immunohistochemistry and Western blot. In situ hybridization was applied to investigate the expression of Stat3 mRNA. The expressions of signal molecules were assessed by KS400 Image Analysis system. The data were statistically evaluated. EGFR, TGFalpha, Stat3 were highly expressed in the stages of liver necrosis and repairment. All hepatocellular carcinoma cases revealed elevated expression of EGFR, TGFalpha. Elevation of Stat3 mRNA and protein levels were identified, increase of activation of Stat3 was also observed. In HCC, there was positive correlation between p-Stat3 level and the expression of TGFalpha and PCNA. Increased expression of Bcl-2 (P < 0.05) coincided with elevated level of p-Stat3. Therefore, the EGFR-Stat3 signal pathway was related to the development of hepatoma in rats. TGFalpha-EGFR autocrine ring formation may lead to the activation of Stat3 and in turn, promote proliferation and regulate the transcription of genes regulating cell apoptosis and cell cycle.
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PMID:Roles of EGFR-Stat3 signal pathway in carcinogenesis of experimental hepatoma in rats. 1703 71

We have examined the mRNA levels for the catalytic subunits of three phosphoseryl/phosphothreonyl protein phosphatases PP1alpha, PP2Aalpha and PP2C by Northern blot analysis in the three primary hepatomas and the three poorly differentiated ascites hepatomas. The mRNA levels were compared with those in regenerating rat livers. In regenerating rat livers, the mRNA levels of PP1alpha, PP2Aalpha and PP2C at 24 h after partial hepatectomy were elevated 5, 14 and 10 times as compared to those of the control livers. But in the three primary hepatomas induced by 3'-methyl-4-dimethyl-aminoazobenzene(3'-Me-DAB), 2-acetylaminofluorene(2-AAF), and induced by the Solt-Farber model, the mRNA levels of PP1alpha, PP2Aalpha and PP2C were almost the same as those of the control livers. On the other hand, in the three poorly differentiated ascites hepatomas, AH13, AH66F and AH130, PP1alpha mRNA levels were 10 times higher than that of the control livers. In these ascites hepatomas, PP2Aalpha mRNA levels were distinctively lower than that of the control livers. PP2C mRNA levels were the same in AH13 and lower in AH66F and AH130 compared to the controls. From these results, it was demonstrated that PP1alpha mRNA levels were selectively increased in poorly differentiated ascites hepatoma cells.
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PMID:Selective high expression of protein phosphatase pp1-alpha messenger-RNA in rat poorly differentiated ascites hepatomas. 2157 43


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