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 change in the activity of several hepatic enzymes during hepatocarcinogenesis suggests a pattern of dedifferentiation. This category of enzymes includes glucose-6-phosphatase and gamma-glutamyltranspeptidase (GGT). A detailed kinetic analysis of microsomal glucose-6-phosphatase activity revealed that both the translocase and phosphohydrolase activities were markedly reduced in Morris 7777 hepatoma transplanted in male Buffalo rats. In addition, the activity of the translocase component increased 2.4-fold, while the phosphohydrolase activity decreased 1.6-fold in the liver of tumor-bearing animals. GGT activity in the host liver was not effected by the presence of the tumor. These results suggest differences in the effect of Morris 7777 hepatoma on: the phosphohydrolase and translocase activities of microsomal glucose-6-phosphatase and the sensitivity of glucose-6-phosphatase and GGT activities in the host liver.
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PMID:Effect of Morris 7777 hepatoma on microsomal glucose-6-phosphatase latent activity. 614 32

The activity of gamma-glutamyltranspeptidase (GGT) as well as glycogen storage within hepatocytes from cirrhotic human liver were investigated by histochemical means. In 4 cases out of 9, many enzyme-altered, PAS positive dysplastic 'foci' were seen. Such lesions may be considered as possible precursors of hepatoma, as already reported in rat liver during chemical carcinogenesis. Among the preneoplastic liver markers, GGT positivity seems the most useful one to be added to the routine histological examination of liver biopsies.
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PMID:[Histochemical identification of preneoplastic hepatocellular lesions in the human liver]. 615 45

The expression of two markers of fetal liver, alpha-fetoprotein (AFP) and gamma-glutamyltranspeptidase (GGT), and the relationship between these markers and tumorigenicity were studied in 17 continuous epithelial-like cell lines derived from normal rat livers and ascitic hepatoma cells. Fourteen cell lines positive for GGT activity included 6 non-transplantable lines. Out of 10 cell lines transplantable to syngeneic rats and/or immuno-depressed hamsters, 2 showed no activity of GGT cytochemically. AFP production was seen in the culture fluid of 4 out of 15 cell lines tested. They consisted of 1 GGT-positive, transplantable, 1 GGT-negative, transplantable, and 2 GGT-positive, non-transplantable cell lines. These results indicate that no correlation exists among these 3 parameters related to neoplastic and preneoplastic states of cells.
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PMID:Lack of correlation among gamma-glutamyltranspeptidase activity, production of alpha-fetoprotein, and transplantability in rat liver epithelial-like cell cultures. 616 94

Alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), alkaline phosphatase (ALP) and gamma-glutamyltranspeptidase (GT) were determined in three groups of patients: 21 with primary liver carcinoma (PLC), 106 with metastatic liver disease, and 110 with various degrees of alcoholic liver diseases. AFP was elevated in 12 out of 14 with hepatocellular carcinoma but in none of 7 with cholangiocarcinoma. CEA was elevated in 8 of 14 with hepatocellular carcinoma and in 5 of 7 with cholangiocarcinoma. In metastatic liver disease, 83% had elevated CEA greater than or equal to 5.0 micrograms/l, 50% having CEA levels greater than 20 micrograms/l. AFP was moderately elevated in 26% of the patients, the values being less than 100 micrograms/l in all but one. In patients with alcoholic liver disease, 31% had elevated CEA levels greater than or equal to 5.0 micrograms/l; one of these had an extremely high value of 245 micrograms/l. AFP was moderately elevated to less than 100 micrograms/l in only 9%. CEA is a sensitive indicator of metastases: a value above 20 micrograms/l is almost always associated with malignancy. However, the presence of alcoholic liver diseases must be considered in evaluating patients with increased CEA levels. AFP and CEA seemed to be of value in differentiation between primary and secondary liver carcinoma. ALP and GT are also relatively sensitive indicators of malignant liver disease, but they are more unspecific than AFP and CEA.
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PMID:Alpha-fetoprotein and carcinoembryonic antigen in patients with primary liver carcinoma, metastatic liver disease, and alcoholic liver disease. 618 10

The mixed-function oxidase system shows a number of variations in the liver of diethyl-nitrosamine (DEN) treated rats. These include a decrease of the cytochrome P450 content and of the aminopyrine demethylase activity both in the hyperplastic nodules and in the hepatoma. Processes of detoxification, such as the glutathione system, show some modifications. These alterations are in accordance with the decrease of glutathione peroxidase and the increase of gamma-glutamyltranspeptidase during diethyl-nitrosamine carcinogenesis.
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PMID:Functional alterations of the endoplasmic reticulum and the detoxification systems during diethyl-nitrosamine carcinogenesis in rat liver. 647 42

Hepatic hyperplastic nodules (HHNs) in rats were studied as an experimental prototype of oral contraceptive-related hepatic tumors. We have found cytoplasmic estrogen receptors in HHNs produced by acetylaminofluorene (AAF) (four cycles of 0.02% in diet). Rats with AAF-induced HHNs were randomized into four groups: (i) AAF-treated control; (ii) estrogen alone (estradiol-17 beta); (iii) tamoxifen alone, and (iv) estrogen + tamoxifen. After 8 months of treatment with estrogen (estradiol-17 beta) in combination with tamoxifen, there was regression of nodular involvement and no evidence of malignant transformation. Decreased nodular proliferation also occurred after 2 and 4 months treatment with estradiol-17 beta and after 8 months of tamoxifen administration. The incidence of hepatocellular carcinoma after 8 months of treatment was significantly less after treatment with estrogen (40%) or tamoxifen (42.9%) when compared to AAF-treated controls (87.5%). The number of gamma-glutamyltranspeptidase-positive foci were reduced in all treatment groups after 2, 4, and 8 months of treatment; these changes were most pronounced in the estrogen-treated group and did not directly correlate with the per cent inhibition of malignant transformation. Our results suggest that the malignant transformation of estrogen receptor-positive HHNs is hormone dependent.
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PMID:Evidence for the hormone dependency of hepatic hyperplastic nodules: inhibition of malignant transformation after exogenous 17 beta-estradiol and tamoxifen. 684 Jun 77

Sequential observations were carried out on the induction of preneoplastic lesions in the liver and the kidney. Rats were initially given N-ethyl-N-hydroxyethylnitrosamine (EHEN) in their drinking water (0.1%) for 3 days (Group 1), 1 week (Group 2) or 2 weeks (Group 3) or tap water (Group 4). Rats in Groups 1-3 were subjected to partial hepatectomy and unilateral nephrectomy (right side) 2 weeks after the end of EHEN treatment. Rats from these groups were killed in week 10, 20, 30 and 40 of the experiment. In the liver, the effect of EHEN in the induction of gamma-glutamyltranspeptidase (gamma-GT) positive foci and hyperplastic nodules (HN) was clearly dependent on the length of treatment. The preneoplastic lesions increased with the lapse of observation time. Changes measured as number of gamma-GT positive foci were 10-40 times greater than those measured as HN, especially among the small size range. Values for changes in Group 1 given 0.1% EHEN for 3 days were very low, indicating that this dose is close to the threshold. Two rats with hepatocellular carcinoma in Group 3 given EHEN for 2 weeks survived until week 40. In the kidney, tubular epithelial proliferations composed of cells with slightly basophilic cytoplasm and slightly atypical nuclei were tentatively named atypical cell foci (ACF). EHEN induced ACF, renal cell adenomas and renal cell carcinomas. The increase in the induction of ACF was dependent on the length of observation period but not on the length of treatment. Even though control rats (not treated with EHEN) also had ACF, their quantitative values were far less than the groups given EHEN and killed at week 40, indicating that a large number of ACF were induced by EHEN. Therefore, EHEN is good for experimental induction of preneoplastic lesions in the liver and kidney of rats. The experimental schedule for Groups 1 and 2 could be used as a shortterm screening test for promoters and the schedule for Group 3 as an assay for inhibitors.
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PMID:Sequential observations on the appearance of neoplastic lesions in the liver and kidney after treatment with N-ethyl-N-hydroxyethylnitrosamine followed by partial hepatectomy and unilateral nephrectomy. 685 Sep 82

The objective of this study was to investigate the induction of liver tumors by arylhydroxamic acids. The potential involvement of sulfate conjugation was minimized by the administration of a N-hydroxy-4-acylaminobiphenyl to female CD rats. This experimental design provided for the exposure of a target organ that has only a low capacity for activation of hydroxamic acids by sulfate conjugation, with a carcinogen that does not induce tumors in liver that possess a high sulfotransferase activity. A single dose of the N-formyl or N-acetyl derivatives of N-hydroxy-4-aminobiphenyl was given i.p. at 0.4 mmol/kg body weight to 34-day-old animals. In attempts to amplify the hepatocarcinogenic potential of the compounds, partial hepatectomy 24 hr before the chemical injection and subsequent long-term treatment with phenobarbital in the diet were carried out. For comparative purposes, other animals were subjected to three additional partial hepatectomies subsequent to the carcinogen administration instead of the phenobarbital treatment. The experiments were terminated 64 weeks after injection. Both the N-formyl and N-acetyl derivatives of N-hydroxy-4-aminobiphenyl, in conjunction with partial hepatectomy and subsequent treatment of dietary phenobarbital, induced a high incidence of neoplastic nodules and gamma-glutamyltranspeptidase-positive foci in the liver. Only one hepatocellular carcinoma was observed in each treatment group. Repeated partial hepatectomies enhanced the yield of gamma-glutamyltranspeptidase-positive foci but were ineffective in producing neoplastic nodules. In addition to the liver lesions, mammary tumors were also induced. Importantly, an inhibitory effect of the subsequent administration of phenobarbital was observed on mammary tumor formation, possibly because of alterations in hormone metabolism resulting from the induction of microsomal enzymes by phenobarbital, which resulted in a decreased promoting effect. There was no difference in the tumorigenicity of the formyl and acetyl derivatives in these experiments.
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PMID:Effects of partial hepatectomy and dietary phenobarbital on liver and mammary tumorigenesis by two N-hydroxy-N-acylaminobiphenyls in female CD rats. 723 40

Insulin-like growth factor II (IGF II) regulated tissue-specific gene expression in hepatoma cell lines, but had no effect on expression of tissue-specific genes in primary cultures of E14 and newborn rat liver cells depleted of erythroid cells. No change was observed in these primary cultures with respect to alpha-fetoprotein (alpha-FP), albumin, cytokeratin 19 (CK19), gamma-glutamyltranspeptidase (GGT), and IGF II receptors. Two well-differentiated hepatoma, HepG2 and FTO-2B, and a poorly differentiated hepatoma, H4AzC2, did not show increased proliferation in the presence of IGF II, yet showed gene expression changes in response to IGF II. In HepG2 cells, IGF II increased albumin mRNA levels and resulted in a shift from clusters of cells positive to 100% of the cells expressing immunohistochemically detectable albumin. The transcription factor HNF-3 beta mRNA and protein levels of the bile duct markers, CK19 and GGT, were also increased in the presence of IGF II. Other genes tested were not affected, including alpha-1-antitrypsin, and two liver-specific transcription factors, HNF-4 and HNF-3 alpha. In FTO-2B cells, IGF II increased the expression of albumin, CK19, and GGT, without accompanying changes in albumin and GGT mRNAs. In H4A7C2 cells, IGF II reduced CK19 and OC.3 protein levels and GGT, transferrin, and HNF-3 beta mRNAs. The effects of IGF II on H4AZC2 cells were not blocked in the presence of an anti-rat IGF II receptor antibody. We conclude that IGF II affects tissue-specific gene expression of hepatomas and qualitative and quantitative aspects of its influence on the hepatomas is dependent on their degree of differentiation.
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PMID:Insulin-like growth factor II regulation of gene expression in rat and human hepatomas. 752 37

Expression of cancerous isoenzymes in various malignant tumors has been extensively studied using different biochemical techniques. Cancerous alkaline phosphatase (ALP) isoenzymes such as variant ALP and placental ALP are apparently detected in sera or tissues from patients with malignant tumors. Variant ALP is a specific tumor marker for hepatocellular carcinoma (HCC). Placental ALP is found in sera of patients with various malignant diseases. However, the positive rate of each ALP isoenzyme is low except for high positivity of placental ALP in seminoma. Novel gamma-glutamyltranspeptidase (gamma-GTP) isoenzyme is specifically found in about 60% of sera from patients with HCC, but in only 3% of patients with benign liver diseases, suggesting high specificity for HCC. Serum prostatic acid phosphatase (PAT), which increases in activity in parallel with the growth of prostatic tissue, is an useful marker for prostatic cancer. Thus, several cancerous isoenzymes are available for diagnosis of various malignant tumors.
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PMID:[Isoenzyme as tumor marker]. 760 66


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