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)

This report presents a review of tumors, except those of pituitary, that have been reported to occur in women taking combined oral contraceptive preparations. Pathologic features, both gross and microscopic, and differential diagnosis are emphasized. Particular attention is given to tumors of the liver: focal nodular hyperplasia (hepatic hamartoma) and liver cell adenoma (benign hepatoma). The characteristic features of these usually distinctive lesions are illustrated, and an attempt is made to evaluate the significance of each with respect to oral contraceptives. Tumorigenic aspects relating to the uterus and the breast are briefly discussed.
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PMID:Tumorigenic aspects. 3 11

Relying heavily on studies of TAT regulation in cultured rat hepatoma cell lines, we have attempted in this brief review to discuss possible mechanisms for posttranscriptional regulation of glucocorticoid-sensitive enzymes and to chronicle the evidence for and against posttranscriptional mechanisms for specific enzyme induction by glucocorticoids. Initially, mechanisms were considered that would reconcile results showing sensitivity of both induction and deinduction of TAT to inhibitors of RNA synthesis with studies demonstrating first that glucocorticoids regulate the rates of specific enzyme synthesis and, then, that glucocorticoids regulate levels of enzyme-specific mRNA. Such reconciliation proved unnecessary when it was demonstrated that inhibitors of RNA synthesis such as actinomycin D were not specific for RNA synthesis, but also had effects on mRNA turnover and protein metabolism. The bulk of evidence to date establishes that glucocorticoids promote the production of enzyme-specific mRNA for the proteins whose synthesis is regulated by thses steroids. Nevertheless, there is still very little direct evidence that steroids can modulate rates of specific gene transcription. The glucocorticoid stimulation of mouse mammary tumor virus RNA production in cultured cell lines is the only example to date where such a mechanism is supported by RNA-DNA hybridization studies. Posttranscriptional actions of steroids on the turnover, processing, or extranuclear transport of specific mRNA precursors remain potential steps at which glucocorticoids might function. The rapid turnover of some glucocorticoid-regulated enzymes and their mRNAs not only ensures a rapid response to steroid addition or withdrawal, but also subjects these proteins to relatively large fluctuations upon alterations in overall protein or mRNA metabolism. Thus many of the inductions and repressions of hepatic TAT and TO by mediators other than the glucocorticoids may be attributable entirely to nonspecific mechanisms.
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PMID:Posttranscriptional regulation of glucocorticoid-regulated functions. 4 Jan 16

The basic phenomena of cell fusion and hybrid cell formation are briefly described and the potential of somatic cell hybridization in studies on the expression of differentiated cellular functions is discussed. The technique of cell hybridization has been applied to two types of cellular responses to glucocorticoids. The induction of specific proteins has been investigated in hybrids of inducible cells with uninducible cells. Most studies dealt with the liver-specific enzyme tyrosine aminotransferase, whose inducibility was extinguished in the majority of the hybrids between hepatoma and nonliver cells. However, upon chromosome segregation, inducibility reappeared in some of these hybrid cells. The current ideas about cellular control of inducibility are discussed. The other major glucocorticoid-responsive system investigated in cell hybridization studies consists of lymphoid cells which are killed when exposed to the steroid. Such sensitive cells were hybridized with several types of glucocorticoid-resistant lymphoid lines, and sensitivity was found to be dominant over resistence. Hybrids between sensitive and resistant lymphoid cells, however, showed an increase in the frequency at which resistance occurred as compared to the rate observed with the wild-type parental cells. No complementation to steroid sensitivity was found in hybrids between different types of resistant cells with defects in the glucocorticoid-specific receptor system.
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PMID:Somatic cell fusion in the study of glucocorticoid action. 4 Jan 17

HTC cells, an established line of rat hepatoma cells in tissue culture, provide a useful experimental model system for studying the interaction of glucocorticoids and insulin in the regulation of protein metabolism. The actions of insulin and glucocorticoids on amino acid transport and protein degradation are antagonistic in this cell line. In contrast, the actions of these two hormones are additive with regard to the induction of tyrosine aminotransferase. The addition of insulin to HTC cells previously incubated with dexamethasone causes a rapid further doubling in the cellular concentration of this enzyme. The properties of the induction by insulin differ in several respects from the induction by glucocorticoids. The former occurs immediately, without the characteristic lag observed during induction by steroids. Insulin induction of transaminase does not require concomitant RNA synthesis, and does not cause the accumulation of specific mRNA for this enzyme as do glucocorticoids. Using specific immunoprecipitation techniques, we have demonstrated that insulin stimulates a nonselective increase in the rate of total protein synthesis in HTC cells, and a selective decrease in the rate of degradation of tyrosine aminotransferase relative to total protein. Thus the induction of transaminase by insulin involves two distinct actions of the hormone, affecting both synthesis and degradation of protein.
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PMID:Syneristic and antagonistic effects of glucocorticoids on insulin action. 4 Jan 18

1. Reuber H 35 hepatoma cell cultures were syncrhonized by serum depletion of the growth medium for 72 hr, which results in arrest of the cells in the G0 or G1 phase of the cell cycle. 2. Induction of tyrosine aminotransferase by dexamethasone was studied. Induction along the cell cycle varies with respect to the sensitivity of the cell towards low hormone concentration and the maximum effect elicited by the hormone. 3. Scatchard analyses of receptor- [3H]triamcinolone binding was performed in cell extracts prepared from cells at various times of G1 and S. Variations were observed in the concentration of glucocorticoid receptor as well as in the affinity of the receptor for the hormone. 4. During the latter part of the cell cycle, variations in the concentrations of the receptor could not explain the variation in enzyme induction, since the maximum rate of induction decreased while an increase in receptor activity still occurred.
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PMID:Variations in some molecular events during the early phases of the reuber H 35 hepatoma cell cycle. I. Glucocorticoid induction of tyrosine aminotransferase. 4 Jun 18

The organizational pattern of hepatocytes in hyperplastic nodules, probable precursors of hepatocellular carcinoma, was examined sequentially at different stages in the carcinogenic process, and compared with the patterns in hepatocellular carcinomas, in developing liver and in regnerating liver. Scanning as well as transmission electron microscopy, and histochemistry with light microscopy were used. The hepatocytes in the hyperplastic lesions were arranged in plates 2 or more cells thick and glands, in contrast to the one-cell-thick plates of hepatocytes in normal mature liver, and showed unusualy separation from eachother, with irregularly dilated bile canaliculi. The organizational pattern found in the hyperplastic lesions shared properties with developing liver in the perinatal period, regenerating liver following the peak of cell division, and some hepatocellular carcinomas. Unlike the normal, in which there is a highly predictable time scale for change, an apparent delay or interruption of maturation may be of importance in lesions that persist and ultimately evolve into hepatocullular carcinoma.
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PMID:Sequential analysis of hepatic carcinogenesis: the comparative architecture of preneoplastic, malignant, prenatal, postnatal and regenerating liver. 4 64

Activity of 5'-nucleotidase was significantly lower in plasmatic membranes of highly malignant hepatoma 22 as compared with the activity found in normal liver tissue. The optimal activity of the enzyme from hepatoma 22 was found at pH 8.5 with AMP as a substrate. Decrease of pH value from 8.5 to 7.4 did not affect the enzymatic activity in homogenates and plasmatic membranes in the normal liver tissue. In all the experiments activity of 5'-nucleotidase was lower towards CMP as compared with AMP. The additive effect of the both substrates was observed only in experiments with hepatoma 22.
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PMID:[Comparison of the activity and properties of 5'-nucleotidase in the homogenates and plasma membranes of the normal liver, hepatomas and of the liver in mice with inoculated hepatomas of varying degrees of malignancy]. 4 19

The Stilbestrol treatment of the female rats with the Morris hepatoma 5123 D resulted in decrease of the gamma-glutamyl-transpeptidase (GGTP) activity in serum and in hepatoma, but only during the treatment. Given to the male rats under the same conditions, Stilbestrol had no influence on the GGTP activity. Castration of males was the cause of the GGTP activity decay in hepatoma and in serum, but it was not the case with females. Sustanon diminished the GGTP activity in serum of the female rats with hepatoma.
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PMID:Influence of sex hormones on gamma-glutamyltranspeptidase activity in rats serum with Morris hepatoma 5123 D. 4 20

We have produced somatic cell hybrids between totipotent mouse teratocarcinoma cells and rat hepatoma cells. These hybrids were tested for the expression of liver specific functions expressed in the hepatoma cell parent and for their ability to differentiate when injected into nude mice. The results of this study indicate that hybrid cell clones do not resemble either of the parental cells, since they do not produce albumin and tyrosine aminotransferase that are expressed in the rat hepatoma parent, and are incapable of forming either teratocarcinomas or hepatomas when injected in experimental animals.
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PMID:Somatic cell hybrids between totipotent mouse teratocarcinoma and rat hepatoma cells. 4 96

The effect of protein deficiency on the hepatotoxicity and carcinogenicity of sterigmatocystin was studied in rats. Sterigmatocystin, 500 ppm/day, fed in a regular diet induced marked toxic effects and there was a high incidence of hepatocellular carcinoma and hyperplastic nodules. The same dosage fed in a protein-deficient diet produced toxic signs followed by a high incidence of death within 27 weeks. Surviving animals showed dysplastic liver cell changes but no tumors were noted. The incidence of hepatocellular carcinoma was 87% in rats receiving 15 ppm of the substance per day for 200 days in a protein-deficient diet. Sequential histologic and histochemical studies revealed that hyperplastic and preneoplastic liver lesions appeared at 28--32 weeks after inseption of the sterigmatocystin-supplemented diet. No cirrhotic changes and only transient fibrosis were noted. The morphogenesis of the sterigmatocystin-induced lesions was compared with that of aflatoxin B1-induced lesions.
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PMID:Sequential hepatic changes during sterigmatocystin-induced carcinogenesis in the rat. 4 22


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