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)

Most of the hybrid clones derived from a cross of Chinese hamster fibroblasts (DON) with rat hepatoma cells (Faza 967) showed preferential loss of rat chromosomes. Two of the hybrid clones retained the rat chromosomes, and both showed extinction of 4 liver-specific enzymes: aldolase B, liver alcohol dehydrogenase, and the inducible enzymes tyrosine aminotransferase and alanine aminotransferase. Subcloning of 1 of these hybrids, which contained 2 sets of hepatoma chromosomes and 1 set of hamster chromosomes, permitted the isolation of some clones which reexpressed 1 or more of the liver-specific enzymes. Liver alcohol dehydrogenase was the most frequently reexpressed enzyme and aldolase B the least. Tyrosine aminotransferase inducibility was reexpressed independently of basal activity, and the enzyme produced by the reexpressing hybrid cells was precipitated by a specific antiserum. No correlation was detected between the presence or absence of the marker chromosomes (large metacentrics) of the hamster parent and the extinction and reexpression of the hepatic enzymes. The results reported confirm and extend to interspecific hybrids the observation of the stable and independent reexpression of tissue-specific enzymes.
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PMID:Expression of differentiated functions in hepatoma cell hybrids: IX extinction and reexpression of liver-specific enzymes in rat hepatoma-Chinese hamster fibroblast hybrids. 1 64

The biosynthesis of aldolase A and B subunits has been studied in rat liver during the administration of carcinogen AAF4. Transition from a predominance of aldolase B to A was observed during carcinogenesis in rat liver. Changes in isozymic pattern and FDP to F-1-P cleavage activity ratio were observed before histological alterations typical of hepatoma could be detected. Our data support the hypothesis of dedifferentiation during hepatocarcinogenesis which in an early stage results in switching on of the gene for aldolase A with simultaneous continuation of biosynthesis of aldolase B within single cells.
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PMID:Isozyme pattern of fructose diphosphate aldolase during hepatocarcinogenesis induced by 2-acetylaminofluorene in rat liver. 17 Feb 26

In acute CCL4 intoxication of rats significantly increased activities of hepatic low-Km hexokinases, glucose-6-phosphate dehydrogenase, phosphofructokinase, aldolase A and pyruvate kinase M2 with concurrently decreased activities of glucokinase, glucose-6-phosphatase, fructose-1,6-diphosphatase, aldolase B and pyruvate kinase L were observed. The resulting enzyme pattern was apparently different from that in dietary induction. Principal component analysis revealed that the degree of enzyme deviation in the injured liver was much greater than that in the regenerating liver after partial hepatectomy and was closer to that in fetal liver or hepatoma tissue.
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PMID:Undifferentiated patterns of key carbohydrate-metabolizing enzymes in injured livers. I. Acute carbon-tetrachloride intoxication of rat. 17 79

The resurgence of aldolase isozymes in cancerous tissues is a well-known but poorly understood phenomenon. This resurgence poses the problem of whether or not adult and fetal aldolase isozymes are produced by the same cells. For clarification of this question, the immunoperoxidase technique was used to locate aldolases A, B, and C in one type of fast-growing hepatoma, the LF hepatoma and, by comparison, in normal adult liver. Under optical microscopy, aldolases A and C were located in the cytoplasm of almost all of the cancerous cells. An isozyme antigenically identical with aldolase B was also demonstrated to be present in almost all of the cells, but the reaction indicating the presence of this isozyme was weaker. In normal adult liver, only aldolases A and B were demonstrated to be present in almost all the hepatocytes. Under electron microscopy in LF hepatoma, the three isozymes were found to be present mainly in the cytoplasm. These facts suggest that the three types of aldolase are very probably present in the same cells at the same time, and they provide indirect arguments leading us to think that the resurgence of fetal aldolase isozymes in cancer is not the consequence of cellular selection but is due to a disturbance at the gene control level.
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PMID:Location of adult and fetal aldolases A, B, and C by immunoperoxidase technique in LF fast-growing rat hepatomas. 20 71

Selective glucose-free media have been used to study the reexpression of liver-specific gluconeogenic enzymes in rat hepatoma X mouse lymphoblastoma somatic hybrids. The utilization for gluconeogenesis of dihydroxyacetone or oxaloacetate requires two enzymes: fructose diphosphatase as well as either triokinase for the former or phosphoenolpyruvate carboxykinase for the latter. By sequential selection with these substrates, the reexpression of the three gluconeogenic enzymes has been dissociated. The reexpression of these enzymes is correlated with the loss of mouse chromosomes. In addition, the characterization of the parental forms of aldolase B, another liver-specific enzyme, shows that reexpression corresponds to the simultaneous production of the rat and mouse enzymes. These results demonstrate the chromosomal origin of extinction and suggest that activation of mouse silent genes which accompanies reexpression can occur without loss of the parental determinations. The hypothesis that determination involves regulatory rather than structural genes is discussed.
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PMID:Expression of differentiated functions in hepatoma cell hybrids: selection in glucose-free media of segregated hybrid cells which reexpress gluconeogenic enzymes. 20 53

The aldolase activity was measured using two substrates fructose-I-phosphate (FIP) and fructose-1,6-diphosphate (FDP) in the supernatant fraction of homogenates of different mice organs (liver, muscle, brain) and hepatoma tissues during growth of hepatoma 22a. Kinetic parameters Km and Vmax were calsulated. The most essential changes in the activity of aldolase were found during the latent and terminal stares of the hepatoma development. The changes in the aldolase activity observed during development of hepatoma 22a were characterized by altered substrate specificity VFDP /VFIP activity gatio). This ratio was not changed distinctly in liver tissue; in muscles the value decreased from 50 (tumor-free control) to 15 during terminal stages; in brain, to the contrary, it was increased from 20 to 50. The values of Km, Vmax and VFDP /VFIP were similar both in the hepatoma at the eleventh day and in normal brain tissue. The specific inhibition of FDP aldolase activity by ATP was found. Substitution of aldolase B by aldolase AC apparantly ossurred in hepatoma 22a. The data obtained suggest that alteration in the parameters studied may be due to variation in the ration of isozymes.
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PMID:[Change in aldolase activity in the organs of mice in the process of hepatoma 22a development]. 49 46

Two independent dedifferentiated variants, H5 and FaoflC2, derived from the Reuber H35 hepatoma, produce trans-acting diffusible substances(s) that extinguish the expression of liver-specific proteins when hybridized with a well-differentiated cell line of the same origin (Fao and Fu5-5, respectively). H5 x Fao hybrids show total and stable extinction of four liver functions and clonal variability in the expression of three others. FaoflC2 x Fu5-5 hybrids are initially flat (like FaoflC2 cells), and die in glucose-free medium where survival requires expression of hepatic gluconeogenic enzymes, but then evolve to hepatoma-like and finally round morphology; these latter cells express all liver functions analyzed including the gluconeogenic enzymes. Two exceptional clones that remained flat long enough for complete analysis showed extinction of all hepatic functions not expressed by FaoflC2 cells. We conclude that this transitory extinction reflects the action and then loss of extinguishing factor(s) contributed by FaoflC2. When crossed with BW1-J mouse hepatoma cells. FaoflC2 causes stable extinction of mouse aldolase B. We propose that production of extinguishing factor(s) is the rule for dedifferentiated variants.
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PMID:Dedifferentiated variants of a rat hepatoma: analysis by cell hybridization. 54 20

The expression of specific and non-specific rat liver messenger RNAs has been studied during 3'-methyl-4-(dimethylamino)azobenzene (3'-MeDAB) carcinogenesis, using cDNA probes complementary to mRNAs encoding aldolase A and B, L-type pyruvate kinase, albumin, alpha-fetoprotein, transferrin and an unidentified 2.7 X 10(3)-base mRNA. mRNAs specific for undifferentiated cells, such as those encoding aldolase A and the unidentified 2.7 X 10(3)-base species were re-expressed very early, being easily detectable at the 1st week of 3'-MeDAB treatment. They reached a maximum of expression at the 4th week. Simultaneously the levels of aldolase B and L-type pyruvate kinase mRNAs dramatically decreased as compared to controls, but remained responsive to induction by a high-carbohydrate diet. Albumin and transferrin mRNA levels were only slightly modified in the course of the carcinogenic diet. At the terminal stage of hepatocarcinogenesis, i.e. in malignant hepatoma cells, expression and inducibility of aldolase B and L-type pyruvate kinase mRNAs were similar to those in normal adult rats while mRNAs specific for undifferentiated or foetal stages were also synthesized. The very early changes in gene expression for aldolases A and B, L-type pyruvate kinase and the 2.7 X 10(3)-base mRNA species could indicate that carcinogenic diet modifies gene control mechanisms long before inducing hepatoma.
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PMID:Modifications of the expression of liver-specific and non-specific messenger RNAs during azo-dye hepatocarcinogenesis. 241 Feb 70

Aldolase A, B, and C were determined in rat liver and serum by radioimmunoassay (RIA) in order to evaluate the alteration of these isozymes in the process of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), and the immunohistochemical technique was also used for the analysis of localization of aldolase isozymes. Aldolase A was increased in cancer tissues of 3'-Me-DAB induced hepatoma, whereas aldolase B was decreased in the same tissues according to both RIA and the immunohistochemical technique. During the promotion stage of hepatocarcinogenesis, the cells in hyperplastic nodules, which are known as preneoplastic lesions, were stained for aldolase A. Aldolase C was slightly increased in cancer tissues by RIA, suggesting the increase of A-C hybrid like A3C which was demonstrated by the electrophoretic method. Serum aldolase A levels were not significantly elevated in rats with liver cancer in comparison to rats with non-cancer.
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PMID:[Biochemical and immunohistochemical studies on alteration of aldolase isozymes in rat liver in the process of hepatocarcinogenesis by administration of a diet containing 3'-methyl-4-dimethylaminoazobenzene]. 251 Nov 29

Chromatin structures of the aldolase B gene locus in repressed and derepressed states were examined by DNase I digestion. Within the gene locus, several structural features were observed with respect to the sensitivity to DNase I; hypersensitive sites, relatively resistant regions, and preferential cleavage sites within the resistant regions. The hypersensitive sites and the resistant regions are tissue- or cell-specifically distributed, but are not simply related to the active or inactive state chromatin. Among these structural features, however, a DNase I-hypersensitive site located about 0.3 kilobase pairs (kb) upstream from the transcription-initiation site is characteristic only in transcriptionally active tissues or cells (liver, kidney and Morris hepatoma 5123D). In addition, analysis with nuclei of fetal liver cells indicated that this hypersensitive site is constructed prior to the transcriptional activation of the aldolase B gene during development. These results may indicate that the structural alteration in chromatin at the 0.3 kb upstream site is related to the regulation of the aldolase B gene expression.
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PMID:Tissue-specific changes in chromatin structure of the rat aldolase B locus. 283 Feb 47


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