Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cross has been performed between dedifferentiated rat hepatoma cells and the differentiated cells from which they were derived. 10 hybrid clones, containing the complete chromosome sets of both parents, show extinction of 4 liver-specific enzymes: tyrosine aminotransferase (E.C. 2.6.1.5), alanine aminotransferase (E.C. 2.6.1.2), and the liver-specific isozymes of alcohol dehydrogenase (E.C. 1.1.1.1) and aldolase (E.C. 4.1.2.13). Moreover, the 4 hybrid clones examined do not produce albumin . The only function of the differentiated parent which is not extinguished in the hybrid cells is inducibility of the aminotransferases. For 3 of the hybrid clones, extinction of 3 of the 4 enzymes is incomplete, but these clones do not differ in modal chromosome number from those which show more complete extinction of the enzymes. Subcloning of several of the hybrids revealed that the phenotype of the hybrids is very stable; 4 subclones showing reexpression of intermediate levels of the enzymes are characterized. These results show that dedifferentiation of the parental cells is not due to the simple loss of some factor required for the maintenance of expression of differentiated functions, and suggest that dedifferentiation is due to the activation of some control mechanism, whose final effect is negative, and which may be a part of the epigenotype of the embryonic hepatocyte.
 ...
PMID:Extinction of liver-specific functions in hybrids between differentiated and dedifferentiated rat hepatoma cells. 1 65

The isoenzymatic pattern of aldolase was determined by immunoprecipitation with specific anti-aldolase A, B and C sera in 21 pathological liver tissues and in the sera of normals (n equals 20), liver cirrhotics (n equals 52) and hepatoma patients (n equals 22). The increase of aldolase A in primary liver cell carcinoma is not reflected in the sera of these patients, cannot be used for diagnostic purposes and is not hepatoma-specific.
 ...
PMID:Aldolase isoenzymes in liver cirrhosis and primary liver cell cancer. 16 80

A Caucasian male developed florid dermatomyositis documented by serum enzyme elevation, electromyography, and histology of skin and muscle. Serum enzymes, including creatine phosphokinase (CPK), aldolase, glutamic oxaloacetic transaminase (SGOT), and lactic dehydrogenase (LDH), decreased initially during high dose systemic corticosteroid therapy, although profound muscle weakness persisted. Subsequent elevation of serum LDH and SGOT levels during treatment provided a clue to underlying neoplasia. Primary hepatoma with widespread metastases was found at necropsy.
 ...
PMID:Aberrant serum enzyme patterns in dermatomyositis associated with hepatoma. 18 84

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.
 ...
PMID:Location of adult and fetal aldolases A, B, and C by immunoperoxidase technique in LF fast-growing rat hepatomas. 20 71

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.
 ...
PMID:[Change in aldolase activity in the organs of mice in the process of hepatoma 22a development]. 49 46

The messenger activity for fructose 1,6-bisphosphate aldolase (EC4.1.2.13) (aldolase) A isozyme has been characterized in the polysome- or the messenger RNA-directed, protein-synthesizing system using the pH 5 fraction of rat liver or wheat germ extracts, respectively. The subunit of aldolase A synthesized in vitro was detected by immunoprecipitation with anti-aldolase A antibody raised in chickens followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The synthesis of the enzyme depended on the addition of polysomes or polyadenylate-containing RNA of rat ascites hepatoma AH 7974 cells which show a complete shift of aldolase isozyme to type A, whereas polysomes of adult rat liver were inactive. The messenger activity for aldolase A was present exclusively on free polysomes but absent on membrane-bound polysomes and in the soluble supernatant fraction of AH 7974 cells. The size of aldolase A messenger RNA determined by formamide-containing sucrose density gradient centrifugation was approximately 5.8 X 10(5) daltons corresponding to 1650 nucleotides. Taking into account the number of amino acid residues in the aldolase A subunit, approximately 400 nucleotides correspond to the noncoding region of aldolase A messenger RNA.
 ...
PMID:Characterization of messenger RNA for fructose 1,6-bisphosphate aldolase A isozyme of rat ascites hepatoma AH 7974 cells. 76 Dec 23

The pattern of gene expression in fetal hepatocytes transformed in culture with a hepatocarcinogen (FRL cells) is studied with respect to a range of markers which are either developmentally regulated and/or shown to be expressed at high levels in hepatoma cells. The relative abundance of the respective mRNAs is determined and immunocytochemistry is used to detect the respective proteins in cultured cells. When compared with its normal counterpart, FRL cells retain the expression of transferrin, alpha 1-acid glycoprotein, gamma-glutamyltranspeptidase, and tyrosine aminotransferase at near normal levels, while expression of the liver-specific isoenzymes of pyruvate kinase (L form) and aldolase (B form) is reduced. The cell lines are different in that they fail to express albumin, alpha-fetoprotein, thiostatin and alpha 2-macroglobulin, and they express high levels of M2-pyruvate kinase and aldolase A, markers often found in abundance in hepatoma cells. Therefore transformation has resulted in different effects on different genes. Furthermore, it is of interest to find that the cells coexpress both forms of the pyruvate kinase isoenzymes which does not occur in the normal developing hepatocyte. These results indicate that it is possible to use this model to study changes which accompany transformation of fetal rat hepatocytes. The resulting cell lines have a stable phenotype and retain the changes which result from transformation even after extended passaging. This facilitates comparisons between the precursor cell and the tumor cell, both of which can be maintained under controlled conditions which exist in culture.
 ...
PMID:Gene expression in clonally derived cell lines produced by in vitro transformation of rat fetal hepatocytes: isolation of cell lines which retain liver-specific markers. 170 49

The serial changes in serum hepatic enzyme activities by transcatheter arterial embolization (TAE) were analyzed in 17 patients with hepatocellular carcinoma to estimate the contribution to the value by the damage of tumor or nontumorous hepatic cells. The serum levels of relatively tumor-specific fructose 1,6-diphosphate (FDP) aldolase were elevated after TAE in the cases of both superselective and nonsuperselective TAE that were performed from the segmental and the nonsegmental hepatic artery, respectively, but we found the marked elevation of FDP aldolase in the cases of the superselective TAE. In contrast, the non-tumor-specific fructose 1-phosphate (F1P) aldolase was markedly elevated only in the cases of nonsuperselective TAE. The total amount of FDP aldolase released by TAE correlated significantly with the integrated tumor tissue volume (P less than 0.005), whereas the total amount of F1P aldolase output correlated significantly with the integrated nontumorous tissue volume (P less than 0.005) as defined by lipiodol accumulation on computerized tomography scan. The consequent changes in the total nontumorous liver volumes after TAE were also analyzed by the follow-up computerized tomography scan. The nonsuperselective TAE caused the significant total nontumorous liver atrophy when compared with the superselective TAE. The progression of the total nontumorous liver atrophy correlated significantly with F1P aldolase output by TAE (P less than 0.001) but not with FDP aldolase output. These results suggest that the outputs of FDP and F1P aldolase are useful to estimate the degree of the tumorous and nontumorous tissue damage by TAE, respectively, and F1P aldolase output can be used to predict the progression of liver atrophy caused by TAE.
 ...
PMID:Evaluation of nontumorous tissue damage by transcatheter arterial embolization for hepatocellular carcinoma. 171 51

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.
 ...
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

The cDNA clones for rat aldolase C mRNA having the nearly complete length were isolated from a rat brain cDNA library and sequenced. The nucleotide sequence of pRAC2-1, a cDNA clone having the largest cDNA insert, indicates that the cDNA is composed of a 105-base-pair 5'-noncoding sequence, a 1089-base-pair coding-sequence and a 382-base-pair 3'-noncoding sequence. The amino acid sequence of aldolase C deduced from a possible open reading frame was composed of 362 residues having a relative molecular mass of 39,164 excluding the initiating methionine, one amino acid shorter than aldolases A and B. The length of aldolase c mRNA was 1750 residues, somewhat longer than that of the aldolase A and B transcripts. The aldolase C mRNA was distributed mainly in the brain, some in ascites hepatoma and fetal liver. Comparison of the amino acid sequences of rat aldolase C with those for rat aldolase A and B [Joh et al. (1985) Gene 39, 17-24; Tsutsumi et al. (1984) J. Biol. Chem. 259, 14572-14575], which have been determined previously, shows the existence of highly conserved stretches of amino acid among the three isozymic forms throughout their sequences. The extent of the homology between aldolases A and C is 81%, while those between aldolases A and B, and B and C are 70%, respectively. The analysis of amino acid substitution among aldolases A, B and C from several species suggests that the isozyme genes diverged much earlier than animal species appeared and that the aldolase C gene has evolved from the aldolase A gene after aldolase A and B genes diverged.
 ...
PMID:The structure of brain-specific rat aldolase C mRNA and the evolution of aldolase isozyme genes. 283 Oct 50


1 2 3 4 Next >>