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)

Proteasomes are multicatalytic proteinase complexes consisting of a set of non-identical polypeptide subunits. A cDNA for component C5 of rat proteasomes was isolated by screening a Reuber H4TG hepatoma cell cDNA library using synthetic oligodeoxynucleotide probes corresponding to partial amino acid sequences of the protein. The polypeptide deduced from the open reading frame consisted of 240 amino acid residues with a calculated molecular weight of 26,479. Computer analysis revealed little similarity of C5 to other proteins reported so far. The primary structure of C5 showed partial sequence homology to that of another component C3, but no regions of homology with the sequence of component C2. Thus C5 is concluded to be a new type of subunit of the proteasome complex.
 ...
PMID:cDNA cloning and sequencing of component C5 of proteasomes from rat hepatoma cells. 233 47

A non-histone protein with mol. wt of 48,000 differentially expressed in normal and tumour cells was identified using immunological criteria. Antibodies were raised against a component specific for Kirkman-Robbins hepatoma of mol. wt about 48,000 separated from hepatoma non-histone proteins by preparative electrophoresis in polyacrylamide gel. It was demonstrated by immunoblotting that Morris hepatoma 7777 and Ehrlich ascites cells share an antigenic non-histone protein with Kirman-Robbins hepatoma. Tumour cells when compared with normal cells, i.e. hamster and rat liver, are characterized by significant enrichment of this component. Intracellular distribution of the polypeptide with mol. wt 48,000 suggests that this component may be a structural protein the biosynthesis of which increases or the antigenic determinants of which change in tumour cells.
 ...
PMID:Identification of a nuclear antigen with molecular weight of 48,000 differentially expressed in tumour and normal cells. 235 Aug 66

Tissue Polypeptide Antigen (TPA) and alpha 1-fetoprotein (AFP) were determined in sera of 21 patients with hepatocellular carcinomas, in 20 patients with extrahepatic carcinomas and metastases of the liver, as well as in 26 patients with cirrhosis of the liver. TPA was increased (greater than 85 U/L) in all patients with malignant hepatomas, in 80% of patients with metastatic liver cancer and in 35% of patients with cirrhosis of the liver. The critical serum TPA level, above which only malignant liver tumours lay, was statistically evaluated and found to be 187 U/L. All patients with benign liver disease and half of the patients with metastatic liver disease showed TPA values lower than 187 U/L. All of the patients with hepatocellular carcinoma and half of the patients with metastatic liver cancer had TPA values greater than 187 U/L; all of our patients with cirrhosis of the liver, as well as half of the patients with metastatic liver cancer had lower TPA values. 86% out of all hepatoma patients showed increased AFP levels (greater than 9 ng/ml), whereby the AFP concentrations were in the range which is highly suggestive of hepatoma (greater than 174 ng/ml) in 67% of all patients with malignant hepatomas. Patients with metastatic liver cancer and cirrhosis of the liver had AFP levels lower than 174 ng/ml AFP. TPA is an unspecific tumour marker, which can be used together with AFP in the diagnosis of unclear defects in liver parenchyma, in supervision of cirrhosis, as well as in control assessment during chemotherapy or after tumour resection.
 ...
PMID:[Serum concentrations of tissue polypeptide antigen and alpha 1-fetoprotein in patients with primary liver cancer, liver metastasis and liver cirrhosis]. 240 89

We have studied the effect of sodium butyrate on RNA populations and on the in vitro translation pattern of RNA from Hepatoma Tissue-Cultured (HTC) cells. Since sodium butyrate inhibits cell growth we have used stationary cells as control. Molecular hybridization study of cDNA with polyadenylated RNAs shows that sodium butyrate induces the formation of additional 15% new RNA sequences, essentially in the class of abundant sequences and of sequences of intermediary abundance. This drug also decreases 5-10 times the frequency of the sequences of intermediary abundance. One- and two-dimensional polyacrylamide gel electrophoreses of the translational products of RNAs show that sodium butyrate induces or strongly increases the synthesis of 13 polypeptides and decreases the synthesis of 6 polypeptides, which is consistent with the effect of sodium butyrate on RNA populations and could result from the effect of this drug at both transcriptional and early post-transcriptional steps. Electrophoretic analysis of the in vitro translation products of RNAs from cells submitted to sodium butyrate and transferred to a normal medium for various lengths of time shows that most of the polypeptides return to a normal pattern after a certain length of time which varies according to the polypeptide.
 ...
PMID:Effect of sodium butyrate on the complexity and the translation activity of hepatoma tissue-cultured cell RNAs. 241 15

H4-II-E-C3 hepatoma cells in culture respond to lipid-depleted media and to mevinolin with increased sterol synthesis from [14C]acetate and rise of 3-hydroxy-3-methylglutaryl coenzyme A reductase levels. Mevalonate at 4 mM concentration represses sterol synthesis and the reductase, and completely abolishes the effects of mevinolin. Mevalonate has little or no effect on sterol synthesis or reductase in enucleated hepatoma cells (cytoplasts) or on reductase in cytoplasts of cultured Chinese hamster ovary (CHO) cells. The sterol-synthesizing system of hepatoma cell cytoplasts and the reductase in the cytoplasts of CHO cells were completely stable for at least 4 hr. While reductase levels and sterol synthesis from acetate followed parallel courses, the effects on sterol synthesis--both increases and decreases--exceeded those on reductase. In vitro translation of hepatoma cell poly(A)+RNAs under various culture conditions gave an immunoprecipitable polypeptide with a mass of 97,000 daltons. The poly(A)+RNA from cells exposed for 24 hr to lipid-depleted media plus mevinolin (1 microgram/ml) contained 2.8 to 3.6 times more reductase-specific mRNA than that of cells kept in full-growth medium, or cells exposed to lipid-depleted media plus mevinolin plus mevalonate. Northern blot hybridization of H4 cell poly(A)+RNAs with [32P]cDNA to the reductase of CHO cells gave two 32P-labeled bands of 4.6 and 4.2 K-bases of relative intensities 1.0, 0.61-1.1, 2.56, and 1.79 from cells kept, respectively, in full-growth medium, lipid-depleted medium plus mevinolin plus mevalonate, lipid-depleted medium plus mevinolin, and lipid-depleted medium. These values approximate the reductase levels of these cells. We conclude that mevalonate suppresses cholesterol biosynthesis in part by being a source of a product that decreases the level of reductase-specific mRNA.
 ...
PMID:Role of mevalonate in regulation of cholesterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A reductase in cultured cells and their cytoplasts. 241 35

A cDNA clone, pAH34, corresponding to a 1.5 kb mRNA present abundantly in various rat tumors was examined for its protein coding capacity. Hybridization-selected RNAs from both poly(A)+ RNAs of a rat ascites hepatoma cell line, AH60C and of normal liver produced a polypeptide of 37 kilo daltons in vitro, but at much higher levels in the AH60C than in the normal rat liver. Two dimensional electrophoresis of the translation product revealed that the pI of this protein was 7.1. Nucleotide sequence analysis of pAH34 showed that the insert of the clone consisted of 462bp and contained the 3' portion of mRNA, including poly(A) stretch with AATAAA signal sequence centered 16 nucleotides upstream, a short untranslated region and an open reading frame corresponding to possibly 67 amino acids of the C-terminal portion.
 ...
PMID:1.5 kb mRNA abundantly expressed in rat tumors encodes a 37 kilodalton protein in vitro. 241 48

Apolipoprotein A-II is the second most abundant polypeptide found in human plasma high density lipoprotein particles. The primary translation product of human apo-A-II mRNA is a prepropolypeptide. We have previously reported (Gordon, J. I., Sims, H. F., Edelstein, C., Scanu, A. M., and Strauss, A. W. (1984) J. Biol. Chem. 259, 15556-15563) that the prosegment of apo-A-II was removed following export from a human hepatoma cell line (Hep G2). This represented a novel processing compartment for prosegments terminating with paired basic residues and differed from the processing of proalbumin which occurred with high efficiency prior to export from these cells. We have now characterized the enzyme responsible for this extracellular cleavage. The proapo-A-II converting activity is blocked by the thiol protease inhibitors antipain, E-64, leupeptin, and Ala-Lys-Arg chloromethyl ketone. Incubation of 125I-iodotyrosylated Ala-Lys-Arg chloromethyl ketone with serum-free media harvested from cell cultures over a 12-h period revealed a time-dependent accumulation of a 54-kDa protease. Although small quantities of the 54-kDa protease were detected in cell lysates, the major intracellular sequences labeled by the affinity probe had masses of 31.5 and 6 kDa. The 54-kDa extracellular, as well as 31.5- and 6-kDa intracellular, species were all immunoprecipitated by monospecific anti-human liver cathepsin B IgG. Addition of this antibody to media inhibited extracellular conversion of proapo-A-II to the mature protein. Based on these observations, we conclude that a "pro" cathepsin B-like protease exported by Hep G2 cells is responsible for proapo-A-II prosegment removal. It appears that cathepsin B-like proteases exhibit a complex pattern of segregation within the secretory pathway and that larger molecular weight forms of cathepsin B-like proteases are capable of accurately processing propolypeptides.
 ...
PMID:Extracellular processing of proapolipoprotein A-II in Hep G2 cell cultures is mediated by a 54-kDa protease immunologically related to cathepsin B. 241 99

Previous studies in this laboratory suggested that in adult liver, either the gene for the tumor-type poly(A) polymerase is poorly transcribed or the mRNA for this enzyme is largely not expressed. To test these possibilities, total RNA from rat liver and Morris hepatoma 3924A RNA were isolated by using a guanidine thiocyanate method; poly(A+) RNA and poly(A-) RNA were separated by oligo(dT)-cellulose chromatography and used for translation in a rabbit reticulocyte lysate system. After in vitro translation, the products were immunoprecipitated with either purified anti-tumor poly(A) polymerase antibodies or control immunoglobulins. When the polypeptides translated from poly(A+) or poly(A-) hepatoma RNA were precipitated with immune sera, a unique [35S]methionine-labeled 35-kilodalton (kDa) protein was observed. This band was not apparent when control serum was used for the immunoprecipitation. The radiolabeled 35-kDa polypeptide was not evident when the products were incubated with highly purified tumor nuclear poly(A) polymerase prior to immunoprecipitation. Prior incubation of the translation products with bovine serum albumin instead of poly(A) polymerase had no effect on the immunoprecipitation. This 35-kDa protein was not apparent when liver poly(A+) RNA was used to direct translation. These data demonstrate that (a) the tumor enzyme is not synthesized as a precursor, (b) tumor mRNA, but not normal liver mRNA, contains detectable sequences coding for tumor-type poly(A) polymerase, and (c) poly(A) polymerase mRNA also exists as a poly(A-) population.
 ...
PMID:Cell-free synthesis of tumor-type poly(A) polymerase. 242 13

Tissue polypeptide antigen (TPA) is a polypeptide isolated from malignant cells and found in high concentration in the serum of patients with various tumors. No information is available with respect to hepatocellular carcinoma (HCC). Serum TPA concentrations were measured in 290 patients with HCC, 85 healthy controls, 33 patients with amebic hepatic abscesses, 43 with chronic hepatitis or cirrhosis, and 39 with acute hepatitis. Raised values were found in 96% of the HCC patients, but also in 61% of patients with amebic abscesses, 86% with chronic hepatic parenchymal disease, and 90% with acute hepatitis. If a cut-off level of 500 IU/L was used, this reduced the sensitivity of TPA in HCC to 46%, but still left 46% of patients with acute hepatitis with raised values. TPA is comparable in sensitivity with alpha-fetoprotein as a marker for HCC, but its lack of specificity severely limits its clinical usefulness.
 ...
PMID:The value of serum concentrations of tissue polypeptide antigen in the diagnosis of hepatocellular carcinoma. 242 21

Four monoclonal antibodies were identified by their ability to bind to 125I-labeled insulin covalently linked to a cytosolic insulin-degrading enzyme from human erythrocytes. All four antibodies were also found to remove more than 90% of the insulin-degrading activity from erythrocyte extracts. These antibodies were shown to be directed to different sites on the enzyme by mapping studies and by their various properties. Two antibodies recognized the insulin-degrading enzyme from rat liver; one inhibited the erythrocyte enzyme directly; and two recognized the enzyme after gel electrophoresis and transfer to nitrocellulose filters. By this latter procedure and immunoprecipitation from metabolically labeled cells, the enzyme from a variety of tissues was shown to be composed of a single polypeptide chain of apparent Mr 110,000. Finally, these monoclonal antibodies were microinjected into the cytoplasm of a human hepatoma cell line to assess the contribution of this enzyme to insulin degradation in the intact cell. In five separate experiments, preloading of cells with these monoclonal antibodies resulted in an inhibition of insulin degradation of 18-54% (average 39%) and increased the amount of 125I-labeled insulin associated with the cells. In contrast, microinjection of control antibody or an extraneous monoclonal antibody had no effect on insulin degradation or on the amount of insulin associated with the cells. Moreover, the monoclonal antibodies to the insulin-degrading enzyme caused no significant inhibition of degradation of another molecule, low density lipoprotein. Thus, these results support a role for this enzyme in insulin degradation in the intact cell.
 ...
PMID:Inhibition of insulin degradation by hepatoma cells after microinjection of monoclonal antibodies to a specific cytosolic protease. 242 18


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>