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)

In 37 patients with Crohn's disease the 25-hydroxycholecalciferol (25-HCC) serum level, serum concentration of calcium and inorganic phosphate, and the enzyme activity of alkaline phosphatase were measured. Furthermore the activity index of Crohn's disease was determined in every patient. There was no statistically significant difference of 25-HCC serum levels in these patients compared to a healthy control group. Correspondingly most patients showed normal alkaline phosphatase enzyme activity and normal serum concentration of calcium and inorganic phosphate. No correlation between 25-HCC concentration and site of inflammation or activity index was found.
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PMID:25-hydroxycholecalciferol serum levels in patients with Crohn's disease. 90 78

Low doses of 1,25-DHCC cause a significant increase in trabecular and cortical bone mass of the mature rat skeleton by stimulated endosteal bone formation. The increased serum contents of calcium and inorganic phosphate give rise to a moderate nephrocalcinosis. An increased bone resorption occurs upon toxic dose levels causing profound nephrocalcinosis. Similar doses of 25-HCC do not affect the mature bone.
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PMID:Low doses of 1,25-dihydroxycholecalciferol increase mature bone mass in adult normal rats. 91 86

The effect on phosphate excretion of graded doses of parathyroid hormone (PTH) and the biologically active vitamin D3 metabolite, 25-hydroxycholecalciferol (25-HCC), administered singly and in combination, were studied in the nonexpanded, vitamin D-depleted thyroparathyroidectomized rat. Infusion of 1 unit of 25-HCC per hour for 6 hours induced an antiphosphaturia only when administered with 0.2 units of PTH per hour, while neither agent alone changed phosphate excretion. A dose of 2.0 units of PTH per hour did not cause phosphaturia unless given with 1 unit of 25-HCC per hour. In pharmacologic dosage (5 units per hour), PTH produced phosphaturia in the absence of the metabolite.
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PMID:Parathyroid hormone and 25-hydroxy vitamin D3: synergistic and antagonistic effects on renal phosphate transport. 116 16

The authors examined and quantified the changes observed in the phosphorus-31 magnetic resonance (MR) spectra of liver tumors after chemotherapy and chemoembolization to investigate the suitability of P-31 MR spectroscopy for follow-up. A 1.5-T unit was used before and at specific times during therapy to obtain spectra of liver tumors in 10 patients with liver metastases from colorectal carcinoma and two patients with hepatocellular carcinoma. A marked increase in inorganic phosphate and a decrease in the alpha- and beta-nucleotide phosphate portions of the spectra were observed during the first few hours after local chemotherapy or chemoembolization. Later, the phosphomonoester signals increased markedly and the phosphodiester signals decreased slightly. The effects of successful chemoembolization or local chemotherapy become apparent in the P-31 MR spectrum during the first few hours after the start of therapy. The results demonstrate that P-31 MR spectroscopy is a suitable method for follow-up. However, long-term studies are needed to determine whether it also yields prognostic information.
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PMID:Liver tumors: follow-up with P-31 MR spectroscopy after local chemotherapy and chemoembolization. 131 Nov 19

The lysosomal cysteine proteinase cathepsin B is synthesized in cultured human hepatoma HepG2 cells as an inactive 44 kDa precursor and subsequently processed to the mature single-chain enzyme with a molecular mass of 33 kDa. Intralysosomal conversion into the two-chain form results in subunits of 27 kDa, 24 kDa (heavy chain) and 5 kDa (light chain). Enzymic deglycosylation reveals that the 27 kDa polypeptide is the glycosylated variant of the carbohydrate-free 24 kDa heavy-chain form. The intracellular transport to the lysosomes is dependent upon mannose 6-phosphate-containing N-linked oligosaccharides. Receptor-mediated endocytosis of human skin-fibroblast-derived procathepsin B by HepG2 cells resulted in processed molecular forms that are not distinguishable from endogenous cathepsin B, thus favouring rather a cell-type-specific processing than structural differences due to the source of the proenzyme. The conversion step of single-chain catehpsin B into the two-chain enzyme is inhibited in vivo by the irreversible cysteine-proteinase inhibitors Z-Phe-Ala-CHN2 and, albeit weaker, Z-Phe-Phe-CHN2. Both substances have no effect on the activation of procathepsin B to the mature enzyme. The carbohydrate moiety of cathepsin B exerts no significant influence on the stability and the enzymatic activity of the enzyme.
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PMID:Proteolytic processing and glycosylation of cathepsin B. The role of the primary structure of the latent precursor and of the carbohydrate moiety for cell-type-specific molecular forms of the enzyme. 131 33

The cell surface expression of three endocytic receptors was studied in human hepatoma Hep G2 cells treated with brefeldin A (BFA). Ligand binding and cell surface iodination revealed that BFA increased the number of mannose 6-phosphate/insulin-like growth factor II receptors twofold and decreased the amount of asialoglycoprotein and transferrin receptors by 40-60%. The altered expression of receptors at the cell surface was paralleled by changes in the respective ligand uptake. The implications of this finding on our understanding of intracellular trafficking are discussed.
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PMID:Brefeldin A affects the cellular distribution of endocytic receptors differentially. 131 46

The identification of free glycoinositol phospholipids (GPIs) following biosynthetic labeling with [3H]glucosamine in cultured cells has been reported by several laboratories. We applied this procedure to two of the cell types used in these studies, H4IIE hepatoma cells and isolated hepatocytes, but were unable to detect a [3H]glucosamine-containing lipid that met any of the criteria for GPIs, including sensitivity to phosphatidylinositol-specific phospholipase C (PIPLC) or GPI-specific phospholipase D. Part of the difficulty in radiolabeling a GPI by this procedure was the rapid metabolic conversion of [3H]glucosamine to galactosamine and neutral or anionic derivatives. A PIPLC-sensitive radiolabeled lipid was detected only after 16 h of labeling. The water-soluble fragments released from this lipid by PIPLC corresponded largely to myo-inositol 1,2-cyclic phosphate and myo-inositol 1-phosphate, products expected from PIPLC cleavage of phosphatidylinositol or lyso-phosphatidylinositol. In an alternative approach that we introduce here, free GPIs in lipid extracts from rat liver plasma membranes were labeled by reductive radiomethylation. This procedure, which radiomethylates primary and secondary amines, has been shown to label a glucosamine residue adjacent to inositol in all GPIs characterized to date. The labeled extracts were fractionated by two-dimensional thin-layer chromatography, and a cluster of polar labeled lipids were assigned as GPIs based upon the following observations. 1) They were cleaved by PIPLC, 2) after hydrolysis in 6 N HCl, both radiomethylated glucosamine and a glucosamine-inositol conjugate were identified by cation exchange chromatography, and 3) hydrolysis in 4 M trifluoroacetic acid generated a fragment consistent with glucosamine-inositol-phosphate. These results illustrate new criteria for the identification of GPIs. The labeled GPIs also contained radiomethylated ethanolamine, another component found in GPI anchors of proteins and in mature lipid precursors of GPI anchors, suggesting that the liver plasma membrane GPIs retained considerable structural homology to GPI anchors.
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PMID:Identification of glycoinositol phospholipids in rat liver by reductive radiomethylation of amines but not in H4IIE hepatoma cells or isolated hepatocytes by biosynthetic labeling with glucosamine. 132 29

A 90-kDa phosphoprotein (p90) of the endoplasmic reticulum was identified by a monoclonal antibody generated against human hepatoma cells. Pulse-chase experiments with [32P]phosphate and [35S]methionine demonstrated that p90 formed both stable and transient complexes with other cellular proteins, suggesting its role as a molecular chaperone. This protein associates with heavy chains of major histocompatibility complex class I proteins, suggesting that it is the human homolog of the recently described 88-kDa protein that transiently associates with murine class I molecules in the endoplasmic reticulum. The p90 protein also associates in B lymphocytes with membrane immunoglobulin mu heavy chains and may serve as a chaperone for many membrane-bound polypeptides. A partial human p90 cDNA was cloned from a lambda gt11 expression library and identified as the human homolog of calnexin, a major canine calcium-binding protein found to be associated with the signal-sequence receptor in endoplasmic reticulum membranes.
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PMID:The major histocompatibility complex class I antigen-binding protein p88 is the product of the calnexin gene. 132 56

Glutamine synthetase and glutaminase activities in human cirrhotic liver tissues and hepatocellular carcinomas were determined for comparison with normal liver tissues. In hepatocellular carcinoma, glutamine synthetase activity was approximately one-third of that in normal liver, whereas no detectable change in the enzyme activity was observed in cirrhotic liver. Phosphate-dependent and phosphate-independent glutaminase activities were increased approximately 20-fold and 6-fold, respectively, both in the carcinoma and cirrhotic liver compared with those from normal liver, Oxypolarographic tests showed that the rate of glutamine oxidation in the tumor and cirrhotic liver mitochondria was about 5-fold higher than that in the liver mitochondria. The rate of glutamate oxidation in the liver mitochondria was comparable to that in the cirrhotic liver and tumor mitochondria. Glutamine oxidation was inhibited by prior incubation of the mitochondria with 6-diazo-5-oxo-L-norleucine, which inhibited mitochondrial glutaminase. These results indicate that the product of glutamine hydrolysis, glutamate, is catabolized in the tumor and cirrhotic liver mitochondria to supply ATP. In the liver and cirrhotic liver mitochondria, glutamate was oxidized via the routes of transamination and deamination. On the other hand, glutamate oxidation was initiated preferentially via a transamination pathway in the tumor mitochondria.
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PMID:Glutaminase and glutamine synthetase activities in human cirrhotic liver and hepatocellular carcinoma. 134 87

The propeptides of lysosomal enzymes have been implicated in membrane association and mannose 6-phosphate-independent sorting to the lysosome (Rijnboutt, S., Aerts, H., Geuze, H. J., Tager, J. M., and Strous, G. J. (1991) J. Biol. Chem. 266, 4862-4868; McIntyre, G. F., and Erickson, A. H. (1991) J. Biol. Chem. 266, 15438-15445). In this report, the function of the propeptide of procathepsin D in sorting to the lysosome was directly assessed using a cathepsin D deletion mutant lacking the propeptide, and using a chimeric cDNA encoding the cathepsin D propeptide fused to the secretory protein alpha-lactalbumin. Proteins encoded by these cDNAs were expressed in mouse Ltk- cells and in human hepatoma Hep G2 cells, and then immunoprecipitated and analyzed by SDS-polyacrylamide gel electrophoresis. The deletion mutant was glycosylated but was rapidly degraded in a chloroquine-independent fashion and did not assume an active conformation. Thus the propeptide appeared to be necessary for correct folding. The chimeric protein was glycosylated and secreted. The coincidence of complex oligosaccharide modification and secretion of the chimeric protein suggested that it was slowly released from the endoplasmic reticulum and rapidly passed through the cell to the extracellular compartment. This was confirmed by immunofluorescent localization of the proteins. The data indicated that the propeptide appeared to be necessary for folding of cathepsin D but, unlike the yeast vacuolar propeptides, was not sufficient to direct a secretory protein to the lysosome in fibroblasts or in epithelial cells.
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PMID:The role of the cathepsin D propeptide in sorting to the lysosome. 140 Apr 84


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