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)

A comparative study was undertaken to characterize the linkages of L-fucose in N-glycans of plasma membrane glycoproteins from Morris hepatoma 7777, host liver and kidney cortex, as well as from rat serum. After in-vivo radiolabelling of rats with L-[6-3H]fucose, the asparagine-linked carbohydrate chains were released from delipidated plasma membrane glycoproteins, as well as from serum glycoproteins, by enzymic digestion with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase from Flavobacterium meningosepticum. They were then converted to their corresponding oligosaccharide alditols by reduction with sodium borohydride. Two specific alpha-L-fucosidases from almond emulsin and from Aspergillus niger, combined with affinity HPLC on immobilized Aleuria aurantia lectin were used to study the linkage of L-fucose in the oligosaccharide chains. Fucose alpha 1-2 linked to galactose, was present only in the plasma membrane of hepatoma 7777 (18% of total L-[3H]fucose in N-glycans), but was not expressed in host liver, kidney cortex and serum. None of the investigated sources contained an appreciable amount of fucose alpha 1-3/4 linked to N-acetyl-D-glucosamine. All the radioactively labelled oligosaccharides from host liver, kidney cortex and serum, but only 82% of these oligosaccharides from hepatoma, contained alpha-fucosyl residues linked at the C6 position of the proximal N-acetyl-D-glucosamine.
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PMID:Occurrence of alpha 1-2-fucosylation in membrane glycoproteins of Morris hepatoma 7777 but not in liver. Aberrant type of fucosylation in a malignant tissue. 139 74

We have studied the effect of insulin stimulation on phosphotyrosine phosphatase (PTPase) activity in the well-differentiated rat hepatoma cell line Fao. PTPase activity was measured using a 32P-labeled peptide corresponding to the major site of insulin receptor autophosphorylation. Of the PTPase activity in Fao cells, 14% was in the cytosolic fraction, whereas 86% was in the particulate fraction; this latter fraction also had a 4-fold higher specific activity. Purification of the particulate fraction by lectin chromatography resulted in a 50% increase in specific activity, although this glycoprotein-rich fraction contained only 1.5% of the total activity. Both the cytosolic and particulate PTPase fractions were active toward the tyrosyl-phosphorylated insulin receptor in vitro. The activity of the particulate fraction but not the cytosolic fraction was inhibited by addition of a micromolar concentration of a phosphorylated peptide corresponding to residues 1142-1153 of the human insulin receptor sequence. By contrast, addition of the nonphosphorylated peptide even at millimolar concentration was without effect. Both PTPase fractions were inhibited by Zn+ at similar concentrations, whereas the cytosolic PTPase activity was 10-fold more sensitive to vanadate inhibition. Treatment of cells with 100 nM insulin increased PTPase activity in the particulate fraction by 40% and decreased activity in the cytosolic fraction by 35%. These effects occurred within 15 min and were half-maximal at 3-4 nM insulin. When assessed as total activity, the magnitude of the changes in PTPase activity in the particulate and cytosolic fractions could not be explained on the basis of a translocation of PTPases between the two pools.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin differentially regulates protein phosphotyrosine phosphatase activity in rat hepatoma cells. 142 Jan 53

Human transferrin receptor was isolated from placenta and from the hepatocarcinoma cell line Hep G2. Asparagine-linked oligosaccharides were released by treatment of tryptic glycopeptides with endo-beta-N-acetylglucosaminidase H or peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Oligosaccharide alditols were fractionated by anion-exchange high-performance liquid chromatography and by high-pH anion-exchange chromatography. Glycans from placental transferrin receptor were further characterized, after desialylation, by methylation analysis and, in part, by liquid secondary-ion mass spectrometry. Sialylation of placental transferrin receptor was examined by lectin affinity blotting with Sambucus nigra agglutinin and Maackia amurensis agglutinin. In order to trace possible inter-individual differences in N-glycosylation of the receptor, two preparations of placental transferrin receptor purified from two donors were compared. The results demonstrate that human transferrin receptor from placenta predominantly carries diantennary and triantennary N-acetyllactosaminic glycans as well as hybrid-type species, the galactose residues of which being almost completely substituted with (alpha 2-3)-linked sialic acid residues. Distinct differences were noted in the glycosylation pattern of the receptor from different individuals. Transferrin receptor from donor A carried predominantly diantennary and triantennary complex-type glycans, in part fucosylated at the innermost N-acetylglucosamine residue, in addition to small amounts of bisected and of incomplete diantennary species. Placental transferrin receptor from donor B predominantly carried triantennary N-acetyllactosaminic glycans without fucose and hybrid-type oligosaccharides with four or five mannose residues. Distinct from placental transferrin receptor, the receptor from Hep G2 cells contained larger amounts of oligomannosidic glycans with six to nine mannose residues and tetrasialylated complex-type oligosaccharides apart from mono-, di- and trisialylated species.
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PMID:Structure of the N-linked oligosaccharides of the human transferrin receptor. 155 86

The relationship between cell differentiation/tumorisation and plasma membrane glycoproteins was approached using peanut agglutinin (PNA) a lectin specific for the Gal-beta(1,3)GalNAc sequence and a homologous cell system consisted of normal rat hepatocytes (HyC) and a poorly differentiated hepatoma (ZHC). This work is focused on the molecular nature of PNA receptors. PNA bound strongly to ZHC, but bound very weakly, if at all to hepatocytes. After sialidase treatment this binding was slightly enhanced in ZHC and HyC. The total number of binding sites on ZHC was 9.6 x 10(6)/cell and 1.2 x 10(7)/cell before and after sialidase treatment respectively. In contrast, this number could not be calculated on HyC, even after sialidase treatment. The PNA receptors were isolated and identified from ZHC using affinity chromatography on immobilized PNA and lectin overlay. Two bands were revealed after SDS-PAGE of PNA receptors: a major one with a relative molecular mass of 160 kDa and a minor one of 110 kDa. The latter disappeared after sialidase treatment of ZHC suggesting the possibility that these two bands could be less and more sialylated forms of the PNA receptors, respectively. In contrast no PNA receptors could be detected on HyC. These PNA receptors could be considered O-linked glycoproteins containing the Gal-beta(1,3)GalNAc disaccharide because: i) PNA carbohydrate specificity toward this disaccharide found in this glycoprotein type; ii) their carbohydrate composition with Gal and GalNAc but not man residues; iii) their sensitivity to alkaline treatment; and iv) strong inhibition of PNA binding to ZHC with the Gal-beta(1,3)GalNAc structure. The absence of PNA receptors on HyC appeared to be related to the absence of this glycoprotein containing the disaccharide but not to the change or failure of glycosylation of the polypeptide chain of PNA receptors. The relationship between the presence of PNA receptors and differentiation/tumorisation phenomena as well as the mechanism that induced the expression of these receptors are discussed.
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PMID:Identification of peanut agglutinin receptors related to the state of tumoral liver cell differentiation. 157 2

Recurrence is an important factor affecting the survival rate of patients with hepatocellular carcinoma (HCC) after curative hepatectomy. Twelve types of lectin receptors in 33 cases of HCC tissues were determined by avidin-biotin-peroxidase complex (ABC) method. The relationship between lectin receptors, HCC grading and recurrence time after curative hepatectomy was investigated. The results showed that tumor-free period of patients after the resection of HCC was not closely related to the size of resected tumors, their pathological gradings as well as most lectin receptors. However, tumors that recurred longer than two years after curative hepatectomy had Bandeiraea simplifolia agglutinin I (BSAI) receptors obviously fewer than those recurring within two years. It is suggested that BSAI receptors in tumor tissues might be a useful index in the prognosis of HCC patients after hepatectomy.
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PMID:[The relation of lectin receptor's activity of hepatocellular carcinoma (HCC) with the recurrence after curative hepatectomy]. 165 Jun 87

The induction of proteolytic enzymes is an important mechanism in the migration of monocytes into tissues and body fluids. The monocytic cell line THP-1 was used as a model system to study the production of a particular gelatinase. Upon stimulation with phorbol myristate acetate (PMA) the cells differentiated to the adherent phenotype and produced significant amounts of a 96-kD gelatinase in a dose-dependent way. The secretion rate was maximal between 12 and 24 h after induction. Study of gelatinase mRNA steady state levels showed that the synthesis of THP-1 gelatinase is regulated by PMA at transcriptional or posttranscriptional levels. Stimulation of signal transduction pathways with other substances, including calcium ionophore A 23187, dibutyryl cyclic AMP, and dexamethasone, were ineffective in inducing gelatinase mRNA or enzyme activity. However, THP-1 cells were responsive to the cytokine interleukin (IL)-1 beta, to bacterial lipopolysaccharide (LPS), and the lectin concanavalin A (Con A), the kinetics of gelatinase induction being similar to those of induction by PMA. The THP-1 cells did not synthesize and/or secrete detectable levels of IL-6 after stimulation with PMA, Con A, LPS, or IL-1 beta. The 96-kD monocytic THP-1 gelatinase was shown to be a neutral metalloproteinase that cross-reacted with hepatoma-derived and neutrophil gelatinases in immunoprecipitation experiments. The active enzyme produced by THP-1 cells consistently showed, however, a molecular mass different from that of normal granulocyte-, monocyte-, and tumor cell-derived gelatinases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The cytokine-protease connection: identification of a 96-kD THP-1 gelatinase and regulation by interleukin-1 and cytokine inducers. 165 55

Liver biopsy specimens with or without liver diseases were examined immunohistochemically to determine the distribution of endothelial cell markers, factor VIII-related antigen (FVIII-RAg). Ulex europaeus agglutinin I (UEA-I) lectin and PAL-E. We also investigated the localization of laminin, a component of the basement membrane. In normal livers, FVIII-RAg, UEA-I and laminin were negative in sinusoidal endothelial cells, but positive in blood vascular endothelia of the portal area. The antigen detected by PAL-E was distributed in venous endothelial cells. PAL-E did not label endothelial cells of the artery. In the lobule, immunoreactivity with PAL-E was weakly detected only in some sinusoids of the periportal area. In chronic active hepatitis and liver cirrhosis, FVIII-RAg and UEA-I stained endothelial cells of neovasculatures in the enlarged portal areas of the fibrous septum surrounding pseudolobules. Some sinusoidal endothelial cells in cirrhotic livers were reactive to UEA-I and FVIII-RAg, whereas PAL-E-positive cells were found rarely in the pseudolobules. In carcinomatous sinusoidal endothelial cells, FVIII-RAg, UEA-I and PAL-E were strongly stained. Laminin underlay these carcinomatous sinusoids. These suggest capillarization of sinusoids in hepatocellular carcinoma. The histochemical approach using endothelial cell markers could be a practical tool in the diagnosis of hepatocellular carcinoma.
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PMID:Histochemical properties of vascular and sinusoidal endothelial cells in liver diseases. 165 46

More than 10(11) killer cells are needed for adoptive immunotherapy, but it is difficult to obtain so many from patients. Peripheral blood lymphocytes (PBL) treated with lectin and then with recombinant interleukin-2 (rIL-2) give many lectin-induced lymphokine-activated killer (LILAK) cells, studied here for proliferation, cytotoxicity, IL-2 receptors (IL-2R) and subsets. PBL obtained from hepatoma patients or healthy adults were incubated with phytohaemagglutinin (PHA) or concanavalin A (ConA) for 3 days and with rIL-2 for 4 days. Then the medium was replaced with fresh medium containing rIL-2 every 3 or 4 days, with the volume increased as cells proliferated. Cytotoxicity was expressed as the percentage lysis of target cells by 4 h 51Cr release. LILAK cells from healthy adults increased 120-fold in 2 weeks when incubated with ConA; the lymphokine-activated killer (LAK) cells increased 7-fold. The percentage of IL-2R+ cells increased more with ConA than with rIL-2 alone. ConA induced more suppressor T cells than PHA. LILAK cells obtained from patients by PHA treatment increased 180-fold in 2 weeks. Their cytotoxicity to Daudi cells was 1% before culture and 91% in 2 weeks; that of LAK cells was 60%. LILAK cells were cytotoxic to the tumour target cells, but not to allogeneic PBL. Adoptive immunotherapy may become more practical if many LILAK cells can be obtained at once by large-scale culture, such as by a hollow-fibre system.
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PMID:Proliferation and cytotoxicity of lectin-induced lymphokine-activated killer (LILAK) cells. 165 42

A cDNA clone encoding a human fibroblast growth factor (FGF) receptor was isolated from a hepatoma cell line cDNA library. The cDNA encodes a three immunoglobulinlike-domain FGF receptor that is similar to a human placental FGF receptor cDNA but lacks two amino acids. The variation observed at these two amino acids, also seen in the two immunoglobulinlike-domain FGF-receptors, can be explained by an alternate splicing mechanism. We have used a baculovirus expression system to produce high levels of a soluble, extracellular domain form of the FGF receptor (EC-FGF receptor). Spodoptera frugiperda (Sf9) insect cells infected with recombinant EC-FGF receptor viruses synthesized and secreted an EC-FGF receptor of apparent Mr = 58,000. The EC-FGF receptor purified from conditioned media of infected Sf9 cells by lentil lectin affinity chromatography was shown to bind basic FGF with high affinity (Kd = 1-5 nM), to inhibit the binding of radioiodinated basic FGF to its high affinity receptor and to inhibit endothelial cell proliferation. Furthermore, binding of basic FGF to the EC-FGF receptor was shown to be significantly enhanced by heparin. The availability of biologically active FGF receptors will allow an analysis of their interaction with members of the FGF family of proteins and viruses of the herpes family that have been shown to use the FGF receptor system for cell entry.
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PMID:Molecular cloning of a human basic fibroblast growth factor receptor cDNA and expression of a biologically active extracellular domain in a baculovirus system. 166 73

Increased serum concentration of alpha-fetoprotein (AFP) can be found in benign and malignant liver diseases, in yolk sac tumors, and in several nonhepatic neoplasms at advanced stage. The frequency and level of elevated serum AFP are highest in hepatocellular carcinoma (HCC) and yolk sac tumors. Most levels of serum AFP in HCC are greater than 500 ng per mL, whereas the serum AFP in most of the benign liver diseases is only moderately elevated and is transient in nature. Determination of lectin reactivity of serum AFP is helpful for the differentiation of HCC from other diseases associated with elevated serum AFP. Determination of Len culinaris agglutinin (LCA) reactivity of serum AFP is useful for the differentiation of HCC from benign liver diseases, and for early detection of hepatoma. Determination of concanavalin A (Con A) nonreactive AFP variant is useful for the differentiation of HCC from yolk sac tumors and may also allow for the differentiation of HCC from nonhepatic neoplasms. However, reaction with several lectins may be required if differentiation among various nonhepatic neoplasms is needed.
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PMID:Serum alpha-fetoprotein and its lectin reactivity in liver diseases: a review. 169 11


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