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)

The cell surface proteins of AH-66 hepatoma ascites cells were examined both by fluorescent labeling with cycloheptaamylose-fluorescamine complex and by radioiodination with lactoperoxidase. The labeled proteins were analyzed by measuring the distribution of fluorescence or radioactivity in polyacrylamide gels after electrophoresis. Although the degree of fluorescent labeling with cycloheptaamylose-fluorescamine complex was substantially different from that obtained by lactoperoxidase-catalyzed iodination, proteins with molecular weights of 130,000, 90,000, 86,000, 50,000--60,000, and 37,000 were strongly labeled in common by both reagents. It is suggested that at least these proteins are exposed on the surface of the plasma membranes of AH-66 cells. One of these proteins labeled strongly by both reagents is the major glycoprotein, with an apparent molecular weight of 130,000 in 10% polyacrylamide gels.
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PMID:Proteins exposed on the outer surface of the plasma membranes of AH-66 hepatoma ascites cells. 76 41

The effect of transforming growth factor beta (TGF beta) on the expression of a group of liver genes has been investigated in the hepatoma cell line Hep 3B. TGF beta induces a decrease of the basal level of apolipoprotein A-II (ApoA-II), retinol binding protein (RBP) and alpha-fetoprotein (alpha Fp). Furthermore, TGF beta efficiently antagonizes the IL-6-induction of hemopexin (Hpx) and haptoglobin (Hp) and alpha 1-acid glycoprotein (AGP). These effects of TGF beta are apparently mediated by post-transcriptional mechanism(s). These findings, together with previously reported data on the inhibitory effect of TGF beta on acute phase genes (e.g. ApoA-I and albumin), suggest a role for TGF beta in the regulation of expression of liver genes.
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PMID:Effect of TGF beta on liver genes expression. Antagonistic effect of TGF beta on IL-6-stimulated genes in Hep 3B cells. 128 May 99

Alpha-fetoprotein (AFP) is a specific glycoprotein which is synthesised in the fetal liver and released into the blood stream together with the closely related protein, albumin. It has been proposed that AFP functions as a carrier of essential fatty acids to certain developing cells and as a possible immunosuppressor. In man its synthesis is under the strict and complicated control of transcription of a single gene on chromosome 4. The concentration of AFP in fetal serum is greatest at about 13 weeks gestation and then decreases up to birth. During pregnancy AFP passes into the amniotic fluid and also across the placenta, so that the concentration of AFP in maternal serum increases during pregnancy in a characteristic way. Greater than normal increases may indicate certain pathological states in the fetus. Serum concentrations of AFP in the newborn infant decrease rapidly to reach levels typical for adults (< 10 micrograms/L) usually by the end of the first year. Raised concentrations of serum AFP appear in a large proportion of patients with primary hepatoma and in a smaller percentage of patients with other malignant diseases (tumours of the testis, ovary, bronchi, gastrointestinal tract). In addition, increases in serum AFP are found in other illnesses accompanied by damage to hepatocytes in the liver (hepatitis, cirrhosis etc.). Certain differences in the structure of the oligosaccharide portion of the molecule have been shown between AFP synthesized by benign or by malignant cells and between AFP synthesised by hepatocytes or by cells of endodermal origin. These differences have been used as an aid in the diagnosis of liver diseases where serum AFP is elevated. Since AFP is not strictly specific for a certain type of carcinoma, its determination is primarily used in medicine for monitoring the effects of therapy and surgery on the course of malignant conditions which initially showed increased levels of serum AFP.
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PMID:[Synthesis, structure and function of alpha-fetoproteins and their importance in medicine]. 128 28

A carcinogen-transformed rat hepatoma cell line (Reuber H-35) was utilized as a model system for investigation of the biochemical factors which may limit the effectiveness of chemotherapy in intrinsically resistant tumors such as hepatocellular carcinoma. Northern blotting demonstrated expression of mRNA coding for the P-170 membrane-glycoprotein associated with the multi-drug resistance phenotype, while Western blotting identified the P-170 glycoprotein in the hepatoma cell membrane. Consistent with these observations, tumor cell sensitivity to the vinca alkaloids, vincristine and vinblastine, to the anthracycline antibiotics, Adriamycin and daunorubicin, and to the demethylepipodophyllotoxin derivative, VM-26, was enhanced by continuous incubation in the presence of the calcium channel antagonist, verapamil. Verapamil produced a minimal change in cell sensitivity to the demethylepipodophyllotoxin derivative, VP-16, and to the aminoacridine, m-AMSA. Relatively high detoxification potential via the glutathione metabolic pathway was also observed in the hepatoma cell. The capacity of topoisomerase II in nuclear extracts from the hepatoma cell to mediate cleavable complex formation stimulated by VM-26, VP-16 and m-AMSA appeared to be at least comparable to, if not greater than that from drug-sensitive HL-60 cells, suggesting that drug resistance may not occur at the level of this enzyme. Consistent with findings in a number of tumor cell lines resistant to antineoplastic drugs, the antiproliferative activity of the topoisomerase II inhibitors VM-26, VP-16 and m-AMSA appeared to be dissociable from the induction of DNA strand breaks, suggesting that such lesions in DNA may fail to fully account for the antiproliferative activity of these agents in the hepatoma cell.
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PMID:Components of intrinsic drug resistance in the rat hepatoma. 131 Aug 53

We have previously shown that glucocorticoids regulate the trafficking and processing of mouse mammary tumor virus (MMTV) proteins in viral-infected M1.54 rat hepatoma cells. To examine the role of intracellular membrane integrity on MMTV protein maturation, brefeldin A (BFA) was utilized to disrupt membrane flow between the endoplasmic reticulum and Golgi. Immunoprecipitation and immunofluorescence microscopy revealed that in the presence of dexamethasone, BFA inhibited the proteolytic processing, cell surface delivery, and externalization of MMTV glycoproteins. Glycosidase digestion and inhibitors of protein glycosylation confirmed that the observed differences in apparent sizes of MMTV glycoprotein products are due to BFA-induced changes in oligosaccharide processing. BFA treatment inhibited the proteolytic processing of the MMTV phosphoprotein precursor, which normally associates with the cytoplasmic face of intracellular membranes. Similarities in salt extraction efficiency revealed that BFA did not affect the membrane affinity of the uncleaved phosphorylated precursor. In a complementary approach, proteolytic processing of the phosphorylated polyprotein did not occur in glucocorticoid-treated HTC cells transfected with a mutant MMTV provirus encoding a normal phosphorylated precursor, but which express a truncated MMTV glycoprotein missing its transmembrane domain and cytoplasmic tail. These results suggest that the MMTV glycoproteins and phosphoproteins may interact at a late step in the transport pathway in a manner required for their mutual processing in response to glucocorticoids and establishes the importance of functional interactions with intracellular membranes for maturation of the cytoplasmic MMTV phosphoproteins.
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PMID:Disruptions in intracellular membrane trafficking and structure preclude the glucocorticoid-dependent maturation of mouse mammary tumor virus proteins in rat hepatoma cells. 131 17

Interleukin-6 (IL-6) induces changes in gene expression and the N-glycosylation pattern of acute-phase proteins in hepatocytes. IL-6 exerts its action via a cell surface receptor complex consisting of an 80 kDa IL-6 binding protein (gp80) and a 130 kDa glycoprotein (gp130) involved in signal transduction. A genetically engineered gp80-derived soluble human IL-6-receptor (shIL-6-R) significantly enhanced the IL-6 effect on N-glycosylation changes (revealed by reactivity with the lectin-concanavalin A) of a1-protease inhibitor (PI) secreted by human hepatoma cells (HepG2). Stable transfection of IL-6-cDNA into HepG2 cells (HepG2-IL-6) resulting in constitutive secretion of 2 micrograms of IL-6 per 10(6) cells in 24 h led to a down-regulation of surface-bound gp80 and subsequent homologous desensitization of HepG2-IL-6 cells towards IL-6. Soluble human IL-6-R functionally substituted membrane-bound gp80 resulting in a reconstitution of responsiveness of HepG2-IL-6 cells.
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PMID:Soluble human interleukin-6-receptor modulates interleukin-6-dependent N-glycosylation of alpha 1-protease inhibitor secreted by HepG2 cells. 132 38

1. Twenty perchloric acid-soluble glycoprotein fractions (PASFs) were separated from carcinomatous and non-carcinomatous regions of the livers of 5 patients with primary hepatocellular carcinoma (HCC) and 5 patients with a complication of HCC and hepatocirrhosis (HC). 2. In autoradiography using 125I-labelled Vicia unijuga lectin (VUA) and 125I-labelled Arachis hypogaea anti-T lectin as probes, 10 PASFs from carcinomatous regions of the livers of 10 patients gave 1 Vgu glycoprotein with T activity and/or 1-4 Vgu glycoproteins, respectively, and among 10 PASFs from non-carcinomatous regions of the livers of 10 patients, 7 PASFs gave no glycoproteins, respectively. 3. These results show that a Vgu glycoprotein with T activity and Vgu glycoproteins occur in HCC and in a complication of HCC and HC as oncofetal antigens.
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PMID:Presence of a Vicia unijuga lectin-binding (Vgu) glycoprotein with Thomsen-Friedenreich (T) activity and Vgu glycoproteins in human primary hepatocellular carcinoma. 133 Jul 63

The transport and proteolytic processing of two individual gene isolates of the mouse mammary tumor virus (MMTV) glycoprotein were compared in transfected rat HTC hepatoma cells. Plasmids were constructed such that the MMTV glycoprotein genes were constitutively expressed from the promoter within the Rous Sarcoma Virus 5' Long Terminal Repeat in the absence of other MMTV proteins. An isolate of the GR strain MMTV glycoprotein was efficiently transported and processed resulting in the localization of MMTV glycoproteins at the cell surface and in the extracellular environment. Moreover, the kinetics of acquisition of endoglycosidase H resistant oligosaccharide side chains and the rate of endoproteolytic cleavage of the glycosylated polyprotein expressed in transfected cells were virtually identical to that observed in viral-infected rat hepatoma cells. In contrast, a natural variant of the C3H strain MMTV glycoprotein expressed in transfected cells was retained in an intracellular compartment by a heavy chain binding protein (BiP)-independent pathway in an endoglycosidase H sensitive and uncleaved form. This MMTV glycoprotein isolate was retained early in the exocytic pathway and displayed a half-life of approximately 45 min in transfected cells. Only a minor fraction of the expressed C3H variant glycoprotein was detected at the cell surface but was not externalized. Our results suggest that the variant C3H MMTV glycoprotein contains one or more mutations that preclude its efficient transport through the exocytic pathway.
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PMID:Differential transport and processing of variant mouse mammary tumor virus glycoproteins. 133 Nov 25

We searched for a new cell aggregation factor for hepatoma AH109A cells, and found one we called HAF in the culture filtrate of Streptomyces sp. strain No. A-6143 isolated from a soil sample. HAF was purified by salting-out with ammonium sulfate. DEAE-cellulose column chromatography, gel filtration on Sephadex G-100, and hydroxylapatite column chromatography, HAF was glycoprotein which had a molecular weight of about 73,000. HAF was stable from pH 6 to 8 at 37 degrees C and up to 40 degrees C at pH 8.0 and the aggregation activity of HAF was maximum around pH 8 at 30 degrees C. The activity was not influenced by some saccharides, but it was inhibited by EDTA and EGTA: moreover HAF activity was restored by the addition of calcium ions. HAF aggregated hepatoma AH136B and COS-7 cells as well as hepatoma AH109A cells, but it was inert to other cancer cells and human erythrocytes. These properties proved that HAF is completely different from other aggregation factors for cancer cells so far reported.
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PMID:HAF, hepatoma aggregation factor produced by Streptomyces sp. strain No. A-6143. 136 99

Tenascin is an oligomeric glycoprotein of the extracellular matrix synthesized during embryonic development. It is prominently expressed in a variety of tumors. The role of tenascin in liver tissue is, however, unknown. We used immunocytochemistry to define the localization of tenascin and compare this with the localization of non-collagenous proteins, such as laminin and fibronectin, in normal human liver and pathological liver from patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. In normal liver, tenascin expression was localized along the sinusoidal and vascular wall. In fibrotic liver, tenascin was also observed in the region between the hepatic parenchyma and the fibrosing portal tracts, especially in areas of piecemeal necrosis in chronic hepatitis. Immuno-EM study of liver tissue in chronic hepatitis strongly suggested the synthesis and secretion of tenascin by fat-storing cells into the space of Disse. In hepatocellular carcinoma, tenascin was expressed in both the capsule and lobular septa, but not in the sinusoidal walls of the tumors. These results led us to postulate a close relationship between the occurrence of this protein and disease processes such as fibrosis and cancer invasion.
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PMID:Tenascin expression in human chronic liver disease and in hepatocellular carcinoma. 137 63


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