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)

Vitamin A level and the cytosol-binding proteins specific for vitamin A ere studied in human tumor and its surrounding tissue. The tissues examined were 10 hepatocellular carcinomas which were surgically removed, 4 other malignant tumors (2 metastatic liver cancer and one each of gastric cancer and glioma), and 3 human fetal livers. Compared with surrounding tissues, considerable decrease of vitamin A content was observed in the hepatocellular carcinoma suggesting local deficient state of the vitamin. In addition to cellular retinol-binding protein (CRBP) and retinoic acid-binding protein (CRABP), a new molecular species having affinity for both retinol and retinoic acid was detected in the cytosols obtained from hepatocellular carcinoma as well as glioma by means of gel filtration on Sephadex G-75. With regard to ligand specificity, the protein was found to be similar to cellular retinol-binding protein, F-type or CRBP(F) which was originally recognized in the fish eye cytosol. Since the protein was also demonstrated in human fetal liver, CRBP(F) is considered to be an oncofetal protein in nature. The present study further revealed that CRBP(F) was detected in 80% of hepatocellular carcinoma (whereas plasma alpha-fetoprotein was significantly elevated only in 50%), and hepatocellular carcinoma contained CRBP(F) in a larger amount than CRABP.
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PMID:Demonstration of a novel cellular retinol-binding protein, F-type, in hepatocellular carcinoma. 8 58

1. A protein which binds retinol in vitro with high affinity and specificity was detected by sucrose gradient centrifugation or by gel filtration after preincubating rat tissue cytosols with all-trans-[3H]retinol. This protein sediments in the 2 S region of sucrose gradients. Molecular size determination by gel filtration indicates a molecular weight of 16 000. 2. Competition studies revealed that only all-trans-retinol, not retinal or retinoic acid, competes for binding. The binding of radioactive retinol is reversible. 3. This protein was detected in cytosols of rat liver, lung, spleen, brain, testis, ovaries, uterus and intestinal mucosa whereas heart or gastrocnemius muscle seem to lack this protein. 4. The cellular retinol binding protein was found in fetuses as early as day 12 of the gestation period and possessed the same specificity for the ligand as the one in adult tissues. 5. This binding component was not detected in cytosols prepared from Novikoff hepatoma, ascites hepatoma AS-30D, mouse Ehrlich ascites tumor and mouse pituitary tumor cell line AtT 20. 6. The cellular retinol binding protein seems to be different from that described to be present in the serum as suggested by difference in size and by the inability of the antisera against the serum retinol binding protein to remove the cellular binding protein from the cytosol preparations.
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PMID:Cellular retinol-binding protein. 81 Jan 77

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

The aim of this study was to investigate if the association of both hyperthermic and Retinol treatment of HTC hepatoma cells could be useful in antitumor therapy. Treatment with 5 microM Retinol was carried out before or after hyperthermia (42 degrees C or 44 degrees C, one hour; in the latter case it was performed in cells already thermo-selected. We took into consideration two parameters, i.e. the number of the collected vital cells (evaluated by the trypan blue-exclusion test) and the clonal efficiency of these cells (calculated as number of colonies obtained from 250 cells cultured for 5 days). Thermal treatment alone caused a decrease of the number of the collected vital cells and of their clonal efficiency only in the cell cultures incubated at 44 degrees C. Instead the control thermo-selected cells, both at 42 degrees C and at 44 degrees C, showed both decreased clonal efficiency and yield of the vital cells. Compared with the control cultures treated with 0.1% Ethanol, used as vitamin A solvent, only cell cultures treated with Retinol before hyperthermia showed a decreased number of collected viable cells, nevertheless their clonal efficiency was unchanged.
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PMID:[Action of retinol on viable cell recovery and clonogenic potential of HTC cells after in vitro hyperthermia]. 130 25

Since cell adhesiveness is very important in the metastatic process and because both hyperthermia and treatment with Retinol can modify the fluidity of the lipid components of the plasma membrane (and therefore its receptor distribution), we investigated if a hyperthermic treatment (at 42 degrees C or 44 degrees C, for one hour) of HTC hepatoma cells, preceded or followed by treatment with 5 microM Retinol, could alter cell adhesiveness to Laminin or to Fibronectin-coated substrata. Hepatoma cells, after such treatments, were collected and processed by Auerbach's method. In the control cells thermal treatment alone caused a decrease of adhesiveness to Laminin but no change in that to Fibronectin. When treatment with Retinol was carried out before hyperthermia, the cells showed an increased adhesiveness to Laminin and a decreased adhesiveness to Fibronectin. Instead, when treatment with Retinol was performed in cells previously thermo-selected, a decrease of adhesiveness to both tested ligands was observed.
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PMID:[Effect of hyperthermia and retinol treatment in vitro on HTC cell adhesiveness to laminin and fibronectin]. 130 26

The influence of extracellular fatty acids on the uptake and esterification of [3H]retinol bound to human retinol-binding protein (RBP), to RBP-transthyretin (TTR), or in dispersed form by the human hepatoma, HepG2, and human mammary epithelial carcinoma, MCF-7, cell lines was studied. The esterification of [3H]retinol was significantly increased in cells incubated with myristic, palmitic, stearic oleic, or linoleic acid-albumin complexes and was observed for all forms of [3H]retinol. Enhancement of [3H]retinol uptake was also observed in cells incubated with these fatty acids, but this increase was relatively small for the dispersed form as compared to that observed for [3H]retinol bound to RBP or RBP-TTR. Comparing equal concentrations of the [3H]retinol donors, cell uptake and esterification was greatest from the dispersed form and least from that bound to RBP-TTR. After preincubation of cells with oleate, uptake and esterification of [3H]retinol was increased but not to the extent observed when oleate and [3H]retinol donor were co-incubated. Incubation of cells with oleate resulted in rapid and correlated increases in the rates of [3H]retinol uptake and esterification which persisted until the steady state for [3H]retinol uptake was achieved. Beyond this time, net esterification of [3H]retinol continued in the presence of oleate. This kinetic pattern was observed for all [3H]retinol donors. These effects on [3H]retinol uptake and esterification were dose-dependent as the oleate to albumin ratio was varied from 0.5 to 3.0 and were observed across a physiological concentration range of RBP-3H-retinol. The data indicate that: 1) the fatty acid status of cells is a determinant of retinol uptake and esterification; and 2) the form of retinol presentation to cells is not qualitatively important for these processes.
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PMID:Regulation of retinol uptake and esterification in MCF-7 and HepG2 cells by exogenous fatty acids. 164 43

Transthyretin (TTR) is a circulatory protein which plays an important role in the transport of both thyroid hormone and retinol. Hep G2 cells, a human hepatoma-derived cell line, have been used extensively in studies of protein secretion by liver cells. The original description of this cell line indicated that this line, unlike primary hepatocytes, does not secrete TTR. We now report studies which reexamine the ability of Hep G2 cells to synthesize and secrete TTR. For this purpose, total RNA was isolated from Hep G2 cells grown on both uncoated and collagen-coated plastic plates and was examined for TTR expression by Northern blot analysis. TTR mRNA was found to be present in nearly equal amounts in Hep G2 cells cultured in either condition. When Hep G2 cells were cultured in [35S]methionine-containing medium, the cells were found both to synthesize and to secrete immunoprecipitable [35S]TTR. Hep G2 cells were found, by sensitive and specific radioimmunoassay, to contain 142 +/- 91 ng TTR/10(6) cells and to secrete TTR into the medium at a nearly constant rate for at least 24 h after medium change. Our data demonstrate that Hep G2 cells do synthesize and secrete TTR and suggest that this cell line might be useful for studies of the secretion of TTR.
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PMID:Studies on the synthesis and secretion of transthyretin by the human hepatoma cell line Hep G2. 165 60

To examine the influence of retinol acetate (retinol, known as an inhibitor of tumor promotion) on 3'-methyl-4-dimethyl-aminoazobenzene (3'MeDAB)-induced hepatocarcinogenesis, rats were fed with a diet containing 0.06% 3'MeDAB for 4 or 7 weeks and then with a normal diet for 21 or 18 weeks. Rats were given retinol (0, 6.25, 12.5 and 25.0 mg/rat, dissolved in DMSO) i.p. every 5 days from the 10th week to the 20th week. As a control, rats were fed a basal diet and given retinol at the same doses as mentioned above. At the 25th week, the incidence of hepatoma (hepatocellular carcinoma and cholangiocarcinoma) of each group was checked. In rats fed diet containing 3'MeDAB for 7 weeks, significant increases in the incidence of hepatoma were seen in retinol-treated groups at various doses. In rats fed 3'MeDAB diet for 4 weeks, all three doses also moderately, though not significantly, increased the incidence of hepatoma. No liver tumor was found in rats fed normal diet followed by treatment with retinol at any dose. Except for slight but detectable elevation of cellular retinoic acid binding protein levels in tumor tissues obtained from rats treated with retinol, no obvious differences in cellular retinol binding protein and gamma-glutamyl transpeptidase in the tumor tissues were observed between retinol-treated and untreated rats. Phytohemagglutinin-induced lymphocyte blastogenesis of the tumor-bearing rats with or without retinol treatment showed approximately 50% inhibition compared with that of rats fed normal diet without retinol treatment. These results indicated that the administration of retinol in the early stages of hepatocarcinogenesis enhanced the tumor induction, possibly due to the fixation of malignant transformation of the cells.
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PMID:The facilitated effect of retinol on rat hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene. 172 Oct 9

Insulin is widely used as a growth factor in hepatocyte culture but its effect on the production of acute-phase proteins has not been studied. By measuring four positive (fibrinogen, alpha 1-antitrypsin, alpha 1-acid glycoprotein, and alpha 1-antichymotrypsin) and four negative (albumin, prealbumin, transferrin, and retinol binding protein) acute-phase proteins produced by the Hep G2 hepatoma cell line, we have shown that insulin is an important modulator of acute-phase protein production. Our data show that insulin is able to inhibit the synthesis of prealbumin, transferrin, and fibrinogen. The results also show a complex interaction between insulin, interleukin 6, and glucocorticoids because insulin is able to inhibit the dexamethasone induction of alpha 1-antichymotrypsin, and in the presence of interleukin 6, dexamethasone is able to regulate the production of fibrinogen and prealbumin. The regulatory role of insulin in fibrinogen production was confirmed by pulse chase labeling followed by immunoprecipitation and fluorography.
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PMID:Insulin modulation of acute-phase protein production in a human hepatoma cell line. 172 87

Retinoic acid regulation of one member of the human class I alcohol dehydrogenase (ADH) gene family was demonstrated, suggesting that the retinol dehydrogenase function of ADH may play a regulatory role in the biosynthetic pathway for retinoic acid. Promoter activity of human ADH3, but not ADH1 or ADH2, was shown to be activated by retinoic acid in transient transfection assays of Hep3B human hepatoma cells. Deletion mapping experiments identified a region in the ADH3 promoter located between -328 and -272 bp which confers retinoic acid activation. This region was also demonstrated to confer retinoic acid responsiveness on the ADH1 and ADH2 genes in heterologous promoter fusions. Within a 34-bp stretch, the ADH3 retinoic acid response element (RARE) contains two TGACC motifs and one TGAAC motif, both of which exist in RAREs controlling other genes. A block mutation of the TGACC sequence located at -289 to -285 bp eliminated the retinoic acid response. As assayed by gel shift DNA binding studies, the RARE region (-328 to -272 bp) of ADH3 bound the human retinoic acid receptor beta (RAR beta) and was competed for by DNA containing a RARE present in the gene encoding RAR beta. Since ADH catalyzes the conversion of retinol to retinal, which can be further converted to retinoic acid by aldehyde dehydrogenase, these results suggest that retinoic acid activation of ADH3 constitutes a positive feedback loop regulating retinoic acid synthesis.
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PMID:Retinoic acid response element in the human alcohol dehydrogenase gene ADH3: implications for regulation of retinoic acid synthesis. 199 13


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