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 cloned line of mouse hepatoma cells (Hepa-1) responded to treatment with dexamethasone by a 30-80-fold increase in synthesis and secretion of functional haptoglobin. Under the same conditions, the production of albumin was only slightly elevated whereas that of alpha 1-fetoprotein was reduced by 50%. The hormone concentration for half-maximal stimulation of haptoglobin synthesis was between 1 and 2 X 10(-8) M. The time course of induction is characteristic for a glucocorticoid-regulated protein. Cell-free translation of RNA indicated an increase in the amount of functional haptoglobin mRNA that can account for the change in the protein production. To correlate our findings on Hepa-1 cells with those on nontransformed liver cells, we tested the hormonal response of isolated hepatocytes in tissue culture. Haptoglobin was first synthesized and secreted by hepatocytes from 17-19-d-old fetuses. But neither prenatal nor adult hepatocytes showed a dexamethasone-dependent increase in haptoglobin synthesis. However, when several independent clones of hybrid cells formed from adult mouse hepatocytes and rat hepatoma cells were treated with dexamethasone, the synthesis of mouse haptoglobin was in all cases elevated. It appears that haptoglobin expression in mouse liver cells is potentially sensitive to glucocorticoids, but this modulation is manifested only in transformed cells and their derivatives.
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PMID:Regulation of mouse haptoglobin synthesis. 619 28

Slices of Morris hepatoma 7777 or rat liver isolated from control or turpentine-injected rats were incubated for 2 h with 14C-leucine. Radioactivities incorporated into albumin, alpha-fetoprotein, fibrinogen, alpha 1-AP-globulin, haptoglobin and alpha 1-acid glycoprotein were determined after the proteins had been isolated from the incubation medium or tissue homogenate by immunoprecipitation with monospecific antisera. It was found that hepatoma synthesizes fibrinogen, alpha 1-AP-globulin and alpha 1-acid glycoprotein in the amounts comparable to rat liver, whereas formation of albumin and haptoglobin is reduced 5- to 10-fold. Local inflammation elicited by injection of turpentine to tissue donors increased formation of acute-phase protein in liver slices but had no effect on synthesis of these proteins in preparations of Morris hepatoma, although certain ultrastructural changes in the Golgi complex were observed not only in the liver but also in the tumour.
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PMID:Synthesis and secretion of some plasma proteins by tissue slices of Morris hepatoma 7777 and liver from control and turpentine-injected rats. 619 67

Human keratinocytes and activated monocytes produces factors which can stimulate the proliferation of thymocytes. The same activity has also been implicated in regulating the expression of plasma proteins in liver cells during the acute phase reaction. To assess whether factors produced by such cells can directly influence liver cells to change the production of acute phase plasma proteins, we studied in tissue culture the response pattern of hepatic cells from three species: human hepatoma cells ( HepG2 cells), and primary cultures of rat and mouse hepatocytes. Conditioned media from the squamous carcinoma COLO-16 cells, normal epidermal cells, and activated peripheral monocytes were able to stimulate the synthesis of specific acute phase plasma proteins: alpha 1-antichymotrypsin in HepG -2 cells, alpha 1-antichymotrypsin, alpha 1-acid glycoprotein, alpha 1-acute phase protein, and alpha 2-macroglobulin in rat hepatocytes, and alpha 1-acid glycoprotein, haptoglobin, and hemopexin in mouse hepatocytes. Only in rat cells, dexamethasone was found to have further enhancing effect. The increased production of plasma proteins could be explained by an elevated level of functional mRNA. Comparing thymocyte-stimulating activities with the effects on plasma protein production, we found some difference both between the conditioned media of epidermal cells and monocytes, and between the responses of the three hepatic cell systems. Furthermore, gel chromatography of conditioned media resulted in partial separation of activities regulating liver cells and thymocytes. Since there is no strict correlation between thymocyte- and hepatocyte-stimulating activities, the presence of different sets of specific factors is assumed.
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PMID:Human keratinocytes and monocytes release factors which regulate the synthesis of major acute phase plasma proteins in hepatic cells from man, rat, and mouse. 620 94

A human hepatoma cell line, HuH-7, which was established from a hepatocellular carcinoma, was found to replicate continuously in a chemically defined medium when the medium was supplemented with Na2SeO3. The cells grew better in this medium than in serum-containing medium without any adaptation period. Other established human hepatoma and hepatoblastoma cell lines, HuH-6 cl-5, PLC/PRF/5, huH-1, and huH-4, also grew in the defined medium. Although HLEC-1 cells failed to proliferate continuously with Na2SeO3 alone, they grew if a cell-free conditioned medium from HuH-7 cells was added to the medium. These cell lines, except the HLEC-1 cell line, produced the following human plasma proteins among those examined: albumin, prealbumin, alpha 1-antitrypsin, ceruloplasmin, fibrinogen, fibronectin, haptoglobin, hemopexin, beta-lipoprotein, alpha 2-macroglobulin, beta 2-microglobulin, transferrin, lipoprotein, alpha 2-macroglobulin, beta 2-microglobulin, transferrin, Complement Components 3 and 4, and alpha 1-fetoprotein. Beside plasma proteins, the media from HuH-7, HuH-6 cl-5, PLC/PRF/5, and huH-1 contained anti-carcinoembryonic antigen-reactive proteins, and those from PLC/PRF/5, huH-1, and huH-4 medium contained hepatitis B surface antigen. These proteins were detected during periods of serial cultivation over 9 months under the above culture conditions. The hepatoma cell lines grown in the fully defined synthetic medium may provide a new approach for investigating the growth and metabolism of human hepatoma cells in vitro.
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PMID:Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. 628 15

The effect of pyridoxine depletion on the expression of serum protein species in control and Morris hepatoma No. 7777-bearing rats was studied with polyacrylamide gel electrophoresis (PAGE). A group of 20 Buffalo female rats was fed ad libitum a complete diet lacking pyridoxine, whereas a similar group was fed the same diet with pyridoxine. After a 22-day feeding period, 12 animals from each group were inoculated with hepatoma No. 7777 cells in the thigh muscles of both hind legs and allowed to grow for 25 days. Sera were obtained from all animals by heart puncture under light ether anesthesia, and protein species were resolved by PAGE. Eight and four protein bands in the haptoglobin and postalbumin regions, respectively, were resolved from control rat serum, whereas sera from depleted animals had eight and three bands, respectively. Protein expression was facilitated by the presence of hepatomas. Ten and six protein bands were seen in the haptoglobin and postalbumin regions, respectively, upon PAGE of sera from control tumor-bearing rats. A positive synergistic effect between pyridoxine lack and tumor presence was also found. Twelve and five bands were resolved in the haptoglobin and postalbumin regions, respectively, when sera from pyridoxine-depleted tumor-bearing rats were electrophoresed. These results showed that vitamin B6, in addition to its well-known coenzymatic function, exercised a type of control over protein expression, which may be positive or negative depending on the nutritional and health status of the animal.
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PMID:Effects of pyridoxine on serum protein expression in hepatoma-bearing rats. 693 82

Transplantation of Yoshida sarcoma (solid type) and Zajdela ascites hepatoma tumors in rats induces a biphasic change in the concentration of the following five acute-phase proteins: alpha-1-acid glycoprotein; alpha-1-antitrypsin; haptoglobin; hemopexin; and ceruloplasmin. These proteins and other plasma proteins were quantitated by two-dimensional immunoelectrophoresis relative to normal serum concentrations. The elevation of most of these acute-phase proteins was greater in the second phase, during which serum levels increased continuously as the tumor burden increased until the animals died. The increase in haptoglobin concentration during the second phase was much higher in rats bearing Yoshida sarcoma than in rats bearing Zajdela tumors. Rats receiving irradiated tumor cells showed neither tumor growth nor second-phase protein changes. Significant increases in uptake of 3H-amino acids by isolated perfused livers of tumor-bearing rats provided evidence for an increase in the hepatic synthesis rates of the acute-phase proteins. Removal of the solid tumor resulted in a gradual decrease of acute-phase protein concentrations with concomitant increase in serum albumin concentration. These alterations in serum acute-phase proteins during tumor growth and after removal of the tumor may make their use attractive as biological markers of the response of the tumor-bearing animal to its tumor.
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PMID:Kinetics of the acute-phase reaction in rats after tumor transplantation. 697 53

Experiments were performed on rats injected with a malignant hepatoma (evoked by aflatoxin B1) or with inflammation induced by turpentine injection. On the 4th or 8th day after the injection, the following determinations were made: concentration of seromucoid, haptoglobin, sialic acid and fucose in blood serum; binding of asialo-glycoproteins by liver extracts; elimination of asialo-[125I]haptoglobin and asialo-[125I]orosomucoid from circulation. It was found that hepatoma and inflammation affected neither the activity of liver receptors for asialo-glycoproteins, nor the rate of asialo-glycoprotein elimination from circulation.
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PMID:Catabolism of desialylated glycoproteins during carcinogenesis and inflammation in rats. 732 99

Transcriptional regulation of gene expression by hypoxia is an important, but yet only marginally characterized mechanism by which organisms adapt to low oxygen concentrations. The human hepatoma cell line HepG2 is a widely used model for studying hypoxic induction of the hematopoietic growth factor erythropoietin. In an attempt to identify additional genes expressed in HepG2 cells during hypoxia, we differentially screened a cDNA library derived from hypoxic (1% O2) HepG2 cells using probes isolated from either normoxic (21% O2) or hypoxic cells. Two genes were identified, one encoding aldolase, a member of the glycolytic enzymes, and the other encoding alpha 1-antitrypsin which belongs to the family of the acute phase (AP) responsive proteins. Whereas hypoxic induction of glycolytic enzymes is well established, oxygen-dependent regulation of AP genes has not been reported so far. AP proteins are liver-derived plasma proteins whose production during inflammation is either up-regulated (positive AP reactants) or down-regulated (negative AP reactants). In the present study, we demonstrate that on the mRNA level hypoxic stimulation of HepG2 cells led to (i) an induction of the positive AP reactants alpha 1-antitrypsin, alpha 1-antichymotrypsin, complement C3, haptoglobin, and alpha 1-acid glycoprotein; (ii) a down-regulation of the negative AP reactant albumin; (iii) an up-regulation of the negative AP reactant transferrin; and (iv) unchanged levels of the positive AP reactants alpha- and beta-fibrinogen as well as hemopexin. Cycloheximide inhibited hypoxic up-regulation of AP mRNAs demonstrating that de novo protein synthesis is required for hypoxic induction. Nuclear run-on assays indicate that the hypoxic increase in AP mRNAs is mainly due to transcriptional regulation. The hypoxic response was compared to AP stimulation by interleukin 6. The results suggest that the adaptive response to hypoxia overlaps with, but is not identical with, the AP response mediated by interleukin 6.
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PMID:Hypoxia, a novel inducer of acute phase gene expression in a human hepatoma cell line. 749 59

Acute inflammation is characterized by increased production of acute phase proteins in the liver. The induction of the hepatocytic response is primarily mediated through soluble cytokines such as IL-1, IL-6, TNF-alpha, and transforming growth factor beta, which bind to specific cell surface receptors and regulate gene expression of acute-phase proteins. Hepatoma cell lines, such as HepG2, represent a model system for studying acute-phase protein synthesis. HepG2 is induced to produce a variety of acute-phase proteins, including alpha 1-antitrypsin, alpha 1-antichymotrypsin, fibrinogen, alpha 1-acid glycoprotein, and haptoglobin, upon stimulation with cytokines. Analysis of HepG2 by reverse transcriptase PCR indicated that this cell line synthesized mRNA specific for the human C5a receptor (CD88). Flow cytometric analysis of HepG2 cells indicated that these cells bound anti-CD88 Ab, thus confirming our RT-PCR data by demonstrating that these cells also express the C5a receptor. Because C5a has been shown to be a potent mediator of inflammation and HepG2 cells express CD88, we assessed the possibility that C5a was capable of stimulating acute-phase protein synthesis by HepG2 cells. The results indicate that binding of human C5a to CD88 on HepG2 cells resulted in an increased production of alpha 1-antitrypsin- and alpha 1-antichymotrypsin-specific mRNA as assayed by RT-PCR. Analysis of culture supernatants derived from C5a-stimulated HepG2 cells showed an increased production of alpha 1-antitrypsin as measured by solid-phase ELISA. alpha 1-antitrypsin production by HepG2 cells was a direct result of C5a stimulation as evidenced by the fact that anti-C5a receptor Ab inhibited the response. These results suggest that C5a may be an important mediator of APP production in the regulation of the inflammatory response.
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PMID:Expression of functional receptors for human C5a anaphylatoxin (CD88) on the human hepatocellular carcinoma cell line HepG2. Stimulation of acute-phase protein-specific mRNA and protein synthesis by human C5a anaphylatoxin. 754 17

Recently, a novel cytokine, cardiotrophin-1 (CT-1), was cloned and found to induce cardiac myocyte hypertrophy in vitro. Amino acid sequence similarity showed CT-1 to be a member of the IL-6/LIF/CNTF/OSM/IL-11 cytokine family. Since all known members of the IL-6 cytokine family induce an hepatic acute phase protein (APP) gene expression, we investigated the ability of CT-1 to induce a liver acute phase response. Upon stimulation of rat hepatoma cells, CT-1 and LIF induced the strongest rat fibrinogen mRNA expression, OSM and IL-6 induced a less pronounced response. When human hepatoma cells and primary rat hepatocytes were stimulated with CT-1, the expression of human haptoglobin and rat alpha 2-macroglobulin mRNA was induced. The induction of the acute phase response was dose- and time-dependent. In this study we demonstrate that CT-1, a novel cytokine belonging to the IL-6 cytokine family, is a hepatocyte stimulating factor.
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PMID:A new hepatocyte stimulating factor: cardiotrophin-1 (CT-1). 755 64


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