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)

Previous work in our laboratory has indicated that free fatty acids stimulate synthesis of fibrinogen by the liver. The effect of the hypolipidemic agent clofibrate on hyperfibrinogenemia associated with tumors was evaluated by monitoring clofibrate-induced changes in plasma fibrinogen concentration and biosynthesis of the protein in Buffalo rats implanted with a localized, nonmetastasizing neoplasm derived from a tumorigenic hepatoma cell line (HTC4). In tumor-bearing animals not treated with clofibrate, cancer growth was associated with elevated rates of fibrinogen synthesis and a doubling of plasma fibrinogen concentrations. Plasma free fatty acid concentrations and serum free fatty acid/albumin molar ratios were also increased in tumor-bearing rats. Treatment with clofibrate in doses which normalized the plasma free fatty acid/albumin ratio also prevented the tumor-associated rise in plasma fibrinogen. Rates of fibrinogen synthesis were lowered significantly in clofibrate-treated animals. Tumor growth was not affected by clofibrate. These results indicate that hyperfibrinogenemia associated with nonmetastasizing tumors may reflect changes in lipid metabolism which are neutralized by clofibrate. Thus, treatment with clofibrate or other hypolipidemic agents should be evaluated in cancer patients with elevated plasma fibrinogen levels and their attendant complications.
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PMID:Suppression of tumor-associated hyperfibrinogenemia and free fatty acidemia with p-phenoxybenzalbutyrate (clofibrate). 47 20

The clonal variation in the rate of albumin production in cultured rat hepatoma cells has been studied on a cellular basis by immunoperoxidase techniques using specific antisera against rat serum albumin. Previously, it has been shown that an array of clonal hepatoma cell populations that produce serum albumin at different rates can be isolated simply by subcloning a single clonal hepatoma cell line (Fu5). The present study demonstrates conclusively that this phenotypic variation is the result of quantal shifts in the rate of albumin production in the individual cells and is not due to changes in the percentage of albumin-producing cells. Also, by analyzing individual colonies as they develop from single cells, it was possible to establish that the rate of variation in albumin content in several hepatoma cell clones is on the order of 0.5-1.4 10(-2) per cell per generation. This variation in albumin content probably reflects shifts in the rate of albumin synthesis. Even after several sequential subclonings, the same clonal variation persists. The variants are not the result of fluctuations in albumin synthesis with different phases of the cell cycle.
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PMID:Analysis of discontinuous variation in albumin production by hepatoma cells at the cellular level. 53 34

The analysis of translational efficiencies of specific mRNAs requires a determination of the polyribosome size. The appropriate value to use in such calculations is the number-average size. A method is described for accurately measuring the number-average size of total and of specific protein synthesizing polyribosomes using isokinetic sucrose density gradients and 125I-labeled antibodies. By this method, we demonstrated that albumin synthesizing polyribosomes from a serum albumin secreting mouse hepatoma cell line exist over a broad range from trimers to 20-mers (mean 6-10). The specificity of antibody interaction with polyribosomes was demonstrated using cells not synthesizing mouse serum albumin, and by demonstrating that 125I-anti ovalbumin does not bind to mouse hepatoma polyribosomes. Treatment of the mouse hepatoma cells with 1 MUM cycloheximide shifted practically all of the monomers into polyribosomes resulting in an increase in the number-average size of the albumin synthesizing polyribosomes. Cycloheximide treatment, however, did not eliminate the size heterogeneity in the albumin synthesizing polyribosomes.
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PMID:Polyribosome size analysis. Measurement of number-average polyribosome sizes. 53 42

The effects of 5-fluorouracil (5-FU) on regenerating liver were studied after two thirds hepatectomy in rats. In Group I, 68% hepatectomy was performed. In Group II, 5-FU in a dose of 20 mg/kg was administered intravenously immediately after, 24 and 48 hours after the same hepatectomy. In Group III, the same amount of 5-FU was given after sham-operation. The mortality rates were 4.5% in Group I, 28.0% in Group II, and 0% in Group III. The treatment with 5-FU following hepatectomy caused not only suppression but delay of liver cell division. Histologic changes such as cellular degeneration, liver steatosis and dilatation of the sinusoidal space were marked and prolonged in the hepatectomy-5-FU group. The metabolic abnormalities in albumin, cholesterol, triglycedides, and phospholipids were further more profound in Group II compared to those in Group I. In Group III, moderate derangements in albumin, triglycerides and phospholipids were observed. The results may indicate that adjuvant chemotherapy with 5-FU or similar drugs immediately after partial hepatectomy in hepatoma patients should be performed with great care if necessary. Otherwise, it should not be carried out until hepatic regneration is almost completed.
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PMID:Effect of 5-fluorouracil on liver regeneration and metabolism after partial hepatectomy in the rat. 63 May 31

The level of albumin mRNA in the normal Buffalo rat liver and Morris hepatoma 7777 was compared by molecular hybridization with albumin complementary DNA (cDNA) and translational assays. Albumin mRNA was found to be 10% of the total rat liver poly(A)-containing RNA population but reduced approximately fourfold in the case of Morris hepatoma 7777. An equivalent decrease of albumin mRNA activity in the hepatoma was detected by translation in a mRNA-dependent cell-free protein-synthesizing system. A proportional increase in total hepatoma poly(A)-containing RNA was not observed, indicating that there was a true fourfold reduction of albumin synthesis in the hepatoma. DNA excess hybridization with albumin cDNA did not reveal any apparent change in albumin gene frequency in the hepatoma compared to normal liver. Complementary DNA copies of total liver and hepatoma poly(A)-containing RNA were synthesized and employed in homologous and heterologous hybridization reactions. Analyses of these reactions showed a high degree of homology between the poly(A)-containing RNA of the liver and hepatoma, with some difference in the relative sequence abundancy. However, qualitative differences were detected in hepatoma 7777 consistent with the concept of alterations in the control of gene expression upon neoplastic transformation.
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PMID:Molecular basis of reduced albumin synthesis in Morris hepatoma 7777. 69 90

Proliferation of a new population of epithelial cells with distinct structure, as well as cytokeratin and alpha-fetoprotein expression, was observed in nonneoplastic liver tissues from 14 cases (13 hepatitis B virus-positive) of human hepatocellular carcinoma. These cells were characterized by oval nuclei; scant, pale cytoplasm; small cell size; and cross-reaction with a monoclonal antibody against rat oval cells. These putative human oval cells were strongly positive for cytokeratin 19 and displayed considerable heterogeneity in alpha-fetoprotein and albumin expression. The oval cells were most prominent in actively regenerating nodules and in liver tissue surrounding the cancer. Oval cells and transitional types of cells appear to be the principal producers of alpha-fetoprotein in the regenerating liver. Cancer cells positive for cytokeratins 8, 18 and 19 were observed in half the hepatocellular carcinomas studied. The data suggest that a new cell population structurally similar to oval cells seen in early stages of chemical hepatocarcinogenesis in rats is consistently present in regenerating liver lesions associated with human hepatocellular carcinoma. Furthermore, it is possible that the proliferation of these oval-type cells may partly account for the elevation of serum alpha-fetoprotein frequently seen in precancerous stages of hepatitis B virus-associated human hepatocellular carcinoma.
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PMID:Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis. 128 Feb 43

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

Transforming growth factor-beta (TGF beta) has been implicated in the regulation of hepatocyte function. We have examined TGF beta 1 regulation of albumin and alpha-fetoprotein (AFP) mRNA levels in a well differentiated mouse hepatoma cell line (BWTG3). TGF beta 1 reversibly decreased steady state mRNA levels of both albumin and AFP. By nuclear run-on assays, we found that TGF beta 1 caused no significant change in transcription rates for albumin or AFP. Pretreatment with actinomycin-D prevented the TGF beta 1-induced decrease in albumin and AFP mRNA levels. Also, if cells were treated with actinomycin-D after a 12-h exposure to TGF beta 1, actinomycin-D abrogated the further decrease in albumin and AFP mRNA levels that occurred after treatment with TGF beta 1 alone. Cycloheximide pretreatment blocked the TGF beta 1-induced decrease in albumin and AFP mRNA levels. TGF beta 1 altered neither the rate of BWTG3 cell growth nor the levels of mRNA for the growth-associated protooncogene c-myc. These data suggest that TGF beta 1 has regulatory effects on specific hepatocyte functions that are independent of growth regulatory effects. The decrease in albumin and AFP mRNAs caused by TGF beta 1 is posttranscriptional and dependent upon de novo RNA and protein synthesis.
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PMID:Posttranscriptional regulation of albumin and alpha-fetoprotein messenger RNA by transforming growth factor-beta 1 requires de novo RNA and protein synthesis. 128 69

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

Small pieces of normal liver tissues were obtained from patients with gallstones undergoing cholecystectomy, and hepatocytes were isolated from these tissues. They were cultured in a medium of DFH containing several growth factors and hormones, successively for more than two years over 60 passages. They showed doubling time about 25 hours, peak mitotic index near 4% and heteroploid karyotype. They kept secreting some enzymes and albumin, that are usually produced by normal liver tissue. In contrast with hepatoma cells, the cultured normal hepatocytes failed to form xenograft tumor in nude mice and their proliferation was depended upon exogenous growth-factors in vitro. The cultured hepatocytes can be used as a cell model for study of carcinogenic process and stored as a cell-pool for clinical cell transplantation in the coming years.
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PMID:[Culture and characterization of normal human hepatocytes]. 130 11


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