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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A clonal strain of epithelial cells (designated MH(1)C(1)) has been established from the transplantable Morris hepatoma No. 7795. The cells have maintained distinctive morphology throughout more than 20 subcultures (split 1:5) at 2- to 4-week intervals in supplemented Ham's F 10 medium. They contain many highly refractile, round, cytoplasmic bodies which stain bright red with Oil Red O. The population doubling time was 2 wk when the clonal strain was first established. It has gradually decreased to 1 wk. The cells synthesize rat serum albumin and secrete it into the culture medium as determined immunologically by microcomplement fixation and double diffusion. Albumin secretion (3-6 microg albumin/mg cell nitrogen/24 hr) occurs throughout the logarithmic phase of cell proliferation and has not diminished during serial propagation since the strain was initiated 15 months ago.
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PMID:Establishment of a clonal strain of hepatoma cells which secrete albumin. 417 59

Albumin (ALB)-positive cells were identified by an immunoperoxidase technique in 52 of 53 autopsy cases and in all of 13 surgical cases of hepatocellular carcinoma (HCC). The distribution pattern of ALB-positive cells could be classified into three groups: diffuse, localized, and sparse. The diffuse type was the most common pattern and was usually seen in well or moderately differentiated HCC, showing a trabecular growth pattern. The localized or sparse patterns were more frequent in poorly differentiated HCC showing a compact growth pattern. alpha-Fetoprotein (AFP)-positive cells were detected in 37 of the 53 autopsy cases of HCC and 11 of the 13 surgical cases. The number of AFP-positive cells and the intensity of the immunoperoxidase reaction were roughly proportional to serum AFP levels in most cases. In most regions of HCC, there seemed to be an inverse relationship between the number of ALB- and AFP-positive cells, suggesting tht most HCC cells synthesized only one of the two antigens studied. ALB-positive hepatocytes were found in all of the normal or cirrhotic livers examined and in the tumor-free regions of the HCC-containing livers. In contrast, AFP was not detected in nonneoplastic hepatocytes.
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PMID:Distribution of albumin- and/or alpha-fetoprotein-positive cells in hepatocellular carcinoma. 616 58

Radioimmunoassay was used to determine alpha-fetoprotein (AFP), albumin, and transferrin production (ng/10(5) cells/24 h) by two cell lines (7777 and 8994) derived from chemically induced rat hepatomas. alpha-Fetoprotein production was high (2000 to 4400) in 7777, but was very low (0.2 to 0.4) in 8994. Albumin production varied from 0.4-0.8 (7777) to 14-26 (8994). Both lines produced substantial amounts of transferrin (180 to 240 by 7777 and 29 to 42 by 8994). Addition of dimethyl sulfoxide (DMSO, 1 to 4%) or sodium butyrate (BA, 0.5 to 2.0 mM) to the medium inhibited growth in both lines, but 8994 was more sensitive to these agents than 7777. Dimethyl sulfoxide treatment (2 to 4%) resulted in a dose-related decrease (less than 10% of control at 4% DMSO) in AFP, albumin, and transferrin production by 7777, but in 8994, DMSO (1 to 2%) resulted in an increase (up to sixfold) in albumin and transferrin production, without affecting AFP production. By contrast, BA (2 to 4 mM) stimulated the production of all three proteins in both lines, most notably that of albumin (up to sixfold) by 7777 and that of AFP (up to 20-fold) by 8994. It is concluded that both DMSO and BA can enhance the expression of differentiated functions of the hepatoma cell, and that DMSO at the same time can suppress the expression of an oncofetal function. However, neither DMSO nor BA is selective in its effects on specific genes (i.e., normal, adult vs. oncofetal genes), and it appears that their effects may be the result of a more general phenomenon, the expression of which may be related to the stage of differentiation of the cell.
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PMID:Differential effects of dimethyl sulfoxide and sodium butyrate on alpha-fetoprotein, albumin, and transferrin production by rat hepatomas in culture. 616 75

Four diploid human cell types (lymphocytes, fibroblasts, amniotic fluid cells, and hepatocytes) were fused to mouse hepatoma cells, HH. HH synthesized and secreted several liver-specific gene products including albumin, transferrin, and alpha-fetoprotein. The resulting interspecific hybrids were compared to determine whether or not the pattern of human hepatic gene expression was similar when these various cells were fused with the mouse hepatoma line. The expression of six human hepatic genes was examined, including albumin, alpha-fetoprotein, ceruloplasmin, transferrin, alpha-1-antitrypsin, and haptoglobin. Albumin was most frequently expressed while alpha-fetoprotein was not detected in any of the hybrids studied. The patterns of expression of human serum proteins differed between the hybrid series. Hybrids derived from human fibroblasts produced primarily albumin, while those derived from lymphoblastoid cells and amniocytes had a higher frequency of clones secreting alpha-1-antitrypsin. The findings reported here suggest that the frequency of hybrid clones expressing human hepatic gene products and the array of proteins produced are influenced by the histogenetic state of the human parental cell type.
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PMID:Expression of human hepatic genes in somatic cell hybrids. 618 Apr 90

The capacity of the human hepatoma cell line Hep G2 to synthesize and secrete components of the fibrinolytic system was examined. Although fibrinogen, plasminogen, and alpha 2-antiplasmin were present in culture supernatants, histidine-rich glycoprotein was not detected. Albumin was monitored for comparative purposes and was also secreted. Intracellular levels of the fibrinolytic proteins were not detected, suggesting that once synthesized, these proteins were rapidly secreted by the cell. The fibrinogen, plasminogen, alpha 2-antiplasmin, and albumin secreted by the cells were immunochemically identical to their plasma counterparts. The concentration of these four molecules increased exponentially with time in the culture medium when normalized to total cellular protein. The kinetics of their secretion were similar, but the amounts of each protein differed. On day 8 the culture medium contained 29.6, 0.64, 0.39, and 0.59 micrograms/ml albumin, fibrinogen, plasminogen, and alpha 2-antiplasmin, respectively, whereas the time required for doubling the concentrations of the proteins in the medium ranged from 2.20 to 2.49 days. A detailed characterization of alpha 2-antiplasmin demonstrated that this inhibitor was synthesized by the cells. The molecular weight of intrinsically labeled alpha 2-antiplasmin was 69,000. The secreted inhibitor was biologically active, since it could inhibit plasmin cleavage of a chromogenic substrate, and this inhibition was neutralized by monospecific antibodies to alpha 2-antiplasmin. In addition, intrinsically labeled alpha 2-antiplasmin and the plasma molecule behaved in an identical manner with respect to their capacity to form a complex with plasmin. These studies suggest that the Hep G2 cell line may provide a model for assessing the regulation of synthesis and secretion of components of the human fibrinolytic system.
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PMID:Synthesis and secretion of the fibrinolytic components, including alpha 2-antiplasmin, by a human hepatoma cell line. 618 56

Cancer cells obtained from human hepatocellular carcinoma nodules were subjected to primary culture, and a hepatoma cell line was established. The cell clumps obtained by needle puncture were plated directly in plastic tissue culture flasks without any cell dissociation procedures. Cell clusters became attached to flasks in 24 h with an efficiency of about 90%. No fibroblast outgrowth was observed. Primary cultured cells were composed of polygonally shaped epithelial cells with dense cytoplasm and one or more large nuclei. They excreted plasma protein biosynthetic markers of hepatocytes into the culture medium. Plasma protein synthesis of primary cultured hepatoma cells decreased as the age of the primary cultures increased. Cells seeded in September 1980 started to grow continuously after 5 months of cultivation. A new hepatocellular carcinoma cell line (designated as KG55T) was established from these growing cells. KG55T cells have been subcultured for more than 20 passages and form a monolayer of polygonal epithelial cells which pile up after they reach confluence. The cells had a doubling time of 50-60 h and a plating efficiency of 60-65%. Albumin, alpha 1-antitrypsin and alpha 2-macroglobulin syntheses and tyrosine aminotransferase activity were detected. At the 10th passage, KG55T cells were pseudotriploid (mode, 69), and 8q+ and 15q+ translocations were distinctive of this cell line. The morphological characteristics and the capacity for plasma protein synthesis of the primary cultured hepatoma cells and cells of the established hepatoma cell line were compared.
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PMID:Primary cultured cells and an established cell line of human hepatocellular carcinomas. 619 59

A cDNA clone complementary to mRNA encoding the precursor (Mr = 165,000) to the rat liver mitochondrial matrix enzyme carbamyl phosphate synthetase I (Mr = 160,000) was employed to compare relative amounts of the messenger in adult and fetal liver and in Morris hepatoma 5123D and 3924A cells. Northern blot analysis gave a size estimate for the messenger of 6,500-6,700 nucleotides. Carbamyl phosphate synthetase mRNA levels in 15-day-old fetal liver were less than 10% of adult levels; 5123D cells expressed the messenger at levels about 2-fold higher than normal adult liver, but the messenger was undetectable in 3924A cells. Albumin mRNA was also expressed in the former but not in the latter. Maintaining rats for 5 days on a diet containing 60% casein augmented the relative amount of carbamyl phosphate synthetase mRNA by about 2-fold, while a protein-free diet resulted in reduced levels of the mRNA (about 50% compared to animals on a normal diet). Finally, the pattern of hybridization of carbamyl phosphate synthetase cDNA to HindIII-digested genomic DNA showed no differences between normal liver and its corresponding hepatoma; however, a HindIII site polymorphism was observed between Buffalo and ACI rats.
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PMID:Regulation and expression of carbamyl phosphate synthetase I mRNA in developing rat liver and Morris hepatoma 5123D. 654 17

Variant subclones of the rat hepatoma cell line FU5-5 have been isolated that are altered in their production of rat serum albumin. Three of these variants, isolated in a random screening, have been categorized as high, intermediate, and low producers. They secrete albumin into the culture medium at different rates: 16, 1.7, and 0.3 microgram/mg cell protein/48 h. A fourth variant, isolated on the basis of altered morphology, secretes no detectable albumin. Unlike the albumin-producing variants, this null variant is also deficient in the level and inducibility of tyrosine aminotransferase activity. Albumin biosynthesis as determined in pulse-labeling experiments is affected similarly in the four variants, yielding albumin synthetic rates of 0.24, 0.035, 0.006, and less than 0.002% of total protein synthesis. The translatable albumin messenger RNA content in these variants was measured using a rabbit reticulocyte lysate system. The null variant contains no detectable mRNA, and the three quantitative variants contain levels of translatable albumin messenger RNA corresponding to 0.07, 0.03, and 0.005% of total stimulated polypeptide synthesis. The highest producing variant contains less translatable albumin mRNA than expected on the basis of cellular biosynthetic measurements, suggesting a translation efficiency difference in this clone. Cell hybrids constructed by fusing the high-producing clone and the null variant produce little or no albumin. This extinction indicates that the null variant contains a diffusible regulatory factor capable of decreasing albumin gene expression. The relatively stable and discrete heritable phenotypic changes exhibited by these clones may serve as a model for similar changes that occur during hepatic differentiation.
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PMID:Rat serum albumin synthesis in variant rat hepatoma cells. 682 59

Rat hepatoma clones whose cells do and do not produce albumin, as well as somatic hybrid between the two types of cells, have been examined for albumin mRNA. A direct proportionality between the rate of albumin production and the concentration of albumin mRNA sequences was found for all albumin-producing hepatoma and hybrid clones, indicating that rate of synthesis of the protein is determined by the concentration of its mRNA. Albumin-negative dedifferentiated variant and somatic hybrid cells contain fewer than one to five molecules of albumin mRNA per cell; the block in expression of the gene appears to be at the same (probably transcriptional) level in variants and their somatic hybrids.
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PMID:Expression of the albumin gene in rat hepatoma cells and their dedifferentiated variants. 689 67

We attempted to detect circulating hepatocellular carcinoma by demonstrating hepatocyte-associated mRNA in the nuclear cell component of peripheral blood using nested reverse transcription-polymerase chain reaction because of the extremely small number of tumor cells in the circulation. Albumin mRNA was demonstrated not only in the liver tissue (hepatocytes) and HepG2 cells but also in nuclear cells of the blood from normal healthy volunteers (neutrophils and lymphocytes) by reverse transcription-polymerase chain reaction. In contrast, alpha-fetoprotein mRNA was demonstrated in the liver tissue, as well as in HepG2 cells, but not in peripheral blood of normal healthy volunteers, indicating the possibility of using alpha-fetoprotein mRNA for detection of benign and malignant hepatocytes among the population of neutrophils and lymphocytes. alpha-Fetoprotein mRNA in peripheral blood was detected in 17 of 33 cases of hepatocellular carcinoma (52%), 2 of 13 cases of cirrhosis (15%) and 2 of 17 cases of chronic hepatitis (12%). alpha-Fetoprotein mRNA was not demonstrated in 26 cases of normal healthy volunteers (0%). Among the patients with hepatocellular carcinoma, total volume of tumor tissue, maximum size of tumor and serum alpha-fetoprotein level were markedly increased in the patients with alpha-fetoprotein mRNA in blood. In addition, alpha-fetoprotein mRNA was detected in the blood of all 6 patients showing metastasis at extrahepatic organs (100%), in contrast to 11 of 27 cases without metastasis (41%). From these results, we conclude that the presence of alpha-fetoprotein mRNA in peripheral blood may be an indicator of circulating malignant or benign hepatocytes, which might predict hematogenous spreading metastasis of tumor cells in patients with hepatocellular carcinoma.
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PMID:Detection of alpha-fetoprotein mRNA, an indicator of hematogenous spreading hepatocellular carcinoma, in the circulation: a possible predictor of metastatic hepatocellular carcinoma. 752 2


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