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)

This is a broad review (140 literature citations) of the possible effects of oral contraceptives on the liver. The oral contraceptives considered consist of combined preparations of estrogens and progestogens although the so-called "minipills" contain only a progestogen. The effects are divided into 1) decrease in excretory liver function; 2) influence on bile acid formation, including cholesterol metabolism; 3) increased synthesis of various transport proteins (ceruloplasmin, transferrin, thyroxine-binding protein, and cortisol-binding protein); 4) the effects of increased tissue circulation caused by sexual hormones and anabolic steroids as a cause for more frequent cavernous angiomas and peliosis hepatis; 5) interference with the metabolism of other drugs by the competitive action of the hepatic metabolites of steroid hormones. This includes the increased formation of delta amino levulinic-acid synthetase, the key enzyme for porphyrin synthesis. The gestagen component of oral contraceptives is responsible for enzyme induction in the smooth endoplasmic reticulum. Morphological liver changes caused by oral contraceptives include parenchyma changes, hepatosis, reactive hepatitis, hepatitis resembling viral hepatitis, vascular changes, sinusoid ectasia, Budd-Chiari syndrome, hyperplasias and neoplasias, focal nodular hyperplasia, adenoma and liver cell carcinoma.
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PMID:[Effects of oral contraceptives on liver function and structure]. 332 30

The clinical features and investigations of 17 patients were analysed. Thirteen of them were Chinese and the rest Indians. Their ages at presentation ranged from 8 to 63 years (mean 18.35 years). Thirteen patients (76%) were symptomatic; 8 with predominantly hepatic manifestations and 5 with neurological features. Four were asymptomatic siblings. At diagnosis, however, 10(59%) had features of liver involvement singly, 3 (18%) had neurological involvement alone and 4 (27%) had mixed presentations. Family histories were available in 15 patients; 26.9% of siblings had Wilson's Disease. Serum ceruloplasmin was low in 82% of the patients. 24-hour urinary copper was measured in 16 patients and was raised in all of them. About half the patients (41%) had evidence of concomittant renal tubular dysfunction with hypouricaemia and aminoaciduria. Three patients (18%) had joint involvement at presentation. All 17 patients were treated with Penicillamine. Complications due to therapy included pemphigus in one and toxic epidermal necrolysis and later a lupus like syndrome in another. The features of clinical improvement included fading of K-F rings, improvement of neurological signs and the normalisation of serum transaminases. One patient developed primary hepatocellular carcinoma 5 years after presentation. Delay in diagnosis was encountered in half of the patients reviewed. Being a treatable condition, Wilson's Disease, although rare, should always be thought of in patients with haemolysis, liver diseases or extrapyramidal disorders.
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PMID:Wilson's disease revisited in the tropics. 375 94

Some peculiarities of mRNA translation of ceruloplasmin (CP) from rat liver were investigated, using three cell-free protein biosynthesis systems (wheat embryo extracts, rabbit reticulocyte lysates and Zajdela ascite hepatoma extracts). It was shown that reticulocyte lysates and tumour cell extracts synthesize full-size CP mRNA translation products, whose molecular mass is close to that of mature CP molecules, i. e., 122-132 kD. Wheat embryo extracts synthesize the NH2-terminal fragment of the CP molecule (Mr = 84 kD). Addition of liver membrane fractions to wheat embryo extracts translating CP mRNA results in the reconstitution of proteolytic steps of CP maturation.
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PMID:[Comparative study of ceruloplasmin biosynthesis in various cell-free systems]. 381 51

The production of plasma proteins has been monitored in somatic cell hybrids between a rat hepatoma cell line (7777) and human fetal liver cells. Production of 14 plasma proteins was assayed in concentrated serum-free culture supernatants by electroimmunoassay. Alpha 2HS-glycoprotein (AHSG) was produced by 10 of 19 hybrids; concordancy for presence or absence of protein production was 100% for human chromosome 3. Orosomucoid (ORM) was produced in 8 of 19 hybrids, with a concordancy for presence or absence of protein of 94.7% with human chromosome 9. The chromosome location for genes for these two proteins, previously assigned by linkage studies, is confirmed by direct assignment. These studies have also suggested possible chromosomal assignments for loci for alpha 1-antichymotrypsin and C1 esterase inhibitor. Other genes for proteins which could not be assigned to specific chromosomes using these hybrids were: complement C3, ceruloplasmin, hemopexin, inter-alpha-trypsin inhibitor, prealbumin, retinol-binding protein, transferrin and apolipoproteins CII, B, and sinking-pre-beta [Lp(a)].
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PMID:Direct assignment of orosomucoid to human chromosome 9 and alpha 2HS-glycoprotein to chromosome 3 using human fetal liver x rat hepatoma hybrids. 385 64

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

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

Many hepatic lesions, ranging from subcellular alterations to malignant tumors, have been attributed to the use of anabolic steroids (AS) and contraceptive steroids (CS). These lesions that have been attributed to AS and CS are discussed with focus on the following: biochemical changes; subcellular alterations; intrahepatic cholestasis; vascular complications (sinusoidal dilatation, peliosis hepatitis, Budd-Chiari syndrome); hyperplasia and neoplasia (diffuse hyperplasia, nodular transformation, focal nodular hyperplasia, hepatocellular adenoma, hepatocellular carcinoma, and miscellaneous malignant tumors); and miscellaneous effects (effects of preexisting liver disease, cholelithiasis, and pancreatitis). OCs have a number of physiologic effects on the liver. These include decreased bile flow, diminished secretion of organic anions, and decreased synthesis and secretion of bile acids. Retention of bromosulfophthalein has been noted with AS during late pregnancy and in the puerperium. It is well established that the CS can lead to elevations of serum ceruloplasmin and copper levels. Subcellular alterations have been reported in both humans and rats on AS or women on CS and involve multiple organelles of the several systems of the liver. Both AS and CS have been implicated in intrahepatic cholestasis. Jaundice usually develops after 2-5 months of therapy with AS or after 3 months of OC use. The lesions attributed to CS and AS can involve any of the systems of the liver. At times more than 1 system is affected simultaneously. Most of the steroid related lesions resemble similar ones caused by other etiologies. Some, such as peliosis hepatitis, are rarely related to other etiologies, but others can be termed steroid specific. A number of diseases associated with the CS or AS also occur in pregnancy. Acute fatty metamorphosis of pregnancy and the periportal hemorrhagic necrosis characteristic of eclampsia have not been reported in patients on CS. Spontaneous rupture of the liver during pregnancy has not been attributed to the CS.
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PMID:Hepatic lesions caused by anabolic and contraceptive steroids. 628 45

We have grown a human hepatoma cell line, designated as HA22T/VGH, from a 52-yr-old male hepatoma patient since July 1, 1980. This cell line has been subcultured more than 100 passages. The chromosome analysis of HA22T/VGH indicated that the chromosome numbers varied from 70 to 146, with the mode of 73. Methylcellulose soft agar assay showed that approximately 40% of the HA22T/VGH cells formed colonies. The HA22T/VGH produced tumors in nude mice. Histopathological studies of the tumor revealed the arrangement of hepatoma. Detected by the complement fixation method HA22T/VGH cells secreted ceruloplasmin, Factor B, C3, C4, Gc-globulin and alpha 1-acid-glycoprotein. These cells contained the liver associated enzymes: alanine amino transferase, tyrosine amino transferase and gamma-glutamyl transferase. HBsAg and alpha-fetoprotein were not detectable in the HA22T/VGH culture media or cell lysates by the radioimmunoassay.
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PMID:[A new human hepatoma cell line: establishment and characterization]. 629 75

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

Subconfluent monolayers of human hepatoma HepG2 cells were cultured for 2 days in serum-free DMEM containing 1 microM dexamethasone and human recombinant hepatocyte growth factor (HGF), retinoic acid (RA), IL-1, IL-6, LIF and mixtures of these factors. Incorporation of labelled thymidine was significantly decreased by IL-6, IL-1 and HGF but only slightly by LIF and RA. Synthesis of acute phase proteins secreted daily to the media was measured by electroimmunoassay with monospecific antisera. In addition, the synthesis and secretion of some proteinase inhibitors (alpha-1-proteinase inhibitor, alpha-1-antichymotrypsin, C1-inactivator, plasminogen activator inhibitor-1, inter-alpha-trypsin inhibitor and pre-alpha-inhibitor) was evaluated by incorporation of labelled methionine and fluorography. Among the cytokines tested IL-6 was the most potent regulator of acute phase protein synthesis. Hepatocyte growth factor stimulated basal synthesis of alpha-1-antichymotrypsin, and to a lesser extent affected some other proteins. Retinoic acid preferentially increased synthesis of alpha-1-antichymotrypsin, ceruloplasmin and plasminogen activator inhibitor-1. Both HGF and RA slightly modulated cytokine-induced synthesis of several acute phase proteins in HepG2 cells.
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PMID:Regulation of synthesis of some proteinase inhibitors in human hepatoma cells HepG2 by cytokines, hepatocyte growth factor and retinoic acid. 768 88


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