Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies in this laboratory (1) have shown that tunicamycin-treatment inhibits the secretion of three secretory glycoproteins--alpha 2-macroglobulin, ceruloplasmin, and alpha 1-protease inhibitor in human hepatoma (Hep G2) cell cultures. In the present study, we have investigated (i) their site of accumulation within the endoplasmic reticulum/Golgi pathway, and (ii) the solubility characteristics of these unglycosylated proteins. Using percoll density gradient centrifugation, we found that tunicamycin-treatment markedly inhibited the transport of alpha 2-macroglobulin, ceruloplasmin and alpha 1-protease inhibitor from the rough endoplasmic reticulum. However, there was no detectable changes in their solubility properties as both the glycosylated and unglycosylated species were associated with the 100,000 xg supernatant fraction following disruption of the microsomal fraction (i) with 0.2% Triton X-100 and (ii) by repeated freeze-thaw cycles. Also no evidence of protein aggregation was detected by liquid chromatography of the unglycosylated proteins on Bio-Gel A-1.5 column.
 ...
PMID:Accumulation of unglycosylated liver secretory glycoproteins in the rough endoplasmic reticulum. 247 24

A model system for studies of mechanisms governing the alterations of glycosylation of plasma glycoproteins was developed. The system employs two human hepatoma cell lines, Hep 3B and Hep G2, as target cells and agarose affinity electrophoresis with lectins for studies of microheterogeneity of alpha 1-protease inhibitor (PI), a model glycoprotein synthesized by hepatocytes. As an example for the application of the system, the effect of cytokines on major microheterogeneity of plasma proteins is demonstrated. The results indicate that interleukin 6, transforming growth factor beta 1 and, to some extent, tumor necrosis factor alpha are directly involved in regulating the pattern of glycosylation of plasma proteins in vitro, but the major effect is obtained by using combinations of interleukin 6, transforming growth factor beta 1, tumor necrosis factor alpha and interleukin 1. In addition, the results underline the dissociation between alteration of gene expression and the changes in the pattern of plasma protein glycosylation.
 ...
PMID:Affinity electrophoresis for studies of mechanisms regulating glycosylation of plasma proteins. 248 77

We have previously shown that export of nine proteins by human hepatoma cells falls into three discrete kinetic classes with intracellular retention half-times of approximately 35 min, 77 min and 115 min. To determine if carbohydrate on secretory glycoproteins determines the secretory class we have measured the kinetics of export of the nine proteins after tunicamycin-treatment of cultures. We found no apparent correlation between the kinetic class of a secretory protein and sensitivity of secretion to tunicamycin-treatment. For example, three glycoproteins are exported with rapid kinetics and secretion of only one, alpha 1-protease inhibitor, is inhibited by tunicamycin treatment. In addition, three glycoproteins are secreted with intermediate kinetics and tunicamycin-treatment inhibits the secretion of two of these proteins, alpha 2-macroglobulin and ceruloplasmin but not the third, plasminogen.
 ...
PMID:Role of carbohydrate in glycoprotein secretion by human hepatoma cells. 258 May 32

In the light of recent findings concerning the importance of intermediate alpha 1-antitrypsin deficiency in the development of chronic liver disease and of hepatocellular carcinoma, we report the case of a 56-year-old woman affected by cirrhosis with significant features of liver cell dysplasia associated with intermediate alpha 1-antitrypsin deficiency (protease inhibitor SZ phenotype). In our paper we emphasize the importance of a precocious diagnosis and identification of individuals carrying the Z allele, also heterozygous.
 ...
PMID:Alpha-1-antitrypsin protease inhibitor SZ phenotype and liver cirrhosis. 278 75

The reactivity of alpha-1-antitrypsin (AAT) with Lens culinaris agglutinin (LCA) was studied by crossed immuno-affinity electrophoresis of the sera of 246 subjects from 6 groups (acute virus hepatitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma (HCC), carcinoma metastatic to the liver and normal controls). Two species of AAT (LCA-reactive and -nonreactive species) were detected on crossed immuno-affinity electrophoresis in a gel containing LCA. The percentages of LCA-reactive species of AAT in neoplastic diseases of the liver were significantly higher than those in benign liver diseases and normal controls. There was no correlation between the percentage of LCA-reactive species of AAT and serum AAT concentration in any group. Furthermore, in studying 15 pairs of serum samples before and after the subsequent development of HCC, the percentage of LCA-reactive species of AAT after HCC occurrence was significantly higher than that before, although there was no statistically significant difference between the serum AAT concentration before and after development of the disease. The latter 15 patients were all of the normal protease inhibitor phenotype (PiMM) and no change in phenotype was observed before and after the development of HCC. The results indicate that measurement of the reactivity of AAT with LCA can be a useful marker for the diagnosis of HCC and carcinoma metastatic to the liver, especially when serum concentrations of alpha-foetoprotein or other tumour markers are within the normal ranges.
 ...
PMID:The reactivity of alpha-1-antitrypsin with Lens culinaris agglutinin and its usefulness in the diagnosis of neoplastic diseases of the liver. 282 74

Alpha-1-antitrypsin (AAT) is the major protease inhibitor in human serum and is primarily expressed in the liver. We have studied AAT expression in fusion hybrids between a rat hepatoma line and either human fetal liver fibroblasts (series XXII) or human skin fibroblasts (series XIX). While the human AAT gene was always activated in series XXII hybrids when it was present, it was only rarely activated in series XIX hybrids. RFLP analysis revealed that both parental AAT alleles in series XIX hybrids were capable of being activated. Molecular analysis of the AAT gene in expressing and nonexpressing hybrids revealed that active AAT genes were hypomethylated, while inactive AAT genes were highly methylated. However, differences in methylation patterns were confined to the 5' end of the gene, on both sides of the first exon. DNaseI sensitivity revealed no hypersensitive sites close to active or inactive AAT genes.
 ...
PMID:Activation of human alpha 1-antitrypsin genes in rat hepatoma x human fibroblast hybrid cell lines is correlated with demethylation. 282 94

Alpha 1 protease inhibitor antigen was identified in the culture medium of the human ascites hepatoma cell line SK-HEP-1. Trypsin inhibitory activity and alpha 1 Pl antigen accumulated in serum-free medium concomitantly over a period of several days. Radioactive alpha 1 Pl antigen was detected in conditioned medium from cultures supplemented with 35S-L-methionine, indicating a synthesis and release of the protein. Alpha 1 Pl antigen in conditioned medium appeared to be antigenically identical to that in human plasma, and the newly synthesized (radiolabeled) antigen co-migrated with plasma, alpha 1 Pl after immunoelectrophoresis or SDS-polyacrylamide gel electrophoresis. Moreover, evidence is presented that the synthesized inhibitor exhibits functional activity, since the 35S-labeled alpha 1 Pl in conditioned medium complexes with trypsin. We conclude that SK-HEP-1 cells in culture produce functionally active alpha 1 Pl which may be identical to that in plasma.
 ...
PMID:Functional alpha 1 protease inhibitor produced by a human hepatoma cell line. 627 80

Alpha 1-antitrypsin (alpha 1 AT) is a glycoprotein of hepatic origin which functions as a systemic protease inhibitor (Pi). Its production is controlled by two autosomal-codominantly transmitted alleles. Among the numerous genetic variants some alleles (predominantly PiZ) may induce alpha 1 AT-deficiency, facultatively associated with childhood liver disease. However, the pathogenesis of this congenital disorder, which may progress to complete cirrhosis remains obscure at present. In addition, no clear cut relationship has been proven between alpha 1 AT-deficiency and deranged liver architecture, observed in advanced aged adults. Possibly this may reflect a more accidental coincidence with the consequences of chronic viral hepatitis (Non A-Non B-type). Nevertheless, this hypothesis is hitherto unestablished as it holds for the supposed association between alpha 1 AT-deficiency and the occurrence of malignant hepatoma.
 ...
PMID:[Alpha 1-antitrypsin deficiency and the liver (author's transl)]. 628 50

The hemorrhagic disposition of patients with hepatic cirrhosis and hepatoma may be associated with DIC. Thus, elucidation of the role of coagulation and fibrinolysis inhibition factors as hemostatic mechanisms in living organisms and in the growth or metastasis of neoplasms is important. Therefore, we measured the levels of serum protease inhibitor and plasminogen in hepatoma patients and compared them with those of patients with other hepatic diseases. Hepatoma was found to induce a marked increase in the alpha 1 AT, alpha 1X and C1 INA levels and a marked decreased in the I alpha I and Pmg levels. The alpha 2 M and AT III levels showed a wide distribution; no significant difference was observed between the hepatoma group and the normal control group. However, hepatoma patients with the DIC syndrome showed a marked decrease in their AT III, Pmg, alpha 2M and I alpha I levels and an increase in their alpha 1 AT and alpha 1X levels. Moreover, the serum protease inhibitor levels corresponded closely with the clinical course.
 ...
PMID:[Clinical studies of serum protease inhibitors in hepatoma]. 630

Alpha-1-antitrypsin (AAT) deficiency resulting from the homozygous protease inhibitor (Pi) ZZ and the heterozygous Pi Z states has been reported to be aetiologically associated with hepatocellular carcinoma (HCC). We studied the phenotype distribution of AAT variants (Pi) by iso-electric focusing on polyacrylamide gel and measured serum AAT concentrations by rocket immuno-electrophoresis in 80 unselected southern African Black patients with HCC and 103 age-, sex- and tribally matched control subjects. Aberrant (non-MM) phenotypes were present in 7 HCC patients (8,7%) and 13 controls (12,6%), an insignificant difference. None of the patients or controls had the Pi ZZ phenotype, while 4 HCC patients (5,0%) and 2 controls (1,9%) (P greater than 0,05) were found to be heterozygous carriers of the Z gene. No HCC patient had a subnormal serum AAT value, and the values in the patients were not lower than those in the controls. We conclude that AAT deficiency does not play an aetiological role in HCC in southern African Blacks. The 4 patients with the heterozygous Z phenotype did not have fibrolamellar carcinomas.
 ...
PMID:Alpha-1-antitrypsin deficiency and hepatocellular carcinoma. Determination of Pi phenotypes using iso-electric focusing. 631 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>