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)

We defined the acute phase behaviour of a number of rabbit plasma proteins in studies (in vivo) and studied the effects of monokine preparations on their synthesis by rabbit primary hepatocyte cultures. Following turpentine injection, increased serum levels of C-reactive protein, serum amyloid A protein, haptoglobin, ceruloplasmin, and decreased concentrations of albumin were observed. In contrast to what is observed in man, concentrations of alpha 2-macroglobulin and transferrin were increased. Co-culture of primary hepatocyte cultures with lipopolysaccharide-activated human peripheral blood monocytes or incubation with conditioned medium prepared from lipopolysaccharide-activated human or rabbit monocytes resulted in dose-dependent induction of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and depression of albumin synthesis, while C-reactive protein synthesis and mRNA levels remained unchanged. A variety of interleukin-1 preparations induced dose-dependent increases in the synthesis and secretion of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and decreased albumin synthesis. Human recombinant tumour necrosis factor (cachectin) induced a dose-dependent increase in synthesis of haptoglobin and ceruloplasmin. In general, human interleukin-1 was more potent than mouse interleukin-1 and tumour necrosis factor. None of the monokines we studied had an effect on C-reactive protein synthesis or mRNA levels. These data confirm that C-reactive protein, serum amyloid A, haptoglobin and ceruloplasmin display acute phase behaviour in the rabbit, and demonstrate that, in contrast to their behaviour in man, alpha 2M and transferrin are positive acute phase proteins in this species. While both interleukin-1 and tumour necrosis factor regulate biosynthesis of a number of these acute phase proteins in rabbit primary hepatocyte cultures, neither of these monokines induced C-reactive protein synthesis. Comparison of these findings with those in human hepatoma cell lines, in which interleukin-1 does not induce serum amyloid A synthesis, suggests that the effect of interleukin-1 on serum amyloid A synthesis may be indirect.
 ...
PMID:Regulation of rabbit acute phase protein biosynthesis by monokines. 246 85

The synthesis of all the major acute phase plasma proteins is stimulated in rat hepatoma and primary cultures of hepatocytes by three, structurally and functionally distinct groups of hormones: 1) hepatocyte-stimulating factors (HSF) and interleukin-6 (IL-6); 2) interleukin-1 (IL-1) and tumor necrosis factor (TNF); and 3) glucocorticoids. Each plasma protein gene requires a specific combination of these 3 hormone types for maximal expression. One set of acute phase proteins, including alpha 2-macroglobulin, alpha 1-antichymotrypsin ( = contrapsin), cysteine protease inhibitor ( = thiostatin), alpha 1-antitrypsin, ceruloplasmin and fibrinogens are predominantly regulated by the keratinocyte-derived HSF-III/-II or IL-6, while a second set of proteins, including alpha 1-acid glycoprotein (AGP), haptoglobin and complement C3 are predominantly regulated by keratinocyte-derived HSF-I, IL-1 or TNF. In conjunction with the above peptide hormones, glucocorticoids synergistically enhance the stimulated expression of most, but not all, acute phase proteins. An exceptionally strong synergy between HSF (or IL-6), IL-1 and glucocorticoids is noted for the activation of the AGP gene. To elucidate the molecular mechanisms of regulation, we have identified the cis-acting genetic elements through which all these hormones control the transcriptional activity of the AGP gene. It appears that acute phase activates a specific nuclear binding protein in the rat liver that interacts with the peptide hormone responsive element located 5 kb upstream of the transcriptional start site.
 ...
PMID:Regulation of acute phase protein genes by hepatocyte-stimulating factors, monokines and glucocorticoids. 248 67

Effects of DMSO on heme synthesis and enzymes of the heme biosynthetic pathway were examined in human HepG2 hepatoma cells. HepG2 cells contain measurable levels of ALA synthase and ALA dehydratase, and their levels are increased after treatment of cells with DMSO. DMSO treatment also led to increases in heme content and the synthesis of haptoglobin, while it decreased the synthesis of albumin and AFP. Changes in plasma protein synthesis after DMSO treatment are characteristic of those known to occur in the acute phase reaction. These findings suggest that profound changes in heme synthesis may occur during the acute phase reaction.
 ...
PMID:The effect of dimethyl sulfoxide on heme synthesis and the acute phase reaction in human HepG2 hepatoma cells. 248 60

Transcription of the human haptoglobin (Hp) gene is induced by interleukin-6 (IL-6) in the human hepatoma cell line Hep3B. Cis-acting elements responsible for this response are localized within the first 186 bp of the 5'-flanking region. Site-specific mutants of the Hp promoter fused to the chloramphenicol acetyl transferase (CAT) gene were analysed by transient transfection into uninduced and IL-6-treated Hep3B cells. We identified three regions, A, B and C, defined by mutation, which are important for the IL-6 response. Band shift experiments using nuclear extracts from untreated or IL-6-treated cells revealed the presence of IL-6-inducible DNA binding activities when DNA fragments containing the A or the C sequences were used. Competition experiments showed that both sequences bind to the same nuclear factors. Polymers of oligonucleotides containing either the A or the C regions confer IL-6 responsiveness to a truncated SV40 promoter. The B region forms several complexes with specific DNA-binding proteins different from those which bind to the A and C region. The B region complexes are identical in nuclear extracts from IL-6-treated and untreated cells. While important for IL-6 induction in the context of the haptoglobin promoter, the B site does not confer IL-6 inducibility to the SV40 promoter. Our results indicate that the IL-6 response of the haptoglobin promoter is dependent on the presence of multiple, partly redundant, cis-acting elements.
 ...
PMID:The human haptoglobin gene promoter: interleukin-6-responsive elements interact with a DNA-binding protein induced by interleukin-6. 278 45

Haptoglobin is a plasma protein scarcely present in fetal but abundant in adult serum, where it is present at a concentration of approximately 150 mg/100 ml. In this paper we show by run-on experiments that the haptoglobin (Hp) gene is actively transcribed in adult but not in fetal liver nuclei. Studies with established cell lines indicate that the Hp gene is expressed in the hepatoma cells HepG2 but not in the hepatoma cell line Hep3B nor in HeLa cells. Plasmids carrying various segments of the 5' flanking region of the Hp gene fused to the chloramphenicol acetyl transferase (CAT) gene direct CAT transcription when introduced into HepG2 but are inactive in Hep3B and in HeLa cells, thus behaving like the resident chromosomal Hp gene. Deletion analysis defines a region, upstream to the transcription initiation site, essential for cell-specific expression. The Hp gene is induced in Hep3B cells by treatment with supernatant from LPS-stimulated monocytes (SMS), in a manner mimicking the acute phase reaction. We characterize the DNA segment necessary and sufficient for cell-specific expression of the Hp-CAT constructions in HepG2 and show that the same segment is also sufficient for acute phase induction in Hep3B.
 ...
PMID:The human haptoglobin gene: transcriptional regulation during development and acute phase induction. 282 Jul 12

Human hepatoma cells mimic the acute phase response after treatment with monocyte-conditioned medium. Levels of secreted fibrinogen, alpha-1 acid glycoprotein, C-reactive protein, haptoglobin, and the third component of complement were elevated compared with control levels after 48 h of incubation with conditioned supernatant medium from an enriched fraction of normal peripheral monocytes. Albumin levels declined and alpha-1 antitrypsin remained unchanged. Levels of specific mRNA were measured by hybridization to slot blots and Northern blots and changed in correspondence with protein alterations. Interleukin-1 and tumor necrosis factor stimulated the third component of complement, but did not elevate any other member of the acute phase group and were therefore only partially active in this system. The identification of an in vitro model of the human acute phase response will permit analysis of the molecular basis for coordinate regulation of this group of facultative genes.
 ...
PMID:Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hepatoma cells in vitro. 301 95

Effects of dimethyl sulphoxide (Me2SO) on the synthesis of plasma proteins by the human hepatoma cell line HepG2 were examined. Me2SO treatment resulted in decreased synthesis of albumin and alpha-fetoprotein, and in increased synthesis of haptoglobin. Plasma-protein profiles induced by Me2SO treatment were very similar to those seen in acute-phase reactions.
 ...
PMID:Effects of dimethyl sulphoxide on the synthesis of plasma proteins in the human hepatoma HepG2. Induction of an acute-phase-like reaction. 314 Jul 93

Nine hundred and ninety nine patients were admitted in our Department (the Third Department of Internal Medicine, School of Medicine, UOEH) during the five years more since the opening date of the University Hospital (July, 9, 1979), and 864 cases in them (86.2%) suffered from the various digestive diseases. Most of the in-patients with digestive diseases in our Department are resident in Kitakyushu city and its suburbs, especially in Yahatanishi-ku, Wakamatsu-ku and Onga county, therefore, it may be possible to investigate the ecological characteristics of the in-patients of our Department in the relation to the outbreak, clinical course and outcome of the digestive diseases. Namely, it may be assumed that the incidence and prevalence of the idiopathic inflammatory bowel disease (IBD) including ulcerative colitis and Crohn's disease are relatively high in this area (Kitakyushu city and its suburbs) as compared with the average of all Japan. Although the true causes of these illness are still unknown, the inclination of haptoglobin phenotypes (HP) which include 2-2, 2-1 & 1-1 type 1-1 strongly suggests to the association with some genetical factors on the high incidence of these diseases (IBD). In this connection, Hp type 1-1 were recognized 4 in 11 cases (36.4%) with ulcerative colitis, and 3 in 7 cases (42.9%) with Crohn's disease in our Department whereas only 3-5% in normal controls. Secondly, the patients with carcinoma of the biliary tree (bile duct and gall bladder) are relatively more, namely, 17 cases of bile duct cancer and 3 cases of gall bladder cancer were admitted in our Department during this term. It is interesting to note that hepatohilar type of the bile duct cancer was observed comparatively high (4 in 17 cases, 52.9%) in the past five years-more although the etiology is unknown. Finally, several characteristics in liver diseases particularly in viral hepatitis were illustrated in this study, namely, the ratio of transient HBV infection to whole (transient and persistent) HBV infection in the patients with acute viral hepatitis (due to HBV) is high (80.9%), HBeAg positivity is high in chronic B-hepatitis (44.9%), the ratio of alcoholic cirrhosis to whole liver cirrhosis is relatively high (34.9%) and HBsAg positivity is lower in liver cirrhosis due to non-alcoholic origin (mainly due to hepatitis virus) than the average of this country, and also, hepatocellular carcinoma (HCC) without liver cirrhosis is higher (23.0%) than the average of whole Japan (less than 15%) statistically.
 ...
PMID:[Ecological approach to the patients with digestive diseases in Kitakyushu City and its suburbs]. 372 13

The antiproteinase activities against trypsin, chymotrypsin, elastase, papain and rat leucocyte proteinases were determined in plasma from control and Morris hepatoma-bearing rats. Bovine trypsin and chymotrypsin were similarly inhibited by the two types of plasma whereas porcine pancreatic elastase, papain and rat leucocyte neutral proteinases were more efficiently inhibited by plasma from tumour-bearing rats. The increased plasma concentrations of some proteinase inhibitors, as determined by rocket immunoelectrophoresis, are suggested to be responsible for the observed differences in inhibition. The highest increases in plasma of tumour-bearing rats were observed for alpha 2-macroglobulin and alpha 1-acute-phase globulin. The synthesis and secretion of six proteinase inhibitors: antithrombin III, alpha 1-proteinase inhibitor, alpha 1-macroglobulin, alpha 2-macroglobulin, alpha 1-acute-phase globulin and haptoglobin, as well as albumin, were measured in tissue slices from rat liver and Morris hepatoma after incubation with [14C]leucine. Local inflammation inflicted upon the tumour-bearing rats increased formation of acute-phase proteins in liver slices but not in hepatoma slices.
 ...
PMID:Plasma proteinase inhibitors in Morris hepatoma-bearing rats: changes in the blood level and synthesis in tissue slices. 407 27

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.
 ...
PMID:Expression of human hepatic genes in somatic cell hybrids. 618 Apr 90


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