UMLS:C0019204 - FACTA Search

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

The early complement components of the classical activation pathway of the complement cascade include the components C1, C4, C2, and C3. These components act in concert to opsonize bacteria, clear immune complexes, and produce inflammatory mediators. They are not structurally homologous nor are they coordinately regulated. The expression of the early complement components is divergent in terms of cytokine responsiveness and tissue specificity. The only pattern of expression shared by the early complement components is inducibility by gamma-IFN and expression in cells of hepatic or monocytic lineage. Nevertheless, four novel conserved promoter motifs were identified in the 5' flanking region of multiple early complement component promoters. Mutation of these four motifs in the C2 promoter decreased transcription in hepatoma cells in transient transfection analyses, and a synthetic promoter consisting of just the four motifs supported transcription in hepatoma cells. Electrophoretic mobility shift assays demonstrate that three of the four conserved elements bind DNA-binding proteins in a tissue-specific manner. One DNA-binding protein is expressed ubiquitously, but the other three are restricted to cells of monocytic or hepatic lineage. Two of the DNA-binding proteins appear to be members of the zinc-finger family of transcription factors. Therefore, these four motifs appear to bind DNA-binding proteins that may function in the tissue-specific expression of C2. Conservation of these four motifs in multiple early complement component genes suggests that these may represent a conserved transcriptional strategy.
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PMID:Four conserved promoter motifs regulate transcription of the gene encoding human complement component C2. 919 Sep 39

Superoxide dismutase (Cu/Zn), a metalloenzyme, activity was found to be significantly lower in the human hepatocellular carcinoma (hepatoma tissue) (0.78 +/- 0.33 U/microg protein) compared with that seen in the surrounding "normal" or cirrhotic tissue (1.40 +/- 0.48 U/microg; 1.27 +/- 0.64 U/microg). The SOD activity of "normal" appearing liver cells adjacent to the tumor or cirrhotic tissue is still lower than that level observed in the normal liver from the subjects without known liver disease (1.40 +/- 0.48 U/microg vs 2.94 +/- 1.53 U/microg). We have also observed that the trace elements of zinc and copper, which are essential in expressing the enzyme activity are also significantly lower in the hepatoma (22.54 +/- 6.73 microg and 2.83 +/- 1.16 microg per gram of tissue) compared with those in the surrounding "normal" hepatic tissue (Zn2+, 64.36 +/- 9.17 microg/g; Cu2+, 11.43 +/- 4.74 microg/g). The difference in the zinc content between the "normal" and the cirrhotic tissue is also significant (64.36 +/- 9.17 microg/g vs 42.37 +/- 10.97 microg/g). However, the copper content in the cirrhotic tissue is higher but not statistically different from that level in the "normal" tissue (15.53 +/- 5.90 microg/g vs 11.43 +/- 4.74 microg/g). Furthermore, the plasma zinc level is significantly lower among the patients who have suffered from hepatoma compared with those subjects without known liver disease (631.73 +/- 52.43 microg/L vs 845.53 +/- 68.13 microg/L). Our data suggest that the superoxide dismutase activity is impaired in the hepatoma tissue. The lower concentration of trace elements (Zn2+ and Cu2+) found in the hepatoma tissue may contribute to cause the difference in the observed enzymic activities.
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PMID:Zinc, copper, and superoxide dismutase in hepatocellular carcinoma. 939 66

Metallothionein is the carrier protein of heavy metal ions, such as copper (Cu) and zinc (Zn). In this study, the relationships among immunohistochemical expression of metallothionein, concentrations of Cu and Zn, histological differentiation and proliferative activity of hepatocellular carcinoma were investigated in 51 cases. The concentrations of Cu and Zn in both tumor and non-tumor tissues were determined using electron probe microanalysis. Immunohistochemical expression of metallothionein in tumor tissues decreased with the degree of differentiation, whereas the number of hepatocytes positive for Ki-67 increased. Furthermore, the concentrations of Cu and Zn in tumor tissues decreased with the degree of histological differentiation in human hepatocellular carcinoma.
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PMID:Metallothionein expression and concentrations of copper and zinc are associated with tumor differentiation in hepatocellular carcinoma. 945 36

During the course of long-term follow-up, we examined the efficacy of interferon (IFN) in the improvement of liver function and prevention of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) associated cirrhosis patients. Fifty-five cirrhotic patients, in whom HCC nodules in the liver were not detected by ultrasonography (US) or computed tomography (CT), received 3 or 6 million units of human lymphoblastoid IFN daily for two weeks and 3 times a week for 22 weeks. Complete response (CR) was defined as normalization of serum alanine aminotransferase (ALT) together with negative HCV RNA at 6 months after IFN therapy completion. Any other pattern of response was defined as non-response (NR). After IFN therapy the patients were followed up every 1-3 months for at least 1 year (average follow-up period, about 40 months) with serological tests and US or CT. In the 8 CR patients, the serum ALT levels remained normal and HCV RNA remained negative. Platelet count, white blood cell count, serum albumin and zinc turbidity test have recovered to the normal range at final follow-up. Ten of the 47 patients with NR have developed HCC, whereas no patients with CR has developed HCC during follow-up. We conclude that IFN improves the liver function and may prevent the development of HCC even in cirrhotic patients who show CR to IFN therapy.
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PMID:Long-term evaluation of interferon therapy in hepatitis C virus-associated cirrhosis: does IFN prevent development of hepatocellular carcinoma? 945 23

The 23 hepatectomized patients with hepatocellular carcinoma (HCC) were studied. Samples were biopsied from both cancerous portion and from non-cancerous cirrhotic portion at operation. MIB-1 LIs were measured in these biopsied samples. Then the relationships between MIB-1 LIs and pathologic feature, clinical data, and prognosis were investigated. LIs of the cancerous portion (10.2 +/- 6.8%, Mean +/- SE) were significantly (p < 0.001) greater than those of non-cancerous cirrhotic portion (3.8 +/- 2.1%). LIs of the cancerous portion in the patients who were dead with in 18 months after their hepatectomies, were significantly (p < 0.05) greater than those in the patients who survived more than 18 months after operations. LIs of the cancerous portion in the patients whose samples revealed Edmondson & Steiners classification grade III, were significantly (p < 0.05) greater than those in the patients whose samples revealed grade II. LIs of the cancerous portion in the patients whose serum AFP levels showed high level (> or = 100 ng/ml) were significantly (p < 0.005) greater than those in the patients whose serum AFP levels showed low level (< 100 ng/ml). And LIs of the non-cancerous portion in the patients whose thymol turbidity test (TTT) showed high level (> 5K-U), were significantly (p < 0.005) greater than those in the patients whose TTT levels showed within normal range. LIs of the non-cancerous potion in the patients whose zinc sulphate turbidity test (ZTT) showed high level (> 12K-U), were significantly (p < 0.01) greater than those in the patients whose ZTT levels showed within normal range. LIs of the non-cancerous portion in the patients whose PT levels were prolonged (14 sec <), were significantly (p < 0.05) greater than those in the patients whose PT levels were within range. MIB-1 LIs were proved to be a good marker for estimation of biological behaviour of HCC tumors.
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PMID:[Estimation of cell proliferation in hepatocellular carcinoma and in background liver cirrhosis, by using MIB-1 LI]. 951 65

A great number of epidemiological data have identified chronic alcohol consumption as a significant risk factor for upper alimentary tract cancer, including cancer of the oropharynx, larynx, and the esophagus, and for the liver. In contrast to those organs, the risk by which alcohol consumption increases cancer in the large intestine and in the breast is much smaller. However, although the risk is lower, carcinogenesis can be enhanced with relatively low daily doses of ethanol. Considering the high prevalence of these tumors, even a small increase in cancer risk is of great importance, especially in those individuals who exhibit a higher risk for other reasons. The epidemiological data on alcohol and other organ cancers are controversial and there is at present not enough evidence for a significant association. Although the exact mechanisms by which chronic alcohol ingestion stimulates carcinogenesis are not known, experimental studies in animals support the concept that ethanol is not a carcinogen, but under certain experimental conditions is a cocarcinogen and/or (especially in the liver) a tumor promoter. The metabolism of ethanol leads to the generation of acetaldehyde and free radicals. These highly reactive compounds bind rapidly to cell constituents and possibly to DNA. Acetaldehyde decreases DNA repair mechanisms and the methylation of cytosine in DNA. It also traps glutathione, an important peptide in detoxification. Furthermore, it leads to chromosomal aberrations and seems to be associated with tissue damage and secondary compensatory hyperregeneration. More recently, the finding of considerable production of acetaldehyde by gastrointestinal bacteria was reported. Other mechanisms by which alcohol stimulates carcinogenesis include the induction of cytochrome P4502E1, associated with an enhanced activation of various procarcinogens present in alcoholic beverages, in association with tobacco smoke and in diets, a change in the metabolism and distribution of carcinogens, alterations in cell cycle behavior such as cell cycle duration leading to hyperregeneration, nutritional deficiencies such as methyl, vitamin A, folate, pyrridoxalphosphate, zinc and selenium deficiency, and alterations of the immune system, eventually resulting in an increased susceptibility to certain viral infections such as hepatitis B virus and hepatitis C virus. In addition, local mechanisms in the upper gastrointestinal tract and in the rectum may be of particular importance. Such mechanisms lead to tissue injury such as cirrhosis of the liver, a major prerequisite for hepatocellular carcinoma. Thus, all these mechanisms, functioning in concert, actively modulate carcinogenesis, leading to its stimulation.
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PMID:Alcohol and cancer. 975 43

The roles of the bHLH-Zip protein, upstream stimulatory factor (USF), in mouse metallothionein-I (MT-I) gene expression were examined. The promoter contains a putative USF binding site which overlaps an antioxidant response element (ARE) located at -101 bp relative to the transcription start point. The USF/ARE composite element increases basal expression of the mouse MT-I gene, and partly mediates response to oxidative stress. However, other functions of this composite element and the in vivo roles for USF in MT-I promoter functions have not been examined. We report studies which indicate that USF participates via the USF/ARE element in cadmium responsiveness of the mouse MT-I promoter. During the course of these studies a second, higher affinity USF binding site at -223 bp was identified. Stable and transient transfection assays in mouse hepatoma cells, using the USF/ARE in the context of a minimal promoter and site-directed and truncation mutants of the MT-I promoter, revealed that the USF and the ARE sites contribute to cadmium (2-30 microM) but not zinc responsiveness, and to basal promoter activity. Overexpression of dominant-negative (dn)USF in co-transfection assays significantly attenuated cadmium induction of the USF/ARE in the context of a minimal promoter, and attenuated cadmium, but not zinc, induction of the intact MT-I promoter. A consensus E-box (CACATG) at -223 bp in the MT-I promoter was also found to bind USF in vitro , and to be constitutively footprinted in vivo . The interaction of USF with E-box1 was apparently 10-fold stronger than that with the USF/ARE. However, in contrast, E-box1 was not a strong basal promoter element nor was it metal ions responsive in mouse Hepa cells. In conclusion, these studies demonstrate a role for USF in cadmium-specific induction of the mouse MT-I gene, but bring into question an obligate role for USF in regulating basal activity of this gene. The data further suggest that USF interacts with ARE-binding proteins to influence MT-I gene expression.
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PMID:Participation of upstream stimulator factor (USF) in cadmium-induction of the mouse metallothionein-I gene. 980 17

Human hepatoma cells (HepG2) were exposed to several heavy metal salts and the induction of heat shock protein 70 (hsp70) mRNA was analysed by the reverse transcriptase-polymerase chain reaction (RT-PCR). Metals were added to the cell medium at concentrations ranging from 0.1 to 100 microM and incubation was continued for 4 h. In addition we analysed the time dependence of hsp70 induction by adding each metal at a certain concentration followed by an incubation for 0.5 to 24 h. CdCl2, NaAsO2, AgNO3 could be classified as very strong inducers (20-, 13- and 10-fold above control level) and they reached their maximum level of induction at 1-10 microM after 2 h. CuCl2, MnCl2, Pb(NO3)2, TlNO3, CoCl2 and NiCl2 were also strong inducing agents, giving a 4-6 fold induction at 10-100 microM after 4-8 h. ZnSO4, Hg(NO3)2 and AlCl3 were only weak inducers (1.5-2 fold at 50-100 microM after 4-8 h) of hsp70 mRNA. Cytotoxic effects (measured by release of lactate dehydrogenase) could only be detected for 100 microM Hg2+ after 4 h and when the cells were incubated with 5 microM Cd2+ for more than 8 h. We also tested a few combinations of these heavy metal salts for their hsp70-inducing ability. Zn2+ and Mn2+ were able to diminish Cd2+ induced hsp70 mRNA levels by 65%. Ag+ mediated induction was reduced by 40% when combined with Cu2+, whereas Hg2+ increased induction by Ag+ about 3-fold and led to a dramatic decrease in cell viability. In our study we were able to demonstrate that the analysis of hsp70 mRNA levels in chemically stressed HepG2 cells by RT-PCR can be a valuable tool for studying mechanisms of toxicity associated with elevated expression of hsp70.
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PMID:Analysis of hsp70 mRNA levels in HepG2 cells exposed to various metals differing in toxicity. 982 Jun 63

The expression of high- and low-molecular weight acid phosphatase (HMr- and LMr-AP) and zinc ion-dependent acid phosphatase (HMr-ZnAP and LMr-ZnAP) was compared in normal human liver and in Hep G2 human hepatocarcinoma cell line extracts. The investigation was carried out using Sephadex G-100 chromatography, molecular weight determination, and analysis of some distinctive biochemical characteristics and immunochemical properties. Normal human liver and Hep G2 cell lines expressed both HMr- and LMr-AP enzymes although in different proportions. HMr-ZnAP was detected only in human liver extract, while LMr-ZnAP was present only in hepatoma cell extract, indicating that they were differentially expressed in normal and transformed human liver cells.
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PMID:Acid phosphatase and zinc ion-dependent acid phosphatase expression in normal human liver and in Hep G2 (human hepatocellular carcinoma) cell line. 983 33

Overexpression and/or mutations of oncogenes, tumour suppressor genes and tumour rejection genes have been observed in several human malignancies. Their analyses might be of diagnostic importance. Therefore, malignant hepatocytes derived from hepatocellular carcinoma (HCC) tissue as well as non-malignant hepatocytes derived from focal nodular hyperplasia (FNH) were studied. Samples containing normal human hepatocytes (HC) served as controls. Cellular material was obtained by fine-needle aspiration biopsy guided by ultrasound. Cells were analysed for expression and mutation of the oncogene MDM2, the genes GAGE-1, -2 coding for tumour-associated antigens and the candidate tumour suppressor gene FHIT. Different patterns of non-mutant FHIT transcripts including precise deletion of exons were found in 7/10 HCC, 2/10 FNH and 2/10 HC. However, expression of non-mutant GAGE-1, -2 RNA was demonstrated exclusively in 6/10 HCC samples. Further genetic features specific of HCC were point mutations in a zinc-finger motif of MDM2 (3/10 HCC samples). Neither GAGE-1, -2 expression nor MDM2 mutations were observed in the FNH samples, or in normal hepatocytes. Our findings suggest that occurrence of variable FHIT transcripts is not restricted to hepatic malignant tumours. In contrast, MDM2 mutations and GAGE-1, -2 expression were associated with HCC specimens. Therefore, the RT-PCR assays for GAGE-1, -2 and MDM2 might be useful adjuncts in cytodiagnosis of liver neoplasms.
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PMID:Different gene expression of MDM2, GAGE-1, -2 and FHIT in hepatocellular carcinoma and focal nodular hyperplasia. 1038 81

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