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)

The nature of soluble factors from liver and hepatomas which inhibit [3H]thymidine incorporation into DNA was studied in Novikoff hepatoma cells. The decreased activity in hepatoma preparations was due to loss of a high-molecular-weight heat-labile factor. Although this factor cochromatographed with arginase activity on Sephadex G-150, it does not appear to result from this activity as judged by the failure of arginine to prevent the inhibitory effect on [3H]thymidine incorporation. Both liver and hepatomas contained a heat-stable factor with inhibitory activity. Studies with ethanol-soluble material suggested that the action was not solely attributable to the presence of unlabeled thymidine, since the apparent molecular weight was too high and since the factor(s) inhibited [3H]leucine incorporation into protein in addition to inhibiting [3H]thymidine incorporation in DNA.
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PMID:Soluble factors from liver and hepatomas which inhibit [3H]thymidine incorporation into DNA of Novikoff hepatoma cells. 42 2

Circulating immune complexes (CIC), complement and alpha-fetoprotein (AFP) were detected in 93 hepatitis B surface antigen (HBsAg)-positive patients with hepatocellular carcinoma (HCC), 16 patients with liver cirrhosis (LC) and 54 healthy controls. The CIC and complements were significantly higher in HCC patients than in LC patients. The complement and polyethylene glycol(PEG)-CIC in HCC patients with LC were higher than those in LC only (P less than 0.0001). The complement levels in LC patients were significantly lower than in controls. There was no difference in C3 and C4 between HCC patients and controls, while the C3 proactivator was higher in HCC patients (P less than 0.02). The C1q-CIC was higher in HCC and LC patients when compared to controls (P less than 0.0001). In patients with HCC, there was no difference in the CIC and complement levels between patients with cirrhosis and those without. There were inverse correlations between C1q-CIC and C3 (P less than 0.05), C1q-CIC and C4 (P less than 0.04). The mean level of 3% PEG-CIC and C1q-CIC increased significantly as AFP elevated, but decreased as AFP was higher than 1599 ng/ml (P less than 0.05). These results imply that CIC increase with tumor growth but further tumor burden may result in a fall in CIC, there was a shifting of CIC from complement-fixing to non-complement-fixing as AFP increased gradually.
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PMID:Relationship of serum alpha-fetoprotein to circulating immune complexes and complements in patients with hepatitis B surface antigen-positive hepatocellular carcinoma. 169 50

Serum complement C3, C4, and C3 proactivator (C3PA) have been evaluated for their diagnostic power in detecting a hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). It was found that serum complement levels were lower in LC patients than in HCC patients and that difference of the serum C4 and C3PA levels between LC patients and HCC patients were statistically significant. In addition, serum C3 PA levels were found to correlate significantly with the serum gamma-GTP levels in HCC patients. Thus, using the cutoff values of C4 and C3PA as the mean values for HCC patients, examination of serum complement levels enabled the detection of 38% of the HCC patients with low AFP levels. These findings suggest that the examination of the serum complements may be a useful a tool for the detection of HCCs in LC patients.
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PMID:[A clinical study of complements as a marker of a hepatocellular carcinoma]. 170 Jan 67

Serum complements, C3, C4, and C3 proactivator (C3PA), were evaluated prospectively for their diagnostic power in detecting hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). Sixty-three LC patients, including 36 LC with HCC patients, were recruited for this study during the period from March to November 1986. The cutoff values of the complements were set according to retrospective study including 17 LC patients and 20 HCC patients. The values with highest accuracy, 75 mg/dl C3, 16 mg/dl C4, and 18 mg/dl C3PA, were selected. Based on these data, the positive predictive values, negative predictive values, and the accuracies of complements were as follows: C3, 88.9%, 85.2%, and 87.3%; C4, 93.8%, 80.6%, and 87.3%; and C3PA, 66.7%, 90.9%, and 70.9%, respectively. The accuracy elevated to 93.7% when C3, C4, and alpha-fetoprotein were combined as the diagnostic criteria. This study supports the use of complement testing as a new diagnostic tool for HCC screening in LC patients and for follow-up evaluation in posttherapy patients of LC with HCC.
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PMID:Complements as new diagnostic tools of hepatocellular carcinoma in cirrhotic patients. 245 20

Factor I is a serine proteinase of complement which together with one of several specific cofactors cleaves activation products of the third and fourth components of complement (C3b and C4b) and modulates the activity of C3 convertase. A heterodimer glycoprotein (Mr = 88,000), factor I is synthesized as a single-chain precursor, prepro-I, which undergoes intracellular proteolytic processing. The human hepatoma line HepG2, however, secretes predominantly the single-chain precursor pro-I. In order to determine the molecular basis for this apparent processing defect, factor I cDNA clones were isolated from a HepG2 mRNA-derived library. Sequencing of the largest insert, HI1971, revealed that it contains 14 base pairs of 5' untranslated region, the complete coding sequence for the 583-residue prepro-I (NH2-signal peptide-heavy chain-linking peptide-light chain-COOH), two polyadenylation signals within the 200-base pair 3' untranslated region, and a portion of poly(A) tail. Analysis of the derived protein structure 1) reveals a mosaic multidomain structure of the heavy chain; 2) demonstrates structural similarity between intracellular conversion of pro-I and activation of other serine proteinase zymogens; and 3) indicates that the light chain of factor I resembles most closely the active subunit of tissue plasminogen activator among all serine proteinases and factor D among complement proteinases. Furthermore, this protein sequence was compared to the sequences of factor I cDNA clones isolated from normal human liver libraries and found to be identical. By exclusion, this defines as cellular the basis for the inefficient processing of pro-I by the HepG2 line. Chromosomal localization by the somatic cell hybrid method maps the factor I gene to chromosome 4.
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PMID:Human complement factor I: analysis of cDNA-derived primary structure and assignment of its gene to chromosome 4. 295 52

Decay accelerating factor (DAF), membrane cofactor protein (MCP), complement receptor 1 and mouse Crry are cell surface-bound complement regulatory proteins capable of inhibiting C3 convertase activity on cell membranes, and therefore provide a substantial protection from attack by homologous complement activated either by the classical or by the alternative pathway. Decrease in complement regulatory activity might lead to spontaneous complement deposition and subsequent cell injury. MoAb 5I2 can inhibit the complement regulatory activity of molecules on rat cells, resulting in deposition of homologous complement. The antigen recognized by 5I2 MoAb in rats is homologous to mouse Crry. Fifteen to 20 h after infection with vaccinia virus, in vitro cultured KDH-8 rat hepatoma cells show a strong decrease in expression of Crry-like antigen, and proved to be sensitive to complement deposition when 1:5 diluted normal rat serum was added to the culture medium as a source of complement. Addition of complement to the cultured KDH-8 cells infected with a very low dose of vaccinia virus (1 plaque-forming unit (PFU)/1000 cells) substantially reduced spreading of virus infection in the cell culture, while inactivation of complement by heat or zymosan treatment abrogated the protective effect.
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PMID:Membrane-bound complement regulatory activity is decreased on vaccinia virus-infected cells. 792 72

We have previously reported that in vitro HCV infection of cells of hepatocyte origin attenuates complement system at multiple steps, and attenuation also occurs in chronically HCV infected liver, irrespective of the disease stage. However, none of these regulations alone completely impaired complement pathways. Modulation of the upstream proteins involved in proteolytic processing of the complement cascade prior to convertase formation is critical in promoting the function of the complement system in response to infection. Here, we examined the regulation of C2 complement expression in hepatoma cells infected in vitro with cell culture grown virus, and validated our observations using randomly selected chronically HCV infected patient liver biopsy specimens. C2 mRNA expression was significantly inhibited, and classical C3 convertase (C4b2a) decreased. In separate experiments for C3 convertase function, C3b deposition onto bacterial membrane was reduced using HCV infected patient sera as compared to uninfected control, suggesting impaired C3 convertase. Further, iC3b level, a proteolytically inactive form of C3b, was lower in HCV infected patient sera, reflecting impairment of both C3 convertase and Factor I activity. The expression level of Factor I was significantly reduced in HCV infected liver biopsy specimens, while Factor H level remained unchanged or enhanced. Together, these results suggested that inhibition of C3 convertase activity is an additional cumulative effect for attenuation of complement system adopted by HCV for weakening innate immune response.
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PMID:Inhibition of c3 convertase activity by hepatitis C virus as an additional lesion in the regulation of complement components. 2498 75

CD55/DAF, one of the regulators of complement activation, is known to limit excess complement activation on the host cell surface by accelerating the decay of C3 convertase. We reported previously that hepatitis C virus (HCV) infection or virus core protein expression upregulates CD55 expression. CD55 associates with HCV particles, potentially protecting HCV from lysis in circulation. An increase in CD55 on the surface of HCV-infected cells may inhibit complement-mediated cell killing. In this study, we show that Abs against cancer cell surface proteins induce complement-dependent cytolysis or Ab-dependent cell-mediated cytotoxicity of immortalized human hepatocytes in the presence of CD55-blocking Ab. CD55 has a secreted isoform (sCD55) that is generated by alternative splicing. We observed that sCD55 is induced in HCV-infected or HCV replicon-harboring cells, as well as in liver biopsy samples from chronically HCV-infected patients. Conditioned medium from HCV-infected hepatoma cells (Huh7.5 cells) or immortalized human hepatocytes inhibited C3 convertase activity and complement-dependent cytolysis of sheep blood erythrocytes. Chronically HCV-infected patient sera inhibited C3 convertase activity, further implicating HCV-specific impairment of complement function in infected humans. CD55-blocking Ab inhibited erythrocyte lysis by conditioned medium, suggesting that CD55/sCD55 impairs convertase activity. Together, our data show that HCV infection induces sCD55 expression in HCV-infected cell culture-conditioned medium and inhibits C3 convertase activity. This may have implications for modulating complement-mediated immune function in the microenvironment and on HCV-harboring cells.
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PMID:Distinct CD55 Isoform Synthesis and Inhibition of Complement-Dependent Cytolysis by Hepatitis C Virus. 2735 52