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)

Costimulation mediated by costimulatory molecules, such as B7-1 and B7-2, which are ligands for the CD28/cytolytic T lymphocyte associated antigen (CTLA)-4 counter-receptor, plays an important role in the induction of T cell-mediated antitumor immunity. We investigated the expressions of B7-1, B7-2, and human leukocyte antigen (HLA) class I in seven human hepatocellular carcinoma (HCC) cell lines by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometric analysis. RT-PCR showed that all these human HCC cell lines were positive for B7-1 and B7-2 at the messenger RNA (mRNA) level. Flow cytometric analysis revealed that they all expressed B7-1, B7-2, and HLA class I on the cell surface. However, the expression levels of B7-1 and B7-2 were very low whereas those of HLA class I were high. B7-1 and B7-2 expression could be increased by treatment with interferon alpha and interferon gamma in a dose-dependent manner, although the expression levels of B7-1 and B7-2 after interferon treatment remained low. By transfecting Hep3B cells with a plasmid containing human B7-1 complementary cDNA (cDNA), we were able to establish Hep3B cell lines strongly expressing B7-1. From mixed lymphocytes and tumor cultures analysis, the primary cytolytic activity against parental Hep3B cells could be induced effectively by B71-transfected Hep3B cells. These findings suggested that B7-1 gene transfer is the best way to induce strong expression of this molecule and this might be useful for immuno-gene therapy against human HCC.
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PMID:Expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on human hepatocellular carcinoma. 914 26

We established a cytotoxic T lymphocyte (CTL) clone directed against an autologous hepatocellular carcinoma (HCC) cell line SUHC-1 which had been established in our department from a patient with HCC associated with hepatitis C virus infection. The CTL clone lysed autologous SUHC-1 cells but did not lyse autologous Epstein-Barr (EB) virus-transformed B cells, natural killer (NK) cell-sensitive erythroleukaemia cell line K562, the NK-resistant B cell line Daudi, or allogeneic HCC cell lines, Hep-G2, Hep-3B, Mahlavu and PLC/PRF/5. The CTL clone expressed CD3 and CD8 molecules. The cytotoxic activity of the clone was inhibited by anti-CD3, anti-CD8 and anti-histocompatibility antigen (HLA) class I monoclonal antibodies. These results indicated that the CTL clone recognized HCC tumour antigen in an HLA class I-restricted manner. Furthermore, we investigated the T cell receptor (TCR) gene usage of the CTL clone. The CTL clone expressed TCR alphabeta. We searched for expression of TCR variable (V) alpha and beta regions and sequenced complementary determining region (CDR) 3 of the clone. The clone expressed V alpha14, junctional (J) region alpha9.7 and V beta7, J beta2.1. The amino acid sequence of the N region of the of chain was S-P-G-G-G-G-A-D-G-L-T and of the N-D-N region of the beta chain was S-W-T-G-A-S-T-D-T-Q-Y. These results suggested that HLA class I-restricted CTL play an important role in the elimination of human HCC cells.
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PMID:Cytotoxic T lymphocyte clone specific for autologous human hepatocellular carcinoma cell line SUHC-1. 973 68

Human leukocyte antigens (HLA) class I molecules can be detected in "soluble" form in the supernatant of cultured cell lines and in serum and plasma of humans. These "soluble" HLA class I molecules are assumed to play a role in liver transplantation. In order to define the nature and composition of HLA class I molecules found in solution, we studied the HLA class I production of an hepatoma carcinoma cell line (HepG2) and of EBV-transformed B-cell lines. Based on molecular weight (MW) analysis, it was demonstrated that different forms of HLA class I molecules were produced by HepG2 cells and EBV B-cells. Monoclonal antibodies (mAbs) specific for HLA class I alleles were able to recognize the mature 45 kDa form, but failed to interact with the 42 kDa and 39 kDa MW forms of HLA class I. Of these different MW forms of HLA class I molecules the mature 45 kDa product was found predominantly to be associated with subcellular vesicles whereas the alternative MW forms of 42 kDa and 39 kDa exist as truly free entities in supernatants.
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PMID:Detection and characterization of HLA class I molecules in the supernatant of an hepatocarcinoma cell line and of EBV-transformed B cell lines. 1044 3

Hepatitis B, C, and D viruses can infect liver cells and in some individuals establish a chronic phase of infection. Presently, relatively little information is available on the antiviral mechanisms in liver cells. Because no good in vitro model infection systems for hepatitis viruses are available, we have used influenza A, Sendai, and vesicular stomatitis (VSV) viruses to characterize interferon (IFN) responses and IFN-induced antiviral mechanisms in human hepatoma cell lines. HepG2 or HuH7 cells did not show any detectable IFN-alpha/beta production in response to influenza A or Sendai virus infections. Treatment of cells with IFN-alpha resulted in upregulation of IFN-alpha-inducible Mx, 2',5'-oligoadenylate synthetase (OAS) and HLA class I gene expression but only with exceptionally high levels of IFN-alpha (>/=100 IU/ml). Accordingly, high pretreatment levels of IFN-alpha, 1000 IU/ml for influenza A and VSV and 100 IU/ml for Sendai virus, were required before any detectable antiviral activity against these viruses was seen. IFN-gamma had some antiviral effect against influenza A virus but appeared to be ineffective against VSV and Sendai virus. IFN-gamma upregulated HLA class I protein expression, whereas Mx or OAS expression levels were not increased. There was a modest upregulation of HLA class I expression during Sendai virus infection, whereas influenza A virus infection resulted, after an initial weak upregulation, in a clear decrease in HLA class I expression at late times of infection. The results suggest that hepatoma cells may have intrinsically poor ability to produce and respond to type I IFNs, which may contribute to their inability to efficiently resist viral infections.
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PMID:Impaired antiviral response in human hepatoma cells. 1054 9

It has been proposed that tumor cells frequently associated with partial or total loss of HLA class Ia expression may abnormally express HLA-G class Ib antigen. Such peculiar HLA class I expression would allow tumor cells to escape not only from CD8+T but also from NK-cell cytotoxicity. We studied the cell surface expression of HLA-G using flow cytometry with two HLA-G specific monoclonal antibodies (87G, 01G). The JEG-3 choriocarcinoma cell line, which constitutively expresses HLA-G antigens was used as a positive control. We did not detect the cell-surface HLA-G antigens in the following 75 tumor cell lines: melanoma (22), neuroblastoma (7), retinoblastoma (1), glioma (2), breast carcinoma (3), ovarian carcinoma (3), cervical carcinoma (1), colon carcinoma (3), bladder carcinoma (2), hepatocarcinoma (1), sarcoma (2) and leukemia cell lines: T-lymphocytes (6), B-lymphocytes (13) and myelo-monocytes (9). We found that some myelomonocytic cell lines express on their surface high affinity FcgammaRI (CD64) that may result in the binding of HLA-G specific mabs to their cell surface even in the absence of HLA-G molecules. Our panel of HLA-G negative tumor cell lines accommodated 62 cell lines for which similar analysis have not been reported and also contained 13 cell lines with total or partial loss of HLA class Ia molecules. Our observation imply that under normal culture conditions the cell surface HLA-G reactive with 87G and 01G mabs is absent in most tumor cell lines of different origin.
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PMID:Expression of the non-classical HLA-G antigen in tumor cell lines is extremely restricted. 1126 57

A hepatoma cell line, Hep G2, reveals the diminished HLA class I surface expression and the reduced expression of LMP2, LMP7, and tapasin transcripts, suggesting that the reduced expression of these transcripts may be associated with the low expression of HLA class I molecules. Introduction of tapasin gene dramatically up-regulates the surface expression of HLA class I molecules on Hep G2 cells, and unexpectedly, enhances the expression of LMP2 and LMP7 transcripts as well. Unlike Hep G2, these tapasin-transfected Hep G2 cells are recognized by allo-specific CTL. However, the transfectant is unable to endogenously present an HIV envelope peptide to an HIV-specific CTL clone, suggesting that a proteasome-independent antigen processing pathway exists and still remains defective in the transfectant. These data may provide significant evidence that the nonproteasomal antigen processing pathway as well as the proteasomal pathway may be impaired in tumor cells to escape immune surveillance performed by CTL.
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PMID:Introduction of tapasin gene restores surface expression of HLA class I molecules, but not antigen presentation of an HIV envelope peptide in a hepatoma cell line. 1144 72

AIM:To investigate the therapeutic potential of gamma interferon (IFN-alpha) genemodified human hepatocellular carcinoma (HCC) cells.METHODS:The IFN-alpha gene was introduced retrovirally into four HCC cell lines.Secreted IFN-alpha activity was assessed using bioassay. The expression of MHC molecules was detected by FACS.Tumorigenicity was analysed by tumor formation in nude mice.RESULTS:Four IFN-alpha gene transduced HCC cell lines secreted different amounts of IFN-alpha, as in the same case of five clones derived from one HCC cell line. Transduction with IFN-alpha caused significant increase in the expression of major histocompatibility complex (MHC) antigens on HCC cells. The expression of HLA class I was increased by 2-3 times in terms of mean fluorescence intensities, while for class II expression, the percentage of positive cells augmented from < 10% to &lg 50%. When equal amount of tumor cells were injected into nude mice, the tumor igenicity some transduced cells decreased dramantically.CONCLUSION:IFN-alpha gene transduction can convert weakly imunogenic HCC cells to activate antitumor immune response, and further pave the way for the future use of such gene modified tumor cells as a modality for the cancer immunotherapy.
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PMID:Transduction of human hepatocellular carcinoma cells with human alpha-interferon gene via retroviral vector. 1181 77

Virus variants escaping from host immunity may be implicated in the pathogenesis of hepatitis B virus (HBV) infection. In this cross-sectional study, the association was evaluated of the frequency of amino acid variation within the immunogenic epitopes of surface gene with different disease stages of chronic HBV infection. The surface gene of HBV encompassing the a determinant (amino acids 124-148) and the putative HLA class I restricted cytotoxic T lymphocyte (CTL) epitope (amino acids 28- 51) were amplified and directly sequenced in 33 asymptomatic carriers (Group I), 31 patients with chronic hepatitis (Group II), 22 with cirrhosis (Group III), and 36 with hepatocellular carcinoma (Group IV). The amino acid sequences were compared subsequently with the consensus sequences of HBV serotype adw or adr. The frequency of amino acid variation per site per sequence (FEQ) was analyzed by generalized estimating equation with Poisson model after stratification by clinical and virological features. The FEQ was 1.21% overall, and was highest in Group IV patients and in patients above 50 years of age. In contrast, nine Group IV patients aged below 50 years who were infected with serotype adw had an inversely higher FEQ than those above 50; the age effect among hepatocellular carcinoma patients was significantly different from that among non-cancerous patients (P = 0.04). Variation of amino acid clustered within a determinant and CTL epitope for serotype adw but was distributed at random for serotype adr. Mutation hotspots differed between serotypes adw and adr. The FEQ of HBV surface protein is correlated positively with advancing age and severity of liver disease, and certain variants may contribute to the persistence of HBV infection.
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PMID:Naturally occurring hepatitis B surface gene variants in chronic hepatitis B virus infection: correlation with viral serotypes and clinical stages of liver disease. 1221 Apr 30

Infection by hepatitis C virus (HCV) is a growing public-health concern. After infection, 80% of infected subjects develop chronic viremia. Some developing chronic liver disease, liver cirrhosis, and hepatocellular carcinoma several years after the initial infection. The remaining 20% are able to control the infection, clearing the virus spontaneously. It is generally accepted that genes within the major histocompatibility complex play a central role in the development of the immune response against HCV. The search has focused on HLA gene products to identify disease susceptibility genes. No significant associations were shown between HLA class I and disease or response to interferon therapy. Several studies have shown an association of class II alleles with clinical outcome after HCV infection. However, which genes are associated with one outcome or another seems to depend on the ethnicity of the infected. Only spontaneous hepatitis virus clearance has been described as being strong associated with mainly, DQB1*0301 or DRB1*1101, DRB1*1104 alleles.
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PMID:[Association between HLA antigens and hepatitis C virus (HCV) infection]. 1559 39

Interferon alpha (IFN-alpha)-based therapy is the currently approved treatment for chronic hepatitis C viral infection. The sustained antiviral response rate is approximately 50% for genotype-1 infection. The major challenge to the HCV community is to improve antiviral efficacy and to reduce the side effects typically seen in IFNalpha-based therapy. One of the strategies is to identify new interferons, which may have better efficacy and less undesirable side effects. In this report, we examined the role of IL-28A (IFN lambda2), a novel type I IFN, in suppression of human hepatitis C viral RNA replication. We have cloned both the human genomic DNA and cDNA of IL-28A, and evaluated their biological activity using HCV RNA replicon cell culture system. The results show that IL-28A effectively inhibits HCV subgenomic RNA replication in a dose-dependent manner. Treatment of human hepatoma cells with IL-28A activates the JAK-STAT signaling pathway and induces the expression of some interferon-stimulated genes (ISGs), such as 6-16 and 1-8U. We also demonstrate that IL-28A induces expression of HLA class I antigens in human hepatoma cells. Moreover, IL-28A appears to specifically suppress HCV IRES-mediated translation. Although IL-28A receptor shares one subunit with the IL-10 receptor, IL-10 treatment has no detectable effect on IL-28A-induced antiviral activity. Interestingly, IL-28A can synergistically enhance IFNalpha antiviral efficacy. Our results suggest that IL-28A antiviral activity is associated with the activation of the JAK-STAT signaling pathway and expression of ISGs. The effectiveness of IL-28A antiviral activity and its synergistic effect on IFN-alpha indicate that IL-28A may be potentially used to treat HCV chronic infection.
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PMID:Novel type I interferon IL-28A suppresses hepatitis C viral RNA replication. 1614 71


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