Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A continuous adherent cell line was established from a hepatocellular carcinoma of an HBsAg-positive Italian male. This cell line, designated Tong/HCC, has been grown in a hormone-supplemented medium for more than 18 months. The cell line secretes HBsAg, alpha-fetoprotein, albumin and alpha 1-antitrypsin. alpha-Fetoprotein production is enhanced by the addition of hydrocortisone and appears to be glucocorticoid concentration-dependent. The concentrates of the supernatant from the cell cultures and cell lysates were negative when tested for HBeAg. The cell culture medium was negative for hepatitis B virus DNA when tested by dot-blot hybridization. However, hepatitis B virus DNA was found to be integrated in the chromosomal DNA by Southern blot analysis. At least five different integration sites were identified, and no free hepatitis B virus DNA was observed. The modal chromosome number was 64, and a translocation on Chromosome 15 was consistently noted. HLA typing revealed sites for A3, Aw24, Bw34 and Cw1.
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PMID:Characteristics of a cell line (Tong/HCC) established from a human hepatocellular carcinoma. 244 44

Relationship between blood transfusion and cancer is considered from five points of view: 1) The cancer patient as a blood donor. Cancer must remain a cause of exclusion from blood donation. 2) Autologous blood transfusion for cancer patients. Predeposited autologous blood transfusion is only possible for a small number of patients. Intraoperative blood salvage carries with it the risk of disseminating tumor cells. 3) History of blood transfusion and the risk of having a cancer: a) the persistence of immune alterations following blood transfusion for years might expose the patient to an increased risk of having a cancer; b) blood transfusion might carry immunosuppressive viruses, and hepatitis viruses are related to the risk of liver cancer. 4) Cancer recurrence and blood transfusion. Conclusion of most of the published studies is that blood transfusion is associated with an increased risk of recurrence of colorectal cancer. The only realistic randomized study would compare different transfusion strategies (allogenic, leukocyte poor allogenic and autologous blood transfusion) to determine which is the best for cancer patients. 5) Post-transfusion GVH in cancer patients. Some cases have recently been published. They all can be explained by a particular HLA compatibility between the recipient and one of the blood donors.
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PMID:[Transfusion and cancer]. 804 22

HHC is the most common inherited metabolic disease among the white population worldwide, with a gene frequency of about 10% and a frequency of homozygosity of about 1 of 250. Many patients harbor a common haplotype of informative markers on chromosome 6p2l.23, suggesting a strong founder effect exerted by a common Celtic ancestor. With the advent of screening tests (serum Tf saturation, fe), many subjects with HHC are being identified before development of cirrhosis or diabetes mellitus, and early detection is important because prompt and vigorous iron reduction prevents development of such complications and assures normal life expectancy. The HIC can be estimated as accurately by specialized magnetic resonance imaging or susceptometric measurements as by chemical measurements on liver biopsy specimens. However, biopsy specimens retain value for showing fibrosis/cirrhosis and dysplastic hepatocytes, both of which increase risks of HCC development. There is growing evidence that iron in the liver plays an important role in non-HHC diseases, such as alcoholic liver disease, chronic viral hepatitis, and porphyria cutanea tarda. The complicated, manifold roles of iron in pathogenesis of the latter disorder include enhancement of production and irreversible oxidation of uroporphyrinogen, as well as formation of an inhibitor targeted specifically at hepatic uroporphyrinogen decarboxylase. The nature of the gene and gene product that are abnormal in HHC remain elusive, despite the intense efforts of several investigative groups. The search has been hampered by a dearth of informative markers in HHC patients in the relevant region of chromosome 6p. Note added in proof: The cloning of a candidate gene, the mutation of which may perhaps cause HLA-linked hemochromatosis, has just been reported (Feder et al: A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature (Genetics) 1996;399-408). These workers identified a 250-kb region move than three megabases telomeric of the MHC that was identical in 85% of chromosomes of HHC patients. Within this region, they identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations one of which is predicted to inactivate this class of proteins. 83% of 178 patients were homozygous for this mutation (Cys 282Tyr). This variant was also found on 3.2% of control chromosomes, as would be expected for such a common disorder. Functional studies are awaited with great interest.
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PMID:An update on iron metabolism: summary of the Fifth International Conference on Disorders of Iron Metabolism. 878 49

We investigated T cell immunity against hepatocellular carcinoma (HCC), and showed that both peripheral blood mononuclear cells and tumor-infiltrating lymphocytes incubated with interleukin-2 alone displayed HLA-nonrestricted but hepatic cancer-specific cytotoxicity in a majority of patients with HCC. Namely, they lysed both HCC and cholangiocellular carcinomas in an HLA-nonrestricted manner, but they did not lyse any tumors with the other histological types tested, normal hepatocytes, or the cells transfected with hepatitis C virus or MUC1 gene. These CTL lines and clones were phenotypically CD3+CD4+CD8-. These unique CTL could play important roles in T cell immunity against HCC.
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PMID:CD4+ hepatic cancer-specific cytotoxic T lymphocytes in patients with hepatocellular carcinoma. 917 45

Soluble HLA-class I and CD8 molecules were determined by sandwich ELISA in patients with viral-induced hepatic disorders. As a whole, the patients with hepatic disorders (acute hepatitis: AH; chronic hepatitis: CH; liver cirrhosis: LC; hepatocellular carcinoma: HCC) showed higher sHLA-class I and sCD8 levels than normal controls (P < 0.001). AH patients had the highest sHLA-class I levels (mean, 3513 +/- 2112 ng/ml), followed by CH (2896 +/- 1290 ng/ml), LC (2293 +/- 1266 ng/ml), and HCC (2221 +/- 1212 ng/ml) sCD8 levels wer highest in AH, followed by HCC, LC, and CH, in that order. Among histologically defined C virus-positive patients, sHLA-I levels were higher in those with chronic active hepatitis (CAH) 2A (3802 +/- 1124 ng/ml) than in those with chronic persistent hepatitis (CPH; 2200 +/- 711 ng/ml; P < 0.01), the levels then decreased as the disease progressed (CAH2B, 3564 +/- 1783 ng/ml, LC, 2376 +/- 1265 ng/ml). In contrast, sCD8 values showed little difference among the disorders. sHLA-class I levels showed a positive correlation with sCD8 values both in whole patients and in patients with AH (P < 0.01), but no correlation was shown, in any patients, with biochemical parameters such as GPT and GOT. These findings, taken together, suggest that hepatic destruction is not the only cause of sHLA-class I production, but that sHLA-class I levels, together with sCD8 levels, may reflect immunological activity in hepatic disorders.
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PMID:Serum concentrations of soluble HLA-class I and CD8 forms in patients with viral hepatic disorders. 921 47

Two adults with primary liver cancer underwent liver transplantation from 5/6 and 4/6 major HLA-antigen mismatched unrelated donors. They were then conditioned with 4 x 2 Gy of total lymphoid irradiation, 120 mg/kg cyclophosphamide, 7.5 Gy total body irradiation and anti-T cell antibodies. Thereafter, the patients received T cell-depleted autologous: unrelated mismatched bone marrow in a proportion of 0.5:3.0 and 0.35:1.1 x 10(6) CD34+ cells/kg, respectively. After allogeneic stem cell transplantation (ASCT), both became mixed chimeras, as determined with polymerase chain reaction amplification of variable number tandem repeats from DNA obtained from CD3+, CD19+ and CD45+ magnetic bead-separated cells. Due to a reduction in donor T cells, the first patient was given 10(5) donor T cells/kg and became a complete donor chimera within 3 months. The second patient rejected all donor cells within 1 month after ASCT. Leucocytes normalized in both patients within 1 month. CD8+ cells normalized after 4 and 2 months in the two patients, respectively. However, CD4+, CD56+ and CD19+ cells remained low, except for a transient increase in patient 2. Lymphocyte responses to mitogens were negative in patient 1 from 1 to 5 months after ASCT. This patient also showed an oligoclonal pattern of the B cell repertoire, performed by CDR3 spectratyping. Epstein-Barr virus DNA in lymphocytes increased by 4-5 log in both patients. Prior to ASCT, recipients and donors were mutually reactive in mixed lymphocyte cultures (MLC). In the first patient, who became a complete donor chimera, the chimera cells showed no response to recipient or donor, but a positive response to third party. In the other patient, recipient cells reacted vigorously against donor lymphocytes at the time of rejection. Both patients suffered from overwhelming bacterial, fungal and viral infections, and died of pneumonia 5 and 3 months after ASCT, respectively. To conclude, with a major HLA-mismatch barrier, stable mixed chimerism seems difficult to achieve. The first patient became a full donor chimera and the second one rejected the graft. Both suffered from immune incompetence.
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PMID:Poor immune reconstitution after four or five major HLA antigens mismatched T cell-depleted allogeneic and autologous stem cell transplantation. 1116 14

The course of hepatitis B virus (HBV) infection may be influenced by the host immune response. A prospective study was carried out in ninety-eight subjects (mean age = 23 years) HBs antigens carriers of hepatitis B and living in Dakar, Senegal. We analysed the HLA-A, -B, and C antigens distribution compared to that one of a control (HBs negative) healthy senegalese population (n = 96) living in Dielmo village where a longitudinal study was set-up since 1990. The HLA class I typing was performed by microlymphocytotoxicity assays. The most frequent HLA-A, -B, -C antigens found were: locus A: A23 (33.6%), A2 (25%), A30 (25%), locus B: B8 (31%), B7 (16.3%), B58 (11.9%), B35 (11%), B49 (11%), B53 (10.8%) and locus C: Cw7 (39.1%), Cw17 (39.1%), Cw3 (36.9%), Cw4 (36.6%). Significant differences (P < 0.001) were found between the donors and the control group for the following HLA antigens: A1, A23, B8 and Cw3. The detection of HBe antigen was positive in 26/84 blood donors. It was observed a significant difference (p < 0.01) between positive and negative HBe donors for HLA-A1 allele with an odds ratio of 6.25. All the donors carrying the HLA haplotype: A1-B8-Cw7 (11.5%) were positive in HBe antigen. HLA: B8-Cw7 haplotype (detected in 8.5% of positive donors) seems to be likely associated with a liver cancer according to many reports. An adequate follow-up should be set-up for positive HBe subjects carrying a susceptible HLA type.
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PMID:[Association between Class I HLA alleles and HBs antigen carrier status among blood donors in Senegal]. 1195 79

Human HCC cell lines (BEL-7402, SMMC-7721 and QGY-7703) do not express CD80 molecules, although they express MHC class I molecules and ICAM-1. HCC's poor immunogenicity may therefore be due to lack of CD80 molecules. This study first investigated whether CD80 molecules could provide minimal co-stimulatory signal for establishing an efficient anti-tumor immunity in HCC and second, whether the transfection of CD80 into the BEL-7402 cell line could induce T cell activation for targeting other HCC cell lines expressing shared common antigens. The transfection of cDNA encoding CD80 into ICAM-1+ HCC BEL-7402 cells was confirmed by flow cytometrical analysis. The CD80-transfected cells could enhance the immunogenicity of BEL-7402 cells as detected by T cell proliferation assay, and also activated the T cells at a higher proliferation rate comparing with the BEL-7402 cells transfected with vector only. The CD80-transfected cell line was also found able to activate T cells which subsequently induced cell lysis of SMMC-7721, QGY-7703 and parent BEL-7402 cell lines as detected by cytotoxicity assay. It can be concluded that the cytotoxicity was due to MHC class I restricted CD8+ cytotoxic T lymphocytes, but not natural killer (NK) cells, since this cytotoxic effect could be blocked by anti-MHC class I antibody and the cytotoxicity was shown very low in NK-cell-sensitive K562 cell line. Electroporation of CD80 cDNA into human HCC cells could increase the expression of the functional CD80 molecules and enhance the immunogenicity of the genetically-modified HCC cells to activate T cells for targeting 3 HCC cell lines in an HLA-restricted manner.
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PMID:CD80 transfected human hepatocellular carcinoma cells activate cytotoxic T lymphocytes to target HCC cells with shared tumor antigens. 1525 13

Epitope-based vaccination strategies designed to induce tumor-specific CD8 CTL are being widely considered for cancer immunotherapy. HLA-A2-transgenic mouse is a useful tool for measuring the CTL responses in vitro. However, tumor vaccine development is required to address the variables that are not easily evaluated by in vitro assays. With the objective of extending the usage of A2-tansgenic mouse in vaccine efficacy assay, here, we established a B16 tumor cell line coexpressing HLA-A*0201/H-2Kb chimeric gene and a polyepitope construct based on the use of a mammalian expression vector pIRES. The value as a tool for evaluating the antitumor efficacy in vitro as well as in experimental tumor challenge model in vivo has been tested. We found that priming with the polyepitope construct and boosting with the mixture of peptide in A2-transgenic mice resulted in: (1) CTL responses not only against the peptide-sensitized T2 and SW480 cell lines but also the non-sensitized reconstructed B16 cell line; (2) expression of HLA-A*0201/H-2Kb chimeric gene and polyepitopes by B16 led to its rejection by immunized A2-transgenic mice. These data established that the reconstructed B16 cell line stably expressed and efficiently presented the HCC-derived CTL epitopes, making B16 based melanoma suitable for the evaluation of the antitumor efficacy of immune responses to these epitopes. Collectively, these data indicate that the use of this method allows for directly testing of HLA-A2 restricted epitope immunogenicity in the A2-transgenic mice.
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PMID:Evaluation of antitumor immunity efficacy of epitope-based vaccine with B16 cell line coexpressing HLA-A2/H-2kb and CTL multiepitope in HLA transgenic mice. 1741 55

The paper highlights the role of different HLA class II molecules in hepatic and lymphoproliferative HCV-related disorders. HLA molecules have been reviewed, according to an in silico cluster classification, based on the sequence, the biochemical structure of the pockets, and the functional characteristics of the HLA II molecules. Thus, by reducing the complexity of HLA II polymorphism, characteristics that unite different HLA molecules with specific HCV-associated pathologies may be recognized with greater case. Results show that HLA clusters associated with better dlimination of the virus are protective against HCC development, while the same clusters are associated with a higher risk of developing cryoglobulinemic syndrome and the concomitant NHL. These data added further acknowledgements on pathogenetic mechanisms associated with HCV infection. Results also highlight differences of NHL occurring in HCV-positive subjects, with or without a concomitant type II autoimmune cryoglobulinemic syndrome, suggesting that cryoglobulinemic background associated with NHL should be considered in the evaluation of the effectiveness of new therapies in the course of HCV-associated NHLs.
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PMID:Role of the HLA class II: HCV-related disorders. 1780 59


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