Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

To investigate a new kind of anti-tumor immunological cells and improve surgical results of hepatocellular carcinoma by anti-recurrence application, we activated T cells isolated from tumor infiltrating lymphocytes by double stimulating signals: the one was autologus HCC cells which were treated with IFN-gamma and TNF-alpha for enhancing expression of MHC class I and presented tumor antigen, and the other was costimulation signals which was from ICAM-1 and B7 molecules expressed on treated HCC cells as well as CD28 mAbs. Activated T cells which bound to HCC cells were expanded selectively as tumor specific cytotoxic T lymphocytes (TS-CTLs), their cytotoxic activity in vitro and anti-tumor effects in vivo were observed. Our results suggested that TS-CTLs expressed high cytotoxicity against autologous HCC cells with MHC class I restriction manner. Adoptive TS-CTLs treatment could decrease serum AFP level, inhibit ascites formation and prolong survival in SCID mice bearing human HCC. In clinical trail of 12 cases of HCC, TS-CTLs treatment was able to delay tumor recurrence after HCC resection. Our data demonstrated that TS-CTLs as new immunological treatment modality, are of great value in further application of tumor comprehensive management.
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PMID:[Experimental and clinical research of cytolytic T lymphocytes specific for hepatocellular carcinoma]. 1037 86

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

Natural killer (NK) cells are important effector cells for the first line of defense against tumor. Distant MHC class I homolog MICA has been identified as human ligand for NK cell activating receptor NKG2D. Engagement of MICA triggers NK cells and augments antigen-specific CTL anti-tumor immunity. However, the expression level of MICA and its clinical significance in hepatocellular carcinoma remains to be elucidated. In the present study, a hospital-based study cohort of 143 HCC patients was involved. MICA expression levels were determined by immunohistochemical staining. The association of MICA expression with tumor clinicopathologic features, disease-free survival, and overall survival of HCC patients were analyzed. Significantly decreased expression of MICA was detected in tumor specimens. MICA expression was significantly associated with AFP level (P < 0.001) and tumor node metastasis stage (P = 0.003). Patients with reduced level of MICA had a statistically significantly shorter disease-free survival and overall survival duration than patients with preserved expression of MICA. However, in multivariate analysis, MICA expression level was found not to be an independent prognostic factor for both disease-free survival and overall survival of HCC patients. Our findings suggest that decreased MICA expression may play an important role in HCC tumor evasion of host immunity, which warrants further investigation in future studies.
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PMID:Loss of expression of MHC class I-related chain A (MICA) is a frequent event and predicts poor survival in patients with hepatocellular carcinoma. 2503 31