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)

We previously identified, through differential screening of a human primary liver cancer library, a novel gene (named HIP) the expression of which is markedly increased in 25% of human primary liver cancers. HIP mRNA expression is tissue specific since it is restricted to pancreas and small intestine. HIP protein consists in a signal peptide linked to a carbohydrate-recognition domain (CRD), typical of C-type lectins without other binding domains. We have proposed that HIP and related proteins belong to a new family of C-type lectins. Drickamer [Drickamer, K. (1993) Curr. Opin. Struct. Biol. 3,393-400] included this group of proteins in his classification of C-type lectins as the free CRD (group VII) lectins. In the present report we describe the genomic organization and the chromosomal localization of HIP. We have shown that HIP is in fact the pancreatitis-associated protein (PAP) and provided a phylogenetic analysis of the free CRD lectins. Furthermore, the analysis of HIP/PAP gene indicates that the HIP/PAP CRD is encoded by four exons, a pattern shared with all members of this group of proteins. This common intron-exon organization indicates an ancient divergence of the free CRD-lectin group from other groups of C-type lectins. We provide evidence for the localization of HIP/PAP on chromosome 2, suggesting previous duplication of HIP/PAP and the related reg I alpha and reg I beta genes from the same ancestral gene. Finally, the sequence of the 5' upstream region of the HIP gene shows several potential regulatory elements which might account for the enhanced expression of the gene during pancreatic inflammation and liver carcinogenesis.
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PMID:Structural organization and chromosomal localization of a human gene (HIP/PAP) encoding a C-type lectin overexpressed in primary liver cancer. 807 48

Liver cancer is one of the most frequent and lethal malignancies worldwide. Early detection is hampered by the absence of reliable markers. Mice transgenic for the SV40 large T antigen under the control of a liver-specific promoter spontaneously develop well-differentiated hepatocellular carcinomas between 8 to 10 weeks of age. They are excellent models to investigate the alterations of protein expression in the early stages of tumor development and to follow these changes during tumor progression. In the present study, we analyzed the glycosylation changes occurring during tumor development in transgenic mice expressing the SV40 T antigen under the control of the antithrombin III promoter. The analysis of serum and liver glycoproteins by an ELISA type assay, using the lectin from Sambucus nigra (SNA) as a probe, revealed the presence of increased levels of Neu5Ac alpha2,6Gal beta1,4GlcNAc on N-glycans in the tumor-bearing transgenic mice as compared to controls. On serum glycoproteins the increase in alpha2,6 sialylation followed tumor progression, reaching up to 10 times control levels. However, significantly higher SNA binding (2-fold) could already be observed on serum glycoproteins from mice exhibiting only microscopically small neoplastic foci. On liver membrane glycoproteins, the increase in alpha2,6 sialylation was less pronounced, reaching two to three times control values in 6-month-old mice. Western blotting of serum and liver proteins with radiolabeled SNA showed that all glycoproteins that bind the lectin in controls exhibit larger amounts of Neu5Ac alpha2,6Gal beta1,4GlcNAc on N-glycans in the tumor-bearing mice. This general increase in alpha2,6 sialylation on all glycoproteins is due to the increased activity of the galactoside:alpha2,6 sialyltransferase (ST6Gal I), which specifically transfers Neu5Ac residues in alpha2,6 linkage to Gal beta1,4GlcNAc units on N-glycans. As for the structures synthesized by the enzyme, the increase of ST6Gal I activity in the serum as well as in liver microsomes of the transgenic mice followed tumor progression. Interestingly, the activity of the galactoside:alpha2,3 sialyltransferase (ST3Gal III), which uses the same acceptor substrate (Gal beta1,4GlcNAc), was unchanged in the earlier stages of tumor development but decreased in the serum and in liver microsomes from later stages. Using a rat ST6Gal I cDNA as a probe, Northern blots of total RNA extracted from the livers of control and transgenic mice revealed an increased (4-fold) expression of the ST6Gal I gene. The single transcripts detected in both normal and cancerous liver showed identical size.
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PMID:Increased alpha2,6 sialylation of N-glycans in a transgenic mouse model of hepatocellular carcinoma. 933 Oct 85

The serum AFP concentration in man falls rapidly after birth and its synthesis in adult life is normally repressed. However, AFP is synthesized in large amounts by human hepatocellular carcinoma in greater than 70% of patients. Elevation of serum AFP in benign hepatic diseases such as acute and chronic viral hepatitis as well as toxic liver injury is associated with small transient increases in serum AFP. Therefore, quantification of serum alpha-fetoprotein (AFP) has been widely used as a diagnostic marker for hepatocellular carcinoma. Measurement of serum AFP levels have also been used in screening populations at high risk of human hepatocellular carcinoma such as those with cirrhosis or carriers of hepatitis B virus. However the specificity of the screening test in patients with only modestly raised AFP (below 400 ng/ml) is low, and false-positive results are frequent. A wide range of overlap in the distribution of serum AFP levels between hepatocellular carcinoma and chronic liver disease patients were observed mainly among HBsAg (+) patients. Therefore the specificity and predictive value of AFP are lower in HBsAg(+) than in HBsAg(-) patients, especially when AFP is between 25 and 200 ng/ml. In patients with chronic hepatitis B, the analysis of lectin reactivity of AFP has the advantages over quantification of serum AFP to detect HCC-specific variants in serum samples with only moderate raised AFP levels. Measurement of AFP serves as an important tool in the care and management of patients with benign and malignant hepatic disorders.
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PMID:[Alpha-fetoprotein: diagnostic value in hepatic disorders]. 1096 24

The lectin-antibody enzyme immunoassay of the alphafetoprotein-L3 carbohydrate chain, a tumor marker of liver cancer, has not been automated. We improved the technique of the assay for automation. Consequently, alphafetoprotein-L3 and total alphafetoprotein were detected with two lectins using an automatic paramagnetic bead handling robot. This indicates that the improved method is potentially applicable to the automated enzyme immunoassay robot.
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PMID:Improvement of the lectin-antibody enzyme immunoassay of the alphafetoprotein carbohydrate chain for automation with the enzyme immunoassay robot. 1611 96

Mistletoe extracts are widely used in complementary and alternative cancer therapy in Europe. The extracts possess cytotoxic, as well as immunostimulatory effects. However, some investigators have suggested that low doses of mistletoe extracts could also induce tumor growth. The mistletoe extracts Helixor A, Helixor M and Helixor P were investigated for growth inhibitory and stimulatory effects in a panel of 38 human tumor cell lines in vitro. Mistletoe lectin I (ML-1), adriamycin and interleukin-6 (IL-6) were used as reference compounds. All three mistletoe preparations showed cytotoxic activity [T/C (Test/Control) < 30%]: Helixor P was the most potent, followed by Helixor M and Helixor A with IC50 (50% inhibitory concentration) values of 68.4, 114 and 133 microg/ml, respectively. The IC50 values of ML-1 and adriamycin were 0.026 and 0.069 microg/ml. None of the human tumor cell lines in the panel showed growth stimulation (T/C (Test/Control) > 125%) by the mistletoe extracts or ML-1, apart from two exceptions in the colon carcinoma cell line HCC-2998, in which Helixor M and ML-1 showed a marginal stimulation (TIC 128% and 131%, respectively) at one concentration only. Further investigations into the latter effect of Helixor M and ML-1 in the HCC-2998 line using five different proliferation assays, modified cell culture conditions and the identical production charge of mistletoe extract, as well as a new one, did not confirm the previous observation. It was concluded that the marginal stimulation found in the earlier experiments was a statistical coincidence. Helixor mistletoe preparations and ML-1 have cytotoxic activity and do not stimulate tumor cell proliferation in vitro which is in accordance with previous scientifically based observations on aqueous mistletoe extracts.
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PMID:Cytotoxic activity and absence of tumor growth stimulation of standardized mistletoe extracts in human tumor models in vitro. 1735 37

We present here an effective technique for the large-scale separation and identification of N-linked glycoproteins from Chang liver cells, the human normal liver cells. To enrich N-linked glycoproteins from the whole cells, a procedure containing the lysis of human liver cells, the solubilization of total proteins, lectin affinity chromatography including Concanavalin A and wheat germ agglutinin was established. Furthermore, captured N-linked glycoproteins were separated by 2-DE, and identified by MS and database searching. Finally, we found 63 N-glycoproteins in Chang liver cells. In addition, using the above method, we identified 7 remarkably up-regulated glycoproteins from MHCC97-H cells, highly metastatic liver cancer cells, compared to Chang liver cells. These up-regulated glycoproteins were associated with liver cancer and might be used as biomarkers for tumor diagnosis. Results showed that we established a high-throughput proteomic analysis for separating N-linked glycoproteins from human liver cells. This strategy greatly improved the glycoprotein analysis method associated with proteome-wide glycosylation changes related to liver cancer. Our work was part of the HUPO Human Liver Proteome Project (HLPP) studies and was supported by CHINA HUPO.
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PMID:Comparative glycoproteomics based on lectins affinity capture of N-linked glycoproteins from human Chang liver cells and MHCC97-H cells. 1762

The association between elevated circulating levels of GP73 (and fucosylated GP73 in particular) and hepatocellular carcinoma suggests that a thorough analysis of the extent of GP73 glycosylation is warranted. Detailed analysis of the glycosylation patterns of such low abundance proteins are hampered by technical difficulties. Using conventional lectin affinity chromatography, we have established that three quarters of the GP73 secreted from a cell line derived from HCC is fucosylated. Using mass spectrometry, we have established that at least two of three potential sites of N-linked glycosylation are occupied on most molecules of GP73 secreted from cultured hepatoma cells. Furthermore, the oligosaccharides added to recombinant GP73 resemble those present in the bulk of secreted protein, mostly bi-antennary with core fucose, with a smaller fraction of tri- and tetra-antennary structures. The frequency of fucosylation observed on the recombinant protein agrees well with the pattern of lectin binding of the endogenous secreted protein. Finally, we have developed a method to interrogate the glycans added to either the near full length protein or at a particular sequon, providing proof of concept that a small peptide embedded in a heterologous context can preserve both fucosylation and a high level of branching of oligosaccharides added.
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PMID:N-linked glycosylation of the liver cancer biomarker GP73. 1800 86

Hepatitis B and C viruses are major causative agents of liver fibrosis, cirrhosis, and liver cancer. Using comparative glycoproteomics, we identified a glycoprotein that is altered both in amount and in glycosylation as a function of liver fibrosis and cirrhosis. Specifically, this altered glycoprotein is an immunoglobulin G (IgG) molecule reactive to the heterophilic alpha-Gal epitope [Galalpha-1-3Galbeta1-(3)4GlcNAc-R]. While similar changes in glycosylation have been observed in several autoimmune diseases, the specific immunoglobulins and their antigen recognition profiles were not determined. Thus, we provide the first report identifying the specific antigenic recognition profile of an immunoglobulin molecule containing altered glycosylation as a function of liver disease. This change in glycosylation allowed increased reactivity with several fucose binding lectins and permitted the development of a plate-based assay to measure this change. Increased lectin reactivity was observed in 100% of the more than 200 individuals with stage III or greater fibrosis and appeared to be correlated with the degree of fibrosis. The reason for the alteration in the glycosylation of anti-Gal IgG is currently unclear but may be related to the natural history of the disease and may be useful in the noninvasive detection of fibrosis and cirrhosis.
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PMID:Increased levels of galactose-deficient anti-Gal immunoglobulin G in the sera of hepatitis C virus-infected individuals with fibrosis and cirrhosis. 1804 39

Hepatocellular carcinoma is the 5th most common cancer in the world. Prognosis for this disease is poor since hepatocellular carcinoma is mostly diagnosed at an advanced stage. Serum alpha-fetoprotein (AFP) is one of the most common diagnostic markers for hepatocellular carcinoma. However, its diagnostic value is more and more questioned. Therefore, research has focussed on AFP related parameters (AFP mRNA and AFP glycoforms). The aim of this paper is to review the present knowledge on AFP and its related parameters in diagnosing and monitoring HCC. AFP related parameters can be arranged in two types: AFP mRNA and AFP glycoforms. AFP mRNA is a potentially prognostic marker and AFP mRNA assays are based on PCR techniques. The AFP glycoforms have diagnostic potential and assays are based on isoelectric focussing and lectin affinity electrophoretic methods. Up to now the diagnostic use of the AFP related parameters is limited. Although some of them are recommended as a complementary test, they cannot (yet) replace serum AFP as the golden standard of diagnostic markers for hepatocellular carcinoma.
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PMID:Diagnosing and monitoring hepatocellular carcinoma with alpha-fetoprotein: new aspects and applications. 1853 35

Liver cancer is the predominant cause of cancer mortality in males of Southern China and Taiwan. The current therapy is not satisfactory, and more effective treatments are needed. In the search for new therapies for liver tumor, we found that Concanavalin A (Con A), a lectin from Jack bean seeds, can have a potent anti-hepatoma effect. Con A after binding to the mannose moiety on the cell membrane glycoprotein is internalized preferentially to the mitochondria. An autophagy is triggered which leads to cell death. Con A as a T cell mitogen subsequently activates the immune response in the liver and results in the eradication of the tumor in a murine in situ hepatoma model. The liver tumor nodule formation is inhibited by the CD8+ T cells, and a tumor antigen-specific immune memory is established during the hepatic inflammation. The dual properties (autophagic cytotoxicity and immunomodulation) via the specific carbohydrate binding let Con A exert a potent anti-hepatoma therapeutic effect. The novel mechanism of the Con A anti-hepatoma effect is discussed. The prototype of Con with an anti-hepatoma activity gives support to the search for other natural lectins as anti-cancer compounds.
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PMID:Lectin of Concanavalin A as an anti-hepatoma therapeutic agent. 1927 70


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