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 effects of lectins with different carbohydrate-binding specificities on human hepatoma (H3B), human choriocarcinoma (JAr), mouse melanoma (B16) and rat osteosarcoma (ROS) cell lines were investigated. Cell viability was estimated by uptake of crystal violet. Wheat germ lectin was the lectin with the most deleterious effect on the viability of H3B, JAr and ROS cell lines. The cytotoxicity of lectins with similar sugar-binding specificity to wheat germ lectin, including Maackia amurensis lectin and Solanum tuberosum lectin, was weaker than that of wheat germ lectin. N-acetylgalactosamine-and galactose-binding Tricholoma mongolicum lectin ranked third, after wheat germ lectin and Maackia amurensis lectin, with regard to its effect on H3B, and ranked, together with Maackia amurensis lectin, as the lectins with the second most pronounced effects on ROS. However, the cytotoxic effects of Tricholoma mongolicum lectin on JAr were much weaker than those of Maackia amurensis lectin, Solanum tuberosum lectin and Anguilla anguilla lectin. Artocarpus integrifolia lectin, Lens culinaris lectin and Anguilla anguilla lectin possessed milder cytotoxicity than the remaining lectins. which were approximately equipotent. The mannose-binding Narcissus pseudonarcissus and Lens culinaris lectins were only weakly cytotoxic, the exception being a stronger effect on H3B. The N-acetylgalactosamine-binding Glycine max lectin and methylgalactose-binding Artocarpus integrifolia lectin similarly exhibited low cytotoxicity. It can thus be concluded that in general the ranking was wheat germ lectin > Maackia amurensis lectin approximately Trichloma mongolicum lectins > other aforementioned lectins in cytotoxicity. A particular lectin may manifest more conspicuous toxicity on certain cell lines and less on others.
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PMID:Effects of lectins with different carbohydrate-binding specificities on hepatoma, choriocarcinoma, melanoma and osteosarcoma cell lines. 1071 33

Three kinds of polymeric adriamycin (ADR) conjugates of dextran were synthesized, namely a dextran-Gly-Leu-Gly-ADR (DGLGA) conjugate with a lysosomally degradable tripeptide spacer group, a dextran-Gly-Leu-Gly-ADR-galactosamine (DGLGA-Ga) conjugate with a targeting moiety of galactosamine on DGLGA, and a dextran-C6H10-ADR (DC6A) conjugate with a hexamethylen spacer group. The content of the ADR moiety in the polymeric-drug conjugate was about 3 mol%. Enzyme hydrolysis of DGLGA and DC6A was carried out by incubation with papain. The total amount of ADR released after 48 h was 43 mol% for DGLGA and less than 1 mol% for DC6A. In an in vitro cytotoxicity experiment, the DGLGA-Ga conjugate has higher cytotoxic efficacy than the other conjugates for incubation with Hep-3B cells and consequently, the capability of targeting hepatoma cells of the galactosamine residue was determined. In contrast, for the incubation with SiHa cells of these conjugates, there was no significant cytotoxicity effect. The in vivo cytotoxic efficacy of each conjugate (20 mg ADR equiv./kg) against CT-26 mice colon cells implanted subcutaneously in Balb-C mice was studied. The DGLGA conjugate generated the best therapeutic effect with the presence of long-term survival (LTS) at day 50 (2/6).
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PMID:Synthesis and biological properties of antitumor-active conjugates of ADR with dextran. 1248 89

A new cyclic heptapeptide phakellistatin 13 (1) had been isolated from the sponge Phakellia fusca Thiele, collected at Yongxing Island of China. Its structure was elucidated as cyclo-(Pro1-Trp-Leu-Thr-Pro2-Gly-Phe) on the basis of MS, UV, IR, and high-field NMR (600 MHz) analysis. The compound was significantly cytotoxic against the human hepatoma BEL-7404 cell line with an ED(50) < 10(-2) microg/mL.
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PMID:Isolation and structure of the cytotoxic cycloheptapeptide phakellistatin 13. 1254 66

PTEN/MMAC1/TEP1 is a tumor suppressor gene. Its mutation has been found in several different types of human cancers. 34 primary human hepatocellular carcinomas have been examined for mutations in exon 5 and exon 8 of the PTEN gene. Exon 5 and exon 8 were amplified by polymerase chain reaction (PCR) with intronic primers and subjected to single strand conformation polymorphism (SSCP) analysis. SSCPs were found in 4 of the 34 hepatocellular carcinomas analyzed. Direct sequencing of the PCR products identified single base-pair substitutions in the four tumor DNA samples, two in intron 4 and two in exon 8. One of the base-pair substitution in exon 8 is a missense mutation, which changed codon 304 of PTEN protein from Cys to Gly. These data suggest that PTEN may be involved in the carcinogenesis and development of hepatocellular carcinoma.
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PMID:[Mutation analysis of the tumor suppressor gene PTEN/MMAC1/TEP1 in human hepatocellular carcinoma]. 1254 40

Conformational diseases are caused by a structural rearrangement within a protein that results in aberrant intermolecular linkage and tissue deposition. This is typified by the polymers that form with the Z deficiency variant of alpha 1-antitrypsin (Glu-342 --> Lys). These polymers are retained within hepatocytes to form inclusions that are associated with hepatitis, cirrhosis, and hepatocellular carcinoma. We have assessed a surface hydrophobic cavity in alpha1-antitrypsin as a potential target for rational drug design in order to prevent polymer formation and the associated liver disease. The introduction of either Thr-114 --> Phe or Gly-117 --> Phe on strand 2 of beta-sheet A within this cavity significantly raised the melting temperature and retarded polymer formation. Conversely, Leu-100 --> Phe on helix D accelerated polymer formation, but this effect was abrogated by the addition of Thr-114 --> Phe. None of these mutations affected the inhibitory activity of alpha 1-antitrypsin. The importance of these observations was underscored by the finding that the Thr-114 --> Phe mutation reduced polymer formation and increased the secretion of Z alpha 1-antitrypsin from a Xenopus oocyte expression system. Moreover cysteine mutants within the hydrophobic pocket were able to bind a range of fluorophores illustrating the accessibility of the cavity to external agents. These results demonstrate the importance of this cavity as a site for drug design to ameliorate polymerization and prevent the associated conformational disease.
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PMID:Targeting a surface cavity of alpha 1-antitrypsin to prevent conformational disease. 1280 89

Hepatitis C virus (HCV) causes a persistent infection, chronic hepatitis, and leads to hepatocellular carcinoma. Nonstructural protein 3 (NS3) of HCV possesses protease, nucleoside triphosphatase, and helicase activities. Using the yeast two hybrid assay, we identified Sm-D1, a host protein that binds to NS3. Sm-D1 is a component of small nuclear ribonucleoprotein (snRNP) complexes which are associated with autoimmune disease. Sm-D1 has Gly-Arg (GR) repeats at the C terminus, which contains dimethylarginine modified by post-translational modification and may constitute an immunoreactive determinant. Deletion mutants revealed that the C-terminal region of Sm-D1 containing the GR repeats was the binding region for NS3, and the expression feature of Sm-D1 was affected by co-expression of NS3. Immunostaining assay demonstrated that NS3 was also present in the nucleus of cells overexpressing Sm-D1, although it was usually found in cytoplasm. The localization of NS3 could change following interaction with Sm-D1 and affect the function of Sm-D1.
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PMID:Hepatitis C virus nonstructural protein NS3 binds to Sm-D1, a small nuclear ribonucleoprotein associated with autoimmune disease. 1452 21

Many secretory proteins are synthesized as proforms that become biologically active through a proteolytic cleavage in the trans-Golgi complex or at a later stage in the secretory pathway. Haptoglobin (Hp) is unusual in that it is cleaved in the endoplasmic reticulum before it enters the Golgi. Here, we present evidence that the recently discovered complement C1r-like protein (C1r-LP) mediates this cleavage. C1r-LP has not previously been shown to possess proteolytic activity, despite its homology to trypsin-like Ser proteinases. We demonstrate that coexpression of the proform of Hp (proHp) and C1r-LP in COS-1 cells effected cleavage of proHp in the endoplasmic reticulum. This cleavage depended on proteolytic activity of C1r-LP because mutation of the putative active-site Ser residue abolished the reaction. Furthermore, incubation of affinity-purified C1r-LP and proHp led to the cleavage of the latter protein. ProHp appeared to be cleaved at the expected site because substitution of Gly for Arg-161 blocked the reaction. C1r-LP showed specificity for proHp, in that it did not cleave the proform of complement C1s, a protein similar to Hp particularly around the cleavage site. C1r-LP accounts for at least part of the endogenous proHp-cleavage activity because suppression of the C1r-LP expression by RNA interference reduced the cleavage of proHp by up to 45% in the cells of a human hepatoma cell line (HepG2).
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PMID:Prohaptoglobin is proteolytically cleaved in the endoplasmic reticulum by the complement C1r-like protein. 1538 75

It has been previously demonstrated that platelets (PLTs) can bind and transport HIV-1 infectious virions. Hepatitis C virus (HCV)-HIV-1 co-infection occurs frequently among users of illicit intravenous drugs, thereby increasing the severity of HIV disease and the evolution towards chronic active hepatitis and hepatocellular carcinoma of HCV-related hepatitis. In the present study we investigated whether or not PLTs can carry HCV, and studied the binding mechanisms. Purified PLTs, obtained from healthy donors, HCV negative and HIV negative, were adsorbed with HCV-containing serum and then employed to infect a THP-1 monocytoid cell line. Replication of HCV was observed as shown by positivity for the E2 antigen within THP-1 cells, by indirect immunofluorescence; moreover, HCV-RNA was detected in supernatants of THP-1 cells at day 7 post-incubation with HCV-adsorbed PLTs. The binding of HCV to PLTs seems to involve fibronectin (FN), as already shown in the case of HIV-1. Indeed, treatment with RGD (Gly-Arg-Gly-Asp-Ser), the key oligopeptide of FN binding, inhibits the ability of HCV to be carried by PLTs in infective forms; the same phenomenon occurs with Mabs to FN. Moreover the infection of THP-1 cells seems to increase FN surface expression, as demonstrated by immunofluorescence tests.
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PMID:HCV infective virions can be carried by human platelets. 1538 45

Hoki (Johnius belengerii) skin gelatin was hydrolyzed with three commercial enzymes to identify radical-scavenging potencies of derived peptides. Peptides derived from tryptic hydrolysate exhibited the highest scavenging activities on superoxide, carbon-centered 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals assessed by ESR spectroscopy. Following consecutive chromatographic separations of tryptic hydroolysate, the peptide sequence His-Gly-Pro-Leu-Gly-Pro-Leu (797 Da) acted as a strong radical scavenger under studied conditions. Further, this peptide could act as an antioxidant against linoleic acid peroxidation and the activity was closer to the highly active synthetic antioxidant butylated hydroxytoluene (BHT). In addition, antioxidative enzyme levels in cultured human hepatoma cells were increased in the presence of this peptide and it was presumed to be the peptide involved in maintaining the redox balance in the cell environment. Present data indicate that free-radical-scavenging activities of hoki skin gelatin peptides substantially contribute to their antioxidant properties measured in different oxidative systems.
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PMID:Antioxidant properties of a radical-scavenging peptide purified from enzymatically prepared fish skin gelatin hydrolysate. 1568 5

Activation of Kupffer cells by gut-derived endotoxin is an important factor in ethanol hepatotoxicity. Further, it was shown that ethanol modulates both the expression and activity of several intracellular signaling molecules and transcription factors in Kupffer cells and chronic ethanol treatment enhances Kupffer cell sensitivity to endotoxin. These findings suggest that inhibition of Kupffer cell activation is effective for clinical application in alcoholic hepatitis. Recently, accumulating lines of evidence suggest a possibility that glycine is useful as an immuno-modulating amino acid. It has been shown that a diet containing glycine improved survival in endotoxin shock by preventing Kupffer cell activation. Glycine most likely prevents the LPS-induced elevation of intracellular Ca concentration in Kupffer cells, thereby minimizing LPS receptor signaling and cytokine production. Indeed, glycine prevents alcohol-induced liver injury in a long-term enteral ethanol feeding rats (Tsukamoto-French) by decreasing production of TNF-alpha in the liver. Moreover, glycine is protective against apoptosis of sinusoidal endothelial cells (SECs) that is one of the initial events in the development of liver injury. On the other hand, epidemiologic data have identified chronic alcohol consumption as a significant risk factor for carcinogenesis. Interestingly, glycine inhibits growth of tumor in vivo most likely because of the inhibition of angiogenesis. It was shown that the inhibitory effect of glycine on growth and migration of endothelial cells is due to activation of a glycine-gated Cl channel. It is hypothesized that the opening of this anion channel hyperpolarizes the cell membrane, blocks influx of Ca through voltage-dependent Ca channel, thereby blunting growth factor-mediated signaling. Therefore, glycine can be used not only for treatment of alcoholic hepatitis, but also for chemoprevention and treatment of hepatocellular carcinoma in alcoholic cirrhosis. Taken together, it is concluded that glycine is a potent therapeutic immuno-nutrient for various kinds of chronic liver diseases including alcoholic liver disease (ALD).
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PMID:Glycine as a therapeutic immuno-nutrient for alcoholic liver disease. 1634 3


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