Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.16.3.1 (ceruloplasmin)
 5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunomodulating properties of ceruloplasmin were determined in vivo on healthy mice line C57BL/6 and mice with Lewis carcinoma. It was established, that ceruloplasmin at the concentration of 1-40 mg/kg stimulated both T- and B--systems of immunity and prevented immunodepression activity of tumor growth.
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PMID:[Immunomodulating activity of exogenous ceruloplasmin in experimental tumor growth]. 142 Dec 78

The study was concerned with the effect of human ceruloplasmin on blastogenic reaction of lymphocytes (BRL) and cyclic nucleotide level in murine organs in the course of Lewis lung carcinoma development. Both ceruloplasmin and an immunomodulator--zymosan--were found to raise the level of cAMP and to lower that of cGMP in the immunocompetent organs (thymus and spleen) of tumor-bearing mice at all stages of the investigation. The results point to an immunomodulating action of human ceruloplasmin involved in tumor growth and the role played by cyclic nucleotides in the process.
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PMID:[Immunomodulating action of ceruloplasmin in tumor growth and the participation of cyclic nucleotides]. 401 29

Transplantation of Yoshida sarcoma (solid type) and Zajdela ascites hepatoma tumors in rats induces a biphasic change in the concentration of the following five acute-phase proteins: alpha-1-acid glycoprotein; alpha-1-antitrypsin; haptoglobin; hemopexin; and ceruloplasmin. These proteins and other plasma proteins were quantitated by two-dimensional immunoelectrophoresis relative to normal serum concentrations. The elevation of most of these acute-phase proteins was greater in the second phase, during which serum levels increased continuously as the tumor burden increased until the animals died. The increase in haptoglobin concentration during the second phase was much higher in rats bearing Yoshida sarcoma than in rats bearing Zajdela tumors. Rats receiving irradiated tumor cells showed neither tumor growth nor second-phase protein changes. Significant increases in uptake of 3H-amino acids by isolated perfused livers of tumor-bearing rats provided evidence for an increase in the hepatic synthesis rates of the acute-phase proteins. Removal of the solid tumor resulted in a gradual decrease of acute-phase protein concentrations with concomitant increase in serum albumin concentration. These alterations in serum acute-phase proteins during tumor growth and after removal of the tumor may make their use attractive as biological markers of the response of the tumor-bearing animal to its tumor.
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PMID:Kinetics of the acute-phase reaction in rats after tumor transplantation. 697 53

There is an emerging link between copper metabolism, tumor growth and efficiency of antitumor treatment with platinum drugs or copper chelators. So there is an urgent need for well-defined and reproduced animal models with different states of copper metabolism. In the present study an animal model (rats and mice) with switching copper status in blood serum (copper concentration, oxidase activity and ceruloplasmin (Cp) protein content) is characterized. The drop of copper status is caused by addition of AgCl to fodder (Ag-animals). In rats and mice, the influence of silver ions on oxidase and ferroxidase activity of blood serum is similar, but copper concentration is reduced by 90% in rats, and by 60% in mice. The absorbed silver ions are transported to liver cells and included to Cp polypeptides, which are secreted to blood serum then. Cp, which circulates in bloodstream of Ag-animals contains silver atoms, and is misfolded, as judged by circular dichroism spectroscopy and differential scanning calorimetry. Single intraperitoneal or per oral injection of Cu(II) salt to Ag-animals causes recovery of oxidase and ferroxidase activity of blood serum within 4 hours in both rodent species, presumably by rapid metabolic insertion of copper into forming Cp in liver. The recovered copper status persists for 3 days under the continuing Ag-diet. The possibilities of use of Ag-rodents with switching copper status in investigation of influence of copper status on tissue-specific intracellular copper metabolism and role of copper in tumor genesis, bone metabolism and neurodegenerative diseases are discussed.
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PMID:Experimental switching of copper status in laboratory rodents. 2096 8

To assess the statistical relationship between tumor growth and copper metabolism, we performed a metaanalysis of studies in which patients with neoplasms were characterized according to any of the copper status indexes (atomic copper serum concentration, serum oxidase activity, ceruloplasmin protein content). Our metaanalysis shows that in the majority of cases (more than 3100 patients), tumor growth positively correlates with the copper status indexes. Nude athymic CD-1 nu/nu mice with subcutaneous tumors of human origin, C57Bl/6J mice with murine melanoma and Apc(Min) mice with spontaneously developing adenomas throughout the intestinal tract were studied to experimentally determine the relationship between tumor progression, liver copper metabolism, and copper status indexes. We showed that the copper status indexes increased significantly during tumor growth. In the liver tissue of tumor-bearing mice, ceruloplasmin gene expression, as well as the expression of genes related to ceruloplasmin metallation (CTR1 and ATP7B), increased significantly. Moreover, the presence of an mRNA splice variant encoding a form of ceruloplasmin anchored to the plasma membrane by glycosylphosphatidyl inositol, which is atypical for hepatocytes, was also detected. The ATP7A copper transporter gene, which is normally expressed in the liver only during embryonic copper metabolism, was also activated. Depletion of holo-ceruloplasmin resulted in retardation of human HCT116 colon carcinoma cell growth in nude mice and induced DNA fragmentation in tumor cells. In addition, the concentration of cytochrome c increased significantly in the cytosol, while decreasing in the mitochondria. We discuss a possible trans-effect of developing tumors on copper metabolism in the liver.
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PMID:Non-hepatic tumors change the activity of genes encoding copper trafficking proteins in the liver. 2379 45

The influence of tumor development on the blood plasma antioxidant system in the area of tumor growth has been studied. Zajdela ascite hepatoma transplanted to the abdominal cavity of Vistar rats was used as a model of tumor growth. It hase been found that tumor development produced and imbalance between pro- and antioxidant systems in the organism of tumor bearer. Besides, a sharp decrease in tocopherol and uric acid concentrations (twice), as well as in the concentration of protein SH-groups (seven times) was noted. In the tumor growth area, along with the tocopherol level decrease, a 5-7 fold increase in the concentrations of uric acid and protein SH-groups was observed. As the concentration of low-molecular antioxidants decreases, the major part is played by protein components which bind or oxidize ions of variable valence. Thus, the level of transferrin (Tf, which is responsible for the transport of iron ions, is reduced in 2.5 to 3 times (from 5.0 to 1.6 mg/ml) in the blood plasma, whereas the Tf level in the ascitic fluid increased from 1.5 to 2.7 mg/ml. The concentration dynamics of the other protein functioning together with Tf, ceruloplasmin (Cp), had opposite (inverse) tendencies. Thus, the Cp concentration in the blood plasma increased 1.5-2 times (from 0.55 to 1.1 mg/ml) whereas it decreased from 0.55 mg/ml to 0.35 mg/ml in the ascites.
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PMID:[Effect of Zajdela ascite hepatoma growth on the extracellular antioxidant system of tumor bearer]. 2459 37

Long noncoding RNAs (lncRNAs) significantly influence the development and regulation of genome expression in cells. Here, we demonstrate the role of lncRNA ceruloplasmin (NRCP) in cancer metabolism and elucidate functional effects leading to increased tumor progression. NRCP was highly upregulated in ovarian tumors, and knockdown of NRCP resulted in significantly increased apoptosis, decreased cell proliferation, and decreased glycolysis compared with control cancer cells. In an orthotopic mouse model of ovarian cancer, siNRCP delivered via a liposomal carrier significantly reduced tumor growth compared with control treatment. We identified NRCP as an intermediate binding partner between STAT1 and RNA polymerase II, leading to increased expression of downstream target genes such as glucose-6-phosphate isomerase. Collectively, we report a previously unrecognized role of the lncRNA NRCP in modulating cancer metabolism. As demonstrated, DOPC nanoparticle-incorporated siRNA-mediated silencing of this lncRNA in vivo provides therapeutic avenue toward modulating lncRNAs in cancer.
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PMID:Long Noncoding RNA Ceruloplasmin Promotes Cancer Growth by Altering Glycolysis. 2668 30

G9a, a H3K9 methyltransferase, shows elevated expression in many types of human cancers, particularly breast cancer. However, the tumorigenic mechanism of G9a is still far from clear. Here we report that G9a exerts its oncogenic function in breast cancer by repressing hephaestin and destruction cellular iron homeostasis. In the case of pharmacological inhibition or short hairpin RNA interference-mediated suppression of G9a, the expression and activity of hephaestin increases, leading to the observed decrease of intracellular labile iron content and the disturbance of breast cancer cell growth in vitro and in vivo. We also provide evidence that G9a interacts with HDAC1 and YY1 to form a multi-molecular complex that contributes to hephaestin silencing. Furthermore, high G9a expression and low hephaestin expression correlate with poor survival of breast cancer are investigated. All these suggest a G9a-dependent epigenetic program in the control of iron homeostasis and tumor growth in breast cancer.G9a is a histone methyltransferase highly expressed in several cancers including breast cancer. Here the authors propose a mechanism through which G9a promotes breast cancer by regulating iron metabolism through the repression of ferroxidase hephaestin.
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PMID:G9a regulates breast cancer growth by modulating iron homeostasis through the repression of ferroxidase hephaestin. 3270 95