Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.4.99.7 (sialyltransferase)
1,534 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antineoplastic alkyl-lysophospholipids were found to exert a strong inhibitory effect on membranous or solubilized asialomucin-sialyltransferase (CMP-N-acetylneuraminate: D-galactosyl-glycoprotein N-acetylneuraminyltransferase, EC 2.4.99.1) activity. This inhibitory effect was dependent on the presence of the choline moiety in position 3 of the glycerol molecule, as well as on the presence of long ether-linked aliphatic side chain in position 1 and the absence of any large substituent in position 2. As an example, 1-octadecyl-2-O-methyl-glycero-3-phosphorylcholine acted as a mixed-type inhibitor. Such an inhibitory process on sialyltransferase activity might be an additional factor in the tumor cell destructive effect of alkyl-lysophospholipids.
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PMID:Biochemical evidence for the role of alkyl-lysophospholipids on liver sialyltransferase. 668 98

The correlation between levels of sialic acid and sialic acid-containing glycolipids (gangliosides) in tumors and serum with the growth characteristics of the tumors was investigated in transplantable hepatomas and squamous cell carcinomas initiated with the carcinogen N-2-fluorenylacetamide and propagated in vivo and in tissue culture. Tumor lines varied in histologic classification, growth rate, and ability to form pulmonary metastases. There was neither a correlation between growth rate and histologic classification nor between either of these two parameters and the ability to metastasize. Total and ganglioside sialic acid levels were elevated in carcinogen-treated liver and in transplantable hepatomas when contrasted with normal liver. Levels of sialic acid showed a weak correlation with the growth rate of hepatomas. Gangliosides from nonmetastatic hepatoma lines exhibited less N-acetylneuraminic acid--galactose--glucose-N--acylsphingosine (GM3) and an increased ratio of total monosialogangliosides to disialogangliosides than did metastatic lines. Ganglioside patterns of metastatic hepatoma lines more closely resembled the ganglioside patterns of normal liver than did those of the nonmetastatic lines. Concomitant elevations of total and ganglioside sialic acid levels were observed in sera of animals bearing subcutaneous implants. Serum levels of total sialic acid did correlate with total sialic acid levels found in the tumor tissues. The levels of serum sialic acid were not correlated directly with levels of serum sialyltransferase activity. Elevations of both tissue and serum ganglioside sialic acid were consistent features of liver tumorigenesis in the rat after N-2-fluorenylacetamide administration. They appeared, furthermore, to be early events not directly related to tumor cell differentiation or metastasis.
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PMID:Characteristics of transplantable tumors induced in the rat by N-2-fluorenylacetamide: elevations in tissue and serum sialic acid. 692 77

Serum-sialyltransferase activity was measured in serum samples of 116 patients with malignant tumors of various origins and different clinical stages using asialo-fetuin as the acceptor and cytidine-5'-mono-phospho[14C]sialic acid as the donor. Only patients with metastatic tumors had significantly elevated serum-sialyltransferase levels. Increased enzyme activity was also associated with rheumatoid arthritis and with acute hepatitis, whereas no significant alteration of enzyme activity was observed in cystic fibrosis patients. In a group of tumor patients, various additional tumor markers were determined (carcinoembryonic antigen, alkaline phosphatase: Regan isoenzyme, creatinekinase: BB-isoenzyme, lactatedehydrogenase: isoenzyme 5) and the data compared to the clinical diagnoses. The sensitivity and specificity of serum-sialyltransferase as a tumor marker is assessed.
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PMID:Serum-sialyltransferase activity in cancer patients. 704 8

Total plasma sialyltransferase (ST) activity was elevated in patients with colonic adenocarcinoma; the incidence of abnormal values ranged from 33% in patients with no evidence of metastases (T2N0M0) to 86% in patients with advanced metastatic disease (T2-5N1M1). Isoenzyme analysis revealed that normal serum contains a major band (ST2) probably derived from red cells, and a minor band (ST1) thought to be derived from platelets. An additional band, designated STN, intermediate in mobility between the two other bands, was found in patients with colonic adenocarcinoma, ranging in incidence from 50% to 86% in patients free of metastases and those with widespread metastases. Histological studies suggested that this abnormal isoenzyme was more likely to occur in the serum of patients whose tumor was well differentiated.
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PMID:Plasma sialyl transferase total and isoenzyme activity in the diagnosis of cancer of the colon. 706 76

In an effort to assess the effect of surface carbohydrates upon the metastasizing properties of tumor cells, lectin-resistant mouse melanoma cells were selected. Wheat-germ-agglutinin-resistant lines displayed mainly decreased metastasis properties as well as well-defined alterations in surface carbohydrates: in a glycopeptide with four side chains, two of them were missing their terminal sialic acid residues while two fucoses were newly attached to the oligosaccharide. The enzymatic defect could be pinpointed to an over-60-fold increase in fucosyltransferase, while the sialyltransferase did not decrease significantly. Revertants were again selected with lectins and their fucosyltransferase activities returned to normal values again. The metastasizing potential of the revertants was not yet assessed carefully but a return of some of the metastasizing potential was noted.
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PMID:The influence of membrane mutations on metastasis. 713 74

A murine melanoma variant (B16-F10ir6), resistant to lymphocytic cytolysis, has been shown previously to produce lower numbers of tumor nodules in the lung of C57BL/6J mice following i.v. inoculations. These differences found in tumor implantation and lymphocyte recognition may be due to changes in surface properties of this cell line. Therefore, membrane-bound sialic acid (released by Vibrio cholerae neuraminidase treatment), ectosialyltransferase activity, and total cellular glycosidase levels were measured in this cell line and compared with levels in its parent melanoma tumor cell line, B16-F10, which was selected for its enhanced ability to form tumor nodules. The results of these studies indicate a correlation between the degree of lung implantation and the amount of tumor cell sialic acid accessible to neuraminidase cleavage, tumor cell surface sialyltransferase activity, and several cellular glycosidase activities. These results are consistent with the idea that membrane structural changes in the glycocalyx may account for the ability of a tumor cell to implant and metastasize.
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PMID:A correlation between cell surface sialyltransferase, sialic acid, and glycosidase activities and the implantability of B16 murine melanoma. 723 26

Cachexia is rare in nude mice bearing human malignant tumors even when the transplanted tumors become as large as the body size of the host. In our series on heterotransplantation of a variety of human malignant tumors into nude mice, a malignant melanoma (SEKI) was found to induce severe body weight loss in the host at the early stage of transplantation. There was no electrolyte disturbance, hyper- or hypoadrenocorticism, hyperthyroidism, or destruction of cells of vital organs to account for the weight loss. Moreover, no evidence was obtained for concomitant infection with bacteria, Mycoplasma or fungi. These cachectic mice revealed remarkably increased levels of serum sialyltransferase and decreased liver catalase activity. The removal of tumor tissues from these mice resulted in prompt recovery of body weight, serum sialyltransferase, and liver catalase activity within 1 to 2 weeks. On the basis of the results obtained, the SEKI melanoma was thought to have produced a pathophysiological state in host nude mice which was very similar to that of cachexia in cancer patients. Nude mice bearing transplants of SEKI melanoma may provide a useful system for the study of cancer cachexia in humans.
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PMID:Serum sialyltransferase and liver catalase activity in cachectic nude mice bearing a human malignant melanoma. 724 51

Sialyltransferase activities and sialic acid concentrations were measured in sera form patients with malignant melanoma (n = 49), healthy control persons (n = 20), and patients with non-malignant skin disorders (n = 30). Both parameters were found to be higher in malignant melanoma patients than in healthy control persons, but they were not significantly higher in primary melanoma patients than in patients with benign skin orders, unless widespread dissemination of metastases had occurred. The highest values were found in patients with liver and lung metastases. In early stages of the disease, shedding from tumor cells seems not to be the major source of elevated serum levels of sialyltransferase and sialic acid, respectively. There is no general correlation between sialyltransferase activities and sialic acid concentrations. However, a correlation was found between serum concentrations of sialic acid and orosomucoid in patients with melanomas stage III, indicating that humoral defense mechanisms contribute to the higher values in advanced stages of the disease.
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PMID:[Clinical significant of sialic acid concentrations in the serum of melanoma patients]. 739 10

The observation that the activity of sialyltransferase (EC 2.4.99.1; serum glycoprotein:N-acetylneuraminic acid transferase) is often elevated in the serum of cancer patients necessitates an elucidation of the interrelationships of this serum enzyme with host tissues. Accordingly, the activity of this enzyme in serum, tumor, and liver was determined at various times after implantation of the R3230AC mammary carcinoma into Fischer rats. Results from samples obtained at numerous, sequential time points demonstrated that significant elevations in serum sialyltransferase enzyme activity occurred only in animals bearing large tumor burdens, i.e., greater than 20 g, or in animals with tumors present for longer than 21 days. In these tumor-bearing rats, the activity of sialyltransferase increased in liver tissue at 21 to 25 days concurrently with the increase in serum enzyme activity, suggesting that the liver may be a potential source of the serum enzyme. Sialyltransferase activity in tumor tissue was quite variable; the activity increased one week after tumor implantation and remained at the same level thereafter. When tumors were excised, the activity of the serum enzyme returned to control values within four days after surgery, suggesting that the half-life of serum sialyltransferase was two days. Serum enzyme levels were again elevated upon regrowth of the tumor. These results show that the serum sialyltransferase alters its activity in conjunction with changes in tumor burden.
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PMID:Correlation of serum, tumor, and liver serum glycoprotein: N-acetylneuraminic acid transferase activity with growth of the R3230AC mammary tumor in rats and relationship of the serum activity to tumor burden. 742 28

Three melanomas of C57BL/6 mice (BL6, JB/MS, and JB/RH) share several phenotypic properties. All these cells contain melanoma-specific ecotropic C-type retrovirus that encodes melanoma-associated antigen recognizable by MM2-9B6 mAb. They do not express H-2Kb molecules, and the alpha-galactosyl epitopes (Gal alpha 1-3Gal beta 1-4GlcNAc-R) they fail to react with soybean agglutinin (SBA), peanut agglutinin (PNA), and vicia villosa (VV) lectins. Previously, we found that failure of BL6 melanoma cells to express alpha-galactosyl epitopes is due to down-regulation of alpha 1,3 galactosyltransferase (alpha 1,3GT) gene expression. To evaluate the possible role of alpha-galactosyl cell membrane carbohydrates in regulation of metastatic properties, individual clones isolated from BL6, JB/MS, and JB/RH melanomas were transfected with alpha 1,3GT cDNA. This resulted in appearance of alpha-galactosyl epitopes, as well as of carbohydrates reacting with SBA, PNA, or VV lectins, but did not affect expression of H-2 class I molecules or melanoma-associated antigen. Appearance of SBA, PNA, and VV lectin binding carbohydrates in the alpha 1,3GT gene-transfected melanoma cells is a result of reduction of cell membrane sialylation and unmasking of these carbohydrates. Reduction in cell membrane sialylation in the alpha 1,3GT gene-transfected melanoma cells is probably due to the competition between alpha 1,3GT with alpha 2,3 sialyltransferase or alha 2,6 sialyltransferase for the common acceptor N-acetyllactosamine in the Golgi apparatus. As a result of this competition, cell membranes of alpha 1,3GT gene-transfected melanoma cells became galactosylated and less sialylated. In parallel with alteration of cell membrane carbohydrates, transfection of the alpha 1,3GT gene leads to the loss of metastatic properties of the transfected melanoma cells in the immunocompetent and immunosuppressed C57BL/6 mice. Thus, the use of specific glycosyltransferase cDNA transfection presents direct experimental confirmation of the importance of cell membrane carbohydrates in the regulation of metastatic properties of tumor cells.
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PMID:Alterations of cell surface carbohydrates and inhibition of metastatic property of murine melanomas by alpha 1,3 galactosyltransferase gene transfection. 754 89


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