Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of a new, liposome-encapsulated muramyldipeptide analog--GMDP--on Lewis lung carcinoma spreading was studied in mice in which primary tumor had been removed. The drug was found to significantly decrease the extent and number of lung metastases, as compared to mice which had not received GMDP. This was matched by recovery of alveolar and splenic macrophages functional activity, as assessed by adenosine deaminase and 5'-nucleotidase levels in these cells.
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PMID:[Antimetastatic effect of a liposome-enclosed analog of muramyl dipeptide]. 283 5

N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-isoglutamine (GMDP), a new liposome-encapsulated muramyl dipeptide analog, was studied for its effect on the Lewis lung carcinoma metastatic spreading as well as on the adenosine deaminase (ADA) and 5'-nucleotidase (5-N) activity in the alveolar and peritoneal mice macrophages. The drug administration was found to cause a sharp dose-dependent decrease in the lung metastases volume and number as compared to those in mice not treated with GMDP. The antimetastatic effect of GMDP is accompanied by an increase in the functional macrophage activity determined by ADA and 5-N level in these cells.
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PMID:[Effect of GMDP encapsulated into liposomes on metastatic spread of Lewis lung carcinoma]. 285 Jan 49

Liver metastases due to the more common neoplastic diseases such as colorectal, breast, or bronchogenic carcinoma are a frequent occurrence and are associated with an ominous prognosis. Earlier detection followed by appropriate therapeutic interventions might have a decided effect on the subsequent course of disease. Controversy exists over the selection of tests with the greatest sensitivity, specificity, and potential utility. Preliminary evidence suggest that gamma-glutamyl transpeptidase and 5'-nucleotidase may be of particular significance. Four enzymes--gamma-glutamyl transpeptidase, 5'-nucleotidase, leucine aminopeptidase, and alkaline phosphatase plus carcinoembryonic antigen--were compared in the same blood samples from selected patients with breast and small cell carcinoma of the lung. Gamma-Glutamyl transpeptidase was the most sensitive test with 28/29 (97%) patients with hepatic metastases having elevated enzymatic activity in their sera. For patients with small cell carcinoma of the lung followed serially, gamma-glutamyl transpeptidase activity was increased an average of 5 months before liver metastases were detected by clinical means. Two factors are important in the interpretation of the results of gamma-glutamyl transpeptidase analysis: (1) Hepatic dysfunction due to diseases other than metastatic tumor involvement can cause a rise in enzyme levels as can (2) medications or ethanol which activate the hepatic microsomal drug metabolizing system. Of particular importance, however, is the fact that antitumor chemotherapy, even intensive and multiple agent, did not appear to effect the enzyme activity in the sera of patients with breast or small cell carcinoma of the lung. Gamma-glutamyl transpeptidase in combination with carcinoembryonic antigen may be of particular value in detecting liver metastases and in assessing subsequent response to therapy.
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PMID:Biological markers as an aid in the clinical management of patients with liver metastases. 612 62

At a nontoxic dose (50 microM), the two potent uridine phosphorylase inhibitors, benzylacyclouridine and benzyloxybenzylacyclouridine (BBAU), potentiated 5-fluoro-2'-deoxyuridine (FdUrd) growth inhibition of human pancreatic carcinoma (DAN) and, to a lesser extent, human lung carcinoma (LX-1) cells in culture. BBAU was more effective than benzylacyclouridine. BBAU (50 microM) enhanced the cytocidal effect of FdUrd (1 microM, 3 hr) on DAN grown on soft agar from 75 to 88%. In antithymocyte serum-immunosuppressed mice bearing DAN, the mean tumor weight in animals treated with FdUrd (50 mg/kg/day for 2 days) was 11% less than that of untreated controls. When BBAU (10 mg/kg/day for 2 days) was coadministered, the mean tumor weight at Day 10 was 78% less than untreated controls, with no apparent host toxicity, clearly demonstrating the potentiation of the antitumor effects of FdUrd by BBAU. The fact that DAN responded better than LX-1 to benzylacyclouridine and BBAU could be due, in part, to the lower relative activity of thymidine phosphorylase to uridine phosphorylase in DAN compared to LX-1. The activities of other enzymes involved in FdUrd metabolism, thymidine kinase, uridine kinase, orotate phosphoribosyltransferase, 5'-nucleotidase, and dihydrouracil dehydrogenase, did not differ between the two cell lines.
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PMID:Potentiation of 5-fluoro-2'-deoxyuridine antineoplastic activity by the uridine phosphorylase inhibitors benzylacyclouridine and benzyloxybenzylacyclouridine. 623 86

IMP/GMP preferring cytosolic 5'-nucleotidase II (cN-II) is a bifunctional enzyme whose activities and expression play crucial roles in nucleotide pool maintenance, nucleotide-dependent pathways and programmed cell death. Alignment of primary amino acid sequences of cN-II from human and other organisms show a strong conservation throughout the entire vertebrata taxon suggesting a fundamental role in eukaryotic cells. With the aim to investigate the potential role of this homology in protein-protein interactions, a two hybrid system screening of cN-II interactors was performed in S. cerevisiae. Among the X positive hits, the Leucin Rich Repeat (LRR) domain of Ipaf was found to interact with cN-II. Recombinant Ipaf isoform B (lacking the Nucleotide Binding Domain) was used in an in vitro affinity chromatography assay confirming the interaction obtained in the screening. Moreover, co-immunoprecipitation with proteins from wild type Human Embryonic Kidney 293 T cells demonstrated that endogenous cN-II co-immunoprecipitated both with wild type Ipaf and its LRR domain after transfection with corresponding expression vectors, but not with Ipaf lacking the LRR domain. These results suggest that the interaction takes place through the LRR domain of Ipaf. In addition, a proximity ligation assay was performed in A549 lung carcinoma cells and in MDA-MB-231 breast cancer cells and showed a positive cytosolic signal, confirming that this interaction occurs in human cells. This is the first report of a protein-protein interaction involving cN-II, suggesting either novel functions or an additional level of regulation of this complex enzyme.
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PMID:Cytosolic 5'-nucleotidase II interacts with the leucin rich repeat of NLR family member Ipaf. 2581 92

Purine homeostasis is maintained by a purine cycle in which the regulated member is a cytosolic 5'-nucleotidase II (cN-II) hydrolyzing IMP and GMP. Its expression is particularly high in proliferating cells, indeed high cN-II activity or expression in hematological malignancy has been associated to poor prognosis and chemoresistance. Therefore, a strong interest has grown in developing cN-II inhibitors, as potential drugs alone or in combination with other compounds. As a model to study the effect of cN-II inhibition we utilized a lung carcinoma cell line (A549) in which the enzyme was partially silenced and its low activity conformation was stabilized through incubation with 2-deoxyglucose. We measured nucleotide content, reduced glutathione, activities of enzymes involved in glycolysis and Krebs cycle, protein synthesis, mitochondrial function, cellular proliferation, migration and viability. Our results demonstrate that high cN-II expression is associated with a glycolytic, highly proliferating phenotype, while silencing causes a reduction of proliferation, protein synthesis and migration ability, and an increase of oxidative performances. Similar results were obtained in a human astrocytoma cell line. Moreover, we demonstrate that cN-II silencing is concomitant with p53 phosphorylation, suggesting a possible involvement of this pathway in mediating some of cN-II roles in cancer cell biology.
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PMID:Cytosolic 5'-Nucleotidase II Silencing in a Human Lung Carcinoma Cell Line Opposes Cancer Phenotype with a Concomitant Increase in p53 Phosphorylation. 3003 8