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)

5'-Nucleotidase is a degrading purine ectoenzyme acting at alkaline pH. It is located in both B and T lymphocytes and its study is of interest in chronic lymphoproliferative diseases. The present work compiles the cytochemical study of lymphocyte 5'-nucleotidase in a control group consisting of 277 haematologically normal subjects and a series of 77 chronic lymphocytic leukaemia (CLL) patients; phenotypic studies had been carried out in 40 of these last. The results were expressed as percentage of 5'-nucleotidase positive lymphocytes, and the value (means +/- SD) for the control group was 25 +/- 7, that of the CLL group being 10.7 +/- 18.12. Increased lymphocyte 5'-nucleotidase was present in a minority of the cases (13%), but the significance of this finding is unknown and unrelated to any clinical or cytomorphological data. Although lacking any statistical value, those B-CLL lymphocytes expressing surface IgM and IgD (thus being more mature cells) showed higher 5'-nucleotidase values than those cells expressing only IgM. This finding suggests that a given lymphocytic population would be more immature the lower 5'-nucleotidase value it may express. The incorporation of 5'-nucleotidase determination into the cytochemical study of CLL is encouraged as it is frequently decreased in this disease; at the same time, the enzyme may provide some information on the maturity of the leukaemic population involved.
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PMID:[Cytochemical detection of lymphocyte 5'-nucleotidase in chronic lymphatic leukemia]. 177 9

Gemcitabine is an inhibitor of ribonucleotide reductase (RR) and DNA polymerization with promising activity in hematologic malignancies. Gemcitabine enters the cell mostly via the human equilibrative nucleoside transporter-1 (hENT1), while drug metabolism occurs by phosphorylation by deoxycytidine kinase (dCK), 5'-nucleotidase (cN-II) and cytidine deaminase (CDA) are the main inactivating enzymes. The aim of this study was to investigate the role of these determinants in gemcitabine cytotoxicity and analyze their expression in lymphoid cells. Cytotoxicity was assessed by MTT, and modulated by simultaneous addition of 2'-deoxycytidine (dCK natural substrate), tetrahydrouridine (CDA competitive inhibitor) and diethylpyrocarbonate (cN-II non-competitive inhibitor), while the expression of hENT1, dCK, cN-II, CDA and RR in WIL2-S, Jurkat and CCRF-CEM cells as well as in lymphoid cells from 25 chronic lymphocytic B-leukemia (B-CLL) patients was studied with quantitative-PCR. Cell cycle modulation and induction of apoptosis were analyzed by cytofluorimetry and bisbenzimide staining. Gemcitabine was highly cytotoxic, increased the cells in S-phase and significantly enhanced apoptosis. The crucial role of metabolism in gemcitabine activity was confirmed by the significant modulation of cytotoxicity by inhibitors of dCK, CDA and cN-II. Furthermore, PCR demonstrated a correlation between gemcitabine sensitivity and expression of its determinants, and that their values were within those observed in patients. These data indicate that gemcitabine is cytotoxic against lymphoid cells, affecting cell cycle and apoptosis. Furthermore, chemosensitivity may be predicted on the basis of gene expression profile of critical determinants involved in gemcitabine mechanism of action, suggesting the use of pharmacogenetic profiling for treatment optimization.
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PMID:Cytotoxic activity of gemcitabine and correlation with expression profile of drug-related genes in human lymphoid cells. 1729 11