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:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dynamics of lymphocyte response in peripheral blood, the tumor draining lymph node, spleen and thymus, was followed in a model system of syngeneically transplanted rat MC-1 tumor. Electrophoretic mobility (EPM) of lymphoid cells was determined by the automatic mode of measurement. The results revealed a two-phase pattern of EPM changes during the course of cancer growth. The first phase (day 3 to 6 following intramuscular injection of tumor cells) was characterized by a prevalence of high-mobility cells, while in the second phase (day 14 to 20), depletion of high-mobility cells was compensated for by an increased number of low-mobility cells. The mean EPM value was found to be increased only in the thymus at that time. Changes in the adenosine deaminase activity proved to be most expressive in the tumor draining lymph node and in the second phase also in splenic and thymic lymphocytes. An increased percentage of active lymphocytes with compact nucleoli with nucleolonemas became evident already on the 3rd day in all the lymphoid organs followed. The response was two-phasic only in the lymphocyte population of the peripheral blood, while their percentage in the other organs remained higher even on day 20. Changes in the proportion of high- and low-mobility cells in the lymphoid organs followed here, in correlation with the adenosine deaminase activity and the percentage of active lymphocytes, were interpreted as a response of immunocompetent cells in animals with a growing tumor.
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PMID:Kinetics of some immunological and biochemical changes of immunocompetent cells during tumor growth in rats. 378 65

7-Amino-3-(2'-deoxy-beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine (2'-deoxyformycin A) was synthesized from formycin A by a sequence consisting of (i) 3',5'-cyclosilylation with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane, (ii) 2'-acylation with phenoxythiocarbonyl chloride and 4-(N,N-dimethylamino)pyridine, (iii) N-trimethylsilylation with hexamethyldisilazane, (iv) reduction of the 2'-O-phenoxythiocarbonyl group with tri-n-butyltin hydride, and (v) desilylation with tetra-n-butylammonium fluoride. 2'-Deoxyformycin A was a potent inhibitor of the in vitro growth of S49 lymphoma, a murine tumor of T-cell origin. The IC50 of 2'-deoxyformycin A against S49 cells was 10-15 microM, whereas that of 2'-deoxyadenosine (dAdo) under the same conditions (72-h incubation in medium containing heat-inactivated horse serum) was 180 microM. In the presence of 10 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) to block intracellular adenosine deaminase (ADA) activity, 2'-deoxyformycin A and dAdo both gave IC50's of 5-10 microM. When assayed against a mutant S49 subline lacking adenosine kinase (AK) or a subline with a combined deletion of AK and deoxycytidine kinase (dCK), 2'-deoxyformycin A in combination with 10 microM EHNA was inactive at concentrations of up to 50 microM. Similar lack of activity against kinase-deficient cells was shown by formycin A. Thus, phosphorylation of 2'-deoxyformycin A appears to be required for biological activity and is probably catalyzed by AK rather than dCK. 2'-Deoxyformycin A and related 2'-deoxyribo-C-nucleoside analogues of the purine type may be of interest as potential T-cell specific cytotoxic agents.
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PMID:Improved synthesis of 2'-deoxyformycin A and studies of its in vitro activity against mouse lymphoma of T-cell origin. 387 61

The antiproliferative effect of 2',5' A3 core and 2',5'-3'dA3 (cordycepin trimer) core was measured in 8 human tumor cell lines. Cells were treated in a dose-response manner for 72 hr and the concentration of drug necessary to inhibit cell growth 50% (GI50) was determined. A wide range of sensitivities to these drugs was found, even among tumors of the same histological type. The cell lines showed different sensitivities and dose-response curves to the 2',5'A3 and 2',5'-3'dA3 cores. Uptake studies of the 2',5'A3 and 2',5'-3'dA3 cores, using high-pressure liquid chromatography, demonstrated that both cores were rapidly degraded in the tissue culture medium and taken up as adenosine or cordycepin, respectively. There was a direct correlation between the uptake of cordycepin and the antiproliferative effect. In contrast, there was no correlation between cell sensitivity and the uptake of the 2',5'A3 core degradation products. Analysis of intracellular nucleosides and nucleotides indicated that differences in intracellular metabolism of adenosine might explain the different sensitivities of the various cell lines to 2',5'A3 core. Molar equivalent concentrations of adenosine and cordycepin inhibited cell growth; however, equimolar concentrations of these nucleosides were not effective. In addition, the antiproliferative effect of both core compounds and their corresponding nucleosides could be potentiated by the addition of the adenosine deaminase inhibitor, deoxycoformycin. The results indicate that these cores act as prodrugs and that the active metabolites are their corresponding nucleosides.
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PMID:Differential antiproliferative actions of 2',5' oligo A trimer core and its cordycepin analogue on human tumor cells. 387 70

We describe a cytotoxic T lymphocyte-mediated cytotoxicity assay in which the release of a cytoplasmic enzyme, adenosine deaminase (ADA), instead of the widely used radioactive chromium is a measure of target lysis. In this enzyme-release assay the target is a mastocytoma P815-derived cell line, noted P815 ADA++, isolated by applying a selection procedure devised to specifically amplify the ADA gene. Gene amplification in P815 ADA++ was indeed demonstrated. Routine measurement of ADA activity from numerous supernatants is performed using a specific and sensitive colorimetric assay. The use of 96-well microtiter plates as well as of an automatic Multiscan spectrophotometer makes this measurement rapid and convenient. We show that this ADA-release assay is significantly more sensitive than the classical chromium-release test because of its consistently lower (5 to 10-fold) spontaneous release in 4 h, short-term cytotoxicity experiments. We also found that it is especially suited for the rapid detection, by visual screening, of rare, active killer clones among large, heterogeneous cytotoxic T lymphocyte populations. The assay could easily be adapted to other tumor targets (EL4, YAC-1, K562) of common use in studies involving immune lysis; indeed, the procedure of amplifying the ADA gene used in the isolation of the P815 ADA++ hyperactive line may be generally applied to these targets.
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PMID:Use of a P815-derived line with an amplified adenosine deaminase gene: an improved target for cellular cytotoxicity. 393 81

Immunoreactive adenosine deaminase complexing protein (ADCP) was studied in 91 human colorectal adenocarcinomas. The expression of ADCP was correlated with that of secretory component (SC) and carcinoembryonic antigen (CEA), with the histological grade and the Dukes' stage of the carcinomas. The histological grade was scored semi-quantitatively according to 5 structural and 4 cytological variables. ADCP expression was observed in 3 different staining patterns, namely: (1) diffuse cytoplasmic (77% of the carcinomas); (2) granular cytoplasmic (13%); and (3) membrane-associated (66%). These patterns were observed alone or in combination. Eleven percent of the carcinomas exhibited no ADCP immunoreactivity. Linear regression analysis showed that the expression of ADCP correlates with that of SC and CEA. However, no significant correlation emerged between the histological parameters or the Dukes' stage and any of the immunohistological parameters. Comparison of the histological characteristics of carcinomas exhibiting little or no ADCP immunoreactivity with those showing extensive immunoreactivity, showed that membranous ADCP immunoreactivity occurs more frequently in well-differentiated carcinomas. Structural parameters showed a better correlation with membranous ADCP expression than the cytological variables. It is concluded that membranous expression of ADCP and CEA are indicators of a high level of differentiation as reflected primarily in the structural characteristics of the tumor.
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PMID:Adenosine deaminase complexing protein (ADCP) immunoreactivity in colorectal adenocarcinoma. 395 58

As an aid in the differential diagnosis of exudative pleural effusions, tumor markers were investigated. We measured immunosuppressive acidic protein (IAP), carbohydrate antigen 19-9 (CA 19-9), tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), adenosine deaminase (ADA), and alpha 1-acid glycoprotein (AGP) in the pleural fluid of 36 patients with carcinomatous pleural effusions and of 35 patients with tuberculous pleurisy because we have frequently found these diseases to be associated with exudative pleuritis. Tuberculous pleural effusions had significantly higher levels of IAP, ADA, and AGP than carcinomatous effusions (p less than 0.005). On the other hand, CEA, CA 19-9, and TPA were significantly higher in carcinomatous pleural fluids than in tuberculous fluids (p less than 0.05). There was a correlation between IAP and AGP levels, and their specificity was low. Therefore, combined assays of CEA, CA 19-9, and ADA may be useful in distinguishing pleural effusions due to malignancies from those of tuberculous origin.
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PMID:Carcinomatous and tuberculous pleural effusions. Comparison of tumor markers. 397 60

The relationship between the intracellular levels of DNA polymerase alpha (DP-alpha), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) and the degree of malignancy of human lymphomas was investigated. Twelve non-neoplastic lymph nodes and 88 malignant lymphomas were examined. For non-Hodgkin's lymphomas (NHL) the low or high grade of malignancy was established according to three classifications: the Rappaport, the Kiel and the Working Formulation for Clinical Usage, with the latter also recognizing an intermediate grade group. Non-neoplastic lymph nodes had significantly lower levels of all the three enzymes than those found in high-grade malignant NHL (the P value ranged from less than 0.02 to less than 0.001). Hodgkin's disease, a slowly evolving neoplasia, showed lower levels of DP-alpha (P less than 0.001) and ADA (P less than 0.001), but not of LDH, than high-grade NHL. Among NHL, whatever classification was used, the low-grade malignant lymphomas had significantly lower levels than the high-grade ones for all the three enzymes (P less than 0.005 or P less than 0.001). The intermediate-grade group of the Working Formulation differed from the high-grade group for DP-alpha (P less than 0.01) and ADA (P less than 0.02) but not for LDH. It differed from the low-grade group only for ADA (P less than 0.005). Lymphoblastic and Burkitt's lymphomas were the groups with the highest levels of the three enzymes. Among low-grade lymphomas very low values were found in the histological entities defined as DLWD in the Rappaport classification, CLL and lymphoplasmacytoid immunocytoma in the Kiel classification and small lymphocytic (group A) in the WF. The levels of all enzymes in these histotypes were always significantly different from the other low-grade histotypes, and from the intermediate-grade ones of the WF. In the Kiel classification polymorphous lymphoplasmacytoid lymphoma, recently recognized as a group with a quite aggressive clinical course, was characterized by high levels of all three enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relation between enzymatic activities and the degree of malignancy of human lymphomas. 404 77

Several observations by independent investigators in the past have indicated that adenosine deaminase complexing protein (ADCP), present in considerable quantities in certain human tissues, was absent or decreased in the cancers originated from them. During the present study, electrophoretic analysis of adenosine deaminase (ADA) isozymes and radioimmunoassay for ADCP in the primary fibroblasts and the transformed as well as certain tumor derived cell lines have demonstrated that ADCP present in large quantities in the primary cells was absent or nearly absent in the transformed or tumor-derived cell lines. Though the mechanisms involved are not yet clear, the above observations indicate that ADCP has the potentials of a useful marker in the studies on transformed cells and cancer tissues.
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PMID:Adenosine deaminase complexing protein (ADCP): a transformation sensitive protein with potentials of a cancer marker. 613 97

The analysis of seven differentiation markers following incubation with the tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) was examined in the human leukemic T-cell line MOLT-3. Significant changes were observed in the activity of the markers terminal deoxynucleotidyl transferase (TdT). spontaneous proliferation and the ability of these cells to bind sheep erythrocytes. Levels of human thymus-leukemia-associated antigen (HThy-L) recently identified as a low molecular weight form of adenosine deaminase (ADA), were reduced by about 50%. No significant changes were observed in ecto-5'-nucleotidase [5'-NT) activities, in the proliferative response to PHA, or in the expression of IA-like antigens. These data and the time kinetics of the changes suggest that following incubation of these T-lymphoblasts with TPA there is a sequential loss of TdT, loss of the capacity for spontaneous proliferation, and the appearance of receptors for sheep erythrocytes. Subsequently there is a decrease in the level of HThy-L/ADA. This sequence appears to follow that proposed for prethymic precursor T-cell differentiation following activation with thymic epithelium.
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PMID:Modulation of human T-cell differentiation markers by 12-O-tetradecanoylphorbol-13-acetate. 627 66

Lymphocytes from patients with chronic lymphatic leukemia, acute lymphoblastic leukemia and acute myeloid leukemia have been characterized by the activity of two enzymes involved in purine metabolism--adenosine deaminase and purine nucleoside phosphorylase and by the analysis of surface marker expression. The data obtained suggest that the activity of enzymes of purine metabolism can be used as a complementary diagnostic marker to conventional cell surface characteristics for the classification of lymphoproliferative diseases, especially in the case of T-acute lymphoblastic leukemia. The changes of the purine pathway enzymes may prove to be useful also as therapeutic determinants in hemopoietic neoplasia, particularly in the lymphoid malignancies.
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PMID:Enzymes of purine metabolism and membrane phenotype in malignant cells of some leukemia patients. 644 Nov 24


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