Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine deaminase activity, with arabinosyladenine (ara-A) used as the substrate, was measured in human leukemic cells and major tissues of man, rat, and mouse. The enzyme is stable in frozen tissues for at least 1 week, in frozen homogenate for several months, or after overnight dialysis at 4 degrees C in 0.25 M sucrose. The adenosine deaminase of chronic myelogenous leukemic (CML) cells has a Km of 0.6 mM and a Vmax of 183 mumols x 10(-2)/g of cells/minute. All species have highest activities in spleen and intestine. Kidney activity is highest in rat and lowest in man. The human brain has higher activity than the mouse or rat brain, and activity is higher in mouse liver than in human or rat liver. Activity in lung tissues is moderate and similar in all three species. The mean activity in CML cells is 195 mumols x 10(-2)/g of cells/minute, and the activity is higher in patients with CML in blast cell crisis. Acute myelogenous and lymphocytic leukemia cells also have very high activities. Drug concentrations required for inhibiting 50% of CML enzyme activity are 10 nM or erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), 0.6 nM of coformycin, and 0.3 nM of 2'-deoxycoformycin. Preincubation of the enzyme with coformycin, but not with EHNA, enhances the inhibition. In view of the high adenosine deaminase activities in tissues and the enhancement of the therapeutic effect of ara-A by inhibitors in mouse tumor systems, clinical trials of these combinations are warranted. They may be particularly beneficial to patients with CML in blast cell crisis.
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PMID:Distribution and inhibition of adenosine deaminase in tissues of man, rat, and mouse. 696 22

2'-deoxycoformycin (2'-dCF) is a powerful inhibitor of adenosine deaminase (ADA), an enzyme found in high concentrations in lymphoid tissue. Although inactive in preclinical tumor models, 2'-dCF has shown clinical antitumor activity as a single agent in lymphoid malignancies. This drug has the added potential of being useful as a potentiator of other antitumor agents which are deactivated by ADA. It is also possible that the drug has potential as an immunosuppressive agent. Phase I studies are ongoing and phase II trials are planned to define the antitumor spectrum of this agent.
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PMID:2'-deoxycoformycin. A new anticancer agent. 701 25

We determined the levels of adenosine deaminase (ADA) activity in peripheral lymphocytes of 22 tumor patients: 54% had metastasis; 59% were undergoing chemotherapy at the time of the study. The mean ADA value of all patients was significantly lower than that of 15 healthy subjects of a similar age. When the patients were allocated by treatment and metastasis, the decrease of ADA activity appeared to be associated to the presence of metastasis.
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PMID:Decreased adenosine deaminase activity in peripheral lymphocytes from tumor patients with metastasis. 745 19

Antimetabolites are rational agents with specific S-phase and enzyme targets. Low levels of target enzymes in tumors are associated with innate drug sensitivity, and the general requirement for transport and metabolic activation of antimetabolites creates several loci of acquired drug resistance. Pharmacodynamic studies of TS inhibition after fluoropyrimidines clearly can predict for tumor sensitivity and response to fluoropyrimidine-based therapy or identify factors related to resistance, and ara-dCTP levels in leukemic cells can be useful for refined dosing of araC. Powerful new DHFR and TS directed agents are in advanced levels of clinical evaluation, and purine analogues directed against adenosine deaminase are newly available for treatment of indolent lymphomas. Progress in analysis of tumors, such as PCR techniques to study gene expression or immunostaining of target enzymes, offer increasing promise for individualization of patient selection. Increased experience with biochemical modulators, including biologic response modifiers, has opened the possibility for selective attack on specific mechanisms of drug resistance. Sophisticated pharmacokinetic modeling and pharmacogenetic testing of metabolic phenotypes can now be done to achieve optimal dosing with less risk of toxicity. Considerations of ultimate genetic mechanisms of antimetabolite effects, especially by programmed cell death, and relationships to mechanisms of cell cycle regulation offer exciting rationales for future drug development.
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PMID:Clinical resistance to antimetabolites. 764 70

A large series of samples obtained after surgical resection of intestinal mucosa of patients affected by intestinal carcinoma was examined in order to define possible relationships between levels of enzymes involved in the purine salvage pathway and clinical/biological parameters of aggressiveness and invasiveness. The results confirm our previous observation on a different pattern of purine salvage enzymes in tumor as compared to normal colon tissues (Camici et al., 1990). In fact, we observed in human colon tumor tissues a significant enhancement of the three enzymes involved in the synthesis of IMP, hypoxanthine guanine phosphoribosyltransferase (HGPRT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP). On the other hand, no variation was observed in the 5'-nucleotidase and alkaline phosphatase activities. While we could not find a significant correlation between HGPRT, ADA and PNP activities and histologic grading or biological parameters of tumor aggressiveness, the significant correlation with the extent of disease, as expressed by the Dukes' stage, would demonstrate at least for human colon tumors, a relationship between enzyme activity and tumor invasiveness.
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PMID:Relationship between the levels of purine salvage pathway enzymes and clinical/biological aggressiveness of human colon carcinoma. 779 89

CD26 is identical to the cell surface ectoenzyme dipeptidyl peptidase IV (DPPIV). CD26/DPPIV is associated with T-cell activation and proliferation and also may function as an auxiliary adhesion factor. Although CD26/DPPIV has been previously studied on lymphoid populations and on leukemias/lymphomas of B- and T-cell phenotype, little is known about its expression and functional role in some specific types of lymphomas, such as CD30-positive anaplastic large cell (ALC) lymphomas and Hodgkin's disease (HD). A series of 81 lymphoma samples, including 23 cases of HD, 17 cases of CD30-positive ALC lymphomas, 41 cases of other non-Hodgkin's lymphomas (NHL), and a panel of HD- or ALC lymphoma-derived human cell lines were evaluated for CD26/DPPIV expression by enzyme histochemistry and immunohistochemistry on frozen sections and cell smears. CD26/DPPIV protein was expressed on neoplastic cells in 12 of 17 (71%) ALC lymphomas irrespective of their antigenic phenotype and in seven of 15 (47%) T-cell NHLs. In contrast, we did not detect CD26/DPPIV expression in tumor cells from 26 cases of B-cell NHL other than ALC lymphomas or in Reed Sternberg (RS) cells and variants of 21 of 23 HD cases. Accordingly, CD26/DPPIV expression was maintained on the CD30-positive ALC lymphoma cell line Karpas 299, but the molecule was not detected on HD-derived cell lines of B, T, or non-B non-T phenotype. These results may support a new potential tool for the phenotypic separation of ALC lymphomas from HD based on the differential expression of the CD26/DPPIV molecule. Moreover, given the demonstration that CD26/DPPIV is identical to the human adenosine deaminase (ADA) binding protein, it could be speculated that CD26/DPPIV also may function by interacting with ADA to regulate the growth of CD26/DPPIV expressing neoplastic cells in ALC lymphomas.
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PMID:CD26/dipeptidyl peptidase IV expression in human lymphomas is restricted to CD30-positive anaplastic large cell and a subset of T-cell non-Hodgkin's lymphomas. 800 32

We have investigated the hypothesis that adenosine, a purine nucleoside produced within hypoxic regions of solid tumors, may interfere with the recognition of tumor cells by cytolytic effector cells of the immune system. We measured the adhesion of murine spleen-derived anti-CD3-activated killer (AK) lymphocytes to syngeneic MCA-38 colon adenocarcinoma cells in a model system. Adenosine, in the presence of the adenosine deaminase inhibitor coformycin to prevent the breakdown of adenosine, inhibited adhesion by up to 60%. The inhibitory effect of adenosine was exerted on the AK cells and not on the MCA-38 targets. The response to adenosine was generated at the cell surface, since the inhibition of adhesion was not abrogated by S-(4-nitrobenzyl)-6-thioinosine or dipyridamole, which block adenosine uptake. The inhibition of adhesion due to adenosine was not blocked by either the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine or the A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine. This suggested that a non-A1, A2 receptor might be involved. The relative order of potencies of adenosine and common analogues was: 5'-N-ethylcarboxamidoadenosine = adenosine = (R)-phenylisopropyladenosine > N6-cyclopentyladenosine > 2-chloro-N6-cyclopentyladenosine = 2-p-(2- carboxyethyl)phenethylamino-5'-N-ethyl-carboxamidoadenosine. This agonist potency profile was again inconsistent with either the A1 or the A2 receptor subtype but indicated that the recently described A3 receptor subtype might be responsible for the inhibition of adhesion. Consistent with this suggestion, aminophenylethyladenosine, an adenosine analogue that binds with high affinity to A3 receptors, inhibited the adhesion of AK cells to MCA-38 tumor cells with high potency (50% inhibitory concentration approximately 1 nM). Adenosine, therefore, interferes with the AK cell recognition of colorectal tumor targets by acting through an A3 receptor on the effector cells. We suggest that this mechanism of immunosuppression, secondary to tissue hypoxia, may be important in the resistance of colorectal and other solid cancers to immunotherapy.
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PMID:Adenosine inhibits the adhesion of anti-CD3-activated killer lymphocytes to adenocarcinoma cells through an A3 receptor. 801 76

We determined activities of adenosine deaminase (ADA), 5' nucleotidase (5NT), xanthine oxidase (XO), superoxide dismutase (Cu-Zn SOD), and catalase (CAT) enzymes in 15 human laryngeal tissues with well-differentiated squamous cell carcinomas, in 15 corresponding tumor-free adjacent tissues and in 7 normal laryngeal tissues. We found lower ADA and 5NT and higher XO, Cu-Zn SOD, and CAT activities in cancerous tissues than those in corresponding noncancerous ones. In the correlation analysis, we established one positive intercorrelation, which was between ADA activities of tumor tissues and noncancerous adjacent tissues. We also found some significant intracorrelations between enzyme activities of the tissues, all of which were positive in cancerous ones.
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PMID:Adenosine deaminase, 5' nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous and noncancerous human laryngeal tissues. 813 95

Clinical and analytic data of 64 patients with firm etiologic diagnosis of pleural effusion with adenosine deaminase (ADA) present, were analyzed retrospectively. The patients had entered our hospital over a 40-month period. ADA activity in pleural fluid was analyzed by the Blake and Berman kinetic method. Mean ADA activity of the total sample was 32 U/l (SD:23.9). In patients with tuberculous pleural effusion ADA activity was higher than in the remaining patients (47.7, SD:21.4, versus 15.5 SD: 13.2; p < 0.0001). In the group of patients with tuberculous pleuritis diagnosed by pleural biopsy (22 cases) the presence of necrotizing granulomas was associated with slightly higher ADA activity although the difference was not statistically significant (49.2 SD 10.1 versus 41.3 SD 8.9; p = 0.07). Among only patients with tuberculous pleuritis or neoplasia with lymphocytic exudate, a cut off point greater than 23 U for ADA predicted a diagnosis of tuberculous pleuritis with a sensitivity of 0.96, specificity of 1, positive predictive value of 1, negative predictive value of 0.94, and a confidence limit of 0.97. In conclusion, ADA activity greater than 23 U determined by the kinetic method in pleural fluid with signs of lymphocytic exudate is strongly suggestive of pleural tuberculosis based on our sample of patients with pleural effusion.
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PMID:[Adenosine deaminase activity in the pleural effusion. A study of 64 cases]. 814 81

Adenosine deaminase is one of the key enzymes in purine nucleotide degradation. This enzyme exists in most of the human tissues and the activity is high in lymphatic tissues, especially in T lymphocytes. Elevated adenosine deaminase activity in T cell leukemia has been reported, and its inhibitor, deoxycoformycin, has been developed as an antitumor agent. In some types of leukemia, serum adenosine deaminase activity increases in accordance with the severity of the disease. Although mycosis fungoides rarely involves peripheral blood, tumor cells do invade the skin. In order to evaluate the clinical significance of adenosine deaminase in mycosis fungoides, adenosine deaminase activity was measured in sera of 15 patients with mycosis fungoides at various stages. The mean enzyme activity was 23.2 IU/l, which was high with statistical significance compared with healthy controls (P < 0.001). Nine of twelve patients in the plaque stage (T2N0M0, IB) showed higher adenosine deaminase activity than did the normal population. The mean adenosine deaminase activity in sera in the patients in the plaque stage (T2N0M0, IB) was as high as 19.0 IU/l (range 13.7-21.4) with statistical significance compared with healthy control (P < 0.001). Three tumor stage patients without visceral involvement (T3N0M0, IIB) showed higher levels of adenosine deaminase activity (19.7, 21.5, 24.4 IU/l). An erythrodermic patient (T4N0M0, III) also had a high adenosine deaminase activity 28.4 IU/l. Two tumor stage patients with organ involvement (T3N0M1, IVB) exhibited extremely high adenosine deaminase activity (60.9, 32.2 IU/l). The adenosine deaminase activity in sera showed a tendency to become higher with the extension of the stages.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical significance of serum adenosine deaminase activity in patients with mycosis fungoides. 840 19


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