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)

Pentostatin, a novel inhibitor of adenosine deaminase, has shown activity in various lymphoid malignancies of both the T and B cell lineage. This agent has unique side effects and in general myelosuppression has been mild. Interferon has both antiviral and antineoplastic properties. This agent has shown activity in hairy cell leukemia, chronic granulocytic leukemia, low grade lymphoma, and myeloma. Side effects from interferon are in general dissimilar to those that have been seen with pentostatin and in particular myelosuppression has not been a major toxicity with low doses of interferon. This current trial explored the combination of pentostatin and interferon in hematologic malignancies. Fifteen patients were enrolled in this phase I trial at a fixed dose of pentostatin of 4 mg/m2 biweekly and interferon at doses of 0.5, 1, 2, or 4 million units/m2 of interferon. At the first three dose levels of interferon nausea and vomiting were the predominant toxicity and appeared to worsen with time on study. Fatigue also was seen at the lowest level of interferon and was severe enough to cause two individuals to discontinue the study medications. At higher dose levels of interferon, myelosuppression, nausea and vomiting, and fatigue were the predominant toxicities. One patient with hairy cell leukemia had a complete response and a second patient with T cell cutaneous lymphoma had a partial response which lasted for 6 to 7 weeks. The maximum tolerated dose of interferon with pentostatin in this patient population was four million units/m2.
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PMID:A phase I trial of alpha-interferon in combination with pentostatin in hematologic malignancies. 205 72

We reviewed 327 patients with pleural effusion who had been examined at our department for identification of its cause during the 14 years between 1974 and 1987, and studied the percentages of definitive diagnosis by examining the pleural fluids of patients with malignant tumor and tuberculosis. We also measured the levels of carcinoembryonic antigen (CEA) and adenosine deaminase (ADA) in the pleural fluids of these patients and evaluated their diagnostic usefulness. We further carried out a detailed clinical study of the factors affecting the CEA and ADA activities in the pleural fluids, which are considered to be particularly important in differential diagnosis of patients with pleural effusion. Of 327 patients with pleural effusion, malignancy-related pleurisy was observed in 166 patients (50.8%), and tuberculous pleurisy in 85 (26.0%). The rate of definitive diagnosis based on the examination of the pleural effusion in these patients indicated that 20-30% of them pose difficulty in clinical diagnosis. CEA was positive in 64.7% of patients with malignancy-related pleurisy, and ADA was positive in 97.7% of those with tuberculous pleurisy. These suggested their usefulness as supportive diagnostic methods of those diseases. In addition, CEA was elevated in patients with complications such as empyema, suggesting an effect of non-specific cross-reacting antigen (NCA). ADA showed high values in patients with conditions related to cell-mediated immunological responses as well as empyema and hemolysis. It suggested the release of ADA from blood cells due to hemolysis. These factors must be carefully evaluated in the interpretation of the CEA and ADA activities in pleural effusion.
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PMID:[Clinical evaluation of pleural effusion--carcinoembryonic antigen (CEA) and adenosine deaminase (ADA) activities in pleural fluids]. 207 54

We have studied the expression of mRNA encoding adenosine deaminase (ADA; EC 3.5.4.4), purine nucleoside phosphorylase (PNP; EC 2.4.2.1), and terminal deoxynucleotidyltransferase (TdT; EC 2.7.7.31) in different leukemic cell lines of B- and T-cell lineage. Incubation of leukemic cells in the presence of the phorbol esters, 12-O-tetradecanoyl-phorbol-13-acetate or phorbol 12,13-dibutyrate, resulted in reduction of ADA and TdT mRNA levels, while PNP mRNA levels increased under the same treatment. The effect of TPA on the activity of these enzymes correlated well with its effects on their mRNA levels. TPA caused a 40% decrease in ADA and a 60% decrease in TdT enzyme activity, after 6 h of treatment. In contrast, PNP activity increased up to 200% after 12 h of incubation with the phorbol ester. The changes induced by the phorbol esters in the levels of mRNA of ADA, PNP, and TdT, and their enzyme activities in human leukemic cell lines mimic the changes in the activities of these enzymes in developing T-lymphocytes during differentiation in vivo, suggesting a role for protein kinase C in the regulation of ADA, PNP, and TdT gene expression during lymphoid cell differentiation.
Cancer Res 1990 May 15
PMID:Phorbol esters induce changes in adenosine deaminase, purine nucleoside phosphorylase, and terminal deoxynucleotidyl transferase messenger RNA levels in human leukemic cell lines. 211 May 2

The enzymatic pattern of five enzymes involved in the purine salvage pathway, namely purine nucleoside phosphorylase (EC 2.4.2.1), adenosine deaminase (EC 3.5.4.4), 5'-nucleotidase (EC 3.1.3.5), alkaline phosphatase (EC 3.1.3.1), and hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) has been evaluated both in human intestinal and breast carcinomas and compared to that of normal tissues. A higher level of hypoxanthine-guanine phosphoribosyltransferase was associated with tumor tissues. This metabolic alteration should lead to an elevated synthesis of nucleotides in cancer cells, might confer selective growth advantages to neoplastic tissues, and account, at least in part, for the difficulties encountered in the chemotherapy of human tumors, by using compounds affecting only the purine de novo biosynthesis.
Cancer Biochem Biophys 1990 Jul
PMID:Purine salvage enzyme activities in normal and neoplastic human tissues. 212 39

The drugs used to treat cancer today are a confusing array of compounds with differing origins, mechanisms of action, antitumour spectra, and toxicities. There are 5 chemically distinct types of alkylating agents; the prototypical agent is chlormethine (mustine) and the most recent addition is ifosfamide. Generally these drugs all work in the same fashion and their activity is cell cycle proliferation-dependent but phase-nonspecific. The antimetabolites consist of methotrexate, the pyrimidine and purine analogues, and pentostatin, an adenosine deaminase inhibitor and relative newcomer to the class. The individual mechanisms of action of these agents differ but cytotoxicity is generally cell cycle phase-specific. Naturally occurring antineoplastic agents include the vinca alkaloids, the antitumour antibiotics, 1-asparaginase, the epipodophyllotoxins, and homoharringtonine; it is the most diverse collection of compounds. For these drugs as well as the antimetabolites, the therapeutic and toxic effects often depend heavily on duration of exposure to the drug, an effect known as schedule dependency. Finally, the agents that do not fit one of the above categories are cisplatin (cis-platinum II) and its analogue carboplatin (which is being actively investigated), hydroxycarbamide (hydroxyurea), procarbazine, hexamethylmelamine, amsacrine, and mitoxantrone (mitozantrone). In the future we can expect not only the emergence of new antineoplastic drugs, but also further refinements in the use of existing drugs. We are beginning to understand the various types of resistance manifested by tumour cells. Our ability to use these potent and highly toxic agents safely should continue to improve.
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PMID:Antineoplastic drugs in 1990. A review (Part I). 219 Jul 92

The effects of ribonucleotide reductase inhibitors on the growth of the human colon carcinoma cell line HT-29 were examined. Inhibitors were chosen for these studies that were specifically directed at each of the subunits of ribonucleotide reductase. The concentrations of drugs required to inhibit the growth of HT-29 cells by 50% (IC50) for hydroxyurea, 2,3-dihydro-lH-pyrazole-[2,3a]imidazole (IMPY), and 4-methyl-5-amino-l-formyl-isoquinoline thiosemicarbazone (MAIQ) were 206, 996, and 3.2 microM, respectively. Although the IC50 for deoxyadenosine alone was greater than 2,000 microM, in the presence of 5 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), which protects deoxyadenosine from deamination by adenosine deaminase, it was reduced to 112 microM. The IC50 for deoxyguanosine was 1,060 microM. The addition of 8-aminoguanosine to protect deoxyguanosine from phosphorolysis by purine nucleoside phosphorylase did not increase the toxicity of deoxyguanosine in HT-29 cells. The combination of MAIQ or IMPY and deoxyadenosine/EHNA gave strong synergistic inhibition of HT-29 cell growth. The results of these studies indicate that ribonucleotide reductase inhibitors effectively block the growth of human colon carcinoma HT-29 cells and that combinations of inhibitors directed at the individual subunits of reductase result in synergistic inhibition of HT-29 cell growth in culture.
Cancer Chemother Pharmacol 1990
PMID:Effect of ribonucleotide reductase inhibitors on the growth of human colon carcinoma HT-29 cells in culture. 220 72

Simultaneous determination of ascitic fluid and serum adenosine deaminase (ADA) activity was evaluated as a diagnostic aid in peritoneal tuberculosis. The ascites was due to peritoneal tuberculosis (group 1), cirrhosis of the liver (group 2), cirrhosis of the liver with spontaneous bacterial peritonitis (group 3), peritoneal malignancy (group 4), Budd-Chiari Syndrome (group 5) and miscellaneous conditions (group 6). Serum from patients of pulmonary tuberculosis and healthy volunteers was analysed for enzyme activity. In patients with peritoneal tuberculosis the ascitic fluid and serum ADA activity was significantly higher than for the other groups (P less than 0.001). Levels above 36 u/l in ascitic fluid and above 54 u/l in the serum suggest tuberculosis. The ascitic fluid/serum ADA ratio was also higher in patients with peritoneal tuberculosis than with other causes of ascites (P less than 0.01). A ratio of more than 0.984 was suggestive of tuberculosis.
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PMID:Adenosine deaminase (ADA) in peritoneal tuberculosis: diagnostic value in ascitic fluid and serum. 221 61

Activities of thymidine kinase, thymidine phosphorylase, adenosine deaminase and 5'-nucleotidase of AMP were studied in blood serum and lymphocytes of healthy women, patients with mastopathy and with mammary gland cancer of 23-70 years old. Age-dependent alterations in the enzymatic activity were detected in blood serum of healthy women. Activity of thymidine kinase was increased simultaneously with a decrease in thymidine phosphorylase activity in 36-70 years old oncological patients, while adenosine deaminase activity was increased in patients with mastopathy and with mammary gland cancer of all the age groups. Dynamics of the enzymatic activity studied before and during chemotherapeutic treatment may be used as one of biochemical tests for evaluation of the therapy efficiency in oncological patients.
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PMID:[Age-dependent characteristics of metabolism of DNA precursors in healthy women, patients with mastopathy and breast cancer]. 225 96

T-cell acute lymphoblastic leukemia is an aggressive disease that responds poorly to "standard" therapy designed for the more common B-lineage ALLs in childhood. The principles of this "standard" therapy were derived from empiric clinical trials. Thus, it is not surprising that the therapy that had the greatest impact on survival in the group as a whole would be found to be most successful for the most common subset of patients. T-cell malignant lymphoblasts share many biologic features that set them apart from the more common B-lineage lymphoblasts. Some of these biologic features suggest therapeutic approaches that should be particularly successful in treating patients with T-cell leukemia. The use of aggressive, multiple-agent "pulse" chemotherapy has been shown through empiric trials to have relative efficacy in T-cell lymphoblastic leukemia, presumably because of the rapid generation time and high growth fraction. Future studies will (1) determine the optimal dose and schedule of cytosine arabinoside needed to exploit the increased Ara-CTP accumulation in T-cell blasts, (2) determine the efficacy of a new agent, deoxycoformycin, an inhibitor of adenosine deaminase, to exploit the biochemical phenotype of T-cell blasts, and (3) assess the ability of conjugated anti-T monoclonal antibodies to deliver a cytotoxic agent, thus exploiting unique antigenic determinants at the cell surface. As more is learned about the biology of T-cell malignancies, further treatment strategies may be suggested to exploit the new features that are discovered. Similarly, it is hoped that the unique features of the B-lineage leukemias will suggest treatment strategies that will improve survival in those patients as well. Certainly, improved survival has already been achieved in the case of the B-cell leukemias and Burkitt's lymphomas, and improvement may also be possible for the pre-B and early pre-B phenotypes of lymphoblastic leukemia.
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PMID:Treatment of T-lineage acute lymphoblastic leukemia. 226 86

The activity of thymidine kinase, thymidine phosphorylase, adenosine deaminase, AMP 5'-nucleotidase was assessed in the serum of healthy females, patients with mastopathia cystica and those with stage IIIB breast cancer. The females age ranged from 23 to 70 years. The activity of the enzymes had significant differences in cancer patients. Minimal thymidine phosphorylase activity was found to suggest fibrous cancer. Changes in the enzymes levels in cancer patients on combined treatment may serve a biochemical test indicating the efficacy of the chemotherapy conducted.
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PMID:[Use of enzyme test in chemotherapy of patients with cancer of the breast]. 228 21


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