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)

Many reports have described the relationship of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities with the immunological subclasses of acute lymphoblastic leukemia (ALL). The clinical significance of these enzymes in leukemias is not yet completely understood. We performed a study in 83 children with untreated ALL to establish the relationships of ADA and PNP to clinical outcome, in vitro drug resistance and differentiation stage of B-cell lineage ALL. ADA and PNP activities were determined radiochemically. In vitro resistance to 6-thioguanine (6-TG) was determined with the MTT assay. ADA activity was not different between proB- and cALL cases but decreased in the sequential differentiation stages cALL----preB-ALL----B-ALL. The PNP level was not different between the four stages of B-lineage ALL. Patients with cALL/preB ALL with low ADA activities had a significantly poorer probability of survival (p = 0.005) than patients with high ADA levels. Patients with cALL/preB ALL with low PNP activities showed a non-significant trend for a poorer prognosis (0.05 less than p less than 0.10) than patients with a high PNP level. Low ADA and PNP activities were not related to in vitro resistance to 6-TG. We conclude that ADA decreases and PNP remains constant in sequential differentiation stages of B-lineage ALL. Patients with precursor B-lineage ALL with low activities of ADA have a poorer prognosis than those with high activities of these enzymes. No relationship could be detected between ADA or PNP activity and resistance to 6-TG.
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PMID:Adenosine deaminase and purine nucleoside phosphorylase in childhood lymphoblastic leukemia: relation with differentiation stage, in vitro drug resistance and clinical prognosis. 159 2

Because of the importance of adenosine deaminase (ADA) in brain function, a histochemical method for visualizing the enzyme in various areas of the human neuraxis was devised, using an MTT [3-(4,5-dimethyl-thiazolyl-2)-2,5-diphenyltetrazolium bromide] method and glutaraldehyde fixation. Controls consisted of preincubation without the substrate, incubation with omission successively of the substrate, MTT tetrazolium, purine nucleoside phosphorylase (PNP), xanthine oxidase (XO), NaCl, boiling for 20 min prior to fixation and incubation, and of incubation of sections with two powerful inhibitors of the enzyme, i.e., 2'-deoxycoformycin and EHNA [erythro-9-(2-hydroxy-3-nonyl)adenine.HCl]. The positive reaction consisted of the deposition of brownish-purple granules, as well as a diffuse nongranular reaction in the cytoplasm of neurons and glial cells, and in the interstitial spaces. Sections from 15 different areas in four brains were examined by this method. This is the first time that adenosine deaminase has been demonstrated histochemically in the nervous system of humans or of any other species.
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PMID:Histochemical demonstration of adenosine deaminase in the human neuraxis. Preliminary observations. 404 5

The effect of sinusoidally varying magnetic fields (SVMF) on chick embryo fibroblasts (CEF) was examined by two independent methods: 1) measurement of cell proliferation at 0.06-0.7 mT (100, 60 and 50 Hz) using a colorimetric assay (MTT); 2) monitoring of specific activity of adenosine deaminase (ADA) at 0.3 and 0.7 mT, 60 Hz. Both increased cell proliferation and reduced ADA specific activity are associated with cell transformation. The MTT test showed an increase in cell proliferation of up to 64% after a 24 h exposure to SVMF at 100 Hz, 0.7 mT. Cell proliferation at constant frequency (100 Hz) depended on SVMF intensity. Cell proliferation at constant intensity (0.7 mT) increased with increasing field frequency. At 0.7 mT, 60 Hz cell proliferation increased by 31%, 28%, and 26% when measured by hemocytometry, 3H-thymidine incorporation, and the MTT assay, respectively. ADA specific activity in CEF decreased by circa 48% on exposure to SVMF at 60 Hz, 0.3 mT for 24 h; only a statistically insignificant trend was seen at 0.7 mT, 60 Hz. Our findings showed that CEF cell proliferation and ADA specific activity were modified by SVMF. Both methods, independently, qualitatively detect a magnetic field effect.
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PMID:Effect of sinusoidally varying magnetic fields on cell proliferation and adenosine deaminase specific activity. 945 6

Adenosine is a regulatory molecule with widespread physiological effects in almost every cells and acts as a potent regulator of cell growth. Adenosine has been shown to inhibit cell growth and induce apoptosis in the several cancer cells via caspase activation and Bcl-2/Bax pathway. The present study was designed to understand the mechanism underlying adenosine-induced apoptosis in the OVCAR-3 human ovarian cancer cells. MTT viability, BrdU and cell counting assays were used to study the cell proliferation effect of adenosine in presence of adenosine deaminase inhibitor and the nucleoside transporter inhibitor. Cell cycle analysis, propidium iodide and annexin V staining, caspase-3 activity assay, cyclinD1, Cdk4, Bcl-2 and Bax protein expressions were assessed to detect apoptosis. Adenosine significantly inhibited cell proliferation in a concentration-dependent manner in OVCAR-3 cell line. Adenosine induced cell cycle arrest in G0/G1 phase via Cdk4/cyclinD1-mediated pathway. Adenosine induced apoptosis, which was determined by Annexin V-FITC staining and increased sub-G1 population. Moreover, down-regulation of Bcl-2 protein expression, up-regulation of Bax protein expression and activation of caspase-3 were observed in response to adenosine treatment. The results of this study suggest that extracellular adenosine induced G1 cell cycle arrest and apoptosis in ovarian cancer cells via cyclinD1/ Cdk4 and Bcl-2/Bax pathways and caspase-3 activation. These data might suggest that adenosine could be used as an agent for the treatment of ovarian cancer.
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PMID:Adenosine induces cell cycle arrest and apoptosis via cyclinD1/Cdk4 and Bcl-2/Bax pathways in human ovarian cancer cell line OVCAR-3. 2334 14

Malignant melanoma is the most deadly type of skin cancer. The lack of effective pharmacological approaches for this tumour can be related to the incomplete understanding of the pathophysiological mechanisms involved in melanoma cell proliferation. Adenosine has growth-promoting and growth inhibitory effects on tumour cells. We aimed to investigate effects of adenosine and its metabolic product, inosine, on human C32 melanoma cells and the signalling pathways involved. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction and bromodeoxyuridine (BrdU) proliferation assays were used to evaluate adenosine, adenosine deaminase and inosine effects, in the absence or presence of adenosine receptor (AR), A3 AR and P2Y1 R antagonists and PLC, PKC, MEK1/2 and PI3K inhibitors. ERK1/2 levels were determined using an ELISA kit. Adenosine and inosine levels were quantified using an enzyme-coupled assay. Adenosine caused cell proliferation through AR activation. Adenosine deaminase increased inosine levels (nanomolar concentrations) on the extracellular space, in a time-dependent manner, inducing proliferation through A3 AR activation. Micromolar concentrations of inosine enhanced proliferation through A3 AR activation, causing an increase in ERK1/2 levels, and P2Y1 R activation via ENT-dependent mechanisms. We propose the simultaneous activation of PLC-PKC-MEK1/2-ERK1/2 and PI3K pathways as the main mechanism responsible for the proliferative effect elicited by inosine and its significant role in melanoma cancer progression.
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PMID:Inosine strongly enhances proliferation of human C32 melanoma cells through PLC-PKC-MEK1/2-ERK1/2 and PI3K pathways. 2490 96

The aim of this study was to investigate the inhibition effects of cordycepin and its derivatives on endometrial cancer cell growth. Cytotoxicity MTT assays, clonogenic assays, and flow cytometry were used to observe the effects on apoptosis and regulation of the cell cycle of Ishikawa cells under various concentrations of cordycepin, cisplatin, and combinations of the two. Validated in silico docking simulations were performed on 31 cordycepin derivatives against adenosine deaminase (ADA) to predict their binding affinities and hence their potential tendency to be metabolized by ADA. Cordycepin has a significant dose-dependent inhibitory effect on cell proliferation. The combination of cordycepin and cisplatin produced greater inhibition effects than did cordycepin alone. Apoptosis investigations confirmed the ability of cordycepin to induce the apoptosis of Ishikawa cells. The in silico results indicate that compound MRS5698 is least metabolized by ADA and has acceptable drug likeness and safety profiles. This is the first study to confirm the cytotoxic effects of cordycepin on endometrial cancer cells. This study also identified cordycepin derivatives with promising pharmacological and pharmacokinetic properties for further investigation in the development of new treatments for endometrial cancer.
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PMID:Experimental and In Silico Analysis of Cordycepin and its Derivatives as Endometrial Cancer Treatment. 2967 23