Disease relevance of CDA

• Adenosine deaminase, 5'-nucleotidase, guanase and cytidine deaminase activities in gastric tissues from patients with gastric cancer [1].
• The activities of the enzymes corresponded well with that seen in acute myeloid leukemia cells except, that the CDD activity was very low in the HL60 cells [2].
• In 1994, the first crystal structure of the dimeric Escherichia coli CDA has been published [3].
• The role of cytidine deaminase and GATA1 mutations in the increased cytosine arabinoside sensitivity of Down syndrome myeloblasts and leukemia cell lines [4].
• This study has shown that serum CD activity is raised in rheumatoid arthritis (RA) compared with osteoarthritis (OA) [5].

Psychiatry related information on CDA

• Agents that affect CDDP accumulation and membrane related systems, cytoplasmic defense mechanisms, as well as DNA accessibility and repair are reviewed [6].
• MG-63 sarcoma cells were stimulated with CDDP for various times and Id expression was assessed by reverse transcription-polymerase chain reaction [7].
• RESULTS: Improvements in processing efficiency (p < 0.001) were noted on tests designed to measure visual scanning and sustained attention (CDS), immediate recall (CDI), and short-term memory (CDD) [8].
• Manifest Anxiety Scale for evaluation of effects of granisetron in chemotherapy with CDDP and 5FU for head and neck cancer [9].
• Since GnRHa increased the cytotoxic effects of CDDP and GnRHa is a compound of high patient compliance, the value of GnRHa as a tumor sensitizer to CDDP should be further tested in clinical trials [10].

High impact information on CDA

• The activation-induced cytidine deaminase (AID) gene, specifically expressed in germinal center B cells in mice, is a member of the cytidine deaminase family [11].
• A novel cytidine deaminase affects antibody diversity [12].
• It was recently reported that APOBEC3G (also known as CEM-15), a cytidine deaminase nucleic acid-editing enzyme, confers this antiviral phenotype on permissive cells [13].
• These results underscore an essential role for the C-terminal domain of AID in CSR that is independent of its cytidine deaminase activity and that is not required for either gene conversion or SHM [14].
• In the present study, we investigated the role of human thioredoxin (hTRX) in the acquisition of cellular resistance to cis-diamminedichloroplatinum (II) (CDDP) [15].

Chemical compound and disease context of CDA

• Thus, our data demonstrate that overexpression of CDD cDNA results in significant protection of human progenitors from cytarabine- as well as gemcitabine-induced toxicity, and allows in vitro selection of transduced cells [16].
• In a separate series of experiments, [4,5-13C]-2'-deoxyuridine was synthesized and found to retain its sp2 hybridization at C-4, after binding by Escherichia coli cytidine deaminase, an enzyme that catalyzes 18O exchange from water into uridine [17].
• Cytidine deaminase activity, C reactive protein, histidine, and erythrocyte sedimentation rate as measures of disease activity in psoriatic arthritis [18].
• CONCLUSION: Homozygous 208G>A alteration in CDA might have caused the severe drug toxicity experienced by a Japanese cancer patient treated with gemcitabine plus cisplatin [19].
• CONCLUSIONS: Our findings indicate that troxacitabine is likely to be effective not only against solid tumors with high CDA activity but also in leukemias which have developed resistance to AraC due to increased CDA levels; this suggests that troxacitabine is a promising agent for the treatment of cancer [20].

Biological context of CDA

• Although 5' flanking sequences for both CDA transcripts exhibited promoter activity in reporter gene assays, activity for the CDAlf was low [4].
• The comparison of our theoretical model with the crystal structure of the human T-CDA, subsequently published in 2004, validates our prediction: not only of the structural features of the monomer and the details of the binding site, but also the multimeric arrangement of the subunits were determined with high accuracy in our model [3].
• The expression of dCK, an activation enzyme, and of CDA, an inactivation enzyme, was decreased and increased in the late phase, respectively [21].
• Cytidine deaminase: a new genetic polymorphism demonstrated in human granulocytes [22].
• Modification of CDD by truncation from the C-terminal end, or by amino acid substitution of an active site glutamate residue, eliminated both the enzyme activity and the growth regulatory potential of CDD [23].

Anatomical context of CDA

• Changes in the activities of cytidine deaminase during differentiation of HL60 cells induced by 1,25 dihydroxy D3 [2].
• Effect of cyclosporin on the activity of cytidine deaminase and adenosine deaminase in the serum and polymorphonuclear leukocytes of patients with rheumatoid arthritis [24].
• Weak correlation of serum CD activity with erythrocyte sedimentation rate (ESR) (r = 0.44) and C-reactive protein (CRP) (r = 0.49) implies that CD estimations supply different though related information about rheumatoid disease activity [5].
• Synovial fluid (SF) CD activity was always less than the corresponding serum activity (mean SF/serum ratio = 0.6) in OA but up to 22 times greater than the corresponding serum activity in RA (mean SF/serum ratio = 13.1), suggesting CD production in inflammatory joints [5].
• Evidence to support the SF neutrophil as a cell of CD origin is provided by the CD gradient running from cells to SF to synovium [5].

Associations of CDA with chemical compounds

• In CLL a significant reduction (P less than 0-001) of AMPA, PNPase and ADA activities was observed without variation of CDA [25].
• A dramatic increase (10-fold or more) in CDA activity was observed in the cells of some patients after only one month of cyclosporin therapy [24].
• CONCLUSIONS: Decreased hENT-1 expression and function is causatively responsible for the acquisition of Ara-C resistance and alterations in dCK and CDA contribute to the higher concentration range [21].
• For this purpose, each of the two forms of CDA was purified close to homogeneity and dissociated into monomers in the presence of a small amount of sodium dodecyl sulfate as a dissociating agent [26].
• Serum osteocalcin (OC) was reduced by 25.8% (P < 0.001), while the levels of CD and pro-MMP-3 increased by 31.2% (P < 0.01) and 53.7% (P < 0.001) during prednisolone treatment compared with the off-treatment period [27].

Regulatory relationships of CDA

• CONCLUSION: APOBEC3G is incorporated into HTLV-1 virions and inhibits the infection of HTLV-1 without exerting its cytidine deaminase activity [28].

Other interactions of CDA

• GUA/CD ratios were however lower and the other ratios higher in the cancerous tissues [29].
• SF IL-8 levels (measured by an ELISA) were significantly elevated in RA compared to SNP (median 2.35 vs 0.22 ng/ml, P < 0.001), as were median levels of CD (55.8 vs 8.11 U/ml, P < 0.01), lactic acid (29.6 vs 16.6 mg/dl, P < 0.001), glucose (57.9 vs 84.5 mg/dl, P < 0.05) and the lactate to glucose ratio (0.85 vs 0.19, P < 0.001) [30].
• SF IL-8 levels correlated strongly with CD, lactate, glucose and the lactate to glucose ratio when both disease groups were considered together (P < 0.001) [30].
• Furthermore, for both CDA 1 and CDA 2 some substrates and inhibitors of CDA were assayed, with the aim of demonstrating different kinetic behavior between the two natural variants [26].
• Serum cytidine deaminase as a measure of disease activity in rheumatoid arthritis and systemic lupus erythematosus [31].

Analytical, diagnostic and therapeutic context of CDA

• The mean CD in pre-treatment samples was 8.64 units/ml (SD 7.09), and after treatment 7.20 units/ml (SD 3.53) [32].
• We have examined in a preliminary study the hypothesis that serum cytidine deaminase (CD) may be valuable in the differential diagnosis of these disorders [32].
• In this study, we have undertaken molecular cloning and purification of recombinant human CDD to elucidate the growth regulatory potential and mechanism behind the growth suppressive effect [23].
• This strongly argues for a potential therapeutic role of CDD gene transfer in conjunction with dose-intensive cytarabine- or gemcitabine-containing chemotherapy regimen [16].
• The timing of the peak in serum cytidine deaminase concentrations after a period of morning physiotherapy, but not during the bedrest morning, suggests that exercise accounts for the circadian rhythm, probably by increasing the lymphatic clearance from inflamed joints [33].

References