Disease relevance of AADAC

• Two extended regions of significant sequence homology with hormone-sensitive lipase and with lipase 2 from Moraxella TA144 were identified, whereas similarity to carboxyl esterases was restricted to the region encompassing the putative active site, indicating that DAC should be classified as esterase [1].
• CONCLUSION: We were able to confirm our previous observation that DAC therapy was effective in half of the studied patients with high-risk myelodysplastic syndrome and is especially active in the patients with the worst prognoses [2].
• We performed a second, multicenter phase II study in a larger group of patients to confirm our findings and to study the toxicity of DAC [2].
• 5-Aza-2'-deoxycytidine (DAC), a demethylating agent, was capable of inducing MAGE-1 expression by a MAGE-1-negative melanoma cell line 888-mel as well as by a number of other melanoma cell lines [3].
• In addition, DAC sensitized lung cancer cells to cisplatin and paclitaxel [4].

Psychiatry related information on AADAC

• Decisions about Aggressiveness of Patient Care (DAC) measures care providers' general perceptions about decision making [5].

High impact information on AADAC

• Either DAC treatment or enforced SOCS-3 expression sensitized the cells to TRAIL-mediated apoptosis [6].
• Treatment of these cell lines with the demethylating agent 5-aza-2'-deoxycytidine (DAC) up-regulated SOCS-1 expression [7].
• PURPOSE: 5-Aza-2'-deoxycytidine (decitabine; DAC) is a DNA hypomethylating agent that has shown a 50% response rate in a small phase II study in elderly patients with high-risk myelodysplastic syndrome [2].
• However, DAC treatment sensitizes the xenografts to cisplatin, carboplatin, temozolomide, and epirubicin [8].
• Because there is emerging data on the role of loss of MMR in clinical drug resistance, DAC could have a role in increasing the efficacy of chemotherapy for patients whose tumors lack MLH1 expression because of hMLH1 promoter methylation [8].

Chemical compound and disease context of AADAC

• Both events were recently shown to occur in a rhabdomyosarcoma cell line (RD-DAC) resistant to actinomycin D, a drug of choice in the treatment of these tumours [9].
• The preliminary data show that DAC is an anti-leukemic agent, comparable to high dose Ara-C with comparable severe toxicity [10].
• METHODS: Eleven lung and esophageal cancer lines and cultured normal human bronchial epithelial (NHBE) cells were exposed to normal media (NM), DAC, DP, or combination DAC/DP at varying concentrations and exposure durations [11].
• 5-Aza-2'-deoxycytidine (decitabine, DAC) is a nucleoside analog, which, at low doses, acts as a hypomethylating agent and is fivefold to tenfold more active than 5-azacytidine (azacitidine, Vidaza)-currently the only approved drug for treatment of myelodysplastic syndrome (MDS) [12].
• Thirty-four patients with advanced soft tissue sarcoma were treated with a three-drug combination including vindesine sulfate (DVA), Adriamycin, and cyclophosphamide (DAC) (S9) [13].

Biological context of AADAC

• Highest sequence similarity of DAC was found in a series of prokaryotic esterases encompassing the putative active site [1].
• Human liver arylacetamide deacetylase. Molecular cloning of a novel esterase involved in the metabolic activation of arylamine carcinogens with high sequence similarity to hormone-sensitive lipase [1].
• Radiation hybrid mapping of human arylacetamide deacetylase (AADAC) locus to chromosome 3 [14].
• Significant responses were observed with regard to megakaryopoiesis, with increases in platelet counts having already occurred after one cycle of DAC therapy in the majority of the responding patients [2].
• With the exception of tumor-infiltrating leukocytes, no normal diploid cell line could be induced with DAC to upregulate MAGE-1 expression [3].

Anatomical context of AADAC

• The demethylating agents 5-azacytidine and 5-aza-2'-deoxycytidine (DAC) have been shown to induce differentiation and inhibit growth of leukemic myeloid cells at low concentrations [15].
• Taken together, these data indicate a role of DAC in changing myeloid progenitor cell expansion and differentiation [15].
• Treatment of MSR3-mel cells with the demethylating agent 5'-aza-2'-deoxycytidine (DAC) allowed HLA-A and -B transcription, restoring cell surface expression of HLA class I antigens and tumor cell recognition by MAGE-specific cytotoxic T lymphocytes [16].
• They resembled arylacetamide deacetylase from human hepatic microsomes with respect to molecular mass and amino-terminal amino acid sequence [17].
• The greatest focal uptake of In 111 DAC occurred in the liver and spleen, followed by the nasal cavity and salivary and lacrimal glands [18].

Associations of AADAC with chemical compounds

• Activity determination and immunoblot analysis of DAC in human target tissues for arylamine carcinogens revealed that in extrahepatic tissues, additional enzymes are responsible for any deacetylation activity, whereas a single enzyme predominantly catalyzes this hydrolytic reaction in liver [1].
• Previous studies revealed that the luminal orientation of 11beta-HSD1 and 50-kDa esterase/arylacetamide deacetylase (E3) is determined by their highly similar N-terminal transmembrane domains [19].
• Consequently, efforts have been directed at re-expressing genes, including genes that affect drug sensitivity, using 5-azacytidine and 2'-deoxy-5-azacytidine (DAC, decitabine) as demethylating agents [20].
• The three complexes investigated were the copper(II) complex Cu(DAC)2+ (DAC = 1,8-bis(9-methylanthracyl)cyclam, cyclam = 1,4,8,11-tetraazacyclotetradecane), the N-nitrosylated ligand DAC-NO, and the Roussin's red salt ester (mu-S,mu-S')-protoporphyrin-IX-bis(2-thioethyl ester)tetranitrosyldiiron (PPIX-RSE) [21].
• MAL gene transcription was induced in three out of 13 esophageal carcinoma cell lines by treatment with the demethylating agent 5-aza-2'-deoxycytidine (DAC), and in nine additional cell lines by simultaneous treatment with trichostatin A, an inhibitor of deacetylation, and DAC [22].

Other interactions of AADAC

• Microsomal arylacetamide deacetylase (DAC) competes against the activity of cytosolic arylamine N-acetyltransferase, which catalyzes one of the initial biotransformation pathways for arylamine and heterocyclic amine carcinogens in many species and tissues [1].
• The lipases involved include arylacetamide deacetylase and/or triacylglycerol hydrolase [23].

Analytical, diagnostic and therapeutic context of AADAC

• Consistent with loss of MMR having no effect on sensitivity in vitro to Taxol, DAC treatment has no effect on the Taxol sensitivity of the xenografts [8].
• Induction of the mitochondrial pathway of apoptosis using a slightly toxic dose of DAC may therefore be a strategy for treating lung cancer, and DAC treatment may have clinical implications when combined with chemotherapy or apoptosis-inducing gene therapy [4].
• Our results suggest that, because of the higher expression of these genes and the possible induction of these genes by DAC, patients with gastric carcinoma may, therefore, be potential candidates for tumor-specific immunotherapy directed against these antigens [24].
• A rhabdomyosarcoma cell line resistant to actinomycin D (RD-DAC) has been used as an in vitro model to investigate, with light and electron microscopy, the degree of differentiation in multidrug-resistant cells [25].
• Treatment of K562/ADM cells with 5-Aza-2'-deoxycytidine (decitabine; DAC), an inhibitor of DNA methyltransferase, caused demethylation of the repressor binding site of MDR-1 gene, as assessed by MSP, and also decreased P-gp expression, as assessed by flow cytometric and Northern blot analysis [26].

References