Disease relevance of Azacitidine

• This drug had greater erythroid toxicity than azaC, and it appeared that the Hb F elevations occurred mainly on the rebound from the early cytotoxicity [1].
• Maximal fetal hemoglobin (Hb F) elevations in the baboon subsequent to phenyl hydrazine-induced hemolytic anemia, bleeding, bleeding plus hydroxyurea (HU), or cytosine arabinoside were two to three times lower than those achieved with bleeding plus 5-azacytidine (azaC) [1].
• Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study [2].
• Eighty-seven consecutive children and young adults with acute nonlymphocytic leukemia (ANLL) were treated uniformly with induction chemotherapy based on daunorubicin and cytarabine (ara-C), with the addition of etoposide (VP-16) and azacytidine (5-Az) for refractory patients [3].
• We confirmed this observation using two additional isogenetically matched human MLH1 (hMLH1)-deficient and -proficient human tumor cell systems: human ovarian cancer cells, A2780/CP70, with or without ectopically expressed hMLH1, and human colorectal carcinoma cells, RKO, with or without azacytidine treatment to reexpress hMLH1 [4].

High impact information on Azacitidine

• These results indicate that an azacytidine-induced structural modification (presumably demethylation) in the DNA of a single locus is sufficient to convert 10T1/2 cells into determined myoblasts [5].
• We show that transfection of 10T1/2 cells with DNA from these azacytidine-induced myoblasts (or from mouse C2C12 myoblasts) results in myogenic conversion of approximately 1 in 15,000 transfected colonies [5].
• A further selection of cells after growth in agar allowed the isolation of Aza-treated clones that had regained the progressed phenotype [6].
• Treatment of vimentin-negative BLCL and Langer-Giedion LCL with azacytidine led to a transient reexpression of vimentin [7].
• It is in myotubes derived from myoblasts obtained by treatment of 10T1/2 cells with azacytidine or transfection with MRF4 [8].

Chemical compound and disease context of Azacitidine

• PURPOSE: This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome [9].

Biological context of Azacitidine

• Azacytidine-induced tumorigenesis of CHEF/18 cells: correlated DNA methylation and chromosome changes [10].
• Clone mu cells, generated from line 10T1/2 by treatment with azacytidine, were known to be capable of undergoing myogenesis [11].
• The results of further studies by restriction analysis, azacytidine treatments, and secondary DNA transfection assays demonstrated that tk repression is associated with changes in DNA methylation [12].
• Azacytidine-induced reactivation of a DNA repair gene in Chinese hamster ovary cells [13].
• The phosphorylation of azacytidine in untreated, wild-type cells, however, is much more inhibited by uridine and cytidine than is its transport into the cell [14].

Anatomical context of Azacitidine

• Treatment with 5-AZAC restored SEMA3B expression in NSCLC cell line [15].
• Fetal bovine epiphyseal chondrocytes were treated with the demethylating agent, 5-azacytidine, for 48 h and then cultured under azacytidine-depleted conditions [16].
• There was evidence for apoptosis in azacytidine-treated cells, as demonstrated by nuclear condensation and fragmentation (days 27 and 35) using transmission electron microscopy, and the detection of exposed phosphatidylserine on the plasma membrane surface of apoptotic chondrocytes (day 27) using fluorescence-labelled annexin V [16].
• Azacytidine-induced reactivation of adenosine deaminase in a murine cytotoxic T cell line [17].
• METHODS: CD34-selected peripheral blood monocytes cultured in a semi-solid serum-free system that mimics in vivo F-cell production are utilized to explore the role of cyclic adenosine monophosphate (cAMP) and cGMP in HbF induction in response to HU, AZA, and SB [18].

Associations of Azacitidine with other chemical compounds

• 5. Reactivated strains, as well as cells that were treated with 5AC, gave rise to cultures that were hypomethylated and partially hygromycin resistant, indicating that some of the original methylation was propagated by a maintenance mechanism [19].
• Treatment of azacytidine-treated, radiation sensitive and resistant cells with four millimolar WR-1065 30 minutes prior to irradiation enhanced survival after exposure to gamma radiation, although the enhancement in survival was less than for wild type Chinese hamster ovary K1 cells [20].
• Pretreatment with the DNA methyltransferase inhibitor, azacytidine, followed by treatment with RA and a histone deacetylase inhibitor, trichostatin A, resulted in partial promoter demethylation and RAR alpha2 induction, which strongly suggested that promoter hypermethylation is responsible for RAR alpha2 underexpression [21].
• Azacytidine (AZA), ethionine (ETH), mitomycin-C (MMC), UV-irradiation (UV) and hydrogen peroxide (H(2)O(2)) were tested for SCE induction in a Chinese hamster ovary cell line after a single pulse, one or two cell cycles before fixation [22].
• The effects of the cytotoxic drugs, adriamycin, cyclophosphamide, daunomycin (daunorubicin), prednisolone, actinomycin D, azacytidine and vincristine at concentrations of 1 microM on mature neutrophil function were examined [23].

Gene context of Azacitidine

• Effect of azacytidine in the release of leukemia inhibitory factor, oncostatin m, interleukin (IL)-6, and IL-11 by mononuclear cells of patients with refractory anemia [24].
• Growth hormone promotes the differentiation of myoblasts and preadipocytes generated by azacytidine treatment of 10T1/2 cells [11].
• We validated the positive correlation between SLC29A1 (nucleoside transporter ENT1) expression and potency of nucleoside analogues, azacytidine and inosine-glycodialdehyde [25].
• However, 5-AZAC treatment restored ERbeta expression in those cell lines, suggesting that methylation inactivates the ERbeta gene in prostate carcinoma [26].
• A combination of azacytidine and phorbol acetate did not have an additive effect on total yield but did alter the kinetics of tPA expression with time [27].

Analytical, diagnostic and therapeutic context of Azacitidine

• A series of cell lines were previously generated from the radiation sensitive Chinese hamster ovary line xrs5 after treatment with azacytidine [20].
• We isolated human adipose tissue stromal cells (hATSCs) from human liposuction tissues and induced neural differentiation with azacytidine [28].
• In clinical trials, Azacytidine results in a significantly higher response rate, improved quality of life, reduced risk of leukemic transformation, and improved survival compared to supportive care [29].
• The prostate carcinoma cell lines DU145 and ND1 were treated with the demethylating agent 5-AZAC and ERbeta mRNA expression was analyzed by reverse transcriptase-polymerase chain reaction [26].
• SCCHN cell lines (PCI-15b, 1483, and UM-22B) were treated with the demethylating agent azacytidine alone or in combination with the cytotoxic drug cisplatin, and expression of STAT1 and p21 were monitored by immunoblotting [30].

References