Comparison of the antileukemic activity of 5-aza-2′-deoxycytidine, 1-β-d-arabinofuranosylcytosine and 5-azacytidine against L1210 leukemia

Momparler, Richard L.; Momparler, Louise F.; Samson, Johanne

doi:10.1016/0145-2126(84)90059-6

Cited by 92 publications

(57 citation statements)

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“…5A). Similar increases in ADCC activity were obtained when NK cells were pretreated with a more potent DNA demethylating agent, 5-aza-2'deoxycytidine 11 (data phagocytosis of HL60cy cells compared to untreated cells (p = 0.018, 2-way ANOVA, Fig. 4A).…”

Section: -Azacytidine Enhances Lintuzumab-mediated Adcp Activity In supporting

confidence: 55%

“…9 Decitabine was reported to be ~10-fold more potent than 5-azacytidine. 10,11 Elevated levels of DNA methyltransferases and hypermethylated DNA were found in blood and bone marrow samples from MDS and AML patients. [12][13][14][15] Altering the methylation status of DNA in leukemic samples promoted the differentiation of tumor cells, [16][17][18] resulting in reduced tumor cell growth, 19 possibly by making them amenable to natural killer (NK) cell killing.…”

Section: -Azacytidine Enhances the Anti-leukemic Activity Of Lintuzumentioning

confidence: 99%

“…18 On the other hand, high concentrations of 5-azacytidine and 5-aza-2'deoxycytidine directly killed tumor cells. 7,11,39 The IC 50 for 5-azacytidine in a 96 h in vitro cytotoxicity assay against KG-1, HL60cy or HEL9217 cell lines was approximately 2 mM (Fig. 2).…”

Section: -Azacytidine Enhances Lintuzumab-mediated Adcp Activity In mentioning

confidence: 99%

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5-Azacytidine enhances the anti-leukemic activity of lintuzumab (SGN-33) in preclinical models of acute myeloid leukemia

Sutherland

Anderson

et al. 2010

mAbs

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Section: -Azacytidine Enhances Lintuzumab-mediated Adcp Activity In supporting

confidence: 55%

Section: -Azacytidine Enhances the Anti-leukemic Activity Of Lintuzumentioning

confidence: 99%

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5-Azacytidine enhances the anti-leukemic activity of lintuzumab (SGN-33) in preclinical models of acute myeloid leukemia

Sutherland

Anderson

et al. 2010

mAbs

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“…In clinical therapy with 5-AZA-CdR an intensive dose with short interval of treatment appears to the optimal schedule for this agent. Clinical investigations on 5-AZA-CdR were stimulated by the observations that this analogue was a much more potent antileukemic agent in the mouse model that cytosine arabinoside (Momparler et al, 1984b). Also, in support of clinical trials on leukemia with this analogue were the observations that it could induce in vitro differentiation of human leukemic cells (Pinto et al, 1984;Momparler et al, 1985).…”

Section: Cancer Therapy With Inhibitors Of Dna Methylationmentioning

confidence: 96%

DNA methylation and cancer

2000

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The methylation of DNA is an epigenetic modification that can play an important role in the control of gene expression in mammalian cells. The enzyme involved in this process is DNA methyltransferase, which catalyzes the transfer of a methyl group from S-adenosyl-methionine to cytosine residues to form 5-methylcytosine, a modified base that is found mostly at CpG sites in the genome. The presence of methylated CpG islands in the promoter region of genes can suppress their expression. This process may be due to the presence of 5-methylcytosine that apparently interferes with the binding of transcription factors or other DNA-binding proteins to block transcription. In different types of tumors, aberrant or accidental methylation of CpG islands in the promoter region has been observed for many cancer-related genes resulting in the silencing of their expression. How this aberrant hypermethylation takes place is not known. The genes involved include tumor suppressor genes, genes that suppress metastasis and angiogenesis, and genes that repair DNA suggesting that epigenetics plays an important role in tumorigenesis. The potent and specific inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5-AZA-CdR) has been demonstrated to reactivate the expression most of these "malignancy" suppressor genes in human tumor cell lines. These genes may be interesting targets for chemotherapy with inhibitors of DNA methylation in patients with cancer and this may help clarify the importance of this epigenetic mechanism in tumorigenesis.

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“…In mice inoculated with L1210 leukaemia. aza-dC was found to be more effective than ara-C (Momparler et al, 1985b). To acquire antileukaemic activity ara-C has to be phosphorylated into its nucleotide form, ara-CTP, by deoxycytidine kinase and this metabolite is responsible for the inhibition of DNA synthesis.…”

mentioning

confidence: 99%

Comparison of the antileukaemic activity of 5 aza-2-deoxycytidine and arabinofuranosyl-cytosine in rats with myelocytic leukaemia

Richel

Colly²,

Lurvink³

et al. 1988

Br J Cancer

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Summary Using a Brown Norway rat leukaemia model (BNML), which is a realistic model of human myelocytic leukaemia, we compared the antileukaemic activity, influence on cell cycle kinetics and effect on normal haematopoiesis of 5 aza-2-deoxycytidine (aza-dC) and arabinofuranosyl-cytosine (ara-C). The antileukaemic activity was evaluated by means of a survival study. For aza-dC a dose-response relationship was demonstrated for doses up to 50mgkg-1 (3 times q 12h); a higher dose resulted in only a slight increase in median survival time (MST). For ara-C a weak dose-response relationship was observed. At the maximum dose of aza-dC and ara-C tested, aza-dC induced a 10-day longer survival time than ara-C, which means 2 logs more of leukaemic cell kill for aza-dC.By means of flow cytometric analysis and a 3HTdR uptake study it was shown that aza-dC does not influence the cell cycle kinetics in the first 24 h after exposure, in contrast to ara-C which caused the characteristic G1 /S blockage and synchronization. The influence of aza-dC and ara-C on normal haematopoiesis was evaluated with the CFU-S assay. The dose-response curve for CFU-S did not show a significant difference in stem cell cytotoxicity between aza-dC and ara-C. In the BNML model aza-dC is a much more effective antileukaemic agent than ara-C, while the toxic effect on normal haematopoiesis is comparable to that of ara-C.

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Comparison of the antileukemic activity of 5-aza-2′-deoxycytidine, 1-β-d-arabinofuranosylcytosine and 5-azacytidine against L1210 leukemia

Cited by 92 publications

References 11 publications

5-Azacytidine enhances the anti-leukemic activity of lintuzumab (SGN-33) in preclinical models of acute myeloid leukemia

5-Azacytidine enhances the anti-leukemic activity of lintuzumab (SGN-33) in preclinical models of acute myeloid leukemia

DNA methylation and cancer

Comparison of the antileukaemic activity of 5 aza-2-deoxycytidine and arabinofuranosyl-cytosine in rats with myelocytic leukaemia

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