scholarly journals Clinical activity and safety of the dual pathway inhibitor rigosertib for higher risk myelodysplastic syndromes following DNA methyltransferase inhibitor therapy

2014 ◽  
Vol 33 (2) ◽  
pp. 57-66 ◽  
Author(s):  
Lewis R. Silverman ◽  
Peter Greenberg ◽  
Azra Raza ◽  
Matthew J. Olnes ◽  
James F. Holland ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Dna Methyltransferase ◽  
Inhibitor Therapy ◽  
Clinical Activity ◽  
Dna Methyltransferase Inhibitor ◽  
Dual Pathway

Six (or More) Drugs in Search of a Mechanism: DNA Methyltransferase and Histone Deacetylase Inhibitors in the Treatment of Myelodysplastic Syndromes

2006 ◽  
Vol 4 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Steven D. Gore
Keyword(s):  
Histone Deacetylase ◽  
Myelodysplastic Syndromes ◽  
Dna Methyltransferase ◽  
Histone Deacetylase Inhibitors ◽  
Conclusive Evidence ◽  
Clinical Activity ◽  
Dna Methyltransferase Inhibitors ◽  
Expression Of Genes ◽  
Measurable Activity ◽  
Epigenetic Modulation

The clinical activity of the DNA methyltransferase inhibitors 5-azacitidine and 2′-deoxy-5-azacytidine in myelodysplastic syndromes (MDS) suggests that epigenetic modulation of gene transcription may play an important pathogenetic role in the development and expression of these diseases. Approximately 50% of patients treated with these compounds experience hematologic improvement, making these the most active single agents for unselected patients with MDS. Responses include complete and partial hematologic responses. Two randomized trials have shown that the use of these drugs significantly alters the natural history of MDS compared with supportive care. Histone deacetylase inhibitors, which may also impact the expression of genes through epigenetic mechanisms, seem to have measurable activity in MDS in preliminary studies. Histone deacetylase inhibitors are most likely used in combination with other agents, including DNA methyltransferase inhibitors. Despite the clinical activity of these classes of drugs, there is no conclusive evidence that their clinical activity is attributable to their impact on the epigenome. Such information will be critical in the development of more effective congeners and drug combinations in ongoing attempts to improve the outcome of patients with MDS.

DNA methyltransferase inhibitor CDA-II inhibits myogenic differentiation

2012 ◽  
Vol 422 (3) ◽  
pp. 522-526 ◽  
Author(s):  
Zirong Chen ◽  
Guorong Jin ◽  
Shuibin Lin ◽  
Xiumei Lin ◽  
Yumei Gu ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Myogenic Differentiation ◽  
Dna Methyltransferase Inhibitor ◽  
Cda Ii

scholarly journals Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers

Oncotarget ◽  
2014 ◽  
Vol 5 (3) ◽  
pp. 587-598 ◽  
Author(s):  
Huili Li ◽  
Katherine B. Chiappinelli ◽  
Angela A. Guzzetta ◽  
Hariharan Easwaran ◽  
Ray-Whay Chiu Yen ◽  
...  
Keyword(s):  
Immune Regulation ◽  
Dna Methyltransferase ◽  
Low Doses ◽  
Epithelial Cancers ◽  
Dna Methyltransferase Inhibitor

The DNA-methyltransferase inhibitor 5-aza-2-deoxycytidine affectsHumicola griseaenzyme activities and the glucose-mediated gene repression

2017 ◽  
Vol 58 (2) ◽  
pp. 144-153 ◽  
Author(s):  
João Heitor C. Manfrão-Netto ◽  
Thiago M. Mello-de-Sousa ◽  
Astrid R. Mach-Aigner ◽  
Robert L. Mach ◽  
Marcio J. Poças-Fonseca
Keyword(s):  
Dna Methyltransferase ◽  
Gene Repression ◽  
Dna Methyltransferase Inhibitor

scholarly journals Prostaglandin E2 Reverses the Effects of DNA Methyltransferase Inhibitor and TGFB1 on the Conversion of Naive T Cells to iTregs

2019 ◽  
Vol 47 (3) ◽  
pp. 244-253
Author(s):  
Mehmet Sahin ◽  
Emel Sahin
Keyword(s):  
T Cells ◽  
Prostaglandin E2 ◽  
Dna Methyltransferase ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Dna Methyltransferase Inhibitor

Naturally occurring regulatory T cells (nTregs) are produced under thymic (tTregs) or peripherally induced (pTregs) conditions in vivo. On the other hand, Tregs generated from naive T cells in vitro under some circumstances, such as treatment with transforming growth factor-β (TGFB), are called induced Tregs (iTregs). Tregs are especially characterized by FOXP3 expression, which is mainly controlled by DNA methylation. nTregs play important roles in the suppression of immune response and self-tolerance. The prostaglandin E2 (PGE2) pathway was reported to contribute to regulatory functions of tumor-infiltrating nTregs. In this study, we examined whether PGE2 contributes to the formation of iTregs treated with TGFB1 and 5-aza-2′-deoxycytidine (5-aza-dC), which is a DNA methyltransferase inhibitor. We found that the protein and gene expression levels of FOXP3 and IL-10 were increased in 5-aza-dC and TGFB1-treated T cells in vitro. However, the addition of PGE2 to these cells reversed these increments significantly. In CFSE-based cell suppression assays, we demonstrated that PGE2 decreased the suppressive functions of 5-aza-dC and TGFB1-treated T cells.

Sign in / Sign up

Export Citation Format

Share Document