• medical citation needed] Azacitidine and its deoxy derivative, decitabine (also known as 5-aza-2′-deoxycytidine) were first synthesized in Czechoslovakia as potential chemotherapeutic agents for cancer. (wikipedia.org)
  • After azanucleosides such as azacitidine have been metabolized to 5-aza-2′-deoxycytidine-triphosphate (aka, decitabine-triphosphate), they can be incorporated into DNA and azacytosine can be substituted for cytosine. (wikipedia.org)
  • Some inhibitors have been already approved by FDA, such as Azacitidine and Decitabine as DNA methyltransferase inhibitors for the treatment of myelodysplastic syndrome 8 and Vorinostat and Romidepsin as inhibitors of histone deacetylase for the treatment of peripheral T-cell lymphoma 9 . (nature.com)
  • Two nucleoside inhibitors of DNA methylation, azacitidine and decitabine, are now standard of care for the treatment of the myelodysplastic syndrome, a deadly form of leukemia. (aacrjournals.org)
  • DNA methyltransferase (DNMT) inhibitors - azacitidine and decitabine - have significant activity in the treatment of MDS. (johnshopkins.edu)
  • Significant advances have been achieved in recent years in the study of methylated drugs, such as demethylation drugs Decitabine and Azacitidine and histone deacetylase inhibitor Sedamine, which provides additional strategies for treatment of clinical diseases [ 2 , 3 ]. (biomedcentral.com)
  • The epigenetic potential of DNA methylation inhibitors may be limited by other epigenetic mechanisms that are also worth exploring as therapeutic targets. (aacrjournals.org)
  • In this study, multiple leiomyosarcoma cell lines, SK-UT1, SK-LMS1, and MES-SA were treated with varying doses of the DNA Methyltransferase Inhibitors (DNMTi) 5-azacitidine (Aza), 5-aza-2-deoxycytidine (DAC), and guadecitabine (SGI-110). (oncotarget.com)
  • Combination therapies with DNMT inhibitors using optimal dosing regimens to focus on methylation reversal with lower doses over longer periods of time, rather than direct cytotoxic effects, are beginning to suggest promising results in MDS and AML. (johnshopkins.edu)
  • These two drugs are mere examples of the principal two classes of epidrugs to obtain FDA approval: DNA methyltransferase inhibitors for treatment of MDS (azacitidine, in 2004) and histone deacetyltransferase inhibitors for T cell lymphoma (Vorinostat, in 2006). (biomedcentral.com)
  • Analogous to DNA methylation and histone modification, RNA modification, as another epigenetic layer, plays an important role in many diseases, especially in tumours. (biomedcentral.com)
  • Although the full scope of epigenetics has not yet been determined, it is generally defined as chemical modification that mainly includes DNA and RNA methylation, histone modification, noncoding RNA modification and chromatin rearrangement. (biomedcentral.com)
  • In epigenetic modification, DNA methylation and histone modification have been well studied. (biomedcentral.com)
  • Multiple mechanisms have evolved to perform these essential functions: DNA methylation, a bewildering array of histone modifications, RNA-based regulation, etc. (aacrjournals.org)
  • Similar to DNA and histone methylation, m 6 A modifications are dynamic and reversible and exert biological effects that are mainly mediated by 'writers', 'erasers' and 'reader' proteins (Fig. 2 ). (biomedcentral.com)
  • Here, we summarize the different types of epigenetic enzymes which target corresponding protein domains, emphasize DNA methylation , histone modifications, and microRNA-mediated cooperation with epigenetic modification, and highlight recent achievements in developing targets for epigenetic inhibitor therapy. (frontiersin.org)
  • DNA methylation, a form of epigenetic control of gene transcription, refers to cytosine methylation at position 5 in the pyrimidine ring, which can result in inappropriate silencing of genes involved in diverse biological processes, including cell proliferation, apoptosis, migration and cell cycle arrest ( 5 ). (spandidos-publications.com)
  • For example, global methylation analysis in MM has identified inactivated tumour suppressor genes that are prognostically important. (touchoncology.com)
  • The epigenome is an inheritable record of changes to the DNA and histone proteins, such as methylation and nucleosome remodelling that directs which genes are to be silenced or expressed. (touchoncology.com)
  • Abnormal DNA methylation modifies HOX genes expression in bone marrow mesenchymal stromal cells of myelodysplasias and de novo acute myeloid leukemias. (lnox-team.org)
  • Then we investigated the demethylating effect of arsenic trioxide and 5-azacitidine on the mRNA and protein expression levels of GRHL2 in cell lines of acute leukemia. (hindawi.com)
  • The methylation level of the GRHL2 promoter region in acute leukemia patients and cell lines was significantly higher than the normal control group, and we found the elevated mRNA and protein levels of GRHL2 in acute leukemia cell lines after the use of the demethylation drug arsenic trioxide and 5-azacitidine. (hindawi.com)
  • Azacitidine is a chemical analogue of the nucleoside cytidine, which is present in DNA and RNA. (wikipedia.org)
  • It is involved in cell differentiation, maintenance of cell differentiation state, tumorigenesis, and cell senescence, mainly through DNA methylation, histone acetylation, and RNA-related silencing [ 6 ]. (hindawi.com)
  • Furthermore, the results of methylation‑specific PCR revealed that the abnormal methylation status of the MEG3 promoter region was present in eight of the 39 bone marrow samples collected. (spandidos-publications.com)
  • In this review, we focus on the relationship between RNA m 6 A methylation and gastrointestinal cancer, especially their role, mechanism and potential clinical application as biomarkers and therapeutic targets for gastrointestinal cancer. (biomedcentral.com)
  • Based on animal studies and its mechanism of action, azacitidine can cause severe fetal damage. (wikipedia.org)
  • The biological role and underlying mechanism of action of zinc-finger protein 326 (ZNF326) in malignant tumors, including breast cancer, are still not clear. (cancerindex.org)
  • A new class of DNA artificial binders that directly block the methyllysine reading functions of reader enzymes in charge of conveying the methylation signal downstream has recently arisen as promising epigenetic drugs 10 . (nature.com)
  • Indeed, huge research efforts have been initiated within academia to address chemical as well as biological aspects of epigenetic drugs and their targets. (biomedcentral.com)
  • Our present research is aimed at studying the abnormal expression of GRHL2 and the association of methylation in patients with acute leukemia and its relationship with prognosis. (hindawi.com)
  • Abnormal methylation of Grainyhead-like 2 (GRHL2) is associated with a substantial role in the malignant phenotype of tumor patients. (hindawi.com)
  • research shows that about 90% of the blood system of malignant tumors with at least the height of single gene methylation is closely related since this is a reversible process of genetic modification can be through to handle to restore the normal expression of gene methylation, to achieve the purpose of prevention and treatment of tumor [ 10 ]. (hindawi.com)
  • The role of DNA methylation in the mediation of multiple tumor suppressor gene and microRNA silencing has been implicated in the development and progression of MM ( 7 ). (spandidos-publications.com)
  • Despite extensive genetic and biological research, significant controversy surrounds our understanding of the specific mechanisms of their pathogenesis. (mdpi.com)
  • Over time, additional mechanisms of primary and secondary resistance to targeted agents have emerged as promising novel predictive biomarkers and potentially actionable target of treatment, although validation is still an issue in most cases, and many steps forward have been made in the biological understanding and molecular characterization of CRC [ 6 ] . (oaepublish.com)
  • However, the molecular mechanisms of MEG3 methylation in the regulation of multiple myeloma (MM) are unknown. (spandidos-publications.com)
  • At the same time, arsenide trioxide and 5-azacitidine are associated with the inhibition of cellular proliferation of acute leukemia cells and also promote the elevated expression of TGF- β signaling pathway-linked proteins, including TGF- β , Smad2, Smad3, and Smad4. (hindawi.com)
  • Azacitidine's incorporation into RNA leads to the disassembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and inhibition of the production of proteins. (wikipedia.org)
  • Increased expression and methylation level of GRHL2 are closely associated with the prognosis and malignant phenotype of acute leukemia patients and play an irreplaceable role in the occurrence and development of patients with acute leukemia. (hindawi.com)
  • Azacitidine, sold under the brand name Vidaza among others, is a medication used for the treatment of myelodysplastic syndrome, myeloid leukemia, and juvenile myelomonocytic leukemia. (wikipedia.org)
  • Azacitidine is indicated for the treatment of myelodysplastic syndrome, for which it received approval by the U.S. Food and Drug Administration (FDA) on May 19, 2004. (wikipedia.org)
  • In two randomized controlled trials comparing azacitidine to supportive treatment, 16% of subjects with myelodysplastic syndrome who were randomized to receive azacitidine had a complete or partial normalization of blood cell counts and bone marrow morphology, compared to none who received supportive care, and about two-thirds of patients who required blood transfusions no longer needed them after receiving azacitidine. (wikipedia.org)
  • Azacitidine is also indicated for the treatment of myeloid leukemia and juvenile myelomonocytic leukemia. (wikipedia.org)
  • It can also be hepatotoxic in patients with severe liver impairment, and patients with extensive liver tumors due to metastatic disease have developed progressive hepatic coma and death during azacitidine treatment, especially when their albumin levels are less than 30 g/L. It is contraindicated in patients with advanced malignant hepatic tumors. (wikipedia.org)
  • Sexually active women of reproductive potential should use contraception during while receiving azacitidine and for one week after the last dose, and sexually active men with female partners of reproductive potential should use contraception during treatment and for three months following the last dose. (wikipedia.org)
  • As the most common form of RNA modification, m 6 A methylation has attracted increasing research interest in recent years. (biomedcentral.com)
  • Azacitidine causes anemia (low red blood cell counts), neutropenia (low white blood cell counts), and thrombocytopenia (low platelet counts), and patients should have frequent monitoring of their complete blood counts, at least prior to each dosing cycle. (wikipedia.org)
  • These old drugs, developed as cytotoxic agents and nearly abandoned decades ago were resurrected by the renewed interest in DNA methylation. (aacrjournals.org)
  • Kidney toxicity, ranging from elevated serum creatinine to kidney failure and death, have been reported in patients treated with intravenous azacitidine in combination with other chemotherapeutic agents for conditions other than myelodysplastic syndrome. (wikipedia.org)
  • Renal tubular acidosis developed in five patients with chronic myelogenous leukemia (an unapproved use) treated with azacitidine and etoposide, and patients with renal impairment may be at increased risk for renal toxicity. (wikipedia.org)
  • Azacitidine and its metabolites are primarily excreted by the kidneys, so patients with chronic kidney disease should be closely monitored for other side effects, since their levels of azacitidine may progressively increase. (wikipedia.org)
  • Common RNA methylation sites include 5-methylcytosine (m 5 C), 7-methylguanosine (m 7 G), m 1 G, m 2 G, m 6 G, N 1 -methyladenosine (m 1 A) and m 6 A. m 5 C modification promotes splicing and translation [ 4 ]. (biomedcentral.com)
  • Finally, we studied the effects of arsenide trioxide and 5-azacitidine on the proliferation of leukemia cells and the TGF- β signaling pathway. (hindawi.com)