Search results for "azacitidine"
showing 8 items of 38 documents
Pevonedistat (PEV) + Azacitidine (AZA) Versus AZA Alone As First-Line Treatment for Patients with Higher-Risk Myelodysplastic Syndromes (MDS)/Chronic…
2021
Abstract Background: Older patients with higher-risk MDS/CMML or AML with 20-30% marrow blasts typically receive single-agent hypomethylating agent (HMA) therapy. Median response duration and survival for these patients is poor, and many patients with MDS transform to secondary AML, which is associated with a particularly dismal prognosis. Novel HMA-based combination therapies that improve survival, delay transformation to AML, and increase depth and duration of response vs single-agent HMA therapy without additional toxicity or myelosuppression are needed. In a randomized, proof-of-concept phase 2 study PEV - a first-in-class, selective inhibitor of NEDD8-activating enzyme - in combination…
Mutational Profiling Predicts Clinical Outcomes to Azacytidine and Low Dose Cytarabine Plus Fludarabine (FLUGA) in Elderly Acute Myeloid Leukemia Pat…
2019
BACKGROUND: Older patients with acute myeloid leukaemia (AML) who are unsuitable for standard induction therapy have limited treatment options. While DNMT3A, TET2, IDH1/2 and TP53 mutations have been previously associated to better response to hypomethylating agents, there are no molecular biomarkers for low-dose cytarabine (LDAC)-based regimens. AIMS: To predict outcome in AML older patients at diagnosis based on mutation status in the context of FLUGAZA trial. FLUGAZA trial was focus on >65 years AML de novo patients comparing azacytidine vs. fludarabine and LDAC (FLUGA Scheme). METHODS: We analyzed bone marrow (BM) samples at diagnosis from 209 out of 285 AML patients treated accordin…
Pharmacological genome demethylation increases radiosensitivity of head and neck squamous carcinoma cells
2011
Aberrant inactivation of tumor suppressor genes by promoter hypermethylation has been recognized as a crucial step of tumor development and is related to aggressiveness and therapy resistance. To identify potential novel treatment strategies, we evaluated pharmacological genome demethylation for the increase of irradiation treatment effectiveness in head and neck squamous cell carcinoma (HNSCC) in this in vitro study. HNSCC cells were cultured with 2 different concentrations of 5-azacytidine (5-Aza) for 72 h, followed by a single fraction irradiation with 4 or 50 Gy, respectively. To show successful genome demethylation, the methylation status of the tumor suppressor gene hic1 (hypermethyla…
Efficacy of Azacitidine (AZA) in Autoimmune and Inflammatory Disorders (AID) Associated with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocyt…
2015
Abstract Background: AID are seen in 10-30% of MDS and CMML. After initial response to steroids, AID are often poorly controlled and steroid-sparing drugs are difficult to use due to the underlying MDS/CMML. Some case reports suggest a beneficial role of AZA treatment in AID associated to MDS/CMML. Methods: We retrospectively analyzed 22 MDS/CMML patients (pts) with AID who received AZA in French centers between January 2007 and May 2014. Results: Median age of the 22 pts was 70y (range 41-84), including 6F/16M. Diagnosis of MDS/CMML preceded AID (n=8) by a median of 17 months (mo), was concomitant with (n=7) or followed AID (n=7) by a median of 20 mo. 14 pts had lower risk IPSS and 8 highe…
5-Azacytidine Inhibits the Activation of Senescence Program and Promotes Cytotoxic Autophagy during Trdmt1-Mediated Oxidative Stress Response in Insu…
2022
5-Azacytidine (5-azaC), a methyltransferase inhibitor and anticancer drug, can promote several cellular stress responses such as apoptosis, autophagy, and senescence. The action of 5-azaC is complex and can be modulated by dose, time of treatment, and co-administration with oxidants. Insulinoma is a rare pancreatic neuroendocrine tumor with limited chemotherapeutic options. In the present study, two cellular models of insulinoma were considered, namely NIT-1 and β-TC-6 mouse cells, to evaluate the effects of 5-azaC post-treatment during hydrogen peroxide-induced oxidative stress. 5-azaC attenuated the development of oxidant-induced senescent phenotype in both cell lines. No pro-apoptotic ac…
Effects of 5-Azacitidine on Dnmt2/Trdmt1 expression levels and endoplasmic reticulum stress in cellular models of insulinoma
2021
Diabetes mellitus affects people all over the world of all ages or social groups making it a worldwide healthcare challenge. Moreover, untreated or badly treated diabetes carries a risk of serious complications including premature death (IDF Diabetes Atlas 9th edition, 2019). The main symptom of diabetes is insulin secretion and/or action disorder leading to hyperglycemia what results in impaired carbohydrate, fat, and protein metabolism (“Diagnosis and Classification of Diabetes Mellitus,” 2013). Dnmt2/ Trdmt1 in its structure and sequence is similar to DNA methyltransferases, however, it has been shown that mainly methylates aspartic acid transfer RNA, specifically at the cytosine-38 resi…
Infectious complications in patients with myelodysplastic syndromes: A review of the literature with emphasis on patients treated with 5-azacitidine.
2017
Myelodysplastic Syndromes are oligo-clonal stem cell disorders that are associated with cytopenias in the peripheral blood. Major causes for morbidity and mortality in myelodysplastic syndromes (MDS) patients are infections mostly due to bacteria or fungi. Beside leucopenia per se in affected patients, function of white blood cells particularly that of neutrophils seems to be impaired. Here we summarize the available data on infections in MDS patients in general and particularly those treated with 5-azacitidine.
Azacitidine-Containing Induction Regimens Followed by Azacitidine Maintenance Therapy in High Risk Acute Myeloid Leukemia: First Results of the Rando…
2012
Abstract Abstract 412 Background: A large proportion of patients are currently not eligible for genotype-adapted strategies in acute myeloid leukemia (AML), in particular those lacking specific genetic aberrations such as PML-RARA, CBFB-MYH11, RUNX1-RUNX1T1, NPM1 or activating FLT3 mutations. This subgroup of patients accounts for about one-third of all AML patients and mainly includes the large group of AML with myelodysplasia-related changes, AML with recurrent cytogenetic abnormalities [inv(3) or t(3;3), t(9;11), t(v;11q23)] and cytogenetically normal AML (CN-AML) with wild-type NPM1 and FLT3. Prognosis in this subgroup of patients is generally poor. Azacitidine has been shown to be acti…