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Azacitidine

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https://www.readbyqxmd.com/read/29242529/decitabine-a-dna-demethylating-agent-promotes-differentiation-via-notch1-signaling-and-alters-immune-related-pathways-in-muscle-invasive-bladder-cancer
#1
Swathi Ramakrishnan, Qiang Hu, Nithya Krishnan, Dan Wang, Evelyn Smit, Victoria Granger, Monika Rak, Kristopher Attwood, Candace Johnson, Carl Morrison, Roberto Pili, Gurkamal Chatta, Khurshid Guru, Geraldine Gueron, Lacey McNally, Jianmin Wang, Anna Woloszynska-Read
Aberrant DNA methylation observed in cancer can provide survival benefits to cells by silencing genes essential for anti-tumor activity. DNA-demethylating agents such as Decitabine (DAC)/Azacitidine (AZA) activate otherwise silenced tumor suppressor genes, alter immune response and epigenetically reprogram tumor cells. In this study, we show that non-cytotoxic nanomolar DAC concentrations modify the bladder cancer transcriptome to activate NOTCH1 at the mRNA and protein level, increase double-stranded RNA sensors and CK5-dependent differentiation...
December 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29241450/azacitidine-improves-clinical-outcomes-in-older-patients-with-acute-myeloid-leukaemia-with-myelodysplasia-related-changes-compared-with-conventional-care-regimens
#2
John F Seymour, Hartmut Döhner, Aleksandra Butrym, Agnieszka Wierzbowska, Dominik Selleslag, Jun Ho Jang, Rajat Kumar, James Cavenagh, Andre C Schuh, Anna Candoni, Christian Récher, Irwindeep Sandhu, Teresa Bernal Del Castillo, Haifa Kathrin Al-Ali, Jose Falantes, Richard M Stone, Mark D Minden, Jerry Weaver, Steve Songer, C L Beach, Hervé Dombret
BACKGROUND: Compared with World Health Organization-defined acute myeloid leukaemia (AML) not otherwise specified, patients with AML with myelodysplasia-related changes (AML-MRC) are generally older and more likely to have poor-risk cytogenetics, leading to poor response and prognosis. More than one-half of all older (≥65 years) patients in the phase 3 AZA-AML-001 trial had newly diagnosed AML-MRC. METHODS: We compared clinical outcomes for patients with AML-MRC treated with azacitidine or conventional care regimens (CCR; induction chemotherapy, low-dose cytarabine, or supportive care only) overall and within patient subgroups defined by cytogenetic risk (intermediate or poor) and age (65-74 years or ≥75 years)...
December 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29236331/reduction-of-histone-marks-h3k9me3-and-h3k27me3-by-epidrug-induces-neuroendocrine-differentiation-in-prostate-cancer
#3
Eunsohl Lee, Jingcheng Wang, Younghun Jung, Frank C Cackowski, Russell S Taichman
Neuroendocrine prostate cancer (NE PCa) is an aggressive malignancy, often presenting with advanced metastasis. We previously reported that reduction of histone marks regulated by DNMT1 following epidrug (5-Azacitidine, 5-Aza) treatment controls induction of epithelial to mesenchymal (EMT) and a cancer stem cell (CSC) phenotype, which facilitates tumorigenesis in PCa cells. Here, we use the epidrug 5-Aza as a model for how histone marks may regulate the reprogramming of prostate adenocarcinoma into NE phenotypic cells...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29227276/alteration-in-the-cytokine-secretion-pattern-in-t-cells-of-patients-with-cystic-fibrosis-caused-by-dna-methyltransferase-inhibitor-5-azacitidine
#4
E Kvaratskhelia, N Dabrundashvili, M Gagua, E Maisuradze, M Kamkamidze, E Abzianidze
Cystic fibrosis (CF) is the autosomal-recessive disorder caused by mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The Airway inflammation plays a central role in the progression of CF disease. Cystic fibrosis characterized by the overproduction of the pro-inflammatory cytokines and reduced expression of anti-inflammatory cytokines. Although the mechanisms of abnormal cytokine expression is still poorly understood, altered epigenetic regulations in T cells might contribute. In the present study we examined the expression of IFN-γ and IL-10 by CF T cells prior to and following 5-azaC treatment...
November 2017: Georgian Medical News
https://www.readbyqxmd.com/read/29222294/incorporating-novel-approaches-in-the-management-of-mds-beyond-conventional-hypomethylating-agents
#5
REVIEW
Olatoyosi Odenike
In the last decade, the treatment of higher-risk myelodysplastic syndromes (MDS) has revolved around the azanucleosides, azacitidine and decitabine, which at lower doses are postulated to work predominantly via their effects on inhibition of DNA methyltransferases and consequent DNA hypomethylation. For patients who relapse after, or do not respond to, hypomethylating agent therapy, the outcome is dismal, and new agents and approaches that have the potential to alter the natural history of these diseases are desperately needed...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29222236/how-and-when-to-decide-between-epigenetic-therapy-and-chemotherapy-in-patients-with-aml
#6
REVIEW
Hervé Dombret, Raphael Itzykson
Remission induction with chemotherapy has long been the frontline treatment of acute myeloid leukemia (AML). However, intensive therapy is limited in frail patients by its associated toxicity and higher rates of failure or relapse in patients with chemoresistant disease, such as secondary AML or poor-risk cytogenetics. Frailty and chemoresistance are more frequent in older adults with AML. In recent years, epigenetic therapies with the hypomethylating agents decitabine and azacitidine have been thoroughly explored in AML...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29214694/myelodysplastic-syndromes-2018-update-on-diagnosis-risk-stratification-and-management
#7
Guillermo Montalban-Bravo, Guillermo Garcia-Manero
DISEASE OVERVIEW: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy. DIAGNOSIS: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry or molecular genetics is usually complementary and may help refine diagnosis...
January 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29212978/-acute-myeloid-leukemia-complicated-by-pneumonia-and-vertebral-osteomyelitis-during-induction-chemotherapy
#8
Yuki Kamata, Yuki Fujiwara, Kentaro Mizuhara, Naoya Mochizuki, Shiro Kubonishi, Yasushi Hiramatsu
A 76-year-old woman was operated on for rectal cancer in 2011 without chemotherapy and was followed up in the outpatient department. Decrease in white blood cell count was observed from 2013, and she developed anemia in 2015. Bone marrow aspiration was performed, and she was diagnosed with acute myeloid leukemia with myelodysplasia-related changes (AML/MRC). First, remission induction therapy was initiated with idarubicin and cytarabine administration, but pneumonia and vertebral osteomyelitis developed during the neutropenic period...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29205204/mthfr-ts-and-xrcc1-genetic-variants-may-affect-survival-in-patients-with-myelodysplastic-syndromes-treated-with-supportive-care-or-azacitidine
#9
G Visani, F Loscocco, A Ruzzo, S Galimberti, F Graziano, M T Voso, E Giacomini, C Finelli, E Ciabatti, E Fabiani, S Barulli, A Volpe, D Magro, P Piccaluga, F Fuligni, M Vignetti, P Fazi, A Piciocchi, E Gabucci, M Rocchi, M Magnani, A Isidori
We evaluated the impact of genomic polymorphisms in folate-metabolizing, DNA synthesis and DNA repair enzymes on the clinical outcome of 108 patients with myelodysplastic syndromes (MDS) receiving best supportive care (BSC) or azacitidine. A statistically significant association between methylenetetrahydrofolate reductase (MTHFR) 677T/T, thymidylate synthase (TS) 5'-untranslated region (UTR) 3RG, TS 3'-UTR -6 bp/-6 bp, XRCC1 399G/G genotypes and short survival was found in patients receiving BSC by multivariate analysis (P<0...
December 5, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29151503/acute-megakaryoblastic-leukemia-developing-as-donor-cell-leukemia-after-umbilical-cord-blood-transplantation
#10
Yoshitaka Adachi, Yohei Yamaguchi, Ken Sagou, Yusuke Yamaga, Nobuaki Fukushima, Kazutaka Ozeki, Akio Kohno
A 64-year-old man with acute myeloid leukemia underwent umbilical cord blood transplantation (UCBT). After 11 months of complete remission (CR) following UCBT, the bone marrow showed 7.5% myeloblasts. CR was obtained after a single course of azacitidine monotherapy, but the myeloblasts gradually increased in the blood. We made a diagnosis of acute megakaryoblastic leukemia derived from donor cell with a fluorescence in situ hybridization (FISH) analysis of the sex chromosomes and an immunophenotypic analysis...
November 20, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29151133/treatment-of-relapsed-aml-and-mds-after-allogeneic-stem-cell-transplantation-with-decitabine-and-dli-a-retrospective-multicenter-analysis-on-behalf-of-the-german-cooperative-transplant-study-group
#11
Thomas Schroeder, Christina Rautenberg, William Krüger, Uwe Platzbecker, Gesine Bug, Juliane Steinmann, Stefan Klein, Olaf Hopfer, Kathrin Nachtkamp, Mustafa Kondakci, Stefanie Geyh, Rainer Haas, Ulrich Germing, Martin Bornhäuser, Guido Kobbe
In contrast to the evidence regarding azacitidine (Aza), there is limited knowledge about the combination of decitabine (DAC) and donor lymphocyte infusions as salvage therapy for relapse after allogeneic stem cell transplantation (allo-SCT) so far. We retrospectively analyzed data of 36 patients with hematological (n = 35) or molecular relapse (n = 1) of acute myeloid leukemia (AML, n = 29) or myelodysplastic syndrome (MDS, n = 7) collected from 6 German transplant centers. Patients were treated with a median of 2 cycles DAC (range, 1 to 11)...
November 18, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29143282/hypomethylating-agents-for-treatment-and-prevention-of-relapse-after-allogeneic-blood-stem-cell-transplantation
#12
REVIEW
Thomas Schroeder, Christina Rautenberg, Rainer Haas, Ulrich Germing, Guido Kobbe
Despite the curative potential of allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), many patients will relapse. Until recently therapeutic options mainly consisted of palliative care, chemotherapy, donor lymphocyte infusions and second transplantation in selected cases. Still many patients either do not tolerate intensive therapies or do not achieve durable remissions and will finally succumb. Given this unmet medical need the hypomethylating agents (HMA), Azacitidine (Aza) and Decitabine (DAC) have been tested as salvage therapy in patients with myeloid malignancies relapsing after allo-SCT...
November 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29138222/decitabine-enhances-targeting-of-aml-cells-by-cd34-progenitor-derived-nk-cells-in-nod-scid-il2rgnull-mice
#13
Jeannette Cany, Mieke W H Roeven, Janneke S Hoogstad-van Evert, Willemijn Hobo, Frans Maas, Rosalia Franco Fernandez, Nicole M A Blijlevens, Walter J van der Velden, Gerwin Huls, Joop H Jansen, Nicolaas P M Schaap, Harry Dolstra
Combining NK cell adoptive transfer with hypomethylating agents (HMA) is an attractive therapeutic approach for patients with acute myeloid leukemia (AML). However, data regarding the impact of HMA on NK cell functionality are mostly derived from in vitro studies with high non-clinical relevant drug concentrations. Here, we report a comparative study of azacitidine and decitabine in combination with allogeneic NK cells generated from CD34+ hematopoietic stem and progenitor cells (HSPC-NK cells) in in vitro and in vivo AML models...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29129488/dna-hypomethylating-agents-as-epigenetic-therapy-before-and-after-allogeneic-hematopoietic-stem-cell-transplantation-in-myelodysplastic-syndromes-and-juvenile-myelomonocytic-leukemia
#14
REVIEW
Christian Flotho, Sebastian Sommer, Michael Lübbert
Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine...
November 9, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29118268/azacitidine-in-lower-risk-myelodysplastic-syndromes-a-meta-analysis-of-data-from-prospective-studies
#15
Rami Komrokji, Arlene S Swern, David Grinblatt, Roger M Lyons, Magnus Tobiasson, Lewis R Silverman, Hamid Sayar, Ravi Vij, Albert Fliss, Nora Tu, Mary M Sugrue
BACKGROUND: After erythropoiesis-stimulating agent (ESA) failure, lenalidomide and hypomethylating agents are the only remaining treatment options for most patients with lower-risk myelodysplastic syndromes (LR-MDS). Optimal choice of these agents as front-line therapy in non-del(5q) LR-MDS is unclear. Because azacitidine clinical data mainly describe experience in higher-risk MDS, we performed a meta-analysis of patient-level data to evaluate azacitidine in patients with red blood cell (RBC) transfusion-dependent LR-MDS...
November 8, 2017: Oncologist
https://www.readbyqxmd.com/read/29114374/prevention-of-chemotherapy-induced-nephrotoxicity-in-children-with-cancer
#16
REVIEW
Fatemeh Ghane Sharbaf, Hamid Farhangi, Farahnak Assadi
Children with cancer treated with cytotoxic drugs are frequently at risk of developing renal dysfunction. The cytotoxic drugs that are widely used for cancer treatment in children are cisplatin (CPL), ifosfamide (IFO), carboplatin, and methotrexate (MTX). Mechanisms of anticancer drug-induced renal disorders are different and include acute kidney injury (AKI), tubulointerstitial disease, vascular damage, hemolytic uremic syndrome (HUS), and intrarenal obstruction. CPL nephrotoxicity is dose-related and is often demonstrated with hypomagnesemia, hypokalemia, and impaired renal function with rising serum creatinine and blood urea nitrogen levels...
2017: International Journal of Preventive Medicine
https://www.readbyqxmd.com/read/29112938/impact-of-baseline-cytogenetic-findings-and-cytogenetic-response-on-outcome-of-high-risk-myelodysplastic-syndromes-and-low-blast-count-aml-treated-with-azacitidine
#17
Marie Sébert, Rami S Komrokji, Mikkael A Sekeres, Thomas Prebet, Thomas Cluzeau, Valeria Santini, Emmanuel Gyan, Alessandro Sanna, Najla HAl Ali, Sean Hobson, Virginie Eclache, Alan List, Pierre Fenaux, Lionel Adès
Karyotype according to the revised IPSS is a strong independent prognostic factor for overall survival (OS) in myelodysplastic syndromes (MDS), however established in untreated patients. The prognostic impact of cytogenetics and cytogenetic response (CyR) in MDS patients receiving azacitidine (AZA) remains uncertain. We examined the prognostic value of baseline cytogenetics and CyR for overall response rate (ORR) and OS in 702 AZA-treated higher risk MDS and low blast count acute myeloid leukemia (AML), including 493 (70%) with abnormal karyotype...
October 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29111375/a-novel-protocol-to-provide-a-suitable-cardiac-model-from-induced-pluripotent-stem-cells
#18
Mahsa Rasekhi, Masoud Soleimani, Behnaz Bakhshandeh, Majid Sadeghizadeh
Cumulative evidence has proven the safety, feasibility and efficacy of stem cell therapy for cardiomyocyte replacement in heart failure treatment. In contrast to embryonic stem cells, induced pluripotent stem cells (iPS cells) provide a route to the production of patient-specific stem cell lines with no ethical concerns. Recent studies have revealed that myogenic transcription factors activated the expression of conserved microRNAs (miRNAs), such as mir-1, that 'fine-tuned' the output of the transcriptional networks...
October 27, 2017: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/29108292/azacitidine-or-intensive-chemotherapy-for-older-patients-with-secondary-or-therapy-related-acute-myeloid-leukemia
#19
Pierre-Yves Dumas, Sarah Bertoli, Emilie Bérard, Clémence Médiavilla, Edwige Yon, Suzanne Tavitian, Thibaut Leguay, Françoise Huguet, Edouard Forcade, Noël Milpied, Audrey Sarry, Mathieu Sauvezie, Pierre Bories, Arnaud Pigneux, Christian Récher
The treatment of older patients with acute myeloid leukemia that is secondary to previous myelodysplastic syndrome, myeloproliferative neoplasm, or prior cytotoxic exposure remains unsatisfactory. We compared 92 and 107 patients treated, respectively, with intensive chemotherapy or azacitidine within two centres. Diagnoses were 37.5% post-myelodysplastic syndrome, 17.4% post-myeloproliferative neoplasia, and 45.1% therapy-related acute myeloid leukemia. Patients treated by chemotherapy had less adverse cytogenetics, higher white blood-cell counts, and were younger: the latter two being independent factors entered into the multivariate analyses...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29108241/identification-of-volasertib-resistant-mechanism-and-evaluation-of-combination-effects-with-volasertib-and-other-agents-on-acute-myeloid-leukemia
#20
Yoshiya Adachi, Yuichi Ishikawa, Hitoshi Kiyoi
Volasertib, a selective PLK1 inhibitor, was effective for acute myeloid leukemia (AML) patients in clinical trials. However, its efficacy was limited in mono-therapy, and a higher incidence of fatal events was revealed in the combination with low-dose cytarabine. Thus, optimization of combination therapy with volasertib and other agents is necessary for its clinical development, and the predictive factors for response or resistance to volasertib remain largely unknown. In this study, we investigated the resistance mechanism in volasertib-resistant cell lines and the combination effects with other agents, such as azacitidine (AZA), on AML cells...
October 3, 2017: Oncotarget
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