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https://www.readbyqxmd.com/read/28445872/successful-management-of-decitabine-prior-to-full-dose-idarubicin-and-cytarabine-in-the-treatment-of-refractory-recurrent-acute-myeloid-leukemia
#1
Hongyu Zhao, Li Xu, Yongjian Yang, Jianhua Shao, Ping Chen, Xuebin Dong, Linping Gu, Daqi Li
AIMS: To investigate the safety and efficacy of the triple therapy of decitabine, idarubicin, and cytarabine in the treatment of refractory or recurrent acute myeloid leukemia (R/R AML). METHODS: We conducted a single-center retrospective study in which decitabine treatment was administered prior to full-dose idarubicin and cytarabine (D-IA) for 21 R/R AML patients. RESULTS: After 1 cycle of D-IA, 10/21 (47.6%) patients experienced a complete remission (CR) and 2/21 (9...
April 27, 2017: Acta Haematologica
https://www.readbyqxmd.com/read/28436707/samhd1-protects-cancer-cells-from-various-nucleoside-based-antimetabolites
#2
Nikolas Herold, Sean G Rudd, Kumar Sanjiv, Juliane Kutzner, Julia Bladh, Cynthia B J Paulin, Thomas Helleday, J I Henter, Torsten Schaller
Recently, we demonstrated that sterile alpha motif and HD domain containing protein 1 (SAMHD1) is a major barrier in acute myelogenous leukemic (AML) cells to the cytotoxicity of cytarabine (ara-C), the most important drug in AML treatment. Ara-C is intracellularly converted by the canonical dNTP synthesis pathway to ara-CTP, which serves as a substrate but not an allosteric activator of SAMHD1. Using an AML mouse model, we show here that wild type but not catalytically inactive SAMHD1 reduces ara-C treatment efficacy in vivo...
April 24, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28435228/erratum-decitabine-reverses-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-non-small-cell-lung-cancer-by-regulating-mir-200-zeb-axis-corrigendum
#3
(no author information available yet)
[This corrects the article on p. 969 in vol. 11.].
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28433417/mechanistic-insights-into-epigenetic-modulation-of-ethanol-consumption
#4
Igor Ponomarev, Claire E Stelly, Hitoshi Morikawa, Yuri A Blednov, R Dayne Mayfield, R Adron Harris
There is growing evidence that small-molecule inhibitors of epigenetic modulators, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), can reduce voluntary ethanol consumption in animal models, but molecular and cellular processes underlying this behavioral effect are poorly understood. We used C57BL/6J male mice to investigate the effects of two FDA-approved drugs, decitabine (a DNMT inhibitor) and SAHA (an HDAC inhibitor), on ethanol consumption using two tests: binge-like drinking in the dark (DID) and chronic intermittent every other day (EOD) drinking...
March 12, 2017: Alcohol
https://www.readbyqxmd.com/read/28427903/atrial-fibrillation-is-associated-with-hypermethylation-in-human-left-atrium-and-treatment-with-decitabine-reduces-atrial-tachyarrhythmias-in-spontaneously-hypertensive-rats
#5
R Doñate Puertas, E Meugnier, C Romestaing, C Rey, E Morel, J Lachuer, N Gadot, A Scridon, C Julien, F Tronc, B Chapuis, C Valla, A Janin, L Pirola, A Méjat, S Rome, P Chevalier
Atrial fibrillation (AF) is the most common cardiac arrhythmia. As the molecular mechanisms underlying the pathology are largely unknown, this cardiac arrhythmia remains difficult to treat. To identify specific molecular actors involved in AF, we have performed a transcriptomic analysis on left atrium (LA) from patients with valvular heart disease with or without AF. We showed that 1627 genes had altered basal expression level in LA tissue of AF patients compared with the control group. The significantly enriched gene ontology biological process "anatomical structure morphogenesis" contained the highest number of genes in line with changes in structure that occur when the human heart remodels following AF development (ie, LA dilatation and interstitial fibrosis)...
March 30, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28406054/decitabine-as-salvage-therapy-for-primary-induction-failure-of-acute-myeloid-leukemia
#6
Pasquale Niscola, Benedetta Neri, Gianfranco Catalano, Luciana Morino, Marco Giovannini, Laura Scaramucci, Stefano Fratoni, Nélida Inés Noguera, Iole Cordone, Paolo de Fabritiis
No abstract text is available yet for this article.
February 17, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28405849/hypomethylation-agent-decitabine-restores-drug-sensitivity-by-depressing-p-glycoprotein-activity-through-mapk-signaling-pathway
#7
Huihan Wang, Xiaobin Wang, Aijun Liao, Zhuogang Liu
The multidrug resistance (MDR) continues to be an obstacle in the treatment of both hematological and solid tumors. Hypomethylation agent, decitabine (5-Aza-dC), is an experimental agent in MDR therapy, while the mechanism is not very clear. In the present study, we demonstrated 5-Aza-dC may reverse MDR induced by P-glycoprotein (P-gp) coded by mdr1 gene in both hematologic K562/ADR cells and solid tumor MCF-7/ADR cells with time and dose-dependent manner. 5-Aza-dC significantly increased drug sensitivity in patients' leukemic cells which had higher expression of mdr1 gene...
April 12, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28405157/decitabine-reverses-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-in-non-small-cell-lung-cancer-by-regulating-mir-200-zeb-axis
#8
Nan Zhang, Yanyang Liu, Yuyi Wang, Maoyuan Zhao, Li Tu, Feng Luo
OBJECTIVE: Epithelial-mesenchymal transition (EMT) is a crucial driver of tumor progression. Tumor growth factor-beta 1 (TGF-β1) is an important factor in EMT induction in tumorigenesis. The targeting of EMT may, therefore, represent a promising approach in anticancer treatment. METHODS: In this study, we determined the effect of decitabine, a DNA methyltransferase inhibitor, on TGF-β1-induced EMT in non-small-cell lung cancer (NSCLC) PC9 and A549 cells. We also assessed the involvement of the miR-200/ZEB axis...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28404876/increasing-timp3-expression-by-hypomethylating-agents-diminishes-soluble-mica-micb-and-ulbp2-shedding-in-acute-myeloid-leukemia-facilitating-nk-cell-mediated-immune-recognition
#9
Aroa Baragaño Raneros, Alfredo Minguela Puras, Ramon M Rodriguez, Enrique Colado, Teresa Bernal, Eduardo Anguita, Adela Vasco Mogorron, Alberto Chaparro Gil, Vidal-Castiñeira Jr, Leonardo Márquez-Kisinousky, Paula Díaz Bulnes, Amelia Martinez Marin, Maria Carmen García Garay, Beatriz Suarez-Alvarez, Carlos Lopez-Larrea
Acute myeloid leukemia (AML) is a disease with great morphological and genetic heterogeneity, which complicates its prognosis and treatment. The hypomethylating agents azacitidine (Vidaza®, AZA) and decitabine (Dacogen®, DAC) have been approved for the treatment of AML patients, but their mechanisms of action are poorly understood. Natural killer (NK) cells play an important role in the recognition of AML blasts through the interaction of the activating NKG2D receptor with its ligands (NKG2DL: MICA/B and ULBPs1-3)...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28388554/synergistic-inhibitory-effects-of-deferasirox-in-combination-with-decitabine-on-leukemia-cell-lines-skm-1-thp-1-and-k-562
#10
Nianyi Li, Qinfen Chen, Jingwen Gu, Shuang Li, Guangjie Zhao, Wei Wang, Zhicheng Wang, Xiaoqin Wang
A multi-center study from the French Myelodysplastic Syndrome (MDS) Group confirmed that iron chelation therapy is an independent prognostic factor that can increase the survival rate of patients who are suffering from transfusion-dependent low-risk MDS. In this study, we aimed to explore this clinical phenomena in vitro, by exploring the synergistic effect of the iron chelator Deferasirox (DFX) and the DNA methyl transferase inhibitor Decitabine (DAC) in the leukemia cell lines SKM-1, THP-1, and K-562. Treatment with both DFX or DAC promoted apoptosis, induced cell cycle arrest, and inhibited proliferation in all three of these cell lines...
March 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28370097/natural-history-of-chronic-myelomonocytic-leukemia-treated-with-hypomethylating-agents
#11
Ana Alfonso, Guillermo Montalban-Bravo, Koichi Takahashi, Elias J Jabbour, Tapan Kadia, Farhad Ravandi, Jorge Cortes, Zeev Estrov, Gautam Borthakur, Naveen Pemmaraju, Marina Konopleva, Carlos Bueso-Ramos, Sherry Pierce, Hagop Kantarjian, Guillermo Garcia-Manero
Hypomethylating agents (HMA) are the most commonly used therapeutic intervention in chronic myelomonocytic leukemia (CMML). Due to the lack of CMML-specific clinical trials, the impact of these agents in the natural history of CMML is not fully understood. We present the largest retrospective series of CMML (n=151) treated with HMA. Mean age at diagnosis was 69 years (range 50-88). According to the CMML-specific prognostic scoring system (CPSS): 17 (15%) were low-risk, 45 (39%) intermediate-1 risk, 42 (36%) intermediate-2, and 12 (10%) high-risk...
March 28, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28367417/lovastatin-reduces-stemness-via-epigenetic-reprograming-of-bmp2-and-gata2-in-human-endometrium-and-endometriosis
#12
Mahdieh Taghizadeh, Mehrdad Noruzinia
OBJECTIVE: The stem cell theory in the endometriosis provides an advanced avenue of targeting these cells as a novel therapy to eliminate endometriosis. In this regard, studies showed that lovastatin alters the cells from a stem-like state to more differentiated condition and reduces stemness. The aim of this study was to investigate whether lovastatin treatment could influence expression and methylation patterns of genes regulating differentiation of endometrial mesenchymal stem cells (eMSCs) such as BMP2, GATA2 and RUNX2 as well as eMSCs markers...
April 2017: Cell Journal
https://www.readbyqxmd.com/read/28359286/the-double-edged-sword-of-re-expression-of-genes-by-hypomethylating-agents-from-viral-mimicry-to-exploitation-as-priming-agents-for-targeted-immune-checkpoint-modulation
#13
REVIEW
Florian Wolff, Michael Leisch, Richard Greil, Angela Risch, Lisa Pleyer
Hypomethylating agents (HMAs) have been widely used over the last decade, approved for use in myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). The proposed central mechanism of action of HMAs, is the reversal of aberrant methylation in tumor cells, thus reactivating CpG-island promoters and leading to (re)expression of tumor suppressor genes. Recent investigations into the mode of action of azacitidine (AZA) and decitabine (DAC) have revealed new molecular mechanisms that impinge on tumor immunity via induction of an interferon response, through activation of endogenous retroviral elements (ERVs) that are normally epigenetically silenced...
March 31, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28345491/a-comparison-of-toxicities-in-acute-myeloid-leukemia-patients-with-and-without-renal-impairment-treated-with-decitabine
#14
Lauren B Levine, Julianna Vf Roddy, Miryoung Kim, Junan Li, Gary Phillips, Alison R Walker
Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min)...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28337888/decitabine-treatment-for-acute-myeloid-leukemia-relapse-after-allogeneic-hematopoietic-stem-cell-transplantation
#15
X L Liu, X Zhao, C Wang, S J Gao, Y H Tan
Therapeutic options for patients with relapse of acute myeloid leukemia (AML) after allo-SCT are limited. Here, we present a case of a 49-year female with AML who underwent myeloablative allo-SCT from a matched sibling donor. Seven months after transplantation she developed cGVHD and suffered from extramedullary plus concurrent medullary relapse. The presence of CNS extramedullary disease is unique. Our patient was treated with decetabine. After one cycle the patient achieved complete remission and full donor chimerism without severe side effects or the occurrence of GVHD...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28337274/decitabine-treatment-sensitizes-tumor-cells-to-t-cell-mediated-cytotoxicity-in-patients-with-myelodysplastic-syndromes
#16
Zheng Zhang, Qi He, Ying Tao, Juan Guo, Feng Xu, Ling-Yun Wu, You-Shan Zhao, Dong Wu, Li-Yu Zhou, Ji-Ying Su, Lu-Xi Song, Chao Xiao, Xiao Li, Chun-Kang Chang
Decitabine treatment improves immunological recognition that increases expression of cancer-testis antigens (CTAs) against solid tumors. The mechanisms of decitabine enhancement of immunogenicity when used for patients with myelodysplastic syndromes (MDS) remain unclear. In the present study, we found relatively low baseline expression of MAGE-A1, MAGE-A3, and SP17 in MDS-derived cell lines. Decitabine treatment significantly improved MAGE-A1, MAGE-A3, and SP17 expression in these cell lines and in MDS patients...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28321548/demethylating-agent-decitabine-disrupts-tumor-induced-immune-tolerance-by-depleting-myeloid-derived-suppressor-cells
#17
Jihao Zhou, Yushi Yao, Qi Shen, Guoqiang Li, Lina Hu, Xinyou Zhang
PURPOSE: The immunoregulatory effect of demethylating agent decitabine (DAC) has been recognized recently. However, little is known about its impact on immune tolerance. In this study, we aimed to determine the impact of DAC on the immune tolerance induced by tumor cells. METHODS: The effects of DAC on immune cells in vivo were measured by flow cytometry. Myeloid-derived suppressor cells (MDSCs) were sorted using magnetic beads and cultured in vitro. The mixed lymphocyte reaction was used to determine the immunoregulatory effect of DAC in vitro...
March 20, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28279036/-predict-response-to-decitabine-in-patients-with-myelodysplastic-syndrome-and-related-neoplasms
#18
Y S Zhao, J Guo, F Xu, D Wu, L Y Wu, L L Song, C Xiao, X Li, C K Chang
Objective: To identify clinical and molecular signatures for predicting response to decitabine (DAC) in patients with myelodysplastic syndrome (MDS) and related neoplasms. Methods: The clinical characteristics of 109 patients with MDS and related neoplasms who were treated with DAC were analyzed retrospectively and the next target sequencing was performed to define recurrently mutated genes in these disease samples, to examine the association of the clinical and molecular signatures with response to DAC treatment...
February 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28278722/gene-expression-analysis-of-decitabine-treated-aml-high-impact-of-tumor-suppressor-gene-expression-changes
#19
Stephan R Bohl, Anna Dolnik, Thomas Jensen, Katharina M Lang, Björn Hackanson, Verena I Gaidzik, Peter Paschka, Steen Knudsen, Konstanze Döhner, Hartmut Döhner, Rainer Claus, Michael Lübbert, Lars Bullinger
No abstract text is available yet for this article.
February 13, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28278716/efficacy-of-single-agent-decitabine-in-relapsed-and-refractory-acute-myeloid-leukemia
#20
Niloufer Khan, Andrew Hantel, Randall W Knoebel, Andrew Artz, Richard A Larson, Lucy A Godley, Michael J Thirman, Hongtao Liu, Jane E Churpek, Darren King, Olatoyosi Odenike, Wendy Stock
Improving therapy for relapsed/refractory AML remains a challenge. We performed a retrospective analysis of outcomes following decitabine treatment in 34 patients with relapsed/refractory AML (median age, 62; median Charlson comorbidity score, 6). Decitabine, 20 mg/m(2) daily, was given in 5- (25%) or 10-day (75%) cycles. Overall response rate (OR) was 30% with 21% complete remission and 9% partial remission rate. Patients with therapy-related myeloid neoplasm (t-MN) and secondary AML had a significantly higher OR compared to those with de novo AML (70 vs...
February 20, 2017: Leukemia & Lymphoma
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