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https://www.readbyqxmd.com/read/28345491/a-comparison-of-toxicities-in-acute-myeloid-leukemia-patients-with-and-without-renal-impairment-treated-with-decitabine
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28261562/inhibition-of-dna-and-histone-methylation-by-5-aza-2-deoxycytidine-decitabine-and-3-deazaneplanocin-a-on-antineoplastic-action-and-gene-expression-in-myeloid-leukemic-cells
#8
Richard L Momparler, Sylvie Côté, Louise F Momparler, Youssef Idaghdour
Epigenetic alterations play an important role in the development of acute myeloid leukemia (AML) by silencing of genes that suppress leukemogenesis and differentiation. One of the key epigenetic changes in AML is gene silencing by DNA methylation. The importance of this alteration is illustrated by the induction of remissions in AML by 5-aza-2'-deoxycytidine (5-AZA-CdR, decitabine), a potent inhibitor of DNA methylation. However, most patients induced into remission by 5-AZA-CdR will relapse, suggesting that a second agent should be sought to increase the efficacy of this epigenetic therapy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28245380/-decitabine-enhances-the-sensitivity-of-leukemia-stem-cell-to-allo-nk-cell-mediated-killing
#9
Qian Li, Shan-Shan Wei, Jin-Gao Li, Shao-Xian Chen, Jing Chen, Hui-Ting Huang, Qi Peng, Ping-Fang Xia, Miao-Rong She
OBJECTIVE: To investigate the allo-NK cell-mediated killing effect enhanced by decitabine on leukemia stem cells(LSC) and the underlying mechanisms. METHODS: LSC were separated from KG1a cells by using immunomagnetic beads. Allo-NK cells were isolated and purified from PBMC of healthy donors. Cytotoxicity of allo-NK cells against LSC were measured by LDH releasing assay. The apoptosis induced by allo-NK cells in LSC and the expressions of NKG2D ligands including MICA/B and ULBP1-3 on LSC were detected by flow cytometry...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28237383/the-curious-case-of-a-cardiac-tamponade-in-the-hypertensive-patient-presenting-as-abdominal-fullness
#10
William Li, Rogin Subedi, Bhaskara Madhira
Cardiac tamponade is a medical emergency consisting of an accumulation of fluid in the pericardial space which is rapidly progressing and fatal. Because cardiac tamponade is ultimately a clinical diagnosis, mindful consideration for atypical presentations is essential for the reduction of mortality in the acute setting. Our patient was a 77year-old female admitted after presenting with general malaise, weakness, somnolence, altered mental status and urinary incontinence found to have CML (chronic myeloid leukemia) on confirmatory bone marrow biopsy after suspicions arose from a leukocytosis of 34,000 cells per mcL with 85% neutrophils and elevated blasts (8%)...
January 19, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28225682/decitabine-in-tp53-mutated-aml
#11
LETTER
John S Welch, Allegra A Petti, Timothy J Ley
No abstract text is available yet for this article.
February 23, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28219126/-clinical-significance-of-hypermethylation-of-dlc-1-gene-in-myelodysplastic-syndrome-patients-and-effects-of-decitabine-on-dlc-1-gene-expression
#12
H Y Fu, H R Zhou, J G Yan, C J Chen, J Z Shen
Objective: To detect the methylation status of DLC-1 gene in the patients with myelodysplastic syndrome(MDS), the effect of abnormal methylation of DLC-1 gene on the expression of DLC-1 gene, the clinical significance of methylation of DLC-1 gene in MDS patients, and the effect of decitabine on DLC-1 gene expression. Methods: A total of 43 MDS patients were treated in Fujian Medical University Union Hospital from 2013 to 2015. Methylation status of DLC-1 gene in MDS patients were detected by the methylation specific PCR(MSP)...
February 14, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28191543/the-third-time-chronic-myeloid-leukemia-in-lymphoblastic-crisis-with-abl1-kinase-mutation-induced-by-decitabine-dexamethason-combined-with-nilotinib-and-dasatinib
#13
Suli Wang, Chun Qiao, Yu Zhu, Wenyi Shen, Guangsheng He, Jianyong Li
Blast crisis (BC) is the major remaining challenge in the management of chronic myeloid leukemia (CML). The prognosis of the BC patient who carries ABL kinase mutation is very poor. One patient, with lymphoid CML-BC third time, was detected with T315A/F359I/M244V compound mutation by direct sequencing after treatment with tyrosine kinase inhibitions three years. The patient was treated with decitabine, dexamethasone, in combination with nilotinib and dasatinib. Then this patient received a complete hematologic response and cytogenetic response after two cycles of treatment...
December 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28185797/evidence-for-selective-benefit-of-sequential-treatment-with-hypomethylating-agents-in-patients-with-myelodysplastic-syndrome
#14
Susmitha Apuri, Najla Al Ali, Eric Padron, Jeffrey E Lancet, Alan F List, Rami S Komrokji
BACKGROUND: Hypomethylating agents (HMAs) remain the mainstay of treatment of patients with myelodysplastic syndrome (MDS). Azacitidine is the only agent shown to improve overall survival in higher risk MDS. The sequential use of HMAs is common practice, given the limited alternatives. The response rate to azacitidine after decitabine is unknown. To investigate the potential benefit of this approach, we reviewed all cases of sequential HMA treatment. PATIENTS AND METHODS: The Moffitt Cancer Center MDS database was reviewed, and 2 groups were identified...
January 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28164571/establishment-of-a-novel-myelodysplastic-syndrome-mds-xenotransplantation-model
#15
Ling Ma, Xia Zhang, Zhiqiong Wang, Yan Chen, Jia Wei, Lihua Hu
BACKGROUND: Myelodysplastic syndrome (MDS) is a clonal disease of the elderly characterized by chronic cytopenia, dysplasia, and a high risk of progression to acute myeloid leukemia (AML). Up until now, few animal models that fully recapitulate clinical features of this disease have been available. METHODS: This study aimed to establish a new MDS xenograft model utilizing a human MDS-derived cell line with heterozygous Y641C mutation of EZH2 (SKM-1). 1 x 107 SKM-1 cells were inoculated into anti-mouse CD122 monoantibody conditioned nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice by intravenous injection...
September 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28162915/simple-in-vitro-generation-of-human-leukocyte-antigen-g-expressing-t-regulatory-cells-through-pharmacological-hypomethylation-for-adoptive-cellular-immunotherapy-against-graft-versus-host-disease
#16
Panagiota Stamou, Dimitra Marioli, Alexandra L Patmanidi, Argyro Sgourou, Angeliki Vittoraki, Efthymia Theofani, Chryso Pierides, Stavros Taraviras, Paul A Costeas, Alexandros Spyridonidis
BACKGROUND: Major barriers in using classical FOXP3+ regulatory T cells (Tregs) in clinical practice are their low numbers in the circulation, the lack of specific cell surface markers for efficient purification and the loss of expression of Treg signature molecules and suppressive function after in vitro expansion or in a pro-inflammatory microenviroment. A surface molecule with potent immunosuppressive function is the human leukocyte antigen-G (HLA-G), which is normally expressed in placenta protecting the "semi-allogeneic" fetus from maternal immune attack...
February 2, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28161120/management-of-venetoclax-posaconazole-interaction-in-acute-myeloid-leukemia-patients-evaluation-of-dose-adjustments
#17
Suresh K Agarwal, Courtney D DiNardo, Jalaja Potluri, Martin Dunbar, Hagop M Kantarjian, Rod A Humerickhouse, Shekman L Wong, Rajeev M Menon, Marina Y Konopleva, Ahmed Hamed Salem
PURPOSE: The effect of posaconazole, a strong cytochrome P450 3A (CYP3A) inhibitor and commonly used antifungal agent, on the pharmacokinetic properties of venetoclax, a CYP3A substrate, was evaluated in patients with acute myeloid leukemia to determine the dose adjustments needed to manage this potential interaction. METHODS: Twelve patients received 20- to 200-mg ramp-up treatment with oral venetoclax and 20 mg/m(2) of intravenous decitabine on days 1 through 5, followed by 400 mg of venetoclax alone on days 6 through 20...
February 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28159832/dna-hypomethylating-drugs-in-cancer-therapy
#18
Takahiro Sato, Jean-Pierre J Issa, Patricia Kropf
Aberrant DNA methylation is a critically important modification in cancer cells, which, through promoter and enhancer DNA methylation changes, use this mechanism to activate oncogenes and silence of tumor-suppressor genes. Targeting DNA methylation in cancer using DNA hypomethylating drugs reprograms tumor cells to a more normal-like state by affecting multiple pathways, and also sensitizes these cells to chemotherapy and immunotherapy. The first generation hypomethylating drugs azacitidine and decitabine are routinely used for the treatment of myeloid leukemias and a next-generation drug (guadecitabine) is currently in clinical trials...
February 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28152502/methylation-decreases-the-bin1-tumor-suppressor-in-escc-and-restoration-by-decitabine-inhibits-the-epithelial-mesenchymal-transition
#19
Xuexiao Wang, Jiali Wang, Yunlong Jia, Yu Wang, Xiaonan Han, Yuqing Duan, Wei Lv, Ming Ma, Lihua Liu
Bridging integrator-1 (Bin1), as a tumor suppressor, is frequently attenuated or even abolished in multiple primary cancers. A reduced expression of Bin1 caused by DNA methylation, has been reported in breast and prostate cancers. However, the methylation status of Bin1 and potent biological functions in esophageal squamous cell carcinoma (ESCC) remain unclear. In a previous study, we showed that the Bin1 expression was low in ESCC tissues. Herein, we further characterized this mechanism, confirming that gene hypermethylation was significantly correlated with the aberrant attenuation of Bin1...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28151481/epigenetic-regulation-of-hgf-met-receptor-axis-is-critical-for-the-outgrowth-of-bone-metastasis-from-breast-carcinoma
#20
Paola Bendinelli, Paola Maroni, Emanuela Matteucci, Maria Alfonsina Desiderio
Our translational research deals with the influence of microenvironment on the phenotype and colonization of bone metastases from breast carcinoma, and on pre-metastatic niche formation. The aim of the present study was to clarify the origin of hepatocyte growth factor (HGF), ligand of Met receptor, the control of the axis HGF/Met by DNA methylation, and its importance for the nexus supportive cells-metastatic cells and for metastasis outgrowth. In bone metastasis of the 1833-xenograft model, DNA methyltransferase blockade using the chemotherapic drug 5-aza-2'-deoxycytidine (decitabine) strongly reduced the expression of HGF/Met receptor axis and of E-cadherin, with decrease of metastasis wideness and osteolysis, prolonging mice survival...
February 2, 2017: Cell Death & Disease
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