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https://www.readbyqxmd.com/read/28818807/early-treatment-initiation-in-lower-risk-myelodysplastic-syndromes-produces-an-earlier-and-higher-rate-of-transfusion-independence
#1
Christopher R Cogle, Sheila R Reddy, Eunice Chang, Elya Papoyan, Michael S Broder, Michael McGuire, Gary Binder
Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis resulting in refractory cytopenias. Red blood cell (RBC) transfusions can improve anemia; however, prolonged transfusion dependence (TD) is associated with increased morbidity and mortality. Disease-modifying therapy (DMT) for MDS can reduce transfusion requirements, although the optimum timing of DMT initiation is unclear. This retrospective study analyzed linked SEER registry and Medicare claims (2006-2012) to estimate the impact of DMT-initiation (azacitidine, decitabine, or lenalidomide) timing (≤ 3 vs...
August 1, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28810323/-the-efficacy-and-safety-of-the-patients-of-myelodysplastic-syndromes-refractory-anemia-with-excess-blasts-treated-with-decitabine-alone-or-cag-hag-regimen
#2
Z F Xu, T J Qin, H L Zhang, L W Fang, Y Zhang, L J Pan, N B Hu, S Q Qu, B Li, Z J Xiao
Objective: To observe the clinical efficacy and safety of the patients of myelodysplastic syndromes-refractory anemia with excess blasts (MDS-REAB) treated with decitabine alone or based on low dose cytarabine (Ara-C) regimen CAG/HAG [aclarubrci (ACR) /homoharring-tonine (HHT) +cytarabine+granulocyte colony stimulating factor (G-CSF) ]. Methods: Totally 121 patients with MDS-REAB were retrospectively analyzed, including 59 patients treated with decitabine alone (20 mg·m(-2)·d(-1) for 5 days) , the rest 62 ones treated with low-dose Ara-C-based regimen CAG/HAG...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28801263/glucocorticoids-regulate-mir-29c-levels-in-vascular-smooth-muscle-cells-through-transcriptional-and-epigenetic-mechanisms
#3
Tsai-Der Chuang, Omid Khorram
AIMS: The objective of this study was to determine the underlying mechanism by which glucocorticoids (GCs) induce of miR-29c expression in vascular smooth muscle cells. MAIN METHODS: QRT-PCR was used for miR-29c detection. Protein levels were determined by western blotting. Knockdown of SP1, DNMT1 and DNMT3A was achieved through transfection with their specific respective siRNAs. The effect of GCs on SP1 activity was determined by luciferase reporter assay and the methylation status in miR-29c promoter was detected by methylation specific PCR...
August 8, 2017: Life Sciences
https://www.readbyqxmd.com/read/28774880/a-randomized-phase-ii-study-of-low-dose-decitabine-versus-low-dose-azacitidine-in-lower-risk-mds-and-mds-mpn
#4
Elias Jabbour, Nicholas J Short, Guillermo Montalban-Bravo, Xuelin Huang, Carlos Bueso-Ramos, Wei Qiao, Hui Yang, Chong Zhao, Tapan Kadia, Gautam Borthakur, Naveen Pemmaraju, Koji Sasaki, Zeev Estrov, Jorge Cortes, Farhad Ravandi, Yesid Alvarado, Rami Komrokji, Mikkael A Sekeres, David P Steensma, Amy DeZern, Gail Roboz, Hagop Kantarjian, Guillermo Garcia-Manero
BACKGROUND: Hypomethylating agents (HMAs) improve survival in patients with higher-risk myelodysplastic syndromes (MDS) but are less well-studied in lower-risk disease. We compared the safety and efficacy of low-dose decitabine versus low-dose azacitidine in this group of patients. METHODS: Adults with low- or intermediate-1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, by the International Prognostic Scoring System were randomized using a Bayesian adaptive design to receive either azacitidine 75 mg/m(2) IV/SC daily or decitabine 20 mg/m(2) IV daily for 3 consecutive days on a 28-day cycle...
August 3, 2017: Blood
https://www.readbyqxmd.com/read/28760688/the-oligodendrocyte-lineage-transcription-factor-2-olig2-is-epigenetically-regulated-in-acute-myeloid-leukemia
#5
Arzu Yalcin, Marlon Kovarbasic, Julius Wehrle, Rainer Claus, Heiko Becker, Mahmoud Abdelkarim, Verena I Gaidzik, Andrea Schmidts, Ralph Wäsch, Heike L Pahl, Konstanze Döhner, Lars Bullinger, Justus Duyster, Michael Lübbert, Björn Hackanson
DNA methylation differences between normal and cancer tissue resulting in differential expression of genes are a hallmark of acute myeloid leukemia (AML) and can provide growth advantage for malignant cells via silencing of specific genes, e.g. transcription factors. The oligodendrocyte lineage transcription factor 2 (OLIG2) was reported to be differentially methylated and associated with prognosis in AML and - as demonstrated for acute lymphoblastic leukemia and malignant glioma - may play a role in malignant transformation...
July 28, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28760054/successful-treatment-of-a-patient-with-acute-promyelocytic-leukemia-with-a-stat5b-rara-fusion-gene-using-decitabine
#6
Anyou Wang, Xiaoyan Cai, Ping Qiang, Qiaohong Duan
No abstract text is available yet for this article.
August 1, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28757548/the-role-of-epigenetic-regulation-in-epstein-barr-virus-associated-gastric-cancer
#7
REVIEW
Jun Nishikawa, Hisashi Iizasa, Hironori Yoshiyama, Munetaka Nakamura, Mari Saito, Sho Sasaki, Kanami Shimokuri, Masashi Yanagihara, Kouhei Sakai, Yutaka Suehiro, Takahiro Yamasaki, Isao Sakaida
The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases throughout the world. In EBV-associated gastric carcinoma (EBVaGC), all tumor cells harbor the clonal EBV genome. The expression of latent EBV genes is strictly regulated through the methylation of EBV DNA. The methylation of viral DNA regulates the type of EBV latency, and methylation of the tumor suppressor genes is a key abnormality in EBVaGC. The methylation frequencies of several tumor suppressor genes and cell adhesion molecules are significantly higher in EBVaGC than in control cases...
July 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28750405/untargeted-dna-demethylation-therapy-neither-prevents-nor-attenuates-ischemia-reperfusion-induced-renal-fibrosis
#8
Benjamin A Vervaet, Lies Moonen, Lode Godderis, Katrien Poels, Patrick C D'Haese
BACKGROUND: Current treatment options for chronic kidney disease (CKD) are limited and their focus is on slowing its progression by addressing comorbidities. Fibrosis, the common histopathological process in CKD, is a major therapeutic research target. In CKD, fibroblasts are terminally activated due to alterations in their DNA-methylation pattern, particularly hypermethylation. Preventing the copying of pathological DNA-methylation patterns in proliferating fibroblasts could be a new effective therapeutic strategy for treating CKD...
July 28, 2017: Nephron
https://www.readbyqxmd.com/read/28745928/low-dose-decitabine-enhances-chidamide-induced-apoptosis-in-adult-acute-lymphoblast-leukemia-especially-for-p16-deleted-patients-through-dna-damage
#9
Pengcheng Shi, Leisi Zhang, Kai Chen, Zhiwu Jiang, Manman Deng, Jie Zha, Xutao Guo, Peng Li, Bing Xu
AIM: To investigate the combined action of decitabine (DAC) with chidamide (CS055) on acute lymphoblastic leukemia (ALL) cells. MATERIALS & METHODS: ALL cell lines as well as primary cells from 17 ALL patients were subjected to different treatments and thereafter cell counting Kit-8 (CCK-8) assay, flow cytometry and western blot were employed to determine IC50, apoptosis and checkpoint kinase 1 and γH2A.X expression. RESULTS: Low-dose DAC combined with CS055 could effectively kill ALL cells by the reduction of cell viability and induction of apoptosis...
July 26, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28729399/decitabine-priming-enhances-mucin-1-inhibition-mediated-disruption-of-redox-homeostasis-in-cutaneous-t-cell-lymphoma
#10
Salvia Jain, Abigail Washington, Rebecca Karp Leaf, Parul Bhargava, Rachael A Clark, Thomas S Kupper, Dina Stroopinsky, Athalia Pyzer, Leandra Cole, Myrna Nahas, Arie Apel, Jacalyn Rosenblatt, Jon Arnason, Donald Kufe, David Avigan
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous neoplasm and patients with relapsed/refractory disease exhibit resistance to standard therapies. We have previously demonstrated that the MUC1-C oncoprotein plays a critical role in protection from oxidative stress in CTCL cells. Targeting of MUC1-C with a pharmacologic inhibitor, GO-203, was associated with apoptosis in CTCL. However, disease responses were incomplete underscoring the need for combinatorial strategies that could exploit the vulnerability of CTCL cells to oxidative signals...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28729302/vosaroxin-in-combination-with-decitabine-in-newly-diagnosed-older-patients-with-acute-myeloid-leukemia-or-high-risk-mds
#11
Naval Daver, Hagop Kantarjian, Guillermo Garcia-Manero, Elias Jabbour, Gautam Borthakur, Mark Brandt, Sherry Pierce, Kenneth Vaughan, Jing Ning, Graciela M Nogueras González, Keyur Patel, Jeff Jorgensen, Naveen Pemmaraju, Tapan Kadia, Marina Konopleva, Michael Andreeff, Courtney DiNardo, Jorge Cortes, Renee Ward, Adam Craig, Farhad Ravandi
Vosaroxin is an anti-cancer quinolone derived DNA topoisomerase II inhibitor. We investigated vosaroxin with decitabine in patients ≥ 60 years of age with newly diagnosed acute myeloid leukemia (AML) (n=58) or myelodysplastic syndrome (MDS) (≥ 10% blasts) (n=7) in a phase 2 non-randomized trial. The initial 22 patients received vosaroxin 90 mg/m2 on Days 1 and 4 with decitabine 20 mg/m2 Days 1-5 every 4-6 weeks for up to 7 cycles. Due to high incidence of mucositis the subsequent 43 patients received vosaroxin 70 mg/m2 Days 1 and 4...
July 20, 2017: Haematologica
https://www.readbyqxmd.com/read/28726739/5-aza-2-2-difluroro-deoxycytidine-nuc013-a-novel-nucleoside-dna-methyl-transferase-inhibitor-and-ribonucleotide-reductase-inhibitor-for-the-treatment-of-cancer
#12
Richard Daifuku, Zhenbo Hu, Yogen Saunthararajah
Tumor suppressor genes can be silenced genetically as well as epigenetically. One approach to reversing epigenetic suppression of tumor suppressor genes is to inhibit DNA methyl transferase. 5-aza-2',2'-diflurorodeoxycytidine (NUC013) is a novel DNA methyl transferase and ribonucleotide reductase inhibitor that is a more potent inhibitor of growth than decitabine in the NCI 60 cancer cell line panel. NUC013 is more active than decitabine against p53-null/mutant cancer cell lines (p = 0.027) but is even more so against p53 wild-type (WT) cell lines (p = 0...
July 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28718760/cd25-expression-and-outcomes-in-older-patients-with-acute-myelogenous-leukemia-treated-with-plerixafor-and-decitabine
#13
John N Allan, Gail J Roboz, Gulce Askin, Ellen Ritchie, Joseph Scandura, Paul Christos, Duane C Hassane, Monica L Guzman
We investigated CD25 expression in older (≥60 years) patients with new acute myelogenous leukemia treated with decitabine and plerixafor. Patients resistant to therapy or survival ≤1 year had significantly higher percentages of CD25(pos) myeloid blasts in baseline bone marrow. CD25(pos) patients had an increased odds of resistance compared to CD25(neg) patients (p = .015). In univariate analysis, we found CD25(pos) patients had inferior survival compared to CD25(neg) (p = .002). In patients with intermediate risk cytogenetics, CD25(pos) status stratified patients associating with inferior survival (p = ...
July 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28710449/combined-deletion-and-dna-methylation-result-in-silencing-of-fam107a-gene-in-laryngeal-tumors
#14
Katarzyna Kiwerska, Marcin Szaumkessel, Julia Paczkowska, Magdalena Bodnar, Ewa Byzia, Ewelina Kowal, Magdalena Kostrzewska-Poczekaj, Joanna Janiszewska, Kinga Bednarek, Małgorzata Jarmuż-Szymczak, Ewelina Kalinowicz, Małgorzata Wierzbicka, Reidar Grenman, Krzysztof Szyfter, Andrzej Marszałek, Maciej Giefing
Larynx squamous cell carcinoma (LSCC) is characterized by complex genotypes, with numerous abnormalities in various genes. Despite the progress in diagnosis and treatment of this disease, 5-year survival rates remain unsatisfactory. Therefore, the extended studies are conducted, with the aim to find genes, potentially implicated in this cancer. In this study, we focus on the FAM107A (3p14.3) gene, since we found its significantly reduced expression in LSCC by microarray profiling (Affymetrix U133 Plus 2.0 array)...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28706011/increased-ifn-%C3%AE-t-cells-are-responsible-for-the-clinical-responses-of-low-dose-dna-demethylating-agent-decitabine-anti-tumor-therapy
#15
Xiang Li, Yan Zhang, Meixia Chen, Qian Mei, Yang Liu, Kai-Chao Feng, Hejin Jia, Liang Dong, Lu Shi, Lin Liu, Jing Nie, Weidong Han
Low-dose DNA demethylating agent decitabine therapy is effective in a subgroup of cancer patients. It remains largely elusive for the biomarker to predict therapeutic response and the underlying anti-tumor mechanisms, especially the impact on host anti-tumor immunity.<br />Experimental Design: The influence of low-dose decitabine on T cells was detected both in vitro and in vivo Moreover, a test cohort and a validation cohort of advanced solid tumor patients with low-dose decitabine-based treatment were involved...
July 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28698788/treatment-of-low-blast-count-aml-using-hypomethylating-agents
#16
REVIEW
Eleonora De Bellis, Luana Fianchi, Francesco Buccisano, Marianna Criscuolo, Luca Maurillo, Laura Cicconi, Mattia Brescini, Maria Ilaria Del Principe, Ambra Di Veroli, Adriano Venditti, Sergio Amadori, William Arcese, Francesco Lo-Coco, Maria Teresa Voso
In 2002, the WHO classification reduced the proportion of blasts in the bone marrow (BM) necessary for the diagnosis of acute myeloid leukemia (AML) from 30% to 20%, eliminating the RAEB-t subtype of myelodysplastic syndromes (MDS). However, this AML subtype, defined as low-blast count AML (LBC-AML, with 20-30% BM-blasts) is characterized by peculiar features, as increased frequency in elderly individuals and after cytotoxic treatment for a different primary disease (therapy-related), poor-risk cytogenetics, lower white blood cell counts, and less frequent mutations of NPM1 and FLT3 genes...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28677424/expansion-of-cancer-germline-antigen-specific-cytotoxic-t-lymphocytes-for-immunotherapy
#17
Deepa Kolaseri Krishnadas, Yali Wang, Kumaran Sundaram, Fanqi Bai, Kenneth G Lucas
The cancer germline antigens MAGE-A1, MAGE-A3, and NY-ESO-1 can be used to target relapsed or therapy-resistant malignant solid tumors, and previous studies have demonstrated that these antigens can be epigenetically upregulated on the surface of tumor cells following exposure to low-dose demethylating chemotherapy agents, such as decitabine. The extent to which cancer germline antigen cytotoxic T lymphocytes can be reliably expanded from healthy donors has not been well characterized, specifically in terms of whether these T cells consistently kill antigen-bearing targets or simply produce interferon-γ in the presence of the antigen...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28668968/cigarette-smoke-extract-changes-expression-of-endothelial-nitric-oxide-synthase-enos-and-p16-ink4a-and-is-related-to-endothelial-progenitor-cell-dysfunction
#18
Zhihui He, Yan Chen, Can Hou, Wenfang He, Ping Chen
BACKGROUND Endothelial dysfunction is an important pathophysiologic feature in many smoke-related diseases. Endothelial progenitor cells (EPCs) are the precursors of endothelial cells and play a fundamental role in the maintenance of endothelial integrity and function. Endothelial nitric oxide synthase (eNOS) is the dominant NOS isoform in the vasculature and plays a central role in the maintenance of endothelial homeostasis. p16(INK4a) is a cyclin-dependent kinase inhibitor and could be regarded as a major dominant senescence gene...
July 2, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28655330/nice-seq-high-resolution-open-chromatin-profiling
#19
V K Chaithanya Ponnaluri, Guoqiang Zhang, Pierre-Olivier Estève, George Spracklin, Stephanie Sian, Shuang-Yong Xu, Touati Benoukraf, Sriharsa Pradhan
Open chromatin profiling integrates information across diverse regulatory elements to reveal the transcriptionally active genome. Tn5 transposase and DNase I sequencing-based methods prefer native or high cell numbers. Here, we describe NicE-seq (nicking enzyme assisted sequencing) for high-resolution open chromatin profiling on both native and formaldehyde-fixed cells. NicE-seq captures and reveals open chromatin sites (OCSs) and transcription factor occupancy at single nucleotide resolution, coincident with DNase hypersensitive and ATAC-seq sites at a low sequencing burden...
June 28, 2017: Genome Biology
https://www.readbyqxmd.com/read/28644756/immunological-effects-of-hypomethylating-agents
#20
Katherine E Lindblad, Meghali Goswami, Christopher S Hourigan, Karolyn A Oetjen
Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets...
July 3, 2017: Expert Review of Hematology
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