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https://www.readbyqxmd.com/read/28718760/cd25-expression-and-outcomes-in-older-patients-with-acute-myelogenous-leukemia-treated-with-plerixafor-and-decitabine
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
June 23, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28621841/hypomethylating-agent-therapy-use-and-survival-in-older-patients-with-chronic-myelomonocytic-leukemia-in-the-united-states-a-large-population-based-study
#9
Amer M Zeidan, Xin Hu, Jessica B Long, Rong Wang, Xiaomei Ma, Nikolai A Podoltsev, Scott F Huntington, Steven D Gore, Amy J Davidoff
BACKGROUND: Despite the approval of azacitidine in 2004 and the approval of decitabine in 2006 in the United States for chronic myelomonocytic leukemia (CMML), the overall survival (OS) benefit with hypomethylating agent (HMA) therapy is unclear. METHODS: Older adults (age ≥ 66 years) who had been diagnosed with CMML from 2001 to 2011 were selected from the Surveillance, Epidemiology, and End Results-Medicare database, and propensity score matching was used to match patients who had been diagnosed after HMA approval (2007-2011) and had received HMA treatment with patients diagnosed before HMA approval (2001-2003)...
June 16, 2017: Cancer
https://www.readbyqxmd.com/read/28618329/therapy-of-older-persons-with-acute-myeloid-leukaemia
#10
REVIEW
Utz Krug, Robert Peter Gale, Wolfgang E Berdel, Carsten Müller-Tidow, Matthias Stelljes, Klaus Metzeler, M Cristina Sauerland, Wolfgang Hiddemann, Thomas Büchner
Most persons age≥60 y with acute myeloid leukaemia (AML) die from their disease. When interpreting clinical trials data from these persons one must be aware of substantial selection biases. Randomized trials of post-remission treatments can be performed upfront or after achieving defined landmarks. Both strategies have important limitations. Selection of the appropriate treatment is critical. Age, performance score, co-morbidities and frailty provide useful data to treatment selection. If an intensive remission induction therapy is appropriate, therapy with cytarabine and an anthracycline is the most common regimen...
June 1, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28607470/a-phase-ii-multicentre-trial-of-decitabine-in-higher-risk-chronic-myelomonocytic-leukemia
#11
V Santini, B Allione, G Zini, D Gioia, M Lunghi, A Poloni, D Cilloni, A Sanna, E Masiera, M Ceccarelli, O Abdel-Wahab, A Terenzi, E Angelucci, C Finelli, F Onida, A M Pelizzari, D Ferrero, G Saglio, M Figueroa, A Levis
Chronic myelomonocytic leukemia (CMML) is a complex clonal hematological disorder classified among myelodysplastic/myeloproliferative neoplasms (MDS/MPNs). Prognosis is poor and there is a lack of effective treatments. The hypomethylating agent decitabine has shown activity against MDS and elderly acute myeloid leukemia, but there is little data focusing specifically on its efficacy in CMML. In this prospective, phase 2 Italian study, CMML patients received i.v. decitabine 20 mg/m(2)/day on Days 1 to 5 of a 28-day treatment cycle...
June 13, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28599286/decitabine-inhibits-t-cell-proliferation-via-a-novel-tet2-dependent-mechanism-and-exerts-potent-protective-effect-in-mouse-auto-and-allo-immunity-models
#12
Xue Wang, Jun Wang, Yong Yu, Tonghui Ma, Ping Chen, Bing Zhou, Ran Tao
Multiple sclerosis (MS) is an autoimmune disease characterized by the dysregulated immune response including innate and adaptive immune responses. Increasing evidence has proven the importance of epigenetic modification in the progression of MS. Recent studies revealed that low-dose decitabine (Dec, 5-Aza-2'-deoxycytidine), which incorporates into replicating DNA and inhibits DNA methylation, could prevent experimental autoimmune encephalomyelitis (EAE) development by increasing the number of regulatory T cells (Tregs)...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28598109/-the-study-of-decitabine-effect-on-the-endometrial-carcinoma-xenografted-in-nude-mice
#13
Ran-Hong Li, Xue-Ping Wang, Hui Liu
OBJECTIVES: To explore the effect of the demethylation drug 5-Aza-CdR on endometrial carcinoma xenografted in nude mice. METHODS: Randomly assigned the mice into decitabine (AZA),cisplatin (DDP),medroxyprogesterone acetate (MPA),AZA+DDP,AZA+MPA,DDP+MPA and model groups (three in each group) after building the models of xenografted tumor by transplanting the HEC-1B cells on nude mice,and dealt them respectively with corresponding drugs (1 μg/g,single or combination) in the experiment groups and normal saline in model group (injected per 3 d,8 injections in total)...
November 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28589904/decitabine-vorinostat-combination-treatment-in-acute-myeloid-leukemia-activates-pathways-with-potential-for-novel-triple-therapy
#14
Christine S Young, Kathryn M Clarke, Laura M Kettyle, Alexander Thompson, Ken I Mills
Despite advancements in cancer therapeutics, acute myeloid leukemia patients over 60 years old have a 5-year survival rate of less than 8%. In an attempt to improve this, epigenetic modifying agents have been combined as therapies in clinical studies. In particular combinations with Decitabine and Vorinostat have had varying degrees of efficacy. This study therefore aimed to understand the underlying molecular mechanisms of these agents to identify potential rational epi-sensitized combinations.Combined Decitabine-Vorinostat treatment synergistically decreased cell proliferation, induced apoptosis, enhanced acetylation of histones and further decreased DNMT1 protein with HL-60 cells showing a greater sensitivity to the combined treatment than OCI-AML3...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28562519/epigenetic-combination-therapy-for-children-with-secondary-myelodysplastic-syndrome-mds-acute-myeloid-leukemia-aml-and-concurrent-solid-tumor-relapse
#15
Chana L Glasser, Alice Lee, Don Eslin, Lianna Marks, Shakeel Modak, Julia L Glade Bender
Secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) is a rare but devastating complication of solid tumor treatment involving high-dose topoisomerase II inhibitor and alkylator chemotherapy. For relapsed or elderly MDS and AML patients ineligible for hematopoietic stem cell transplantation, epigenetic therapies, including DNA methyltransferase inhibitors and histone deacetylase inhibitors, have been utilized as palliative therapy, offering a well-tolerated approach to disease stabilization, prolonged survival, and quality of life...
May 29, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28555084/mitoxantrone-etoposide-and-cytarabine-mec-following-epigenetic-priming-with-decitabine-in-adults-with-relapsed-refractory-acute-myeloid-leukemia-or-other-high-grade-myeloid-neoplasms-a-phase-1-2-study
#16
A B Halpern, M Othus, E M Huebner, S A Buckley, E L Pogosova-Agadjanyan, K F Orlowski, B L Scott, P S Becker, P C Hendrie, T L Chen, M-Em Percival, E H Estey, D L Stirewalt, R B Walter
DNA methyltransferase inhibitors sensitize leukemia cells to chemotherapeutics. We therefore conducted a phase 1/2 study of mitoxantrone, etoposide, and cytarabine following 'priming' with 5-10 days of decitabine (dec/MEC) in 52 adults (median age 55 [range: 19-72] years) with relapsed/refractory acute myeloid leukemia (AML) or other high-grade myeloid neoplasms. During dose escalation in cohorts of 6-12 patients, all dose levels were well-tolerated. As response rates appeared similar with 7 and 10-days of decitabine, a 7-day course was defined as the recommended phase 2 dose (RP2D)...
May 30, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28498449/bioinformatic-analysis-of-the-effects-and-mechanisms-of-decitabine-and-cytarabine-on-acute-myeloid-leukemia
#17
Shiyong Zhou, Pengfei Liu, Huilai Zhang
Acute myeloid leukemia (AML) is a frequently occurring malignant disease of the blood and may result from a variety of genetic disorders. The present study aimed to identify the underlying mechanisms associated with the therapeutic effects of decitabine and cytarabine on AML, using microarray analysis. The microarray datasets GSE40442 and GSE40870 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine via the Linear Models for Microarray Data package, following data pre‑processing...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28494506/minimal-residual-disease-eradication-with-epigenetic-therapy-in-core-binding-factor-acute-myeloid-leukemia
#18
Brittany Knick Ragon, Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Tapan Kadia, Betul Oran, Maro Ohanian, Alessandra Ferrajoli, Naveen Pemmaraju, Hagop M Kantarjian, Gautam Borthakur
Recurrent translocations, t(8;21) or inv(16), in core binding factor acute myeloid leukemia (CBF-AML) are amenable to monitoring for minimal residual disease (MRD) with reverse transcriptase polymerase chain reaction (RTPCR). Despite a favorable prognosis, disease relapse remains the single cause of treatment failure in CBF-AML. Fusion products of these translocations recruit epigenetic silencing complexes resulting in hematopoietic maturation arrest. We hypothesized that maintenance therapy with hypomethylating agents (HMA), including decitabine (DAC) and azacitidine (AZA) after induction/consolidation, can be used for MRD elimination to ultimately prolong relapse free survival...
May 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28489568/efficacy-and-safety-of-decitabine-in-treatment-of-elderly-patients-with-acute-myeloid-leukemia-a-systematic-review-and-meta-analysis
#19
Pin-Fang He, Jing-Dong Zhou, Dong-Ming Yao, Ji-Chun Ma, Xiang-Mei Wen, Zhi-Hui Zhang, Xin-Yue Lian, Zi-Jun Xu, Jun Qian, Jiang Lin
Elderly patients with acute myeloid leukemia (AML) have limited treatment options concerned about their overall fitness and potential treatment related mortality. Although a number of clinical trials demonstrated benefits of decitabine treatment in elderly AML patients, the results remains controversial. A meta-analysis was performed to evaluate efficacy and safety of decitabine in treatment of elderly AML patients. Eligible studies were identified from PubMed, Web of Science, Embase and Cochrane Library. Nine published studies were included in the meta-analysis, enrolling 718 elderly AML patients...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488914/decitabine-treatment-of-multiple-extramedullary-acute-myeloid-leukemia-involvements-after-essential-thrombocytemia-transformation
#20
Pasquale Niscola, Elisabetta Abruzzese, Malgorzata Monika Trawinska, Massimiliano Palombi, Andrea Tendas, Marco Giovannini, Laura Scaramucci, Luca Cupelli, Stefano Fratoni, Nélida Inés Noguera, Gianfranco Catalano, Paolo de Fabritiis
No abstract text is available yet for this article.
May 10, 2017: Acta Oncologica
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