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Azacitidine

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https://www.readbyqxmd.com/read/29046731/promoter-methylation-inhibits-expression-of-tumor-suppressor-kibra-in-human-clear-cell-renal-cell-carcinoma
#1
Katrin Schelleckes, Boris Schmitz, Giuliano Ciarimboli, Malte Lenders, Hermann J Pavenstädt, Edwin Herrmann, Stefan-Martin Brand, Eva Brand
BACKGROUND: KIBRA has been suggested as a key regulator of the Hippo signaling pathway, regulating organ size, cell contact inhibition, tissue regeneration as well as tumorigenesis and cystogenesis. We recently reported that human KIBRA expression depends on a complex alternative CpG-rich promoter system. Our current study aimed at the identification of epigenetic mechanisms associated with alterations in KIBRA expression regulation. RESULTS: We identified two separated methylation-sensitive CpG islands located to independent KIBRA promoter regions...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29044459/azacitidine-induced-sweet-syndrome-two-unusual-clinical-presentations
#2
Shevya M Tiwari, Tony Caccetta, Sujith P Kumarasinghe, Nathan Harvey
No abstract text is available yet for this article.
October 18, 2017: Australasian Journal of Dermatology
https://www.readbyqxmd.com/read/29033451/dasatinib-and-azacitidine-followed-by-haploidentical-stem-cell-transplant-for-chronic-myeloid-leukemia-with-evolving-myelodysplasia-a-case-report-and-review-of-treatment-options
#3
Fabian Lang, Lydia Wunderle, Heike Pfeifer, Susanne Schnittger, Gesine Bug, Oliver G Ottmann
BACKGROUND CML presenting with a variant Philadelphia translocation, atypical BCR-ABL transcript, additional chromosomal aberrations, and evolving MDS is uncommon and therapeutically challenging. The prognostic significance of these genetic findings is uncertain, even as singular aberrations, with nearly no data on management and outcome when they coexist. MDS evolving during the course of CML may be either treatment-associated or an independently coexisting disease, and is generally considered to have an inferior prognosis...
October 16, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/29018892/novel-treatment-opportunities-for-sulfur-mustard-related-cancers-genetic-and-epigenetic-perspectives
#4
REVIEW
Soheila Rahmani, Mohammad Abdollahi
Sulfur mustard (SM), also known as mustard gas, is a chemical weapon which by now has been used in many wars. The most concerning SM toxic effect is probable carcinogenicity. In this study, the genetic and epigenetic mechanisms of SM carcinogenicity, by focusing on treatment of SM-associated malignancies, particularly gene therapeutics, cancer vaccines, and epigenetic medications, have been criticized. The required data were collected through an organized search on valid scientific databases. For SM carcinogenicity due to acute or chronic exposure, the entire original and review articles were evaluated...
October 10, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28985529/multiplex-crispr-cas9-based-genome-editing-in-human-hematopoietic-stem-cells-models-clonal-hematopoiesis-and-myeloid-neoplasia
#5
Zuzana Tothova, John M Krill-Burger, Katerina D Popova, Catherine C Landers, Quinlan L Sievers, David Yudovich, Roger Belizaire, Jon C Aster, Elizabeth A Morgan, Aviad Tsherniak, Benjamin L Ebert
Hematologic malignancies are driven by combinations of genetic lesions that have been difficult to model in human cells. We used CRISPR/Cas9 genome engineering of primary adult and umbilical cord blood CD34(+) human hematopoietic stem and progenitor cells (HSPCs), the cells of origin for myeloid pre-malignant and malignant diseases, followed by transplantation into immunodeficient mice to generate genetic models of clonal hematopoiesis and neoplasia. Human hematopoietic cells bearing mutations in combinations of genes, including cohesin complex genes, observed in myeloid malignancies generated immunophenotypically defined neoplastic clones capable of long-term, multi-lineage reconstitution and serial transplantation...
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28976600/midostaurin-a-new-oral-agent-targeting-flt3-mutant-acute-myeloid-leukemia
#6
Lindsay C Stansfield, Daniel A Pollyea
Acute myeloid leukemia (AML), a clonal hematologic malignancy that results in bone marrow failure, is the most common acute leukemia in adults (median age of diagnosis 67 years), and treatment options, especially in the elderly population, are limited. Induction chemotherapy with 7+3, the combination of continuous-infusion cytarabine and intermittent dosing of an anthracycline administered over 7 and 3 days, respectively, has remained the standard of care since its introduction in 1973 in the United States...
October 4, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28962071/thrombopoietin-mimetics-for-patients-with-myelodysplastic-syndromes
#7
REVIEW
Helga Dodillet, Karl-Anton Kreuzer, Ina Monsef, Nicole Skoetz
BACKGROUND: Myelodysplastic syndrome (MDS) is one of the most frequent haematologic malignancies of the elderly population and characterised by progenitor cell dysplasia with ineffective haematopoiesis and a high rate of transformation to acute myeloid leukaemia (AML). Thrombocytopenia represents a common problem for patients with MDS. ranging from mild to serious bleeding events and death. To manage thrombocytopenia, the current standard treatment includes platelet transfusion, unfortunately leading to a range of side effects...
September 30, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28958288/optimizing-the-use-of-hypomethylating-agents-in-myelodysplastic-syndromes-selecting-the-candidate-predicting-the-response-and-enhancing-the-activity
#8
REVIEW
Yazan Madanat, Mikkael A Sekeres
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders that have a substantial impact on patients' quality of life, in addition to causing significant morbidity and mortality. The hypomethylating agents (HMAs) azacitidine and decitabine are approved for use in the United States and in Europe for the treatment of MDS or acute myeloid leukemia (AML) and, in the case of azacitidine, prolong survival in higher-risk patients. Neither is curative, though, and given the lack of clear treatment guidelines after HMA treatment failure, it is imperative to optimize patient selection and identify the right timing of HMA treatment initiation and response evaluation to maximize patient benefit...
July 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28949050/a-phase-1-2-study-of-the-wt1-peptide-cancer-vaccine-wt4869-in-patients-with-myelodysplastic-syndrome
#9
Yasunori Ueda, Michinori Ogura, Shigesaburo Miyakoshi, Takahiro Suzuki, Yuji Heike, Shuzo Tagashira, Satoru Tsuchiya, Kazuma Ohyashiki, Yasushi Miyazaki
WT4869 is a synthetic peptide vaccine derived from the Wilms' tumor gene 1 (WT1) protein. This phase 1/2 open-label study evaluated the safety and efficacy of WT4869, and biomarkers for response, in patients with myelodysplastic syndrome. WT4869 (5-1200 μg/dose) was administered intradermally every 2 weeks, according to a 3+3 dose-escalation method in higher-risk (International Prognostic Scoring System score ≥1.5) or lower-risk (score <1.5) red blood cell transfusion-dependent patients with myelodysplastic syndrome...
September 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28947565/ny-eso-1-vaccination-in-combination-with-decitabine-induces-antigen-specific-t-lymphocyte-responses-in-patients-with-myelodysplastic-syndrome
#10
Elizabeth A Griffiths, Pragya Srivastava, Junko Matsuzaki, Zachary Brumberger, Eunice S Wang, Justin Kocent, Austin Miller, Gregory W Roloff, Hong Yuen Wong, Benjamin E Paluch, Linda G Lutgen-Dunckley, Brandon L Martens, Kunle Odunsi, Adam R Karpf, Christopher S Hourigan, Michael J Nemeth
PURPOSE: Treatment options are limited for patients with high-risk myelodysplastic syndrome (MDS). The azanucleosides, azacitidine and decitabine, are front-line therapy for MDS that induce promoter demethylation and gene expression of the highly immunogenic tumor antigen NY-ESO-1. We demonstrated that AML patients receiving decitabine exhibit induction of NY-ESO-1 expression in circulating blasts. We hypothesized that vaccinating against NY-ESO-1 in MDS patients receiving decitabine would capitalize upon induced NY-ESO-1 expression in malignant myeloid cells to provoke an NY-ESO-1-specific-MDS directed cytotoxic T-cell immune response...
September 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28905323/phase-i-study-of-panobinostat-and-5-azacitidine-in-japanese-patients-with-myelodysplastic-syndrome-or-chronic-myelomonocytic-leukemia
#11
Yukio Kobayashi, Wataru Munakata, Michinori Ogura, Toshiki Uchida, Masafumi Taniwaki, Tsutomu Kobayashi, Fumika Shimada, Masataka Yonemura, Fumiko Matsuoka, Takeshi Tajima, Kimikazu Yakushijin, Hironobu Minami
The current therapy for high-risk myelodysplastic syndrome (MDS) involves repeated cycles of the DNA demethylating agent 5-azacitidine (5-Aza), but combination treatments have been proposed to improve patient outcomes. We performed a phase Ib study to investigate the safety and tolerability of 5-Aza (75 mg/m(2)) combined with the histone deacetylase inhibitor panobinostat (PAN) in adult Japanese patients with MDS or chronic myelomonocytic leukemia (CMML). Eleven patients were enrolled; five received 20 mg PAN + 5-Aza and six received 30 mg PAN + 5-Aza...
September 13, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28881739/a-phase-i-trial-of-azacitidine-and-nanoparticle-albumin-bound-paclitaxel-in-patients-with-advanced-or-metastatic-solid-tumors
#12
Adam L Cohen, Abhijit Ray, Matthew Van Brocklin, David M Burnett, Randy C Bowen, Donna L Dyess, Thomas W Butler, Theresa Dumlao, Hung T Khong
BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC), an albumin-binding protein, is downregulated by hypermethylation in many cancers. Hypomethylating agents such as azacitidine can upregulate SPARC in tumors, which may enhance the accumulation of albumin-bound drugs at tumor site. The objectives of this phase I trial was to determine the safety and maximum tolerated dose and to assess any clinical activity of the combination of azacytidine and weekly nanoparticle-albumin-bound (nab®) paclitaxel...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881728/the-mtor-inhibitor-everolimus-in-combination-with-azacitidine-in-patients-with-relapsed-refractory-acute-myeloid-leukemia-a-phase-ib-ii-study
#13
Peter Tan, Ing Soo Tiong, Shaun Fleming, Giovanna Pomilio, Nik Cummings, Mark Droogleever, Julie McManus, Anthony Schwarer, John Catalano, Sushrut Patil, Sharon Avery, Andrew Spencer, Andrew Wei
Therapeutic options are limited in relapsed/refractory acute myeloid leukemia (AML). We evaluated the maximum tolerated dose (MTD) and preliminary efficacy of mammalian target of rapamycin (mTOR) inhibitor, everolimus (days 5-21) in combination with azacitidine 75 mg/m(2) subcutaneously (days 1-5 and 8-9 every 28 days) in 40 patients with relapsed (n = 27), primary refractory (n = 11) or elderly patients unfit for intensive chemotherapy (n = 2). MTD was not reached following everolimus dose escalation (2.5, 5 or 10 mg; n = 19) to the 10 mg dose level which was expanded (n = 21)...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28844816/guadecitabine-sgi-110-in-treatment-naive-patients-with-acute-myeloid-leukaemia-phase-2-results-from-a-multicentre-randomised-phase-1-2-trial
#14
RANDOMIZED CONTROLLED TRIAL
Hagop M Kantarjian, Gail J Roboz, Patricia L Kropf, Karen W L Yee, Casey L O'Connell, Raoul Tibes, Katherine J Walsh, Nikolai A Podoltsev, Elizabeth A Griffiths, Elias Jabbour, Guillermo Garcia-Manero, David Rizzieri, Wendy Stock, Michael R Savona, Todd L Rosenblat, Jesus G Berdeja, Farhad Ravandi, Edwin P Rock, Yong Hao, Mohammad Azab, Jean-Pierre J Issa
BACKGROUND: The hypomethylating drugs azacitidine and decitabine have shown efficacy in myelodysplastic syndromes and acute myeloid leukaemia, but complete tumour responses are infrequent and of short duration, possibly because of the short half-lives and suboptimal bone marrow exposure of the drugs. Guadecitabine, a next-generation hypomethylating drug, has a longer half-life and exposure than its active metabolite decitabine. A phase 1 study established 60 mg/m(2) guadecitabine for 5 days as an effective treatment schedule...
October 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28841236/phase-1-dose-escalation-multicenter-trial-of-pracinostat-alone-and-in-combination-with-azacitidine-in-patients-with-advanced-hematologic-malignancies
#15
Yasmin M Abaza, Tapan M Kadia, Elias J Jabbour, Marina Y Konopleva, Gautam Borthakur, Alessandra Ferrajoli, Zeev Estrov, William G Wierda, Ana Alfonso, Toh Han Chong, Charles Chuah, Liang-Piu Koh, Boon-Cher Goh, Julie E Chang, Daniel E Durkes, Maria Cielo Foudray, Hagop M Kantarjian, Xiao Qin Dong, Guillermo Garcia-Manero
BACKGROUND: Pracinostat is a potent histone deacetylase inhibitor with antitumor activity in both solid tumor and acute myeloid leukemia (AML) cell lines. Pracinostat is reported to have modest clinical activity in patients with advanced solid tumors. Given the higher preclinical sensitivity of hematologic malignancies to pracinostat, the authors conducted a phase 1 study to assess the safety, maximum tolerated dose, recommended phase 2 dose, efficacy, pharmacokinetics, and pharmacodynamics of pracinostat in patients with advanced hematological malignancies...
August 25, 2017: Cancer
https://www.readbyqxmd.com/read/28839454/donor-cell-origin-high-risk-myelodysplastic-syndrome-synchronous-with-an-intracranial-meningioma-like-tumor-8-years-after-allogeneic-hematopoietic-stem-cell-transplantation-for-chronic-lymphocytic-leukemia
#16
G Brás, C Pinho-Vaz, A Campos
Secondary neoplasias are well known consequences of radiotherapy or chemotherapy for a primary cancer. In this report, we describe two rare secondary neoplasias occurring in the same patient: a meningioma-like intracranial tumor and high-risk myelodysplastic syndrome (MDS) of donor-cells origin, both diagnosed simultaneously, 8 years after an allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic lymphocytic leukemia (CLL). Due to an engraftment failure during the first allo-HSCT of a matched related donor for CLL treatment, the salvage treatment was a second allo-HSCT...
2017: Case Reports in Medicine
https://www.readbyqxmd.com/read/28838276/real-life-experience-with-frontline-azacitidine-in-a-large-series-of-older-adults-with-acute-myeloid-leukemia-stratified-by-mrc-lrf-score-results-from-the-expanded-international-e-alma-series-e-alma
#17
José Falantes, Lisa Pleyer, Sylvain Thépot, António M Almeida, Luca Maurillo, Violeta Martínez-Robles, Reinhard Stauder, Raphael Itzykson, Ricardo Pinto, Adriano Venditti, Joan Bargay, Sonja Burgstaller, María Pilar Martínez, Valerie Seegers, Emilia Cortesão, María Ángeles Foncillas, Claude Gardin, Pau Montesinos, Pellegrino Musto, Pierre Fenaux, Richard Greil, Miguel Angel Sanz, Fernando Ramos
Azacitidine (AZA) prolonged overall survival (OS) in the AZA-AML-001 trial. However, few subjects were randomized to AZA or intensive chemotherapy (IC). The Medical Research Council (MRC) and the Leukemia Research Foundation (LRF) developed a score for older AML patients receiving IC or non-intensive regimens, whereas the E-ALMA study validated a score for survival and response in elderly patients receiving AZA in daily practice. Both identified three groups with different risk estimates. This analysis evaluates the efficacy of frontline AZA in older AML patients (N = 710) unfit for IC from different national registries (E-ALMA + series) stratified by the MRC/LRF risk score...
August 24, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28836866/prospective-randomized-trial-of-5-days-azacitidine-versus-supportive-care-in-patients-with-lower-risk-myelodysplastic-syndromes-without-5q-deletion-and-transfusion-dependent-anemia
#18
Joaquin Sanchez-Garcia, Jose Falantes, Angeles Medina Perez, Francisca Hernandez-Mohedo, Lourdes Hermosin, Angeles Torres-Sabariego, Alicia Bailen, Jesus M Hernandez-Sanchez, María Solé Rodriguez, Francisco Javier Casaño, Cristina Calderon, Maria Labrador, Maria Vahí, Josefina Serrano, Eva Lumbreras, Jesus Maria Hernández-Rivas
In this prospective trial, the efficacy of azacitidine in lower-risk myelodysplastic syndromes (LR-SMD) lacking del(5q) was compared to best supportive care (BSC) at 1:1. The primary endpoint was the achievement of erythroid hematologic improvement (HI-E) after nine cycles. Thirty-six patients received at least ≥1 cycle. HI-E was confirmed 44.4% randomized to Aza and in 5.5% of patients receiving BSC (p < .01). After entry in Aza extension period, transfusion independence was achieved in all Aza responders with a median duration of 50 weeks (range: 17-231)...
August 24, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28828639/therapeutic-decision-making-in-elderly-patients-with-acute-myeloid-leukemia-conventional-intensive-chemotherapy-versus-hypomethylating-agent-therapy
#19
Sang-Bo Oh, Sung-Woo Park, Joo-Seop Chung, Won-Sik Lee, Ho-Seop Lee, Su-Hee Cho, Yoon-Suk Choi, Sung-Nam Lim, Ho-Jin Shin
Standards of care for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy remain undefined. We aimed to compare outcomes of hypomethylating agent (HMA) therapy and intensive chemotherapy (IC) in elderly AML patients and identify the subgroup of patients who are eligible for HMA therapy. We reviewed data on the outcomes of 86 AML patients aged ≥ 65 years, who had undergone treatment between 2010 and 2015. These treatments included IC (25 patients, 29.1%) or therapy using HMA including azacitidine or decitabine (61 patients, 70...
August 21, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28818807/early-treatment-initiation-in-lower-risk-myelodysplastic-syndromes-produces-an-earlier-and-higher-rate-of-transfusion-independence
#20
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...
September 2017: Leukemia Research
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