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Hydroxyurea

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https://www.readbyqxmd.com/read/28916784/p-body-proteins-regulate-transcriptional-rewiring-to-promote-dna-replication-stress-resistance
#1
Raphael Loll-Krippleber, Grant W Brown
mRNA-processing (P-) bodies are cytoplasmic granules that form in eukaryotic cells in response to numerous stresses to serve as sites of degradation and storage of mRNAs. Functional P-bodies are critical for the DNA replication stress response in yeast, yet the repertoire of P-body targets and the mechanisms by which P-bodies promote replication stress resistance are unknown. In this study we identify the complete complement of mRNA targets of P-bodies during replication stress induced by hydroxyurea treatment...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28915422/determination-of-hydroxyurea-in-human-plasma-by-hplc-uv-using-derivatization-with-xanthydrol
#2
Tiphaine Legrand, Marie-Georgine Rakotoson, Frédéric Galactéros, Pablo Bartolucci, Anne Hulin
A simple and rapid high performance liquid chromatography (HPLC) method using ultraviolet (UV) detection was developed to determine hydroxyurea (HU) concentration in plasma sample after derivatization with xanthydrol. Two hundred microliters samples were spiked with methylurea (MeU) as internal standard and proteins were precipitated by adding methanol. Derivatization of HU and MeU was immediately performed by adding 0.02M xanthydrol and 1.5M HCl in order to obtain xanthyl-derivatives of HU and MeU that can be further separated using HPLC and quantified using UV detection at 240nm...
September 7, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28913922/a-clinically-meaningful-fetal-hemoglobin-threshold-for-children-with-sickle-cell-anemia-during-hydroxyurea-therapy
#3
Jeremie H Estepp, Matthew P Smeltzer, Guolian Kang, Chen Li, Winfred C Wang, Christina Abrams, Banu Aygun, Russell E Ware, Kerri Nottage, Jane S Hankins
Hydroxyurea has proven clinical benefits and is recommended to be offered to all children with sickle cell anemia (SCA), but the optimal dosing regimen remains controversial. Induction of red blood cell fetal hemoglobin (HbF) by hydroxyurea appears to be dose-dependent. However, it is unknown whether maximizing HbF% improves clinical outcomes. HUSTLE (NCT00305175) is a prospective observational study with a primary goal of describing the long-term clinical effects of hydroxyurea escalated to maximal tolerated dose (MTD) in children with SCA...
September 14, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28893786/novel-cell-killing-mechanisms-of-hydroxyurea-and-the-implication-towards-combination-therapy-for-the-treatment-of-fungal-infections
#4
Amanpreet Singh, Ameeta Agarwal, Yong-Jie Xu
We have previously reported that an erg11 mutation affecting ergosterol synthesis and a hem13 mutation in the heme synthesis pathway significantly sensitize the fission yeast Schizosaccahromyces pombe to hydroxyurea (HU) (1, 2). Here we show that treatment with the inhibitors of Erg11 and the heme biosynthesis phenocopies the two mutations in sensitizing wild type cells to HU. Importantly, HU synergistically interacts with the heme biosynthesis inhibitor sampangine and several Erg11 inhibitors, the antifungal azoles, in causing cell lethality...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28893518/curative-approaches-for-sickle-cell-disease-a-review-of-allogeneic-and-autologous-strategies
#5
Daniel E Bauer, Christian Brendel, Courtney D Fitzhugh
Despite sickle cell disease (SCD) first being reported >100years ago and molecularly characterized >50years ago, patients continue to experience severe morbidity and early mortality. Although there have been substantial clinical advances with immunizations, penicillin prophylaxis, hydroxyurea treatment, and transfusion therapy, the only cure that can be offered is hematopoietic stem cell transplantation (HSCT). In this work, we summarize the various allogeneic curative approaches reported to date and discuss open and upcoming clinical research protocols...
September 1, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28891355/fertility-challenges-for-women-with-sickle-cell-disease
#6
Djamila L Ghafuri, Sarah-Jo Stimpson, Melissa E Day, Andra James, Michael R DeBaun, Deva Sharma
Sickle cell disease (SCD) represents one of the most common monogenic blood disorders worldwide, with an incidence of over 300,000 newborns affected per year. Reproductive challenges for men and women with SCD have been previously reviewed; however, evidence-based strategies to prevent and manage infertility and increase fecundity are lacking in women with SCD, which is one of the most important factors for quality of life. Areas covered: This review article summarizes the known risk factors for infertility, low fecundity, and premature menopause related to SCD...
September 11, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28884840/hydroxycarbamide-in-children-with-sickle-cell-anemia-after-first-dose-vs-chronic-therapy-pharmacokinetics-and-predictive-models-for-drug-exposure
#7
Jeremie H Estepp, Paweł Wiczling, Joseph Moen, Guolian Kang, Joana Marie Mack, Robert Liem, Julie A Panepinto, Uttam Garg, Gregory Kearns, Kathleen A Neville
AIMS: The purpose of this work was to (1) compare pharmacokinetic (PK) parameters for hydroxycarbamide in children receiving their first dose (HCnew ) versus those receiving chronic therapy (HCchronic ), (2) assess the external validity of a published PK dosing strategy, and (3) explore the accuracy of dosing strategies based on a limited number of HC measurements. METHODS: Utilizing data from two prospective, multicenter trials of hydroxycarbamide (Pharmacokinetics of Liquid Hydroxyurea in Pediatric Patients with Sickle Cell Anemia; NCT01506544 and Single-Dose (SD) and Steady-State (SS) Pharmacokinetics of Hydroxyurea in Children and Adolescents with Sickle Cell Disease), plasma drug concentration versus time profiles were evaluated with a model independent approach in the HCnew and HCchronic groups...
September 8, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28883275/successful-management-of-intraperitoneal-bleeding-with-platelet-apheresis-and-von-willebrand-factor-supplementation-in-a-patient-with-essential-thrombocythemia-and-acquired-von-willebrand-syndrome
#8
Toshimitsu Ueki, Kanako Takeshige, Masahiko Sumi, Mayumi Ueno, Naoaki Ichikawa, Hikaru Kobayashi
A 36-year-old woman with essential thrombocythemia (ET) was admitted to our hospital for acute lower abdominal pain. Given no family history of bleeding disorder, she was diagnosed with acquired von Willebrand syndrome. Despite having a medical history of venous thrombosis, she had never been treated for ET because of her preferences. On admission, CT scan revealed massive hemorrhage in the ascending colon with the leakage of a contrast agent. Furthermore, a delayed enhancement of fluid collection in the Douglas fossa followingcontrast CT indicated bloody ascites...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28880374/skeletal-and-myocardial-microvascular-blood-flow-in-hydroxycarbamide-treated-patients-with-sickle-cell-disease
#9
Vandana Sachdev, Stanislav Sidenko, Melinda D Wu, Caterina P Minniti, Hwaida Hannoush, Cynthia L Brenneman, Myron A Waclawiw, Andrew E Arai, Alan N Schechter, Gregory J Kato, Jonathan R Lindner
In sickle cell disease (SCD), abnormal microvascular function combined with chronic anaemia predisposes patients to perfusion-demand mismatch. We hypothesized that skeletal muscle and myocardial perfusion, normalized to the degree of anaemia, is reduced at basal-state compared to controls, and that this defect is ameliorated by hydroxycarbamide (HC; also termed hydroxyurea) therapy. Twenty-one SCD patients, of whom 15 were treated with HC, and 27 controls underwent contrast-enhanced ultrasound (CEU) perfusion imaging of the forearm as well as the myocardium...
September 7, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28877686/disease-stabilizing-treatment-based-on-all-trans-retinoic-acid-and-valproic-acid-in-acute-myeloid-leukemia-identification-of-responders-by-gene-expression-profiling-of-pretreatment-leukemic-cells
#10
Håkon Reikvam, Randi Hovland, Rakel Brendsdal Forthun, Sigrid Erdal, Bjørn Tore Gjertsen, Hanne Fredly, Øystein Bruserud
BACKGROUND: Acute myeloid leukemia (AML) is an aggressive malignancy only cured by intensive therapy. However, many elderly and unfit patients cannot receive such treatment due to an unacceptable risk of treatment-related morbidity and mortality. Disease-stabilizing therapy is then the only possible strategy, one alternative being treatment based on all-trans retinoic acid (ATRA) combined with the histone deacetylase inhibitor valproic acid and possibly low-toxicity conventional chemotherapy...
September 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28869184/the-treatment-landscape-of-myelofibrosis-before-and-after-ruxolitinib-approval
#11
Andrew T Kuykendall, Chetasi Talati, Najla Al Ali, Kendra Sweet, Eric Padron, David A Sallman, Jeffrey E Lancet, Alan F List, Kenneth S Zuckerman, Rami S Komrokji
INTRODUCTION/BACKGROUND: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm that presents with a heterogeneous clinical phenotype and prognosis. Before the US Food and Drug Administration approval of ruxolitinib, treatment options were varied and had limited effect. The increased use of ruxolitinib has drastically altered the MF treatment landscape. In this study, we aimed to clarify the clinical situations in which ruxolitinib is being used and analyze its effect on this landscape...
August 5, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28868627/hydroxyurea-prescription-availability-and-use-for-children-with-sickle-cell-disease-in-italy-results-of-a-national-multicenter-survey
#12
Raffaella Colombatti, Giovanni Palazzi, Nicoletta Masera, Lucia Dora Notarangelo, Elisa Bonetti, Piera Samperi, Angelica Barone, Silverio Perrotta, Elena Facchini, Maurizio Miano, Giovanni Carlo Del Vecchio, Maria Elena Guerzoni, Paola Corti, Federica Menzato, Simone Cesaro, Maddalena Casale, Paolo Rigano, Gian Luca Forni, Giovanna Russo, Laura Sainati
BACKGROUND: The number of patients with sickle cell disease (SCD) has increased in Italy in the past decade due to immigration. In spite of the established efficacy of hydroxyurea (HU) in childhood, population-based data regarding its prescription and effectiveness come mainly from studies performed in adults or outside Europe. POPULATION AND METHODS: The Hydroxyurea in SCD: A Large Nation-wide Cohort Study from Italy was a retrospective cohort study of adult and pediatric patients with SCD attending 32 centers...
September 4, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28868518/associations-of-%C3%AE-thalassemia-and-bcl11a-with-stroke-in-nigerian-united-states-and-united-kingdom-sickle-cell-anemia-cohorts
#13
Santosh L Saraf, Titilola S Akingbola, Binal N Shah, Chinedu A Ezekekwu, Omowunmi Sonubi, Xu Zhang, Lewis L Hsu, Mark T Gladwin, Roberto F Machado, Richard S Cooper, Victor R Gordeuk, Bamidele O Tayo
Alpha-thalassemia and the BCL11A rs1427407 T allele are commonly observed in sickle cell anemia (SCA) patients and are associated with reduced hemolysis and higher hemoglobin F levels, respectively. We investigated whether a high-risk genetic profile, defined as SCA patients who did not inherit either α-thalassemia or the BCL11A rs1427407 T allele, had stronger associations with clinical and laboratory variables than the individual genetic components in the University of Ibadan cohort (n=249). We then replicated our findings in SCA cohorts from the University of Illinois at Chicago (UIC)(n=260) and Walk-Treatment of Pulmonary Hypertension and Sickle cell disease with Sildenafil Therapy (Walk-PHaSST)(n=387)...
April 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/28863145/associations-between-endothelial-dysfunction-and-clinical-and-laboratory-parameters-in-children-and-adolescents-with-sickle-cell-anemia
#14
Rozana Santos Teixeira, Regina Terse-Ramos, Tatiane Anunciação Ferreira, Vinícius Ramos Machado, Marya Izadora Perdiz, Isa Menezes Lyra, Valma Lopes Nascimento, Ney Boa-Sorte, Bruno B Andrade, Ana Marice Ladeia
BACKGROUND: Hematological changes can drive damage of endothelial cells, which potentially lead to an early endothelial dysfunction in patients with sickle cell anemia (SCA). An association may exist between endothelial dysfunction and several clinical manifestations of SCA. The present study aims to evaluate the links between changes in endothelial function and clinical and laboratory parameters in children and adolescents with SCA. METHODS: This study included 40 children and adolescents with stable SCA as well as 25 healthy children; aged 6-18 years...
2017: PloS One
https://www.readbyqxmd.com/read/28854230/heterologous-expression-of-anti-apoptotic-human-14-3-3%C3%AE-%C3%AE-enhances-iron-mediated-programmed-cell-death-in-yeast
#15
Rawan Eid, David R Zhou, Nagla T T Arab, Eric Boucher, Paul G Young, Craig A Mandato, Michael T Greenwood
The induction of Programmed Cell Death (PCD) requires the activation of complex responses involving the interplay of a variety of different cellular proteins, pathways, and processes. Uncovering the mechanisms regulating PCD requires an understanding of the different processes that both positively and negatively regulate cell death. Here we have examined the response of normal as well as PCD resistant yeast cells to different PCD inducing stresses. As expected cells expressing the pro-survival human 14-3-3β/α sequence show increased resistance to numerous stresses including copper and rapamycin...
2017: PloS One
https://www.readbyqxmd.com/read/28852484/sickle-cell-disease-and-albuminuria-recent-advances-in-our-understanding-of-sickle-cell-nephropathy
#16
Vincent Audard, Pablo Bartolucci, Thomas Stehlé
Albuminuria is considered to be a relevant biomarker for the detection of early glomerular damage in patients with sickle cell disease (SCD). Improvements in our understanding of the pathophysiological processes and molecular mechanisms underlying albuminuria are required, because increasing numbers of patients with SCD are developing chronic kidney disease. The early recognition of sickle cell nephropathy (SCN) and studies of the natural course of this emerging renal disease are therefore crucial, together with identification of the associated clinical and biological risk factors, to make it possible to initiate kidney-protective therapy at early stages of renal impairment...
August 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28851297/an-a%C3%AE-globin-g-a-gene-polymorphism-associated-with-%C3%AE-0-39-thalassemia-globin-gene-and-high-fetal-hemoglobin-production
#17
Giulia Breveglieri, Nicoletta Bianchi, Lucia Carmela Cosenza, Maria Rita Gamberini, Francesco Chiavilli, Cristina Zuccato, Giulia Montagner, Monica Borgatti, Ilaria Lampronti, Alessia Finotti, Roberto Gambari
BACKGROUND: Increase of the expression of γ-globin gene and high production of fetal hemoglobin (HbF) in β-thalassemia patients is widely accepted as associated with a milder or even asymptomatic disease. The search for HbF-associated polymorphisms (such as the XmnI, BCL11A and MYB polymorphisms) has recently gained great attention, in order to stratify β-thalassemia patients with respect to expectancy of the first transfusion, need for annual intake of blood, response to HbF inducers (the most studied of which is hydroxyurea)...
August 29, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28845406/in-vitro-hb-production-in-b-thalassemia-patients-is-not-a-predictor-of-clinical-responsiveness-to-hydroxyurea
#18
Mohammad Reza Mahdavi, Farzin Pourfarzad, Mehrnoush Kosaryan, Mohammad Taghi Akbari
BACKGROUND: The hematologic response to hydroxyurea (HU) is varied among β-thalassemia (BT) patients. The BCL11A and SOX6 genes are involved in response to HU. This study aimed to investigate the in-vitro responsiveness of HU among BT major patients homozygote for IVSII-1G>A mutation and XmnI single nucleotide polymorphism (SNP) in order to find whether the in-vitro Hb concentration is a predictor of clinical (HU) responsiveness. METHODS: In this case-control study, twenty BT patients homozygote for IVSII-1G>A mutation and XmnI SNP from Thalassemia Research Center, Sari, Iran in 2015 were selected and categorized into two groups of 10 Responder (R) and 10 Non-Responder (NR) according to their clinical HU response...
July 2017: Iranian Journal of Public Health
https://www.readbyqxmd.com/read/28837865/valproic-acid-sensitizes-breast-cancer-cells-to-hydroxyurea-through-inhibiting-rpa2-hyperphosphorylation-mediated-dna-repair-pathway
#19
Youjia Tian, Guochao Liu, Hui Wang, Zhujun Tian, Zuchao Cai, Fengmei Zhang, Yue Luo, Shue Wang, Gongshe Guo, Xiaowei Wang, Simon Powell, Zhihui Feng
It was reported that valproic acid (VPA, a histone deacetylase inhibitor) can sensitize cancer cells to hydroxyurea (HU, a ribonucleotide reductase inhibitor) for chemotherapy, although the mechanism of VPA-induced HU sensitization is unclear. In this study, we systematically characterized VPA-induced HU sensitization of breast cancer cells. Multiple breast cancer cell models were employed to investigate whether the safe concentration of 0.5mM VPA and 2mM HU can result in DNA double-strand breaks (DSBs) and impact cell survival...
August 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28827411/ruxolitinib-for-essential-thrombocythemia-refractory-to-or-intolerant-of-hydroxyurea-long-term-phase-2-study-results
#20
Srdan Verstovsek, Francesco Passamonti, Alessandro Rambaldi, Giovanni Barosi, Elisa Rumi, Elisabetta Gattoni, Lisa Pieri, Huiling Zhen, Muriel Granier, Albert Assad, Mario Cazzola, Hagop M Kantarjian, Tiziano Barbui, Alessandro M Vannucchi
No abstract text is available yet for this article.
August 21, 2017: Blood
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