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Hydroxyurea

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https://www.readbyqxmd.com/read/29136238/regulation-of-transcriptional-silencing-and-chromodomain-protein-localization-at-centromeric-heterochromatin-by-histone-h3-tyrosine-41-phosphorylation-in-fission-yeast
#1
Bingbing Ren, Hwei Ling Tan, Thi Thuy Trang Nguyen, Ahmed Mahmoud Mohammed Sayed, Ying Li, Yu-Keung Mok, Henry Yang, Ee Sin Chen
Heterochromatin silencing is critical for genomic integrity and cell survival. It is orchestrated by chromodomain (CD)-containing proteins that bind to methylated histone H3 lysine 9 (H3K9me), a hallmark of heterochromatin. Here, we show that phosphorylation of tyrosine 41 (H3Y41p)-a novel histone H3 modification-participates in the regulation of heterochromatin in fission yeast. We show that a loss-of-function mutant of H3Y41 can suppress heterochromatin de-silencing in the centromere and subtelomere repeat regions, suggesting a de-silencing role for H3Y41p on heterochromatin...
November 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29127675/clinical-features-of-%C3%AE-thalassemia-and-sickle-cell-disease
#2
Patrick T McGann, Alecia C Nero, Russell E Ware
Sickle cell disease (SCD) and β-thalassemia are among the most common inherited diseases, affecting millions of persons globally. It is estimated that 5-7% of the world's population is a carrier of a significant hemoglobin variant. Without early diagnosis followed by initiation of preventative and therapeutic care, both SCD and β-thalassemia result in significant morbidity and early mortality. Despite great strides in the understanding of the molecular basis and pathophysiology of these conditions, the burden of disease remains high, particularly in limited resource settings...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29122152/biologic-agents-for-the-treatment-of-hypereosinophilic-syndromes
#3
Fei Li Kuang, Amy D Klion
Hypereosinophilic syndromes (HES) are a heterogeneous group of rare disorders defined by the presence of marked peripheral or tissue eosinophilia resulting in end-organ damage. Although conventional therapies, including glucocorticoids, hydroxyurea, and IFN-α, are initially effective in reducing eosinophilia and symptoms in a majority of patients with platelet-derived growth factor mutation-negative HES, the development of resistance and treatment-related toxicity are common. In contrast, targeted therapy with the tyrosine kinase inhibitor, imatinib, is well tolerated but effective only in the subset of patients with HES with a primary myeloid disorder...
November 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/29108926/a-thalidomide-hydroxyurea-hybrid-increases-hbf-production-in-sickle-cell-mice-and-reduces-the-release-of-proinflammatory-cytokines-in-cultured-monocytes
#4
Carolina Lanaro, Carla Franco-Penteado, Fabio H Silva, Kleber Y Fertrin, Jean Leandro Dos Santos, Marlene Wade, Shobha Yerigenahally, Thais R de Melo, Chung Man Chin, Abdullah Kutlar, Steffen E Meiler, Fernando Ferreira Costa
Fetal hemoglobin induction by hydroxyurea therapy is associated with decreased morbidity and mortality in SCA patients, but not all respond to or tolerate hydroxyurea, which provides a rationale for the development of novel HbF inducers as treatment options for SCA. Thalidomide analogs have a combined ability to induce HbF production and to inhibit the release of tumor necrosis factor α. Molecular hybridization of hydroxyurea and thalidomide was used to synthesize 3-(1,3-dioxoisoindolin-2-yl) benzyl nitrate (compound 4C)...
November 3, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29107441/real-life-experience-with-hydroxyurea-in-sickle-cell-disease-a-multicenter-study-in-a-cohort-of-patients-with-heterogeneous-descent
#5
Paolo Rigano, Lucia De Franceschi, Laura Sainati, Antonio Piga, Frédéric B Piel, Maria Domenica Cappellini, Carmelo Fidone, Nicoletta Masera, Giovanni Palazzi, Barbara Gianesin, Gian Luca Forni
We conducted the first nation-wide cohort study of sickle cell disease (SCD) in Italy, a Southern European country exposed to intense recent flux migration from endemic areas for SCD. We evaluate the impact of hydroxyurea on a total of 652 pediatric and adult patients from 33 Reference Centers for SCD (mean age 24.5±15years, 51.4% males). Hydroxyurea median treatment duration was 7years (range: <1year to 29years) at a mean therapeutic dose of 18±4.7mg/kg/day. Hydroxyurea was associated with a significant increase in mean total and fetal hemoglobin and a significant decrease in mean hemoglobin S, white blood and platelet counts, and lactate dehydrogenase levels...
October 9, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/29102950/fibrotic-lung-toxicity-induced-by-hydroxycarbamide
#6
Elena Bargagli, Marco Palazzi, Francesco Perri, Elena Torricelli, Elisabetta Rosi, Alessandra Bindi, Massimo Pistolesi, Luca Voltolini
A patient treated for 4 months with hydroxycarbamide (hydroxyurea) for chronic myelomonocytic leukemia was admitted to hospital for recently developed severe dyspnea and acute respiratory failure. The computed tomographic scan of the chest showed diffuse ground glass opacities, some centrilobular low-density nodules (resembling hypersensitivity pneumonitis-like pattern), and minimal interstitial reticulation of the subpleural region. The analysis of bronchoalveolar lavage fluid excluded infection, as did serological examinations...
November 2017: In Vivo
https://www.readbyqxmd.com/read/29100978/cd209-336a-g-promotor-polymorphism-and-its-clinical-associations-in-sickle-cell-disease-egyptian-pediatric-patients
#7
Rasha Abdel-Raouf Afifi, Dina Kamal, Riham El Sayed, Sherif M M Ekladious, Gehan H Shaheen, Sherif M Yousry, Rania Elsayed Hussein
OBJECTIVES: To detect the frequency of CD209 A>G polymorphism in sickle cell disease (SCD) Egyptian patients and to evaluate the use of CD209 A>G polymorphism as a genetic predictor of SCD clinical heterogeneity. METHODS: A total of 100 Egyptian children with SCD and 100 Egyptian controls were tested for CD209 A>G polymorphism and were followed up prospectively between June 2012 and December 2014. RESULTS: Comparison of CD209 A>G polymorphism among cases and controls did not show statistically significant difference (p = ...
October 26, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/29099956/recycling-drug-screen-repurposes-hydroxyurea-as-a-sensitizer-of-glioblastomas-to-temozolomide-targeting-de-novo-dna-synthesis-irrespective-of-molecular-subtype
#8
Jian Teng, Seyedali Hejazi, Lotte Hiddingh, Litia Carvalho, Mark de Gooijer, Hiroaki Wakimoto, Marco Barazas, Marie Tannous, Andrew S Chi, David P Noske, Pieter Wesseling, Thomas Wurdinger, Tracy T Batchelor, Bakhos A Tannous
Background: Glioblastoma (GBM) is the most common and most aggressive primary malignant brain tumor. Standard-of-care treatment involves maximal surgical resection of the tumor followed by radiation and chemotherapy (temozolomide; TMZ). The five-year survival rate of patients with GBM is <10%, a colossal failure that has been partially attributed to intrinsic and/or acquired resistance to TMZ through MGMT (O6-methylguanine DNA methyltransferase) promoter methylation status in the tumor...
November 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29082557/the-nuclear-dek-interactome-supports-multi-functionality-the-dek-interactome
#9
Eric A Smith, Eric F Krumpelbeck, Anil G Jegga, Malte Prell, Marie M Matrka, Ferdinand Kappes, Kenneth D Greis, Abdullah M Ali, Amom R Meetei, Susanne I Wells
DEK is an oncoprotein that is overexpressed in many forms of cancer and participates in numerous cellular pathways. Of these different pathways, relevant interacting partners and functions of DEK are well described in regard to the regulation of chromatin structure, epigenetic marks, and transcription. Most of this understanding was derived by investigating DNA-binding and chromatin processing capabilities of the oncoprotein. To facilitate the generation of mechanism-driven hypotheses regarding DEK activities in underexplored areas, we have developed the first DEK interactome model using tandem-affinity purification and mass spectrometry...
October 30, 2017: Proteins
https://www.readbyqxmd.com/read/29080451/curcumin-sensitizes-lymphoma-cells-to-dna-damage-agents-through-regulating-rad51-dependent-homologous-recombination
#10
Qian Zhao, Jiawei Guan, Yuanhua Qin, Peng Ren, Zhiwei Zhang, Jian Lv, Shijie Sun, Cuili Zhang, Weifeng Mao
Curcumin is a natural compound isolated from the rhizome of Curcuma longa. It possesses anti-tumor activity through arresting cell cycles and promoting cell apoptosis. However, the effect of curcumin on DNA damage is not well defined. In this study, we investigated the effect of curcumin on inducing DNA damage and on sensitizing lymphoma cells to anti-tumoral DNA damage drugs. Western blot showed curcumin induced γ-H2AX foci in CH12F3 lymphoma cells, which suggests curcumin induces DNA breaks. In addition, curcumin decreased the expression of Rad51, which suggests curcumin induces DNA damage through regulating Rad51-dependant homologous recombination...
October 25, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29061162/whole-transcriptome-analysis-of-human-erythropoietic-cells-during-ontogenesis-suggests-a-role-of-vegfa-gene-as-modulator-of-fetal-hemoglobin-and-pharmacogenomic-biomarker-of-treatment-response-to-hydroxyurea-in-%C3%AE-type-hemoglobinopathy-patients
#11
Vasiliki Chondrou, Petros Kolovos, Argyro Sgourou, Alexandra Kourakli, Alexia Pavlidaki, Vlasia Kastrinou, Anne John, Argiris Symeonidis, Bassam R Ali, Adamantia Papachatzopoulou, Theodora Katsila, George P Patrinos
BACKGROUND: Human erythropoiesis is characterized by distinct gene expression profiles at various developmental stages. Previous studies suggest that fetal-to-adult hemoglobin switch is regulated by a complex mechanism, in which many key players still remain unknown. Here, we report our findings from whole transcriptome analysis of erythroid cells, isolated from erythroid tissues at various developmental stages in an effort to identify distinct molecular signatures of each erythroid tissue...
October 23, 2017: Human Genomics
https://www.readbyqxmd.com/read/29057997/defining-the-domains-of-cia2-required-for-its-essential-function-in-vivo-and-in-vitro
#12
Amanda T Vo, Nicholas M Fleischman, Melissa D Marquez, Eric J Camire, Stephanie U Esonwune, John D Grossman, Kelly A Gay, Jessica A Cosman, Deborah L Perlstein
The cytosolic iron-sulfur cluster assembly (CIA) system biosynthesizes iron-sulfur (FeS) cluster cofactors for cytosolic and nuclear proteins. The yeast Cia2 protein is the central component of the targeting complex which identifies apo-protein targets in the final step of the pathway. Herein, we determine that Cia2 contains five conserved motifs distributed between an intrinsically disordered N-terminal domain and a C-terminal domain of unknown function 59 (DUF59). The disordered domain is dispensible for binding the other subunits of the targeting complex, Met18 and Cia1, and the apo-target Rad3 in vitro...
November 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29056404/changes-in-transcranial-doppler-flow-velocities-in-children-with-sickle-cell-disease-the-impact-of-hydroxyurea-therapy
#13
Samuel Ademola Adegoke, Rejane de Souza Macedo-Campos, Josefina Aparecida Pellegrini Braga, Maria Stella Figueiredo, Gisele Sampaio Silva
BACKGROUND AND OBJECTIVES: Hydroxyurea (HU) was recently described as a substitute for chronic transfusion for children with sickle cell disease (SCD) and abnormal transcranial Doppler (TCD) velocities who have received at least 1 year of transfusions. However, the role of HU in reverting elevated TCD velocities in patients not treated with transfusion is still debatable. The objective of the study was to examine whether HU influences the progression of TCD velocities in children with SCD...
October 19, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29051184/novel-use-of-hydroxyurea-in-an-african-region-with-malaria-noharm-a-trial-for-children-with-sickle-cell-anemia
#14
Robert O Opoka, Christopher M Ndugwa, Teresa S Latham, Adam Lane, Heather A Hume, Phillip Kasirye, James S Hodges, Russell E Ware, Chandy C John
Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic sub-Saharan Africa, where the greatest sickle cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at 20 ± 2...
October 19, 2017: Blood
https://www.readbyqxmd.com/read/29044676/world-health-organization-defined-eosinophilic-disorders-2017-update-on-diagnosis-risk-stratification-and-management
#15
REVIEW
Jason Gotlib
DISEASE OVERVIEW: The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end-organ damage. DIAGNOSIS: Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1500/mm(3) and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic myeloid or lymphoproliferative disorder...
November 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29042365/ruxolitinib-induced-defects-in-dna-repair-cause-sensitivity-to-parp-inhibitors-in-myeloproliferative-neoplasms
#16
Margaret Nieborowska-Skorska, Silvia Maifrede, Yashodhara Dasgupta, Katherine Sullivan, Sylwia Flis, Bac Viet Le, Martyna Solecka, Elizaveta A Belyaeva, Lucia Kubovcakova, Morgan Nawrocki, Martin Kirschner, Huaqing Zhao, Josef T Prchal, Katarzyna Piwocka, Alison R Moliterno, Mariusz Wasik, Steffen Koschmieder, Tony R Green, Radek C Skoda, Tomasz Skorski
Myeloproliferative neoplasms (MPNs) often carry JAK2(V617F), MPL(W515L), or CALR(del52) mutations. Current treatment options for MPNs include cytoreduction by hydroxyurea and JAK1/2 inhibition by ruxolitinib, both of which are not curative. We show here that cell lines expressing JAK2(V617F), MPL(W515L) or CALR(del52) accumulated reactive oxygen species-induced DNA double-strand breaks (DSBs) and were modestly sensitive to poly-ADP-ribose polymerase (PARP) inhibitors olaparib and BMN673. At the same time primary MPN cell samples from individual patients displayed a high degree of variability in the sensitivity to these drugs...
October 17, 2017: Blood
https://www.readbyqxmd.com/read/29042194/knockdown-of-rmi1-impairs-dna-repair-under-dna-replication-stress
#17
Chang Xu, Lianying Fang, Yangyang Kong, Changyan Xiao, Mengmeng Yang, Li-Qing Du, Qiang Liu
RMI1 (RecQ-mediated genome instability protein 1) forms a conserved BTR complex with BLM, Topo IIIα, and RMI2, and its absence causes genome instability. It has been revealed that RMI1 localizes to nuclear foci with BLM and Topo IIIα in response to replication stress, and that RMI1 functions downstream of BLM in promoting replication elongation. However, the precise functions of RMI1 during replication stress are not completely understood. Here we report that RMI1 knockdown cells are hypersensitive to hydroxyurea (HU)...
October 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29036551/comparative-study-of-the-growth-and-nutritional-status-of-brazilian-and-nigerian-school-aged-children-with-sickle-cell-disease
#18
Samuel A Adegoke, Maria S Figueiredo, Adekunle D Adekile, Josefina A P Braga
Background: Comparative studies of patients in different sociogeographic/ecological zones may unravel potential environmental and nutritional factors influencing disease phenotype. In sickle cell disease (SCD), differential access to comprehensive care may influence their growth and nutritional status. Methods: From June 2015 to February 2016, steady-state nutritional parameters of 109 Brazilian and 95 Nigerian children with SCD attending routine clinic visits at Universidade Federal de São Paulo, Brazil and Obafemi Awolowo University Teaching Hospital, Ile-Ife (Ilesa unit), respectively, were compared...
September 28, 2017: International Health
https://www.readbyqxmd.com/read/29026400/hydroxyurea-therapy-in-adult-nigerian-sickle-cell-disease-a-monocentric-survey-on-pattern-of-use-clinical-effects-and-patient-s-compliance
#19
Ademola Samson Adewoyin, Omokiniovo Sunday Oghuvwu, Omolade Augustina Awodu
BACKGROUND: The clinical prospects of hydroxyurea therapy in the management of sickle cell disease (SCD) require evaluation in the Nigerian setting to develop indigenous guidelines. This survey examines the pattern of hydroxyurea therapy, its clinico-haematologic benefits and safety profile in Nigerian SCD subjects. METHODS: A cross sectional pilot survey was carried out among 60 adult SCD subjects over 3 months. Data on clinical phenotypes, relevant haematological parameters and details of hydroxyurea therapy were obtained using a structured questionnaire through an interview process and case file review...
March 2017: African Health Sciences
https://www.readbyqxmd.com/read/29017784/arginine-rich-cross-linking-peptides-with-different-sv40-nuclear-localization-signal-content-as-vectors-for-intranuclear-dna-delivery
#20
Mariia Bogacheva, Anna Egorova, Anna Slita, Marianna Maretina, Vladislav Baranov, Anton Kiselev
The major barriers for intracellular DNA transportation by cationic polymers are their toxicity, poor endosomal escape and inefficient nuclear uptake. Therefore, we designed novel modular peptide-based carriers modified with SV40 nuclear localization signal (NLS). Core peptide consists of arginine, histidine and cysteine residues for DNA condensation, endosomal escape promotion and interpeptide cross-linking, respectively. We investigated three polyplexes with different NLS content (10 mol%, 50 mol% and 90 mol% of SV40 NLS) as vectors for intranuclear DNA delivery...
October 3, 2017: Bioorganic & Medicinal Chemistry Letters
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