Disease relevance of hydroxyurea

• The long-term safety of hydroxyurea in patients with sickle cell anemia is uncertain [1].
• We then treated eight additional patients in the blast phase of chronic granulocytic leukemia with a combination of alternate-day plicamycin and daily hydroxyurea [2].
• Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis [3].
• Successful use of hydroxyurea in beta-thalassemia major [4].
• Hydroxyurea in essential thrombocytosis [5].

Psychiatry related information on hydroxyurea

• In an open field situation in which fly locomotor activity is recorded by video tracking, we show that center avoidance is greatly diminished in flies with hydroxyurea-ablated MBs, suggesting a new role for these structures [6].
• Here we first show, by injecting hydroxyurea into staged embryos to ablate dividing cells, that PIC neuron precursors begin to divide at a low rate before E17, during the critical period [7].
• Possible adrenal involvement in hydroxyurea toxicity defense mechanisms [8].
• Patients in the telemedicine group were younger (p< 0.005), more likely to have Medicaid insurance (p = 0.009), and more likely be taking hydroxyurea (p = 0.003) than patients in the control encounter group [9].
• The association between hydroxyurea and multiple aggressive squamous cell carcinomas, Bowen's disease, and multiple actinic keratoses in sun-exposed areas after a variable latency period has been increasingly reported [10].

High impact information on hydroxyurea

• Unlike the response to DSBs, Mre11 and recombination proteins are not recruited to hydroxyurea-stalled replication forks unless the forks collapse [11].
• Unlike conventional poly(A) polymerases, which act in the nucleus and indiscriminately polyadenylate all mRNA, Cid13 is a cytoplasmic enzyme that specifically targets suc22 mRNA that encodes a subunit of ribonucleotide reductase (RNR). cid13 mutants have reduced dNTP pools and are sensitive to hydroxyurea, an RNR inhibitor [12].
• Proliferating cells depleted of Yph1p arrest in G(1) or G(2), with no cells in S phase, or significantly delay S phase progression after release from a hydroxyurea arrest [13].
• BACKGROUND AND METHODS: On behalf of the Gynecologic Oncology Group, we performed a randomized trial of radiotherapy in combination with three concurrent chemotherapy regimens -- cisplatin alone; cisplatin, fluorouracil, and hydroxyurea; and hydroxyurea alone -- in patients with locally advanced cervical cancer [14].
• Hydroxyurea-mediated DNA synthesis arrest of S phase MCF7 cells led to a loss of BRCA1 from these structures [15].

Chemical compound and disease context of hydroxyurea

• We treated 17 patients who had Philadelphia-chromosome-positive chronic myelogenous leukemia (4 of whom had not received therapy and 13 of whom had been treated with hydroxyurea or busulfan for less than six months) with recombinant human interferon alpha A (Roferon-A) [16].
• Stimulation of F-cell production in patients with sickle-cell anemia treated with cytarabine or hydroxyurea [17].
• In all three patients given hydroxyurea, treatment with this drug was associated with reduced hemolysis, shown by decreases in serum bilirubin and lactic dehydrogenase and prolongation of red-cell survival [18].
• Combination of hydroxyurea with the nucleoside analog didanosine (2',3'-dideoxyinosine, or ddl) generated a synergistic inhibitory effect without increasing toxicity [19].
• Long-term suppression of HIV-1 by hydroxyurea and didanosine [20].

Biological context of hydroxyurea

• When DNA replication is blocked by hydroxyurea, pHi continues to oscillate with a similar period as the uninhibited division cycle [21].
• Mitosis and cytokinesis occur in the presence of hydroxyurea or in the double mutant cdc10-cut5 (the cdc10 mutation alone blocks progression from G1 to S) [22].
• A total of 114 patients with essential thrombocythemia (77 women and 37 men; median age, 68 years; range, 40 to 85) and a median platelet count of 788,000 per cubic millimeter (range, 533,000 to 1,240,000 per cubic millimeter) were randomly assigned to receive hydroxyurea (56 patients) or no myelosuppressive therapy (58 patients) [3].
• Maximal tolerated doses of hydroxyurea may not be necessary to achieve a therapeutic effect [1].
• By constructing double mutants between bimE7 and S phase or G2 phase mutants and blocking DNA replication with hydroxyurea, we demonstrate that bimE7 can cause chromatin condensation and spindle formation in cells held in S or G2 [23].

Anatomical context of hydroxyurea

• Upon polyclonal stimulation of B lymphocytes or in proliferating B-lymphocyte-derived cell lines, the synthesis of XM1 is switched off, but it is reinduced by agents that arrest replication, such as mitomycin C, hydroxyurea, ultraviolet light or gamma irradiation [24].
• The proportion of BFU-E normally engaged in DNA synthesis is low in adult B6 (C57BL/6) mice of genotype Fv2rr (resistant to Friend erythroleukemia virus), as shown by 3H-thymidine or hydroxyurea "cell suicide" experiments in vivo and vitro [25].
• In contrast, hydroxyurea treatment was associated with a 3-to-25-fold increase in F reticulocytes, a 1.6-to-7-fold increase in F cells, and a 2.3-to-16-fold increase in the percentage of hemoglobin F [18].
• Hydroxyurea inhibits human immunodeficiency virus-type 1 (HIV-1) DNA synthesis in activated peripheral blood lymphocytes by decreasing the amount of intracellular deoxynucleotides, thus suggesting that this drug has an antiviral effect [19].
• Wild-type flies made a discrete choice that switched from one alternative to the other as the relative salience of color and shape cues gradually changed, but this ability was greatly diminished in mutant (mbm1) flies with miniature mushroom bodies or with hydroxyurea ablation of mushroom bodies [26].

Associations of hydroxyurea with other chemical compounds

• Both RNR1 and RNR3 transcripts are inducible by treatments that damage DNA, such as 4-nitroquinoline-1-oxide and methylmethanesulfonate, or block DNA replication, such as hydroxyurea [27].
• Hydroxyurea (HU) was used to block DNA synthesis and cell division, and 5-bromo-2'-deoxyuridine (BUdR) was used to probe for the expression of new cell-specific genes [28].
• Addition of morpholine blocked NO2-/NO3- generation from hydroxyurea and led to formation of nitrosomorpholine, as detected by gas chromatography/mass spectrometry [29].
• Thymidine analogues and hydroxyurea also appear to produce clinically relevant increases in radiation sensitivity [30].
• The in vitro effect of S-stage-specific drugs on the fetal hemoglobin (Hb F) potential of erythroid precursors and progenitors was tested by exposing bone marrow cells to 5-aza-2'-deoxycytidine, Ara-C, or hydroxyurea in suspension cultures and reculturing the cells in drug-free clonal cultures [31].
• These data add to an expanding appreciation of the role of hydroxyurea as an inducer of the NO/cGMP pathway in EPCs [32].

Gene context of hydroxyurea

• HU-induced phosphorylation is associated with increased catalytic activity of Spk1p [33].
• In this study, we show that BRCA1 phosphorylation is only partially ATM dependent in response to IR and ATM independent in response to treatment with UV light, or the DNA replication inhibitors hydroxyurea (HU) and aphidicolin (APH) [34].
• Furthermore, the absence of a functional Xrs2p complex leads to sensitivity to deoxynucleotide depletion and to an inability to efficiently slow down cell cycle progression in response to hydroxyurea [35].
• Like BRCA1 and RAD51, BRCA2 relocates to PCNA+ replication sites following exposure of S phase cells to hydroxyurea or UV irradiation [36].
• The critical role of Mrc1p in HU is therefore to promote fork recovery in a Rad53p-independent manner, presumably through the formation of a stable fork-pausing complex [37].

Analytical, diagnostic and therapeutic context of hydroxyurea

• Sixty-two days after initiation of phlebotomy, hydroxyurea (50 mg per kilogram of body weight per day for five days) induced only a small and transient increase in F cells and fetal hemoglobin [38].
• Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia [1].
• Cells infected with vaccinia virus in the presence of hydroxyurea (HU), which blocks DNA replication, were examined in thin sections by electron microscopy at intervals after removal of HU [39].
• These same sites in Smc1 are phosphorylated after treatment with UV irradiation or hydroxyurea in an Atm-independent manner, thus demonstrating that another kinase must be involved in responses to these cellular stresses [40].
• Hematopoietic stem cells in Friend murine leukemia virus-infected mice undergoing chemotherapy: remission and relapse of erythropoietin-independent erythropoiesis induced by hydroxyurea [41].

References