SEARCH · PubMed Health

Results for “hydroxyurea”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources

PubMed2005

Treatment with hydroxyurea and tyrphostin-1 significantly improves the transduction efficiency of recombinant adeno-associated viruses in human cancer cells.

To enhance the transduction efficiency (TE) of a recombinant adeno-associated virus 2 (rAAV2) in human cancer cells, we examined the combined effects of various chemicals known to influence the rAAV2 transduction process at distinct steps. Among the agents tested were trichostatin A, a histone deacetylase inhibitor, MG-132, a proteosome inhibitor, the genotoxic agents hydroxyurea, aphidicolin, etoposide and camptothecin, and tyrphostin-1, an epidermal growth factor receptor inhibitor. During or after chemical treatment, various human cancer cells were infected with rAAV2 expressing beta-galactosidase. Treatment with hydroxy-urea or etoposide plus tyrphostin-1 dramatically increased the TE in most cell lines. The combination of hydroxyurea plus tyrphostin-1 increased TE to 37.7+/-7.9%, 32.8+/-2.0% and 31.8+/-2.1% in SK-Hep1, HeLa, and HCT116 cells, respectively. In addition, following rAAV2 infection and treatment with hydroxyurea plus tyrphostin-1, long-term transgene expression was observed for up to 6 months, with no damage to the transduced cells. These results indicate that rAAV2 transgene expression can be significantly enhanced by a combination of chemical agents with distinct activity and prolonged gene expression can occur following rAAV2 gene transfer into human cancer cells.

Adenoviridae↗

PubMed1992

Hydroxyurea with concomitant radiotherapy for locally advanced head and neck cancer.

Hydroxyurea is an active single agent in squamous cell cancer of the head and neck. It has been used clinically, most frequently as a radiation-enhancing agent with concomitant radiotherapy. Pilot trials testing hydroxyurea in this setting reported encouraging results. Two randomized trials have been conducted with inconclusive results, possibly relating to study cohort size and short period of follow-up. More recently, hydroxyurea has been investigated with 5-fluorouracil and concomitant radiotherapy. A sound theoretic rationale can be made for this approach and data derived from a phase I/II study are presented. These support the further investigation of this regimen.

Administration, Oral↗

PubMedDate not supplied

[Cutaneous side effects of a long-term treatment by hydroxyurea].

Hydroxyurea is an antitumour agent used most commonly to treat myeloproliferative disorders. We present a clinical observation illustrating different cutaneous side effects susceptible to occur during a long-term treatment by hydroxyurea : leg ulceration, oral ulcer and spinocellular carcinoma. This clinical observation is completed by a review of the literature published on the cutaneous side effects of hydroxyurea treatment.

Aged↗

PubMed1990

Effect of hydroxyurea on foetal haemoglobin in myeloproliferative & myelodysplastic syndromes.

The effect of hydroxyurea on foetal haemoglobin (HbF) levels was evaluated in 36 patients of myeloproliferative and myelodysplastic disorders. In 17 (47.2%) patients, HbF levels increased from 1.40 +/- 1.17 to 3.03 +/- 1.97 per cent after 4 wk therapy with hydroxyurea. In the responders this increase was highly significant (P less than 0.001). The rise in the HbF levels after hydroxyurea therapy was significant in patients with chronic myeloid leukaemia but not in the other groups.

Adolescent↗

PubMed1991

Effect of hydroxyurea on blood viscosity in chronic myelogenous leukemia with hyperleukocytosis.

The effect of hydroxyurea on blood viscosity was studied in 10 patients with Philadelphia chromosome positive chronic myelogenous leukemia (CML) and hyperleukocytosis (white blood cell counts over 200 x 10(9)/l). All the patients had visible manifestations of leukostasis such as headache, blurred vision, retinal hemorrhage, pulmonary infiltrates, etc. Contraves LS 30 viscometer was used to measure the blood viscosity at 37 degrees C and at different shear rates on paired leukemic blood samples obtained before and after the hydroxyurea treatment. The blood viscosity was significantly higher in CML patients then normal subjects and decreased after treatment with hydroxyurea. In all the cases plasma viscosity was unaffected by the treatment.

Adolescent↗

PubMed1990

Hydroxyurea and p-aminophenol are the suicide inhibitors of ascorbate peroxidase.

Guaiacol peroxidase from spinach catalyzes the oxidation of p-aminophenol to produce the aminophenoxy radical as the primary product which is converted further into a stable oxidation product with an absorption peak at 470 nm. The p-aminophenol radicals oxidize ascorbate (AsA) to produce monodehydroascorbate radicals. Kinetic analysis indicates that p-aminophenol radicals also oxidize monodehydroascorbate to dehydroascorbate. Incubation of AsA peroxidase from tea leaves and hydrogen peroxide with p-aminophenol, p-cresol, hydroxyurea, or hydroxylamine results in the inactivation of the enzyme. No inactivation of the enzyme was found upon incubation of the enzyme with these compounds either in the absence of hydrogen peroxide or with the stable oxidized products of these compounds. The enzyme was protected from inactivation by the inclusion of AsA in the incubation mixture. The radicals of p-aminophenol and hydroxyurea were produced by AsA peroxidase as detected by their ESR signals. These signals disappeared upon the addition of AsA, and the signal characteristic of monodehydroascorbate was found. Thus, AsA peroxidase is inactivated by the radicals of p-aminophenol, p-cresol, hydroxyurea, and hydroxylamine which are produced by the peroxidase reaction, and it is protected from inactivation by AsA via the scavenging of the radicals. Thus, these compounds are the suicide inhibitors for AsA peroxidase. Isozyme II of AsA peroxidase, which is localized in chloroplasts, is more sensitive to these compounds than isozyme I. In contrast to AsA peroxidase, guaiacol peroxidase was not affected by these various compounds, even though each was oxidized by it and the corresponding radicals were produced.

Aminophenols↗

PubMed1985

The effect of hydroxyurea on hemoglobin F in patients with myeloproliferative syndromes.

Fetal hemoglobin (Hb F) may increase in patients receiving chemotherapeutic drugs, a result of potential use in patients with symptomatic hemoglobinopathies. We examined Hb F in 13 patients with myeloproliferative disease (six polycythemia vera, five polycythemia vera with myeloid metaplasia, one agnogenic myeloid metaplasia, and one chronic myelogenous leukemia) who were treated with hydroxyurea. Four patients showed an increase in Hb F from less than 1% to between 5% and greater than 8% while on hydroxyurea, and a decline to less than 1% when the drug was discontinued. This group of "responders" received a higher average daily dose of hydroxyurea, which was administered continuously rather than intermittently, when compared to the "nonresponders." Mean corpuscular volumes (MCVs) rose in most patients, and i antigen remained elevated or decreased; neither parameter correlated with Hb F levels. Both responders and nonresponders had therapeutically desirable suppression of WBCs and platelets, and almost all had no depression of reticulocytes or Hb.

Adult↗

PubMed1986

Hydroxyurea-induced conversion of mammalian ribonucleotide reductase to a form hypersensitive to bleomycin.

Bleomycin is a commonly used chemotherapeutic agent known to cause extensive DNA damage. In this paper we show that bleomycin inhibits ribonucleotide reductase activity in mouse L-cells. The effectiveness of the drug is a result of its metal-chelating properties which enable it to inactivate the iron containing M2 subunit of the enzyme. A hydroxyurea-resistant mouse L-cell line was used to show that the degree of inhibition caused by bleomycin can be greatly enhanced if ribonucleotide reductase has been previously exposed in vivo or in vitro to agents, such as hydroxyurea, which destroy the tyrosine free radical of subunit M2. The increased effectiveness of bleomycin appears to result from a decrease in the stability of the iron center of protein M2 following exposure to hydroxyurea. These findings have important implications in terms of the use of bleomycin as an anticancer agent, especially in combination chemotherapy where it can be used with other drugs that act at ribonucleotide reductase.

Adenosine Diphosphate↗

PubMed1989

Metabolic differentiation of bloodstream forms of Trypanosoma brucei brucei into procyclic forms. Effect of hydroxyurea, arabinosyl adenine, and serum omission.

Bloodforms of Trypanosoma brucei brucei STIB 247 taken from rats and containing more than 80 per cent short stumpy forms, differentiated in vitro to procyclic forms in medium SDM 79 (Brun and Schönenberger 1979), enriched with 3 mmol.dm-3 cis-aconitate. Cell division was abolished by the addition of hydroxyurea (200 micrograms.ml-1) or arabinosyl adenine (20 micrograms.ml-1 to the cultivation medium, or by the omission of serum from the medium. The ultrastructure of exponentially growing controls was rearranged within 24 h. The endogenous respiration and the respiration stimulated by proline, succinate, and 2-oxoglutarate were detectable within 12 h; after 48 h the respiration rates were comparable to those found in the established procyclic forms. After 12 h the respiration was inhibited by 200 mumol.dm-3 KCN, and by 20 mumol.dm-3 antimycin to the extent found in procyclic forms. Hydroxyurea did not significantly affect respiration. Activities of procyclic-stage enzyme markers malate dehydrogenase, threonine dehydrogenase, succinate: cytochrome c reductase, and NADH: cytochrome c reductase rose within 48 h of differentiation to values which were close to those found in established procyclic forms. The activity of glutamate dehydrogenase (NAD-specific), however, was only 1/3 of that in the procyclics, and no citrate synthase was detected in differentiating culture. Glycosomal malate dehydrogenase was detected after 6 h. In the presence of hydroxyurea or arabinosyl adenine, or in the absence of serum, respiration rates, marker enzyme activities, and glycosomal malate dehydrogenase developed to the extent comparable to the untreated controls. The results suggest that it is possible to separate the process of differentiation from cell proliferation. Cell division is not a necessary prerequisite of differentiation.

Alcohol Oxidoreductases↗

PubMedDate not supplied

[P-glycoprotein and treatment with plicamycin + hydroxyurea in myeloid blastic crisis of chronic myeloid leukemia].

The authors studied P-glycoprotein (P-gp) expression in three patients affected by myeloid blast crisis of chronic myeloid leukemia undergoing chemotherapy with plicamycin + hydroxyurea. P-gp is the molecular marker of multidrug resistance (MDR), and is able to promote the efflux of various drugs (including plicamycin) from the neoplastic cell. When resistance towards plicamycin and hydroxyurea association was observed, the blasts obtained from the three patients were found to express P-gp. Although P-gp may be not the unique mechanism responsible for resistance towards plicamycin and hydroxyurea association, the MDR phenotype may play an important role in the resistance towards this treatment protocol in the blast crisis of chronic myeloid leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1987

The gene for ornithine decarboxylase is co-amplified in hydroxyurea-resistant hamster cells.

We have constructed a cDNA library from the highly hydroxyurea-resistant hamster cell line 600H in which the activity of ribonucleotide reductase is elevated more than 80-fold. Using the technique of differential hybridization, we have isolated a number of cDNA clones from this library which are homologous to genomic DNA sequences amplified in the 600H cell line compared to the V79 parental line. One of these cDNA clones by sequence analysis was found to code for ornithine decarboxylase. This was confirmed by in vitro translation of poly(A+) RNA isolated by hybridization-selection followed by immunoprecipitation with antiserum specific for mouse ornithine decarboxylase. Genomic sequences homologous to the cDNA clone were shown to be sequentially amplified 6-20-fold in hamster cell lines selected stepwise for resistance to increasing concentrations of hydroxyurea. Genomic sequences homologous to a cDNA for the M2 subunit of ribonucleotide reductase were also amplified in these cell lines, and the degree of M2 sequence amplification corresponded to the degree of amplification of ornithine decarboxylase sequences, suggesting that the two genes had been co-amplified during the selection of the hydroxyurea-resistant phenotype.

Amino Acid Sequence↗

PubMed1977

Haemopoietic recovery in spleen and marrow after transplantation of bone marrow from either normal or hydroxyurea treated mice.

Haemopoietic regeneration was studied following x-irradiation and transplantation of bone marrow from either normal or hydroxyurea-treated donor mice, to ascertain the contribution of proliferating progenitor cells to regeneration. With transplantation of equivalent numbers of CFU-S, total DNA and 3HTdR uptake into DNA in spleen and femoral bone marrow and the erythroid, granulocytic and mononuclear cell populations were not significantly different between normal (NBM) and hydroxyurea-treated (HUBM) marrow. The response of hypertransfused x-irradiated mice to erythropoietin (EPO) administration was also not significantly different in spleens of mice receiving normal or hydroxyurea-treated marrow.

Animals↗

PubMed1979

Effect of hydroxyurea on T4 ribonucleotide reductase.

Phage T4-induced ribonucleotide reductase, purified to homogeneity, catalyzes the reduction of the four ribonucleotides CDP, UDP, ADP, and GDP to the corresponding deoxyribonucleotides. The enzyme is an order of magnitude more sensitive to hydroxyurea than the corresponding Escherichia coli enzyme. Fifty per cent inhibition occurs at 10 micrometer hydroxyurea. Inhibition is complete at a high concentration of the drug, and there is no differential effect on the four substrates. Treatment of T4 ribonucleotide reductase or its isolated subunits with hydroxyurea does not lead to their irreversible inactivation.

Coliphages↗

PubMed1985

Increased expression of fragile site Xq by hydroxyurea. Preliminary communication.

The addition of hydroxyurea in final concentration 1.3 X 10(-5) M increases the frequency of fraX in comparison with cultures without hydroxyurea. The same concentration of hydroxyurea did not induce fraX formation and "nonspecific" gaps in cultures of lymphocytes derive from healthy individuals. The possible explanation of this effect is discussed.

Cells, Cultured↗

PubMed1984

[Cutaneous lesions induced by long-term use of hydroxyurea].

The authors report 3 cases of patients having myeloid chronic leukemia presenting skin changes after long-term hydroxyurea therapy. Some of these side effects are already known; such as dryness, pigmentation, spontaneous necrotizing ulceration and chromonychia with longitudinal pigmented bands. Two new signs are described: a band-like erythema on the dorsum of the fingers and toes, as in dermatomyositis and a plantar keratoderma which interpretation is difficult in such a context. The hydroxyurea's imputability is discussed. These lesions altogether are very suggestive of skin changes after hydroxyurea therapy. The occurrence of such phenomena is quite frequent.

Aged↗

PubMedDate not supplied

Treatment of renal carcinoma: a phase III randomized trial of oral medroxyprogesterone (Provera), hydroxyurea, and nafoxidine.

Seventy patients with metastatic renal carcinoma were randomized to receive hydroxyurea, nafoxidine, or medroxyprogesterone (Provera) orally. Sixty patients were considered evaluable, with a response rate of 5% for medroxyprogesterone (one complete remission) and hydroxyurea (one partial remission) and a response rate of 16% for nafoxidine (two complete remissions and one partial remission). Differences in response rates and duration of survival were not statistically significant. The major toxicity observed with hydroxyurea was hematologic, and the major toxic effect of nafoxidine was an ichthyosis-like skin rash. Toxicity for medroxyprogesterone was minimal.

Clinical Trials as Topic↗

PubMed1984

Hydroxyurea inhibition of thymidine kinase is dependent on the developmental stage of the brain region.

Hydroxyurea, when administered intraperitoneally as three consecutive and varying doses into 7-day-old rats, showed no inhibitory effect on thymidine kinase activity in the cerebral region of the brain. However, when injected intraperitoneally as a single dose into pregnant rats, the activity was found to be significantly inhibited in 16-day-old embryonic cerebrum. The inhibitory effect of the drug was time-dependent. The drug, however, showed no effect on thymidine kinase activity in vitro in either case. On the basis of these results along with our earlier observation regarding the action of hydroxyurea on thymidine kinase activity in 7-day-old cerebellum (1), we conclude that the inhibitory action of hydroxyurea on thymidine kinase activity is dependent on the proliferative stage of cells under study. We further speculate that there may be different forms of thymidine kinase in rapidly dividing and non-dividing cells.

Aging↗

PubMed1978

Tissue specificity for incorporation of [3H]thymidine by the 10- to 12-somite mouse embryo: alteration by acute exposure to hydroxyurea.

Radioautograms from 10- to 12-somite mouse embryos labeled for 30 min in vitro with [3H]thymidine were examined for frequency and intensity of incorporation. Results from ten tissues showed that values ranged from 82% of nuclei with a mean of 16.6 grains for visceral yolk sac to 17% of nuclei labeled with a mean of 4.4 grains for epithelium of the anterior gut tube. Labeling in the ten tissues indicated (1) a tissue-specific spectrum of incorporation of [3H]thymidine, (2) close correlation between frequency and intensity of labeling within a tissue and (3) asymmetrical quantities of incorporation between right and left somatopleure. Treatment with hydroxyurea in vitro reduced the frequency of labeled nuclei by 85% to 12% of control values. Mean numbers of grains over treated nuclei, 3.3-4.6 grains, were well above background but were clustered below the low end of the control range. Tissues exposed to hydroxyurea showed (1) labeling of significant numbers of nuclei, (2) inhibition of labeling in selected tissues and (3) equalization of bilateral asymmetry in quantity (frequency and intensity) of incorporation in somatopleure. The selective reduction of thymidine incorporation and equalization of asymmetrical rates of proliferation may constitute mechanisms by which hydroxyurea causes abnormal morphogenesis.

Animals↗