Abstract:
:Celecoxib, a specific cyclooxygenase-2 (Cox-2) inhibitor, has been shown to possess antitumor activity in a variety of cancer cells. However, the antitumor activity of celecoxib in hematopoietic tumors, especially in chronic myeloid leukemia (CML), has not been well established. This study was designed to investigate the effect of celecoxib on growth and apoptosis in a human CML cell line (K562 cells) or in primary CML cells, and to examine the synergistic actions of celecoxib and hydroxyurea or imatinib on K562 cell proliferation and apoptosis. Celecoxib significantly inhibited the growth of both K562 and primary CML cells and induced apoptosis in a dose-dependent fashion. The IC50 of celecoxib was 46 microM for inhibition of K562 cell proliferation. The effect of celecoxib on growth inhibition was accompanied by the downregulation of cyclin D1 and cyclin E and p-Rb expression, the upregulation of P16(INK4a) and P27KIP expression, and a G1-S phase arrest of the cell cycle. The pro-apoptotic effect of celecoxib was determined to be mediated by caspase-3 activation. When K562 cells were pretreated with DEVD-fmk, a specific inhibitor of caspases, the apoptotic activity of celecoxib was, in part, abrogated. Importantly, we demonstrated for the first time that K562 cells were Cox-2-positive both at the mRNA and protein levels. We noted the following observations: (i) we detected Cox-2 mRNA in K562 cells by reverse transcription-PCR (RT-PCR) and protein expression by western blot analysis; (ii) Cox-2 expression in K562 cells was stimulated by IL-1beta, a specific inducing agent of Cox-2 expression; (iii) primary CML cells from CML patient bone marrow also exhibited Cox-2 protein expression. Furthermore, Cox-2 expression was downregulated at higher doses of celecoxib (80-160 microM), suggesting a Cox-2-dependent mechanism was involved in the drug's effects of growth inhibition and induction of apoptosis. In addition, a synergistic effect was observed when cells were exposed to low-dose celecoxib (40 microM) and hydroxyurea (10 mM) or a combination of celecoxib (40 microM) and imatinib (0.2 microM). These findings provide the basis for uncovering the mechanism of celecoxib's antitumor effects and developing a new therapeutic strategy for treating CML.
journal_name
Am J Hematoljournal_title
American journal of hematologyauthors
Zhang GS,Liu DS,Dai CW,Li RJdoi
10.1002/ajh.20542keywords:
subject
Has Abstractpub_date
2006-04-01 00:00:00pages
242-55issue
4eissn
0361-8609issn
1096-8652journal_volume
81pub_type
杂志文章abstract::Red blood cells from patients with sickle cell disease (SS RBC) adhere to laminin and over-express the high-affinity laminin receptor basal cell adhesion molecule/Lutheran protein (B-CAM/LU). This receptor has recently been shown to undergo activation in vitro through a protein kinase A-dependent mechanism. Low-densit...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.10442
更新日期:2004-02-01 00:00:00
abstract::Six patients and their parents from five different families with Hb H have been evaluated clinically and hematologically. Previous studies using restriction endonuclease mapping technique indicated that alpha-thalassemia determinants in these cases are heterogeneous. Only one of the five cases have the usual genotype ...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830090304
更新日期:1980-01-01 00:00:00
abstract::Liquid culture of the mononuclear fraction of the blood of marmosets without any added stimulator resulted in the appearance of megakaryocytes. These cells could not be identified by light microscopy or by indirect immunofluorescence using antiplatelet antiserum. Ultrastructural identification was made using platelet ...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830080108
更新日期:1980-01-01 00:00:00
abstract::The temporal development of the erythrocyte sedimentation rate (ESR) was studied in wide, short vacuum tubes. It was found that in about 3% of the specimens arriving in the laboratory the ESR developed in three different phases during 60 min, whereas the other showed only two. The specimens with three phases behaved s...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830370310
更新日期:1991-07-01 00:00:00
abstract::Mutation of the VHL tumor suppressor gene is a frequent genetic event in the carcinogenesis of renal-cell carcinoma (RCC). Circulating endothelial progenitor cells (EPCs) have important role in neoangiogenesis, and mobilization of these cells is induced by various growth factors including erythropoietin (EPO). With th...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.21019
更新日期:2008-02-01 00:00:00
abstract::Clinical management of lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM) has changed considerably over recent years, reflected in the use of new therapeutic agents (purine analogs, monoclonal antibodies, thalidomide- and bortezomib-based therapies). No population-based studies and few randomized tria...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.23351
更新日期:2013-01-01 00:00:00
abstract::Unprecedented advances in our understanding of the pathobiology, prognostication, and therapeutic options in mantle cell lymphoma (MCL) have taken place in the last few years. Heterogeneity in the clinical course of MCL-indolent vs aggressive-is further delineated by a correlation with the mutational status of the var...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.25487
更新日期:2019-06-01 00:00:00
abstract::With the emerging success of treating CD19 expressing B cell malignancies with ex vivo modified, autologous T cells that express CD19-directed chimeric antigen receptors (CAR), there is intense interest in expanding this evolving technology to develop effective modalities to treat other malignancies including solid tu...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.24794
更新日期:2017-09-01 00:00:00
abstract::The effect of the synthetic vasopressin derivative 1-desamino-8D-arginine vasopressin (DDAVP = desmopressin) on bleeding time was studied in three patients with Hermansky Pudlak syndrome. A good response was observed in this type of storage pool disease. DDAVP might be useful in managing the bleeding disorder found in...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830300307
更新日期:1989-03-01 00:00:00
abstract::Sickle cell disease (SCD) nephropathy and lower estimated glomerular filtration rate (eGFR) are risk factors for early mortality. Furthermore, rate of eGFR decline predicts progression to end-stage renal disease in many clinical settings. However, factors predicting renal function decline in SCD are poorly documented....
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.25263
更新日期:2018-12-01 00:00:00
abstract::Older patients with acute myeloid leukemia (AML) have poor outcomes, with median durations of complete remission lasting less than 1 year. Increased toxicity in older patients limits the delivery of standard consolidation therapies, such as allogeneic stem cell transplant or high-dose cytarabine. Azacitidine, a nucleo...
journal_title:American journal of hematology
pub_type: 杂志文章,多中心研究
doi:10.1002/ajh.24087
更新日期:2015-09-01 00:00:00
abstract::Serologic diagnosis for Epstein-Barr virus (EBV) infection is problematic when patients receive exogenous immunoglobulin. We recently diagnosed primary EBV infection by detecting EBV-determined nuclear antigen (EBNA) and EBV-DNA in peripheral blood mononuclear cells (PBMC) using immunofluorescence, in situ hybridizati...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830360416
更新日期:1991-04-01 00:00:00
abstract::Precursor B-ALL blasts may be positive for CD20 in up to 50% of cases. There are few reports on the use of the anti CD20 monoclonal antibody, rituximab, in children with B-ALL. We report on two adult patients with precursor B-ALL who developed significant hepatic toxicity during induction chemotherapy. Single agent ri...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.20675
更新日期:2006-12-01 00:00:00
abstract::Fetal calf serum (FCS) is used as a component of the media for cells grown in culture. However, the high cost of FCS has stimulated a search for a possible alternative. Approximately 10% of human platelet concentrates prepared for clinical transfusions are outdated. Sera prepared from platelet concentrates were compar...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830170104
更新日期:1984-07-01 00:00:00
abstract::After the patents of biopharmaceuticals have expired, based on specific regulatory approval pathways copied products ("biosimilars" or "follow-on biologics") have been launched in the EU. This article summarizes experiences with hematopoietic medicines, namely the epoetins (two biosimilars traded under five different ...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.21805
更新日期:2010-10-01 00:00:00
abstract:DISEASE OVERVIEW:The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic th...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.24102
更新日期:2015-09-01 00:00:00
abstract::Pulmonary hypertension (PH) of sickle cell disease (SCD), as defined by a tricuspid regurgitant jet velocity by echocardiogram of >or=2.5 m/sec, occurs in approximately 1/3 of HbSS adults and is an independent risk factor for mortality. Although studies of the past few years have greatly expanded our knowledge of the ...
journal_title:American journal of hematology
pub_type: 社论
doi:10.1002/ajh.21083
更新日期:2008-01-01 00:00:00
abstract::This study investigated the clinical characteristics and prognostic relevance of CD34 expression in 47 patients with acute promyelocytic leukemia (APL), showing t(15;17) or PML/RARalpha. Ten (21.3%) of the APL patients were CD34(+). CD34 expression was associated with hypogranular morphology (P = 0.002) and hyperleuko...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.10337
更新日期:2003-07-01 00:00:00
abstract::A case of red cell adenosine deaminase (ADA) overproduction associated with hereditary hemolytic anemia is reported here. This appears to be the second report. Proband is a 38-year-old Japanese male who had hemoglobin, 15.8 g/100 ml; reticulocyte count, 4.5%; serum indirect bilirubin, 4.9 mg/100 ml; 51Cr-labeled red c...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830050205
更新日期:1978-01-01 00:00:00
abstract::A 50-year-old woman with muscular fatigue and monoclonal gammopathy of unknown significance was shown to have high levels of antibodies against the acetylcholine receptor of the skeletal muscle endplate. The specific antibody activity was exclusively associated with the monoclonal component. There were no objective si...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830290112
更新日期:1988-09-01 00:00:00
abstract::Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in patients undergoing treatment for acute leukemia (AL). Antifungal prophylactic strategies are associated with significant toxicities and cost. We performed a retrospective study of the incidence and risk factors for IFD among patients n...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.21776
更新日期:2010-09-01 00:00:00
abstract::Most reports of prognosis and therapy in diffuse small non-cleaved cell lymphoma (DSNCL), an aggressive high-grade non-Hodgkin's lymphoma (NHL) which appears to be of two histopathologic subtypes, have included predominantly a pediatric population and very few adults. We studied 20 newly diagnosed, previously untreate...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830460408
更新日期:1994-08-01 00:00:00
abstract::The investigation of kindreds with recurrent thrombotic disease has advanced the understanding of the mechanisms of coagulation and fibrinolysis. In those cases where an etiology has been established, congenital thrombotic disorders are associated either with deficiencies or qualitative abnormalities in inhibitors of ...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.2830210411
更新日期:1986-04-01 00:00:00
abstract::Acute myeloid leukemia (AML) with mutated NPM1 is a newly recognized separate entity in the revised 2016 WHO classification, and is associated with a favorable prognosis. While previous studies have evaluated NPM1 in a binary fashion, we recently demonstrated a significant independent negative prognostic effect of hig...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.25544
更新日期:2019-08-01 00:00:00
abstract::Evaluation of pharmacologic agents that stimulate fetal hemoglobin production has been done mainly in baboons and macaques. We investigated whether results in transgenic mice can predict the stimulation of fetal hemoglobin in primates, by testing gamma globin induction in response to a new ribonucleotide reductase inh...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830450208
更新日期:1994-02-01 00:00:00
abstract::Regulatory T-cells (Tregs) are increased in chronic lymphocytic leukemia(CLL) and correlates with clinical and biological features of active/progressive disease. However, little is known about their ability to predict the time to first treatment (TFT). We evaluated 75 patients with Rai stage 0 CLL, in whom the absolut...
journal_title:American journal of hematology
pub_type: 信件
doi:10.1002/ajh.23170
更新日期:2012-06-01 00:00:00
abstract::Systemic light-chain (AL) amyloidosis may be associated with acquired factor X (FX) deficiency and optimal management of this coagulopathy is unknown. We reviewed our experience with 60 patients with isolated FX deficiency (< or =50%) due to AL amyloidosis that underwent an invasive procedure between 1975 and 2007. Th...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.21603
更新日期:2010-03-01 00:00:00
abstract::The activation pathways for the generation of enzymes involved in blood clotting, clot lysis, complement activation, and kinin generation are briefly reviewed. The interrelationship of the four systems is illustrated by the multiple functions of four key enzymes: Factor XIIa, kallikrein, plasmin, and C1 esterase. The ...
journal_title:American journal of hematology
pub_type: 杂志文章,评审
doi:10.1002/ajh.2830040412
更新日期:1978-01-01 00:00:00
abstract::In southeast Asia, the carrier frequency of two-gene alpha-thalassemia deletions is quite high, ranging from 4% to 14% depending on the population. The most common alpha-thalassemia-1 deletion is the so-called southeast Asian deletion (--(SEA)). In addition, a significant proportion of cases involve two other deletion...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/(sici)1096-8652(200001)63:1<54::aid-ajh12>
更新日期:2000-01-01 00:00:00
abstract::Specific anti-human thymus xenoantiserum (ATS) was utilized for characterizing a human thymus antigen (HTA) preferentially expressed on human thymocytes. Binding of ATS with different cell types was studied by immunofluorescence and immunoperoxidase techniques, as well as by radioimmunoprecipitation (RIP) followed by ...
journal_title:American journal of hematology
pub_type: 杂志文章
doi:10.1002/ajh.2830100206
更新日期:1981-01-01 00:00:00