Abstract:
OBJECTIVE:Differentiation-inducing therapy by agents such as 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) represents a useful approach for the treatment of acute myelogenous leukemia (AML). We previously showed that Gemini-23-yne-26,27-hexafluoro-D(3) inhibited the proliferation of MCF-7 breast cancer cells in association with inhibition of the mammalian target of rapamycin (mTOR) signaling. This study explored the drug interaction of 1,25(OH)(2)D(3) and rapamycin analog RAD001 (everolimus) in AML cells. MATERIALS AND METHODS:Effects of RAD001 and 1,25-(OH)(2)D(3) on the proliferation and differentiation of U937 cells were assessed by colony-forming assay and quantification of CD11b cell surface antigens and their endocytic capability, respectively. Effects of RAD001 and 1,25-(OH)(2)D(3) on Akt/mTOR complex-1 (mTORC1) signaling and cell-cycle-related molecules were explored by Western blot analysis. The reporter gene and chromatin immunoprecipitation assays were employed to examine the effects of RAD001 and 1,25-(OH)(2)D(3) on the promoter of the p21(waf1) gene. U937 murine xenograft model was utilized to explore the effects of RAD001 and 1,25-(OH)(2)D(3) in vivo. RESULTS:RAD001 potentiated the ability of 1,25(OH)(2)D(3) to induce growth arrest and differentiation of AML cells in parallel with downregulation of the levels of p-S6K and p-4E-BP1, substrates of mTORC1. In addition, RAD001 significantly enhanced 1,25(OH)(2)D(3)-mediated transcriptional activity of p21(waf1) in association with increased levels of the acetylated forms of histone H3 and vitamin D receptor bound to the p21(waf1) promoter in U937 cells. Moreover, RAD001 (3 mg/kg, every another day) significantly enhanced 1,25(OH)(2)D(3)-induced growth inhibition of U937 tumor xenografts in nude mice without adverse effects. CONCLUSIONS:Concomitant administration of 1,25(OH)(2)D(3) and the mTORC1 inhibitor may be a promising treatment strategy for individuals with AML.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Yang J,Ikezoe T,Nishioka C,Ni L,Koeffler HP,Yokoyama Adoi
10.1016/j.exphem.2010.03.020subject
Has Abstractpub_date
2010-08-01 00:00:00pages
666-76issue
8eissn
0301-472Xissn
1873-2399pii
S0301-472X(10)00136-0journal_volume
38pub_type
杂志文章abstract::CD34 is a cell-surface glycoprotein expressed in a developmental, stage-specific manner by bone marrow stem and progenitor cells. In this study we explored a possible role for c-Myb in CD34 regulation during developmental hematopoiesis. The results indicate that c-Myb can induce CD34 expression in hematopoietic and no...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-10-01 00:00:00
abstract:OBJECTIVE:Beta-thalassemia results from beta-globin gene mutations that lead to ineffective erythropoiesis, shortened red cell survival, and anemia. Patients with beta-thalassemia develop iron overload, despite which, hepcidin levels are low. This suggests that hepcidin regulation in beta-thalassemia is more sensitive ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.10.004
更新日期:2009-02-01 00:00:00
abstract::Recently, several human bone marrow stromal cell lines have established and produced hematopoietic growth factors. One of these factors, a burst-promoting activity (BPA), was purified from 6 liters of serum-free conditioned medium cultured from stromal cell line KM-102, which was stimulated by phorbol myristate acetat...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::Type IV nuclear bodies are classified as true intranuclear inclusions that ultrastructurally contain numerous densely packed 20- to 30-nm osmiophilic granules surrounded by a microfibrillar cortex. In the present study, we have found statistically significant ultrastructural differences in the frequency and size of ty...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-02-01 00:00:00
abstract::Previous studies have suggested that Steel factor (SF) can influence the behavior of many types of hematopoietic progenitor cells both in vivo and in vitro, although whether these may include the most primitive populations of totipotent repopulating cells remains controversial. To approach this question, we measured t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::The modulatory effect of 1,25 dihydroxyvitamin D3 (vit D) and 13 cis retinoic acid (retinoic acid) on the growth and differentiation of normal human pluripotent stem cell, erythroid, and myeloid progenitor cell growth was studied using semisolid methylcellulose clonal assay. Dose response curves showed that maximal in...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::The anemia of Belgrade b/b rats has been shown to be due to intracellular iron deficiency. The aim of this study of erythropoiesis at the progenitor cell level in these rats was to determine if a defect is present in the early phase of red cell production. Both erythroid colony-forming unit (CFU-E)- and erythroid burs...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-08-01 00:00:00
abstract::We have utilized two well-characterized human leukemia/lymphoma (LL) cell lines, UTMB-460 and CEM, to determine the role of integrin very late antigen-alpha 4 beta 1 (VLA-4) and its ligand vascular cell adhesion molecule-1 (VCAM-1) in the adherence of the LL cells to marrow stromal cells (MSC). Both these LL cell line...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract:OBJECTIVE:To investigate the role of perforin-mediated cell apoptosis in murine models of immune-mediated bone marrow (BM) failure. MATERIALS AND METHODS:We compared C57BL/6J (B6) mice carrying a perforin gene deletion (Prf(-/-)) with wild-type (WT) controls for cellular composition in lymphohematopoietic tissues. Lym...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.12.001
更新日期:2009-04-01 00:00:00
abstract::Vascular endothelial cells can affect hematopoiesis by releasing granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, we show that GM-CSF production in murine aorta-derived vascular endothelial cells is regulated by two cytokines:interleukin-1 (IL-1), which induces the production of GM-CSF,...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::Embryonic and adult stem cell populations have great potential value in medicine, and hematopoietic stem cells are already being used in transplantation. Definition of these populations to increase our understanding of the programs that control differentiation, self-renewal, and possibly plasticity would be of great i...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2003.08.012
更新日期:2003-12-01 00:00:00
abstract::Allogeneic bone marrow recipients exhibit a complex and multifactorial immunodeficiency affecting numerous effector functions for various periods of time. In order to evaluate their Fc-mediated monocyte-macrophage (MM) function we studied the clearance of IgG-coated Rh-positive erythrocytes (EA) in healthy control sub...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-10-01 00:00:00
abstract::The expression of exogenous genes in long-lived primary T cells is potentially beneficial for the treatment of various diseases including cancer, AIDS, genetic defects of the lymphoid compartment, and systemic enzyme deficiencies such as hemophilia. One approach for genetic modification of T cells is to introduce ther...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract:OBJECTIVE:New nonmyeloablative strategies to improve acceptance of mismatched bone marrow (BM) may compensate for the inadequate supply of compatible grafts. Recently we proposed to facilitate engraftment of mismatched BM by selective depletion of activated donor-reactive host cells with cyclophosphamide (CY). Here we ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.07.017
更新日期:2004-11-01 00:00:00
abstract::The pool size of erythroid burst-(BFUe) and colony-forming units (CFUe) has been evaluated in normal or hypoxia-induced polycythemic mice at sequential times after either transfusion or administration of purified erythropoietin (Ep). The present investigations were focused on the in vitro tritiated thymidine (3H-TdR) ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-01-01 00:00:00
abstract::The ectopic implantation of mouse marrow to the kidney capsule offers considerable scope as an assay of the hemopoietic microenvironment. Our previous work has shown that whole-body irradiation of the graft recipient prior to implantation results in superior ossicle formation in the kidney of the host. Here we report ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-07-01 00:00:00
abstract::When cultured mast cells of (WB X C57BL/6)F1-+/+(WBB6F1-+/+) and WB-+/+(WB) mice were directly injected into the skin of genetically mast cell-deficient WBB6F1-W/Wv mice, mast cell clusters appeared at the injection sites. Although in vitro colony-forming ability is comparable between cultured mast cells of WB mice an...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-12-01 00:00:00
abstract::The relationship between the hematopoietic stem cell (HSC) population and its surrounding bone marrow microenvironment is a rapidly evolving area of research. Normal HSC processes rely heavily on a complex communication network involving various marrow niches. Although leukemogenesis largely results from abnormal gene...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2018.07.001
更新日期:2018-10-01 00:00:00
abstract::Collagen gel was used as a substance for the assay of human granulocyte-macrophage colony-forming units (CFUc). The number of colonies formed in collagen gel was consistently higher than that in a conventional soft-agar system. In six out of eight experiments, the difference was statistically significant. Whole perman...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract::Granulocyte colony-stimulating factor (G-CSF) has proven effective in the prophylaxis of chemotherapy-induced neutropenia and as a mobilizer of peripheral blood progenitor cells. The longevity of G-CSF action is limited by its removal from the body by two mechanisms. The first is thought to be mediated via receptors (...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00112-5
更新日期:1999-12-01 00:00:00
abstract::Chloramphenicol, an antibiotic associated with reversible bone marrow suppression and fatal aplastic anemia, was found to increase human bone marrow granulocyte-macrophage colonies (CFU-GM) in vitro. Maximal stimulation was at a concentration of 1.0 micrograms/ml (3.1 microM), with inhibition at concentrations greater...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-02-01 00:00:00
abstract::The use of neonatal instead of fetal calf serum, as a constituent of the culture medium, confronted the authors with the problem of toxicity in the fetal liver cell erythropoietin assay. Tested human sera were toxic at rather low concentrations. Heating the human sera for 30 min at 56 degrees C abolished the toxicity....
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1976-05-01 00:00:00
abstract:OBJECTIVE:Progenipoietin-1 is an agonist of both the granulocyte colony-stimulating factor and fetal liver tyrosine kinase-3 receptors capable of inducing the proliferation of multiple hematopoietic cell lineages. The potential of progenipoietin-1 to mobilize transplantable hematopoietic stem cells into the peripheral ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00675-0
更新日期:2001-08-01 00:00:00
abstract::The megakaryocytopoiesis in rats was studied following a single dose of thio-TEPA to determine the mechanisms for the thrombocytopenia and subsequent recovery. The blood platelet number, platelet production (measured by 35S incorporation into platelets), mean platelet volume, and the number and DNA content of bone mar...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::Acute disseminated intravascular coagulation (DIC) is a life-threatening condition that may be encountered in many situations, especially in cases of shock with uncontrollable hemorrhage. Anisodamine, an alkaloid extracted from a Chinese herb, is well known for its dramatic therapeutic effect on DIC. Sixty male rabbit...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::The effect of recombinant interleukin 3 (IL-3) on the function of murine resident peritoneal macrophages was investigated. IL-3 enhanced the phagocytosis of Candida pseudotropicalis and Candida albicans and enhanced killing of the former. The enhanced killing is inhibited by scavengers of oxygen radicals, suggesting t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-09-01 00:00:00
abstract::Cyclooxygenase (COX) plays a key regulatory role in prostaglandin synthesis. COX-2 is inducible and is the major isoform of inflammatory cells. COX-2-deficient mice were shown to have normal basal hematopoiesis and hematology. We hypothesized that COX-2 induction plays a role in the recovery phase of 5-fluorouracil (5...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00087-9
更新日期:1999-10-01 00:00:00
abstract:OBJECTIVE:The CD15 (Lewis x) cell surface oligosaccharide moiety is expressed in a variety of normal and tumor cells and recognized by selectins. The detection of CD15 on malignant Hodgkin-Reed-Sternberg (HRS) cells serves as a diagnostic marker of Hodgkin's lymphoma (HL). Retrospective studies suggest that the express...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00237-6
更新日期:2003-11-01 00:00:00
abstract:OBJECTIVE:We previously demonstrated the presence of nucleoside diphosphate kinase NDPK/NM23 in normal human plasma. It also was reported that extracellular NM23 could inhibit differentiation of certain hematopoietic cell lines. We further investigated the extracellular effect of NM23 on hematopoiesis by adding recombi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00809-3
更新日期:2002-07-01 00:00:00
abstract:OBJECTIVE:Mobilized peripheral blood (PB) progenitors are increasingly used in autologous and allogeneic transplantation. However, the short- and long-term engraftment potential of mobilized PB or bone marrow (BM) has not been directly compared. Although several studies showed that BM-derived Lin(-)CD34(-) cells contai...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00506-3
更新日期:2000-09-01 00:00:00