Abstract:
:Primary effusion lymphoma (PEL) constitutes a subset of non-Hodgkin lymphoma whose incidence is highly increased in the context of HIV infection. Kaposi sarcoma-associated herpesvirus is the causative agent of PEL. The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays a critical role in cell proliferation and survival, and this pathway is dysregulated in many different cancers, including PEL, which display activated PI3K, Akt, and mammalian target of rapamycin (mTOR) kinases. PELs rely heavily on PI3K/Akt/mTOR signaling, are dependent on autocrine and paracrine growth factors, and also have a poor prognosis with reported median survival times of less than 6 months. We compared different compounds that inhibit the PI3K/Akt/mTOR pathway in PEL. Although compounds that modulated activity of only a single pathway member inhibited PEL proliferation, the use of a novel compound, NVP-BEZ235, that dually inhibits both PI3K and mTOR kinases was significantly more efficacious in culture and in a PEL xenograft tumor model. NVP-BEZ235 was effective at low nanomolar concentrations and has oral bioavailability. We also report a novel mechanism for NVP-BEZ235 involving the suppression of multiple autocrine and paracrine growth factors required for lymphoma survival. Our data have broad applicability for the treatment of cytokine-dependent tumors with PI3K/mTOR dual inhibitors.
journal_name
Bloodjournal_title
Bloodauthors
Bhatt AP,Bhende PM,Sin SH,Roy D,Dittmer DP,Damania Bdoi
10.1182/blood-2009-10-251082subject
Has Abstractpub_date
2010-06-03 00:00:00pages
4455-63issue
22eissn
0006-4971issn
1528-0020pii
blood-2009-10-251082journal_volume
115pub_type
杂志文章相关文献
BLOOD文献大全abstract::Hypodiploidy <40 chromosomes is an uncommon genetic feature of acute lymphoblastic leukemia (ALL) in both children and adults. It has long been clear by cytogenetic analyses, and recently confirmed by mutational profiling, that these cases may be further subdivided into 2 subtypes: near-haploid ALL with 24 to 30 chrom...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2016-10-743765
更新日期:2017-01-26 00:00:00
abstract::Anemia and neutropenia often develop in cats that are infected with the feline immunodeficiency virus (FIV), a lentivirus biologically similar to the human immunodeficiency virus (HIV). To assess the role of FIV in the pathogenesis of these abnormalities, marrow culture studies were performed on nine asymptomatic, hem...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-10-15 00:00:00
abstract::Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-08-01 00:00:00
abstract::The relationship between class switch recombination (CSR) and somatic hypermutation has been unclear. By using human CD27(-) naive B cells, we investigated the somatic hypermutation and producibility of immunoglobulins (Igs) that occur after CSR. Although neither adult CD27(-) nor cord blood B cells, which showed the ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.2.567
更新日期:2002-01-15 00:00:00
abstract::The human interleukin-3 receptor (IL-3R) is expressed on myeloid, lymphoid, and vascular endothelial cells, where it transduces IL-3-dependent signals leading to cell activation. Although IL-3R activation may play a role in hematopoiesis and immunity, its aberrant expression or excessive stimulation may contribute to ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::We have examined the effect of graft-versus-host disease (GVHD) on the reconstitution of donor hematopoiesis in a murine bone marrow transplant (BMT) model of GVHD to minor histocompatibility antigens. GVHD had no effect on peripheral blood counts, which normalized by 1 month after BMT, and did not affect numbers of h...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-11-15 00:00:00
abstract::There are many reports in the literature of blood test abnormalities occurring in patients with venous or arterial thrombosis. Most of these have not used acceptable criteria for establishing an association between thrombosis and blood tests and, therefore, their interpretation is questionable. Recently, sensitive and...
journal_title:Blood
pub_type: 杂志文章,评审
doi:
更新日期:1981-01-01 00:00:00
abstract::The LAZ3 gene encodes a novel zinc-finger protein that shares homology with several Drosophila transcription factors. This gene was identified by its disruption in translocations involving chromosome 3q27 in diffuse large-cell lymphomas. To assess the frequency and role of this gene's involvement in lymphomagenesis an...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-05-15 00:00:00
abstract::Retinoids triggers differentiation of acute promyelocytic leukemia (APL) blasts by transcriptional regulation of myeloid regulatory genes. Using a microarray approach, we have identified a novel retinoid-responsive gene (CXXC5) encoding a nuclear factor, retinoid-inducible nuclear factor (RINF), that contains a CXXC-t...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-07-170035
更新日期:2009-04-02 00:00:00
abstract::Interleukin 2 (IL-2) rescued human natural killer (NK) KHYG-1 cells from apoptosis along with a reduction of ceramide. Conversely, an increase of ceramide inhibited IL-2-rescued survival. IL-2 deprivation-induced activation of acid sphingomyelinase (SMase) and inhibition of glucosylceramide synthase (GCS) and sphingom...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-03-0900
更新日期:2004-11-15 00:00:00
abstract::CD4+CD25+ regulatory T (Treg) cells are potent modulators of alloimmune responses. In murine models of allogeneic bone marrow transplantation, adoptive transfer of donor CD4+CD25+ Treg cells protects recipient mice from lethal acute graft-versus-host disease (aGVHD) induced by donor CD4+CD25- T cells. Here we examined...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-05-2044
更新日期:2005-03-01 00:00:00
abstract::The myelodysplastic syndromes (MDSs) are hematologically diverse hematopoietic stem cell malignancies primarily affecting older individuals. The incidence of MDS in the United States is estimated at 3.3 per 100 000; however, evidence suggests underreporting of MDS to centralized cancer registries. Contrary to clinical...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-02-337964
更新日期:2011-06-30 00:00:00
abstract::Hematopoietic suppression is one of the serious problems induced by whole body irradiation. Granulocyte colony-stimulating factor (G-CSF) stimulates the progenitors of granulocytes and accelerates their recovery from bone marrow suppression induced by cytotoxic chemotherapy or radiation. On the other hand, G-CSF stimu...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::To assess the frequency and significance of nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia (ALL), we analyzed our experience with 398 consecutive cases with completely banded karyotypes. Forty cases (10%) with abnormalities of 9p were identified: 26 with deletions, nine with unbalan...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::We previously showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) stimulate the differentiation of human monocytes into two phenotypically distinct types of macrophages. However, in vivo, not only CSF but also many other cytokines are produced under va...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-11-15 00:00:00
abstract::Affinity purified anticardiolipin antibodies (ACLA) raised in rabbits showed cross-reactivities with various negatively charged phospholipids as shown by both the solid phase enzyme-linked immunosorbent assay (ELISA) and inhibition studies. In ELISA, ACLA showed strong cross-reactivity to both sphingomyelin (SM) and p...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-12-15 00:00:00
abstract::To clarify the nature of null cell acute lymphoblastic leukemia (ALL) we tested null lymphoblasts and other leukemic cells for human T and B lymphocyte antigens detected by reciprocally absorbed rabbit antisera prepared against autologous T and B lymphoblast cell lines HSB-2 and SB. Blasts from 4 of 4 patients with T ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1977-03-01 00:00:00
abstract::Regulated adherence of polymorphonuclear leukocytes (PMNs) to endothelium and subendothelial matrix is a critical event for PMN localization at and migration into inflammatory sites. We previously reported that human PMNs stimulated in vitro adhere to laminin, the major glycoprotein of mammalian basement membrane, by ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-03-15 00:00:00
abstract::T-cell development requires a series of discrete selection and activation signals delivered to maturing progenitors in the thymic cortex and medulla. We have previously shown the constitutive activity of the integrin, alpha4beta1 (VLA4), on a unique subpopulation of immature cortical thymocytes and proposed a role for...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::Chronic graft-versus-host disease (GVHD) requires long-term immunosuppressive therapy after hematopoietic cell transplantation. We retrospectively analyzed a cohort of 751 patients with chronic GVHD to identify characteristics associated with the duration of immunosuppressive treatment. Among the 274 patients who disc...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-01-0200
更新日期:2004-12-01 00:00:00
abstract::The principal aim of our study was to investigate whether patients transplanted more than 20 years ago for β-thalassemia major had a different health-related quality of life (HRQoL) compared with the general population. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Functional Assessment o...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-05-502658
更新日期:2013-09-26 00:00:00
abstract::Nitric oxide is a short-lived reactive mediator that inhibits bone marrow (BM) cell proliferation induced by granulocyte-macrophage colony-stimulating factor (GM-CSF). The present studies show that nitric oxide also inhibits macrophage colony-stimulating factor (M-CSF)-induced growth of mouse BM cells, an effect that ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::Terminal erythroid differentiation starts from morphologically recognizable proerythroblasts that proliferate and differentiate to generate red cells. Although this process has been extensively studied in mice, its characterization in humans is limited. By examining the dynamic changes of expression of membrane protei...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-01-476390
更新日期:2013-04-18 00:00:00
abstract::Hydroxyurea, interferon, and HLA-identical sibling bone marrow transplantation are common therapies for chronic myelogenous leukemia (CML) in chronic phase. Which is best is controversial. The purpose of this study was to compare survival of patients with CML receiving HLA-identical sibling transplants versus hydroxyu...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1998-03-01 00:00:00
abstract::MCL-1 is a Bcl-2 family member that has been described as antiapoptotic in various myeloid neoplasms. Therefore, MCL-1 has been suggested as a potential new therapeutic target. Systemic mastocytosis (SM) is a myeloid neoplasm involving mast cells (MCs) and their progenitors. In the present study, we examined the expre...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-07-032714
更新日期:2007-04-01 00:00:00
abstract::To examine the role of the fibrinogen gamma chain in the assembly and secretion of this multichain protein, we synthesized a series of fibrinogen variants with truncated gamma chains, terminating between residues gamma379 and the C-terminus, gamma411. The variant fibrinogens were synthesized from altered gamma-chain c...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.10.3654
更新日期:2002-05-15 00:00:00
abstract::Thirty-two patients treated on consecutive Southwest Oncology Group (SWOG) protocols for malignant lymphoma were subsequently diagnosed as having lymphoblastic lymphoma. Combination chemistry, usually adriamycin-based, produced complete responses (CR) in 17 patients (53%). Median survival was 15 mo. Patients achieving...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1981-01-01 00:00:00
abstract::Highly purified natural killer (NK) cell suspensions were tested for their capacity to release colony-stimulating activity (CSA) in vitro. NK cell suspensions comprised primarily CD16+ cells and were devoid of CD3+ T cells, CD15+ monocytes, and of B cells. CSA was detected in the NK cell supernatants and sustained the...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::A strategy to phenotype rare populations of hematopoietic cells expressing the cell-surface marker CD34 was studied. The antigenic phenotype of umbilical core blood (CB) CD34+ cells was investigated using flow cytometry and compared with the mRNA-phenotype determined by cDNA-polymerase chain reaction (cDNA-PCR) analys...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-04-15 00:00:00
abstract::We previously reported the characterization of human osteoclast-associated receptor (hOSCAR), a novel Fc receptor gamma-chain (FcRgamma)-associated receptor expressed by myeloid cells. Here we show that ligation of hOSCAR by specific antibodies promotes dendritic cell (DC) survival by an extracellular signal-regulated...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-07-2809
更新日期:2005-05-01 00:00:00