Abstract:
:Oncogenic RAS alleles encode proteins that accumulate in the guanosine triphosphate (GTP)-bound state. Because post-translational processing of Ras by farnesyltransferase is essential for biologic function, inhibitors of this enzyme have been developed as rational cancer therapeutics. We have investigated farnesyltransferase inhibitor (FTI) L-744,832 in an in vivo murine model of myeloid leukemia that is associated with inactivation of the Nf1 tumor suppressor gene. Nf1 encodes a GTPase activating protein for Ras, and Nf1-deficient (Nf1-/-) hematopoietic cells show hyperactive Ras signaling through the mitogen-activated protein (MAP) kinase pathway. L-744,832 inhibited H-Ras prenylation in cell lines and in primary hematopoietic cells and abrogated the in vitro growth of myeloid progenitor colonies in response to granulocyte-macrophage colony-stimulating factor (GM-CSF). This FTI also partially blocked GM-CSF-induced MAP kinase activation, but did not reduce constitutively elevated levels of MAP kinase activity in primary Nf1-/- cells. Injection of a single dose of 40 or 80 mg/kg of L-744, 832 increased the amount of unprocessed H-Ras in bone marrow cells, but had no detectable effect on N-Ras. Adoptive transfer of Nf1-/- hematopoietic cells into irradiated mice induces a myeloproliferative disorder that did not respond to L-744,832 treatment. We speculate that the lack of efficacy in this model is due to the resistance of N-Ras and K-Ras processing to inhibition by this FTI.
journal_name
Bloodjournal_title
Bloodauthors
Mahgoub N,Taylor BR,Gratiot M,Kohl NE,Gibbs JB,Jacks T,Shannon KMsubject
Has Abstractpub_date
1999-10-01 00:00:00pages
2469-76issue
7eissn
0006-4971issn
1528-0020journal_volume
94pub_type
杂志文章相关文献
BLOOD文献大全abstract::We have performed a retrospective analysis of the development of T- and B-cell functions after HLA-nonidentical T-cell-depleted bone marrow transplantation (BMT) performed in 193 patients with severe combined immunodeficiency (SCID) at 18 European centers between December 1982 and December 31, 1993. One hundred sixtee...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:
更新日期:1998-05-15 00:00:00
abstract::Since its approval in 2011, the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib has evolved to become the centerpiece of therapy for myelofibrosis (MF), and its use in patients with hydroxyurea resistant or intolerant polycythemia vera (PV) is steadily increasing. Several other JAK2 inhibitors have entered clinical te...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2017-04-742288
更新日期:2017-07-13 00:00:00
abstract::Coagulation factors VII (FVII), IX (FIX), X (FX), and protein C share the same domain organization but display very different plasma half-lives. It is plausible that the half-life is influenced by the activation peptide, differing in length and glycosylation and missing in FVII. To test this hypothesis, the influence ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-06-290098
更新日期:2011-03-24 00:00:00
abstract::The role of hematopoietic growth factors in lineage commitment and differentiation is unclear. We present evidence that heterologous expression of an erythroid specific receptor allows granulocytic differentiation of a myeloid cell line. We have previously characterized a truncation mutant of the erythropoietin recept...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-08-15 00:00:00
abstract::We tested the ability of CD34+lin- precursor cells isolated from marrow after treatment with 4-hydroperoxycyclophosphamide (4HC) to generate colony-forming cells (CFC). In liquid cultures, recombinant human stem cell factor (SCF), in combination with interleukin-1 (IL-1), IL-3, IL-6, granulocyte-macrophage colony-stim...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::The POEMS syndrome (polyradiculoneuropathy, organomegaly, multiple endocrinopathies, monoclonal protein, skin changes) is a rare disease associated with a plasma cell dyscrasia. Patients with disseminated POEMS can be treated with high-dose therapy and autologous stem cell transplantation (ASCT). While clinical improv...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-04-423178
更新日期:2012-07-05 00:00:00
abstract::Allogeneic stem cell transplantation (SCT) is a unique procedure, primarily in patients with hematopoietic malignancies, involving chemoradiotherapy followed by the introduction of donor hematopoietic and immune cells into an inflamed and lymphopenic environment. Interruption of the process by which recipient alloanti...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2016-02-697250
更新日期:2016-06-16 00:00:00
abstract::The effect of shear force (depending on shear rate and viscosity of extracellular medium) and hematocrit of RBC suspension on RBC deformation was studied quantitatively using a cone-plate rheoscope with various kinds of cells, ie, partially hemolyzed (PH) cells, density-fractionated intact cells, and diamide-treated c...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-03-01 00:00:00
abstract::Protein C is activated by thrombin with a value of k(cat)/K(m) = 0.11mM(-1)s(-1) that increases 1700-fold in the presence of the cofactor thrombomodulin. The molecular origin of this effect triggering an important feedback loop in the coagulation cascade remains elusive. Acidic residues in the activation domain of pro...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-03-415323
更新日期:2012-07-19 00:00:00
abstract::The nuclear factor-kappa B (NF-kappaB) gene transactivator serves in the formation of immune, inflammatory, and stress responses. In quiescent cells, NF-kappaB principally resides within the cytoplasm in association with inhibitory kappa (IkappaB) proteins. The status of IkappaB and NF-kappaB proteins was evaluated fo...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
abstract::Genome and transcriptome sequencing have revealed a rich assortment of noncoding RNAs in eukaryote cells, including long noncoding RNAs (lncRNAs), which regulate gene expression independent of protein coding potential. LncRNAs modulate protein coding gene expression in many cell types by regulating multiple processes,...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2013-03-456111
更新日期:2013-06-13 00:00:00
abstract::Factor VII levels have been studied in hemophilia A and B plasmas and normal controls in a controlled, prospective study. Three assay methods were used: a standard clotting assay (FVIIc-A); a modified clotting assay (FVIIc-B) (Seligsohn et al, Blood 52:978-988, 1978); and a coupled amidolytic assay. By the FVIIc-B ass...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-04-01 00:00:00
abstract::Dendritic cells (DCs) express many endocytic receptors that deliver antigens for major histocompatibility class (MHC) I and II presentation to CD8(+) and CD4(+) T cells, respectively. Here, we show that targeting Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) to one of them, the human multilectin DEC-205 receptor,...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-03-148072
更新日期:2008-08-15 00:00:00
abstract::Familial hemophagocytic lymphohistiocytosis (FHL) is a rare genetic disorder associated with the onset early in life of overwhelming activation of T lymphocytes and macrophages invariably leading to death. Allogeneic bone marrow transplantation (BMT) from an HLA-identical related donor is the treatment of choice in pa...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-12-15 00:00:00
abstract::We have developed a new helper-dependent (HD) adenoviral vector FTC that contains 3 cis-acting sequences as stuffer DNA: a human fragment of alphoid repeat DNA, matrix-attachment regions (MARs), and the hepatocyte control region enhancer. To determine the most robust human coagulation factor IX (hFIX) expression casse...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.11.3923
更新日期:2002-06-01 00:00:00
abstract::Pharmacologic and immunologic methods of ex-vivo bone marrow (BM) purging for acute nonlymphocytic leukemia (ANLL) were combined to augment the effect of either method alone. Etoposide (VP16; 20 to 30 micrograms/mL) with or without cytosine arabinoside (Ara C; 10 mg/mL) was used in tandem with the anti-CD33 monoclonal...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-01-15 00:00:00
abstract::The primitive hematopoietic stem/progenitor cells (HSPCs) during embryonic hematopoiesis are thought to be short-lived (SL) with limited self-renewal potential. The fate and consequence of these short-lived HSPCs, once reprogrammed into "long-lived" in a living animal body, remain unknown. Here we show that targeted e...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-12-327908
更新日期:2011-10-06 00:00:00
abstract::To elucidate the role of retinoic acid (RA) in anti-CD40 + interleukin-4 (IL-4)-mediated B-cell activation, the effect of 10(-12) to 10(-6) mol/L RA was studied in anti-CD40 (1 microgram/mL) + IL-4 (5 ng/mL)-mediated proliferation and Ig synthesis by human peripheral blood mononuclear cells (PBMC) and B cells in healt...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
abstract::To obtain information relevant to the question of bone marrow transplantation, we examined the prognostic significance of disease features recorded at the time of diagnosis among 625 patients, aged 5 to 45, with Philadelphia chromosome-positive, nonblastic chronic granulocytic leukemia. The actuarial death rate for th...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-12-01 00:00:00
abstract::Investigators in the United Kingdom have shown that hereditary amyloidosis can be misdiagnosed as Ig light-chain (AL) amyloidosis because family history is an ineffective screen, and tissue staining used to type amyloid is unreliable. Misdiagnosis of AL can lead to inappropriate use of chemotherapy and failure to diag...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-10-4148
更新日期:2006-05-01 00:00:00
abstract::Localized tumors composed of immature cells of the myelogenous series have been recognized for many years as an uncommon manifestation of granulocytic leukemia. The histologic diagnosis of chloroma (granulocytic sarcoma) may be extremely difficult when the myeloblastic cells are poorly differentiated and the tumor lac...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1980-07-01 00:00:00
abstract::We have analyzed the binding of Sp1, a ubiquitously expressed transactivator, to the promoter region of the gamma genes. Low-affinity Sp1 sites were found at -50 and -200. A high-affinity site was detected at -140, over the CACCC sequence. To analyze the function of these sites, Drosophila SL-2 cells, which lack Sp1, ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::The extended use of brentuximab-vedotin was reported for CD30(+) nonanaplastic peripheral T-cell lymphomas (PTCLs) with promising efficacy. CD30 status assessment is thus a critical factor for therapeutic decision, but the reliability of immunohistochemistry (IHC) in evaluating its expression remains to be defined. Th...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-07-584953
更新日期:2014-11-06 00:00:00
abstract::We investigated the effects of granulocyte colony-stimulating factor (G-CSF) on cytokine and cytokine receptor plasma levels and on the in vivo host response to Salmonella abortus equi endotoxin in healthy males. Twenty volunteers received 0.8 ng/kg endotoxin and saline intravenously 1 week apart in randomized order. ...
journal_title:Blood
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1996-02-01 00:00:00
abstract::We assessed primary cutaneous large B-cell lymphoma, leg type (PCLBCL, leg type; n = 13), and primary cutaneous follicle center lymphoma (PCFCL; n = 19) for somatic hypermutation (SHM) of BCL6, and aberrant SHM of MYC, RhoH/TTF, and PAX5. We demonstrate SHM of BCL6 in 8 PCLBCLs (62%), leg type, and 7 PCFCL patients (3...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-08-3443
更新日期:2006-06-15 00:00:00
abstract::The plasminogen activator inhibitor PAI-1 is markedly elevated in vivo and in vitro upon exposure to the inflammatory mediators tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), and bacterial lipopolysaccharide. Here we report that the isoflavone compound genistein prevents the increase in synthesis of PA...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::The CXC-chemokines interleukin-8 (IL-8), neutrophil-activating peptide-2 (NAP-2), and melanoma growth-stimulatory activity (MGSA) are chemoattractants with high selectivity for neutrophils. Although IL-8 has been shown to act as an extremely potent mediator, reports on NAP-2 and MGSA are still contradictory. Here we s...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-12-01 00:00:00
abstract::Little is known about mechanisms involved in skin-specific homing of cutaneous T-cell lymphoma (CTCL). Chemokine/chemokine receptor interactions have been implicated in the homing of lymphoma cells to various tissue sites. We investigated tissue samples and tumor cell suspensions of patients with CD30(+) CTCL (n = 8) ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-02-0475
更新日期:2003-02-15 00:00:00
abstract::Leukemia in infants is rare but generates tremendous interest due to its aggressive clinical presentation in a uniquely vulnerable host, its poor response to current therapies, and its fascinating biology. Increasingly, these biological insights are pointing the way toward novel therapeutic approaches. Using represent...
journal_title:Blood
pub_type: 杂志文章,随机对照试验
doi:10.1182/blood-2018-04-785980
更新日期:2019-01-17 00:00:00
abstract::Factor VIII (FVIII) functions as a cofactor within the intrinsic pathway of blood coagulation. Quantitative or qualitative deficiencies of FVIII result in the inherited bleeding disorder hemophilia A. Expression of FVIII (domain structure A1-A2-B-A3-C1-C2) in heterologous mammalian systems is 2 to 3 orders of magnitud...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-10-3591
更新日期:2004-05-01 00:00:00