Abstract:
:A series of alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation is considered to be the main cause of cancer. These mutational events include activation of oncogenes and inactivation of tumor suppressor genes. The elucidation of human cancer at the molecular level allows the design of rational, mechanism-based therapeutic agents that antagonize the specific activity of biochemical processes that are essential to the malignant phenotype of cancer cells. Because the frequency of RAS mutations is among the highest for any gene in human cancers, development of inhibitors of the Ras-mitogen-activated protein kinase pathway as potential anticancer agents is a very promising pharmacologic strategy. Inhibitors of Ras signaling have been shown to revert Ras-dependent transformation and cause regression of Ras-dependent tumors in animal models. The most promising new class of these potential cancer therapeutics are the farnesyltransferase inhibitors. The development of these compounds has been driven by the observation that oncogenic Ras function is dependent upon posttranslational modification, which enables membrane binding. In contrast to many conventional chemotherapeutics, farnesyltransferase inhibitors are remarkably specific and have been demonstrated to cause no gross systemic toxicity in animals. Some orally bioavailable inhibitors are presently being evaluated in phase II clinical trials. This review presents an overview on some inhibitors of the Ras signaling pathway, including their specificity and effectiveness in vivo. Because Ras signaling plays a crucial role in the pathogenesis of some hematologic malignancies, the potential therapeutic usefulness of these inhibitors is discussed. (Blood. 2000;96:1655-1669)
journal_name
Bloodjournal_title
Bloodauthors
Reuter CW,Morgan MA,Bergmann Lsubject
Has Abstractpub_date
2000-09-01 00:00:00pages
1655-69issue
5eissn
0006-4971issn
1528-0020journal_volume
96pub_type
杂志文章,评审相关文献
BLOOD文献大全abstract::The human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) introduced in association with the luciferase reporter gene into Jurkat T cells was strongly activated by a combination of human neutrophils and phorbol myristate acetate (PMA). Activation was not observed when normal neutrophils were replaced ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract::The most frequently recurring translocations in mucosa-associated lymphoid tissue (MALT) B-cell non-Hodgkin lymphoma, t(11;18)(q21;q21) and t(14;18)(q32; q21), lead to formation of an API2-MALT1 fusion or IgH-mediated MALT1 overexpression. Various approaches have implicated these proteins in nuclear factor kappaB (NF-...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-06-2297
更新日期:2005-04-01 00:00:00
abstract::Peripheral blood progenitor cells (PBPCs) are increasingly being used to replace bone marrow cells (BMCs) as a source of hematopoietic stem cells also in the field of allogeneic transplantation. Whereas it is well known that PBPC grafts and BM differ significantly in progenitor cell content and lymphocyte dose, the cl...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-08-15 00:00:00
abstract::The W locus of mice encodes the c-kit receptor tyrosine kinase. Heterozygous WJic/+ and Wn/+ mice and homozygous Wf/Wf mice were similar in appearance; all of them have large depigmented areas lacking any well-defined pattern. The WJic, Wn, and Wf mutant alleles were characterized and their molecular nature was correl...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-05-15 00:00:00
abstract::The bcl-2 gene is translocated into the Ig loci in about 80% of human follicular lymphomas and in 10% of B-type chronic lymphocytic leukemias (B-CLL), resulting in a high level of expression. We have compared the expression of bcl-2 transcripts and protein in B-CLL cells in their normal equivalent CD5+ B cells and in ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::The calcium ionophore A23187 promotes histamine synthesis in murine bone marrow cells by increasing the expression of mRNA encoding histidine decarboxylase (HDC), the histamine-forming enzyme. The cells responsible for this biological activity copurify with hematopoietic progenitors in terms of density, light scatter ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-04-15 00:00:00
abstract::The purpose of this study was to compare transplantation outcomes in patients with hematologic malignancies who received marrow grafts from either phenotypically matched unrelated, one-antigen-mismatched unrelated, or highly human leukocyte antigen (HLA)-disparate family donors. Between 1993 and 2000, 139 patients und...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.3.806
更新日期:2002-02-01 00:00:00
abstract::We have isolated and characterized the human cardiac mast cell (CMC) and compared this novel mast cell (MC type with MC obtained from uterus, skin, and lung. Heart tissue was obtained from 14 patients with cardiomyopathy (CMP, heart transplantation). CMC were isolated by enzymatic digestion using collagenase, pronase-...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::For many in vivo gene therapy clinical applications, it is desirable to control the expression of the transferred transgene using pharmacologic agents. To evaluate the feasibility of accomplishing this using corticosteroids, pharmacologic agents widely used in clinical medicine, we constructed replication deficient ad...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::Identification of the regulatory inputs that direct megakaryocytopoiesis and platelet production is essential for the development of novel therapeutic strategies for the treatment of thrombosis and related hematologic disorders. We have previously shown that primary human megakaryocytes express the N-methyl-d-aspartat...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-11-3553
更新日期:2003-08-15 00:00:00
abstract::Infection with human T-cell leukemia virus type II (HTLV-II) has been associated with rare chronic T-cell malignancies and has recently been demonstrated in a significant proportion of American intravenous drug abusers (IVDA). Identification of an HTLV-II-infected cohort of IVDA has allowed analysis of the HTLV-II car...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-07-15 00:00:00
abstract::Numerous studies have reported significant associations between ABO blood group and risk of cardiovascular disease. These studies have consistently demonstrated that thrombotic risk is significantly reduced in individuals in blood group O. Nevertheless, the biological mechanisms through which ABO influences hemostasis...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2020005843
更新日期:2020-12-17 00:00:00
abstract::Severe elevation of red blood cell number is often associated with hypertension and thromboembolism resulting in severe cardiovascular complications. However, some individuals such as high altitude dwellers cope well with an increased hematocrit level. We analyzed adaptive mechanisms to excessive erythrocytosis in our...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-01-0283
更新日期:2003-09-15 00:00:00
abstract::Tumor angiogenesis is crucial for the progression and metastasis of cancer. The vasculature of tumor tissue is different from normal vasculature. Therefore, tumor vascular targeting therapy could represent an effective therapeutic strategy with which to suppress both primary tumor growth and tumor metastasis. The use ...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2005-10-4114
更新日期:2006-04-15 00:00:00
abstract::Lymphomas afflict all age groups of people, with certain types demonstrating a female predilection in adolescents and young adults. A proportion of lymphomas that are diagnosed in this population demographic occur in the setting of pregnancy. Most of these behave aggressively at presentation and require immediate or u...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019000961
更新日期:2020-11-05 00:00:00
abstract::The present studies investigated the effects of the recently cloned flt3 ligand (FL) on the in vitro growth and differentiation of primitive and committed subsets of human CD34+ bone marrow (BM) progenitor cells. FL alone was a weak growth stimulator of CD34+ BM cells, but synergistically and directly enhanced colony ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-02-15 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::The receptor for hyaluronic acid-mediated motility (RHAMM) is an antigen eliciting both humoral and cellular immune responses in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). We initiated a phase 1 clinical trial vaccinating 10 patients with R3 (ILSLELMKL), a hi...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-07-099366
更新日期:2008-02-01 00:00:00
abstract::Lipoprotein (a) [Lp(a)] has been associated with both anti-fibrinolytic and atherogenic effects. However, no direct link currently exists between this atherogenic lipoprotein and intravascular coagulation. The current study examined the binding and functional effects of Lp(a), its lipoprotein constituents, apoliprotei...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.10.2980
更新日期:2001-11-15 00:00:00
abstract::Expression of the myeloperoxidase (MPO) gene is tightly regulated in a tissue- and development-specific manner. Accumulation of MPO messenger RNA (mRNA) occurs only at the late myeloblastic and promyelocytic stages of myeloid differentiation and is negligible at other stages of myeloid development and in other tissues...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-07-15 00:00:00
abstract::Kaposi sarcoma-associated herpesvirus (KSHV)-related multicentric Castleman disease (MCD) is potentially lethal. Growing evidence indicates that, as in Epstein-Barr virus-driven lymphoproliferative disorders after transplantation, KSHV DNA burden in peripheral blood mononuclear cells (PBMCs) may represent the most acc...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v98.12.3473
更新日期:2001-12-01 00:00:00
abstract::Erythropoiesis is a robust process of cellular expansion and maturation occurring in murine bone marrow and spleen. We previously determined that sublethal irradiation, unlike bleeding or hemolysis, depletes almost all marrow and splenic erythroblasts but leaves peripheral erythrocytes intact. To better understand the...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-11-394304
更新日期:2012-09-20 00:00:00
abstract::Oncogenic EZH2 is overexpressed and extensively involved in the pathophysiology of different cancers including extranodal natural killer/T-cell lymphoma (NKTL). However, the mechanisms regarding EZH2 upregulation is poorly understood, and it still remains untargetable in NKTL. In this study, we examine EZH2 protein tu...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019000381
更新日期:2019-12-05 00:00:00
abstract::Phosphoglycerate kinase (PGK) deficiency is generally associated with chronic hemolytic anemia, although it can be accompanied by either mental retardation or muscular disease. Genomic DNAs of two PGK-deficient patients previously described in France were sequenced directly after polymerase chain reaction amplificatio...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::Mammalian 15-lipoxygenases, which have been implicated in the differentiation of hematopoietic cells are commonly regarded as cytosolic enzymes. Studying the interaction of the purified rabbit reticulocyte 15-lipoxygenase with various types of biomembranes, we found that the enzyme binds to biomembranes when calcium i...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::MRP8 and MRP14 are two S100-like calcium-binding proteins of unknown function, associated with numbers of human inflammatory disorders. Both molecules have been described as L1 complex, cystic fibrosis antigen, or p8 and p14. We report here the cloning of mouse MRP8 and MRP14 and their pattern of expression during hem...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-04-15 00:00:00
abstract::T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy that accounts for ∼20% of ALL cases. Intensive chemotherapy regimens result in cure rates >85% in children and <50% in adults, warranting a search of novel therapeutic strategies. Although immune-based therapies have tremendously improved the trea...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019003801
更新日期:2020-09-10 00:00:00
abstract::Mutations in the TET2 gene are frequent in myeloid disease, although their biologic and prognostic significance remains unclear. We analyzed 355 patients with myelodysplastic syndromes using "next-generation" sequencing for TET2 aberrations, 91 of whom were also subjected to single-nucleotide polymorphism 6.0 array ka...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-03-274704
更新日期:2010-11-11 00:00:00
abstract::Isolated splenic hairy cells from three untreated patients were cultured in presence of recombinant human interferon alpha-2C (IFN alpha). Ultrastructural cytochemistry and immunophenotype analysis with a large panel of monoclonal antibodies were performed to study cellular modification induced by IFN alpha. Hairy cel...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-02-01 00:00:00
abstract::When overexpressed in primary erythroid progenitors, oncogenic Ras leads to the constitutive activation of its downstream signaling pathways, severe block of terminal erythroid differentiation, and cytokine-independent growth of primary erythroid progenitors. However, whether high-level expression of oncogenic Ras is ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-09-047050
更新日期:2007-06-15 00:00:00