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 (receptor mediated clearance [RMC]) predominantly on neutrophils, the second process is likely the result of renal clearance. With the intention of developing a novel form of Filgrastim (r-met HuG-CSF) with a sustained duration of action in vivo, a new derivative named SD/01 has been made by association of Filgrastim with poly(ethylene glycol). The desired properties of this new agent would include a prolonged duration of action sufficient to cover a complete single course of chemotherapy. SD/01 is shown here to sustain significantly elevated neutrophil counts in hematopoietically normal mice for 5 days. In neutropenic mice effects were noted for at least 9 days, accompanying a significant reduction in the duration of chemotherapy induced neutropenia. Normal human volunteers showed higher than baseline ANC for around 9 to 10 days after a single injection of SD/01. Data from these normal volunteers also indicate that mobilization of CD34+ cells and progenitors may occur in a more timely manner and to around the same absolute numbers as with repeated daily injections of unmodified Filgrastim. These data indicate that SD/01 represents an efficacious novel form of Filgrastim with actions sustained for between one and two weeks from a single injection.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Molineux G,Kinstler O,Briddell B,Hartley C,McElroy P,Kerzic P,Sutherland W,Stoney G,Kern B,Fletcher FA,Cohen A,Korach E,Ulich T,McNiece I,Lockbaum P,Miller-Messana MA,Gardner S,Hunt T,Schwab Gdoi
10.1016/s0301-472x(99)00112-5keywords:
subject
Has Abstractpub_date
1999-12-01 00:00:00pages
1724-34issue
12eissn
0301-472Xissn
1873-2399pii
S0301-472X(99)00112-5journal_volume
27pub_type
杂志文章abstract::Retroviral gene marking has been used successfully in preclinical and clinical transplantation settings. Highly sensitive techniques for vector insertion-site determination, such as linear amplification-mediated polymerase chain reaction (LAM-PCR) in conjunction with next-generation sequencing, have been introduced to...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2012.09.003
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVE:About one third of patients requiring allogeneic hematopoetic stem cell transplantation (HSCT) would not find a matched sibling or alternative donor. Allogeneic HSCT from matched unrelated and mismatched donors carries an increased risk of graft-vs-host disease (GVHD) and transplant-related mortality (TRM). ...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2008.03.011
更新日期:2008-08-01 00:00:00
abstract::G-banded metaphase chromosomes prepared from 14 male CBA/Ca mice with histologically confirmed myeloid leukemia (ML) were studied in an effort to identify specific chromosomal changes associated with radiation leukemogenesis. The chromosome studies were undertaken as part of a larger investigation of radiation carcino...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::Dtk (Tyro 3/Sky/Rse/Brt/Tif) belongs to a recently recognized subfamily of receptor tyrosine kinases that also includes Ufo (Axl/Ark) and Mer (Eyk). Ligands for Dtk and Ufo have been identified as protein S and the related molecule Gas6, respectively. This study examined expression of Dtk during ontogeny of the hemato...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::The prototypic human acute phase reactant, C-reactive protein (CRP), and a structurally modified form of CRP (mCRP) were studied as agents which could stimulate thrombopoiesis in both in vitro and in vivo mouse models. mCRP, but not the widely studied (native) pentameric form of CRP, demonstrated significant megakaryo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::Among 75 consecutive allogeneic bone marrow transplant recipients, 24 developed chronic graft-versus-host disease (GVHD), which was diagnosed from day 31 to day 368 after transplantation. Eight (33%) patients had more extensive chronic GVHD, and five patients died. The actuarial incidence of chronic GVHD was 48% at 40...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-11-01 00:00:00
abstract::Using an accurate technique for staining and scoring soft agar cultures, this study defines the incidence of circulating CFUEOS in normal donors. With whole mononuclear cells as the source of colony stimulating factor (CSF) and fetal calf serum, 49.6% +/- 3.5 of the colonies were eosinophilic; with human placental con...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::We investigated the interactions between the bone marrow microenvironment and T cell populations at different stages of maturation. Thymocytes were seeded onto confluent layers of bone marrow stromal cell lines (MBA-13 or 14F1.1). Within a few hours two main thymocyte populations were observed; one remained in the liq...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::The plasma membrane is a dynamic organelle whose function includes receptor-mediated signal transduction into the cell. Conversely, the plasma membrane is the origin of inter-cellular signaling. In addition to expressing and releasing growth factors in a soluble form(through exocytosis) and via proteolysis of cell sur...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/s0301-472x(03)00050-x
更新日期:2003-06-01 00:00:00
abstract::The development of a hematopoietic reporter is crucial for determining the fate of lineages derived from cell-based therapies. A marking system will enable safer embryonic stem and induced pluripotent stem cell-based derivation of blood lineages and facilitate the development of efficient cellular reprogramming strate...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2014.05.005
更新日期:2014-09-01 00:00:00
abstract:OBJECTIVE:Several requirements need to be fulfilled for clinical use of expanded hematopoietic stem cells (HSCs). Because most cord blood (CB) samples are frozen in single bags and only an aliquot ( approximately 25%) of the blood can be expanded, the thawing and refreezing of samples must be validated in the current E...
journal_title:Experimental hematology
pub_type: 杂志文章,多中心研究
doi:10.1016/j.exphem.2007.08.030
更新日期:2008-02-01 00:00:00
abstract:OBJECTIVE:It is well known that hypoxic stress strongly enhances erythropoiesis, but the effect of hypoxia on erythroid progenitors has not been examined precisely. In the present study, using the erythropoietin-dependent cell line UT-7/Epo, which has characteristics of erythroid progenitors, we investigated a novel ro...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.01.013
更新日期:2005-05-01 00:00:00
abstract:OBJECTIVES:GPIIb integrin expression has been found on platelets and megakaryocytes, and more recently on immature hematopoietic progenitors. We set out to investigate expression of GPIIb in other hematopoietic cell lineages and, having detected it on mast cells, aimed to determine what possible role it might perform. ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.01.011
更新日期:2005-04-01 00:00:00
abstract:OBJECTIVE:Umbilical cord blood (CB) provides an alternative source of hematopoietic progenitor cells for transplantation; however, prolonged thrombocytopenia remains a major obstacle due to the low numbers of megakaryocyte progenitor (Mk-prog) cells and their subsequent delayed engraftment. In this study, we improved t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00884-6
更新日期:2002-09-01 00:00:00
abstract::Bone marrow-derived mast cell precursors form large mast cell colonies in methylcellulose and are designated as L-CFU-Mast. The effect of differentiated mast cells on recruitment and differentiation of L-CFU-Mast was investigated by using genetically mast cell-deficient WBB6F1-W/Wv mice. Giant granules of C57BL/6-bgJ/...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::Effects of thyroid hormones on the production of erythropoietin (Epo) were investigated in isolated perfused rat kidneys and in the human hepatoma cell line, HepG2. Epo protein was measured by radioimmunoassay. L-triiodothyronine and L-thyroxine stimulated hypoxia-induced Epo formation both in the kidney and in HepG2 ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-03-01 00:00:00
abstract::In vitro exposure of murine hematopoietic stem cells (HSCs) to cell cycle-inducing cytokines has been shown to result in a defect in the ability of these cells to engraft. We used a porcine microvascular endothelial cell (PMVEC) line in conjunction with exogenous interleukin (IL)-3, IL-6, granulocyte-macrophage colony...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
abstract::Four types of colonies can be formed by progenitor cells (CFUc) in double layer agar cultures: eosinophil, granulocyte, macrophage, and mixed granulocyte-macrophage. We have developed a method for in situ staining of intact agar plates with luxol fast blue and acetoorcein employed to differentiate the type of colonies...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-11-01 00:00:00
abstract:OBJECTIVE:alpha4 Integrins are major players in lymphoid cell trafficking and immune responses. However, their importance in lymphoid reconstitution and function, studied by antibody blockade or in genetic models of chimeric animals with alpha4(KO) embryonic stem (ES) cells, competitive repopulation experiments with fe...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.03.008
更新日期:2008-08-01 00:00:00
abstract::We have investigated the effect of hematopoietic cytokines on the survival of severe combined immune-deficient (SCID) mice that received a high dose of radiation. In this study, female SCID mice were irradiated at doses ranging from 500 to 600 cGy and then transplanted with 2 x 10(6) male Balb/c marrow cells. Groups o...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
abstract::Despite its growing use as a marker of proliferation, the relationship between expression of the nuclear antigen Ki67 and other indices of proliferation in acute myelogenous leukemia (AML) has not been elucidated. In this study, short-term primary suspension cultures of human AML bone marrow cells were used to compare...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::In adult hematopoiesis, the hematopoietic stem cell (HSC) sits at the top of a hierarchy of hematopoietic progenitors responsible for generating the diverse repertoire of blood and immune cells. During embryonic development, however, the initial waves of hematopoiesis provide the first functioning blood cells of the d...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2017.12.008
更新日期:2018-04-01 00:00:00
abstract::Haploinsufficiency of erythroid Krüppel-like factor (EKLF/KLF1) has been shown recently to ameliorate the clinical severity of β-thalassemia by increased expression levels of fetal hemoglobin (HbF). The underlying mechanisms for role of EKLF in regulating HbF are of great interest but remain incompletely understood. I...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2018.03.004
更新日期:2018-07-01 00:00:00
abstract::The high affinity Fc gamma receptor, Fc gamma RI, is unique among the three classes of macrophage Fc gamma receptors not only in its affinity for IgG, but also in the structure of its cytoplasmic domain. Fc gamma RIIA and the gamma subunit of Fc gamma RIIIA have tyrosine-containing motifs within their cytoplasmic doma...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract:OBJECTIVE:The tumor suppressor p15Ink4b (Ink4b) is a cell-cycle inhibitor that is inactivated in a high percentage of acute myeloid leukemia and myeloid dysplasia syndrome cases. Despite this, the role of Ink4b in hematopoiesis remains unclear. Here we examined the role of Ink4b in blood cell formation using Ink4b-defi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.11.005
更新日期:2007-03-01 00:00:00
abstract::Anemia is a frequently observed adverse effect in cancer patients who receive chemotherapy or drugs designed to block specific oncogenic signaling pathways, although the underlying mechanisms are poorly understood. An article first published online (Zhu HH, Luo X, Zhang K, et al. Proc Natl Acad Sci USA 2015;112:13342-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.01.004
更新日期:2016-05-01 00:00:00
abstract:OBJECTIVE:In utero hematopoietic cell transplantation (IUHCT) is a non-ablative approach that achieves mixed allogeneic chimerism and donor-specific tolerance. However, clinical application of IUHCT has been limited by minimal engraftment. We have previously demonstrated in the murine model that low-level allogeneic ch...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.11.011
更新日期:2006-03-01 00:00:00
abstract::Serum albumin has long been an essential supplement for ex vivo hematopoietic and immune cell cultures. However, serum albumin medium supplements represent a major source of biological contamination in cell cultures and often cause loss of cellular function. As serum albumin exhibits significant batch-to-batch variabi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2019.11.007
更新日期:2019-12-01 00:00:00
abstract::Although macrophages account for 70-90% of the adherent cells in mouse long-term bone marrow cultures (LTBMC) and CFU-F colonies, the predominant nonhematopoietic stromal cell is endothelial-like (EL), expressing cytoplasmic collagen IV, laminin, and an antigen recognized by the monoclonal antibody MECA-10. We report ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::Epitopes on the CD34 molecule detected by some CD34 antibodies can be cleaved by a unique glycoprotease from Pasteurella haemolytica, which cleaves only glycoproteins rich in O-linked glycans. A method to isolate CD34+ cells from adult bone marrow was developed subsequently, in which CD34+ cells were isolated in high ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-06-01 00:00:00