Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of recombinant canine granulocyte colony-stimulating factor (rcG-CSF) and recombinant canine stem cell factor (rcSCF), a c-kit ligand, on the circulation of hematopoietic progenitor and stem cells were studied in a canine model. Administration of rcG-CSF (10 micrograms/kg) for 7 days led to a 5.4-fold increase in CFU-GM/mL of blood, while 7 days of rcSCF (200 micrograms/kg) led to an 8.2-fold increase. Although treatment with low-dose rcSCF (25 micrograms/kg) had no effect on the level of peripheral blood progenitors, 7-day exposure to a combination of G-CSF plus low dose SCF led to a 21.6-fold increase (P = .03). To assess the ability of these factors to increase the circulation of cells capable of rescuing animals after lethal total body irradiation (TBI), 1 x 10(8) peripheral blood mononuclear cells (PBMC)/kg were collected and cryopreserved from animals after 7 days of treatment with G-CSF, SCF or a combination of the two. One month later, animals were exposed to 9.2 Gy TBI and transplanted with the previously collected cells. Control animals transplanted with 1 x 10(8) PBMC/kg collected without pretreatment died with marrow aplasia 11 to 29 days after TBI as did animals treated with only low-dose SCF before cell collection. In contrast, all animals given PBMC collected after G-CSF, high-dose SCF, or a combination of G-CSF plus low-dose SCF recovered granulocyte function. Recovery to 500 granulocytes/microL after transplant took 17, 18.8, and 13.6 days, respectively, (P = .056 for the difference between the combination G-CSF-SCF group and the other two groups). In both the G-CSF and SCF groups, 4 of 5 animals completely recovered while 1 of 5 in each group died with prolonged thrombocytopenia. In the combination group, all 5 animals became long-term survivors. These studies demonstrate that both G-CSF and SCF dramatically increase the level of peripheral blood hematopoietic progenitor and stem cells and support the view that these factors can act synergistically.
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PMID:Effects of granulocyte colony-stimulating factor and stem cell factor, alone and in combination, on the mobilization of peripheral blood cells that engraft lethally irradiated dogs. 751 22

The effect of soluble c-kit ligand (stem cell factor, SCF) on human megakaryocytopoiesis of the cells from umbilical cord blood was evaluated in a methylcellulose culture containing human plasma. SCF alone did not stimulate megakaryocyte colony formation by non-phagocytic mononuclear cells (NPMNC), but did so in combination with interleukin (IL)-3, dose-dependently. This stimulatory effect was exhibited more strongly on large megakaryocyte colonies than on small ones. The effects of SCF + IL-3 on the number and size of megakaryocyte colonies exceeded those of IL-6 + IL-3 or of IL-11 + IL-3. The synergistic interaction of SCF with IL-3 was confirmed by using CD34-positive cells. In particular, addition of SCF to the culture with optimal and suboptimal concentrations of IL-3, significantly increased mixed megakaryocyte colony formation as compared with IL-3 alone. Although SCF in combination with IL-6 or IL-11 induced megakaryocyte colonies from NPMNC, these interactions disappeared entirely in the culture using CD34-positive cells. IL-6 or IL-11 significantly increased the size and DNA content of megakaryocytes in the presence of IL-3, while SCF did not affect, or rather decreased, the DNA content. These findings suggest that SCF promotes more strongly the proliferation of primitive rather than mature megakaryocytic progenitors, but does not affect megakaryocytic maturation.
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PMID:Stem cell factor promotes proliferation of human primitive megakaryocytic progenitors, but not megakaryocytic maturation. 751 2

We have studied the effects of recombinant human interleukin-9 (IL-9), alone and combined with stem cell factor (SCF, c-kit ligand), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the clonogenic proliferation of highly enriched human hematopoietic CD34+ and CD34+CD33-DR- progenitor cells. Colony assays were performed under serum-containing and serum-free conditions. IL-9, as a single agent, did not support colony formation. The addition of erythropoietin (Epo) to IL-9 induced the growth of erythroid progenitors (BFU-E) derived from both CD34+ and CD34+CD33-DR- cells. The IL-9-dependent growth of BFU-E derived from CD34+ cells was increased in an additive manner by SCF and, to a lesser extent, by IL-3, whereas CD34+CD33-DR- erythroid precursors were also responsive to GM-CSF in combination with IL-9. The addition of SCF to IL-9 did stimulate the development of CD34+ and CD34+CD33-DR- macroscopic, multicentered BFU-E and multilineage colonies (CFU-GEMM). When IL-9 was used in serum-free conditions, the growth of CD34+ and CD34+CD33-DR- BFU-E was observed in the presence of Epo. Moreover, a marked synergy on BFU-E colony formation was evident when IL-9 was combined with SCF, and their activity was enhanced by the addition of IL-3. IL-9 showed a negligible proliferative activity on colony-forming units-granulocyte/macrophage (CFU-GM). However, it increased the number of CD34+CD33-DR- CFU-GM responsive to IL-3 (37% of the colonies generated by phytohemagglutinin-stimulated lymphocyte conditioned medium [PHA-LCM]). The effects of IL-9 on CD34+CD33-DR- cells were also studied in a short-term suspension culture system, which evaluates the proliferation of progenitors earlier than day 14 CFU-C (Delta assay). In this system, IL-9 had a minimal activity on its own. In combination with SCF, however, it induced a nine-fold expansion of CD34+CD33-DR- cells, which generated a greater number of CFU-GM than BFU-E in secondary methylcellulose cultures. These experiments indicate that IL-9 induces the proliferation of very primitive human erythroid cells, and this effect is potentiated by SCF and other cytokines. Furthermore, IL-9 synergizes in vitro with the c-kit ligand in expanding the pool of early pluripotent hematopoietic progenitor cells.
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PMID:Stem cell factor (c-kit ligand) enhances the interleukin-9-dependent proliferation of human CD34+ and CD34+CD33-DR- cells. 752 Mar 94

Molecular genetic alterations of known protoncogenes and growth factors, e.g. c-kit and its ligand SCF as well as hst1 and c-myc, are likely to play a role in the development of testicular cancer. In addition, identification and analysis of genes located on the frequently altered chromosome 12 represent an important focus of research. Genetic alterations may occur in a stepwise fashion, as described in other human tumors, leading to the development of the various histologic subtypes of testicular germ cell tumors. The characterization of these alterations are most likely to extend the traditional histopathologic tumor classifications.
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PMID:Molecular biologic investigations of proto-oncogenes and growth factors in human testicular tumors. 752 81

Stem cell factor is a recently identified earliest-acting hematopoietic growth factor and a ligand for the c-kit proto-oncogen. Based on our recent observations that recombinant rat interleukin-3 (IL3), human interleukin-6 (IL6) and murine granulocyte-macrophage colony stimulating factor (GM-CSF) possessed different degrees of suppressive activities on the proliferation of LT 12 cell line derived from BNML rat leukemic model, SCF was evaluated alone and in combination with either IL3, IL6 or GM-CSF for effects on leukemopoiesis in vitro. The results indicated that SCF alone had suppressive effect on DNA synthesis and colony forming unit-leukemic blast (CFU-L) in LT12 cells. 100ng/ml of SCF caused substantial reduction in colony number and 3H-TdR uptake although this suppression was of lower magnitude than those induced by IL3, IL6 or GM-CSF. Enhanced suppression on the proliferation of LT12 cells was observed when SCF was used in combination with one of these three factors. Among these combinations, SCF+GM-CSF or SCF+IL6 resulted in more suppression on LT12 cells than SCF+IL3 did. Combination of SCF with two or three factors produced even more suppression. No apparent effect on the size of leukemic colony was seen. Furthermore, in growth kinetics study of LT12 cells in the presence of SCF production of LT12 cells declined. Thus, SCF appears to have divergent hematopoietic activities on BNML rat model: effective stimulation of granulopoiesis and weak suppression of leukemopoiesis.
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PMID:[Effects of recombinant stem cell factor on the proliferation in vitro of LT12 acute promyelocytic leukemic cell line]. 752 53

Retroviral-mediated gene transfer is the most attractive modality for gene transfer into hematopoietic stem cells. However, transduction efficiency has been low using amphotropic Moloney murine leukemia virus (MoMLV) vectors. In this study, we investigated modifications of gene transfer using amphotropic MoMLV vectors in cell-free supernatant for their ability to increase the currently low transduction of both committed hematopoietic progenitors, granulocyte-macrophage colony-forming units (CFU-GMs), and their precursors, long-term culture-initiating cells (LTC-IC). First, based on the observation that bone marrow cells express more gibbon ape leukemia virus (GALV) receptor (Glvr-1) than amphotropic receptor (Ram-1), PG13/LN, which is a MoMLV vector pseudotyped with the GALV envelope, was compared with the analogous amphotropic envelope vector (PA317/LN). Second, progenitor cell transduction efficiency was compared between CD34 enriched and nonenriched progenitor populations. Third, the duration of transduction in vitro was extended to increase the proportion of progenitor cells that entered cell cycle and could thereby integrate vector cDNA. In 20 experiments, 1 x 10(6) marrow or peripheral blood mononuclear cells (PBMCs)/mL were exposed to identical titers of pseudotyped PG13/LN vector or PA317/LN vector in the presence of recombinant human interleukin-1 (IL-1), IL-3, IL-6, and stem cell factor (SCF; c-kit ligand) for 5 days. 50% of fresh vector supernatant was refed daily. Hematopoietic progenitor cells as measured by G418-resistant granulomonocytic colony (CFU-GM) formation were transduced more effectively with PG13/LN (19.35%) than with PA317/LN (11.5%, P = .012). In 11 further experiments, enrichment of CD34 antigen positive cells significantly improved gene transfer from 13.9% G418-resistant CFU-GM in nonenriched to 24.9% in CD34-enriched progenitor cells (P < .01). To analyze gene transfer after extended growth factor-supported long-term culture, 1 x 10(6) marrow cells/mL were cultured with IL-1, IL-3, IL-6, and SCF (50 ng/mL each) for 1, 2, and 3 weeks. Fifty percent of PG13/LN supernatant with growth factors was refed on 5 days per week. Five percent of marrow CFU-GM and 67% of LTC-IC were G418 resistant at 1 week (n = 4), 60% of CFU-GM and 100% of LTC-IC were resistant at 2 weeks (n = 2) and 74% of CFU-GM (n = 4) and 82% of LTC-IC (n = 2) were resistant at three weeks.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Increased gene transfer into human hematopoietic progenitor cells by extended in vitro exposure to a pseudotyped retroviral vector. 752 56

Stem cell factor (CSF), also called c-kit ligand (KL) or mast cell growth factor (MGF) is a peptide growth factor/cytokine with broad activities, especially on hematopoiesis. Its physiological role is best understood through the naturally occurring steel and W mutations in the mouse. This cytokine has recently been made available because of molecular cloning and its expression in recombinant form SCF is produced by a variety of cells, especially fibroblast, and interacts with target cells in each of the hematopoietic lineages to stimulate proliferation and differentiation. It has been found that SCF is important for the survival, proliferation and differentiation of mast cells and that it influences all stages of their development. SCF activity is not restricted to hematopoiesis, as it plays an important role in the development of germ cells and melanocytes as well. Preclinical studies show that SCF can protect against lethal irradiation, elicit multilineage responses in peripheral blood and bone marrow cellularity and increase circulating peripheral blood progenitor cells in a dose-dependent manner. Recombinant human SCF has major clinical potential through its synergy with other factors, especially G-CSF, to enhance mobilization of stem cells in peripheral blood.
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PMID:[Stem cell factor]. 752 11

Cultured mast cells (CMC) derived from the bone marrow of mice express the receptor encoded by the W (c-kit) locus (W receptor), and the WCB6F1(+/+)-3T3 fibroblasts express the ligand encoded by the Sl locus (stem cell factor [SCF]). CMC attach to the fibroblasts through the W receptors and cell-bound SCF. We investigated the effect of phorbol 12-myristate 13-acetate (PMA) and recombinant murine SCF (rmSCF) on the attachment. PMA induced both the internalization and shedding of W receptors, whereas rmSCF induced only the internalization. Moreover, both PMA and rmSCF reduced the expression of c-kit mRNA levels in CMC. Addition of either PMA or rmSCF to the coculture of CMC and fibroblasts resulted in the inhibition of attachment. Since the magnitude of the attachment between CMC and fibroblasts may be manipulated by changing the doses of either PMA or rmSCF, the present experimental system may be useful as a model for the attachment between blood cells and stromal cells.
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PMID:Inhibition of attachment between cultured mast cells and fibroblasts by phorbol 12-myristate 13-acetate and stem cell factor. 752 84

We examined the expression of Fc epsilon-RI and Fc gamma-RII/III on mouse bone marrow cells enriched for hematopoietic progenitors including mast cell progenitors. Bone marrow cells were depleted of mature hematopoietic lineages and a primitive population of cells that express the proto-oncogene c-kit (KIT+ lineage- cells) was isolated. KIT+ lineage- cells stain positively using the Ab 2.4G2, indicating surface expression of Fc gamma-RII and/or Fc gamma-RIII. Fluorescent staining of intracytoplasmic domains of Fc gamma-RII and Fc gamma-RIII revealed that these cells express primarily Fc gamma-RII on their surface. KIT+ lineage- cells did express Fc gamma RIII alpha-chain protein, but predominately in the nuclear/perinuclear area. We could not detect surface expression of Fc epsilon-RI by KIT+ lineage- cells, although a heterogeneous population of KIT- cells does bind IgE with high affinity and may reflect cells of the basophilic lineage. KIT+ lineage- cells cultured with SCF and IL-3 generate numerous mast cells, whereas equivalent numbers of KIT- cells or naive bone marrow cells do not. In these cultures, surface expression of Fc epsilon-RI is detected on a small number of cells by day 3 of culture with increased surface expression levels correlating roughly with metachromatic granule formation. The fact that Fc gamma-RIII and Fc epsilon-RI are not expressed on the cell surface of KIT+ lineage- cells but appear later in hematopoietic development makes it unlikely that these receptors influence early hematopoietic differentiation. The role that might justify such a complete surface expression of Fc gamma-RII by bone marrow progenitors remains to be identified.
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PMID:Murine KIT+ lineage- bone marrow progenitors express Fc gamma-RII but do not express Fc epsilon-RI until mast cell granule formation. 752 15

The proto-oncogene c-kit encodes the receptor for a stem cell factor (c-kit molecule). Expression of the c-kit molecule on the gated leukemic blast cells from newly diagnosed patients with leukemia was analysed by flow cytometry using the monoclonal antibody (17F11). Among 35 myeloid leukemia cases examined, significant c-kit-positive blast cells were detected in 24 cases (69%), even though the percentage of positive cells was widely variable. The correlation between the percentage of cells positive for the c-kit molecule and the percentage of cells positive for CD34 was found to be statistically significant (rs = 0.36, p < 0.05). Fifteen cases of myeloid leukemia were positive for lymphoid markers. The mean percentage of the cells expressing c-kit molecule among the lymphoid marker-positive cases was significantly larger than that among the lymphoid marker-negative cases (p < 0.05). All 19 lymphoid leukemia cases were c-kit-negative, including 8 cases which were positive for some myeloid markers. Stem cell factor enhanced the colony growth in five out of six acute myeloblastic leukemia cases expressing the c-kit molecule. On the other hand, SCF did not stimulate colony growth in any of the four cases which were not positive for the c-kit molecule. These findings indicated that the distribution of flow cytometrically detectable c-kit molecules on leukemic cells is related to the morphologic and immunologic classification of these leukemic cells and to the expression of the CD34 cell surface molecule on some myeloid leukemic cells. On such cells, expression of the c-kit molecule may have a functional role and be related to the maturation process.
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PMID:The c-kit molecule and the surface immunophenotype of human acute leukemia. 752 77


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