TY - JOUR. T1 - Effects of stem cell factor on osteoclast-like cell formation in long-term human marrow cultures. AU - Demulder, A.. AU - Suggs, S. V.. AU - Zsebo, K. M.. AU - Scarcez, T.. AU - Roodman, G. David. PY - 1992/11. Y1 - 1992/11. N2 - Stem cell factor (SCF) is a newly described hematopoietic growth factor that stimulates the growth of primitive hematopoietic progenitors and mast cells. Since the osteoclast precursor is hematopoietic in origin, we tested SCF for its capacity to stimulate the formation of osteoclast-like multinucleated cells (MNC) in long-term human marrow cultures. These MNC express an osteoclast phenotype and form resorption lacunae on calcified matrices. Addition of SCF alone (0.1 pg/ml to 100 ng/ml) to long-term marrow cultures did not increase MNC formation. However, treatment of these cultures sequentially with SCF for 1 week followed by 1,25-(OH)2D3 for the second and third weeks of culture significantly enhanced MNC formation. [3H]Thymidine incorporation studies ...

Interactions between products of the mouse W locus, which encodes the c-kit tyrosine kinase receptor, and the Sl locus, which encodes a ligand for c-kit receptor, which we have designated stem cell factor (SCF), have a critical role in the development of mast cells. Mice homozygous for mutations at either locus exhibit several phenotypic abnormalities including a virtual absence of mast cells. Moreover, the c-kit ligand SCF can induce the proliferation and maturation of normal mast cells in vitro or in vivo, and also can result in repair of the mast cell deficiency of Sl/Sld mice in vivo. We now report that administration of SCF intradermally in vivo results in dermal mast cell activation and a mast cell-dependent acute inflammatory response. This effect is c-kit receptor dependent, in that it is not observed when SCF is administered to mice containing dermal mast cells expressing functionally inactive c-kit receptors, is observed with both glycosylated and nonglycosylated forms of SCF, and ...

|strong|Rabbit anti Mouse stem cell factor antibody|/strong| recognizes mouse stem cell factor (SCF).|br||br|SCF is a stromal cell derived cytokine that synergizes with other haemapoietic growth facto…

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23328669 Various physiologically relevant processes are regulated by the interaction of the receptor tyrosine kinase (c-Kit) and its ligand stem cell factor (SCF), being SCF known to be the most important growth factor for mast cells (MCs). In spite of their traditional role in allergic disorders and innate immunity, MCs have lately emerged as versatile modulators of a variety of physiologic and pathologic processes. Katja Woidacki, a member of Prof. Ana Zenclussens working group demonstrated that MCs are critical for pregnancy success. Recently, this work was published in Cell Death and Disease. Uterine MCs presented a unique phenotype, accumulated during receptivity and expanded upon pregnancy establishment. KitW-sh/W-sh mice, whose MC-deficiency is based on restricted c-Kit gene expression, exhibited severely impaired implantation, which could be completely rescued by systemic or local transfer of wild-type bone marrow-derived MCs. ...

Mast cell (MC) differentiation, survival, and activation are controlled by the membrane tyrosine kinase c-Kit upon interaction with stem cell factor (SCF). Here we describe a single point mutation induced by N-ethyl-N-nitrosurea (ENU) mutagenesis in C57BL/6J mice-an A to T transversion at position 2388 (exon 17) of the c-Kit gene, resulting in the isoleucine 787 substitution by phenylalanine (787F), and analyze the consequences of this mutation for ligand binding, signaling, and MC development. The Kit(787F/787F) mice carrying the single amino acid exchange of c-Kit lacks both mucosal and connective tissue-type MCs. In bone marrow-derived mast cells (BMMCs), the 787F mutation does not affect SCF binding and c-Kit receptor shedding, but strongly impairs SCF-induced cytokine production, degranulation enhancement, and apoptosis rescue. Interestingly, c-Kit downstream signaling in 787F BMMCs is normally initiated (Erk1/2 and p38 activation as well as c-Kit autophosphorylation) but fails to be ...

Alzheimers disease (AD) is widely recognized as a serious public health problem and heavy financial burden. Currently, there is no treatment that can delay or stop the progressive brain damage in AD. Recently, we demonstrated that stem cell factor (SCF) in combination with granulocyte colony-stimulating factor (G-CSF) (SCF+G-CSF) has therapeutic effects on chronic stroke. The purpose of the present study is to determine whether SCF+G-CSF can reduce the burden of β-amyloid deposits in a mouse model of AD. APP/PS1 transgenic mice were used as the model of AD. To track bone marrow-derived cells in the brain, the bone marrow of the APP/PS1 mice was replaced with the bone marrow from mice expressing green fluorescent protein (GFP). Six weeks after bone marrow transplantation, mice were randomly divided into a saline control group and a SCF+G-CSF-treated group. SCF in combination with G-CSF was administered subcutaneously for 12 days. Circulating bone marrow stem cells (CD117+ cells) were quantified 1 day

TY - JOUR. T1 - Transforming growth factor β1 inhibits expression of the gene products for steel factor and its receptor (c-kit). AU - Heinrich, Michael C.. AU - Dooley, Douglas C.. AU - Keeble, Winifred W.. PY - 1995/4/1. Y1 - 1995/4/1. N2 - Transforming growth factor β1 (TGF-β1), a product of marrow stromal cells, inhibits the proliferation and differentiation of hematopoietic progenitor cells within the hematopoietic microenvironment. Steel factor (SF), also a product of marrow stromal cells, is an essential positive regulator of hematopoiesis in vivo. TGF-β1 has been shown to repress human and murine leukemic cell and murine lin- bone marrow mononuclear cell expression of the receptor for SF (c-kit). We speculated that TGF-β1 might exert its inhibitory effect on hematopoiesis in part by decreasing SF/c-kit interactions. Therefore, we tested the hypothesis that TGF-β1 inhibits both stromal cell expression of SF and hematopoietic progenitor cell expression of c-kit. We measured stromal ...

Our most important conclusion is that during erythroid differentiation, activation of the Epo-R occurs by two different mechanisms; these generate different intracellular signals essential for proliferation and terminal differentiation of committed erythroid progenitors. Erythroid progenitors from Epo-R−/− fetal livers, infected in vitro with a retrovirus expressing the wt Epo-R, require the addition of both Epo and SCF to form CFU-E colonies. Thus, signals from both Epo and SCF receptors are essential. At least one signal emanating from KIT must use the Epo-R as a downstream signal-transduction protein, because the Epo-R−/− fetal liver cells were exposed to SCF in vivo, yet required SCF in vitro after expression of the exogenous Epo-R. Indeed, CFU-E colony formation in vitro by normal fetal liver progenitors requires only Epo; the essential interaction between activated KIT and the Epo-R must have occurred in vivo before or at the CFU-E stage. This is consistent with our previous report ...

Mast cells are found in tissues throughout the body where they play important roles in the regulation of inflammatory responses. One characteristic feature of mast cells is their longevity. Although it is well established that mast cell survival is dependent on stem cell factor (SCF), it has not been described how this process is regulated. Herein, we report that SCF promotes mast cell survival through inactivation of the Forkhead transcription factor FOXO3a (forkhead box, class O3A) and down-regulation and phosphorylation of its target Bim (Bcl-2 [B-cell lymphoma-2] interacting modulator of cell death), a Bcl-2 homology 3 (BH3)-only proapoptotic protein. SCF induced a rapid and transient phosphorylation of Akt (protein kinase B) and FOXO3a. SCF treatment prevented up-regulation of Bim protein expression and led to increased Bim phosphorylation. Bim phosphorylation was inhibited by PD98059 and LY294002 treatment, suggesting the involvement of mitogen-activated protein kinase ...

The c-KIT receptor tyrosine kinase mediates the cellular response to stem cell factor (SCF). Whereas c-KIT activity is important for the proliferation of hematopoietic cells, melanocytes and germ cells, uncontrolled c-KIT activity contributes to the growth of diverse human tumors. Suppressor of cytokine signaling 6 (SOCS6) is a member of the SOCS family of E3 ubiquitin ligases that can interact with c-KIT and suppress c-KIT-dependent pathways. Here, we analyzed the molecular mechanisms that determine SOCS6 substrate recognition. Our results show that the SH2 domain of SOCS6 is essential for its interaction with c-KIT pY568. The 1.45-Å crystal structure of SOCS6 SH2 domain bound to the c-KIT substrate peptide (c-KIT residues 564-574) revealed a highly complementary and specific interface giving rise to a high affinity interaction (K(d) = 0.3 μm). Interestingly, the SH2 binding pocket extends to substrate residue position pY+6 and envelopes the c-KIT phosphopeptide with a large BG loop insertion that

The cDNA coding for the soluble form of bovine stem cell factor (boSCF-Ala-105) was cloned and recombinant protein was produced in bacteria as a histidine tagged-protein. The protein was purified from the inclusion bodies in one step by metal chelation chromatography under denaturing conditions. Recombinant bovine SCF was shown to act synergistically with interleukin 3 (IL-3) and erythropoietin (EPO) in stimulating the growth of bone marrow progenitor cells such as colony forming units-granulocyte macrophage (CFU-GM) and burst forming units-erythroid (BFU-E). Analysis of SCF mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR) revealed that the transcripts were detectable in bone marrow, lymph node and spleen of cattle, and that the level of transcription was upregulated in lymph nodes of cattle infected with Trypanosoma congolense. Two isoforms of SCF mRNA were amplified by RT-PCR. The availability of recombinant bovine SCF provides a valuable tool for studying the role ...

BACKGROUND AND OBJECTIVES: The small total number of hematopoietic progenitor cells (HPC) in cord blood limited its use in adult recipients. Since the hematopoiesis might be controlled by both positive and negative factors, the finding of negative cellular components and thereafter depletion of them would be of importance for further expansion of HPC from cord blood in vitro. The role of natural killer cells (NK cells) in hematopoiesis remains unclear and needs to be elucidated. DESIGN AND METHODS: Cord blood mononuclear cells were co-cultured in a liquid culture system containing the hematopoietic cytokines interleukin (IL)-1, IL-3, IL-6, stem cell factor (SCF), granulocyte-monocyte colony-stimulating factor (GM-CSF) and G-CSF for a total of 20 days with or without depletion of NK cells. RESULTS: The percentage of CD34+ cells was significantly higher in the NK-cell-depleted group at each time point (day 5, day 10, day 15, day 20). This finding was further confirmed by examination of functional ...

Cytokine regulation of prethymic T-lymphoid progenitor-cell proliferation and/or differentiation has not been well-defined, although much is known of cytokine regulation of hemopoietic stem- and progenitor-cell development. Here we use a recently identified hemopoietic growth factor, stem-cell factor (SCF) (a form of the c-kit ligand), and a transplant model of thymocyte regeneration to assess the effect of SCF on the in vivo generation of prethymic, thymocyte progenitor-cell activity. We show that recombinant rat SCF (rrSCF164) administered to weanling rats selectively induces an increase in thymocyte progenitor activity in the spleens of treated rats as compared to rats treated with vehicle, polyethylene glycol (PEG)-conjugated rat albumin, or recombinant human granulocyte colony-stimulating factor (rhG-CSF). These data demonstrate that administration of SCF in vivo affects extrathymic-origin thymocyte regenerating cells and may influence, directly or indirectly, early prethymic stages of T-cell

The stem cell factor (SCF)-KIT signal transduction pathway plays a role in the proliferation, differentiation and survival of a range of stem and progenitor cell types but little is known about its function in embryonic stem (ES) cells. We generated ES cells carrying a null allele of Kit as well as a knock-in allele that encodes an SCF-independent hybrid KIT receptor that can be activated by the FKBP binding drug, AP20187. KIT null ES cells die when induced to differentiate upon withdrawal of leukaemia inhibitory factor in monolayer culture. This phenotype is recapitulated in wild-type ES cells treated with a KIT-neutralising antibody and reversed in mutant cells by activation of the hybrid KIT receptor. Differentiating KIT null ES cells exhibit elevated levels of DNA laddering and reduced BCL2 expression, indicative of apoptosis. We conclude that mouse ES cell differentiation in vitro is dependent on the SCF-KIT pathway contrasting with the apparently normal differentiation of KIT null inner ...

BACKGROUND AND OBJECTIVES: Megakaryocyte (Mk) engraftment is often poor and delayed after cord blood (CB) transplantation. Ex vivo manipulations of the cells that will be infused may be a way to achieve better Mk engraftment. In this study we investigated the ability of different hematopoietic growth factor combinations to generate large numbers of Mk cells ex vivo. DESIGN AND METHODS: To find the best cytokine combination capable of generating large numbers of Mks, baseline CB CD34+ (bCD34+) cells and CD34+ and CD34- cells, immunoselected after 4 weeks of expansion with thrombopoietin (TPO), stem cell factor (SCF) and Flt-3 ligand (FL) (eCD34+, eCD34-), were further cultured in the presence of different cytokine combinations (containing interleukin(IL)-3, SCF, TPO and IL-6). To evaluate Mk reconstitution in vivo, Mk-committed cells, generated during 10 days of in vitro culture, were injected into NOD/SCID mice and the kinetics of human platelet production was evaluated. RESULTS: TPO and SCF ...

Increased fetal hemoglobin (HbF) in b-globin gene disorders ameliorates the clinical symptoms of the underlying disease. 5-azacytidine, butyrate and hydroxyurea, have been shown to activate g-globin gene expression. It has also been found that hematopoietic growth factors can influence expression of g-globin in erythroid cultures and in animal models. This study was designed to evaluate the in vitro effects of the stem cell factor (SCF) and transforming growth factor-b (TGF-b) on g-globin gene reactivation of erythroid precursors derived from CD133+ cells in vitro. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) analysis showed increased expression of the g-globin transcript in cell culture groups containing either TGF- b or SCF or both as compared to control (2.2-, 2.7- and 5.5-fold, respectively) (p|0.01). Production of HbF in a differentiated population was demonstrated using flow cytometry. The results of this study suggest that SCF and TGF-b warrant further evaluation as potential

Introduction: The proto-oncogene c-KIT encodes a receptor tyrosine kinase(KIT) whose ligand is stem cell factor. KIT is expressed by and critical for the development and growth of mast cells, melanocytes, hematopoetic stem cells, and the interstitial cells of Cajal. In this study, c-kit gene mutatio...

Cediranib is a potent inhibitor of the vascular endothelial growth factor receptor (VEGFR)-2 and -3 tyrosine kinases. This study assessed the activity of cediranib against the VEGFR-1 tyrosine kinase and the platelet-derived growth factor receptor (PDGFR)-associated kinases c-Kit, PDGFR-α and -β. Cediranib inhibited VEGF-A-stimulated VEGFR-1 activation in AG1-G1-Flt1 cells (IC50, 1.2nM). VEGF-A induced greatest phosphorylation of VEGFR-1 at tyrosine residues Y1048 and Y1053; this was reversed by cediranib. Potency against VEGFR-1 was comparable to that previously observed versus VEGFR-2 and R-3. Cediranib also demonstrated significant activity against wild-type c-Kit in cellular phosphorylation assays (IC50, 1-3nM) and in a stem cell factor-induced proliferation assay (IC50, 13-nM). Furthermore, phosphorylation of wild-type c-Kit in NCI-H526 tumor xenografts was reduced markedly following oral administration of cediranib (≥1.5 mg/kg/day) to tumor-bearing nude mice. The activity of cediranib ...

Recombinant human c-KIT (Y823D) (amino acids 544-end) was expressed by baculovirus in Sf9 insect cells using a N-terminal GST tag. c-KIT is a proto-oncogene and a type 3 transmembrane receptor for MGF (mast cell growth factor, also known as stem cell factor).

Principal Investigator：Kubota Yasue, Project Period (FY)：2013-04-01 - 2016-03-31, Research Category：Grant-in-Aid for Scientific Research (C), Section：一般, Research Field：Urology

Regulation of hematopoietic stem and progenitor cell (HSPC) steady-state egress from the bone marrow (BM) to the circulation is poorly understood. While glycogen synthase kinase-3β (GSK3β) is known to participate in HSPC proliferation, we revealed an unexpected role in the preferential regulation of CXCL12-induced migration and steady-state egress of murine HSPCs, including long-term repopulating HSCs, over mature leukocytes. HSPC egress, regulated by circadian rhythms of CXCL12 and CXCR4 levels, correlated with dynamic expression of GSK3β in the BM. Nevertheless, GSK3β signaling was CXCL12/CXCR4 independent, suggesting that synchronization of both pathways is required for HSPC motility. Chemotaxis of HSPCs expressing higher levels of GSK3β compared with mature cells was selectively enhanced by stem cell factor-induced activation of GSK3β. Moreover, HSPC motility was regulated by norepinephrine and insulin-like growth factor-1 (IGF-1), which increased or reduced, respectively, GSK3β ...

Yung, Y and Moore, M A., Long-term in vitro culture of murine mast cells. Iii. Discrimination of mast cell growth factor and granulocyte-csf. (1982). Subject Strain Bibliography 1982. 4470 ...

The CD117 antigen is the 145 kDa protooncogene c-kit. It belongs to the class III receptor tyrosine kinase family. This antigen is the receptor for the stem-cell factor (SCF) encoded by the steel locus (Steel Locus Factor "SLF"). The CD117 antigen is expressed on very few normal bone marrow cells. The majority of CD117+ marrow cells co-express CD34. CD117 is also expressed on mast cells.

UT Southwestern molecular biologists today report the unexpected finding that selectively deleting a stem cell transcription factor in adult mice promotes recovery after traumatic brain injury (TBI).

Molecular regulation of mast cell development and maturation.: Mast cells play a crucial role in the pathogenesis of allergic diseases. In recent years, tremend

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The effect of c-kit activation on cardiac differentiation of CPCs.Murine c-kit+ CPCs were induced to differentiate in dexamethasone-containing media as describe

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The cochlea, as a microvascular organ, is very susceptible to conditions that result in a disruption of vascularisation. Transforming Growth

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Oocyte control of granulosa and theca cell function may be mediated by several growth factors via a local feedback loop(s) between these cell types. This study examined both the role of oocyte-secreted factors on granulosa and thecal cells, cultured independently and in co-culture, and the effect of stem cell factor (SCF); a granulosa cell derived peptide that appears to have multiple roles in follicle development. Granulosa and theca cells were isolated from 2-6 mm healthy follicles of mature porcine ovaries and cultured under serum-free conditions, supplemented with: 100 ng/ml LR3 IGF-1, 10 ng/ml insulin, 100 ng/ml testosterone, 0-10 ng/ml SCF, 1 ng/ml FSH (granulosa), 0.01 ng/ml LH (theca) or 1 ng/ml FSH and 0.01 ng/ml LH (co-culture) and with/without oocyte conditioned medium (OCM) or 5 oocytes. Cells were cultured in 96 well plates for 144 h, after which viable cell numbers were determined. Medium was replaced every 48 h and spent medium analysed for steroids.Oocyte secreted factors were ...

AIC2A and AIC2B are closely related genes encoding components of the receptors for murine interleukin-3 (IL-3) (AIC2A) and granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-5 (AIC2B). We have studied the parallel regulation of expression of these genes in erythroid and myeloid progenitor cell lines. AIC2A and AIC2B transcription was transiently induced in these cells in response to a variety of hematopoietic growth factors, including erythropoietin (EPO), monocyte-CSF, IL-3, GM-CSF, and stem cell factor (SCF or kit ligand). Run-on assays established that the increase occurred mainly at the transcriptional level. Immunoprecipitation experiments confirmed that the increase in messenger RNA expression resulted in augmented synthesis of both AIC2A and AIC2B proteins, and binding studies further showed these proteins to be functional. We observed a fourfold increase in low-affinity IL-3 sites in an erythroid precursor cell line stimulated with EPO, and a threefold increase in GM-CSF ...

SRMS (Src-related tyrosine kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites) belongs to a family of non-receptor tyrosine kinases, which harbours a Src homology 3 and a Src homology 2, as well as a protein kinase domain. SRMS was first identified in a screen for the genes that regulate the growth and differentiation of neuroepithelial cells. SRMS, however, is an understudied member of this family. The present study was undertaken in order to explore the role of SRMS in signaling downstream of KIT. The receptor tyrosine kinase KIT, also known as the stem cell factor receptor, plays a key role in several developmental processes and have been implicated in many human cancers such as gastrointestinal stromal tumors, acute myeloid leukemia and testicular carcinoma. To understand the role of SRMS in KIT signaling, we generated Ba/F3 cell lines overexpressing KIT and SRMS. We observed that SRMS regulates normal and oncogenic KIT signaling differentially with respect to ...

INCLUSION CRITERIA:. Patients with Hb SS, Sbeta-thal, SD, or SO-Arab. Age greater than or equal to 18 years.. Patient must have had a previous neurologic event (either symptomatic or found by imaging alone).. More than one painful crises per year for the last 2 years, each requiring hospitalization.. A previous acute chest syndrome.. Evidence of renal damage but with a creatinine clearance of greater than 50 percent of normal.. Red cell alloimmunization.. Bilateral retinopathy.. Osteonecrosis of multiple bones.. Unilateral or bilateral leg ulcers.. Patients who have failed a course of hydroxyurea or who have declined to take hydroxyurea.. Able to give informed consent.. No active sickle cell crises or acute chest syndrome.. No active uncontrolled infection.. No hydroxyurea, erythropoietin, and/or arginine butyrate therapy in the previous month.. No patients receiving hypertransfusion therapy.. No current treatment (or within 2 weeks) with hematopoietic growth factors.. No allergy to E. coli ...

Our previous work shows that the stem cell factor SALL4 plays a central role in embryonic and leukemic stem cells. In this study, we report that SALL4 expression was higher in drug resistant primary acute myeloid leukemic patients than those from drug-responsive cases. In addition, while overexpression of SALL4 led to drug resistance in cell lines, cells with decreased SALL4 expression were more sensitive to drug treatments than the parental cells. This led to our investigation of the implication of SALL4 in drug resistance and its role in side population (SP) cancer stem cells. SALL4 expression was higher in SP cells compared to non-SP cells by 2-4 fold in various malignant hematopoietic cell lines. Knocking down of SALL4 in isolated SP cells resulted in a reduction of SP cells, indicating that SALL4 is required for their self-renewal. The SP phenotype is known to be mediated by members of the ATP-binding cassette (ABC) drug transport protein family, such as ABCG2 and ABCA3. Using ...

Mutations in TGFBRI, encoding the receptor for TGFβ, cause Loeys-Dietz syndrome (LDS), a Mendelian disorder associated with an increased risk of developing nearly all forms of allergic disease, including food allergy. To better understand the mechanisms responsible for this association, knock-in mice harboring LDS mutations have been developed, which recapitulate nearly all aspects of the human phenotype. Mast cells are the main effector cells of allergic disease and several studies have identified TGFβ as a critical mediator of mast cell development and function. We hypothesized that LDS mast cells are altered in a manner that would promote greater susceptibility to allergic outcomes. To address this possibility, in vitro assays were performed with peritoneal mast cells (pMCs) cultured in IL-3 and stem cell factor and stimulated with IL-33, TGFβ, or IgE crosslinking agents. LDS pMCs expressed higher levels of ST2, the receptor for IL-33, and greater secretion of IL-9 following IL-33 ...

An adaptor protein (growth factor receptor bound protein 2, 217 aa), the mammalian homologue of Caenorhabditis elegans Sem-5 and Drosophila Drk that links the cytoplasmic domain of growth factor receptors to downstream elements of the signalling pathway through its SH2 and SH3 domains. The SH2 domain binds autophosphorylated residues on the growth factor receptors cytoplasmic tail and the SH3 domain binds nucleotide exchange factors such as sos1. Grb2-associated binder-1 (gab-1, 694 aa) binds to Grb-2 and has homology with IRS-1 (insulin receptor substrate-1). It is a substrate for the EGF receptor and may integrate signals from different receptors into the control of cellular responses. Grb2-related adaptor protein-1 (GRAP1; 217 aa) interacts in vitro with c-kit (stem cell factor receptor) and the erythropoietin receptor, linking them to the ras signalling pathway. Grb2-related adaptor protein-2 (GRAP2, GADS, 330 aa) is another of the Grb2/Sem5/Drk family and reportedly involved in ...

STI571 (Gleevec) is a member of the 2-phenylaminopyrimidine family of adenosine triphosphate (ATP) binding site inhibitors of protein tyrosine kinase. It potently inhibits the tyrosine kinase activity of Abl and Bcr-Abl,[1-3] platelet-derived growth factor receptor (PDGF-R), and Kit (stem cell factor receptor).[4-6]

Melanoma can be stratified into unique subtypes based on distinct pathologies. The acral/mucosal melanoma subtype is characterized by aberrant and constitutive activation of the proto-oncogene receptor tyrosine kinase C-KIT, which drives tumorigenesis. Treatment of these melanoma patients with C-KIT inhibitors has proven challenging, prompting us to investigate the downstream effectors of the C-KIT receptor. We determined that C-KIT stimulates MAP kinase-interacting serine/threonine kinases 1 and 2 (MNK1/2), which phosphorylate eukaryotic translation initiation factor 4E (eIF4E) and render it oncogenic. Depletion of MNK1/2 in melanoma cells with oncogenic C-KIT inhibited cell migration and mRNA translation of the transcriptional repressor SNAI1 and the cell cycle gene CCNE1. This suggested that blocking MNK1/2 activity may inhibit tumor progression, at least in part, by blocking translation initiation of mRNAs encoding cell migration proteins. Moreover, we developed an MNK1/2 inhibitor (SEL201), ...

We have assessed tumor contamination of peripheral blood progenitor cells (PBPC) in 203 high-risk breast cancer patients who were prospectively randomized to mo

387558135 - EP 1127577 A3 2002-11-27 - Ligand for the c-kit receptor and methods of use thereof - [origin: US6159461A] Compositions comprising c-kit ligand, TNF- alpha , and a hematopoietic factor are useful to promote the expansion of peripheral blood cells or the expansion and differentiation of hematopoietic progenitor cells.[origin: US6159461A] Compositions comprising c-kit ligand, TNF- alpha , and a hematopoietic factor are useful to promote the expansion of peripheral blood cells or the expansion and differentiation of hematopoietic progenitor cells.

The three strains assessed were A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2) and B/Brisbane/60/2008.. Seroconversion factor (SCF) was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination.. Seroconversion factor (SCF) was defined as the geometric mean of the within subjects ratios of the post-vaccination reciprocal HI titer to the Day 0 reciprocal HI titer. SCFs were calculated at Day 28 following the complete vaccination regimen.. Subjects in each group were also stratified in the following age-strata: 3-4 years, 5-8 years and 9-17 years. ...

Investigation of the role of target cell factors in retrovirus transduction. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.

HIV-1 employs its structural proteins to orchestrate assembly and budding at the plasma membrane of host cells. The Gag polyprotein is sufficient to form virus-like particles in the absence of other viral proteins and provides a platform to interact with numerous cellular factors that regulate Gag trafficking to the site of assembly and budding. Notably endosomal sorting complexes required for transport have attained much attention over the last decade because of their essential role in virion release. Here we review recent advances in understanding the role of host cell factors recruited by Gag during HIV-1 assembly and budding.

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Affiliation：愛知学院大学,歯学部,教授, Research Field：General surgery,Digestive surgery,Surgical dentistry,Pathobiological dentistry/Dental radiology,Experimental pathology, Keywords：癌,発現アレイ,メチル化アレイ,HF10,腫瘍溶解性ウイルス,Stem Cell Factor,ウイルス,扁平上皮癌,SNPアレイ,肝細胞癌, # of Research Projects：11, # of Research Products：62, Ongoing Project：オーダーメイド治療を目指した口腔癌の発生や進展に関わる新規分子の臨床応用の研究

EA can improve the high quality embryo rate, which may be related to its effect in increasing serum and follicular fluid SCF levels.

Rabbit polyclonal c-Kit (phospho Y823) antibody validated for WB and tested in Human. Immunogen corresponding to synthetic peptide

In addition to those powerful mushrooms, K9 Daily Care boasts the nutrient-rich proteins that are found in our K9 Trans Factor Plus supplement. Derived from cows milk, K9 Trans Factor Plus features colostrum which stimulates your dogs immune system to distinguish aberrant cells from normal cells.. As dog owners, we want the best products because we want whats best for our pets. Turn to the non-toxic and top-grade ingredients in K9 Daily Care. This supplement will help your dog enjoy years of continued health. When you take your daily vitamin, remember to give your pooch a Daily Care chewable wafer.. This product is available in chewable wafers. You can purchase 100 count or 450 count Daily Care formulas.. ...

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It's not easy being first. Biotech company Geron (GERN) had to wait more than a year before getting the green light from federal regulators in January to begin the first study using human

c-Kit immuno EM pictures showing c-Kit+ ICC in wild-type proximal colon and c-Kit- FL-ICC in Ws/Ws mid colon. (a) A c-Kit+ ICC-AP (ICC, dark stained with DAB)

受体酪氨酸激酶Kit, 也被称为CD117或C-kit受体，在造血过程中发挥重要作用。Kit获得功能突变频发于多种恶性肿瘤，包括急性髓系白血病，胃肠道间质瘤及睾丸癌。KIT突变通常是成群出现的，包