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

Patients with head and neck squamous cell carcinoma (HNSCC) have profound immune deficiencies. In 65% of these patients, there is an increased intra-tumoral presence of immune-suppressive CD34+ progenitor cells. The goal of the present study was to determine whether CD34+ cell levels were also increased in the peripheral blood of HNSCC patients and if these immune-suppressive cells could be differentiated into dendritic cells. Our results showed that CD34+ cell levels are increased in the peripheral blood of HNSCC patients. To assess if these CD34+ cells could differentiate into dendritic cells, they were isolated from the blood of HNSCC patients and cultured for 12 days with various cytokine combinations. Culturing CD34+ cells with stem cell factor (c-kit ligand) plus granulocyte-macrophage colony-stimulating factor resulted in the appearance of a significant proportion of cells expressing phenotypic markers characteristic of dendritic cells. Also, including tumor necrosis factor-alpha yielded a significant proportion of cells resembling the bipotential precursor cells for dendritic cells and monocytes (CD14+CD1a+), in addition to the dendritic-like cells. When the differentiation inducer 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] was added along with the cytokine combinations, the yield of cells having characteristics of dendritic cells was further increased. Cells that were derived from CD34+ cell cultures containing 1,25(OH)2D3 had a more potent capacity to present the recall antigen tetanus toxoid to autologous peripheral blood leukocytes and to stimulate a mixed leukocyte response compared to cultures to which 1,25(OH)2D3 had not been added. Our results show that CD34+ cells, whose frequency is increased in HNSCC patients, can be differentiated into cells that phenotypically and functionally resemble dendritic cells and that 1,25(OH)2D3 accentuates this differentiation.
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PMID:Increased presence of CD34+ cells in the peripheral blood of head and neck cancer patients and their differentiation into dendritic cells. 939 43

Dendritic cells (DCs) are powerful antigen-presenting cells. Because DCs are rare cells, methods to produce them in vitro are valuable ways to study their biologic properties and to generate cells for immunotherapy. This study defines the antigen-presenting properties of DCs generated in vitro from CD34+ cells of patients with breast cancer. The combination of cytokines flt3 ligand + c-kit ligand + granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-4 (IL-4) + tumor necrosis factor-alpha (TNF-alpha) was used to maximize the output of mature DCs in the culture of CD34+ cells while minimizing the production of monocytes. Cells grew and differentiated into DCs as measured by a time-dependent upregulation of cell surface antigens major histocompatibility complex class II, CD1a, CD80, CD86, CD40, and CD4, so that 40% +/- 9% (n = 6) of cells in culture at day 15 were CD1a+CD14-. Markers were acquired in the same sequence as on monocytes induced to differentiate with GM-CSF + IL-4. Differentiation was marked by a time-dependent increase in allostimulatory function, which, at its peak, was more potent than in cultures of DCs generated from monocytes with GM-CSF + IL-4, but was comparable on a cell-to-cell basis to that of mature monocytes cultured in flt3-ligand + c-kit-ligand + GM-CSF + IL-4 + TNF-alpha. Both CD34+ cell-derived and monocyte-derived DCs were able to process and to present tetanus toxoid and keyhole limpet hemocyanin to autologous T cells and to present major histocompatibility class I-binding peptides to CD8+ cytotoxic T lymphocytes inducing interferon-gamma production. Altogether, these results suggest that DCs generated from CD34+ cells of patients with breast cancer with flt3 ligand, c-kit ligand, GM-CSF, IL-4, and TNF-alpha are competent antigen-presenting cells, particularly for CD8+ cytotoxic T lymphocytes, and resemble mature monocyte-derived DCs in the assays described here.
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PMID:Dendritic cells generated from CD34+ progenitor cells with flt3 ligand, c-kit ligand, GM-CSF, IL-4, and TNF-alpha are functional antigen-presenting cells resembling mature monocyte-derived dendritic cells. 1068 37

The c-kit receptor tyrosine kinase encoded by the white-spotting (W) gene is highly expressed in rat hippocampal CA1-CA4 regions. We found an impaired spatial learning and memory in homozygous c-kit (Ws/Ws) mutant rats that have a 12-base deletion in the tyrosine kinase domain of the c-kit gene and a very low kinase activity. Electrophysiological studies in hippocampal slices revealed that the long-term potentiation (LTP) induced by the tetanic stimulation (100 Hz, 1 sec) in the mossy fiber (MF)-CA3 pathway, but not in the Schaffer collaterals/commissural-CA1 pathway, was significantly reduced in c-kit mutants compared with wild-type (+/+) rats. The paired-pulse facilitation (PPF) was measured before the tetanus and after the establishment of the LTP in each slice. The initial PPF in the MF-CA3 pathway positively correlated with the amplitude of the LTP in the wild-type rats but not in the c-kit mutant rats. Furthermore, they failed to show the normal characteristics observed in the MF-CA3 pathway of +/+ rats; that is, the negative correlation between the initial PPF and the changes in PPF measured after the LTP. These findings suggest an involvement of SCF/c-kit signaling in hippocampal synaptic potentiation and spatial learning and memory.
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PMID:Impairment of spatial learning and hippocampal synaptic potentiation in c-kit mutant rats. 1111 97

The effects of recombinant mouse stem cell factor (rmSCF) on paired-pulse facilitation (PPF) and long-term potentiation (LTP) in the mossy fiber (MF)-CA3 pathway were examined in mouse hippocampal slices by recording field EPSPs. When PPF was measured before and 30 min after tetanic stimulation, the initial PPF positively correlated with the amplitude of LTP and negatively correlated with changes in PPF (PPF after LTP minus initial PPF), indicating a presynaptic component in MF-CA3 LTP. Bath application of rmSCF for 30 min also produced negative correlation between initial PPF and changes in PPF after rmSCF, suggesting common mechanisms of the LTP- and rmSCF-induced modulation of PPF. The rmSCF-induced negative correlation was abolished by simultaneous perfusion with K252a, a receptor tyrosine kinase inhibitor, and by wortmannin, a phosphatidylinositol-3'-kinase inhibitor. Although SCF activates phospholipase A(2) (PLA(2)) and diacylglycerol (DAG) lipase to produce arachidonic acid (AA) in mast cells, mepacrine, a PLA(2) inhibitor, but not RHC80267, a DAG lipase inhibitor, abolished the negative correlation. The induction of LTP was prevented by perfusion with rmSCF started 30 min before tetanus, while preincubation of slices with antibody for SCF receptor, c-kit, blocked LTP, suggesting that the intrinsic SCF is involved in the induction of LTP and the blockade of LTP by rmSCF might be due to an occlusion of SCF/c-kit signaling. In addition, since c-kit is expressed on the postsynaptic CA3 neurons but not on the MF terminals in mice, effects of rmSCF on PPF may be mediated by the PLA(2)-induced AA acting as a retrograde messenger.
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PMID:Stem cell factor modulates paired-pulse facilitation and long-term potentiation in the hippocampal mossy fiber-CA3 pathway in mice. 1213 20

Chronic prostatitis (CP) with complex pathogenesis is difficult for treatment. c-kit has been associated with the control of cell proliferation of prostate cells. This study aims to evaluate the role of resveratrol, an activator of Sirt1, in regulating the expression of c-kit in CP and investigate the consequent effects on cell cycle. Rat model of CP was established through subcutaneous injections of diphtheria-pertussis-tetanus vaccine and subsequently treated with resveratrol. Hematoxylin and eosin staining was performed to identify the histopathological changes in prostates. Western blotting and immunohistochemical staining examined the expression level of c-kit, stem cell factor (SCF), Sirt1, and cell cycle-associated proteins. The model group exhibited severe diffuse chronic inflammation, characterized by leukocyte infiltration and papillary frond protrusion into the gland cavities, and a notable increase in prostatic epithelial height. Gland lumen diameter was also significantly smaller; the activity of c-kit/SCF in the CP rats was increased significantly compared to the control group. Meanwhile, the cell cycle proteins are dysregulated significantly in CP rats. Resveratrol treatment significantly improved these factors by Sirt1 activation. Dysregulation of cell cycle was involved in the pathological processes of CP, which was improved after resveratrol treatment by the downregulation of c-kit/SCF by activating Sirt1.
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PMID:Resveratrol Improves Cell Cycle Arrest in Chronic Prostatitis Rats, by C-kit/SCF Suppression. 2860 67