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)

It was the aim of our study to determine the collection efficiency and yield of CD34+ cells in 88 cancer patients (pts, 44 males/44 females) who underwent 154 large-volume leukaphereses (LV-LPs). The diagnoses were as follows: 18 patients had Non-Hodgkin's lymphoma, 9 Hodgkin's disease, 24 multiple myeloma, 6 acute leukemia, 27 breast cancer, and 4 patients had solid tumors of different types. During the course of LV-LPs, 20 liters (1) of blood were processed at a median flow-rate of 85 ml/min (CS 3000 Baxter) and 130 ml/min (COBE Spectra), respectively. Peripheral blood stem cells (PBSC) were collected following granulocyte colony-stimulating factor (G-CSF)-supported cytotoxic chemotherapy. A 31% and 21% mean decrease in the platelet and white blood count was noted at the end of the LV-LPs when compared with the pre-leukapheresis values. The aphereses were well tolerated without adverse effects. The level of circulating CD34+ cells was closely related to the number of CD34+ cells contained in the respective leukapheresis product (R = 0.89, P < 0.001). Compared with 270 patients who underwent 838 regular 10 1 LPs, the yield of CD34+ cells/kg was almost two-fold greater (4.84 +/- 0.63 x 10(6) [Mean +/- SEM] vs. 2.60 +/- 0.16 x 10(6), P < 0.001). The antigenic profile of CD34+ cells was assessed in 54 separate products collected on the occasion of 27 LV-LPs following the processing of 10 1 and 20 1, respectively. The intra-individual comparison included differentiation- as well as lineage-associated markers (CD38, Thy-1, c-kit, CD33, CD45RA). No difference in the subset composition was observed between the first and second product, arguing against a preferential release of particular CD34+ cell subsets during the procedure. As shown by molecular biological or immunocytochemical examination, the likelihood of harvesting malignant cells using large-volume aphereses was not increased in comparison with regular leukaphereses. Single harvests of > or = 2.5 x 10(6) CD34+ cells/kg could be obtained in 74% of the patients, compared with 52% in case of regular LPs. As the majority of patients were autografted with more than 2.5 x 10(6) CD34+ cells/kg following high-dose therapy, hematological recovery in general was rapid and not related to the type of apheresis product used. Considering patient comfort and savings in resource utilization, large-volume leukaphereses have become the standard procedure for PBSC collection in our center.
 ...
PMID:Successful collection and transplantation of peripheral blood stem cells in cancer patients using large-volume leukaphereses. 898 64

Stem cell factor receptor (SCFR, c-kit), normally expressed on haematopoietic and mast cells, plays a regulatory role in cellular growth and differentiation. Dysregulated expression of SCFR may contribute to neoplastic transformation. We investigated expression of SCFR on malignant canine mast cells obtained directly from spontaneous canine mast cell neoplasms, in an attempt to determine whether these undifferentiated cells maintained expression of this growth-promoting cytokine receptor. Malignant mast cells (histological grade 2) from skin tumours or lymph node metastases were collected from canine patients, and SCFRs were detected by flow cytometric analysis of these cells. All of the tumours bound mouse and canine recombinant stem cell factor (SCF), indicating that the cells not only expressed SCFRs, but that the receptors possessed the functional property of ligand binding. Immunoglobulin Fc receptors for canine IgE were identified on these cells by flow cytometry, a further indication that the cells analysed were mast cells and retained some differentiated features. Immunohistochemical analysis of formalin-fixed, paraffin wax-embedded mast cell tumour biopsies confirmed expression of SCFRs by malignant cells from each tumour. The relative binding of SCF to suspensions of tumour cells, as assessed by flow cytometry, correlated with the intensity of immunolabelling for SCFR in sections of the same tumours, suggesting variability in SCFR expression between tumours. Agarose gel electrophoresis of the products of SCFR reverse transcription-polymerase chain reaction derived from each tumour had the molecular weight predicted for canine SCFR cDNA on the basis of the mouse and human counterparts. This further confirmed SCFR expression by malignant canine mast cells. Taken together, these results show that a membrane receptor capable of triggering cell growth is expressed by malignant canine mast cells, suggesting a role for this receptor in the aetiology of canine mast cell cancer. This relatively common malignancy of the dog would seem to present an opportunity for the investigation of the potential role of the SCF/SCFR pathway in the development of spontaneous malignancies of mast cells.
 ...
PMID:Expression of stem cell factor receptor (c-kit) by the malignant mast cells from spontaneous canine mast cell tumours. 900 81

Mobilized peripheral blood haematopoietic progenitor cells are increasingly being used as against bone marrow (BM) transplants, following high dose chemotherapy and/or radiotherapy for the management of chemosensitive malignancies. Rapid haematopoietic reconstitution as evidenced by reduced duration of neutropaenia, fewer donor platelet infusions, shorter hospital stay and reduced cost of treatment are the advantages of this procedure. Reduced tumour cell contamination of mobilized blood compared to bone marrow however, has not been substantiated. Mobilization of lymphokine activated killer cells (LAK), use of blood stem cells (BSC) for allogeneic transplants and ex vivo expansion of the mobilized cells are emerging as the future areas for research. Addition of interleukin-3 (IL-3), stem cell factor (c-kit ligand) and PIXY-321 appear to open-up new vistas by enforcing trilineage and multilineage haematopoietic reconstitution.
 ...
PMID:Blood stem cell transplantation: current concepts. 902 28

Most small cell lung cancers (SCLCs) ectopically express high levels of the c-kit receptor. We have examined if the receptor can serve as a target for a chimeric toxin, mSCF-PE40 composed of murine stem cell factor (SCF) genetically fused to the N terminus of a modified form of Pseudomonas exotoxin (PE) lacking its cell recognition domain. Selective cytotoxicity was found for human c-kit receptor-negative cells. This agent thus warrants further evaluation for therapy of human CSLCs.
Cancer Lett 1997 Feb 26
PMID:In vitro effects of a recombinant toxin, mSCF-PE40, targeting c-kit receptors ectopically expressed in small cell lung cancers. 906 15

In the hematopoietic lineage, the transcription factors GATA-1 and GATA-2 show restricted and largely overlapping expression profiles, but GATA-2 is uniquely expressed in early hematopoietic progenitors. GATA-3 is found exclusively in T cells of hematopoietic lineage. To clarify whether these expression profiles are preserved or changed during the development of malignancies, we analyzed the expression of GATA factors in the blasts from leukemic children. A total of 18 myelogenous leukemia and 24 lymphoblastic leukemia (ALL) cases were investigated. In the majority of the former cases, GATA-2 mRNA expression and the expression of CD34 and c-kit antigens on leukemic cells were demonstrated. In contrast, GATA-2 mRNA and c-kit antigen could not be detected in CD34-positive cells from ALL patients. GATA-3 mRNA was expressed in all T-ALL cases, but not in any precursor B-ALL. These findings suggest that down-regulation of GATA-2 and expression of GATA-3 are important events for the commitment of cells to lymphoid and T cell lineage, respectively. The expression profiles of GATA factors in leukemic cells are generally consistent with those in their normal counterparts, and thus provide a useful tool to determine the lineage commitment of unclassified leukemia.
 ...
PMID:Expression of GATA transcription factors in myelogenous and lymphoblastic leukemia cells. 911 95

We have previously cloned and sequenced a novel 3.5 kb c-kit mRNA expressed in a colon carcinoma cell line Colo201. Here we examined the expression of this truncated form of c-kit in 14 gastrointestinal cancer cells and 16 hematopoieic cancer cells by RT-PCR. Expression of the aberrant c-kit transcript was observed in various cancer cell lines. Furthermore, a new transcript which is 78 bp shorter than the transcript previously described was identified and characterized. These results indicate that two kinds of aberrant c-kit transcript produced by alternative promoter in intron 15 are expressed in human cancer cells.
Cancer Lett 1997 May 19
PMID:Expression and identification of aberrant c-kit transcripts in human cancer cells. 914 33

The product of the protooncogene c-kit is the receptor for the hematopoietic cytokine stem cell factor (SCF). C-kit is expressed on leukemic cells of the erythroid, myeloid, and mast-cell lineage and SCF has a proliferative effect on some of these cells. The role of SCF and c-kit in lymphoid malignancies is much less clear. Here we review the role of c-kit in normal lymphopoiesis and summarize its role in lymphoid malignancies. C-kit is expressed in normal lymphopoiesis and its ligand SCF synergizes with IL-7 to enhance the proliferation of B- and T-cell progenitors. In malignant lymphopoiesis, c-kit can also be expressed in B and T-lymphoblastic cells from children with non Hodgkin's lymphoma (NHL) or acute lymphoblastic leukemia (ALL) when analyzed by the highly sensitive reverse transcriptase polymerase chain reaction (RT-PCR). While c-kit receptors were detected by flow cytometric (FCM) analysis on about 40% of fresh T-lymphoblastic biopsy tumor cell preparations or T-lymphoblastic cell lines, no receptors were detected on B-lymphoblastic fresh cells or cell lines from children with B-ALL or Burkitt's lymphoma (BL). Almost all of the lymphoblastic cells expressing c-kit protein responded to recombinant human (rh)SCF with a downregulation of c-kit receptors. A proliferative response was detected only in a minority of these cells. B-ALL or BL cell lines showed no response to rhSCF. Upregulation of c-kit in T-lymphoblastic cells could be demonstrated by the addition of IL-1 beta, TNF-alpha, TGF-beta or A23187, and downregulation by rhSCF or phorbol myristate acetate (PMA). Despite upregulation of c-kit mRNA, protein remained undetectable on B-ALL or BL cells in the presence of A23187. The metabolic state of the cells seemed to influence c-kit expression, since c-kit was upregulated in T-lymphoblastic cells by the addition of new medium. C-kit appears to play a role in the growth of some malignant T-lymphoblastic but not B-lymphoblastic cells.
 ...
PMID:C-kit receptors in childhood malignant lymphoblastic cells. 916 31

We sought to determine the functional significance of the c-kit receptor (Kit) in melanoma, breast carcinoma, and non-small cell lung cancer (NSCLC). To explore these issues, we first screened cell lines of each type for c-kit mRNA expression using a reverse-transcription polymerase chain reaction. We found that WM-39 melanoma cells, HTB-22 breast carcinoma cells, and A549 NSCLC cells all expressed c-kit mRNA. Of interest, all of these cells expressed the c-kit ligand, Steel factor (SF). We then assessed the functional significance of c-kit and SF expression by disrupting the gene's expression with antisense (AS) oligodeoxynucleotides (ODN) targeted to c-kit mRNA codons 1-6 and SF mRNA codons 2-7, respectively. Nonhybridizing sequences [sense (5) and scrambled (SCR)] were also employed as controls. WM-39, HTB-22, and A549 cells were exposed to ODN (approximately 25 microM) for 5-7 days. Downregulation of c-kit and SF mRNA, and c-kit protein was demonstrated in cells treated with AS ODN. Effects on viable cell growth were demonstrated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) or 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4 -sulfophenyl)- 2H-tetrazolium (MTS) assay. In fact, c-kit antisense ODN inhibited the viable cell growth of A549 cells 66% and 79% compared to sense and untreated controls (P = .0003; P < .0001). Additionally, WM-39 cell growth was inhibited 48% and 21% (P < .0001, P < .03) and HTB-22 cell growth was inhibited 50% (P < .001) compared to sense and untreated controls. Viable cell growth was also significantly inhibited by SF AS ODN compared to S and SCR controls in all cell lines. These results demonstrate that WM-39, HTB-22, and A549 NSCLC cells all express the c-kit and SF protooncogenes and suggest that the encoded receptor and ligand are important for cell growth. By finding the presence, and functional importance, of both the receptor and ligand in these cells, this study suggests the existence of an autocrine loop growth mechanism worthy of further study.
Cancer Gene Ther
PMID:Evidence for a functional kit receptor in melanoma, breast, and lung carcinoma cells. 917 36

Activation of the receptor tyrosine kinase c-kit by the kit-ligand, also known as stem cell factor (SCF), is essential to melanocyte and germ cell development and during the early stages of hematopoiesis. Deregulated expression of c-kit has been reported in malignancies affecting these lineages, i.e., myeloid leukemias, melanomas, and germ cell tumors. In addition, c-kit and SCF are coexpressed in some breast and colorectal cancer (CRC) cells, raising the question of whether c-kit serves an autocrine role in normal or malignant epithelial tissues. In this study, we demonstrate that human colorectal carcinomas, but not normal colorectal mucosa cells, coexpress SCF and c-kit in situ. Expression of c-kit was also observed in mucosa adjacent to colorectal tumor tissue. Consistent with a growth-regulatory role of SCF in CRC cells, exogenous SCF stimulated anchorage-dependent and anchorage-independent growth in four out of five CRC cell lines. Exogenous transforming growth factor (TGF)-beta 1 added at nanomolar concentrations to HT-29 CRC cells, which express the type I, II, and III TGF-beta receptors, downregulated c-kit expression to background levels and inhibited c-kit-dependent proliferation. Similarly, TGF-beta 1 inhibited SCF-dependent proliferation of three first-passage CRC cell lines. In summary, expression of the potential autocrine SCF/ c-kit axis is a tumor-associated phenomenon in colorectal cancer that can be suppressed by TGF-beta 1 in TGF-beta-responsive CRC cells.
 ...
PMID:Growth stimulation of colorectal carcinoma cells via the c-kit receptor is inhibited by TGF-beta 1. 920 20

The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor. It is expressed by the primitive CD34 positive haemopoietic stem cells and interacts with the Kit ligand for signal transduction. It was reported to be expressed in over 80% of acute myelogenous leukaemia (AML) patients in North America and Japan. We analyzed 20 AML patients for c-kit expression using either Northern blot analysis or flow cytometry with the YB5.B8 anti-c-kit antibodies. Only 6 out of 20 AML patients expressed the c-kit mRNA or protein product. However, a previously unreported abnormal sized 1.7-1.9 kb transcript was detected in the blast cells of 1 AML patient, 1 acute mixed lineage leukaemia patient and 1 chronic myelogenous leukaemia (CML) patient in myeloblastic transformation. Our data suggested that in most Hong Kong Chinese AML patients, leukaemia transformation may have occurred at a c-kit negative stage. Alternatively, the abnormal sized c-kit transcript that was detected in some Chinese myeloid leukaemia patients may represent an aberrant c-kit receptor that plays an important role in leukaemogenesis.
Cancer Lett 1997 Jun 24
PMID:Low frequency of c-kit expression and detection of an aberrant Kit message among Hong Kong Chinese myelogenous leukaemia patients. 921 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>