Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The surface antigenic profile of 10 surgically removed uveal melanoma lesions and 5 conjunctival melanomas was analyzed with a panel of 22 monoclonal antibodies (mAbs) raised against membrane bound cutaneous melanoma-associated antigens (MAA). In addition these lesions were tested for their reactivity with mAbs against MHC class I and II molecules, CD7 (Pan-T) and CD10 (CALLA). The anti-MAA mAbs can be divided into two major groups: first those mAbs detecting markers expressed by the majority of uveal melanomas such as NKI-Beteb, NKI/C3, G7E2, M-2-2-4, Mel-14, G7A5, AMF6, AMF7, Pal M1, Pal M2, Me14/D12. The staining intensity for these mAbs was rather high, ranging in intensity between 70 and 100%. The second group of antibodies includes mAbs detecting markers not or very poorly expressed on ocular melanomas. The anti-ICAM-1 mAb P358 did not react with any of the lesions tested and mAb Muc18 and Muc54 only with one and two out of 15 lesions, respectively. The majority of spindle lesions and mixed type lesions and half of the epitheloid type lesions expressed HLA class I molecules, while HLA class II molecules were found on half of the spindle and epitheloid type lesions and on a small number of mixed cell type lesions. All spindle lesions were found to express the CD10 (CALLA) molecule and less than half of the other type of lesions were stained with an anti CD10 mAb. The melanoma associated ganglioside GD3 was mainly expressed on epitheloid type lesions while GD2 was predominantly expressed on mixed type lesions. In essence, the overall surface phenotype of the uveal melanoma lesions tested, as defined by the panel of mAbs used, differs markedly from the surface phenotype of cutaneous melanoma lesions defined by a very similar antibody panel.
 ...
PMID:Surface antigenic profile of uveal melanoma lesions analysed with a panel of monoclonal antibodies directed against cutaneous melanoma. 169 97

We have previously shown that neutral endopeptidase (NEP; EC 3.4.24.11) regulates neuropeptide-induced responses. Recently, Pierart et al. reported that NEP degraded purified interleukin-1 (IL-1) using thymocyte proliferation assay. Since IL-1 is an important cytokine in the immune response and inflammation, we have assessed whether NEP hydrolyzes recombinant human IL-1 beta using three assay systems (bioassay, immunoassay, and HPLC analysis). NEP on the NALM-6 cells (both intact cells and the solubilized plasma membrane fraction) efficiently hydrolyzed Met5-enkephalin and substance P. However, NEP did not significantly decrease the amount of rhIL-1 beta assessed by the growth inhibitory activity of a human melanoma, by the immunoassay, or by the direct analysis on HPLC. Therefore, we conclude that NEP does not significantly hydrolyze rhIL-1 beta. Our results suggest that, in contrast to the regulatory role of NEP in neuropeptide-induced responses, NEP is not a regulatory enzyme for IL-1-induced responses.
 ...
PMID:Neutral endopeptidase (EC 3.4.24.11) does not hydrolyze recombinant human interleukin-1 beta. 171 45

The rap1/Krev-1 gene encodes a ras-related protein that suppresses transformation by ras oncogenes. We have purified an 88 kd GTPase activating protein (GAP), specific for the rap1/Krev-1 gene product, from bovine brain. Based on partial amino acid sequences obtained from this protein, a 3.3 kb cDNA was isolated from a human brain library. Expression of the cDNA in insect Sf9 cells resulted in high level production of an 85-95 kd rap1GAP that specifically stimulated the GTPase activity of p21rap1. The complete deduced amino acid sequence is not homologous to any known protein sequences, including GAPs specific for p21ras. Northern and Western blotting analysis indicate that rap1GAP is not ubiquitously expressed and appears most abundant in fetal tissues and certain tumor cell lines, particularly the Wilms' kidney tumor, SK-NEP-1, and the melanoma, SK-MEL-3, cell lines.
 ...
PMID:Molecular cloning of a GTPase activating protein specific for the Krev-1 protein p21rap1. 190 17

The common acute lymphoblastic leukemia antigen (CALLA) is identical to human endopeptidase 24.11 (E-24.11) and is expressed on certain human melanoma lines. This work was conducted in order to investigate whether alpha-melanocyte-stimulating hormone (alpha-MSH) could be a substrate for E-24.11, its degradation leading to the negative alpha-MSH radiobinding assay results observed with some CALLA-positive cell lines. We used 3 human melanoma cell lines (GLL-19, Mel Juso and G361) which lack receptors to alpha-MSH and express CALLA, and, as a control, one CALLA-negative melanoma cell line (HBL) with specific receptors for alpha-MSH. Radioimmunoassays give evidence that alpha-MSH was degraded in the presence of the 4 melanoma cell lines and that disappearance of the peptide was significantly reduced by phosphoramidon in 2 lines (GLL-19 and G361). Upon incubation of alpha-MSH with GLL-19 and G361 cell membranes, 3 degradation products were completely abolished in the presence of phosphoramidon. Amino acid content analysis of alpha-MSH fragments produced by purified E-24.11 permitted identification of 6 peptide bonds in the sequence of alpha-MSH susceptible to cleavage by the enzyme. It is concluded that alpha-MSH is a substrate in vitro for purified E-24.11 and for the enzyme present on the human melanoma cell lines GLL-19 and G361, expressing a high level of endopeptidase activity. However, hydrolysis of alpha-MSH by this enzyme does not seem to represent the main factor responsible for the apparent absence of receptors for the hormone on some cell lines.
 ...
PMID:Degradation of alpha-melanocyte stimulating hormone (alpha-MSH) by CALLA/endopeptidase 24.11 expressed by human melanoma cells in culture. 217 14

We have previously reported that the amino acid sequence of the common acute lymphoblastic leukemia antigen (CALLA, CD10) translated from a normal human kidney cDNA clone is identical to that of neutral endopeptidase (NEP, EC 3.4.24.11). In this study, we show that by flow cytometry, a monoclonal antibody (135A3) produced against rabbit NEP reacted selectively with leukemia and melanoma cell lines expressing CALLA on their surface. A glycoprotein of apparent Mr 100,000 was immunoprecipitated from surface labeled NALM-1 leukemia or Mel-1477 melanoma cells with monoclonal antibodies to NEP (135A3) or CALLA (44C10). mRNAs hybridizing to a NEP-specific probe were present in CALLA+ leukemia and melanoma cell lines, but absent from CALLA- lines. NEP enzymatic activity was detected on intact cells from CALLA+ lines, but not CALLA- lines. The activity was blocked by two selective inhibitors of NEP, thiorphan and phosphoramidon. CALLA antigen purified from the NALM-6 leukemic cell line by affinity to 44C10-IgG Sepharose retained a peptidase activity that was completely blocked by thiorphan and phosphoramidon. Thus the CALLA antigen present at the surface of leukemia and melanoma cell lines is an enzymatically active neutral endopeptidase.
 ...
PMID:Common acute lymphoblastic leukemia antigen expressed on leukemia and melanoma cell lines has neutral endopeptidase activity. 252 92

Several established human glioma cell lines have been previously shown to express the common acute lymphoblastic leukemia antigen (cALLa, CD 10), an important marker in the diagnosis of human acute lymphocytic leukemia (ALL). The amino acid sequence of cALLa is identical to that of neutral endopeptidase (NEP,E.C.3.4.24.11), and cALLa expressed on leukemia and melanoma cell lines is enzymatically active NEP. In the present study, we investigated whether cALLa expressed on glioma cell lines is active NEP. We detected cALLa on 10 out of 13 glioma cell lines using 2 different anti-cALLa MAbs (A12-G4 and FAH99). NEP antigen, as detected by immunostaining with an anti-NEP MAb (135A3), was expressed on the same 10 lines. cALLa-positive, but not cALLa-negative cell lines displayed an endopeptidase activity. This activity could be blocked by phosphoramidon, a specific inhibitor of NEP. Furthermore, mRNAs hybridizing to an NEP-specific probe were present in cALLa-positive glioma cells but not in cALLa-negative cells. Taken together, the results provide strong evidence that cALLa-positive glioma cell lines express endopeptidase activity on the cell surface.
 ...
PMID:Human glioma cell lines expressing the common acute lymphoblastic leukemia antigen (cALLa) have neutral endopeptidase activity. 253 Nov 22

Recently, great interest has been shown in the histological identification of small cell tumours of childhood--nephroblastoma (Wilms' tumour), neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma--using immunohistochemical methods. However, several antigens operationally specific for leucocyte typing in blood and marrow are also expressed on cells of epithelial and neural origin. We undertook phenotypic characterization of 17 non-haemopoietic small cell tumours of childhood using a panel of 30 monoclonal antibodies to leucocyte, epithelial and cytoskeletal antigens using a sensitive alkaline phosphatase-anti-alkaline phosphatase technique on cryostat sections of fresh tumour. Our results demonstrated frequent expression of the leucocyte-associated antigens CD10 (CALLA), CD9 (p24) and CDw32 (FcRII) in these small cell tumours and occasional expression of MHC class II (HLA-DR) and HNK-1 antigens. However, the leucocyte-associated antigens CD45 (leucocyte common), CD22 (pan B-cell), CD11b (C3bi receptor), CD15 (Lewisx) or CDw42 (platelet gp Ib) were not detected on any tumour. Aberrant expression of desmin, neurofilament and UJ13A antigen was found in nephroblastoma and of epithelial-associated markers (CIBr17 and 43-9F) in neuroblastoma. Our results also demonstrated broad reactivity in frozen section with two monoclonal antibodies specific for melanoma (NKI/C-3) or epithelial cells (OM-1) in paraffin sections. Hence, it is necessary to include monoclonal antibodies to CD45 and pan-epithelial antigens, e.g. LP34 (cytokeratin) or HEA125 for the precise immunohistochemical identification of small round cell malignancies of childhood.
 ...
PMID:Phenotypic characterization of non-haemopoietic small cell tumours of childhood with monoclonal antibodies to leucocytes, epithelial cells and cytoskeletal proteins. 254

Immunoperoxidase localization of monoclonal antibodies in sections of melanoma has been used to identify histological features which may be of prognostic importance in melanoma, in particular whether certain structures on melanoma cells may determine the degree and nature of lymphoid infiltrates and whether these may be related to prognosis. Monoclonal antibodies to lymphocyte subpopulations were used to identify and quantitate lymphoid infiltrates in 15 primary melanomas and 8 cutaneous metastases. These were correlated with histological features identified in routine sections. There was a wide variation in the numbers of mononuclear cells associated with both primary and metastatic melanoma. T cells and to a lesser extent macrophages accounted for the majority of the cells, B cells and natural killer (NK) cells for only 2% of the infiltrates. The Leu 3a (helper) T cell subpopulation predominated in primary tumours, OKT8 positive (suppressor/cytotoxic) cells in metastases. Infiltrates in which OKT8 cells predominated were associated with ulceration, a high mitotic rate and thick primary tumours. The converse applied to Leu 3a infiltrates. Infiltrates with a high proportion of Leu 3a positive cells tended to be associated with Thy-1 positive, DR antigen negative tumours. Thy-1 antigens were predominantly expressed on primary tumours and rarely on metastases whereas the converse applied to expression of the acute lymphoblastic leukemia antigen (CALLA) on melanoma cells. These findings suggest that certain melanoma antigens may be related to the nature of the lymphoid infiltrate associated with melanoma and possibly with the behaviour of the tumour in the host. They further suggest that identification of cell surface structures and lymphoid infiltrates by these techniques may be a valuable extension of routine histopathological assessment of prognosis in melanoma.
 ...
PMID:Current research on immunopathology of melanoma: analysis of lymphocyte populations in relation to antigen expression and histological features of melanoma. 286 82

Indirect immunofluorescence staining with a large battery of monoclonal antibodies of primary and autologous metastatic lesions removed from seven patients with melanoma has detected heterogeneity in the expression of various types of melanoma-associated antigens (MAAs), of distinct determinants of the high molecular weight melanoma-associated antigen (HMW-MAA), of the two subunits of Class I HLA antigens, and of the gene products of the HLA-D region. Among the 10 MAAs tested, the HMW-MAA had the highest frequency and the Mr 87,000 MAA the lowest. Furthermore, the HMW-MAA displayed the lowest heterogeneity. These findings, in conjunction with the restricted tissue distribution of the HMW-MAA, its lack of susceptibility to antibody-mediated modulation, and the high affinity of the available anti-HMW-MAA monoclonal antibodies, indicate that this antigen may be a useful marker for radioimaging and immunotherapy in patients with melanoma. The common acute lymphoblastic leukemia antigen was detected only in five lesions. Class I HLA antigens were detected in a larger number of lesions than HLA-DR antigens, which had a significantly higher frequency than HLA-DQ antigens. The degree of antigenic heterogeneity did not appear to correlate with the histopathological features of the lesions and/or with the clinical course of the disease. The results of the present study indicate that immunodiagnostic and immunotherapeutic approaches to melanoma should rely on the use of combinations of monoclonal antibodies to distinct MAAs.
 ...
PMID:Heterogeneous expression of melanoma-associated antigens and HLA antigens by primary and multiple metastatic lesions removed from patients with melanoma. 315 50

Fifteen human melanoma cells lines were tested by an antibody-binding radioimmunoassay using a monoclonal antibody (A12) directed against the common acute lymphoblastic leukemia antigen (CALLA). Cells from six melanoma lines were found to react with this antibody. The level of antigen and the percentage of positive cells in these six melanoma lines showed wide variation, as demonstrated by analysis in the fluorescence-activated cell sorter (FACS). Immunoprecipitation of solubilized 125I-labeled membrane proteins from CALLA positive melanoma cells with A12 monoclonal antibody revealed a major polypeptide chain with an apparent m.w. of 100,000 daltons, characteristic for CALLA as determined on SDS-polyacrylamide gel electrophoresis. The expression of CALLA on MP-6 melanoma cells was modulated when the cells were cultured in the presence of A12 antibody. Reexpression of CALLA on these cells occurred within 5 days after transfer of the modulated cells into medium devoid of monoclonal antibody.
 ...
PMID:Expression of common acute lymphoblastic leukemia antigen (CALLA) on human malignant melanoma cell lines. 633 29


1 2 3 4 5 6 Next >>