UMLS:C0025202 - FACTA Search

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Query: UMLS:C0025202 (melanoma)
69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene that encodes the membrane-bound Mr 100,000 human melanoma-associated antigen (MAA) defined by mouse mAb 376.96, a leukocyte and fibroblast interferon-modulated glycoprotein having preferential distribution on melanoma and carcinoma cells, has been transfected into the mouse melanoma cell line B78H1 as a step toward molecular cloning and characterization of the MAA. Primary, secondary, and tertiary B78H1 transfectants expressing the Mr 100,000 MAA gene were generated by treatment with coprecipitated DNA from Mr 100,000 MAA+ human or transfectant mouse cells and they were detected by an indirect RBC rosetting assay. The Mr 100,000 MAA gene was also transferred into K-1735 mouse melanoma cells and into nonmalignant and malignant mouse fibroblast lines. The species immunoprecipitated by mAb 376.96 from human melanoma cells (Mr 100,000) and from mouse melanoma transfectant cells (Mr 97,000-100,000) were both converted to molecule(s) having an Mr of approximately 70,000 by enzymatic removal of asparagine-linked carbohydrate residues. Two independent secondary transformant clones of B78H1 cells express Mr 100,000 MAA antigenicity at levels significantly higher than those observed when one or two copies of the gene are present. Clone Mr 100,000 secondary-A spontaneously overexpresses Mr 100,000 MAA at least 5-fold and has greater than or equal to 10 times elevated levels of putatively Mr 100,000 MAA gene-associated human alu family repeat element (h-alu)-positive restriction fragments relative to "single" copy secondary transfectant cells. Clone Mr 100,000 secondary-B has increased copy number and expression of Mr 100,000 MAA as a consequence of a selective co-amplification procedure which is targeted to a mouse wild type dihydrofolate reductase (dhfr) gene expression vector. This vector was co-introduced into B78H1 cells in addition to the DNA of Mr 100,000 MAA+ primary transfectant cells and the initially selected aminoglycoside phosphotransferase (neo) gene vector. Stepwise selections of a secondary Mr 100,000 MAA+ transfectant clone with increasing concentrations of the dihydrofolate reductase-inhibitory antimetabolite methotrexate led to progressive increases in copy numbers of the introduced dhfr gene and to parallel increases in h-alu sequences, in cellular levels of dihydrofolate reductase protein, and in cellular mAb 376.96 reactivity. Levels of these entities ultimately reached 50-fold, relative to levels expressed prior to amplification. The array of h-alu+ restriction fragments amplified in Mr 100,000 secondary-B cell DNA is very similar to that observed in Mr 100,000 secondary-A cell DNA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Interspecific DNA-mediated transfer and amplification of a gene specifying a Mr 100,000 human melanoma-associated cell surface glycoprotein. 230 16

Hanganutziu-Deicher (H-D) antigen is classified as a heterophile antigen and chemically defined as a glycoconjugate which contains N-glycolylneuraminic acid. H-D antigens are absent from normal human tissues, but can be expressed on a variety of human malignant cells, including melanoma. Natural anti-H-D antibodies have been detected in man with and without malignancies, but in this study when the level of antibody was compared between healthy adults and patients with melanoma, elevated anti-H-D antibody levels were found more frequently in melanoma patients for both IgM (p = 0.0001) and IgG (p = 0.0001). The present study was designed to evaluate the significance of the H-D antigen-antibody system in melanoma suppression. Sera from melanoma patients containing anti-H-D antibody reacted strongly to H-D antigen expressed on melanoma by means of flow cytometry. In a complement-dependent cytotoxicity assay this antibody killed melanoma cells in vitro. In vivo significance of the antibody was assessed by evaluating the relationship between the antibody levels and the clinical course in patients with stage II melanoma. Antibody levels were measured by enzyme-linked immunosorbent assay using a H-D glycoprotein antigen isolated from bovine erythrocytes. A significantly higher level of IgG (p = 0.0640) and IgM (p = 0.0644) anti-H-D antibody was demonstrated in those patients who were free of disease more than 5 years after surgery than in those who relapsed within 2 years. This study provides a rational basis for immunotherapy targeting H-D antigen in human melanoma.
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PMID:Hanganutziu-Deicher antigen as a possible target for immunotherapy of melanoma. 235 74

Neuroglandular antigen (NGA) was identified as a human melanoma-associated antigen by a panel of murine monoclonal antibodies of both IgG2a (LS62, LS76, LS159) and IgG1 (LS113, LS140, LS152) subclasses, developed in this laboratory (L. Sikora, A. Pinto, D. Demetrick, W. Dixon, S. Urbanski, and L. M. Jerry, Int. J. Cancer, 39: 138-145, 1987). Monoclonal antibody LS62 was used to immunoprecipitate NGA from radiolabeled cultured melanoma cells, and it behaved as a heterogeneous glycoprotein "smear" on sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis (Mr 29,000-70,000). Radioactive pulse-chase time course experiments using human melanoma cells cultured in the presence or absence of inhibitors of protein glycosylation showed that the antigen consisted of a core protein with a molecular weight of 22,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This molecule was modified by the addition of at least three N-linked oligosaccharide side chains (as revealed by limited N-glycanase digestion) to give a precursor form with a molecular weight of approximately 34,000. Subsequent processing steps yielded a heterogeneous family of glycoproteins with varying amounts of covalently attached carbohydrate. Much of this heterogeneity in both molecular weight and pI (as revealed by two-dimensional electrophoresis) could be removed by treatment of the antigen with neuraminidase, suggesting heavy sialylation of the glycoprotein. NGA could be detected on the surface of melanoma cells by fluorescence-activated cell sorter analysis, surface radioiodination, and, as previously shown, immunoperoxidase staining. However, there was a larger intracellular pool of the molecule and the antigen was rapidly released into the culture supernatant. The function of NGA remains unknown but its elevated expression in transformed melanocytes have prompted this characterization to understand its biochemical nature and relation to other melanoma-associated antigens.
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PMID:Biosynthesis, glycosylation and intracellular processing of the neuroglandular antigen, a human melanoma-associated antigen. 236 31

The influence of 2 kinds of transplantable melanomas differing in biological properties on the contents of glycoprotein components and heterogeneity of the surface material in hamster peritoneal macrophages was studied. Distinct changes in the content of protein and glycoprotein components were found. Biochemical differences in the degree of these changes in macrophage surface material in relation to the kind of melanoma were observed. The electrophoretic patterns of the surface material derived from macrophages of hamsters bearing 2 kinds of melanoma showed some differences as well. It has been suggested that these differences seem to be related to the biological properties of the melanoma lines and reflect alterations of macrophage tumoricidal activity.
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PMID:Surface glycoproteins of peritoneal macrophages in hamsters bearing transplantable melanomas. 238 64

Thirty-two murine monoclonal antibodies (MAbs) against the external domain of the human transferrin (Tf) receptor have been obtained using human Tf receptor glycoprotein produced in a baculovirus expression system as immunogen. The MAbs were tested separately, and in combination, for their ability to inhibit growth of CCRF-CEM leukemic T-cells in tissue culture. One MAb, D65.30, an IgG1, inhibited growth of CCRF-CEM cells as effectively as the anti-Tf receptor MAb 42/6, an IgA, previously found to have the highest antiproliferative activity in this assay. Some combinations of two or more MAbs inhibited the in vitro growth of CCRF-CEM much more effectively than single MAbs. Eleven IgG1 anti-Tf receptor MAbs, when combined individually with D65.30, increased the inhibition of CCRF-CEM growth from approximately 65% to greater than 90% in a 7-day growth assay. Similarly, many IgG MAbs in combination with 42/6 also inhibited CCRF-CEM growth by greater than 90%. The growth-inhibitory effects of certain combinations of MAbs were clearly synergistic, because either one or both MAbs tested separately were inactive. These pairs of MAbs also inhibited the growth of HL-60 and KG-1 leukemic cells by greater than 90% and partially inhibited the growth of K562 erythroleukemia and M21 melanoma cells, which are resistant to MAb 42/6. However, not all combinations of anti-Tf receptor MAbs were more effective; eight MAbs markedly antagonized the antiproliferative effects of D65.30, whereas 12 others had little or no effect. Preincubation of HL-60 cells with three different pairs of MAbs, D65.30 and A27.15, B3/25 and 42/6, and B3/25 and TR3A, inhibited subsequent colony formation by greater than 95%, demonstrating that their action is cytotoxic, not cytostatic. The antiproliferative activity of these pairs of MAbs correlates with their ability to block Tf-mediated 59Fe uptake and perturb Tf receptor expression. Treatment of nude mice bearing established s.c. CCRF-CEM tumors with a combination of MAbs D65.30 and A27.15 inhibited tumor growth and in some animals led to complete tumor regression. Each MAb administered separately was much less effective. We conclude that combinations of two or more anti-Tf receptor MAbs can interact synergistically to inhibit cell growth in vitro and tumor growth in vivo.
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PMID:Combinations of anti-transferrin receptor monoclonal antibodies inhibit human tumor cell growth in vitro and in vivo: evidence for synergistic antiproliferative effects. 240 Sep 93

Murine monoclonal antibody (MAb) LS109 was one of a series of MAbs produced by hyperimmunization of mice with detergent extracts of pooled melanoma cell lines and metastatic melanoma patient tumors. ELISA screening of extracts of individual cultured melanoma cell lines and single patient tumors with MAb LS109 gave an interesting pattern of reactivity. The antibody was strongly positive with some of these extracts, yet negative or weakly positive with others. In addition, there was strong reactivity with a restricted set of normal necropsy tissues and certain non-melanoma tumor extracts. Taken together, our data suggest that MAb LS109 recognizes a normal differentiation antigen which is perhaps aberrantly expressed or over-produced during certain stages of melanoma tumor progression. The antigen recognized by LS109 is a heterodimeric surface glycoprotein molecule, consisting of an 89-kDa "heavy" chain linked by disulfide bonds to an 83-kDa "light" chain. Under non-reducing SDS-PAGE conditions, the intact dimer migrates with an Mr of approximately 140kDa. The 89-kDa component appears to be heavily N-glycosylated whereas the 38-kDa component has little, if any, covalently attached carbohydrate. Our data show the biosynthesis, glycosylation and turnover of the LS109 antigen, as well as evidence of its surface localization. In addition, evidence is presented that the LS109 antigen is identical to the 4F2 cell activation/proliferation molecule previously described on a variety of normal and neoplastic cells.
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PMID:Isolation and characterization of a heterodimeric surface antigen on human melanoma cells and evidence that it is the 4F2 cell activation/proliferation molecule. 240 79

Metabolic labelling of K-1735 melanoma variants with 3H-glucosamine and cell harvesting with the commonly used protease inhibitor phenylmethylsulfonylfluoride revealed a Triton-insoluble fibronection-like 230 kd component in poorly metastatic cells. This component was not evident in highly metastatic cells. Significantly improved surface labelling and detection of the 230 kd glycoprotein in the highly metastatic variant was achieved by zinc chloride-aprotinin treatment of cells prior to harvesting. This procedure also revealed an increase in a trypsin-sensitive glycoprotein of higher molecular weight in the Triton-insoluble fraction of the highly metastatic cell variant. Glycoprotein labelling in this fraction showed an electrophoretic pattern strongly resembling that reported by others for the high-molecular-weight human melanoma-associated glycoprotein complex. The differential detection of the high-molecular-weight glycoprotein species in melanoma variants with differing metastatic abilities in an animal model provides a means of studying their possible relevance to metastatic melanoma. Our data also suggest that zinc chloride-aprotinin can be used to improve the detection of labile cell-surface components.
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PMID:Improved detection of labile cell-surface components with zinc chloride-aprotinin: demonstration of glycoprotein differences in K-1735 metastatic melanoma variants. 241 34

Plasmodium falciparum infected erythrocytes containing mature trophozoites and schizonts sequester along venular endothelium and are not in the peripheral circulation of patients with malaria. Knobs appear on infected erythrocytes and are the points of attachment to endothelium. Sequestration may protect the parasite from splenic destruction and may play a role in the pathogenesis of cerebral malaria. Correlates of sequestration have been developed in vitro using cultured human endothelium and an amelanotic melanoma cell line. Knobless strains (K-) of P. falciparum fail to sequester in vivo and to bind to cells in vitro. We now present evidence that the receptor for cytoadherence is the glycoprotein, thrombospondin. Aotus monkey or human erythrocytes containing knobby (K+) but not Aotus erythrocytes containing knobless strains of P. falciparum bind to immobilized thrombospondin. Neither binds to the adhesive proteins laminin, fibronectin, factor VIII/von Willebrand factor or vitronectin. Both soluble thrombospondin and anti-thrombospondin antibodies inhibit binding of parasitized Aotus erythrocytes to immobilize thrombospondin and to melanoma cells which secrete thrombospondin.
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PMID:Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence. 241 70

In previous studies we showed that human sarcoma and melanoma cell lines synthesize and secrete into culture medium a glycoprotein, migrating in urea sodium dodecyl sulfate-polyacrylamide gel electrophoresis at Mr 140,000. It is not detected in cultures of the corresponding normal cells. Conditioned medium of the melanoma cell line HMB-2, producing among the cell lines tested the largest amounts of this glycoprotein, has now been used as a source for purification of the protein. NH2-terminal amino-acid sequence determination of the purified glycoprotein showed that it is identical to human alpha 2-macroglobulin (alpha 2M). Rabbit antibodies raised against the glycoprotein specifically reacted in immunoblotting and immunodiffusion tests with alpha 2M present in human plasma. Likewise, these antibodies immunoprecipitated from the conditioned media of 35S-methionine-labelled melanoma and osteosarcoma cell lines the protein which had a molecular weight corresponding to alpha 2M. alpha 2M was also synthesized and secreted by 2 strains of fetal lung fibroblasts but not by fetal skin fibroblasts or adult skin fibroblasts autologous to the osteosarcoma cell line.
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PMID:Human tumor cells synthesize and secrete alpha-2-macroglobulin in vitro. 241

The relationship of antigenic heterogeneity to the epitope recognized by an antibody was examined with monoclonal antibodies to human melanoma-associated antigens. Expression of the human melanoma-associated antigens, 250-Kd glycoprotein/proteoglycan and p97, was examined quantitatively by flow cytometry on fresh cell suspensions of human melanoma. Percent positive cells and mean fluorescence intensity were consistently higher with antibody 9.2.27 to the 250-Kd glycoprotein/proteoglycan than with antibody to p97. In addition, assessment of percent positive cells in multiple skin lesions biopsied from individual patients indicated that in 26 of 30 lesions, greater than 90% of the cells stained positively with 9.2.27. This relative lack of antigenic heterogeneity with antibody 9.2.27 contrasted with previous reports which showed considerable antigenic heterogeneity with other antibodies to the 250-Kd glycoprotein/proteoglycan. The explanation for this distinction was sought by quantitative flow cytometric and sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) techniques. Comparison by flow cytometry and immunoperoxidase of three antibodies, which recognized distinct epitopes of the 250-Kd glycoprotein/proteoglycan, indicated that 9.2.27 reacted more intensely with cultured cells and tissue sections than other antibodies to the same antigen. Examination by SDS-PAGE indicated that 9.2.27 could immunoprecipitate a larger proportion of 250-Kd glycoprotein molecules than other antibodies. In addition, immunodepletion experiments in gels indicated that the 9.2.27 determinant was present on a higher proportion of 250-Kd glycoprotein molecules than PG-2 antibody to a separate determinant. It is likely that 9.2.27 antibody displays less antigenic heterogeneity because its epitope is represented on a higher proportion of the antigen molecules. Thus, not only the nature of the antigen but also the epitope recognized by an antibody influences the degree of antigenic heterogeneity.
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PMID:Human melanoma-associated antigens: analysis of antigenic heterogeneity by molecular, serologic and flow-cytometric approaches. 242 45

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