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

Human monoclonal antibodies (mAbs) were derived from lymph node lymphocytes and peripheral blood lymphocytes (PBL) from patients with melanoma. Four methods for generating human mAbs were compared: fusion with human [LICR-LON-HMy-2 (LICR-2)] or mouse (NS-1) cells; transformation by Epstein-Barr virus (EBV); and EBV transformation followed by NS-1 fusion. NS-1 fusion with lymph node lymphocytes resulted in a higher number of growing hybrids than LICR-2 fusion. Virtually no hybrids were obtained from NS-1 or LICR-2 fusions with PBL. EBV transformed lymphocytes from lymph node and peripheral blood with equal efficiency, and the yield of proliferating cultures for antibody screening was more than 10- to 30-fold greater than that obtained by fusion techniques. However, once antibody-producing cultures had been identified, stability and clonability of EBV-transformed cells were poorer than that of NS-1 hybrid cells. To combine the strengths of both methods, cultures of EBV-transformed cells were fused with NS-1; and hybrid clones were isolated that showed vigorous growth, clonability, and stable antibody secretion. Detailed specificity analysis of the mAbs produced by six of these clones indicated detection of a class 1 (unique) melanoma antigen, a class 3 melanoma antigen, and four ganglioside antigens (GD3, GM3, and two other, as yet uncharacterized, heterophile antigens).
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PMID:Cell-surface antigens of melanoma recognized by human monoclonal antibodies. 303 84

The biological functions of murine melanoma-associated antigens recognized by monoclonal antibodies (MAbs) (M562, M622 and M2590) were examined by using mutant clones which differed in their degree of expression of these antigens. Four clones of high expressors of 3 types of antigen (MEA group), 5 clones of low or non-expressors of M562- and M622-recognizing antigens (MEB group) and 4 clones of non-expressor of GM3 recognized by M2590 (MEC group) were used. Attachment of these clones to components of extracellular matrix was different between the groups. Two clones of the MEA group showed the highest ability to adhere to laminin and type-IV collagen, whereas the clones of the MEB and MEC groups significantly lost their ability to attach to laminin and type-IV collagen. In experimental lung metastasis, metastasizing ability of MEA-group cells was higher than that of MEB- and MEC-group cells. Our results suggest that these antigens play some functional role in metastasis mediated by increasing capacity for attachment to laminin and type-IV collagen.
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PMID:Melanoma antigen expression and metastatic ability of mutant B16 melanoma clones. 305 66

The specificity of antibody to NeuGc alpha 2-3Gal beta 1-4Glc-cer (GM3(NeuGc] was carefully reexamined by the method of enzyme-immunostaining on a thin layer plate. The affinity-purified antibody was found to react with NeuGc alpha 2-8NeuGc alpha 2-3Gal beta 1-4Glc-cer (GD3(NeuGc-NeuGc] and NeuGc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc-cer (GD3(NeuGc-NeuAc], but not with NeuAc alpha 2-8NeuGc alpha 2-3Gal beta 1-4Glc-cer (GD3(NeuAc-NeuGc)) or NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc-cer (GD3(NeuAc-NeuAc]. From this result together with the previous results, it (GD3(NeuAc-NeuAc], From this result together with the previous results, it could be concluded that the antibody recognizes the outer portion of molecular species of sialic acids in the gangliosides. By using this antibody, the expression of Hanganutziu-Deicher (HD) gangliosides could be demonstrated in human malignant melanoma. The molecular species were different among individuals examined. Among HD-antigenic gangliosides, GM3(NeuGc) was commonly found in melanoma tissues. One of the patients examined expressed GD3(NeuGc-NeuGc) and GD 3(NeuGc-NeuAc), which may be characteristic gangliosides in human melanomas, since these gangliosides could not be detected in human colon cancer or human fetal tissues.
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PMID:Occurrence of tumor-associated ganglioside antigens with Hanganutziu-Deicher antigenic activity on human melanomas. 311 76

The gangliosides expressed by normal melanocytes are predominantly GM3 (greater than 90%) and GD3 (less than 5%). Malignant melanoma can express several other types of gangliosides in significant quantities, including GM2 and GD2. Melanoma patients can develop an immune response against some of these ganglioside antigens on autologous melanoma cells. The four major gangliosides expressed by human melanoma cells (GM3, GD3, GM2, and GD2) were examined for their immunomodulatory effect on lymph node lymphocytes from melanoma patients. Gangliosides were added exogenously to lymphocytes grown in the presence of IL-2. Preferential interactions of specific melanoma gangliosides on IL-2 stimulation were found. While GM2 and GD2 enhanced the lymphocyte response to IL-2, GM3 and GD3 significantly inhibited this response. GM2 and GD2 differ from GM3 and GD3 by the presence of a terminal N-acetylgalactosamine. Since different gangliosides can up-regulate and down-regulate lymphocyte responses to IL-2, the ganglioside phenotype of melanoma cells may play a major role in determining whether an individual tumor causes immune stimulation or suppression.
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PMID:Gangliosides from human melanoma immunomodulate response of T cells to interleukin-2. 312 73

In previous studies, an IgM monoclonal antibody (M2590), established after immunization of C57BL/6 mice with syngeneic B16 melanoma cells, was found to react with melanoma cells, but not with various normal cells and tissues (Taniguchi, M., and Wakabayashi, S., Jpn. J. Cancer Res., 75:418-426, 1984). The structure defined by this antibody was identified as GM3 (Hirabayashi, Y., et al., J. Biol. Chem., 260:13328-13333, 1985) organized in membranes at high density, although the real immunogen was suggested to be GM3 lactone (Nores, G. A., et al., J. Immunol., 139:3171-3176, 1987). Since GM3 lactone was found to be highly immunogenic, we subsequently immunized C57BL/6 mice with GM3 lactone coated on Salmonella minnesotae and established hybridoma DH2, secreting an IgG3 antibody showing preferential reactivity with GM3 lactone over GM3 under certain conditions. The reactivity of the DH2 antibody was competitively inhibited by M2590, and it showed a preferential reactivity with melanoma cells and displayed various immunochemical and immunobiological properties similar to those of M2590. However, DH2 antibody inhibited melanoma cell growth in vivo, induced antibody-dependent cytotoxicity in vitro, and showed a preferential accumulation in melanoma growth in vivo. These properties are characteristic of the IgG3 subclass, in striking contrast to IgM antibody M2590, which does not inhibit cell growth in vivo or in vitro and does not induce antibody-dependent cytotoxicity. Thus, immunization with lactone forms of tumor-associated ganglioside antigens might be useful in the production of antibodies and prevention of tumor cell growth in vivo (antitumor vaccines).
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PMID:An IgG3 monoclonal antibody established after immunization with GM3 lactone: immunochemical specificity and inhibition of melanoma cell growth in vitro and in vivo. 316 27

The specificities of two human monoclonal antibodies (2-39M and 32-27M), produced by hybridomas derived from the lymphocytes of melanoma patients (Yamaguchi, H., Furukawa, K., Fortunato, S. R., Livingston, P. O., Lloyd, K. O., Oettgen, H. F., and Old, L. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 2416-2420) have been elucidated. Using a large panel of glycolipids, it has been shown that the two monoclonal antibodies (mAbs) identified a number of N-glycolylneuraminic acid (NeuGc)-containing gangliosides. mAb 2-39M reacted with (NeuGc)GM3, (NeuGc)sialylparagloboside, and (NeuGc)sialylhexaglycosylceramide; no reactivity was observed with gangliosides containing only N-acetylneuraminic acid (NeuAc) or with disialogangliosides. These reactive species have the NeuGc alpha 2----3Gal- sequence in common. mAb 32-27M reacted strongly with (NeuGc)2 GD3 and (NeuGc)2disialylparagloboside, and moderately with (NeuAc-NeuGc-)GD3 and (NeuAc-NeuGc-)disialylparagloboside. The reactive species have sialic acid alpha 2----8NeuGc alpha 2----3Gal- sequences in common. These two antibodies were used to demonstrate the species-related presence of different NeuGc-containing gangliosides in various animal erythrocytes by thin layer chromatography immunostaining. No reactivity of either mAb was observed with gangliosides isolated from fresh human colon cancer, melanoma specimens, or some normal tissues, including brain. On the other hand, it was shown that mAb 32-27M reacted with gangliosides isolated from human melanoma and astrocytoma cells grown in fetal bovine serum but not from those grown in synthetic medium. Within the sensitivities of the methods used, these data, and related chemical analyses, do not support the presence of NeuGc-containing gangliosides in human tumors.
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PMID:Analysis of the expression of N-glycolylneuraminic acid-containing gangliosides in cells and tissues using two human monoclonal antibodies. 319 44

Gangliosides were purified from melanoma tissue extracts obtained from 5 patients. GM3 and GD3 were identified as the major components in ganglioside fractions of the melanoma tissues. Following thin-layer chromatography, enzyme immunostaining with Hanganutziu-Deicher (H-D) antigen-specific chicken antisera demonstrated the presence of NeuGc-neolactotetraosylceramide (H-D5) and NeuGc-lacto-N-norhexa-osylceramide (H-D7) in all 5 melanoma extracts.
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PMID:Heterophile Hanganutziu-Deicher antigen in ganglioside fractions of human melanoma tissues. 325 90

A lectin that can specifically bind to O-acetylsialic acids, found in glycoproteins and gangliosides, was purified to homogeneity from a crab Cancer antennarius (crab lectin) (Ravindranath, M. H., Higa, H. H., Cooper, E. L., and Paulson, J. C. (1985) J. Biol. Chem. 260, 8850-8856; Correction (1986) J. Biol. Chem. 261, 1983; Ravindranath, M. H., and Paulson, J. C. (1987) Methods Enzymol. 138, 520-527). We tested lectin binding to human melanoma cell lines to identify O-acetylsialylated gangliosides on the melanoma cell surface. The highest degree of binding of the crab lectin was demonstrated on a melanoma cell line, UCLASO-M25. To confirm that the binding was due to O-acetylsialic acid in the alkali-labile gangliosides, the gangliosides were isolated and purified from M25 cells and individually coated onto sheep asialoerythrocytes, which served as targets in an agglutination assay using the lectin. The crab lectin agglutinated the asialo-sheep erythrocytes coated with alkali-labile gangliosides, but the lectin failed to agglutinate the asialoerythrocytes coated with GM3, GD3, and base-treated gangliosides. Subsequently, the purified alkali-labile M25 ganglioside was base-treated and applied to TLC, and we found that it was converted to a slower migrating species identical to the disialolactosylceramide (GD3). These results indicate that O-acetyl GD3 expressed on the melanoma cell surface is recognized by the lectin. Because O-acetyl GD3 is not expressed on human normal tissues, we examined the capability of O-acetyl GD3 to induce immune responses in man. Sera from patients with melanoma were tested against M25 cells in an immuneadherence assay, and those positive to the M25 cell line were further tested for specificity to O-acetyl gangliosides. The presence of autoantibodies to O-acetyl-GD3 in melanoma sera was confirmed by blocking of the antigen sites on M25 cells by the lectin or preabsorption of the sera with erythrocytes bearing O-acetyl gangliosides. The data provide evidence that O-acetyl-GD3 may represent an important tumor marker for detection and treatment of human melanoma.
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PMID:Human melanoma antigen O-acetylated ganglioside GD3 is recognized by Cancer antennarius lectin. 333 3

Expression of the gangliosides GM3, GD3 and GD2 was studied in tissue sections from 19 naevi, 29 primary and 83 metastatic melanoma using the ABC immunoperoxidase technique. GM3 was not detected in normal skin whereas GD2 was detected on the basal and stratum spinosum of the epidermis and on peripheral nerves in the dermis. GD3 was expressed on melanocytes but not on most other components of normal skin. However, GD3 was strongly expressed on epidermis adjacent to naevi and primary melanoma whereas GD2, in contrast to that in normal skin, was not expressed on the epidermis adjacent to 26/29 primary melanoma. All naevi were positive for GM3 and GD3 except that GM3 was not detected on junctional components of naevi. GD2 was not expressed on naevi except in areas showing neuroid differentiation. Studies on melanoma revealed that approximately 60% of primary and 75% of metastatic melanoma expressed GM3 to a varying extent. With 2 exceptions, all primary and metastatic melanomas expressed GD3 although there was variable expression within most of the individual tumours. GD2 was detected in only approximately 25% of primary and 50% of metastatic melanomas. Both GD2 and GD3 were detected on lymphocytes surrounding melanoma. The higher expression of GD2 on metastases compared to primary melanomas was consistent with the view that GD2 expression was associated with increased metastatic potential. However, the low proportion of metastases expressing GD2 and the absence of any correlation with thickness of the primary tumour suggested that GD2 expression was not a reliable marker of metastatic potential. No differences could be detected in ganglioside expression on metastases in skin or lymph nodes. These results appear to have implications for the use of MAbs against gangliosides in therapy of melanoma and in the study of melanocytic differentiation.
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PMID:Expression of the gangliosides GM3, GD3 and GD2 in tissue sections of normal skin, naevi, primary and metastatic melanoma. 334 97

Gangliosides from benign and malignant melanomas and from normal skin of the fish genus Xiphophorus were isolated and analyzed by thin-layer chromatography. Individual ganglioside components were characterized by mapping according to their sialic acid content and by cleavage with neuraminidases. In all three tissues examined, sulfatide and the gangliosides NeuAc-GalCer (GM4), II3NeuAc-LacCer (GM3), II3NeuAc-GgOse3Cer (GM2), and II3(NeuAc)2-LacCer (GD3) were found. Ganglioside GD3 yielded a positive reaction, following immunoadsorption with mouse monoclonal antibody R24 on thin-layer plates. Two alkali-labile disialoganglioside species were specifically recognized by mouse monoclonal antibody D1.1, thus indicating the presence of O-acetyl-neuraminic acid residues. One of them, a major ganglioside component of the malignant melanoma, was identified as O-acetyl-GD3, since it could be converted to the R24-positive GD3 ganglioside after alkaline saponification. The other one appears to be restricted to the malignant tumor and represents a novel melanoma-associated ganglioside derivative. It was characterized as O-acetyl(NeuAc)2-nLc4Cer by exoglycosidase cleavage, by proving its neutral carbohydrate backbone as type II-chain lacto-series oligosaccharide using mouse monoclonal antibody 1B2, and by its cross-reaction with antibody R24 following alkaline treatment. Using antibody R24 and cryopreserved tissue sections of both benign and malignant amelanotic melanomas from albino fishes, it was demonstrated that one of the main melanoma-associated gangliosides, GD3, was exposed predominantly in the malignant tumor. Thus, the chemical nature and even the immunohistochemical localization of the gangliosides in fish melanomas proved to be very similar to those of the known gangliosides in the phylogenetically distant human melanomas.
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PMID:Melanoma-associated gangliosides in the fish genus Xiphophorus. 337 Jun 42


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