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)

We investigated the ability of GM3-lactone liposomes to induce anti-melanoma T cell responses in mice. GM3-lactone liposomes, like murine B16 melanoma cells, induced anti-melanoma cytotoxic T cells (CTL) and also suppressor T cells (Ts). A small dose of GM3-lactone (0.0003 micrograms/ml) was enough to generate CTL in the in vitro primary response, whereas relatively large amounts of the antigen (0.03-0.3 microgram/ml) were required for anti-melanoma Ts induction. As the epitope for anti-melanoma Ts is NeuAc but not NeuGc residue on GM3, and anti-melanoma CTL are effectively induced by either GM3(NeuAc) or GM3(NeuGc)-lactone liposomes, GM3(NeuGc)-lactone or GM3(NeuGc) liposomes have potent activity as an artificial melanoma antigen to induce anti-melanoma CTL in vitro.
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PMID:Induction of mouse anti-melanoma cytotoxic and suppressor T cells in vitro by an artificial antigen, GM3-lactone. 214 51

We and others previously described the melanoma-associated oncofetal glycosphingolipid antigen 9-O-acetyl-GD3, a disialoganglioside O-acetylated at the 9-position of the outer sialic acid residue. We have now developed methods to examine the biosynthesis and turnover of disialogangliosides in cultured melanoma cells and in Golgi-enriched vesicles from these cells. O-Acetylation was selectively expressed on di- and trisialogangliosides, but not on monosialogangliosides, nor on glycoprotein-bound sialic acids. Double-labeling of cells with [3H]acetate and [14C]glucosamine introduced easily detectable labels into each of the components of the ganglioside molecules. Pulse-chase studies of such doubly labeled molecules indicated that the O-acetyl groups turn over faster than the parent molecule. When Golgi-enriched vesicles from these cells were incubated with [acetyl-3H]acetyl-coenzyme A, the major labeled products were disialogangliosides. [Acetyl-3H]O-acetyl groups were found at both the 7- and the 9-positions, indicating that both 7-O-acetyl GD3 and 9-O-acetyl GD3 were synthesized by the action of O-acetyltransferase(s) on endogenous GD3. Analysis of the metabolically labeled molecules confirmed the existence of both 7- and 9-O-acetylated GD3 in the intact cells. Surprisingly, the major 3H-labeled product of the in vitro labeling reaction was not O-acetyl-GD3, but GD3, with the label exclusively in the sialic acid residues. Fragmentation of the labeled sialic acids by enzymatic and chemical methods showed that the 3H-label was exclusively in [3H]N-acetyl groups. Analyses of the double-labeled sialic acids from intact cells also showed that the 3H-label from [3H]acetate was exclusively in the form of [3H]N-acetyl groups, whereas the 14C-label was at the 4-position. Pulse-chase analysis of the 3H/14C ratio showed that the N-acetyl groups of both GD3 and of the monosialoganglioside GM3 were turning over faster than the parent molecules. Selective periodate oxidation showed that both the inner and outer sialic acid residues of GD3 incorporated 3H-label in the in vitro reaction, and showed similar turnover of N-acetylation in the pulse-chase study. Taken together, these results indicate that both the O- and N-acetyl groups of the sialic acid residues of gangliosides turn over faster than the parent molecules. They also demonstrate a novel re-N-acetylation reaction that predicts the existence of de-N-acetyl gangliosides in melanoma cells.
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PMID:Biosynthesis and turnover of O-acetyl and N-acetyl groups in the gangliosides of human melanoma cells. 219 84

A new immunohistochemical assay was developed for the detection of human monoclonal antibody (HuMAb) bound to human biopsied tumor tissues. A murine anti-idiotype monoclonal antibody, alpha type, 18C6 (IgGl), was raised against an IgM HuMAb, L612, defining a tumor-associated ganglioside antigen (GM3) and used as a probe in a three step cell-binding assay (HuMAb + anti-id + biotinylated anti-mouse Ig). Anti-id 18C6 has an exclusive binding specificity for HuMAb L612, but does not interfere with the binding of L612 to antigen positive melanoma cell lines or to a purified antigen, GM3. The applicability of 18C6 in the three step cell-binding assay was tested first using a melanoma cell line, UCLASO-M12. L612 bound to M12 cells was specifically detected by 18C6 without any background reactivity in ELISA. When this assay was compared with the standard two-step cell-binding assay (HuMAb + peroxidase-conjugated anti-human IgM) using various cultured tumor cell lines, parallel reactivity was observed. The three-step cell-binding assay was then applied to various fresh-frozen human tumor sections. Positive reactivity was demonstrated on various histologic types of human tumor tissues: primary melanoma (10/10), metastatic melanoma (4/4), nevus (10/10), lung cancer (3/6), breast cancer (2/6), and colon cancer (1/1). Adjacent normal tissues were unstained. Control experiments included the cell-binding assay with L612 alone, 18C6 alone. L612 + unrelated mouse IgG, and unrelated IgM HuMAb (L72) + 18C6; but biotinylated anti-mouse IgG did not react with these control preparations. The results indicate that anti-id 18C6 is a highly specific probe to assess the expression of the ganglioside antigenic epitope recognized by the L612 HuMAb on biopsied human tumor tissues.
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PMID:Murine monoclonal anti-idiotype antibody (alpha) as a probe to detect human monoclonal antibody bound to human tumor tissues. 223 Jan 46

Based on melanoma pathogenesis, phenotypic dynamics in pigment cell tumor progression detected with 11 MoAb have been defined. Anti-melanosomal A4F11 antibody reacts with every type of pigment cell tumor tested except for a few specimens. TNKH1 and anti-K.1.2 antibodies recognize nevocytic benign to premalignant tumors. HLA-DR, A.1.43, and A.10.33 antigens are expressed in advanced melanomas. Staining with anti-ganglioside GM3 and GD3 antibodies, M2590 and 4.2, respectively, reveals that most pigment cell tumors express gangliosides GM3 and GD3. But A2B5 antibody, which detects some polysialogangliosides such as GQ1C, reacts with highly progressed melanoma cells. Anti-ras p21 antibodies, RASK-3 and RASK-4, react with malignant melanomas and their premalignant lesions. These findings suggest the following: A4F11 is a universal marker of pigment cell tumors. TNKH1 and anti-K.1.2 antibodies might not be markers of melanocytic tumors but of nevocytic benign to premalignant tumors. Melanoma cells express gangliosides GM3 and GD3 as common pigment cell antigens and synthesize aberrant polysialogangliosides. Anti-ganglioside MoAb, including A2B5, are possible markers of the level of malignancy in melanoma cells like anti-A.1.43 and anti-A.10.33 antibodies. Enhanced ras p21 expression already appears on premalignant pigment cells.
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PMID:Antigen dynamics in melanocytic and nevocytic melanoma oncogenesis: anti-ganglioside and anti-ras p21 antibodies as markers of tumor progression. 229 92

Human skin melanocytes and melanocytes cultured in vitro express GM3 ganglioside almost exclusively, whereas malignant melanomas express high levels of both GM3 and GD3. We now show that treatment of cultured melanocytes with tumor necrosis factor-alpha, particularly in the presence of tetradecanoylphorbol-13-acetate, results in a change in morphology from spindle-shaped to epithelioid and greatly enhanced expression of GD3 ganglioside. This effect is specific and no other ganglioside is affected, except that GM3 expression (which is already high) is also increased. In contrast, these agents did not enhance the already high expression of GD3 on melanoma cells. This result provides an example of the plasticity of glycolipid expression in mammalian cells and their susceptibility to the influence of biological agents.
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PMID:Tumor necrosis factor enhances GD3 ganglioside expression in cultured human melanocytes. 238 25

Ganglioside composition of human melanoma was correlated with sensitivity of melanoma to antitumor treatment with chemotherapeutic agents and radiation. The cytotoxic effect of each treatment was evaluated on 16 melanoma cell lines using the human tumor colony-forming assay. Ganglioside fractions were extracted and purified from each cell line and analyzed for the four major gangliosides in melanoma (GM3, GM2, GD3, and GD2) by thin-layer chromatography (TLC) and TLC scanner. GD2 content positively correlated with sensitivity to radiation (r = 0.753, p less than 0.001) and vincristine (r = 0.779, p less than 0.001). In contrast, GM3 content inversely correlated with sensitivity to radiation (r = -0.658, p less than 0.01) and vincristine (r = -0.692, less than 0.01). The gangliosides GD3 and GM2 were shown to have no significant correlation with any of these treatments.
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PMID:Ganglioside composition of human melanoma and response to antitumor treatment. 240 Sep 37

A new method for determination of epitopes defined by monoclonal antibodies has been developed using thin layer chromatography/enzyme-immunostaining. Using this method, monoclonal antibody recognizing the species-interspecies cross-reactive melanoma antigenic determinants widely shared by various mammalian species was shown to react with N-acetyl neuraminic acid containing GM3 ganglioside. We have found the presence of gangliosides containing N-glycolylneuraminic acid in human melanoma tissues. These molecular species were determined to be GM3 (NeuGc), GM2 (NeuGc) and GD3 gangliosides, which have never been detected in normal human tissues and are expected to be strong immunogens. Thus, sialic-acid containing glycoconjugates play important roles in tumor-associated cell surface antigens.
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PMID:[Biochemistry of melanoma-associated ganglioside antigens]. 242 44

Human anomalous killer (AK) cells lyse freshly isolated human melanoma cells which are insensitive to human natural killer cell-mediated lysis. Monoclonal antibody Leo Mel 3, an IgM (k), produced by a hybridoma obtained from a mouse immunized with human melanoma cells, binds to melanoma cells and inhibits their conjugate formation with AK cells as well as their AK cell-mediated lysis. Other IgM antibodies from the same fusion that bind melanoma cells do not inhibit (Werkmeister, J. A., Triglia, T., Andrews, P., and Burns, G. F. (1985) J. Immunol. 135, 689-695). Leo Mel 3 binds several different gangliosides from melanoma cells, as determined by immunostaining thin layer chromatograms. Binding is abolished by treatment of the gangliosides with neuraminidase. In solid-phase radioimmunoassay, Leo Mel 3 binds strongly to ganglioside GD2 and less strongly to gangliosides GT3, GD3, and GQ1b. It does not bind to other gangliosides including GM1, GM2, GM3, GD1a, GD1b, and GT1b. Thus, the epitope recognized by antibody Leo Mel 3 is found in the sugar sequence of ganglioside GD2, GalNAc beta 1-4[NeuAc alpha 2-8NeuAc alpha 2-3]Gal beta 1-4Glc beta 1 .... This sequence may contain a target in melanoma cells recognized by AK cells.
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PMID:Monoclonal antibody Leo Mel 3, which inhibits killing of human melanoma cells by anomalous killer cells, binds to a sugar sequence in GD2 (II3(NeuAc)2-GgOse3Cer) and several other gangliosides. 243 16

A mouse melanoma (B16) antigen was investigated at a cellular level by three blocking experiments using monoclonal antimelanoma antibodies, soluble melanoma antigen, and enzyme-treated B16 melanoma cells as inhibitors. The activity of antimelanoma cytotoxic T-lymphocytes (CTL) was specifically reduced by addition of the mixture of two monoclonal antimelanoma antibodies, one (M2590) recognizing the cross-species melanoma epitope on GM3(NeuAc) and the other (M562) reactive with the mouse melanoma-specific epitope on protein molecules. The CTL activity was also blocked by GM3 liposome as well as by the soluble antigen. However, 3,000 times more GM3 than the soluble melanoma antigen is required to obtain a similar inhibitory effect. When pronase-treated B16 melanoma cells, which have had protein molecules removed but GM3 left intact on the surface, were used as an inhibitor, their blocking activity was greatly reduced but was still partly observed at a high inhibitor/target ratio. These results indicate that the melanoma antigen is not GM3 itself but is composed of the GM3-protein complex. This finding was also supported by using an interleukin 2-dependent CTL clone whose activity was blocked by both M562 and M2590. Antimelanoma CTL were found to belong to a double-negative T-cell population with Thy-1+, Lyt-2-, L3T4- phenotypes. L3T4+ T-cells were also demonstrated to be necessary for induction of double negative antimelanoma CTL.
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PMID:Mouse melanoma antigen recognized by Lyt-2- and L3T4- cytotoxic T-lymphocytes. 245 12

We demonstrate in the B16 melanoma (C57BL/6 derived) system that the soluble form of tumor Ag preferentially suppresses immune responses 1) by inhibiting CTL activity in the effector phase and 2) by induction of specific Ts that block CTL generation in the induction phase. Soluble melanoma antigen Ag injected i.p. into the tumor-bearing host can effectively augment melanoma growth in vivo. Two T cell types with the L3T4+ or double-negative/I-J+ phenotype are involved in the suppression of anti-melanoma CTL responses and can easily be generated in the in vitro primary 12 h-culture. Anti-melanoma Ts recognizes the GM3(NeuAc) structure and distinguishes GM3 molecular species. This is because liposomes constructed with GM3(NeuAc) but not with GM3(NeuGc) gangliosides alone can effectively induce the melanoma-specific Ts. It is thus likely that tumor cells can escape from the immunologic surveillance system by stimulating the repertoire of Ts for self-Ag, GM3, which has existed even in the unprimed conditions in order to maintain self-tolerance. These would appear to be the major escape mechanisms.
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PMID:Escape mechanisms of melanoma from immune system by soluble melanoma antigen. 245 2


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