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)

The lipid pattern of thirteen human melanoma tumors from various tissues were investigated. In seven of the tumors, an estimate was given about the proportion of malignant melanocytes to the total cell population, and a reverse correlation was determined between the proportion of malignant cells in these tumors and their neutral lipid content. The phospholipids did not show any modification, nor did the cholesterol in the cancerous tissues. The ganglioside pattern was found to be similar in all analyzed samples, with GM3, GM2 and GD3 as major components, although no correlation was found between the malignant level and the ganglioside content of the tumors.
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PMID:Lipid composition of human malignant melanoma tumors at various levels of malignant growth. 43 39

The relationships between the ganglioside composition of melanomas and their biologic behavior were investigated. (1) The amount of GM2 and/or GD2 in melanoma cells injected into nude mice correlated with the tumor growth rate. (2) GD2 content of melanoma cell lines correlated with sensitivity to radiation and vincristine. (3) GM2 expression of melanoma cells correlated with sensitivity to lymphokine-activated killer cells. (4) Gangliosides inhibited the proliferation of human T cells stimulated with interleukin-4 or interleukin-2. Based on these results, we proposed a hypothesis for the role of melanoma-associated gangliosides in the biologic behavior of melanomas and suggested a prospective melanoma treatment related to the gangliosides.
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PMID:Gangliosides of melanoma. 129 69

Cell surface gangliosides in human melanoma cell lines were modulated by pretreatment and adaptation to 6-thioguanine and 5-bromo-deoxyuridine. Chemo- and radiation sensitivities were compared in original cell lines and modulated cells by the human tumor colony-forming assay. Modulated cells showed decreased expression of cell surface GM2 and GD2 gangliosides. This reduction was correlated with increased resistance to bleomycin, vincristine, cisplatin and radiation treatment. These results suggest that cell surface GM2 and GD2 ganglioside expression in human melanoma cells is intimately associated with several cellular biological properties, such as drug or radiation sensitivity and cellular differentiation.
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PMID:Modulation of ganglioside expression in human melanoma cell lines; increased resistance to chemo- and radiation treatment. 138 69

GM2 is usually significantly elevated in human melanoma cells. The lysosomal hydrolase beta-hexosaminidase A (Hex A), is an isoenzyme required for terminal GalNAc hydrolysis from intact GM2 to GM3. The objective of the present studies is to determine if the elevated levels of gangliosides, particularly GM2, correlate with the activity of Hex A in cultured melanoma cells. The Hex A activity in 13 melanoma cell lines ranged from 26%-88.3% There was a inverse correlation between GM2 nmole/g and Hex A activity (r = -0.48; p less than 0.003). An inverse correlation (p less than 0.03) occurred between GD2 nmole/g and Hex A activity. There was an inverse correlation (r = -0.53; p less than 0.05 and r = -0.51; p less than 0.05, respectively) between the ratio of substrate/product (GM2/GM3) and (GD2/GD3) and Hex A activity. These results indicate that the level of GM2 in melanoma is inversely correlated with the level of activity of Hex A.
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PMID:Ganglioside GM2 levels in human melanoma cells: inverse correlation with lysosomal beta-hexosaminidase A activity. 138 84

In order to elucidate some of the factors that determine the characteristic expression of gangliosides in malignant melanoma and neuroblastoma the levels of ganglioside synthases (glycosyltransferases) were determined in a panel of cell lines from those tumors that exhibited a wide range of ganglioside composition. Sialyltransferases (GM3, GD3, GD1a, and GT1b synthases), N-acetylgalactosaminyltransferases (GM2 and GD2 synthases), and galactosyltransferase (GM1 and GD1b synthases) were analyzed in crude membrane preparations from these cells. The results confirmed the importance of GM3 and GD3 synthases in determining the prominence of the a (GM3 to GT1a) or b (GD3 to GQ1b) biosynthetic pathways. The overall ganglioside composition in cells was found to be dependent on the relative levels of specific enzymes acting sequentially or in competing pathways. In general, the pattern and levels of transferases correlated with the actual ganglioside content of the cell line, although several important discrepancies were noted. For example, in cell lines containing high amounts of GD2 ganglioside, the level of the preceding enzyme in the pathway (GD3 synthase) was unexpectedly low. Thus, the high GD2:GD3 ratios characteristic of most neuroblastomas result from low levels of GD3 synthase as well as high levels of GD2 synthase. In other cell lines, GD3 synthase was completely absent, resulting in the synthesis of GM2, but not GD2, by N-acetylgalactosaminyltransferase I, as would be expected. It was concluded that different glycosyltransferases play key roles in determining glycolipid expression in different cell types.
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PMID:Glycosylation pathways in the biosynthesis of gangliosides in melanoma and neuroblastoma cells: relative glycosyltransferase levels determine ganglioside patterns. 139 96

Gangliosides may play an important role in the proliferation and spread of human malignant melanoma. Because the frequency of metastases in uveal and cutaneous melanoma differs, it is possible that they may express different gangliosides. We analyzed the ganglioside profiles of primary uveal melanoma in 14 cases and of cutaneous melanoma metastasis in 19 cases. In cutaneous melanoma, GM3 ranged from 4.2% to 74.6% and GD3 from 22.1% to 91.8% of total lipid-bound sialic acid. GM2 (found in 13 of 19 cases, ranging from 0.5% to 11.7%), GD2 (11/19, 0.5%-22.0%) and 9-O-acetyl-GD3 (13/19, 0.5%-12.6%) were also frequently observed. By contrast, in 11 cases of uveal melanoma, GM3 was > 90%, GD3 was < 10%, GM2 was < 1.1%; neither GD2 nor 9-O-acetyl-GD3 were detected. The ganglioside profiles of these uveal melanomas were virtually identical to those of normal melanocytes obtained from foreskins. Histological examination of these 11 biopsies showed a monomorphous cell composition, but neither infiltration of lymphocytes or melanophages nor cell necrosis was observed. In 3 other cases, GD3 was increased to 19.5%-46.0%. Histological examination of these 3 biopsy specimens showed at least 2 populations of tumor cells that were separable based on morphological grounds, and mononuclear inflammatory cells interspersed among the tumor cells. An increase in GD3 appears to be related to tumor polyclonality and infiltration of the tumor by lymphocytes and macrophages. These results suggest that ganglioside expression of uveal melanoma is associated with host immune responses to the tumor. Furthermore, the low metastatic capacity of uveal melanoma, in contrast to the high metastatic rate of cutaneous melanoma, may be a result of its differentiated ganglioside expression, which is strikingly similar to that of normal melanocytes.
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PMID:Variations in the ganglioside profile of uveal melanoma correlate with cytologic heterogeneity. 142 27

The reactivity of a panel of antiganglioside monoclonal antibodies with a number of melanoma cell lines having different ganglioside composition profiles was studied. One cell line synthesized only GM3, one produced both GM3 and GD2, 2 had GM3 and GD3 as their major gangliosides, and 2 others synthesized approximately equal amounts of GM3, GM2, GD3, and GD2 gangliosides. Antibody reactivity with viable cells was analyzed by: (a) flow cytometry on suspension cells; and (b) mixed hemagglutination assays or immune adherence assays on monolayer cells in culture. GM3 was efficiently detected only in the cell line having GM3 as its sole ganglioside. In the other cell lines, GM3 was difficult to detect even in cells in which it made up a high proportion (up to 50%) of the total ganglioside content. GM2 was easily detectable only in JB-RH melanoma cells (which contain only GM3 and GM2). GD3 was the most reactive ganglioside in 2 cell lines and GD2 in 2 other lines. In general, the most complex ganglioside present in a cell was the one most accessible to antibody. The differential exposure at the cell surface of specific gangliosides may have implications for antibody-directed tumor detection and therapy and for cell-protein or cell-cell interactions that involve glycolipids.
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PMID:Cell surface accessibility of individual gangliosides in malignant melanoma cells to antibodies is influenced by the total ganglioside composition of the cells. 151 51

GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids expressed in some normal tissues such as brain and in various tumors such as neuroblastomas, astrocytomas, and malignant melanomas. We used a eukaryotic cell transient expression system to isolate cDNA clones that determine GM2 expression. We developed a new cell line from murine melanoma line B16 by transfecting with the polyoma T antigen gene that was suitable for this purpose. Two cDNA clones, both of which have a continuous open reading frame of 1683 base pairs, were isolated. Although the cloned cDNAs had no primary sequence similarity to reported glycosyltransferases, the deduced amino acid sequence predicted a type II transmembrane protein with an overall structure similar to other glycosyltransferases. The cDNA clones, when stably transfected, determined the expression of GM2 in B16 cells and GM2 and GD2 in the human melanoma line MeWo. Northern blot analysis revealed two transcripts in all cells that expressed either GM2 or GD2 or both. These findings indicate that the cDNAs catalyze the transfer of GalNAc onto GM3 and GD3 by a beta 1,4 linkage, resulting in the synthesis of GM2 and GD2, respectively. Namely they suggest that these cDNAs derive from the UDP-GalNAc: GM3/GD3 beta 1,4 N-acetylgalactosaminyltransferase (EC 2.4.1.92) gene.
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PMID:Expression cloning of beta 1,4 N-acetylgalactosaminyltransferase cDNAs that determine the expression of GM2 and GD2 gangliosides. 812 69

Murine anti-idiotype monoclonal antibodies were generated against a human IgM monoclonal antibody (L612) that recognizes ganglioside GM3 on human melanoma. Hybridomas secreting antibodies that bound specifically to L612 were selected by enzyme-linked immunosorbent assay using L612 and three negative control human IgMs, including monoclonal anti-GM2 and anti-GD2 antibodies, as well as purified serum IgM, as antigen sources. GM3-binding inhibition and cell-binding inhibition assays were used to identify seven anti-idiotype monoclonal antibodies that recognized determinants located within the antigen-combining sites of L612. To determine whether these anti-idiotype monoclonal antibodies possessed the internal image of the original antigen, we immunized syngeneic BALB/c mice with one of the anti-idiotype monoclonal antibodies, 4C10, coupled with keyhole limpet hemocyanin. Sera from the immunized mice reacted strongly with an antigen-positive M12 melanoma cell line and with purified GM3. Because L612 detects and kills melanoma tumor cells in vitro and in vivo in the presence of complement without affecting normal tissues, anti-idiotype monoclonal antibodies carrying the internal image of GM3 may be an effective tool for active specific immunotherapy in patients with melanoma.
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PMID:Anti-idiotype monoclonal antibody carrying the internal image of ganglioside GM3. 170 Jan 34

Gangliosides shed by tumors enhance tumor formation, possibly by suppressing host antitumor immune function, and gangliosides purified from animal tissues and cultured cells inhibit human cellular immune function in vitro. Determination of immunosuppressive activity of highly purified gangliosides, to uncover structure-activity relationships, is therefore important. Here we have studied a series of gangliosides obtained from human tissue and determined their effects on human natural killer (NK) activity. Total gangliosides from human brain tissue were moderately inhibitory; 100 nmol/ml reduced NK activity of human nonadherent PBMC by 43%. The influence of carbohydrate structure upon inhibitory activity was determined by study of eight highly (HPLC) purified individual gangliosides. Of these, we unexpectedly found that the two minor brain gangliosides with the simplest carbohydrate structures, GM2 and GM3, were very active inhibitors (75 and 47%, respectively, at 50 nmol/ml). In contrast, the structurally more complex major species, GM1, GD1a, GD1b, GT1b, and two other minor gangliosides, GD2 and GD3, were inactive. Reduced effector-target binding in a single-cell binding assay by GM2 but not GM3 suggests different mechanisms of inhibition by these two active gangliosides. Since GM2 and GM3 are present in high concentrations in, and are shed by, several common human tumors (e.g., neuroblastoma, melanoma, and glioma), their ability to inhibit NK cytotoxicity supports the hypothesis of a role of shed tumor gangliosides in the enhancement of tumor formation.
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PMID:Immunosuppression by human gangliosides. II. Carbohydrate structure and inhibition of human NK activity. 172 65


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