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)

Gangliosides are normal cell surface components of all animal cells. Altered ganglioside biosynthesis during malignant transformation results in expression of a qualitatively and quantitatively different ganglioside profile in many tumors. While their physiological function is largely unclear, gangliosides expressed by cancer cells, e.g. GD3, GD2 and GM2 in malignant melanoma, have proven to be suitable targets for passive immunotherapy with monoclonal antibodies and for active immunotherapy with vaccines. Studies aimed at further augmenting the effectiveness of these approaches are currently underway.
 ...
PMID:Ganglioside antigens expressed by human cancer cells. 181 Apr 68

Immune cytokines have been shown to play important roles in regulating immune cell functions. Interleukin-4 (IL4), originally described as a B-cell growth factor, is known to activate and differentiate other immune cells. IL4 has been given as an immunotherapeutic to tumor-bearing hosts. In this report, we set out to determine whether IL4 can directly modulate growth and expression of surface antigens on human melanoma cells. The effect of recombinant IL4 alone and in combination with recombinant gamma-interferon (IFN) or recombinant alpha-tumor necrosis factor (TNF) on melanoma cell lines was examined. IL4 significantly inhibited cell growth of all cell lines examined at 100-500 units/ml; but a dose-dependent differential response to individual cell lines occurred. The effect of IL4 was augmented by combination with IFN or TNF. Melanoma-associated ganglioside antigens (GM3, GD3, GM2, GD2) and human leukocyte antigen class I and DR on the cell surface of melanoma cells were assessed by flow cytometry and/or a radiometric binding assay. IL4, IFN, or TNF alone enhanced human leukocyte antigen class I, DR, and beta 2-microglobulin antigen expression. IL4 alone and in combination with IFN or TNF increased the GM3/GD3 ratio expression. GD2 was enhanced significantly by IL4, IFN, and TNF. Pretreatment of melanoma with IL4 or with other cytokines prior to stimulation with peripheral blood lymphocytes significantly enhanced mixed lymphocyte tumor reaction activity as compared with non-treated melanoma used as stimulators. These studies demonstrate that IL4 alone or in combination with IFN and TNF can modulate melanoma growth activity and surface antigen expression to a more differentiated and immunogenic phenotype.
 ...
PMID:Modulation of human melanoma cells by interleukin-4 and in combination with gamma-interferon or alpha-tumor necrosis factor. 190 Dec 39

Several studies have shown that melanoma-associated gangliosides are immunogenic in melanoma patients and that antibodies against them have a favorable prognostic effect. Our study aims at characterizing the humoral immune response in disease-free, advanced melanoma patients vaccinated with a total ganglioside fraction extracted from pooled metastases of human melanoma, containing as major gangliosides GM3 and GD3, and as minor ones GM2 and GD2. Prior to vaccination, all patients were made disease-free by surgical removal of skin, lymph-node or other distant metastases. Repeated vaccinations were carried out intradermally with gangliosides either in the native form in buffered solution, or in the form of liposomes. Serum samples were collected at regular intervals and assayed by ELISA for the presence of specific IgG and IgM antiganglioside antibodies. Selected samples were tested by immunostaining on thin-layer plates to specify the ganglioside species involved in the reactivity. Out of 32 evaluable patients, 17 presented a significant increase in antibody titer, mostly of the IgG isotype, which was maximal between 2 and 4 months after starting injections of gangliosides, and gradually disappeared within 1 year. No significant difference could be seen between the group of 20 patients treated with native gangliosides and the group of 12 vaccinated with the gangliosides in liposomes. All gangliosides seemed to be immunogenic, but GM2 and GD2 were somewhat more reactive. The disease-free intervals for the patients who showed an antibody response to the treatment were significantly higher (p less than 0001) than those of the non-responding group, as compared by the Kaplan-Meier method.
 ...
PMID:Humoral immune response in disease-free advanced melanoma patients after vaccination with melanoma-associated gangliosides. EORTC Cooperative Melanoma Group. 195 94

The carbohydrate structures of the major glycosphingolipids from the liver of the rainbow trout Oncorhynchus mykiss have been examined. We have isolated and identified four major neutral (glucosylceramide, galactosylceramide, lactosylceramide, and globoside) and five acidic (sulfatide, GM3, GM2, GD1a, and 9-O-Acetyl GD3) glycosphingolipids from trout liver. They have been characterized by 1H nuclear magnetic resonance spectroscopy, methylation analysis, fast atom bombardment mass spectrometry, and specific monoclonal antibodies. Significantly, the relatively scarce ganglioside 9-O-acetyl GD3 was found to comprise approximately 23% of the total ganglioside content of normal rainbow trout liver. 9-O-Acetyl GD3 is, however, abundant in human melanoma and as such, trout liver may be a suitable source of this antigen.
 ...
PMID:Isolation and characterization of the major glycosphingolipids from the liver of the rainbow trout (Oncorhynchus mykiss): identification of an abundant source of 9-O-acetyl GD3. 198 25

This report evaluates the relevance of the ratio of the melanoma-associated ganglioside, GD3, and its precursor, GM3, to prognosis and management of Stage II disease. Tumor biopsy specimens from 42 melanoma patients were examined for the ratio and found that GD3 and GM3 constitute 80% of the total lipid bound sialic acids (LBSA) of melanoma. Although the ratio of GM3:GD3 in melanocytes, the progenitors of melanoma, is 19:1 (based on %LBSA), it ranged from 15:1 to 1:5 in tumor biopsy specimens. Patients are categorized into three groups based on their GM3:GD3 ratio (%LBSA) of tumor tissues as Group I (ratio ranged from 15:1 to 1.5:1) (10 of 42), Group II (1.4:1 to 1:1.4) (13 of 42), and Group III (1:1.5 to 1:5) (19 of 42). When the overall survival of patients from the onset of Stage II disease was evaluated among different groups, patients belonging to Group I survived significantly longer than patients of Group II (P = 0.02) and Group III (P = 0.01). Interestingly, Group III expressed immunogenic gangliosides (GD2, GM2, and O-AcGD3) better than the other groups and may benefit more from therapies targeted against these gangliosides antigens. The results of this study indicate that GM3:GD3 ratio is an unusual but well-defined biochemical criteria that may be useful for prognosis and therapeutic management of the disease. Therefore, we propose a routine analysis of the GM3:GD3 ratio of tumors excised after surgery. Screening the ratio is feasible since melanoma expresses a simple profile of gangliosides unlike other forms of cancer.
 ...
PMID:Ganglioside GM3:GD3 ratio as an index for the management of melanoma. 204 49

GM2 ganglioside is a common cell surface constituent of human melanoma and other tumors of neuroectodermal origin, and vaccination with GM2 ganglioside results in high levels of anti-GM2 antibodies in patients with melanoma. Lymphocytes from a GM2-vaccinated patient (VS) were transformed by Epstein-Barr virus and tested for production of antibodies with reactivity for GM2-positive tumor cells. A high percentage of antibody-producing B cells was detected, but antibody reactivity was generally lost during culture expansion. Two cultures, however, remained stable for antibody productivity and one was used to develop a stable hybrid line with mouse myeloma. The monoclonal antibody (designated 3-207) derived from patient VS has dual specificity for GM2 and GD2, despite the fact that only GM2 antibody could be detected in the patient's serum. Monoclonal antibody 3-207 shows high-titered reactivity with a range of melanoma, astrocytoma, neuroblastoma, and leukemia cell lines, cells with prominent cell surface expression of GM2 and GD2. The cell surface reactivity of monoclonal antibody 3-207 was not abolished by treatment of target cells with neuraminidase, as the enzyme converted GD2 to GM2, which was still detected by monoclonal antibody 3-207.
 ...
PMID:Human monoclonal antibody with dual GM2/GD2 specificity derived from an immunized melanoma patient. 215 45

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.
 ...
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.
 ...
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.
 ...
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

The cell-surface antigen detected by the monoclonal antibody JONES is expressed in the retina and a number of other central nervous system regions of the rat during the latter part of embryonic development and the early postnatal period. In addition to the expression on certain neuroblast populations it is found on some but not all axons and is also expressed at high levels on the end feet of radial glia in regions through which axons actively grow. In the perinatal rat retina, almost all the antigenic activity was carried on a ganglioside migrating between GM1 and GM2. The epitope recognized by antibody JONES was base labile and treatment with 0.1 M sodium carbonate or ammonia vapor converted the antigen into GD3. Resistance to oxidation by sodium periodate and reformation of the epitope by chemical acetylation of base-treated gangliosides with N-acetylimidazole identify the antigen as 9-O-acetyl GD3. The acetylation of GD3 seems to be regulated independently from GD3 expression itself since acetylated and nonacetylated GD3 do not have identical immunocytochemical distributions in the developing central nervous system. In addition, five independent human melanoma cell lines varied substantially in their expression of 9-O-acetyl GD3, even though they all expressed high levels of GD3. Acetylation of ganglioside-linked sialic acid provides a mechanism for generating unique patterns of surface carbohydrates, which may influence cell interactions in development.
 ...
PMID:O-acetylation of a cell-surface carbohydrate creates discrete molecular patterns during neural development. 244 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>