Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ganglioside GD3 was distributed widely on melanocytes, naevi, and practically all melanomas. Not all the cells in melanoma appeared to express GD3, so that treatment with MAbs to GD3 could be expected to leave foci of tumor cells resistant to the effects of the MAbs. GM3 had a similar distribution of GD3 on melanoma, but was expressed on a lower percentage of cells in individual tumors. Expression of GM3 appeared to be suppressed on melanoma and naevus cells in the epidermis. Addition of MAbs to GM3 to those against GD3 in the treatment of melanoma may increase the lytic effect against cells coexpressing both gangliosides, but as GM3 did not appear to be expressed on GM3 -ve cells, the percentage of resistant cells may not be decreased. GD2 was expressed on only approximately 25% of primaries and less than 50% of metastases. In individual tumors there was some evidence of reciprocal expression of GD3 and GD2, so the combination of MAbs to GD3 and GD2 may decrease the percentage of melanoma cells that are resistant to either MAb alone. Both GD3 and GD2, but not GM3, was expressed on lymphocytes around melanoma metastases in LNs and around melanomas in skin. GD2 was detected on a large percentage of lymphocytes around metastases in lymph nodes, but not in the skin, suggesting that the gangliosides GD2 and GD3 may be expressed on different subsets of T-lymphocytes. These findings, together with previous studies showing that the MAbs can enhance lymphocyte responses to a variety of stimuli, provide support for the hypothesis that the clinical effects of the MAbs may reflect activation of host responses against the tumor. Further analysis of the role of gangliosides in lymphocyte function is needed.
 ...
PMID:Ganglioside antigens in tissue sections of skin, naevi, and melanoma--implications for treatment of melanoma. 167 56

Sixteen monoclonal antibodies that were obtained after immunization of BALB/c mice with intact melanoma cells or extracts of melanoma cells were tested for reactivity with normal and malignant melanocytic cells in situ, using an immunoperoxidase technique on frozen tissue sections. Sections representing six histopathologically defined stages of tumor progression, ranging from normal melanocytes to highly malignant metastatic lesions, were used. Thirteen monoclonal antibodies (MAbs) did not stain normal melanocytes in situ, whereas three MAbs weakly stained between 1 and 12.5% of melanocytes in 6-22% of the skin sections examined. MAb B 73.1, which was produced by immunization of mice with human natural killer cells and which binds to the Fc receptor of natural killer cells and granulocytes, reacted exclusively with malignant cells that represent the last two stages of tumor progression, vertical growth phase (VGP) primary melanoma and metastatic melanoma. All other antibodies showed variable reactivity with benign proliferative lesions or radial growth phase (RGP), an early stage of primary melanoma. Staining by MAbs that were reactive with gangliosides, unknown antigens, receptors, and two proteins (120/94 kDa protein and 250 kDa glycoprotein) showed a gradual increase in subsequent stages of tumor progression. Two steps in tumor progression were characterized by significant quantitative changes in the expression of antigens detected by the MAbs used in this study. First, mature nevus cells showed significantly higher reactivity with a panel of six MAbs, when compared to normal melanocytes. Second, a separate panel of six MAbs discriminated between RGP and VGP primary melanoma cells. No significant differences in antigen expression were found between dysplastic nevus cells and RGP melanoma, except that some antigens (nerve growth factor receptor and GD2/GD3 gangliosides) appear to be expressed at lower levels in RGP lesions, nor did VGP primary and metastatic melanomas show significant differences in antigen expression. These results suggest that (a) tumor progression of melanocytic cells in vivo is accompanied by significant quantitative differences in the expression of antigens, (b) some of the antigens examined here are associated with biologically aggressive malignant lesions but not normal or premalignant melanocytic cells, and (c) RGP primary melanoma cells are antigenically more similar to nevus cells than to VGP primary melanoma cells.
 ...
PMID:Antigenic profile of tumor progression stages in human melanocytic nevi and melanomas. 254 11

Infection of normal human melanocyte and nevus cultures with an adenovirus 12-Simian Virus 40 hybrid virus (Ad12-SV40) produced transformed cells that expressed SV40-T antigen. The Ad12-SV40 cells exhibited rapid cell proliferation to high cell densities and efficient growth in soft agar, but none of 15 transformed melanocyte and nevus cultures formed tumors when injected s.c. or under the renal capsule into athymic nude mice. While the Ad12-SV40-transformed cells lost certain properties associated with the melanocytic phenotype, i.e., pigmentation, tyrosinase activity and melanosome content, the expression of melanoma-associated antigens, including nerve growth factor receptor, p97 melano-transferrin, and chondroitin sulfate proteoglycan, remained stable. The transformed melanocytes acquired the ability to express HLA-DR antigen, which is found on nevus and melanoma cells. Total ganglioside patterns in Ad12-SV40-transformed cells changed to reflect more advanced stages of tumor progression. Transformed melanocytes, like nevus and melanoma cells, showed increased GD3 content and transformed nevus cells increased GD2 which is a feature of malignant melanoma cells. Ad12-SV40-transformed human melanocytes and nevus cells are useful tools for studying tumor progression under experimental conditions.
 ...
PMID:Transformation of normal human melanocytes and non-malignant nevus cells by adenovirus 12-SV40 hybrid virus. 255 80

The reactivity of 12 surgically removed uveal melanoma lesions with monoclonal antibodies (MoAb) to 14 membrane-bound and 2 cytoplasmic cutaneous melanoma-associated antigens (MAA), to the 2 subunits of HLA Class I antigens and to the gene products of the HLA-D region was compared with that of cutaneous melanoma lesions and correlated with their histiotype. The membrane-bound determinants defined by the anti-Mr 92,000 and 45,000 MAA MoAb TP39.1, anti-Mr 110,000 MAA MoAb M111, anti-Mr 118,000 MAA MoAb TP36.1, anti-Mr 115,000 MAA MoAb 345.134, anti-ICAM-1 MoAb CL203.4 and anti-Mr 31,000 MAA MoAb M2590, and the cytoplasmic determinants defined by the anti-MAA MoAb 465.12 and 2G-10 display a distribution in uveal melanoma lesions similar to that in cutaneous melanoma lesions. On the other hand, membrane-bound determinants defined by the anti-Mr 100,000 MAA MoAb 376.96, anti-9-O-acetyl-GD3 ganglioside MoAb ME311 and anti-GD2-GD3 ganglioside MoAb ME361 were not detected in the uveal melanoma lesions tested. Furthermore, the membrane-bound determinants defined by the anti-GD3 MoAb R24, anti-nerve growth factor receptor MoAb ME20.4, anti-Mr 97,000 MAA MoAb 140.240, anti-carcinoembryonic antigen MoAb B1.1 and anti-HMW-MAA 149.53, 225.28, and 763.74 have a markedly lower expression in uveal than in cutaneous melanoma lesions. Incubation of uveal melanoma lesions with the pool of the MoAb 149.53, 225.28, and 763.74 recognizing distinct and spatially distant determinants of the HMW-MAA increased the intensity of staining of six lesions and stained four lesions which were not stained by the individual monoclonal antibodies. The distribution of HLA Class I antigens in uveal melanoma lesions resembles that in cutaneous melanoma lesions, since they are expressed in all the lesions of the mixed and epithelioid type but were not detected in those of the spindle type, i.e., the counterparts of nevocellular nevi. HLA Class II antigens are expressed with a lower frequency in uveal than in cutaneous melanoma lesions, since they were detected only in 2 of the 12 lesions. One of them is of the mixed type and the other one of the epithelioid type. Besides HLA antigens the determinants defined by the anti-carcinoembryonic MoAb B1.1, anti-ICAM-1 MoAb CL203.4, and anti-GD3 MoAb R24 displayed a differential distribution in the different histiotypes of uveal melanoma, since they are preferentially expressed in lesions of the mixed and epithelioid type.
 ...
PMID:Analysis of the antigenic profile of uveal melanoma lesions with anti-cutaneous melanoma-associated antigen and anti-HLA monoclonal antibodies. 291 56

The specific tissue distribution of melanoma-associated ganglioside II3-alpha-N-acetylneuraminosyl-alpha 2----8-N-acetylneuraminosyllactosylceramide (GD3) was studied on 175 cryopreserved, unfixed human tissue sections with R-24 mouse monoclonal antibody by indirect immunoperoxidase staining. A striking specificity of monoclonal antibody R-24 for malignant melanoma tissues was established. Ganglioside GD3 was detected in all 21 tissue sections of 21 patients with primary melanoma and in all 37 probes of 24 patients with metastatic malignant melanoma. The majority of tumor cells in the samples of primary malignant melanoma expressed GD3; however, GD3 expression was more heterogeneous in samples of metastatic lesions even in different metastases of the same patient. Of 11 nevi, 9 reacted with monoclonal antibody R-24, while melanocytes in the basal layer of normal skin stained only weakly and irregularly. None of the 32 normal and 12 fetal human tissue types were R-24 positive, but a strong cytoplasmic staining was observed with single cells in the dermis and in the interstitial tissue of the gastrointestinal tract, in the interlobular septa of the thymus, and in other distinct locations. Only two malignant carcinoid tumors of 38 nonmelanomatous tumors tested reacted with monoclonal antibody R-24.
 ...
PMID:Immunohistochemical localization of ganglioside GD3 in human malignant melanoma, epithelial tumors, and normal tissues. 389 88

Normal melanocytes and melanocytes of normal nevi, primary melanoma in the radial (RGP) and vertical (VGP) growth phases, and metastatic melanoma exhibited and maintained phenotypic differences when grown in tissue culture or in experimental animals. Only metastatic and VGP primary melanoma cells were tumorigenic in athymic nude mice and had nonrandom chromosomal abnormalities involving chromosomes 1, 6, and 7. The colony-forming efficiency in soft agar was also highest in these two cell types. A cell line of RGP primary melanoma had characteristics of both benign and malignant cells: nevus-like morphology; nontumorigenicity in nude mice; but karyotypic abnormality of chromosome 6. It also had a ganglioside pattern similar to that of normal melanocytes but not melanomas, i.e., a high GM3 ganglioside content compared to the amounts of GM2, GD2, and GD3 gangliosides. Binding of monoclonal antibodies secreted by hybridomas generated by immunization of mice with VGP primary and metastatic melanoma was highest with cells and supernatants of cultures from advanced melanoma and least with nevus cells. There was no binding to normal melanocytes except with the monoclonal antibodies specific for nerve growth factor receptor or 9-O-acetyl-GD3 ganglioside. On the other hand, monoclonal anti-nevus antibodies bound to melanocytes, nevus cells, and RGP primary melanoma cells but not to VGP primary or metastatic melanoma cells. Cultured human melanocytic cells appear to be a unique model for the study of tumor progression.
 ...
PMID:Characteristics of cultured human melanocytes isolated from different stages of tumor progression. 405 39

The interactions of dpPC with ganglioside GD3 and two lactones. GD3LacI or GD3LacII, in lipid monolayers occur with reduced, unaltered, or increased molecular area and surface potential/molecule, respectively. dpPC is fully miscible with GD3 and GD3LacI but films with GD3LacII show immiscibility above 75 mol% lactone. At low proportions of GD3 in mixtures with dpPC, GD3 undergoes condensation and depolarization; dpPC is depolarized and its molecular area is reduced above 50 mol% GD3. GD3LacI forms ideally mixed films with dpPC. Mixtures of dpPC with GD3LacII at mole fractions below 0.3 show increased mean molecular area and surface potential/molecule mostly due to lactone alterations. Between mole fractions of 0.3 and 0.75 the surface parameters of dpPC are altered, and above these proportions both lipids are immiscible. Defined variations of molecular properties induced by ganglioside lactonization are selectively transduced to changes of the intermolecular organization and surface electrostatics in mixed interfaces with dpPC. Thus, changes in the relative proportions of a ganglioside and its lactone forms may act as sensitive biotransducers for membrane-mediated cellular functions, without the need for metabolically altering the concentration of gangliosides.
 ...
PMID:Ganglioside GD3 and GD3-lactone mediated regulation of the intermolecular organization in mixed monolayers with dipalmitoylphosphatidylcholine. 945 Mar 21

The expression of complement regulatory antigens C3b/C4b receptor, (CD35) membrane cofactor protein (CD46), decay accelerating factor (CD55), and homologous restriction factor 20 (CD59) was determined immunohistochemically on ten primary malignant melanomas, 16 metastatic lesions, and ten melanocytic nevi. All of the melanocytic nevi and 9/10 primary melanomas showed both expression of CD46 and CD59. In one primary melanoma lacking CD46, expression of CD35 could be detected. In metastatic melanoma, 9/16 metastases were CD46+/CD59+, two were CD46-/CD59+, one CD46+/CD59-, and four CD46-/CD59-. Additionally, CD55 could be detected in two CD46+/CD59+ metastases, and CD35 in one. Expression or lack of complement regulatory antigens did not correlate with the expression of GD2, GD3, HMB-45 or S-100. In conclusion, some cases of metastatic melanoma show loss of normal expression of complement regulatory proteins. This might have implications on the immune response or the efficacy of immune therapy in malignant melanoma.
 ...
PMID:Expression of complement regulator proteins in primary and metastatic malignant melanoma. 1040 45