UMLS:C0025202 - FACTA Search

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Query: UMLS:C0025202 (melanoma)
69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three melanomas of C57BL/6 mice (BL6, JB/MS, and JB/RH) share several phenotypic properties. All these cells contain melanoma-specific ecotropic C-type retrovirus that encodes melanoma-associated antigen recognizable by MM2-9B6 mAb. They do not express H-2Kb molecules, and the alpha-galactosyl epitopes (Gal alpha 1-3Gal beta 1-4GlcNAc-R) they fail to react with soybean agglutinin (SBA), peanut agglutinin (PNA), and vicia villosa (VV) lectins. Previously, we found that failure of BL6 melanoma cells to express alpha-galactosyl epitopes is due to down-regulation of alpha 1,3 galactosyltransferase (alpha 1,3GT) gene expression. To evaluate the possible role of alpha-galactosyl cell membrane carbohydrates in regulation of metastatic properties, individual clones isolated from BL6, JB/MS, and JB/RH melanomas were transfected with alpha 1,3GT cDNA. This resulted in appearance of alpha-galactosyl epitopes, as well as of carbohydrates reacting with SBA, PNA, or VV lectins, but did not affect expression of H-2 class I molecules or melanoma-associated antigen. Appearance of SBA, PNA, and VV lectin binding carbohydrates in the alpha 1,3GT gene-transfected melanoma cells is a result of reduction of cell membrane sialylation and unmasking of these carbohydrates. Reduction in cell membrane sialylation in the alpha 1,3GT gene-transfected melanoma cells is probably due to the competition between alpha 1,3GT with alpha 2,3 sialyltransferase or alha 2,6 sialyltransferase for the common acceptor N-acetyllactosamine in the Golgi apparatus. As a result of this competition, cell membranes of alpha 1,3GT gene-transfected melanoma cells became galactosylated and less sialylated. In parallel with alteration of cell membrane carbohydrates, transfection of the alpha 1,3GT gene leads to the loss of metastatic properties of the transfected melanoma cells in the immunocompetent and immunosuppressed C57BL/6 mice. Thus, the use of specific glycosyltransferase cDNA transfection presents direct experimental confirmation of the importance of cell membrane carbohydrates in the regulation of metastatic properties of tumor cells.
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PMID:Alterations of cell surface carbohydrates and inhibition of metastatic property of murine melanomas by alpha 1,3 galactosyltransferase gene transfection. 754 89

MHC class I-restricted CTLs specific for antigens expressed by malignant cells are an important component of immune responses against human cancer. Recently, in melanoma a number of melanocyte differentiation antigens have been identified as potential tumor rejection antigens. In the present study, we show that by applying peptide-loaded dendritic cells, induced by granulocyte-macrophage colony-stimulating factor and interleukin 4 from peripheral blood monocytes of healthy donors, we were able to elicit melanoma-associated antigen-specific CTL in vitro. We demonstrate the induction of CTLs directed against HLA-A2.1 presented epitopes derived from tyrosinase, gp100, and Melan A/MART-1. Apart from lysis of peptide-loaded target cells, these CTLs displayed reactivity with HLA-A2.1+ melanoma tumor cell lines and cultured normal melanocytes endogenously expressing the target antigen. These data indicate that these CTLs recognize naturally processed and presented epitopes and that precursor CTLs against melanocyte differentiation antigens are present in healthy individuals. The ability to generate tumor-specific CTLs in vitro, using granulocyte-macrophage colony-stimulating factor/interleukin 4-induced dendritic cells, illustrates the potential use of this type of antigen-presenting cells for vaccination protocols in human cancer.
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PMID:Generation of antimelanoma cytotoxic T lymphocytes from healthy donors after presentation of melanoma-associated antigen-derived epitopes by dendritic cells in vitro. 758 96

To determine whether IL-1 alpha and/or IL-1 beta protein is expressed by human melanoma tumor in vivo, we first analyzed nine human melanoma cell lines and optimized the in situ detection of these proteins. Three of the melanoma cell lines stained positively for both IL-1 alpha and IL-1 beta using immunohistochemistry (IHC). THe specificity of IHC was confirmed by the ability of purified recombinant IL-1 alpha and IL-1 beta protein to abolish the staining after being adsorbed by their respective antibodies before use in IHC. The three positively staining cell lines were also the only lines to demonstrate IL-1 production by western blot analysis as well as IL-1 secretion by ELISA. Next we examined 29 surgically obtained melanoma tumor specimens (6 primary and 23 metastases) that had been formalin fixed and paraffin embedded. Using the same anti-IL-1 antibodies, 5 of 23 metastatic tumors stained positively. None of the 6 primary lesions stained for either IL-1 alpha or IL-1 beta. Comparison of staining pattern performed on serially sectioned tissue using preimmune serum and antibodies against S-100 protein, melanoma-associated antigen (HMB-45), and CD68 (kappa P1), which recognizes monocyte-macrophage cell lineage, demonstrates for the first time that IL-1 protein is produced by human melanoma tumor cells in vivo. These findings provide the basis for examination of what may be a previously unrecognized biologically distinct subset of patients.
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PMID:Interleukin-1 production in tumor cells of human melanoma surgical specimens. 762 8

A case of mediastinal malignant epithelioid schwannoma (MES) is reported. The tumor probably arose in the vagal nerve, and the trachea was involved. A few months after excision of the primary tumor, multiple metastases appeared in lung, cervical spine, and neck lymph nodes. Microscopically, the tumor showed a highly cellular area resembling melanoma or carcinoma. Immunolabeling was done for S-100 protein, keratin, and melanoma-associated antigen. Examination of the entire lesion and in situ characteristics of the tumor involving the vagal nerve were helpful in making the correct diagnosis. Mediastinal MES, to our knowledge, has not been reported to date in the English-language medical literature.
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PMID:Mediastinal malignant epithelioid schwannoma. 763 4

The mouse anti-idiotypic (anti-id) monoclonal antibody (mAb) MK2-23 bears the internal image of the determinant defined by the syngeneic immunizing anti-human high molecular weight melanoma-associated antigen (HMW-MAA) mAb 763.74, since it induces anti-HMW-MAA antibodies in syngeneic and xenogeneic hosts. To dissect the humoral immune response induced by mAb MK2-23 at the clonal level, 1351 hybridomas were generated from a BALB/c mouse immunized with mAb MK2-23. Serological and immunochemical assays showed that the anti-anti-idiotypic (anti-anti-id) mAb GH827, GH1002 and GH1081 react only with the immunizing anti-id mAb MK2-23 and that the anti-anti-id mAb GH149, GH368, GH464, GH518, GH586, GH704, GH786 and GH1151 react with both mAb MK2-23 and HMW-MAA. The eight HMW-MAA binding anti-anti-id mAb resembled mAb 763.74 in their reactivity patterns with a panel of cell lines, although the extent of reactivity was lower. Staining of surgically removed melanoma lesions detected subtle differences in the reactivity patterns of the eight HMW-MAA binding anti-anti-id mAb. This finding in conjunction with the differential ability of the eight anti-anti-id mAb to inhibit the binding of anti-HMW-MAA mAb 763.74 to melanoma cells and to mAb MK2-23 and with the different avidity of the binding to mAb MK2-23 suggest diversity in the fine specificity of the eight HMW-MAA binding anti-anti-id mAb. Like mAb 763.74, the eight HMW-MAA binding anti-anti-id mAb express the idiotopes recognized by the anti-id mAb MK2-23 and MK2-120. In contrast, the three anti-anti-id mAb GH827, GH1002 and GH1081, which do not bind HMW-MAA binding anti-anti-id mAb to the antibodies elicited by the membrane-bound HMW-MAA corroborates the validity of the use of anti-id mAb MK2-23 as an immunogen to implement active specific immunotherapy in patients with malignant melanoma.
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PMID:Idiotypic cascade in the human high molecular weight melanoma-associated antigen system: fine specificity and idiotypic profile of anti-anti-idiotypic monoclonal antibodies. 768 58

We have previously reported the purification and partial characterization of a human melanoma-associated antigen (M-66) recognized by autologous antibody. This antigen was found to be an unusually acidic 66 kDa glycoprotein. In studies of murine melanoma, a 67-kDa albumin-like melanoma-associated antigen (MAA) isolated from B16 melanoma cells has also been reported by our laboratories. Because the murine MAA, B700, has a molecular weight that is nearly the same as M-66, we sought to determine what similarities and differences existed between these two antigens. Human sera S150, which is known to recognize M-66, was found to bind to murine melanoma cell line B16. The addition of purified M-66 inhibited binding of S150 to B16 cells. Binding by S150 was not noted against murine melanoma cell line S91, which is known not to express cell surface B700. Conversely, reactivity of S150 against Y-Mel 84:420, known to express M-66, could be inhibited by preincubation with B16 cells. Four monoclonal antibodies known to recognize B700 were evaluated for-binding against murine B16 and human melanoma cell line Y-Mel 84:420. Binding was noted against both B16 and Y-Mel 84:420 which could be inhibited by the addition of M-66. Binding of S150 was also noted against purified B700 as tested by ELISA. While a comparison of the amino acid composition of the two antigens revealed similarities, M-66 contained 2.8 times as much serine and 0.4 times as much proline as B700. B700 has been reported to be related to serum albumin, which is not the case for M-66.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cross-reactivity between murine melanoma antigen B700 and a human melanoma-associated antigen (M-66) recognized by autologous antibody: evidence suggesting shared epitopes. 768 77

A human melanoma-associated antigen immunogenic in patients was recently identified by screening an expression cDNA library constructed from cultured human melanoma cell line with sera from patients with melanoma. The nucleic acid sequence of the cloned D-1 cDNA has no significant homology with previously reported mammalian genes. The cDNA D-1 encodes a peptide of about 37 kDa, which showed fivefold higher reactivity with sera from patients with melanoma than with sera from normal donors. In order to detect D-1 gene expression in vivo, in-situ hybridization and immunostaining with cRNA probe and murine anti-D-1 sera were carried out on surgically removed tissues. Digoxigenin-labeled cRNA D-1 was exclusively hybridized with mRNA in the cytoplasm of melanoma cells but not with keratinocytes and fibroblasts adjacent to melanoma nests. Polyclonal anti-D-1 antibodies were obtained by immunization of Balb/c mice with recombinant D-1 peptide and clearly reacted with melanoma cells but not with keratinocytes and fibroblasts, similar to the results of in-situ hybridization. The above information will help to assess the suitability of recombinant D-1 peptide to implement active specific immunotherapy in patients with melanoma.
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PMID:Tissue distribution of an immunogenic melanoma associated antigen, D-1. 776 54

Melanoma in hybrids of Xiphophorus is due to the unrestricted activity of a cellular oncogene locus, Tu, encoding the growth factor receptor gene Xmrk. In nonhybrid parental fish, Tu is controlled by a tumor suppressor gene. Thus, its restricted activity leads there only to a nonmalignant, species- and population-specific macromelanophore spot pattern. Prompted by enigmatic reports on nonhybrid Xiphophorus with pigmentation abnormalities resembling melanoma, we have studied pigmentation in descendants of wild-caught fish and purebred laboratory stocks derived from wild populations. Whereas most stocks exhibiting macromelanophore patterns never developed pigmentation abnormalities, an exceptional situation for some nonhybrids was found. In X. variatus carrying the macromelanophore pattern "punctatus-2" and in X. cortezi with "spotted caudal," expressivity of the pigmentation gene ranges from a few black spots to extreme melanosis and eventually to malignant melanoma. In X. maculatus with the mutant pigmentation gene striped" carrying in addition the micromelanophore pattern "anal fin black" or "lower comet," testosterone-dependent melanoma develop originating from the corresponding micromelanophore pattern. The tumors are highly malignant and express a melanoma-associated antigen. Overexpression of the Xmrk oncogene appears as the underlying molecular mechanism for tumor induction. These findings clearly demonstrate that tumors can also develop in purebred wild-type fish. The classical model for formation of hereditary melanoma in Xiphophorus hybrids does not explain the development of melanoma in the absence of hybridization. However, their existence gives additional support to the reasoning that the Xmrk oncogene associated with the macromelanophore locus is potentially injurious.
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PMID:Spontaneous melanoma formation in nonhybrid Xiphophorus. 780 27

A model to study passive humoral immunotherapy of experimental melanoma was generated by subcutaneous injection of B16 F10 murine melanoma cells in the midtail of BALB/C nude (nu/nu) mice. Mice were challenged with melanoma cells pretreated: (1) with complete culture medium, (2) with 10% adjuvant control serum, (3) with 10% anti-fECA (formalinized extracellular antigens) immune serum, or (4) with a monoclonal antibody (mAB H2-3-3) specific for the B700 melanoma-associated antigen. All control mice challenged with melanoma cells pretreated either with culture medium or with medium containing adjuvant control serum (Groups I and II) died during the observation period of 84 days. At day 84, 60% of the mice challenged with melanoma cells pretreated with anti-fECA immune serum (Group III) survived, as did 100% of the mice challenged with cells pretreated with mAb H2-3-3 (Group IV). Injection of melanoma cells pretreated with mAb H2-3-3 was associated with the greatest reduction of subsequent local tumor growth and the lowest number of metastatic lung tumors. The inhibitory effects of immune sera in vivo also correlated with in vitro effects of anti-fECA immune serum and mAb H2-3-3, determined on B16 F10 melanoma target cells using assays for DNA synthesis and antibody dependent cellular cytotoxicity (ADCC). In sum, this nude mouse model for the study of passive humoral immunotherapy of experimental melanoma was utilized to demonstrate significant protective effects against B16 F10 melanoma cell challenge by treatment with anti-fECA immune sera or a melanoma-specific monoclonal antibody.
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PMID:Nude mouse model to study passive humoral immunotherapy directed against B16 F10 murine melanoma. 806 54

We have previously demonstrated that transfection of BL6-8 melanoma cells with the H-2Kb gene increased their sensitivity to natural killer (NK)- and natural cytotoxic (NC) cell-mediated cytotoxicity, and resulted in alterations of various cell characteristics such as the loss of melanoma-associated antigen (MAA), and the appearance of Griffonia simplicifolia 1B4 (GS1B4)- and soybean agglutinin (SBA)-lectin-binding sites. In the present study the BL6-8 melanoma clone was transfected with the H-2Kb gene without cotransfection of the neomycin resistance (neor) gene, and transfected cells were isolated on the basis of their low sialylation and ability to bind to SBA-agarose beads. 38 out of 47 analyzed clones were morphologically distinguishable, expressed the H-2Kb gene, lost the MAA and gained SBA- and GS1B4-lectin-binding sites (H-2Kb+, MAA-, SBA+, GS1B4+), whereas only 5 clones were morphologically and phenotypically unchanged (H-2Kb-, MAA+, SBA-, GS1B4-). The remaining 4 clones were morphologically changed, lost MAA and gained SBA- and GS1B4-binding epitopes, but did not express H-2Kb antigen (H-2Kb-, MAA-, SBA+, GS1B4+). Analysis of the NK sensitivity of H-2Kb-gene-transfected clones revealed that H-2Kb+, MAA-, SBA+, GS1B4+ clones were highly sensitive to NK cell lysis, whereas H-2Kb-, MAA+, SBA-, GS1B4- clones were NK resistant. It is of particular note that the 4 clones that did not express H-2Kb antigen but had other phenotypic changes (H-2Kb-, MAA-, SBA+, GS1B4+) were also highly sensitive to NK cells. The NK sensitivity of H-2Kb-transfected cells was closely associated with their increased ability to compete with YAC-1 cells for effector cells in a cold-target inhibition assay. Thus, the data obtained indicate that H-2Kb molecules in BL6-8 melanoma cells are not required for interaction with the effector cells, and H-2Kb-induced alterations in membrane carbohydrates and/or expression of the retrovirus-associated MAA might be important for the increase NK sensitivity of BL6-8 melanoma cells.
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PMID:Evidence for indirect involvement of the H-2Kb gene in the regulation of natural killer sensitivity of BL6 melanoma cells. 811 Nov 89

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