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 human genes MAGE-1 and -3 encode melanoma peptide antigens that are recognized by autologous cytotoxic T lymphocytes. Tumors expressing MAGE genes are potential targets for cancer immunotherapy, because MAGE genes are expressed only in tumor tissue and not in any normal tissue except testis and placenta. However, little is known about MAGE gene expression in human esophageal carcinoma. The purpose of this study was therefore to analyze MAGE gene status in human esophageal carcinoma. We studied the expression status of these genes in 42 surgical samples and in 12 cell lines of human esophageal carcinoma using the reverse transcription polymerase chain reaction (RT-PCR). Various clinicopathological factors were also analyzed. No MAGE gene expression was seen in any of the 42 normal esophageal tissue specimens. In contrast, tumor tissue expressed MAGE-1, -2, and -3 in 26, 18 and 24 specimens, respectively. Thirty-three of 42 tumors expressed at least one MAGE gene. Significant clinicopathologic differences between the tumors were not observed, regardless of the presence or absence of MAGE gene expression. In cell lines, MAGE-1, -2, and -3 gene expression was recognized in 5, 4 and 4 cell lines, respectively. This study demonstrates that MAGE genes are frequently expressed in clinical samples as well as in cell lines of esophageal carcinoma. The identification of MAGE genes, therefore, may open up a new modality of treatment, namely specific immunotherapy, for patients with esophageal carcinoma.
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PMID:Human esophageal carcinomas frequently express the tumor-rejection antigens of MAGE genes. 759 Dec 61

Human melanoma cells can process the MAGE-1 gene product and present the processed nonapeptide EADPTGHSY on their major histocompatibility complex class I molecules, HLA-A1, as a determinant for cytolytic T lymphocytes (CTLs). Considering that autologous antigen presenting cells (APCs) pulsed with the synthetic nonapeptide might, therefore, be immunogenic, melanoma patients whose tumor cells express the MAGE-1 gene and who are HLA-A1+ were immunized with a vaccine made of cultured autologous APCs pulsed with the synthetic nonapeptide. Analyses of the nature of the in vivo host immune response to the vaccine revealed that the peptide-pulsed APCs are capable of inducing autologous melanoma-reactive and the nonapeptide-specific CTLs in situ at the immunization site and at distant metastatic disease sites.
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PMID:Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells. 764 41

Human genes MAGE-1 and MAGE-3 code for distinct antigens, which are recognized on melanoma cells by autologous cytolytic T lymphocytes (CTL). These antigens may constitute useful targets for anti-cancer immunotherapy, since no expression of MAGE genes has been observed in normal tissues other than testis. Out of 57 samples of primary transitional-cell carcinomas of the bladder, 12 (21%) expressed MAGE-1 and 20 (35%) expressed MAGE-3. All but one of the tumors expressing MAGE-1 also expressed MAGE-3. Genes MAGE-2 and MAGE-4, which are closely related to MAGE-1 and MAGE-3, were expressed by 30% and 33% of the tumors respectively. MAGE expression was more frequent in advanced tumor stages: 61% of the invasive tumors (stage > or = T2) were positive for expression of at least one of the four genes, whereas only 28% of the superficial tumors (stages Ta and T1) expressed these genes.
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PMID:Expression of MAGE genes in transitional-cell carcinomas of the urinary bladder. 766 50

The recent identification of the sequences of the peptides derived from a number of human melanoma-associated antigens has presented opportunities for developing a specific-peptide-based vaccine in this form of cancer. Since antigen-presenting cells (APC) play a crucial role in the induction of the T-cell-mediated immune response, we examined whether or not ex vivo cultured APC, bearing the appropriate MHC restricting elements, when pulsed with a relevant melanoma-specific cytotoxic-T-lymphocyte (CTL)-determined peptide, can present the peptide to the CTL. Here we show that a population of cells, derived from the monocyte/macrophage lineage from peripheral blood and grown in granulocyte/macrophage-colony-stimulating factor, exhibit many essential characteristics of "professional" APC (dendritic-type morphology with a proportion of the population, the B7 molecule, and high levels of MHC class I and class II molecules, CD11b and CD54 molecules) and are capable of efficiently presenting the nonapeptide, EADPTGHSY, encoded by the melanoma antigen MAGE-1 gene, to the MAGE-1-specific CTL clone, 82/30. These results suggest that this type of autologous ex vivo cultured population of professional APC, when pulsed with the relevant-CTL-determined peptide, can serve as a novel type of candidate vaccine for active specific immunization against HLA-A1-positive patients with melanoma expressing the MAGE-1 antigen.
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PMID:Presentation of synthetic peptide antigen encoded by the MAGE-1 gene by granulocyte/macrophage-colony-stimulating-factor-cultured macrophages from HLA-A1 melanoma patients. 775 Jan 25

The human MAGE-3 gene encodes a melanoma antigenic epitope recognized by specific cytotoxic T lymphocytes, but its gene product has not been identified thus far. We produced a recombinant MAGE-3 gene product by expression cloning of the entire reading frame in the context of a fusion protein characterized by a 10-histidine tail, allowing purification by metal chelation on a nickel Sepharose column. The semipurified product was used to generate MAGE-3-specific monoclonal antibodies. One reagent could identify by immunoblotting the native MAGE-3 gene product as a M(r) 48,000 protein in lysates of cell lines showing evidence of MAGE-3 gene expression. No apparent cross-reactivity with recombinant or native MAGE-1 gene product was observed. Immunohistochemistry shows that, closely resembling the MAGE-1 gene product, MAGE-3 is a cytoplasmic protein.
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PMID:Identification and intracellular location of MAGE-3 gene product. 775 70

The MAGE-1 gene was recently characterized to encode an immunogenic tumor Ag on several types of human tumors, including melanoma. This Ag is expressed in a wide variety of human tumors and not in normal cells, except testicular tissue, as assessed through specific mRNA analysis. In this study we cloned the MAGE-1 gene exon 3 region from a colon carcinoma cell line and expressed it in Escherichia coli. The recombinant MAGE-1 protein was affinity purified. By using Western blot analysis, IgG and IgM anti-MAGE-1 Abs were detected in the sera of melanoma patients. Fifty-three patients immunized with a melanoma cell vaccine (MCV) were assessed for anti-MAGE-1 IgG responses by using a MAGE-1 Ag-specific ELISA. The MCV consisted of three melanoma cell lines that expressed MAGE-1. Comparisons of anti-MAGE-1 IgG response pre-MCV treatment with 12- to 16-wk post-MCV treatment were made. Fifty-seven percent of the patients immunized with the MCV showed significant enhancement of IgG response to recombinant MAGE-1 protein. Patients who responded had no particular HLA-A or -B allele expression pattern. Melanoma patients immunized with whole cell MCV containing MAGE-1 can enhance anti-MAGE-1 IgG Abs. Recombinant MAGE-1 protein can be used to assess patient response to MAGE-1 and will be investigated as a potential cancer vaccine against a wide variety of human tumors that express MAGE-1.
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PMID:Melanoma patients immunized with melanoma cell vaccine induce antibody responses to recombinant MAGE-1 antigen. 781 79

Identification of CTL epitopes for tumor-specific responses is important for the development of immunotherapies to treat cancer patients. We have developed a strategy to identify potential CTL epitopes based on screening of sequences of target proteins for presence of specific motifs recognized by the most common HLA-A alleles, and identification of high affinity binding peptides using in vitro quantitative assays. A systematic analysis using the sequence of the product of the tumor-associated MAGE-1 gene has been carried out. All possible peptides of nine and ten residues, containing binding motifs for HLA-A1, -A2.1, A-3.2, -A11 and -A24 were synthesized and tested for binding using a quantitative assay. Out of 237 possible peptide/MHC combinations, 47 cases demonstrated good binding affinity (Kd < or = 500 nM). Several peptides were identified as good MHC binders for each one of the five HLA-A alleles studied (five for HLA-A1, 11 for HLA-A2.1, 10 for HLA-A3.2, 16 for HLA-A11 and five for HLA-A24. Furthermore, eight of these peptides were found to bind well to more than one HLA-A allele. These results have important implications for the development of immunotherapeutic vaccines to treat malignant melanoma.
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PMID:Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles. 782 68

Several tumor antigens are recognized by autologous cytolytic T lymphocytes (CTL) on human melanoma MZ2-MEL. Some of them are encoded by genes MAGE-1 and MAGE-3, which are not expressed in normal tissues except in testis. Here, we report the identification of a new gene that codes for another of these antigens. This gene, named BAGE, codes for a putative protein of 43 aa and seems to belong to a family of several genes. The antigen recognized by the autologous CTL consists of BAGE-encoded peptide AARAVFLAL bound to an HLA-Cw 1601 molecule. Gene BAGE is expressed in 22% of melanomas, 30% of infiltrating bladder carcinomas, 10% of mammary carcinomas, 8% of head and neck squamous cell carcinomas, and 6% of non-small cell lung carcinomas. Like the MAGE genes, it is silent in normal tissues with the exception of testis. Because of its tumor-specific expression, the BAGE-encoded antigen may prove useful for cancer immunotherapy.
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PMID:BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. 789 73

We reported previously that human gene MAGE-1 directs the expression of a tumor antigen recognized on a melanoma by autologous cytolytic T lymphocytes. Probing cosmid libraries with a MAGE-1 sequence, we identified 11 closely related genes. The analysis of hamster-human somatic cell hybrids indicated that the 12 MAGE genes are located in the q terminal region of chromosome X. Like MAGE-1, the 11 additional MAGE genes have their entire coding sequence located in the last exon, which shows 64%-85% identity with that of MAGE-1. The coding sequences of the MAGE genes predict the same main structural features for all MAGE proteins. In contrast, the promoters and first exons of the 12 MAGE genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The expression of each MAGE gene was evaluated by reverse transcription and polymerase chain reaction amplification. Six genes of the MAGE family including MAGE-1 were found to be expressed at a high level in a number of tumors of various histological types. None was expressed in a large panel of healthy tissues, with the exception of testis and placenta.
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PMID:Structure, chromosomal localization, and expression of 12 genes of the MAGE family. 792 40

MAGE-1 gene encodes a human melanoma antigen, recognized by syngeneic cytotoxic T lymphocytes (CTL). MAGE-1 transcripts are also detectable in breast cancers, in non-small-cell lung carcinomas and in central nervous system tumors. In order to identify, in cellular preparations, the protein encompassing the antigenic peptide, we generated a panel of monoclonal antibodies (MAbs) against the MAGE-1 gene product by using, as immunogen, a full-length recombinant preparation (rMAGE-1), obtained through expression cloning of the relevant gene in E. coli. Four reagents were obtained recognizing both rMAGE-1 and the 46-kDa native protein in cell lines expressing MAGE-1 mRNA. No positivity could be detected in MAGE-1-mRNA-negative melanoma lines. No surface labelling of MAGE-1-positive cell lines could be observed. In contrast, on permeabilization of MZ2 melanoma cells, all 4 MAbs induced efficient staining, as detected by cytofluorography. Fluorescence microscopy shows that MAGE-1 gene product is a cytoplasmic protein clustered in paranuclear organelle-like structures. Thus, MAGE-1 protein location closely resembles that of P91A and P198 murine-tumor antigens.
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PMID:MAGE-1 gene product is a cytoplasmic protein. 792 54


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