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 MAGE-1 protein has been localized to the cytosol of human melanoma culture cells (MZ2-MEL.43) by subcellular fractionation. Its distribution between nuclear, mitochondrial, microsomal and cytosolic fractions was established by SDS-PAGE and immunoblotting with a rabbit antiserum and compared to that of markers for the main cell compartments. The immunoreactive material was recovered in the cytosolic fraction as a polypeptide migrating at 42 kDa, which has been further identified as the MAGE-1 protein because it comigrates with the product of cell-free transcription-translation of the MAGE-1 cDNA. Location to the cytosol was confirmed by immunofluorescence microscopy.
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PMID:The tumor protein MAGE-1 is located in the cytosol of human melanoma cells. 798 May 33

Transplantation experiments have demonstrated that most mouse tumors express antigens that can constitute targets for rejection responses mediated by syngeneic T lymphocytes. For human tumors, autologous cultures mixing tumor cells and blood lymphocytes or tumor-infiltrating lymphocytes have produced CD8+ and CD4+ cytolytic T cell (CTL) clones that recognize tumor cells specifically. Attempts to identify the target antigens by biochemical fractionation of tumor cells up to now have failed, with the important exception of the identification of underglycosylated mucins present on breast and pancreatic carcinomas. Gene transfection approaches have proved more successful. A gene family named MAGE codes for antigens recognized by autologous CTL on a melanoma tumor. These genes are not expressed in normal tissues except for testis. They are expressed in many tumors of several histological types. Differentiation antigens coded by genes such as tyrosinase are also recognized on human melanoma by autologous CTL. The identification of human tumor rejection antigens opens new possibilities for systematic approaches to the specific immune therapy of cancer.
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PMID:Tumor antigens recognized by T lymphocytes. 801 Dec 85

The spectrum of MAGE gene expression in the human melanoma cell line DM150 was examined using reverse transcription polymerase chain reaction and cDNA cloning. We have isolated five full-length cDNAs from DM150 which were identified as MAGE-1, MAGE-3, MAGE-12 and two previously undescribed MAGE genes, MAGE-3b and MAGE-X2. DNA sequence analysis of the coding regions of the MAGE-3b and MAGE-X2 genes revealed 83% and 88% identity with MAGE-1, while MAGE-3b was 98% homologous with the full length MAGE-3 clone. The predicted amino acid sequences of MAGE-X2 and MAGE-3b contain consensus HLA-A1 peptide binding motifs, suggesting that, like MAGE-1, they may code for tumor-associated antigens. In addition, a nonamer peptide encoded by both the MAGE-3 and MAGE-12 genes was shown by direct binding studies to contain an aggretope for HLA-A2.
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PMID:Cloning and analysis of MAGE-1-related genes. 803 61

MAGE-1 has been identified as a human gene, which directs the expression of an antigen being recognized on melanoma cells by autologous cytolytic T cells. MAGE-1 is expressed in melanomas and some other tumors. It has been proposed that this gene may be linked to the transformation event and therefore might serve as an approach to precisely targeted immunotherapy. Prior to such an approach, extensive testing of normal human tissue is necessary to establish the tumor-specific nature of MAGE-1 expression. Similar to events that occur during neoplastic tumor growth and spreading, wound healing involves a complex interrelationship between various cell types which migrate, proliferate and differentiate. Therefore, we investigated the expression of MAGE-1 in skin during wound repair. We could detect MAGE-1 mRNA by RT-PCR followed by specific hybridization as well as by Northern blotting in human skin from the 1st to the 7th day after wounding. Comparison of the expression of MAGE mRNA with that of beta-actin mRNA showed that it is expressed in amounts equal to about and at least one-fifth that of beta-actin. Our data strongly suggest that MAGE mRNA expression is not necessarily linked to neoplastic transformation, but rather represents the function of a cellular gene which is activated during inflammation or early tissue repair.
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PMID:A member of the melanoma antigen-encoding gene (MAGE) family is expressed in human skin during wound healing. 805 Aug 15

Cell lineage-specific cellular proteins, oncogenes from viral or cellular origin and tumor suppressor genes encode tumor-specific/associated antigens. Such antigens can elicit an major compatibility complex (MHC) class I-restricted cytotoxic T lymphocyte (CTL) response, either naturally in cancer patients or following appropriate immunostimulation (in vitro or in vivo). The reported immune responses in humans to the melanoma-associated MAGE gene products, GP100 and tyrosinase, all self-proteins, support the idea to use wild-type p53 products as targets for T cells. An important step towards this goal is identification of potential p53 CTL epitopes. We identified the wild-type p53 peptides with the highest affinity to the HLA-A*0201 molecule using two assays: the previously described MHC peptide-binding assay and the peptide competition assay. We obtained CTL against four p53 peptides with a high affinity for the HLA-A*0201 molecule. These findings are discussed next to a short review concerning the p53 literature.
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PMID:p53, a potential target for tumor-directed T cells. 808 74

Human melanoma cell line MZ2-MEL expresses several antigens recognized by autologous cytolytic T lymphocyte (CTL) clones. We reported previously the identification of a gene, named MAGE-1, that codes for one of these antigens named MZ2-E. We show here that antigen MZ2-D, which is present on the same tumor, is encoded by another member of the MAGE gene family named MAGE-3. Like MAGE-1, MAGE-3 is composed of three exons and the large open reading frame is entirely located in the third exon. Its sequence shows 73% identity with MAGE-1. Like MZ2-E, antigen MZ2-D is presented by HLA-A1. The antigenic peptide of MZ2-D is a nonapeptide that is encoded by the sequence of MAGE-3 that is homologous to the MAGE-1 sequence coding for the MZ2-E peptide. Competition experiments using single Ala-substituted peptides indicated that amino acid residues Asp in position 3 and Tyr in position 9 were essential for binding of the MAGE-1 peptide to HLA-A1. Gene MAGE-3 is expressed in many tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma, but not in normal tissues except for testes. It is expressed in a larger proportion of melanoma samples than MAGE-1. MAGE-3 encoded antigens may therefore have a wide applicability for specific immunotherapy of melanoma patients.
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PMID:Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes. 811 84

Human gene MAGE-I codes for an antigen that is recognized on melanoma cells by autologous cytolytic T lymphocytes (CTL). This antigen is potentially useful as a target for cancer immunotherapy because gene MAGE-I is not expressed in any normal tissues except the testis. We tested 46 surgical samples of non-small-cell lung carcinomas and observed MAGE-I expression in 16 of them (35%). Genes MAGE-2 and 3, which are closely related to MAGE-I, were expressed by a similar proportion of these tumors. Some small-cell lung tumors also express MAGE genes. The proportion of tumors expressing MAGE-I suggests that lung tumor patients may constitute the largest group of patients potentially eligible for pilot studies involving MAGE-I immunization.
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PMID:Expression of mage genes by non-small-cell lung carcinomas. 811 72

Previous studies have shown that recognition of melanoma by cytotoxic T lymphocytes may be restricted by HLA-A1, A2 and other HLA antigens. The present study examined the cytotoxic specificity and major histocompatibility complex restriction of cloned cytotoxic T lymphocytes (CTL) isolated from a patient with the HLA phenotype A3,31 who had been immunized with a vaccine prepared from HLA-A1,3 melanoma cells. Cytotoxic assays against HLA-typed allogeneic melanoma cells indicated that cloned CTL from the patient were able to kill allogeneic melanoma cells expressing HLA-A1 but not other HLA-A1-positive cells. Studies on a representative clone indicated that proliferation and cytokine (tumour necrosis factor alpha) production in response to melanoma cells was also associated with HLA-A1 on melanoma cells. Response to the melanoma cells was associated with interleukin-4 (IL-4) rather than IL-2 production. The antigen recognized in the context of HLA-A1 on allogeneic melanoma cells was detected in cytotoxic assays on cells from 9 of 12 HLA-A1+ melanoma cell lines and did not appear to be the product of the MAGE-1 or -3 genes. These findings suggest that T cells can recognize melanoma antigens in the context of alloantigens and that allogeneic vaccines containing "immunodominant" alloantigens may generate CTL that are ineffective against autologous melanoma. The study does not, however, exclude the possibility that CTL with specificity to the latter may be activated by allogeneic vaccines, and further studies are needed to answer this question.
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PMID:T cell recognition of melanoma antigens in association with HLA-A1 on allogeneic melanoma cells. 820 60

In order to define the antigens recognized by cytolytic T lymphocytes (CTLs) on autologous tumors, we derived tumor-specific CTL clones from autologous mixed lymphocyte tumor cell cultures. The gene coding for a tumor rejection antigen expressed on a melanoma was isolated by transfecting genomic DNA of the tumor into an antigen-loss variant of the melanoma. Transfectants were identified on the basis of their ability to stimulate tumor necrosis factor release by the CTL clone. The gene that transferred the expression of the antigen was named MAGE-1. It is a new gene, silent in normal tissues with the exception of testis, but expressed in several types of tumors. The antigen recognized by the CTL clone is a nonapeptide derived from the protein encoded by gene MAGE-1, and presented by the HLA class I molecule HLA-A1. Using two other antimelanoma CTL clones, we identified the tyrosinase gene as coding for an antigen presented by HLA-A2 on this type of tumors. The identification of these tumor rejection antigens open new possibilities for the specific immunotherapy of cancer.
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PMID:Genes coding for tumor antigens recognized by human cytolytic T lymphocytes. 828 Jul 1

The human MAGE-1 gene encodes a melanoma peptide antigen recognized by autologous cytotoxic T lymphocytes. To produce antibodies against the MAGE-1 gene product, several approaches were taken. Three oligopeptides were synthesized based on predicted MAGE-1 amino acid sequences and were used to generate rabbit anti-peptide anti-sera. In addition, a truncated MAGE-1 cDNA was cloned into an Escherichia coli expression vector, and recombinant protein was produced and purified. All three rabbit anti-peptide antisera showed reactivity against the immunizing peptide, and one reacted with the recombinant MAGE-1 protein by immunoblotting, but none reacted with cell lysates from MAGE-1 mRNA-positive cells. The recombinant MAGE-1 protein was then used for the generation of mouse monoclonal and rabbit polyclonal antibodies. One IgG1 monoclonal antibody, MA454, as well as rabbit polyclonal antisera recognized a 46-kDa protein in extracts of MAGE-1 mRNA-positive melanoma cell lines. The antibodies showed no apparent cross-reactivity with products of the closely related MAGE-2 and MAGE-3 genes. Serological typing of normal and tumor cell lysates was in full agreement with mRNA analysis, showing expression of MAGE-1 protein in MAGE-1 mRNA-positive testis and a subset of melanomas but not in MAGE-1 mRNA-negative normal or tumor tissues. Transfection of the MAGE-1 gene into a MAGE-1 mRNA-negative melanoma cell line resulted in the expression of the 46-kDa protein, confirming the identity of this protein as the MAGE-1 gene product.
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PMID:Identification of the MAGE-1 gene product by monoclonal and polyclonal antibodies. 830 24


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