Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic studies have implicated the early involvement of a gene on chromosome arm 9p in the development of cutaneous melanoma. We have performed loss-of-heterozygosity studies to confirm these original findings and identify the most frequently rearranged or deleted region of 9p. Eight markers were analyzed, including (from 9pter to proximal 9q) D9S33, the beta-interferon (IFNB1) locus, the alpha-interferon (IFNA) gene cluster, D9S126, D9S3, D9S19, the glycoprotein 4 beta-galactosyltransferase (GGTB2) gene, and the argininosuccinate synthetase pseudogene 3 (ASSP3). Two or more of these loci were found to be hemizygously reduced in 12 of 14 (86%) informative metastatic melanoma tumor and cell line DNAs, and homozygous deletions of the marker D9S126 were observed in 2 of 20 (10%) melanoma cell lines. These findings have resulted in the identification of a small critical region of 2-3 megabases on 9p21 in which a putative melanoma tumor-suppressor gene appears likely to reside. Several 9p candidate genes, including IFNB1, the IFNA gene cluster, GGTB2, and the tyrosinase-related protein (TYRP) locus, have all been eliminated as potential targets because they are located outside of the homozygously deleted regions.
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PMID:Homozygous deletions within human chromosome band 9p21 in melanoma. 143 46

Therapy for metastatic melanoma has been disappointing to date. Treatment with chemotherapy only uncommonly results in complete responses and rarely results in long-term survivors. The identification of human melanoma cell surface antigens has led to the development of an array of mouse monoclonal antibodies (MAb) for use in the diagnosis and therapy of patients with metastatic melanoma. Strategies utilizing MAbs based on immunologic approaches have been developed. Naked MAbs directed against glycoprotein surface antigens or conjugated to toxins or radionuclides have shown little biologic or clinical activity. However, phase I studies of MAb directed against glycolipid antigens have yielded objective tumor shrinkage with occasional complete responses. Severe toxicity has been seen infrequently. Possible anti-tumor mechanisms include complement activation and antibody-dependent cellular cytotoxicity utilizing natural killer cells or monocytes as effector cells. Strategies to enhance the anti-tumor effects of MAb, including combinations with cytotoxic agents and cytokines, have been introduced with limited success thus far. The development of a human IgG anti-mouse antibody has been seen in nearly all treated patients. A new generation of MAb engineered to overcome the immunogenicity of mouse MAb and to enhance immune effector function will soon enter clinical trials.
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PMID:Immunotherapy with monoclonal antibodies in metastatic melanoma. 156 8

The gp75 antigen is an abundant intracellular glycoprotein expressed in melanosomes of human pigmented melanocytes and melanomas. IgG antibodies in sera of a patient with metastatic melanoma have been shown to immunoprecipitate gp75, suggesting that immunological tolerance against gp75 can be broken. The mouse mAb TA99, which specifically recognizes gp75, was used to isolate and purify the antigen. Amino acid sequences of three internal peptides were determined from the purified gp75 polypeptide. cDNA clones were isolated by screening with oligonucleotides based on these peptide sequences. The gp75 peptides and cDNA had approximately 90% identity with, respectively, the derived amino acid and nucleotide sequences of a mouse gene that maps to the b (brown) locus. The brown locus determines coat color in the mouse, suggesting that gp75 regulates or influences the type of melanin synthesized.
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PMID:The melanoma antigen gp75 is the human homologue of the mouse b (brown) locus gene product. 232 88

Murine monoclonal antibody (MAb) LS109 was one of a series of MAbs produced by hyperimmunization of mice with detergent extracts of pooled melanoma cell lines and metastatic melanoma patient tumors. ELISA screening of extracts of individual cultured melanoma cell lines and single patient tumors with MAb LS109 gave an interesting pattern of reactivity. The antibody was strongly positive with some of these extracts, yet negative or weakly positive with others. In addition, there was strong reactivity with a restricted set of normal necropsy tissues and certain non-melanoma tumor extracts. Taken together, our data suggest that MAb LS109 recognizes a normal differentiation antigen which is perhaps aberrantly expressed or over-produced during certain stages of melanoma tumor progression. The antigen recognized by LS109 is a heterodimeric surface glycoprotein molecule, consisting of an 89-kDa "heavy" chain linked by disulfide bonds to an 83-kDa "light" chain. Under non-reducing SDS-PAGE conditions, the intact dimer migrates with an Mr of approximately 140kDa. The 89-kDa component appears to be heavily N-glycosylated whereas the 38-kDa component has little, if any, covalently attached carbohydrate. Our data show the biosynthesis, glycosylation and turnover of the LS109 antigen, as well as evidence of its surface localization. In addition, evidence is presented that the LS109 antigen is identical to the 4F2 cell activation/proliferation molecule previously described on a variety of normal and neoplastic cells.
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PMID:Isolation and characterization of a heterodimeric surface antigen on human melanoma cells and evidence that it is the 4F2 cell activation/proliferation molecule. 240 79

Metabolic labelling of K-1735 melanoma variants with 3H-glucosamine and cell harvesting with the commonly used protease inhibitor phenylmethylsulfonylfluoride revealed a Triton-insoluble fibronection-like 230 kd component in poorly metastatic cells. This component was not evident in highly metastatic cells. Significantly improved surface labelling and detection of the 230 kd glycoprotein in the highly metastatic variant was achieved by zinc chloride-aprotinin treatment of cells prior to harvesting. This procedure also revealed an increase in a trypsin-sensitive glycoprotein of higher molecular weight in the Triton-insoluble fraction of the highly metastatic cell variant. Glycoprotein labelling in this fraction showed an electrophoretic pattern strongly resembling that reported by others for the high-molecular-weight human melanoma-associated glycoprotein complex. The differential detection of the high-molecular-weight glycoprotein species in melanoma variants with differing metastatic abilities in an animal model provides a means of studying their possible relevance to metastatic melanoma. Our data also suggest that zinc chloride-aprotinin can be used to improve the detection of labile cell-surface components.
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PMID:Improved detection of labile cell-surface components with zinc chloride-aprotinin: demonstration of glycoprotein differences in K-1735 metastatic melanoma variants. 241 34

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.
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PMID:Antigenic profile of tumor progression stages in human melanocytic nevi and melanomas. 254 11

Murine monoclonal antibodies (MAbs) were produced with reactivity to human malignant melanoma. Six MAbs, 3 of the IgGI (LS113, LS140, LS152) and 3 of the IgG2a (LS59, LS62, LS76) subclasses, were selected for their binding, with an identical pattern of reactivity, to a novel melanoma-associated antigen. As characterized by the enzyme-linked immunosorbent assay (ELISA), these MAbs were found to be positive on n-octyl-beta-D-glucopyranoside extracts of all 10 melanoma cell lines tested and on extracts of 22 metastatic melanoma tumors. The antibodies had minimal reaction with a panel of 14 normal adult tissue extracts. A degree of cross-reactivity was observed with 50% of 39 non-melanoma tumor extracts. The results obtained with the ELISA on cell line and tissue extracts were duplicated using the ABC method of peroxidase staining. The pattern of cross-reactivity, as demonstrated by the intense staining of paraffin-embedded and frozen tissue sections of normal, benign and malignant tissues, defines the recognized protein as a neuroglandular antigen (NGA). Immunoadsorbents made with the antibodies were used to purify the antigen shed from cultured melanomas. All 6 MAbs recognized this purified antigen while 5 other antimelanoma antibodies did not react with it. On gel electrophoresis this antigen is a highly glycosylated glycoprotein with a protein core of 21 kDa.
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PMID:Characterization of a novel neuroglandular antigen (NGA) expressed on abnormal human melanocytes. 380 88

Our purpose in conducting this study was to evaluate the efficacy of an 111In-labeled murine monoclonal antibody directed against a high-molecular-weight glycoprotein in localizing metastatic melanoma in 15 patients with previously documented disease and to determine the effect of antibody mass (2.5, 5.0, and 10.0 mg) on blood clearance, biodistribution, and lesion detection. Five mCi of 111In-antibody were infused over 1 hour, and patients were scanned at 24 and 72 hours after injection without computer enhancement or background subtraction techniques. No significant differences in the organ distribution, urine excretion, or plasma disappearance curves were noted at the three antibody dose levels. There were no acute reactions. The scan detected tumor in 9 of 12 (75%) patients with active disease, and 26 of 33 (79%) lesions greater than 1 cm. Patient management in 3 of 15 (20%) of patients studied was changed as a result.
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PMID:Radioimmunodetection of human melanoma with indium-111-labeled monoclonal antibodies. 382 15

Analysis of a number of B16 melanoma clones has revealed a high correlation between metastatic activity and the quantitative expression of a 72,000 dalton glycoprotein, Met 72. In the present study, metastatic tumor cell variants have been directly isolated from a heterogeneous, poorly metastatic melanoma (B16-F1) by anti-Met 72 monclonal antibodies and cell sorting procedures. These studies provide direct proof that Met-72 antigens are in fact surface markers of B16 melanoma metastatic variants and may provide the means of monitoring their presence, influence and autonomy during tumor progression.
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PMID:Isolation of metastatic B16 melanoma variants using anti-Met 72 monoclonal antibodies and flow cytometry. 382 95

Mouse monoclonal antibodies (mAb) detecting 13 distinct systems of surface antigens on cultured melanocytes and melanomas were tested for reactivity with panels of (a) normal and malignant cultured cells; (b) normal adult and fetal tissues; and (c) specimens of metastatic melanoma and other tumor types. The objectives of this study were to compare antigen expression in cultured versus noncultured cells, to develop a panel of mAbs that identify subsets of melanomas, and to provide requisite information about antibody specificity in preparation for the use of antibodies in the diagnosis, imaging, and therapy of melanoma. Five of the melanoma surface antigens have been well characterized biochemically [GD3, chondroitin sulfate proteoglycan, HLA Class II antigens, glycoprotein of molecular weight 130,000 (gp130), and glycoprotein Mr 95,000/protein Mr 97,000 (gp95/p97)]. Three antigens have been related to melanocyte differentiation (HLA Class II, M111/M231, and M144), and six provide additional markers for subsets of cultured melanomas. mAb R24 reacts with the disialoganglioside GD3, a predominant ganglioside on cultured melanoma cells and other cells of neuroectodermal origin. A high proportion of melanoma, astrocytoma, and sarcoma tissue specimens were GD3+. In normal tissues, reactivity of mAb R24 was restricted to melanocytes, neuronal and glial cells in the central nervous system, parotid gland, adrenal medullary cells, and rare cells in the connective tissue. mAb B5 detects a chondroitin sulfate proteoglycan that is expressed by most melanoma and astrocytoma cell lines and by cultured melanocytes. Most of the melanoma and astrocytoma specimens were B5+, whereas other tumor types tested were B5-. mAb 13-17, which detects a monomorphic determinant of HLA Class II antigens, reacted with melanomas, and with a variety of other cancers, but not with normal skin melanocytes. There is considerable variability in the expression of GD3 and HLA Class II antigens in individual melanoma specimens; cotyping for these two antigens showed no evidence for coordinate expression. mAb L101 detects gp130 and mAb L235 detects gp95, antigens that are strongly expressed on a broad range of cultured cell types. In contrast to their wide distribution on cultured cells, gp130 expression in tissues was generally restricted to a subset of melanomas and some normal cells, and gp95 was detected on only a small number of melanomas. mAb M111/mAb M231 and mAb M144 define intermediate and late stage differentiation markers of cultured melanocytes and melanomas.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Surface antigens of melanomas and melanocytes defined by mouse monoclonal antibodies: specificity analysis and comparison of antigen expression in cultured cells and tissues. 402 24


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