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

A variety of factors were found to modify the toxicity of L-dopa in HeLa cells (D37 16 microM) and in dopa-sensitive, nonpigmented human melanoma cells (MM96) (D37 5 microM) having a similar size and doubling time. Dopa toxicity was decreased by concurrent treatment with superoxide dismutase, peroxidase or catalase, by erythrocytes, or by hypoxia. Toxicity could be increased by the enzyme inhibitors L- and D-penicillamine, sodium diethyldithiocarbamate or 3-amino-1,2,4-triazole. The two cell lines had similar levels of superoxide dismutase and peroxidase; in 6 human melanoma lines, no correlation was found between dopa killing and tyrosinase activity as determined either by formation of dopa from tyrosine or by formation of melanin from dopa. Uptake of L-dopa was similar in HeLa and MM96 cells, and the toxicity of D-dopa was the same in both lines as that of the L-isomer. Dopa decomposed within 12 hr in culture medium, the rate and products being influenced by addition of the above enzymes and by the cell density. Dopa-melanin and medium containing decomposed dopa were also selectively toxic to MM96 cells. Adenovirus 5 was used in two different ways to assess the relative importance of DNA damage and inhibition of DNA synthesis by dopa. Viral replication was found to be unaffected in cells being treated with dopa but was strongly inhibited in cells treated with the DNA polymerase inhibitor cytosine arabinoside. Secondly, the virus was itself inactivated by treatment with dopa for 24 hr (D37 1.3 mM); similar dose response curves were obtained for replication of dopa-treated virus in untreated HeLa or MM96 cells. These results show that the initial events of dopa toxicity occur outside the cell and lead to the formation of a stable, toxic product (probably melanin) which does not strongly inhibit DNA polymerase activity. Melanoma hypersensitivity was not due to differences in oxygen-metabolizing enzymes, dopa uptake, or DNA repair.
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PMID:Modification of dopa toxicity in human tumour cells. 392 49

Tunicamycin, an inhibitor of glycosylation, was used to examine whether glycosylation is required for shedding of tumor antigens and other macromolecules by human melanoma cells. Cellular proteins were labeled with [35S]methionine, glycoproteins with [14C]glucosamine, and external surface components with 125I by the lactoperoxidase method; 0.5 and 2.5 microgram tunicamycin/ml effectively inhibited glycosylation without significantly reducing protein synthesis. We found that release of labeled macromolecules in the presence or absence of tunicamycin was similar. Tunicamycin-treated cells released 10.2% of [35S]methionine, 29.8% of [14C]glucosamine, and 57.2% of 125I-labeled macromolecules in 24 h compared to 5.5, 14.9, and 50.8%, respectively, for untreated control cells; 62.5% of the radioactivity associated with cell-surface melanoma-associated antigens defined by specific antiserum were released in 24 h as opposed to 50.4% by untreated cells. These results indicate that release of many cellular proteins, including glycoproteins, external surface proteins, and some melanoma-associated antigens, does not require glycosylation.
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PMID:Effect of tunicamycin on release of macromolecules and tumor antigens by human melanoma cells. 397 39

The ability of radiolabeled monoclonal antibodies to accumulate in and image small human tumors growing in the spleen of athymic mice was assessed. The antibodies B6.2 and B72.3, which reacted against human breast (Clouser) and colon (LS174T) tumor cells in vitro and in vivo, respectively, and the isotype matched anti-horseradish peroxidase antibody which did not bind to these tumors were used in pharmacokinetic and imaging experiments. Human melanoma cells and tumors (A375) which did not react with any of the three antibodies were used as additional controls. Radioiodinated "tumor specific" and non-specific antibodies were injected i.v. into athymic mice bearing intrasplenic tumors and the mice were sacrificed at various times to assess the specificity of uptake of these antibodies into tumor and normal host tissues. The accumulation of B6.2 in the Clouser tumor was maximal at 24 h as indicated by a localization index (specific/nonspecific antibody in tumor divided by the same ratio in blood) of about 4.0. The uptake of B72.3 in LS174T tumor increased with time with a localization index of about 12.0 observed at 50 h post-antibody injection. Localization indices for the control A375 tumor and for all normal mouse tissues, including the uninvolved portion of the tumor bearing spleen, were between 0.8 and 1.0, thus indicating no specific antibody accumulation. The relative blood flows of the Clouser and A375 tumors, as determined by the 86RbCl method, were similar. The results suggested that immunospecificity was a major factor in antibody localization in vivo. Specific images of approximately 100-mg Clouser tumors with radiolabeled B6.2 and of LS174T tumor with radiolabeled B72.3 were seen by 24 h after antibody injection. Images of smaller (about 20 mg) LS174T tumors were seen by 48 h following B72.3 injection. The control antibody, anti-horseradish peroxidase, did not image either Clouser or LS174T tumor. Also the control tumor was not imaged with any of the three antibodies tested. The data generated with this novel animal model support the concept of using radiolabeled monoclonal antibodies for detecting and possibly treating small metastatic visceral tumors in cancer patients.
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PMID:Radioimmunodetection of small human tumor xenografts in spleen of athymic mice by monoclonal antibodies. 405 53

Peroxide-dependent enzymic oxidation of tyrosine to dopachrome and melanin was demonstrated in cell-free melanoma homogenates. Histochemical methods for distinguishing peroxidase activity from aerobic dopa (3,4-dihydroxyphenylalanine) oxidase activity are not reliable with cell-free preparations. Therefore the presence of peroxidase activity in such preparations precludes assay of cresolase activity of mammalian ;tyrosinase'.
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PMID:Peroxidatic oxidation of tyrosine to melanin in supernatant of crude mouse melanoma homogenates. 444 86

A case of a malignant neoplasm with features suggestive of both malignant melanoma and squamous cell carcinoma is reported. The neoplastic cells were positive for both S-100 protein and keratin when stained by the indirect peroxidase-antiperoxidase method. The literature on other instances of bi- or multidirectional differentiation of neoplastic cells is reviewed. The significance of these findings for terminology of neoplasms is discussed.
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PMID:A malignant neoplasm with features of both squamous cell carcinoma and malignant melanoma. 608 56

Cell surface glycoconjugate patterns of human epidermal cells and of melanoma cells (MC) in primary culture derived from 11 primary and metastatic melanomas were investigated using fluorescent and horseradish peroxidase conjugated lectins for visualization at the light and electron microscopic level. The lectin labeling profiles of human melanocytes (M) and MC were found to be identical. According to their binding patterns, the lectins tested were grouped into three categories: (1) lectins binding to both keratinocytes (K) and M/MC, irrespective of neuraminidase pretreatment (concanavalin-A, wheatgerm agglutinin, succinylated wheatgerm agglutinin); (2) lectins binding to K but not to M/MC, irrespective of neuraminidase pretreatment (Ulex europaeus agglutinin I); (3) lectins binding to K, but to M/MC only after neuraminidase pretreatment (soybean, Helix pomatia, and peanut agglutinins). Untreated M were reactive for soybean and peanut agglutinins only at contact sites with K. Since the lectins from soybean, Helix, and peanut bind specifically to D-galactose and N-acetyl-D-galactosamine residues, we conclude that these particular glycoconjugates are normally masked by sialic acid on M/MC surfaces and can be unmasked by neuraminidase. These features, which have been previously observed in guinea pig M, appear to be interspecies surface markers of melanocytic cells which remain unaltered in the course of malignant transformation.
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PMID:Identical lectin binding patterns of human melanocytes and melanoma cells in vitro. 618 69

The presence of myelin basic protein (MBP) within a skin neoplasm would support its derivation from Schwann's cells, since this substance is routinely present within Schwann's cells in the peripheral nervous system. Using a monoclonal antibody prepared against MBP and an unlabeled antibody peroxidase-antiperoxidase assay, we surveyed a variety of skin lesions suspected of being derived from Schwann's cells to determine whether MBP was present. Myelin basic protein was detected within the cytoplasm of cells composing benign solitary schwannoma (neurilemmoma) and neurofibroma, confirming the association of these lesions with proliferation of Schwann's cells. Myelin basic protein was not found in a variety of intradermal and compound nevus cell nevi nor in malignant melanoma. This negative finding supports electron microscopic evidence suggesting that nevus cells have no relationship to Schwann's cells even though some nevus cell arrangements suggest Schwann's cell derivation under the light microscope.
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PMID:A survey of cutaneous neural lesions for the presence of myelin basic protein. An immunohistochemical study. 619 73

Thirty monoclonal antibodies from eight laboratories exchanged after the First Workshop on Monoclonal Antibodies to Human Melanoma held in March 1981 at NIH were tested in an antibody-binding radioimmunoassay using a panel of 28 different cell lines. This panel included 12 melanomas, three neuroblastomas, four gliomas, one retinoblastoma, four colon carcinomas, one lung carcinoma, one cervical carcinoma, one endometrial carcinoma, and one breast carcinoma. The reactivity pattern of the 30 monoclonal antibodies tested showed that none of them were directed against antigens strictly restricted to melanoma, but that several of them recognize antigenic structures preferentially expressed on melanoma cells. A large number of antibodies were found to crossreact with gliomas and neuroblastomas. Thus, they seem to recognize neuroectoderm associated differentiation antigens. Four monoclonal antibodies produced in our laboratory were further studied for the immunohistological localization of melanoma associated antigens on fresh tumor material. In a three-layer biotin-avidin-peroxidase system each antibody showed a different staining pattern with the tumor cells, suggesting that they were directed against different antigens.
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PMID:Reactivity spectrum of 30 monoclonal antimelanoma antibodies to a panel of 28 melanoma and control cell lines. 620 35

The antigenic relationships between human tumors of neuroectodermal origin and fetal brain were investigated by the production of hybridoma antibodies derived from a fusion of P3-NS1/1-Ag 4-1 (NS1) myeloma cells with splenocytes from a mouse multiply immunized with an homogenate of second-trimester human fetal brain tissue. Two monoclonal antibodies (MAs), 4D2cl 6 and 7H10cl 4, were studied in detail by cell surface radioimmunoassay (CS-RIA), quantitative absorption, indirect immunofluorescence, and peroxidase-anti-peroxidase (PAP) immunohistology. MA 4D2cl 6 binds to 5 of 14 glioblastoma (GBM) cell lines, 1 of 2 melanoma cell lines, 1 of 3 neuroblastoma cell lines, and 1 of 5 fetal fibroblast lines by CS-RIA and to 13 of 13 GBM, 1 neuroblastoma, and fetal brain, liver, spleen, and adult spleen unfixed frozen tissue by PAP analysis. MA 7H10cl 4 binds to 13 of 14 GBM, 1 of 3 neuroblastoma, and 1 medulloblastoma cell line(s) by CS-RIA analysis and to 13 of 13 GBM, 1 neuroblastoma, fetal brain, liver, spleen, thymus, and adult spleen by PAP analysis. Control non-central nervous system tumors and normal adult tissue, including brain, were unreactive with both MAs by CS-RIA, PAP, and absorption analysis. Tissue distribution and localization analyses established that MAs 4D2cl 6 and 7H10cl 4 recognize specificities of shared fetal-neuroectodermal-lymphoid distribution which are operationally specific within the adult central nervous system and which are not related to previously described oncofetal or onconeural antigens.
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PMID:Expression of human fetal brain antigens by human tumors of neuroectodermal origin as defined by monoclonal antibodies. 627 12

The antigenic relationship between human tumors of neuroectodermal origin and fetal brain were further investigated by characterization of two hybridoma antibodies derived from a fusion of P3-NS1/1-Ag 4-1 (NSI) myeloma cells and splenocytes hyperimmunized to second trimester human fetal brain homogenate. Monoclonal antibodies (MAs) 1H8cl 2 and 1H8cl 3 were analyzed by cell surface radioimmunoassay (CS-RIA), quantitative absorption, indirect immunofluorescence, and peroxidase-antiperoxidase (PAP) immunohistology. MA 1H8cl 3 is the more broadly reactive, binding to 9/14 glioblastoma (GBM), 2/3 neuroblastoma, 1/2 melanoma, and 1 medulloblastoma cell line(s) by CS-RIA analysis, and to 12/15 GBM, fetal brain, spleen, and liver, and adult spleen by PAP analysis. MA 1H8cl 2 is more restricted, binding to 7/14 GBM, 2/3 neuroblastoma, 1 medulloblastoma, and 2/3 fetal skin fibroblast cell line(s) by CS-RIA, and to 9/15 GBM and fetal brain and spleen by PAP analysis. Control non-central nervous system tumors and normal adult tissue including brain, thymus, lymph node, liver, kidney, lung, skin, and pancreas, were unreactive with both 1H8cl 2 and 1H8cl 3 by CS-RIA, PAP, and absorption analysis. The data presented here establish the unique nature of the detected antigenic specificities as compared to previously described oncofetal and onconeural antigens, and define two immune reagents which are operationally specific for tumors of neuroectodermal origin within the adult central nervous system.
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PMID:Human fetal brain antigen expression common to tumors of neuroectodermal tissue origin. 628 96


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