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)

Tumor necrosis factor (TNF) is cytocidal for human and murine cells when protein synthesis is inhibited by cycloheximide, but some protease inhibitors completely protect these cells from TNF cytotoxicity. Inhibitors of chymotrypsin-like proteases are active at lower concentrations than inhibitors of trypsin-like proteases. Both irreversible inhibitors, such as alkylating compounds, and reversible inhibitors, such as substrates of proteases, protect cells from the cytocidal activity of TNF. This protection is most effective when the cells are pretreated with these inhibitors before addition of TNF. When the protease inhibitors are removed, the cells gradually lose resistance to TNF cytotoxicity. The inhibitors do not interfere with the functioning of TNF-receptor complexes, since SK-MEL-109 melanoma cells treated with a protease inhibitor synthesize a TNF-induced protein. These findings suggest that a protease in involved in the cytocidal action of TNF.
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PMID:Protection from tumor necrosis factor cytotoxicity by protease inhibitors. 359 75

The anticancer agent doxorubicin has two different effects on human SK-MEL-170 melanoma cells: the well known direct cytotoxicity and a marked enhancement of their susceptibility to killing by the R24 monoclonal anti-GD3) ganglioside antibody and human complement. This complement-enhancing effect of doxorubicin is also present after covalent immobilization onto glycerol-coated glass beads preventing cellular uptake of the drug (M. Panneerselvam, R. Bredehorst, and C-W. Vogel, Proc. Natl. Acad. Sci. USA, 83: 9144-9148, 1986). In order to investigate the effect of doxorubicin resistance on the complement-enhancing activity of the drug, we have established a doxorubicin-resistant SK-MEL-170 subline. The development of drug resistance in these melanoma cells was associated with multiple phenotypical changes including an increased expression of at least four high molecular weight plasma membrane proteins or glycoproteins with molecular weights of approximately 220,000, 180,000, 150,000, and 130,000, respectively. The drug-resistant cells accumulated doxorubicin at approximately 2-fold lower amounts in accordance with a 2-fold higher efflux of doxorubicin from these cells. The basal complement susceptibility of the doxorubicin-resistant cells was reduced by more than 60% presumably as a result of the observed reduced expression of GD3 sites and decreased binding of C3b. Most importantly, the doxorubicin-resistant cells were also resistant against the complement-enhancing effect of the free and immobilized drug. The two doxorubicin resistance phenomena, the resistance to the cytotoxic and to the complement-enhancing activities of the drug, seem to be fundamentally different: (a) to achieve comparable cytotoxic and complement-enhancing effects on drug-sensitive and -resistant SK-MEL-170 cells, the drug-resistant cells required 178-fold higher concentrations of free doxorubicin for the cytotoxic effect but only 5-fold higher amounts of the free drug and 12-fold higher amounts of the immobilized drug for the complement-enhancing effect; (b) resistance against the cytotoxic activity of doxorubicin is associated with reduced intracellular drug accumulation, while the data obtained with immobilized doxorubicin indicate that resistance to the complement-enhancing activity of the drug is independent of cellular drug uptake. These data suggest that different mechanisms are responsible for the two resistance phenomena in doxorubicin-resistant melanoma cells.
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PMID:Resistance of human melanoma cells against the cytotoxic and complement-enhancing activities of doxorubicin. 362 Nov 56

There is a wealth of information about monoclonal antibody (MAb) specificity and function on fixed tissues, yet little is known about formation and release of antigen-antibody complexes and their functional behavior in vivo. We analyzed the pathway of radiolabeled MAbs directed against melanoma-associated antigens by radioimmunoelectron microscopy (RIEM) on metabolically active cells of the melanoma cell lines SK-MEL-28, MeWo and Colo 38 at different time intervals. In parallel, binding and release of MAbs were investigated by the radioantibody binding assay (RBA). Both procedures gave essentially concordant results. Preferentially stable binding of immune complexes (ICs) to the cell surface after 30 and 120 min was shown for the MAb L10. Internalization was demonstrated for the MAb M.2.9.4. At the ultrastructural level, direct evidence of this phenomenon was obtained by visualization of radioactivity within the cytoplasm after 120 min. In the RBA this process was indicated by resistance of bound MAbs to acid buffer desorption. RIEM pointed to different transport mechanisms: constitutive internalization by endocytotic vesicles, or receptor-mediated endocytosis by coated vesicles. Shedding was indicated for the MAb R24 by release of the ICs from the cell membrane. It was demonstrated that stable fixation of ICs on the cell surface or modulation by internalization led to high accumulation rates, while shedding of antigen-antibody complexes resulted in a low accumulation of the MAb in tumor cells. Assuming that the potential of MAbs for clinical application is determined by the biological behavior of antigen-antibody complexes, these methods are suitable for demonstration of antigenic modulation by MAbs and eventually enable us to predict the localization, penetration and distribution pattern of individual MAbs in the melanoma patient.
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PMID:Modulation of melanoma-associated antigens by monoclonal antibodies as visualized by radioimmunoelectron microscopy and radioantibody binding assay. 366 2

The effects of human interferon-beta (IFN-beta, MR-21) on the growth of xenografted human tumors in nude mice were examined. IFN-beta was administered to mice with malignant melanoma (SK-MEL-28 and Sk-14) intratumorally at a dose of 1 X 10(5)-3 X 10(5) IU/mouse, with acute leukemia (CCRF-HSB-2) intratumorally at a dose of 3 X 10(5) IU/mouse, with glioblastoma (U-373 MG) intravenously or intratumorally at a dose of 1 X 10(5)-6 X 10(5) IU/mouse, or with uterine cervical tumor (HeLa S3) intravenously at a dose of 0.3 X 10(5)-1 X 10(5) IU/mouse. IFN-beta inhibited the growth of all of these tumors in a dose-dependent manner.
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PMID:[Basic study on interferon-beta: Part IV. Antitumor effect on nude mouse-transplanted human tumors]. 371 59

A mouse monoclonal IgM antibody, 4.2, has previously been shown to bind preferentially to the surface of human malignant melanoma cells and to have specificity for the GD3 ganglioside (NeuAc alpha 2----8NeuAc alpha 2----3Gal beta 1----4GlcCer). Using overlay of antibodies on thin-layer chromatograms with glycolipids of various sources, it was shown that antibody 4.2, a further IgM and two IgG3 mouse monoclonal antibodies, selected on the basis of reactivity with GD3, also bound with similar strength to the structural analogue NeuAc alpha 2----8NeuAc alpha 2----3Gal beta 1----4GlcNac beta 1----3Gal beta 1----4GlcCer or disialylparagloboside. The SK-MEL 28 melanoma cell line used for immunization was shown to contain a large amount of GD3 but to lack disialylparagloboside. The demonstrated cross-reactivity may be of importance when considering the use of these antibodies for biochemical and medical purposes.
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PMID:Mouse monoclonal antibodies with specificity for the melanoma-associated ganglioside disialyllactosylceramide (GD3) also react with the structural analogue disialylparagloboside. 384 Jun 99

The immunohistochemical reactivity of the monoclonal antimelanoma antibody MEL-1 was evaluated on frozen sections of 9 malignant melanomas, 5 nevi, 1 squamous cell carcinoma, 1 basal cell carcinoma, 2 benign dermal fibrous histiocytomas, 1 infiltrating ductal and 2 infiltrating lobular carcinomas of the breast, 1 primary squamous cell carcinoma and 1 adenocarcinoma of the lung, 1 lung metastasis of gastric adenocarcinoma, 1 adenocarcinoma of the large bowel, 1 lymph node, 1 case of malignant histiocytosis and one of lymph nodal immunoblastic lymphoma, and 1 biopsy of oral cavity mucosa. In primary and metastatic malignant melanoma, junctional nevi, and the upper half of compound and dermal nevi, the staining was intense. Also, benign dermal fibrous histiocytoma and the case of lymph nodal malignant histiocytosis showed an intense reactivity, whereas the immunostaining positivity of the squamous cell carcinoma of the skin, the lung adenocarcinoma, the squamous cutaneous and mucosal epithelium, and the sweat and sebaceous glands was slight. In ductal and lobular infiltrating carcinoma of the breast only focal areas or isolated tumor cells were positive. The lack of reactivity of deep dermal melanocytes of compound and dermal nevi may be correlated with a different antigenic phenotype of the melanocytes. After discussion of the technical problems, the application of MEL-1 was suggested, for diagnostic purpose, to identify lymph nodal metastases in cases of primary self regressed malignant melanoma and to detect lymph nodal metastatic microfoci of malignant melanoma.
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PMID:Immunohistochemical reactivity of the antimelanoma monoclonal antibody MEL-1. 389 83

The functional properties of cytotoxic lymphocytes from patients with Vogt-Koyanagi-Harada disease ( VKH ) specific for human melanoma cells (P-36 melanoma cell line established from a patient with malignant melanoma) were investigated by using monoclonal antibodies specific for human T cell subsets. Peripheral blood lymphocytes (PBL) from patients with VKH showed significant cytotoxic activity against the P-36 (SK-MEL-28) human melanoma cell line, but not against a human cervical carcinoma of the uterus cell line (HeLa-S3 cell line) or against a mouse melanoma cell line (B-16 cell line) originating from a C57BL/6 strain mouse or against the EL-4 mouse lymphoma cell line from a C57BL/6 mouse. The cytotoxic activity of the patients' PBL against the P-36 melanoma cell line was markedly reduced by pretreatment of the PBL with monoclonal anti-human Leu-1 antibody plus rabbit complement, but it was reduced to much less extent by pretreatment with either monoclonal anti-human Leu-2a or Leu-3a antibody plus rabbit complement. The specific cytotoxic activity of the patients' PBL against the P-36 human melanoma cell line is, therefore, mediated by T cells bearing Leu-1+ Leu-2a+ or Leu-1+ Leu-3a+ antigens. Furthermore, the cytotoxic activity was shown to be blocked not only by anti-Leu-2a antibody specific to human cytotoxic/suppressor T cells but also unexpectedly by anti-Leu-3a antibody which has previously been considered to be specific to human inducer/helper T cells. The results of this study suggest that at least two distinct subpopulations of cytotoxic T cells specific for P-36 human melanoma cells are present in the peripheral blood of VKH patients. These cytotoxic T cells have different surface antigens, Leu-2a and Leu-3a.
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PMID:Two distinct cytotoxic T lymphocyte subpopulations in patients with Vogt-Koyanagi-Harada disease that recognize human melanoma cells. 620 18

The 30 workshop monoclonal antibodies identify a number of distinct cell surface antigens of human melanoma. Indirect 125I-protein A binding assays showed that virtually all of the antibodies recognized antigens at the surface of SK-MEL-28 melanoma cells. Immunoprecipitation from detergent lysates of surface-radioiodinated cells showed that 16 of the antibodies recognized cell surface proteins. Antibodies 96.5, 118.1, 133.2 and two antibodies from the Sloan-Kettering group, I12 and L10, recognized a 97,000 MW protein, p97, but none of the other antibodies did so. Many of the antigens appear to have sufficient specificity for melanoma to be of interest as potential diagnostic markers and therapeutic targets and to merit structural and functional studies.
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PMID:Workshop on monoclonal antibodies to human melanoma-associated antigens: findings of the Seattle group. 620 36

Melanoma-associated antigens (MAAs) recognized by murine monoclonal and rabbit polyclonal antibodies were compared. Two rabbit antimelanoma sera raised in our laboratory recognized five human cell-surface MAAs with approximate MWs of 75, 95, 120, 150, and 240 kd. These antigens were easily detected by SDS-PAGE of specific immunoprecipitates on a melanoma cell (HM31) which failed to reveal antigens reactive with the panel of murine monoclonal antibodies studied. By contrast, these five antigens could not be detected on another melanoma cell (SK-MEL-28), which was reactive with several of the murine monoclonals. These results suggest that the MAAs recognized by rabbit and murine antibodies are different and imply that the antigens which are immunogeneic in man may not necessarily be immunogeneic in mice.
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PMID:Comparison of cell-surface human melanoma-associated antigens identified by rabbit and murine antibodies. 620 41

A mouse MAb3 50H.19 raised against the human melanoma cell line MEL-T binds to carcinoma cell lines, carcinoma biopsy material, and certain epithelia of normal tissues. It immunoprecipitates two components from carcinoma cell lines, a major component of 22 kd which is O-glycosylated and a minor one of 24 kd which is additionally N-glycosylated. The immunocomplexed 50H.19 antigen exhibits protein kinase activity with substrate-specificity for casein and phosvitin, but not for histones. It phosphorylates on serine and threonine, but not tyrosine residues. Enzyme activity is cyclic AMP-independent.
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PMID:Human tumor cell membrane glycoprotein associated with protein kinase activity. 651 Nov 25


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