UMLS:C0025202 - FACTA Search

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

The simultaneous injection of monoclonal antibody 9.2.27, directed against a chondroitin sulfate proteoglycan preferentially expressed on human melanoma cells, and 2 X 10(7) mononuclear splenocytes, eradicated established, progressively growing human melanoma tumors in nude mice. Neither splenocytes nor antibody alone achieved significant tumor regression. The cells responsible for tumor elimination are most likely natural killer (NK) cells: they are present in splenocytes of T cell-deficient nude mice, and cloned cells with NK activity are able to suppress tumor growth. Moreover, splenocytes treated with anti-asialo GM1 and complement or harvested from NK-deficient C57BL/6 beige mice did not cause tumor rejection. Furthermore, treatment of BALB/c nude mice just before injection with anti-asialo GM1 antiserum, which is known to eliminate NK activity in vivo, resulted in better tumor growth. In addition, evidence is presented that cells with NK activity are probably the effectors responsible for melanoma target cell lysis in vitro: Antibody-dependent and -independent cell-mediated lysis of M21 melanoma cells was suppressed when splenocytes were preincubated with complement and antibodies specific for cell surface antigens of NK cells, i.e., anti-asialo GM1, anti-Qa5, and anti-NK1.1. Moreover, splenocytes of C57BL/6 beige mice were not able to lyse M21 cells in vitro. These results strongly support the conclusion that cells with NK activity are indeed responsible for the antibody-dependent destruction of M21 melanoma cells in vivo and in vitro.
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PMID:Eradication of established human melanoma tumors in nude mice by antibody-directed effector cells. 400 16

The effect of thioglycollate-elicited macrophages (TG-M phi) on natural killer (NK)-cell activity and metastases formation in mice was investigated. Intravenously (i.v.) inoculated TG-M phi inhibited spleen NK activity of normal mice and abrogated polyinosinic: polycytidylic (poly I:C) induced augmentation of NK cell function. TG-M phi also inhibited the clearance of i.v.-injected radiolabeled B16 melanoma cells from the lungs of normal or poly I:C stimulated mice. Formation of experimental B16 melanoma metastases was dramatically increased in mice pretreated with TG-M phi. Administration of TG-M phi increased metastasis formation to a greater extent than anti-asialo GM1 serum, while anti-asGM1 serum was more efficient than TG-M phi in depressing spleen NK cell activity. When mice with low NK reactivity (beige mice or mice treated with anti-asialo GM1 serum) were inoculated with TG-M phi, there was a substantial additive augmenting effect on metastasis formation in the lungs. Treatment with poly I:C elevated NK-cell activity and had profound antimetastatic effects in normal but not in TG-M phi pretreated mice. The metastasis augmenting effect of TG-M phi was fully expressed in poly I:C-treated mice as well as in athymic nude mice. Inoculation of proteose peptone-elicited macrophages (PM phi), unlike TG-M phi, did not depress NK activity or augment metastasis formation in normal or poly I:C-treated mice. However, since the inhibition of NK activity in TG-M phi-treated mice was relatively weak, and a substantial additional increase in metastases was observed in NK-depressed mice after transfusion of TG-M phi, it seems unlikely that the TG-M phi-induced inhibition of NK reactivity is entirely responsible for the augmented formation of metastases. Further studies revealed that i.v. inoculation of TG-M phi, but not PM phi, induced intravascular inflammatory reactions, and damage to endothelial cells and basement membrane of the lung vasculature. These reactions may contribute to increased tumor cell extravasation and metastasis formation in mice pretreated with TG-M phi.
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PMID:Influence of adoptively transferred thioglycollate-elicited peritoneal macrophages on metastasis formation in mice with depressed or stimulated NK activity. 404 60

Monoclonal antibody D1.1 originally prepared against the B49 cell line derived from a rat brain tumor was shown to react with a ganglioside present in fetal rat brain. We have found that this antigen is also present in human malignant melanoma tumors as well as many melanoma cell lines. The ganglioside from human melanoma cell lines migrates between GM1 and GM2 on one-dimensional thin layer chromatography. Analysis by two-dimensional thin layer chromatography with intermediate ammonia treatment suggests that the ganglioside contains one or more base-labile O-acyl esters. Mild base hydrolysis under conditions known to remove O-acyl esters results in complete loss of antigenic reactivity. Thus, the alkali-labile moiety is a critical component of the epitope recognized by the antibody. Analysis of the sialic acids of total gangliosides from [6-3H]glucosamine-labeled melanoma cells showed that approximately 10% of these molecules are O-acylated. Similar analysis of the purified ganglioside showed that greater than 30% of the sialic acids comigrated with authentic 9-O-acetyl-N-acetylneuraminic acid. The antibody did not cross-react with normal human skin melanocytes nor with any of a large number of normal human adult and fetal tissues. The antibody also did not react with numerous other malignant cell lines studied. These findings suggest that the antigenic epitope defined by antibody D1.1 contains an O-acylated sialic acid and may arise from aberrant O-acetylation occurring in human malignant melanoma cells.
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PMID:A monoclonal antibody recognizes an O-acylated sialic acid in a human melanoma-associated ganglioside. 620 95

Natural killer (NK) cell activity of mice given a single injection of manganese chloride (MnCl2) was significantly enhanced as measured in a 4-hr in vitro 51Cr release assay. Enhanced activity persisted for several days after injection. This cytotoxic activity was associated with nonadherent spleen cells and was completely eliminated by injecting MnCl2-treated mice with anti-asialo GM1 serum. Manganese-enhanced natural cytotoxicity was observed in several mouse strains with differing NK cell reactivity (CBA/J, C57BL/6, A/J, C3H/HeJ, and C57BL/6 beige mice) and with several tumor target cells with differing sensitivity to NK cytolysis (YAC-1, RBL-5, EL-4, and P815). The growth of B16-F10 melanoma lung tumors was inhibited in mice injected with MnCl2 one day before tumor challenge. Manganese chloride enhancement of NK cell activity appeared to be mediated by interferon (IFN). Low levels of IFN were detected in the serum of mice as early as 4 hr after MnCl2 injection. Rabbit anti-mouse IFN alpha, beta but not anti-mouse IFN gamma completely eliminated the MnCl2-enhanced NK cell activity in the spleens of mice. The observed enhancement of NK cell activity by MnCl2 is similar to that reported for more complex molecules that act by inducing IFN production.
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PMID:Manganese chloride enhances murine cell-mediated cytotoxicity: effects on natural killer cells. 620 61

The antimetastatic effects of heparin (40 units) and prostacyclin (PGI2, 100 microgram)1 were investigated in normal mice and in mice with depressed or activated natural killer (NK) cell activity. Both anticoagulants inhibited the formation of lung metastases after inoculation of the FI or F10 sublines of B16 melanoma. Inhibition of NK activity by treatment of mice with anti-asialo GM1 serum abrogated the antimetastatic effects of PGI2 or heparin. Conversely, augmentation of NK-cell activity by poly I:C plus treatment with anticoagulants produced synergistic antimetastatic effects. A similar pattern of results was obtained with heparin treatment of mice challenged with the Madison lung carcinoma (M109), but PGI2 alone or in combination with theophylline had little or no detectable antimetastatic effect on M109 or on the parental B16 melanoma. Studies of the mechanism of the interaction between heparin nd NK cells revealed that the anticoagulant treatment did not affect splenic NK activity in vitro. However, heparin treatment caused a significant increase in the clearance of radiolabelled tumor cells from the lungs of normal mice. Combined treatment of mice with poly I:C and heparin synergistically accelerated the elimination of radiolabelled tumor cells. In contrast, heparin did not affect the clearance of tumor cells from the lungs of mice with depressed NK activity. Thus the antimetastatic effects of heparin and PGI2 are dependent on levels of NK activity in the host. Platelet aggregation and fibrin coating of the surface of tumor cells may be among the mechanisms by which hematogenously spread tumor cells are protected from destruction by NK cells. Anticoagulant drugs may exert antimetastatic effects by making tumor cells more vulnerable to the cytotoxic effects of NK cells, rather than by blocking adherence of tumor cells to vascular endothelium.
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PMID:Role of NK cells in the antimetastatic effect of anticoagulant drugs. 636 8

The mechanism of artificial and spontaneous metastases of tumor was analyzed in B16 melanoma cells and C57BL/6 mice by using anti-asialo GM1 antibody and anticancer agents. Single administrations of 500 micrograms anti-asialo GM1 antibody resulted in significantly decreased NK activity in spleen cells of C57BL/6 mice, lasting 10 days from the day following administration. Treatment with anti-asialo GM1 antibody never decreased the function of T lymphocytes measured by blastogenesis with phytohemagglutinin or T cell growth factor. The tumoricidal functions of activated macrophages but not of resident macrophages were decreased by in vivo treatment with anti-asialo GM1 antibody. The anti-asialo GM1 antibody was evaluated in terms of the enhancing effect on pulmonary metastases with regard to the timing of administration. Treatment with anti-asialo GM1 antibody 1 day before or on the day of tumor inoculation resulted in a substantial increase in the number of artificial pulmonary metastases. In the experimental system of spontaneous metastases, anti-asialo GM1 antibody most effectively increased the number of pulmonary metastases when administered 1-2 weeks before the removal of primary tumor, when the tumor cells are thought to be released into blood circulation from the primary site. In addition, accelerated growth of transplanted tumors at the primary site was observed in mice treated with anti-asialo GM1 antibody. These results strongly suggest that anti-asialo GM1 antibody enhances the incidence of in vivo tumor metastases and the growth of transplanted tumor mainly by suppressing the function of NK cells. The maximum effective dose (MED) of mitomycin C or its derivative (M-83) suppressed NK activity significantly, and pretreatment with these anticancer agents enhanced the growth of the artificial pulmonary and liver metastases. In contrast, the MED of cDDP showed no effect on the NK activity or the numbers of pulmonary and liver metastases. These results indicate that the depression of NK activity induced by chemotherapy results in the promotion of metastatic disease. From these studies it can be concluded that NK cells have a key role in the control of metastases of malignant disease, and that support of NK activity is very important for the prevention of metastases.
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PMID:Analysis of metastatic spread and growth of tumor cells in mice with depressed natural killer activity by anti-asialo GM1 antibody or anticancer agents. 673 2

The role of asialo GM1 positive cells was studied in artificial and spontaneous pulmonary metastases as well as in tumor growth by using B-16 melanoma cells in C57BL/6 mice. Single administration of 50 microliters of anti-asialo GM1 antibody resulted in the significant decrease of NK activity in the spleen cells of C57BL/6 mice lasting 13 days from the following day of administration. The anti-asialo GM1 antibody was evaluated in terms of for its effect on pulmonary metastases with regard to the timing of administration. Treatment with anti-asialo GM1 antibody 1 day before or on the day of tumor inoculation resulted in a substantial increase in the number of artificial pulmonary metastases. In the experimental system of spontaneous metastases, the anti-asialo GM1 antibody most effectively increased the number of pulmonary metastases when administered 1 to 2 weeks before the amputation of the tumor primary site. In addition, in mice treated with anti-asialo GM1 antibody, the acceleration of the growth of the transplanted tumor was observed. These results strongly suggest that asialo GM1 positive cells not only inhibit pulmonary metastases acting mainly on circulating tumor cells but also suppress the growth of transplanted tumor.
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PMID:[Role of asialo GM 1 positive cells in the control of metastatic spread of tumor cells in mice]. 688 3

The major problem associated with ELISA of serum antiganglioside antibodies is the high background values (absorbancy of sera added to wells without ganglioside), which interfere with the accurate assessment of the fine specificity and sensitivity of these antibodies. This investigation identifies factors elevating the background values and/or decreasing the fine specificity, and describes strategies to minimize their influence. Using sera of neuropathy and melanoma patients, we found that highest background values were observed with the polystyrene 'tissue culture' microtiter plates; of the various 'non-tissue culture' microtiter plates tested, the lowest background values (> 0.060) were observed with Costar-3590 (H), Immunolon-3, Immunolon-1, Falcon-3915 (in increasing order). Background artifact of polystyrene microtest plates was significantly reduced by gamma irradiation (at 40 kRad) and/or use of detergent Tween-20 (0.1%) in the washing step. Even after controlling the background values, the fine specificity, namely, the ability of the antibody to distinguish between the target epitope of an antigen and epitopes of related antigens (when moles of antigen/well is constant) varied with different microtiter plates. Using sera with high affinity and specificity for GM2, GD3 or GM3, we observed that Immunolon-1, Immunolon-3 and particularly Falcon-3915 were superior for assessing the abilities of the antibodies to distinguish closely related epitopes found on other gangliosides. The reactivity of antiganglioside antibodies was more consistent after detergent treatment. The reactivity of antibodies to GD3 is significantly enhanced after treatment with Tween-20, but that of antibodies reacting to GM1 and GM2 is reduced. Fine specificity of the antiglycolipid antibodies was resolved better by coating glycolipids in mol/well rather than by weight/well. Based on these results, a protocol for a sensitive and reproducible ELISA for serum antiganglioside antibodies is recommended. The protocol takes into consideration the suitability of polystyrene plates, coating based on the number of molecules, pertinency of the solvent for coating, use of human serum albumin for blocking, dilution and washing steps and use of 0.1% Tween-20 to further minimize the background absorbancy.
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PMID:Factors affecting the fine specificity and sensitivity of serum antiganglioside antibodies in ELISA. 751 Jul 61

Differential cell- and immuno-biological properties of two murine melanoma B16 variants, B16-F1 and F10, were investigated. Studies focused on the expression of proto-oncogene c-fos, sensitivities to LAK cells and/or IL-2, and modulation of the expression of ganglioside components after treatment with IL-2. Proto-oncogene c-fos was found to be highly expressed in F10 lines by an in situ hybridization technique and also in F10 lung metastatic nests by immunofluorescent staining with anti-c-fos antibody. F1 melanomas were more sensitive to local injection of IL-2. F10 melanomas hardly responded to IL-2 treatment, but successive injections of a combination of LAK cells and IL-2 did cause prolongation of survival rates, even of F10 melanoma-burdened mice. A major component of gangliosides of both F1 and F10 melanomas was GM3. Production of GM3 in F10 melanomas treated with IL-2 for 4 days increased, and, if the treatment was continued for 7 days, minor components of gangliosides, such as GM2, GM1, and GD1a, appeared only in F1 melanomas, while the increase of production of GM3 disappeared in both melanomas. These experimental results may provide clues for additional mechanisms which allow these two murine melanoma variants to show different implantation and metastasis rates.
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PMID:Differential cell- and immuno-biological properties of murine B16-F1 and F10 melanomas: oncogene c-fos expression, sensitivity to LAK cells and/or IL-2, and components of gangliosides. 756 Apr 51

The effects of sublethal radiation (3 Gy) and anti-asialo GM1 (anti-ASGM1) on engraftment of human tumour cell lines and fresh tumour were evaluated in the severe combined immunodeficient (SCID) mouse. Four tumour cell lines (colonic adenocarcinoma LS174T, malignant melanoma MEWO, lung adenocarcinoma H125, chronic myelogenous leukemia K562) and a fresh colon cancer metastasis were injected subcutaneously, intraperitoneally or intravenously into SCID mice. Tumour volume and metastatic spread of implanted tumours were evaluated 3-8 weeks following inoculation. Pretreatment with radiation and anti-ASGM1 resulted in more rapid and extensive uptake of subcutaneous and intraperitoneal tumours. Tail vein injection into pretreated animals also resulted in a greater number of lung metastases of H125, MEWO and K562 cell lines. This study demonstrates that sublethal radiation and the elimination of murine NK cell activity with anti-ASGM1 improves tumour take rates. These findings should prove useful for investigations of human cancer immunotherapy using SCID mice engrafted with human lymphocytes and human tumours.
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PMID:Improved engraftment of human tumours in SCID mice pretreated with radiation and anti-asialo GM1. 784 29

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