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)

In human tumors of neuroectodermal origin cell surface expression of individual gangliosides is either increased or decreased relative to comparable normal cells. We have previously shown that gangliosides shed from melanoma cells can immunomodulate T cell activity. Monocytes/macrophages (m/m) are known to play an important role as accessory and effector cells in immune responses. We therefore investigated the effect of exogenous gangliosides derived from melanoma on m/m functions in vitro. Gangliosides commonly expressed on human melanoma such as GM3, GD3, GM2, and GD2 were investigated, as well as GM1, a major component of human neural tissue. Monocytes were isolated from human peripheral blood mononuclear cell populations, treated with gangliosides in vitro, and evaluated in several functional assays. Treatment of m/m with GM2 and GM3 gave the greatest inhibition of Fc receptor expression. GM1 and GD3 on the other hand most inhibited the production of interleukin-1 (IL-1) by m/m. Production of tumor necrosis factor (TNF) like monocytoxin was not affected by incubation with individual gangliosides. These studies suggest that individual melanoma gangliosides have different regulatory effects on m/m functions.
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PMID:Modulation of human macrophage functions by gangliosides. 278

We attempted to investigate if the in vivo administration of concanavalin A (Con A), a potent T cell stimulator, would render anti-metastatic activity in hosts. Assays of activity were performed 20 days after iv inoculation of two clones of the B16 melanoma, B16-H (H-2+, highly metastatic), B16-L (H-2-, low metastatic), or 3LL cells into C57BL mice by enumerating lung colonies. In some experiments, hosts treated with anti-asialo GM1 Ab were used to evaluate effector mechanisms other than NK cells. While the injection of Con A alone had no significant effect on anti-metastatic activity, in nonimmunized hosts the effect by Con A was displayed when the mice were preimmunized with B16-H cells but not in those immunized with B16-L cells. Immunization with B16-H or B16-L cells alone resulted in the generation of killer cells with promiscuous lytic activity and induced an anti-metastatic effect against B16-H, B16-L, and 3LL cells. Con A treatment significantly augmented the killer activity of spleen cells of mice preimmunized with B16-H cells but not of those immunized with B16-L cells. The effectors from mice immunized with B16-H alone or given both Con A and B16-H were mainly of Thy 1+ Lyt2+ asialo GM1- cells, on the other hand, those from mice immunized with B16-L cells expressed asialo GM1 antigen. We showed the efficacy of Con A on the anti-metastatic effect in relation to the host immune response.
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PMID:Anti-metastatic effect by in vivo administration of concanavalin A through augmentation of T-derived activated killer activity: efficacy to B16 melanoma expressed MHC antigen. 278 62

The author took interest in the existence of effector cells which had natural killer (NK) activity on the lung, in other words organ-associated NK cells, compared the augmented effect of pulmonary NK activity by poly I:C with that of spleen NK activity, and also investigated the effect of activated pulmonary NK cells on established pulmonary metastasis. It was shown that pulmonary NK cells in C57BL/6 mice had significant cytotoxicity against YAC-1 target cells in a 4 h-51Cr release assay, although their cytotoxicity was remarkably low as compared with that of spleen cells. However, by treatment with poly I:C, pulmonary NK activity was significantly augmented compared with spleen NK activity. This cytotoxicity was abrogated by treatment with anti-asialo GM1 antibody. From these results, it was considered that the effector cells was a NK cell. When poly I:C was administrated intraperitoneally from 3 days after intravenous inoculation of B16-F10 melanoma cells, the number of the pulmonary metastatic nodules was significantly decreased. The number of pulmonary metastatic nodules was not suppressed by a combination treatment of poly I:C and anti-asialo GM1 antibody to the same degree as in treatment by anti-asialo GM1 antibody alone. The experimental group which underwent a combination treatment of poly I:C and carrageenan showed a suppression of the number of pulmonary metastatic nodules to the same degree as the group treated with poly I:C alone. Therefore it was shown that the effect of pulmonary metastatic suppression with poly I:C was caused not by macrophages but by pulmonary NK cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of activated pulmonary natural killer (NK) cells by poly I:C on the established pulmonary metastasis]. 280 48

The effects of pure recombinant human interferon alpha A/D (IFN alpha A/D) on natural killer (NK) activity and the experimental lung metastasis of B16-F10 melanoma were studied. Treatment of C57BL/6 mice with IFN alpha A/D augmented splenic NK activity and also inhibited the experimental lung metastasis of B16-F10 melanoma in a dose-dependent manner. The augmentation of NK activity and the inhibition of experimental lung metastasis by IFN alpha A/D were completely abolished in anti-asialo GM1-pretreated mice. These results suggested that the effector cells which inhibited melanoma metastasis in the present system were mainly NK cells, and that it was by activating NK cells that IFN alpha A/D had its effect. We next studied the timing of IFN alpha A/D administration for the most effective prevention of melanoma metastasis. The inhibitory effect of IFN alpha A/D was most pronounced when it was given 12 hr before or at the same time as melanoma inoculation. This suggested that melanoma cells were susceptible to NK cells only for a short period of time after intravascular invasion.
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PMID:Inhibition of intravascular mouse melanoma dissemination by recombinant human interferon alpha A/D. 308 19

The antitumor effect of murine recombinant interferon (beta) [Mu-rIFN(beta)] was examined on artificial metastasis of B-16 melanoma in C57BL/6 mice. The numbers of pulmonary nodules were significantly decreased to 16.7 +/- 4.7 (P less than 0.01), 9.5 +/- 4.2 (P less than 0.01), 7.1 +/- 5.6 (P less than 0.01) in mice given 20,000 units of Mu-rIFN(beta) intraperitoneally (ip) 24, 6, and 3 hr before intravenous tumor inoculation, respectively, compared with the control group of mice (57.1 +/- 1.4), if B-16 melanoma cells (5 X 10(5] were intravenously injected 28 days before the experiment. In mice given 20,000 units of Mu-rIFN(beta) ip 24, 6, and 3 hr before the experiment, the natural killer (NK) activities of spleen cells against YAC-1 cells were elevated to 45.5 +/- 6.1%, 53.7 +/- 3.4%, 43.2 +/- 6.5%, respectively, compared with NK activities in control mice (20.3 +/- 3.1%). Similarly, NK activities against B-16 melanoma cells were also elevated in mice given Mu-rIFN(beta). Pretreatment with anti-asialo GM1 antibody and carrageenan reduced the inhibitory effect of Mu-rIFN(beta) on the pulmonary metastasis. In vitro colony inhibition of more than 50% was not observed even if B-16 melanoma cells were incubated with 100,000 units/ml of Mu-rIFN(beta). From these results, it can be concluded that the inhibition of pulmonary metastasis by Mu-rIFN(beta) is mediated via host defense mechanisms and that NK cells and macrophages are both important for the inhibition.
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PMID:Inhibitory effect of murine recombinant interferon (beta) on the pulmonary metastasis of B-16 melanoma. 309 26

Swainsonine, an indolizidine alkaloid, has been found to inhibit the experimental metastasis of B16-F10 melanoma cells when administered systemically to syngeneic C57BL/6 mice. The inhibition was both potent and dose dependent with greater than or equal to 80% reduction in pulmonary colonization being observed after only 24-h exposure to 3 micrograms/ml of swainsonine in drinking water. In contrast, the inhibitory activity of swainsonine was completely abrogated when assays were performed in mice depleted of their natural killer (NK) cell activity either experimentally (anti-asialo-GM1 antibody- or cyclophosphamide-treated C57BL/6 mice) or as a result of genetic mutation (homozygous C57BL/6bg/bg beige mice). Swainsonine elicited a 32.0% increase in spleen cell number 2 days after administration and induced a concomitant 2- to 3-fold increase in splenic NK cell activity. These results indicate (a) an absolute requirement for a functional NK cell population in order for swainsonine to exert its inhibitory effects on experimental metastasis, and (b) that the antimetastatic activity of swainsonine is mediated primarily through the ability of the drug to augment NK cell reactivity. On the basis of these findings, swainsonine can be classified as a new immunomodulator that has the ability, at least in a prophylactic setting, to block tumor metastasis.
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PMID:Augmentation of murine natural killer cell activity by swainsonine, a new antimetastatic immunomodulator. 312 63

The antimetastatic effects of defibrinogenation with batroxobin were investigated in normal mice and in mice with depressed or activated natural killer (NK) cell activity. Batroxobin inhibited the formation of lung metastases after intravenous inoculation of the F10 subline of B16 melanoma. Inhibition of NK activity by treatment of mice with anti-asialo GM1 antibody abrogated the antimetastatic effects of Batroxobin. Conversely, augmentation of NK cell activity by poly I:C plus treatment with batroxobin produced additive antimetastatic effects. Studies on the mechanism of interaction between Batroxobin and NK cells revealed that Batroxobin treatment did not affect splenic NK activity in vitro. From these data, it was found that the antimetastatic effects of batroxobin are dependent on the level of NK activity in the host.
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PMID:[Role of natural killer cells in the antimetastatic effect of defibrinogenation with batroxobin]. 330 May 62

Three malignant tumors (3LL carcinoma, mFS6 sarcoma, and B16 F1 melanoma) were transplanted in mice with congenital (beige) or acquired (anti-asialo GM1-treated) defects of natural killer cell (NK) activity. The macrophage content of the neoplastic tissues was not influenced by host NK activity levels. These data suggest that NK cell-mediated resistance does not play an appreciable role in the regulation of the levels of tumor-associated macrophages in established malignancy.
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PMID:The macrophage content of tumors is unrelated to levels of NK cell-mediated resistance. 345 8

The administration of anti-B16 monoclonal antibody of the IgG2b isotype to mice bearing established B16 melanoma liver metastases caused a significant and consistent reduction of up to 90% in the number of these metastases. No reduction in the number of metastases was noted when antigenically unrelated tumor or nonspecific immunoglobulin were employed. The antibody-mediated antitumor effect was completely abrogated by total body irradiation of the host. Treatment of the tumor-bearing host with antiserum directed against asialo GM1 prior to anti B16 antibody administration, abrogated the therapeutic effect indicating the involvement of a radiosensitive, ASGM1-positive cell in the tumor regression. The antitumor effect of the antibody treatment could be augmented by the concomitant administration of recombinant interleukin-2. The effect seen may have possible application in the treatment of liver metastases in humans by combined immunotherapy using recombinant interleukin-2 and specific antitumor monoclonal antibodies.
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PMID:Effect of anti-B16 melanoma monoclonal antibody on established murine B16 melanoma liver metastases. 349 4

A method was described for the generation of cells from tumor-bearing mice; these cells were capable of exhibiting significant antitumor reactivity when adoptively transferred into tumor-bearing hosts. Tumor cell suspensions from a variety of tumors were able to be separated using enzymatic techniques and they were cultured in medium containing recombinant interleukin-2. Activated infiltrating lymphocytes within these tumors expanded; and, by 6-8 days after initiation of culture, lymphocytes predominated and were able to grow to large numbers. The adoptive transfer of these tumor-infiltrating lymphocytes (TILs) made possible mediation of the reduction of established 3-day pulmonary micrometastases from 5 of 7 tumors tested, including two 3-methylcholanthrene (CAS: 56-49-5)-induced sarcomas, one 1,2-dimethylhydrazine (CAS: 540-73-8)-induced colon carcinoma, and the B16 melanoma, all in C57BL/6 mice, as well as the 1660 bladder carcinoma in BALB/c mice. Approximately 2-4 X 10(6) transferred cells were capable of totally eliminating 3-day established metastases. These cells were thus 50 to 100 times more effective than lymphokine-activated killer cells in reducing established metastases; however, they could not be generated from all tumors. The concomitant administration of recombinant interleukin-2 enhanced, by approximately fivefold, the in vivo activity of these cells. The specificity of action of TILs in vivo was different from that determined by classic amputation rechallenge experiments. The tumor-infiltrating lymphocytes that developed this antitumor reactivity appeared to be Thy-1+ and did not bear the asialo GM1 antigen. The potent antitumor effect of these TILs, when transferred in vivo to tumor-bearing hosts, raises the possibility of utilizing similar approaches for the isolation and therapeutic use of lymphocytes with antitumor reactivity from human tumors.
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PMID:In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2. 350 Mar 55


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