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)

Ginsenosides, the glycosides of Panax ginseng, are metabolized (deglycosylated) by intestinal bacteria after oral administration. 20(S)-Protopanaxatriol (M4) is the main bacterial metabolite of protopanaxatriol-type ginsenosides and mediates their antitumor effects. To clarify the mechanism of the M4-mediated antitumor effect, the antitumor activity and metabolism of M4 was examined, using the C57BL/6 mice implanted with B16-BL6 melanoma. The chronic oral administration of M4 inhibited the growth of B16-BL6 melanoma at the implanted site. Analyses using TLC, HPLC, MS and NMR suggest that orally administered M4 was absorbed from the small intestine into the mesenteric lymphatics followed by the rapid esterification of M4 with fatty acids and its accumulation in the tissues including the liver and lung. The administration of M4 prior to the intravenous injection of B16-BL6 cells abrogated the enhanced lung metastasis in the mice pretreated with 2-chloroadenosine more effectively than in those pretreated with anti-asialo GM1. The esterified M4 (EM4) did not directly affect tumor growth in vitro, whereas it stimulated splenic NK cells to become cytotoxic to tumor cells. These results indicate that the antitumor activity of M4 is based on the NK cell-mediated tumor lysis enhanced by EM4.
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PMID:Prevention of growth and metastasis of murine melanoma through enhanced natural-killer cytotoxicity by fatty acid-conjugate of protopanaxatriol. 1213 58

Ten B16 mouse melanoma cell lines with increasing metastatic potential to lungs (B16LuF1 to B16LuF10) were generated by in-vitro & in-vivo selection technique starting with B16F1 melanoma cell line. The number of metastatic tumor nodules in lungs rose with increasing metastatic potential. Tumor cell gangliosides of B16LuF1 to B16LuF10 cell lines, analysed and compared with TLC, showed eight major ganglioside bands. Band1 to band6 corresponded with standard gangliosides GT1b, GD1b, GD1a, GM1, GM2 and GM3 respectively. Band7 and Band8 could not be identified. The concentration of total as well as individual ganglioside bands of B16LuF1 to B16LuF10 cells appeared to rise with increasing metastatic potential. Gangliosides from the plasma of these cell lines (B16LuF1 to B16LuF10) maintained in-vivo in C57BL/6 mice on TLC analysis gave eight major ganglioside bands, similar to those of cells. Plasma gangliosides appeared to rise with increasing metastatic potential. However, it was interesting to see that only band5 and band6 gangliosides in plasma increased almost linearly with increasing metastatic potential. The remaining six ganglioside bands in the plasma did not show such correlation. Band5 and Band6 gangliosides corresponded with standard gangliosides GM2 and GM3 respectively. Gangliosides of the spent culture media, secreted by these cell lines in-vitro in tissue culture also gave eight major ganglioside bands, similar to that of cells. Spent culture media gangliosides appeared to increase with increasing metastatic potential. However, concentration of only band5 and band6 gangliosides of spent culture media increased almost linearly with increasing metastatic potential, thus further confirming the role of band5(GM2) and Band6(GM3) gangliosides in regulating metastatic potential of B16-melanoma cells to lung.
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PMID:Correlation of gangliosides GM2 and GM3 with metastatic potential to lungs of mouse B16 melanoma. 1272 32

IgM antibodies to gangliosides, sialic acid-containing glycosphingolipids, have been shown to mediate anti-tumor effects in cancer patients with melanoma and neuroblastoma and to correlate with survival. Mechanisms by which the antibodies induce tumor suppression, however, have not been systematically studied. To investigate this point, we produced and characterized C57BL/6 mice transgenic for IgM antibody to ganglioside GD2. The transgenic (TG) mice showed high IgM, but not IgG antibody titers against GD2 in their sera. No significant clinical symptoms were observed. When EL4 cells, syngeneic T lymphoma that express ganglioside GD2, were injected into TG mice, prolonged survival was observed. Complement-dependent cytotoxicity (CDC) of EL4 cells was mediated with TG mice sera. Neither antibody-dependent cellular cytotoxicity with their sera nor cytotoxic T lymphocyte activity to EL4 cells was shown in TG mice. Spleen lymphocytes from TG mice had increased numbers of natural killer (NK) cells, but not T cells, B cells, or macrophages compared with wild-type mice. Depletion of NK cells with anti-asialo GM1 rabbit serum reduced or abrogated the observed anti-tumor effects, suggesting that NK cells play a major role in tumor eradication or suppression. NK cell activity in TG mice was much higher than wild-type mice. Moreover, TG mice showed prolonged survival after injection with syngeneic B16 melanoma cells, which express GM3, but not GD2 or GD3. Taking these results together, our studies demonstrate that the TG mice have significant anti-tumor characteristics, probably due to CDC and NK cell expansion and activation with anti-ganglioside GD2 antibody.
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PMID:Expansion of natural killer cells in mice transgenic for IgM antibody to ganglioside GD2: demonstration of prolonged survival after challenge with syngeneic tumor cells. 1285 87

Provoking a specific cellular immune response against tumor-associated antigens is a promising therapeutic strategy to treat cancers with defined antigens such as melanoma. In recent clinical trials, however, immune responses against melanoma antigens have been elicited without consistent clinical responses, suggesting the need for approaches that potentiate the specific cellular immune response. Since B lymphocytes have been reported to exert a negative effect on the cellular arm of the immune response in certain model systems, the authors compared the protective immunity elicited by melanoma antigens in B cell-deficient microMT mice to that obtained in fully immunocompetent C57BL/6 mice. Immunization with melanoma-associated antigens was accomplished using recombinant adenovirus (Ad) vectors encoding human gp100 (Ad2/gp100) or murine TRP-2 (Ad2/mTRP-2). A single dose of Ad2/gp100 or Ad2/mTRP-2 inhibited the growth of established subcutaneous B16 melanoma tumors in B cell-deficient but not wild-type C57BL/6 mice. The enhanced tumor protection observed in B cell-deficient mice appeared to be associated with potentiation of the magnitude and longevity of the specific cellular immune response. Natural killer (NK) cells were also found to be essential to the protective immune response in microMT mice because NK cell depletion with anti-asialo-GM1 antibody resulted in both the loss of tumor growth suppression and attenuation of the specific cellular immune response. The authors conclude that the protective cell-mediated immunity provoked by Ad-based cancer vaccines is enhanced in the absence of B cells, suggesting that a therapeutic regimen that includes depletion of B lymphocytes may be beneficial to cancer vaccine therapy.
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PMID:Enhanced efficacy of melanoma vaccines in the absence of B lymphocytes. 1523 88

Mouse B16LuF1 melanoma cells of lower metastatic potential to lung were treated in vitro with same concentration (50 microM) of gangliosides isolated from B16LuF5, B16LuF9 or B16LuF10 cells with higher metastatic potential to lung (LuF1< LuF5< LuF9< LuF10) and injected to groups of normal mice through tail vein. The number of metastatic tumor nodules formed in lung increased in mice receiving B16LuF5, B16LuF9 and B16LuF10-ganglioside-treated B16LuF1 cells compared to mice receiving B16LuF1 cells without any ganglioside treatment. Metastatic potential of B16LuF1 cells gradually increased after treatment with gangliosides of B 16-melanoma cells of increasing metastatic potential to lung. The six major gangliosides isolated from B16LuF10 cells corresponded with standard gangliosides GT1b, GD1b, GD1a, GM1, GM2 and GM3 respectively on TLC-analysis. When B16LuF1 cells were treated in vitro with each of these six individual gangliosides and injected to groups of normal mice through tail vein the number of tumor nodules formed in lung varied. The four groups of mice receiving B16LuF1 cells treated with each of four gangliosides corresponding to GT1b, GD1b, GD1a or GM1 produced lung metastasis comparable to that of untreated control group. Only remaining two gangliosides which corresponded with standard gangliosides GM2 and GM3 increased metastatic potential of B16LuF1 cells. Thus, these results indicated that gangliosides GM2 and GM3 of B16-melanoma cells are definitely associated with metastatic potential of these tumor cells.
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PMID:Enhancement of metastatic potential of mouse B16-melanoma cells to lung after treatment with gangliosides of B-16-melanoma cells of higher metastatic potential to lung. 1533 92

The migration of B16LuF1 cells, B16-melanoma cells of lower metastatic potential to lung was enhanced through artificial basement membrane in presence of gangliosides of B16LuF1 cells as well as gangliosides of B16-melanoma cells of higher metastatic potential to lung, namely, B16LuF5 and B16LuF10 cells. The same concentration (50 microM) of gangliosides of B16LuF1, B16LuF5 and B16LuF10 cells gradually increased the migration of B16LuF1 cells through basement membrane. Moreover, B16LuF10 cell gangliosides modified the migratory effect of laminin and fibronectin on B16LuF1 cells. Laminin alone increased migration of B16LuF1 cells whereas fibronectin alone decreased migration of the same cells. When B16LuF10 cell gangliosides were used in combination with fibronectin, gangliosides removed the migration inhibitory effect of fibronectin resulting in net enhancing effect. Gangliosides in association with laminin also increased the enhancing effect of laminin on migration of B16LuF1 cells. Thus, gangliosides showed additive enhancing effect when used in combination with laminin. However, effect of individual gangliosides were different. Out of six gangliosides isolated from B16LuF10 cells only two gangliosides corresponding to standard gangliosides GM2 and GM3 enhanced migration of B16LuF1 cells. The migration of B16LuF1 cells in presence of each of the remaining four gangliosides corresponding to GT1b, GD1b, GD1a and GM1 was not altered and was comparable to that of untreated control. Thus, gangliosides of B16 melanoma cells alone or in combination with laminin or fibronectin enhanced migration of B16 melanoma cells through artificial basement membrane, suggesting possible role of tumor gangliosides during invasion of metastatic tumor cells through basement membrane of the surrounding tissues in vivo.
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PMID:Gangliosides enhance migration of mouse B16-melanoma cells through artificial basement membrane alone or in presence of laminin or fibronectin. 1635 23

The close cooperation of both innate and acquired immunity is essential for the induction of truly effective antitumor immunity. We tested a strategy to enhance the cross-talk between NKT cells and conventional antigen-specific T cells with the use of alpha GalCer-loaded dendritic cells genetically engineered to express antigen plus chemokine, attracting both conventional T cells and NKT cells. DC genetically engineered to express a model antigen, OVA, along with SLC/CCL21 or monokine induced by IFN-gamma/CXCL9, had been generated using a method based on in vitro differentiation of DC from mouse ES cells. The ES-DC were loaded with alpha-GalCer and transferred to mice bearing MO4, an OVA-expressing melanoma, and their capacity to evoke antitumor immunity was evaluated. In vivo transfer of either OVA-expressing ES-DC, stimulating OVA-reactive T cells, or alpha-GalCer-loaded non-transfectant ES-DC, stimulating NKT cells, elicited a significant but limited degree of protection against the i.p. disseminated MO4. A more potent antitumor effect was observed when alpha-GalCer was loaded to ES-DC expressing OVA before in vivo transfer, and the effect was abrogated by the administration of anti-CD8, anti-NK1.1 or anti-asialo GM1 antibody. alpha-GalCer-loaded double transfectant ES-DC expressing SLC along with OVA induced the most potent antitumor immunity. Thus, alpha-GalCer-loaded ES-DC expressing tumor-associated antigen along with SLC can stimulate multiple subsets of effector cells to induce a potent therapeutic effect against peritoneally disseminated tumor cells. The present study suggests a novel way to use alpha-GalCer in immunotherapy for peritoneally
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PMID:Therapeutic effect of alpha-galactosylceramide-loaded dendritic cells genetically engineered to express SLC/CCL21 along with tumor antigen against peritoneally disseminated tumor cells. 1636 9

The contribution of tumor associated macrophage (TAM) to the induction of major histocompatibility complex (MHC) class I expression in vivo has not been reported precisely. In this study, we utilized Interleukin-2 (IL-2) cDNA-introduced B16 melanoma cells (B16/IL-2) and vehicle-alone control cells (B16/mock) to examine whether TAM could contribute to the induction of MHC class I on B16 cells in vivo. Interestingly, although B16/mock and B16/IL-2 did not express MHC class I in vitro, MHC class I was strongly expressed in vivo in B16/IL-2 in comparison to B16/mock. Although in vivo treatment of anti-NK1.1 antibody abolished MHC expression in B16/mock in vivo, the same treatment did not influence MHC expression in B16/IL-2. Interestingly, both anti-asialo GM1 and anti-CD11b treatment strongly decreased MHC expression in B16/IL-2. TAM expressed both asialo GM1 and CD11b antigen, and TAM recovered from B16/IL-2 produced interferon gamma (IFNgamma) 6 times more than that from B16/mock. In addition, TAM recovered from B16/IL-2 secreted 33.64 times more IFNgamma in response to in vitro administration of IL-2. Therefore, we checked whether or not IL-2 could influence the expression of IL-2 receptors. TAM recovered from IL-2 expressed middle affinity receptor of IL-2 (CD122 and CD132) while that from B16/mock expressed low affinity receptor (CD25 and CD132). Finally, we observed that B16 cells became apoptotic with IFNgamma treatment in vitro. These results suggested that IL-2 augmented activation of TAM would play the main role in induction of the MHC class I molecule through secretion of IFNgamma, and would contribute to the IFNgamma-mediated apoptosis induction in tumor cells.
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PMID:Interleukin-2 augmented activation of tumor associated macrophage plays the main role in MHC class I in vivo induction in tumor cells that are MHC negative in vitro. 1659 36

Although obesity is known as a risk factor for several human cancers, the association of obesity with cancer recurrence and metastasis remains to be characterized. Here, B16-BL6 melanoma and Lewis lung carcinoma cells were intravenously injected into diabetic (db/db) and obese (ob/ob) mice. The number of experimental lung colonies was markedly promoted in these mice when compared with C57BL/6 mice. In contrast, tumor growth at the implanted site was comparable when cells were inoculated orthotopically. The use of B16-BL6 cells stably transfected with the luciferase gene revealed that the increased metastasis reflected a difference mainly within 6 hr after the intravenous inoculation of tumor cells. Administration of recombinant leptin in ob/ob mice abolished the increase in metastasis early on as well as the decrease in the splenic NK cell number. In addition, depletion of NK cells by an anti-asialo-GM1 antibody abrogated the enhanced metastasis in db/db mice. These results demonstrate that metastasis is markedly promoted in diabetic and obese mice mainly because of decreased NK cell function during the early phase of metastasis.
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PMID:Severe pulmonary metastasis in obese and diabetic mice. 1699 95

In order to investigate the immunity of unloaded dendritic cells (DCs) derived from murine bone marrow to preexisting lung melanoma metastases of mice, MO5 were intravenously injected to induce lung metastases in syngeneic C57BL/6 mice. Unloaded GM-CSF DCs, PBS and DCs+SIINFEKEL were subcutaneously injected into the mice, which were divided as experimental group, negative control group and positive control group respectively. Monoclonal antibody was used to deplete NK or T cells separately. The immunity-inhibitory effects on the lung melanoma were observed and the corresponding effector cells were examined. It was found that in the experimental and positive groups, the regression was induced in metastatic nodules in the lungs of tumor-bearing mice, but abrogated by treatment with anti-asialo-GM1 but not anti-CD8. It was concluded that the unloaded DCs could suppress the lung melanoma metastases to some extent, which was mediated by NK cells, and could be used as a potent therapeutic agents for lung tumor.
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PMID:Immunity of unloaded dendritic cells in lung melanoma of mice. 1782 91

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