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

B7-1 expression, induced by transfection in poorly immunogenic murine tumours, was shown to elicit a T cell-mediated rejection of these tumours and further active immunity against the non-transfected tumour. We therefore asked to what level similarly induced expression of B7 on human melanoma cells would affect the antigen-dependent responses of tumour-specific T cell clones in vitro. Data presented show that B7-1 expression by melanoma lines: (i) significantly induced, or improved, an IL-2-dependent proliferative response of such clones to the antigen; (ii) increased the amount of IL-2 produced by two clones in response to the parental non-transfected tumour cells; and (iii) increased the TNF responses of all the CD4+ clones. However, despite these clear co-stimulatory effects on antigen-induced responses of all T cell clones, which demonstrated an effective interaction of the B7-1 transfected molecule with one or the other of its counter-receptors expressed on T cell clones, B7 co-stimulation did not correct the defect of IL-2 secretion exhibited by many of these clones in response to in vitro antigen presentation by melanoma cells. We further show that defective IL-2 secretion in response to melanoma antigens was not due to a T cell clone refractoriness induced by the culture, since one of these clones could be induced to secrete IL-2 by an antigen-expressing melanoma line, upon increased lymphocyte function associated antigen-3 expression induced by gene transfection. Together these data suggest that defective IL-2 secretion by many tumour-infiltrating lymphocytes clones in response to antigen presentation by melanoma cells in vitro is not exclusively due to the inability of these cells to provide an appropriate co-stimulation through the B7-1 molecule.
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PMID:T cell activation by antigens on human melanoma cells--co-stimulation by B7-1 is neither sufficient nor necessary to stimulate IL-2 secretion by melanoma-specific T cell clones in vitro. 856 98

In this study, we have examined the relationship between the expression of the high molecular weight, cytosolic form of PLA2 (cPLA2) and ability of inhibitors of transcription or translation (ITT) to induce susceptibility to TNF. S Susceptibility to lysis was assayed by 51CR release, and the expression of cPLA2 was assayed by activity assay and by Western blot. The panel of cells that we examined included two murine cell lines, six human melanoma-derived cell lines, two samples of freshly explanted melanoma tumor tissue, and a culture of normal epidermal melanocytes. Our experiments revealed a near perfect correlation between the activity of cPLA2 per cell and susceptibility to TNF in the presence of either cycloheximide (CHI) or actinomycin D (r = 0.97). These results suggest that the activity of cPLA2 is both necessary and rate-limiting in this form of programmed cell death, conclusions that were confirmed in transfection experiments and in experiments with antisense oligonucleotides. Over-expression of cPLA2 in two melanoma-derived cell lines, WM793 and SK-MEL-131, led to enhanced susceptibility to TNF and CHI. Conversely, suppression of cPLA2 with antisense oligonucleotides dramatically decreased susceptibility to TNF and CHI in C3HA fibroblasts. These experiments also revealed a coupled, transformation-released change in the expression of cPLA2 and susceptibility to lysis. Normal melanocytes contained the lowest levels of cPLA2 and were completely resistant to sensitization with ITT. In contrast, all of the melanoma-derived cell lines and samples of melanoma tumor tissue we examined has higher levels of cPLA2 and could be killed, to some extent, by treatment with TNF and ITT.
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PMID:Susceptibility to TNF in the presence of inhibitors of transcription or translation is dependent on the activity of cytosolic phospholipase A2 in human melanoma tumor cells. 859 63

Optimal conditions for immunohistochemical staining of tumor necrosis factor-alpha (TNF-alpha) in paraffin-embedded tissue sections were established to investigate TNF-alpha expression in human primary malignant melanomas. Seventeen malignant melanomas of the nodular (NMM) and superficially spreading (SSM) subtypes were analyzed. Twelve of these were TNF-alpha+, while 5 did not stain for the cytokine. To evaluate how TNF-alpha expression affected the immune response to the tumors, infiltration by CD3+ and mac387+ cells was investigated in NMM. TNF-alpha expression seemed to selectively affect the capability of T cells to infiltrate the tumors since TNF-alpha+ tumors were found to have significantly lower levels of infiltrating CD3+ cells, while there was no difference in numbers of mac387+ cells. These results demonstrate that TNF-alpha is variably expressed in primary malignant melanoma in vivo and that the T-cell response to TNF-alpha-expression NMM is inhibited.
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PMID:Tumor necrosis factor-alpha expression in human primary malignant malanoma and it relationship to tumor infiltration by CD3+ cells. 860 64

The proliferation of human melanoma cell line A375-6 is inhibited by interleukin l (IL-l). However, the cells acquired resistance to IL-l after a long period of culture. We have reported that 2 resistant subclones, A375-R8 and -R19, produced IL-l alpha constitutively and that IL-l induced IL-6 production in an autocrine manner. Therefore, we supposed that IL-l alpha production renders the cells resistant to IL-l. To investigate the relationship between IL-l alpha production and IL-l resistance, we transfected the IL-l alpha expression plasmid to the IL-l-sensitive clone, A375-6, and the anti-sense mRNA expression plasmid to IL-l-resistant cells, A375-R8 and -R19. A375-6MS, a transfectant of mature IL-l alpha expression plasmid, expressed IL-l alpha mRNA and produced IL-l activity at a level comparable to the resistant cells. The transfectant also produced IL-6 and exhibited augmented expression of Mn-SOD mRNA. However, IL-l sensitivity of this transfectant was not affected. With respect to sensitivity to anti-proliferative effects of other cytokines, such as IL-6 and TNF alpha, there was no difference between the transfectant and parent cells. Although A375-R8PH10 and -R19PH10, transfectants of IL-l alpha anti-sense mRNA expression plasmid, exhibited a decrease in the level of IL-l production, their IL-l sensitivity did not differ from parent cells. These results, therefore, suggest that IL-l alpha production is not essential or sufficient for the acquisition of resistance to the anti-proliferative effect of IL-l.
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PMID:Interleukin 1 (IL-1) production is not essential for acquired resistance of human A375 melanoma cells to anti-proliferative effect of IL-1. 863 96

We examined the influence of surgical stress on hematogenous metastasis of malignant tumor cells. The study was performed by focusing on the involvement of inflammatory cytokines in the serum, raised acutely after surgery, and endothelial adhesion molecules in the metastatic process. Surgical stress, given to C57BL/6 mice before B16-BL6 melanoma inoculation, significantly enhanced the pulmonary metastasis. This enhancement was seen when the surgery lasted for more than 2 h. After the 2-h surgery, the enhancement of pulmonary metastasis was seen most remarkably when B16-BL6 was inoculated 24 h after surgery. The serum level of tumor necrosis factor alpha (TNF alpha) in the mice that underwent the 2-h surgery peaked 12 h after the surgery. In contrast, serum interferon gamma was not detectable. Administration of an anti-TNF alpha mAb before the surgery inhibited the enhanced metastasis by inhibiting the increased expression of vascular cell adhesion molecule 1 (VCAM-1) on lung vascular endothelium after the surgery. Pretreatment of B16-BL6 cells with an anti-very late activation antigen 4 (anti-VLA-4) mAb completely inhibited the enhanced metastasis after surgery. Administration of an anti-VCAM-1 mAb before surgery also inhibited the enhancement. These results indicate that serum TNF alpha, raised by surgical stress, is critically involved in the enhanced pulmonary metastasis of mouse melanoma by inducing VCAM-1 expression on lung vascular endothelium.
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PMID:Involvement of tumor necrosis factor alpha and very late activation antigen 4/vascular cell adhesion molecule 1 interaction in surgical-stress-enhanced experimental metastasis. 866 70

It has been recently suggested that soluble tumour necrosis factor receptors (sTNF-Rs) may represent prognostic factors in cancer. In malignant melanoma, the intercellular adhesion molecule (ICAM-1) has been described as involved in progression of the disease and is upregulated by TNF alpha. We report in this study the serum concentrations of sTNF-R1 and sTNF-R2 in 32 patients with primary melanoma and in 21 patients with metastatic melanoma, in correlation with those of soluble ICAM-1 (sICAM-1). Significantly raised sTNF-R1 levels were detected only in patients with metastatic melanoma compared with normal controls (P < 0.002), whereas sTNF-R2 levels were increased both in primary and metastatic melanoma (P < 0.001). The ratio of type 2 to type 1 proteins increased in malignant melanoma compared with the controls but remained constant with the progression of the disease. A correlation between sTNF-Rs and sICAM-1 concentrations in patients' sera was observed in metastatic melanoma. The combined adverse effects of these soluble proteins on normal immune effector functions may contribute to tumour progression.
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PMID:Tumour necrosis factor (TNF) soluble receptors in malignant melanoma: correlation with soluble ICAM-1 levels. 881 90

Interleukin-8 (IL-8) is a cytokine that is thought to promote melanoma tumour progression. We evaluated and adapted a non-radioactive, reverse transcriptase-polymerase chain reaction method for semiquantitative analysis of IL-8 mRNA expression. Using this technique we studied the regulation of IL-8 levels in the melanoma cell line Colo 38. Seeding of melanoma cells into culture dishes resulted in a significant increase of IL-8 expression, which could be attributed to adherence. A pronounced increase of IL-8 mRNA expression and protein production was induced by tumour necrosis factor-alpha (TNF alpha). Interferon-gamma (IFN gamma) partially inhibited TNF alpha-induced IL-8 secretion, whereas no influence on IL-8 mRNA levels was detected. The inhibitory affect of IFN gamma on melanoma cells is in contrast to its stimulatory effect on melanocytes.
Melanoma Res 1996 Aug
PMID:Regulation of interleukin-8 mRNA expression and protein secretion in a melanoma cell line by tumour necrosis factor-alpha and interferon-gamma. 887 50

In the present study an acidic polysaccharide ginsan, with a molecular weight of 150,000, devoid of lectin properties, was purified from Panax ginseng C.A. Meyer (Araliaceae). Ginsan induced the proliferation of T cells and B cells. Spleen cells became cytotoxic to a wide range of tumor cells without major histocompatibility complex-restriction after 4 or 5 days culture in vitro with ginsan. For the generation of these ginsan-activated killer (AK) cells adherent macrophages and CD4+ cells were needed as accessory cells. The generation of ginsan-AK cells was blocked in the presence of anti-IL-2, anti-IFN gamma, anti-IL-1 or anti-TNF alpha antibodies, showing the importance of these cytokines in the process. The surface phenotypes of the 4 day-cultured ginsan-AK cells was Thy1+, AsGM1+, CD8+, which is distinct from rIL-2 induced lymphokine activated killer (LAK) cells that were CD8. The ginsan also activated macrophages to produce reactive nitrogen intermediates and become tumoricidal. It also exhibited significant in vivo antitumor activity against B16 melanoma cells lines, and in the benzo(a)pyrene-induced autochthonous lung tumor model, at much lower doses than the maximum tolerate doses. Indeed, no mice died, which injected with ginsan at 1g/kg body weight intraperitoneally. In conclusion, 'ginsan' could potentially be an ideal nontoxic antineoplastic immunostimulator by activating multiple effector arms of the immune system.
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PMID:Activation of multiple effector pathways of immune system by the antineoplastic immunostimulator acidic polysaccharide ginsan isolated from Panax ginseng. 906 72

The constitutive and cytokine-mediated expression of MHC class I and II antigens and intercellular adhesion molecule-1 (ICAM-1) was evaluated on eight human melanoma cell lines derived from primary and metastatic malignancies from patients (WM human melanoma series) including three pairs of related cell lines derived from the same individual. The cytokines IL-1 beta, IL-4, IL-6, TNF alpha, TGF beta 2, IFN gamma and IFN alpha were assessed for their ability to modulate the expression of cell surface antigens. MHC class I and class II antigen expression was unregulated by IFN gamma, IFN alpha and/or TNF alpha in cell lines established from primary melanoma. In contrast the cell lines derived from metastatic deposits did not show an increase in expression of MHC antigens in response to these cytokines. Both primary and metastatic WM cell lines were shown to be resistant to spontaneous natural killer cell (NK) activity, but susceptible to effector lymphocytes mediating lymphotine activated killer (LAK) cytotoxicity as a result of activation by IL-2. Although the constitutive and cytokine-induced level of expression of ICAM-1 and MHC antigens varied between paired primary and metastatic cell lines, this did not correlate with susceptibility of the cell line target to NK or LAK cytotoxicity. Whereas the IFNs, TNF alpha, TGF beta 2 and IL-1 beta differentially modulated the expression of ICAM-1 and MHC class I, treatment with IFNs (but not IL-1 beta, TNF alpha or TGF beta 2) resulted in a significant reduction in the sensitivity of the melanoma cells to NK and LAK cytotoxicity. Constitutive ICAM-1 expression was positively correlated with the ability of WM cell lines to colonise the lungs of SCID mice upon i.v. injection. The acquisition of cytokine resistance and inability to demonstrate enhanced cell surface expression may represent an important feature associated with the development of the metastatic phenotype.
Melanoma Res 1997 Feb
PMID:Cytokine modulation of antigen expression in human melanoma cell lines derived from primary and metastatic tumour tissues. 906 63

Tumor necrosis factor alpha (TNF alpha) is a cytokine, produced by lymphocytes and monocytes, with cytotoxic activity against some but not all tumor cell lines. Resistance to the cytolytic effects of TNF alpha has been reported in cell lines with autocrine TNF alpha production. The purpose of this study was to investigate whether human primary malignant melanoma and tumor infiltrating lymphocytes produce TNF alpha in vivo. Optimal conditions for in situ hybridization for TNF alpha mRNA in paraffin-embedded tissue were established. Analysis of 13 primary malignant melanomas and 3 metastatic lesions with different degrees of immunohistochemical TNF alpha positivity demonstrated that, in some tumors, both melanoma cells and leukocytes contained TNF alpha mRNA and protein. These findings demonstrate variable production of TNF alpha in primary and metastatic melanoma in vivo. The previously described resistance to TNF alpha cytolytic activity may, therefore, be clinically important.
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PMID:Variable expression of tumor necrosis factor alpha in human malignant melanoma localized by in situ hybridization for mRNA. 929 36


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