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)

IFN-gamma is an effective inducer of MHC class II antigen expression in cell lines of malignant melanoma. To investigate the possibility that IFN-gamma may increase MHC class I and II and melanoma tumour associated antigens in vivo, immunohistochemical analyses of biopsies from six patients with metastatic disease undergoing IFN-gamma treatment were performed. Before IFN-gamma treatment, the melanomas were class I positive and class II negative. After treatment, class I expression was neither enhanced nor class II expression induced in any tissue sample regardless of biopsy time or dose of IFN-gamma. TAA was similarly unchanged. However, in one of the six patients a primary cell line was established and IFN-gamma induced expression of MHC products. The possible reasons for lack of MHC induction are discussed, although qualitative changes in antigen expression cannot be excluded on the basis of qualitative immunocytochemical techniques alone.
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PMID:Effect of in vivo administration of interferon gamma on expression of MHC products and tumour associated antigens in patients with metastatic melanoma. 251 72

NK cells kill a wide variety of tumor cells, but usually leave normal cells intact. It was earlier reported that low class I HLA expression can be one of the factors that render target cells relatively susceptible to NK lysis. In this contribution, we show that in human melanomas the class I HLA expression is down-modulated by high expression of transfected c-myc oncogenes. The extent of down-modulation depended on the level of c-myc expression in a dose-dependent way. Taken together, these data suggested to us that one of the results of high c-myc expression could be the induction of a NK susceptible phenotype in melanoma cells. Therefore, we analyzed the effect of c-myc on NK susceptibility. We have found that high expression of transfected c-myc genes indeed converts the melanoma cell lines from poor into good targets for NK cells. IFN-gamma was used to restore the class I HLA expression of the c-myc transfectants, and the resulting cells showed a decreased NK susceptibility. These results suggest the possibility that the c-myc-induced NK susceptibility is mediated by the reduction of class I HLA expression.
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PMID:High expression of the c-myc oncogene renders melanoma cells prone to lysis by natural killer cells. 251 56

Clones were isolated from the cultured human melanoma cell line MeM 50-10, which metastasizes in nude mice with a pattern similar to that in patients with melanoma. Analysis with monoclonal antibodies detected heterogeneity among the clones in the expression of HLA class I antigens, HLA class II antigens, intercellular adhesion molecule 1 and high molecular weight melanoma associated antigen. The clones MeM A16 and MeM A18 were also shown to display differential susceptibility to modulation by immune interferon (IFN-gamma) and/or tumor necrosis factor (TNF-alpha) of the expression of the four types of antigens analyzed. In spite of differences in the antigenic profile, the two clones did not differ in their susceptibility to lysis by lymphokine-activated killer (LAK) cells and by anti-HLA-A2 cytotoxic T cells. The increase in the expression of HLA class I antigens induced by IFN-gamma and/or TNF-alpha on the two clones was associated with an increased susceptibility to lysis by anti-HLA-A2 cytotoxic T cells. Because of the metastasizing properties of cultured melanoma cells MeM 50-10, the clones we have isolated, with their distinct antigenic profile and differential susceptibility to modulation by cytokines, may represent useful models to investigate the role of distinct antigenic structures in the metastatic process.
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PMID:Modulation by cytokines of HLA antigens, intercellular adhesion molecule 1 and high molecular weight melanoma associated antigen expression and of immune lysis of clones derived from the melanoma cell line MeM 50-10. 251 11

ZME-018 monoclonal antibody (MAb, IgG2a subclass, 0.04 mg), recombinant human tumor necrosis factor-alpha (rHuTNF-alpha, 10(4) units), and recombinant human interferon-gamma (rHuIFN-gamma, 10(6) units) were injected intravenously into athymic nude mice bearing human malignant melanoma (Brown C5513) xenografts. Sixty-four animals were injected subcutaneously with 0.2 ml tumor chunks 4 days prior to administration of one or more of the treatments. The mice were randomized into eight groups so that mean tumor volume/group before initiation of treatment was similar (212-360 mm3); (a) saline, 2X; (b) rHuTNF-alpha, 1X; (c) rHuIFN-gamma, 1X; (d) ZME-018, 1X; (e) rHuIFN-gamma + rHuTNF-alpha, 1X each; (f) rHu-IFN-gamma + ZME-018 + rHuTNF-alpha, 1X each; (g) rHuTNF-alpha + ZME-018, 2X each; (h) rHuTNF-alpha + ZME-018, 3X each. The order of administration of the agents in those groups given more than one modality is as shown above and each injection was separated by a 24 h period. Tumor volume was measured daily for 9 days after the beginning of treatment. Compared to control mice, minimal suppression of tumor growth was noted when ZME-018, rHuTNF-alpha, or rHuIFN-gamma was used singly, but significantly (p less than or equal to 0.05) slower tumor progression occurred in animals given rHuIFN-gamma + rHuTNF-alpha or ZME-018 + rHuTNF-alpha when compared to controls. Histopathologic analyses of tumor biopsies obtained at 1 and 4 days after the last treatment for each group indicated that 15-95% necrosis was present. Necrosis was most striking in the animals given rHuIFN-gamma + rHuTNF-alpha or the ZME-018 MAb alone. However, the group receiving all three agents exhibited a tumor growth rate similar to that seen in the controls and demonstrated minimal necrosis. These results suggest that ZME-018, rHuIFN-gamma, and rHuTNF-alpha may be useful in the treatment of human melanoma. However, the effects of administration of all three of these agents in a single host needs to be evaluated further.
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PMID:Effects of monoclonal antibody, recombinant interferon-gamma, and tumor necrosis factor-alpha in the treatment of human melanoma xenografts. 251 78

A panel of 8 new Mabs have been produced against neuroblastoma cells (LAN-1) previously treated with IFN-gamma. All selected Mabs from 2 different fusions have been shown to detect epitopes on the GD2 ganglioside molecules highly expressed on all cells of neural crest origin including neuroblastoma, glioblastoma and melanoma. Our results imply that modulation of GD2 exposure on NB cells is dependent on culture conditions and moreover that IFN-gamma increases the surface expression of GD2 and thereby enhances their immunogenicity.
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PMID:Monoclonal antibodies to gamma-interferon treated LAN-1 cells detect modulation of ganglioside GD2 exposure on human neuroblastoma cells. 251 14

Twenty-one interferon (IFN)-alpha species were evaluated for their ability to enhance monocyte-mediated lysis of the human melanoma cell line, A375. A wide variation in the potency of the different species in inducing monocyte tumoricidal action was observed. In addition, many IFN-alpha species were found to induce as much or more tumoricidal activity than recombinant IFN-gamma. The degree of monocyte activation induced by the various species generally correlated with their antiviral activity. Those which were better at inducing monocyte tumoricidal action also gave the highest antiviral specific activities. Studies were conducted to determine if the relative potency of the IFN-alpha species could be changed by altering certain parameters of the cytotoxicity assay. All IFN-alpha species tested required only 30 min in culture with the monocytes to induce activation. There were no changes in the relative potency of the species when cytotoxicity was measured at different times, nor when the effector:target ratio was altered. Competitive binding studies revealed that those IFN-alpha species which induced little activity in the bioassays were also generally poor in their ability to bind the IFN-alpha receptor on human monocytes, while the IFN-alpha species which induced relatively more activity in the bioassays were better able to bind to the IFN-alpha receptor. These data indicate that there are dramatic differences in activities among the IFN-alpha species which may, in part, be explained by different binding affinities. In addition, the differences observed among the IFN-alpha species demonstrate the need for further functional and structural characterization of the individual IFN-alpha species which could lead to a more effective clinical application of IFN-alpha.
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PMID:Enhancement of monocyte-mediated tumoricidal activity by multiple interferon-alpha species. 252 78

In order to evaluate their divergent effects on binding and lysis of the NCMC, rH IFN-alpha and rH IL-2 were used for the in vitro-preincubation of normal donors' PBL, which were then tested as effector cells against K562 and the long-term cultured melanoma cell line RIMA in the SCCA. Both lymphokines significantly augmented the cytolysis of K562 without relevant influence on the conjugate formation. However, against RIMA IFN-alpha additionally amplified the binding affinity. This in keeping with the other authors' opinion that IFNs have target-specific effects at the single cell level, with the principal activation of already conjugated pre-killer cells against all the target cell lines tested. We performed a therapy-follow-up of the i.p. administration of rH IFN-gamma to patients with ovarian carcinomas in vivo. With the SCCA we detected a significant correlation of the duration of therapy with the autologous cytotoxicity in the ascitic compartment. In one case the increase of this parameter was even exponential. However, the countercurrent trend of the conjugate formation delayed and reduced the activation of the autologous total killer activity. This relative stagnation resulted in the inadequate clinical response of two patients. Moreover, we observed a discrepancy in the development of the autologous and allogeneic SCCA-parameters suggesting strong effects of the peritumorally administered IFN directly on the effusion tumor cells.
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PMID:Autologous and allogenic natural cell mediated cytotoxicity at the single cell level: divergent effects of interferons and interleukin 2 on binding and lysis. 263 34

From the peripheral blood of the melanoma patient (AV), we derived cytolytic T lymphocyte (CTL) clones that lysed the autologous tumor line SK-MEL-29, but not autologous EBV-B cells, K562, and other tumor targets. By immunoselection experiments it was shown that the CTL clones recognized at least three different antigens on the autologous tumor cells. We demonstrate here that these melanoma antigens are presented to the CTL in association with HLA-A2. First, HLA-A2-reactive pregnancy sera as well as an mAb against HLA-A2 inhibited the CTL lysis. Second, immunoselected melanoma subclones that were resistant to lysis by CTL clones against the three antigens described were found to lack expression of HLA-A2. By sensitizing the patient's lymphocytes against an HLA-A2- melanoma clone, we established a new series of CTL clones recognizing autologous AV melanoma cells. However, efficient lysis was only seen when target cells were pretreated with IFN-gamma. The lytic activity of these CTL was selectively inhibited by an mAb against a common HLA-B determinant. These results indicate that in addition to HLA-A2, other class I antigens are involved in the recognition of AV melanoma cells by autologous CTL.
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PMID:Lysis of human melanoma cells by autologous cytolytic T cell clones. Identification of human histocompatibility leukocyte antigen A2 as a restriction element for three different antigens. 278 8

Interferon (IFN) is a protein with antiviral activity that has been shown to inhibit the growth of many different types of cells. We have measured the IFN sensitivity of nine cell cultures isolated from patients with squamous cell carcinoma and one with malignant melanoma of the head and neck. Normal-appearing fibroblast cultures isolated from these tissues appear quite sensitive to the antiviral effects of IFN. When the encephalomyocarditis virus yield reduction assay is used, these diploid cells are as sensitive to IFN-alpha as are newborn foreskin fibroblast cultures. A similar antiviral effect is seen with IFN-gamma. These cells are relatively insensitive to the antigrowth effect of both IFN preparations as measured by 3H thymidine incorporation and direct observations of cell growth. This is the same relative sensitivity as fibroblasts derived from normal patients. Since these cells are at least 100 times less sensitive to the antigrowth action of the IFNs, it appears unlikely that the IFNs play a significant role in the control of normal fibroblast growth, in contrast to the sensitivity of malignant cell lines.
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PMID:Interferon sensitivity of fibroblast cell cultures derived from patients with neoplasms of the head and neck. 299 1

Fever is frequently an important side effect of interferon (IFN) therapy. Studies have shown that culturing interferon-treated cells at elevated temperature heightens the antiproliferative activity of IFN-alpha and IFN-beta. Since IFN-gamma has also been shown to be a potent antiproliferative agent, the effect of elevated temperature on IFN-gamma activity was compared to its effect on IFN-alpha and IFN-beta. Mouse B-16 melanoma cells were simultaneously cultured under cloning conditions at a range of temperatures (37.3, 38.1, 38.6, and 39.4 degrees C) in the presence of MuIFN-alpha, MuIFN-beta, and MuIFN-gamma. The antiproliferative activities of all three interferons were enhanced by incubation at the elevated temperatures. However, the elevated temperatures had a more dramatic enhancing effect on the antiproliferative activity of MuIFN-gamma (10-fold enhancement) than of either MuIFN-alpha or MuIFN-beta (2.9- and 3.4-fold enhancement, respectively). Next, the enhancing effect of elevated temperature (39.4 degrees C) was examined for a range of interferon concentrations. The degree of the enhancing effect increased with increasing concentrations of MuIFN-gamma but not with increasing concentrations of MuIFN-alpha or MuIFN-beta. Enhancing effects of temperature as high as 14-fold were observed for 100 units of MuIFN-gamma/ml. This dramatic enhancement was observed for both natural and recombinant MuIFN-gamma and was neither a function of greater relative perception of MuIFN-gamma titer at elevated temperature nor a function of greater relative stability of MuIFN-gamma at the elevated temperature. The differential enhancement of MuIFN-gamma activity by elevated temperature appeared to be specific for the antiproliferative activity, since the antiviral activity of MuIFN-gamma was not relatively more enhanced at 39.4 degrees C than were the antiviral activities of MuIFN-alpha and MuIFN-beta. These results suggest that fever may be an important factor in maximizing the antitumor effects of MuIFN-gamma and perhaps of human IFN-gamma. They also raise the possibility that a combination treatment regimen of hyperthermia and interferon therapy, particularly IFN-gamma therapy, may provide a significant antitumor effect.
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PMID:Effect of hyperthermia on the antiproliferative activities of murine alpha-, beta-, and gamma-interferon: differential enhancement of murine gamma-interferon. 299 11


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