Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present studies were undertaken to characterize Ag presentation by cultured human melanoma cell lines. Cell lines established from "biologically early" lesions of malignant melanoma were able to present the soluble Ag tetanus toxoid (TT) to autologous and HLA-DR-matched allogeneic, TT-immune T cell clones. Proliferation of T cell clones in response to Ag presented by primary melanoma peaked on day 2 of culture with Ag. Ag presentation was blocked by pretreatment of TT-pulsed and fixed melanoma cells with mAb against HLA-DR, but not HLA-DQ, HLA-DP, or HLA-ABC. Ag processing and presentation were inhibited by treating the melanoma cells with ammonium chloride. In parallel with previous findings from this laboratory demonstrating the inability of cell lines cultured from "advanced" primary or metastatic melanoma to induce autologous T cell proliferation, such cell lines also failed to present this exogenous Ag despite the presence of cell-surface HLA-class II molecules. Thus, in contrast to the finding in biologically early melanoma, none of the multiple TT-immune, T cell clones from autologous patients or HLA-DR matched donors was able to respond to TT presented by melanoma cells cultured from advanced disease. Co-incubation studies revealed that metastatic melanoma cells did not secrete inhibitory substances during the APC assay, however, they were able to process TT, rendering it "immunogenic" in the presence of fixed, autologous non-T cells. When fixed, autologous melanoma cells were assayed for their ability to present processed Ag; fixed cells of early but not advanced disease were able to present Ag in this setting, indicating that the presenting limb becomes flawed in the evolution of the metastatic phenotype. Finally, studies of chloroquine inhibition of the capacity of melanoma cells derived from early primary disease to stimulate autologous peripheral blood T cells suggest that such cells process and present tumor-associated Ag in the same fashion as the "model" Ag TT.
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PMID:Defective antigen presentation by human melanoma cell lines cultured from advanced, but not biologically early, disease. 246 32

Pleiotropic drug resistance is supposed to be associated with a particular tumor cell phenotype, defined by certain plasma membrane glycolipids. Therefore we wondered how far chemosensitivity in vitro correlates with phenotypic characteristics of melanoma cells, which are known to be highly refractory to cytocidal agents. 13 monolayer cell cultures of metastatic melanoma derived from 9 patients were tested with 12 monoclonal antibodies against constitutive, differentiation- and progression-associated antigens. In parallel these primary cell cultures were subjected to a proliferation inhibition assay in the presence of dacarbazine, cis-platinum and carboplatinum. Transferring melanoma cells from original tissue-suspensions into short-term monolayer cultures caused a change in the expression of certain tumor antigens in 54% of 104 assays. In addition, the incubation of the cultivated cells with various cytostatic agents caused them to alter their phenotype in 32% of 128 assays. Irrespective of the spontaneous or induced changes in the antigen patterns, cells lacking HLA-ABC and/or HLA-DR were inhibited more markedly by cytostatic agents as compared to those other cells expressing these antigens. The data suggest, that pretherapeutic determination of tumor cell phenotype may provide clinically useful information for therapeutic decisions in patients with metastatic melanoma.
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PMID:Alteration of melanoma cell phenotype following in vitro culturing and exposure to cytostatic agents. 268 98

Interferon-gamma (IFN-gamma) is a potent monocyte/macrophage activating agent that in animal models exhibits a bell-shaped dose-response curve of immunomodulatory activity and antitumor efficacy. Previous clinical trials of IFN-gamma conducted at the maximal tolerated dose (MTD) have been associated with low response rates that may have been due to failure to treat at an optimal immunomodulatory dose (OID). The objective of this study was to test the hypothesis that optimal immunomodulatory activity of IFN-gamma in patients with metastatic melanoma would be obtained at a dose below the MTD. Groups of five patients each were given daily subcutaneous injections of IFN-gamma at doses of 0.01, 0.1, or 0.25 mg/m2. In vivo immunomodulation was assessed by serial measurement of serum neopterin and by flow cytometry. IFN-gamma doses of 0.1 or 0.25 mg/m2 induced significantly greater immunomodulation of monocyte-associated immune parameters than 0.01 mg/m2. Changes in immunologic parameters included marked elevation of serum neopterin levels, significant increases in monocyte expression of CD64, beta 2-microglobulin, and HLA-ABC, and decreased monocyte expression of CD14. The most dramatic decreases in CD14 expression were observed on monocytes obtained from patients treated at 0.25 mg/m2. The 0.25-mg/m2 dose group had significantly lower white blood cell counts on day 14. No bell-shaped curve of immunologic response was observed over the dosage range tested. Based on the similarity of the immunologic effects at 0.1 and 0.25 mg/m2, treatment at the MTD of IFN-gamma (0.25 mg/m2) represents treatment at the OID for patients with metastatic malignant melanoma.
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PMID:Immunomodulatory effects of interferon-gamma in patients with metastatic malignant melanoma. 847 92